%PDF-1.3
1 0 obj
<< /Type /Catalog
/Outlines 2 0 R
/Pages 3 0 R >>
endobj
2 0 obj
<< /Type /Outlines /Count 0 >>
endobj
3 0 obj
<< /Type /Pages
/Kids [6 0 R
93 0 R
138 0 R
147 0 R
149 0 R
169 0 R
183 0 R
185 0 R
187 0 R
189 0 R
191 0 R
193 0 R
195 0 R
]
/Count 13
/Resources <<
/ProcSet 4 0 R
/Font << 
/F1 8 0 R
/F2 9 0 R
/F3 10 0 R
/F4 11 0 R
/F5 12 0 R
>>
/XObject << 
/I1 13 0 R
/I2 14 0 R
/I3 109 0 R
/I4 142 0 R
>>
>>
/MediaBox [0.000 0.000 612.000 792.000]
 >>
endobj
4 0 obj
[/PDF /Text /ImageC ]
endobj
5 0 obj
<<
/Creator (DOMPDF)
/CreationDate (D:20180721193808+00'00')
/ModDate (D:20180721193808+00'00')
/Title (Age-at-onset in Huntington disease � PLOS Currents Huntington Disease)
>>
endobj
6 0 obj
<< /Type /Page
/Parent 3 0 R
/Annots [ 15 0 R 17 0 R 19 0 R 21 0 R 23 0 R 25 0 R 27 0 R 29 0 R 31 0 R 33 0 R 35 0 R 37 0 R 39 0 R 41 0 R 43 0 R 45 0 R 47 0 R 49 0 R 51 0 R 53 0 R 55 0 R 57 0 R 59 0 R 61 0 R 63 0 R 65 0 R 67 0 R 69 0 R 71 0 R 73 0 R 75 0 R 77 0 R 79 0 R 81 0 R 83 0 R 85 0 R 87 0 R 89 0 R 91 0 R ]
/Contents 7 0 R
>>
endobj
7 0 obj
<<
/Length 22898 >>
stream

q
375.000 0 0 39.000 222.000 738.000 cm /I2 Do
Q
q
15.000 709.302 577.500 28.698 re W n
0.267 0.267 0.267 rg
BT 15.000 718.042 Td /F2 21.0 Tf  [(Age-at-onset in Huntington disease)] TJ ET
Q
0.271 0.267 0.267 rg
BT 15.000 700.036 Td /F3 9.8 Tf  [(July 29, 2011)] TJ ET
BT 72.681 700.036 Td /F3 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
BT 77.556 700.036 Td /F3 9.8 Tf  [(Epidemiology)] TJ ET
BT 26.250 688.195 Td /F1 9.8 Tf  [(Michael Orth)] TJ ET
0.271 0.267 0.267 rg
BT 81.513 688.195 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 86.934 688.195 Td /F1 9.8 Tf  [(Carsten Schwenke)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 676.290 Td /F1 9.8 Tf  [(Orth M, Schwenke C. Age-at-onset in Huntington disease. PLOS Currents Huntington Disease. 2011 Jul 29 . Edition 1. doi: )] TJ ET
BT 26.250 664.386 Td /F1 9.8 Tf  [(10.1371/currents.RRN1258.)] TJ ET
q
15.000 24.826 577.500 637.179 re W n
0.271 0.267 0.267 rg
BT 26.250 635.283 Td /F4 12.0 Tf  [(Abstract)] TJ ET
BT 26.250 615.329 Td /F1 9.8 Tf  [(Background: In Huntington disease, the accurate determination of age-at-onset is critical to identify modifiers and therapies that )] TJ ET
BT 26.250 603.424 Td /F1 9.8 Tf  [(aim to delay it.)] TJ ET
BT 26.250 584.019 Td /F1 9.8 Tf  [(Methods: Retrospective data from the European Huntington�s Disease Network�s REGISTRY. Data \(age, gender, CAG repeat )] TJ ET
BT 26.250 572.115 Td /F1 9.8 Tf  [(length, parent affected, and Unified Huntington�s Disease Rating Scale motor score, total functional capacity\) from at least three )] TJ ET
BT 26.250 560.210 Td /F1 9.8 Tf  [(visits in 423 REGISTRY participants were included. Data based extrapolations of individual age-at-onset using generalized )] TJ ET
BT 26.250 548.305 Td /F1 9.8 Tf  [(linear mixed models based on individual slopes of motor score or total functional capacity, and predictions using the Langbehn, )] TJ ET
BT 26.250 536.400 Td /F1 9.8 Tf  [(or Ranen formula, were compared with clinicians� estimates.)] TJ ET
BT 26.250 516.996 Td /F1 9.8 Tf  [(Results: Concordance was best for the calculated onset using the REGISTRY UHDRS longitudinal motor scores. For total )] TJ ET
BT 26.250 505.091 Td /F1 9.8 Tf  [(functional capacity, the investigator�s estimate was 4 years before the data derived age-at-onset. The concordance of )] TJ ET
BT 26.250 493.186 Td /F1 9.8 Tf  [(predictions of probability of age-at-onset was �20 years \(difference in 25%tile\).)] TJ ET
BT 26.250 473.781 Td /F1 9.8 Tf  [(Conclusions: Estimating or predicting age-at-onset in Huntington disease may be inaccurate. It can be useful to 1\) add in the )] TJ ET
BT 26.250 461.877 Td /F1 9.8 Tf  [(manifest population motor score regression derived age-at-onset as additional motor onset and 2\) add total functional capacity )] TJ ET
BT 26.250 449.972 Td /F1 9.8 Tf  [(regression derived age-at-onset for the onset of functional impact of Huntington disease when patients are in mid- to late-stage.)] TJ ET
BT 26.250 413.369 Td /F4 12.0 Tf  [(Formal Correction)] TJ ET
BT 26.250 393.415 Td /F1 9.8 Tf  [(This article has been formally corrected to address the following. All reference to and analysis of thePREDICT-HD dataset has )] TJ ET
BT 26.250 381.510 Td /F1 9.8 Tf  [(been removed from the original version of this article at the request of the PREDICT-HD Statistics Team.)] TJ ET
BT 26.250 344.908 Td /F4 12.0 Tf  [(INTRODUCTION)] TJ ET
BT 26.250 324.954 Td /F1 9.8 Tf  [(Age-at-onset \(AAO\) in Huntington disease \(HD\) describes the point in time when a carrier of the mutated gene develops )] TJ ET
BT 26.250 313.049 Td /F1 9.8 Tf  [(unequivocal HD signs. The accurate determination of AAO is critical to find factors that modify AAO and to develop and )] TJ ET
BT 26.250 301.144 Td /F1 9.8 Tf  [(evaluate therapies that aim to delay it. In manifest HD, an autosomal dominant disease with a highly penetrant CAG repeat )] TJ ET
BT 26.250 289.239 Td /F1 9.8 Tf  [(expansion mutation in the )] TJ ET
BT 140.062 289.239 Td /F5 9.8 Tf  [(HTT)] TJ ET
BT 159.016 289.239 Td /F1 9.8 Tf  [( gene, )] TJ ET
0.267 0.267 0.267 rg
BT 188.831 289.239 Td /F1 8.7 Tf  [([1])] TJ ET
0.271 0.267 0.267 rg
BT 198.469 289.239 Td /F1 9.8 Tf  [( a clinician estimates AAO retrospectively based on information from manifest patients, )] TJ ET
BT 26.250 277.335 Td /F1 9.8 Tf  [(relatives, and carers. For AAO predictions in the prodromal phase the formula of Langbehn and colleagues uses CAG repeat )] TJ ET
BT 26.250 265.430 Td /F1 9.8 Tf  [(length and age because of their well known influences on AAO and calculates the time to a predefined degree of probability of )] TJ ET
BT 26.250 253.525 Td /F1 9.8 Tf  [(manifesting signs of HD. )] TJ ET
0.267 0.267 0.267 rg
BT 134.621 253.525 Td /F1 8.7 Tf  [([2])] TJ ET
0.271 0.267 0.267 rg
BT 144.259 253.525 Td /F1 9.8 Tf  [( However, CAG repeat length accounts for only about 50-60% of the variability, so other factors not )] TJ ET
BT 26.250 241.620 Td /F1 9.8 Tf  [(modelled in this formula likely influence AAO. )] TJ ET
0.267 0.267 0.267 rg
BT 224.029 241.620 Td /F1 8.7 Tf  [([3])] TJ ET
0.271 0.267 0.267 rg
BT 233.666 241.620 Td /F1 9.8 Tf  [( Another formula published by Ranen and colleagues uses CAG repeat length )] TJ ET
BT 26.250 229.716 Td /F1 9.8 Tf  [(and parental onset age to estimate AAO. )] TJ ET
0.267 0.267 0.267 rg
BT 205.104 229.716 Td /F1 8.7 Tf  [([4] , )] TJ ET
BT 221.969 229.716 Td /F1 8.7 Tf  [([5)] TJ ET
BT 229.197 229.716 Td /F1 8.7 Tf  [(])] TJ ET
0.271 0.267 0.267 rg
BT 231.607 229.716 Td /F1 9.8 Tf  [( This may accommodate for some other inherited factors as an advantage over )] TJ ET
BT 26.250 217.811 Td /F1 9.8 Tf  [(the Langbehn formula. However, it was derived from a small sample of affected parent-child pairs and needs to be validated in )] TJ ET
BT 26.250 205.906 Td /F1 9.8 Tf  [(larger numbers of patients. )] TJ ET
0.267 0.267 0.267 rg
BT 144.927 205.906 Td /F1 8.7 Tf  [([5])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 186.501 Td /F1 9.8 Tf  [(The aim of this study is to compare clinicians� estimates with data-based extrapolations of AAO, and predictions using the )] TJ ET
BT 26.250 174.597 Td /F1 9.8 Tf  [(Langbehn, or Ranen formula. To this end we used data from the European Huntington�s Disease Network�s \(EHDN\) )] TJ ET
BT 26.250 162.692 Td /F1 9.8 Tf  [(REGISTRY, a longitudinal observational study of HD for preparing statistical models. )] TJ ET
0.267 0.267 0.267 rg
BT 393.640 162.692 Td /F1 8.7 Tf  [([6] , [7])] TJ ET
0.271 0.267 0.267 rg
BT 420.142 162.692 Td /F1 9.8 Tf  [( REGISTRY enrols participants at )] TJ ET
BT 26.250 150.787 Td /F1 9.8 Tf  [(any stage of HD including the prodromal phase. )] TJ ET
0.267 0.267 0.267 rg
BT 234.890 150.787 Td /F1 8.7 Tf  [([6] , [7])] TJ ET
0.271 0.267 0.267 rg
BT 261.393 150.787 Td /F1 9.8 Tf  [( We hypothesized that in the REGISTRY data agreement rates between )] TJ ET
BT 26.250 138.882 Td /F1 9.8 Tf  [(the clinicians� estimates of AAO and data based AAO would be low since we expected that the retrospective estimate of AAO in )] TJ ET
BT 26.250 126.978 Td /F1 9.8 Tf  [(REGISTRY was imprecise. We further expected that data-based calculations of a motor onset is possible and less variable than )] TJ ET
BT 26.250 115.073 Td /F1 9.8 Tf  [(clinicians� estimates of AAO, and, similarly, that it is possible to calculate an onset of functional impairment.)] TJ ET
BT 26.250 78.470 Td /F4 12.0 Tf  [(METHODS)] TJ ET
BT 26.250 58.516 Td /F4 9.8 Tf  [(Participants)] TJ ET
BT 26.250 39.111 Td /F1 9.8 Tf  [(Retrospective data from an ongoing multicentre, longitudinal observational research study, EHDN�s REGISTRY, was used. )] TJ ET
Q
q
15.000 709.302 577.500 28.698 re W n
0.267 0.267 0.267 rg
BT 15.000 718.042 Td /F2 21.0 Tf  [(Age-at-onset in Huntington disease)] TJ ET
Q
0.271 0.267 0.267 rg
BT 15.000 700.036 Td /F3 9.8 Tf  [(July 29, 2011)] TJ ET
BT 72.681 700.036 Td /F3 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
BT 77.556 700.036 Td /F3 9.8 Tf  [(Epidemiology)] TJ ET
BT 26.250 688.195 Td /F1 9.8 Tf  [(Michael Orth)] TJ ET
0.271 0.267 0.267 rg
BT 81.513 688.195 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 86.934 688.195 Td /F1 9.8 Tf  [(Carsten Schwenke)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 676.290 Td /F1 9.8 Tf  [(Orth M, Schwenke C. Age-at-onset in Huntington disease. PLOS Currents Huntington Disease. 2011 Jul 29 . Edition 1. doi: )] TJ ET
BT 26.250 664.386 Td /F1 9.8 Tf  [(10.1371/currents.RRN1258.)] TJ ET
q
15.000 24.826 577.500 637.179 re W n
0.271 0.267 0.267 rg
BT 26.250 635.283 Td /F4 12.0 Tf  [(Abstract)] TJ ET
BT 26.250 615.329 Td /F1 9.8 Tf  [(Background: In Huntington disease, the accurate determination of age-at-onset is critical to identify modifiers and therapies that )] TJ ET
BT 26.250 603.424 Td /F1 9.8 Tf  [(aim to delay it.)] TJ ET
BT 26.250 584.019 Td /F1 9.8 Tf  [(Methods: Retrospective data from the European Huntington�s Disease Network�s REGISTRY. Data \(age, gender, CAG repeat )] TJ ET
BT 26.250 572.115 Td /F1 9.8 Tf  [(length, parent affected, and Unified Huntington�s Disease Rating Scale motor score, total functional capacity\) from at least three )] TJ ET
BT 26.250 560.210 Td /F1 9.8 Tf  [(visits in 423 REGISTRY participants were included. Data based extrapolations of individual age-at-onset using generalized )] TJ ET
BT 26.250 548.305 Td /F1 9.8 Tf  [(linear mixed models based on individual slopes of motor score or total functional capacity, and predictions using the Langbehn, )] TJ ET
BT 26.250 536.400 Td /F1 9.8 Tf  [(or Ranen formula, were compared with clinicians� estimates.)] TJ ET
BT 26.250 516.996 Td /F1 9.8 Tf  [(Results: Concordance was best for the calculated onset using the REGISTRY UHDRS longitudinal motor scores. For total )] TJ ET
BT 26.250 505.091 Td /F1 9.8 Tf  [(functional capacity, the investigator�s estimate was 4 years before the data derived age-at-onset. The concordance of )] TJ ET
BT 26.250 493.186 Td /F1 9.8 Tf  [(predictions of probability of age-at-onset was �20 years \(difference in 25%tile\).)] TJ ET
BT 26.250 473.781 Td /F1 9.8 Tf  [(Conclusions: Estimating or predicting age-at-onset in Huntington disease may be inaccurate. It can be useful to 1\) add in the )] TJ ET
BT 26.250 461.877 Td /F1 9.8 Tf  [(manifest population motor score regression derived age-at-onset as additional motor onset and 2\) add total functional capacity )] TJ ET
BT 26.250 449.972 Td /F1 9.8 Tf  [(regression derived age-at-onset for the onset of functional impact of Huntington disease when patients are in mid- to late-stage.)] TJ ET
BT 26.250 413.369 Td /F4 12.0 Tf  [(Formal Correction)] TJ ET
BT 26.250 393.415 Td /F1 9.8 Tf  [(This article has been formally corrected to address the following. All reference to and analysis of thePREDICT-HD dataset has )] TJ ET
BT 26.250 381.510 Td /F1 9.8 Tf  [(been removed from the original version of this article at the request of the PREDICT-HD Statistics Team.)] TJ ET
BT 26.250 344.908 Td /F4 12.0 Tf  [(INTRODUCTION)] TJ ET
BT 26.250 324.954 Td /F1 9.8 Tf  [(Age-at-onset \(AAO\) in Huntington disease \(HD\) describes the point in time when a carrier of the mutated gene develops )] TJ ET
BT 26.250 313.049 Td /F1 9.8 Tf  [(unequivocal HD signs. The accurate determination of AAO is critical to find factors that modify AAO and to develop and )] TJ ET
BT 26.250 301.144 Td /F1 9.8 Tf  [(evaluate therapies that aim to delay it. In manifest HD, an autosomal dominant disease with a highly penetrant CAG repeat )] TJ ET
BT 26.250 289.239 Td /F1 9.8 Tf  [(expansion mutation in the )] TJ ET
BT 140.062 289.239 Td /F5 9.8 Tf  [(HTT)] TJ ET
BT 159.016 289.239 Td /F1 9.8 Tf  [( gene, )] TJ ET
0.267 0.267 0.267 rg
BT 188.831 289.239 Td /F1 8.7 Tf  [([1])] TJ ET
0.271 0.267 0.267 rg
BT 198.469 289.239 Td /F1 9.8 Tf  [( a clinician estimates AAO retrospectively based on information from manifest patients, )] TJ ET
BT 26.250 277.335 Td /F1 9.8 Tf  [(relatives, and carers. For AAO predictions in the prodromal phase the formula of Langbehn and colleagues uses CAG repeat )] TJ ET
BT 26.250 265.430 Td /F1 9.8 Tf  [(length and age because of their well known influences on AAO and calculates the time to a predefined degree of probability of )] TJ ET
BT 26.250 253.525 Td /F1 9.8 Tf  [(manifesting signs of HD. )] TJ ET
0.267 0.267 0.267 rg
BT 134.621 253.525 Td /F1 8.7 Tf  [([2])] TJ ET
0.271 0.267 0.267 rg
BT 144.259 253.525 Td /F1 9.8 Tf  [( However, CAG repeat length accounts for only about 50-60% of the variability, so other factors not )] TJ ET
BT 26.250 241.620 Td /F1 9.8 Tf  [(modelled in this formula likely influence AAO. )] TJ ET
0.267 0.267 0.267 rg
BT 224.029 241.620 Td /F1 8.7 Tf  [([3])] TJ ET
0.271 0.267 0.267 rg
BT 233.666 241.620 Td /F1 9.8 Tf  [( Another formula published by Ranen and colleagues uses CAG repeat length )] TJ ET
BT 26.250 229.716 Td /F1 9.8 Tf  [(and parental onset age to estimate AAO. )] TJ ET
0.267 0.267 0.267 rg
BT 205.104 229.716 Td /F1 8.7 Tf  [([4] , )] TJ ET
BT 221.969 229.716 Td /F1 8.7 Tf  [([5)] TJ ET
BT 229.197 229.716 Td /F1 8.7 Tf  [(])] TJ ET
0.271 0.267 0.267 rg
BT 231.607 229.716 Td /F1 9.8 Tf  [( This may accommodate for some other inherited factors as an advantage over )] TJ ET
BT 26.250 217.811 Td /F1 9.8 Tf  [(the Langbehn formula. However, it was derived from a small sample of affected parent-child pairs and needs to be validated in )] TJ ET
BT 26.250 205.906 Td /F1 9.8 Tf  [(larger numbers of patients. )] TJ ET
0.267 0.267 0.267 rg
BT 144.927 205.906 Td /F1 8.7 Tf  [([5])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 186.501 Td /F1 9.8 Tf  [(The aim of this study is to compare clinicians� estimates with data-based extrapolations of AAO, and predictions using the )] TJ ET
BT 26.250 174.597 Td /F1 9.8 Tf  [(Langbehn, or Ranen formula. To this end we used data from the European Huntington�s Disease Network�s \(EHDN\) )] TJ ET
BT 26.250 162.692 Td /F1 9.8 Tf  [(REGISTRY, a longitudinal observational study of HD for preparing statistical models. )] TJ ET
0.267 0.267 0.267 rg
BT 393.640 162.692 Td /F1 8.7 Tf  [([6] , [7])] TJ ET
0.271 0.267 0.267 rg
BT 420.142 162.692 Td /F1 9.8 Tf  [( REGISTRY enrols participants at )] TJ ET
BT 26.250 150.787 Td /F1 9.8 Tf  [(any stage of HD including the prodromal phase. )] TJ ET
0.267 0.267 0.267 rg
BT 234.890 150.787 Td /F1 8.7 Tf  [([6] , [7])] TJ ET
0.271 0.267 0.267 rg
BT 261.393 150.787 Td /F1 9.8 Tf  [( We hypothesized that in the REGISTRY data agreement rates between )] TJ ET
BT 26.250 138.882 Td /F1 9.8 Tf  [(the clinicians� estimates of AAO and data based AAO would be low since we expected that the retrospective estimate of AAO in )] TJ ET
BT 26.250 126.978 Td /F1 9.8 Tf  [(REGISTRY was imprecise. We further expected that data-based calculations of a motor onset is possible and less variable than )] TJ ET
BT 26.250 115.073 Td /F1 9.8 Tf  [(clinicians� estimates of AAO, and, similarly, that it is possible to calculate an onset of functional impairment.)] TJ ET
BT 26.250 78.470 Td /F4 12.0 Tf  [(METHODS)] TJ ET
BT 26.250 58.516 Td /F4 9.8 Tf  [(Participants)] TJ ET
BT 26.250 39.111 Td /F1 9.8 Tf  [(Retrospective data from an ongoing multicentre, longitudinal observational research study, EHDN�s REGISTRY, was used. )] TJ ET
Q
q
15.000 709.302 577.500 28.698 re W n
0.267 0.267 0.267 rg
BT 15.000 718.042 Td /F2 21.0 Tf  [(Age-at-onset in Huntington disease)] TJ ET
Q
0.271 0.267 0.267 rg
BT 15.000 700.036 Td /F3 9.8 Tf  [(July 29, 2011)] TJ ET
BT 72.681 700.036 Td /F3 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
BT 77.556 700.036 Td /F3 9.8 Tf  [(Epidemiology)] TJ ET
BT 26.250 688.195 Td /F1 9.8 Tf  [(Michael Orth)] TJ ET
0.271 0.267 0.267 rg
BT 81.513 688.195 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 86.934 688.195 Td /F1 9.8 Tf  [(Carsten Schwenke)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 676.290 Td /F1 9.8 Tf  [(Orth M, Schwenke C. Age-at-onset in Huntington disease. PLOS Currents Huntington Disease. 2011 Jul 29 . Edition 1. doi: )] TJ ET
BT 26.250 664.386 Td /F1 9.8 Tf  [(10.1371/currents.RRN1258.)] TJ ET
q
15.000 24.826 577.500 637.179 re W n
0.271 0.267 0.267 rg
BT 26.250 635.283 Td /F4 12.0 Tf  [(Abstract)] TJ ET
BT 26.250 615.329 Td /F1 9.8 Tf  [(Background: In Huntington disease, the accurate determination of age-at-onset is critical to identify modifiers and therapies that )] TJ ET
BT 26.250 603.424 Td /F1 9.8 Tf  [(aim to delay it.)] TJ ET
BT 26.250 584.019 Td /F1 9.8 Tf  [(Methods: Retrospective data from the European Huntington�s Disease Network�s REGISTRY. Data \(age, gender, CAG repeat )] TJ ET
BT 26.250 572.115 Td /F1 9.8 Tf  [(length, parent affected, and Unified Huntington�s Disease Rating Scale motor score, total functional capacity\) from at least three )] TJ ET
BT 26.250 560.210 Td /F1 9.8 Tf  [(visits in 423 REGISTRY participants were included. Data based extrapolations of individual age-at-onset using generalized )] TJ ET
BT 26.250 548.305 Td /F1 9.8 Tf  [(linear mixed models based on individual slopes of motor score or total functional capacity, and predictions using the Langbehn, )] TJ ET
BT 26.250 536.400 Td /F1 9.8 Tf  [(or Ranen formula, were compared with clinicians� estimates.)] TJ ET
BT 26.250 516.996 Td /F1 9.8 Tf  [(Results: Concordance was best for the calculated onset using the REGISTRY UHDRS longitudinal motor scores. For total )] TJ ET
BT 26.250 505.091 Td /F1 9.8 Tf  [(functional capacity, the investigator�s estimate was 4 years before the data derived age-at-onset. The concordance of )] TJ ET
BT 26.250 493.186 Td /F1 9.8 Tf  [(predictions of probability of age-at-onset was �20 years \(difference in 25%tile\).)] TJ ET
BT 26.250 473.781 Td /F1 9.8 Tf  [(Conclusions: Estimating or predicting age-at-onset in Huntington disease may be inaccurate. It can be useful to 1\) add in the )] TJ ET
BT 26.250 461.877 Td /F1 9.8 Tf  [(manifest population motor score regression derived age-at-onset as additional motor onset and 2\) add total functional capacity )] TJ ET
BT 26.250 449.972 Td /F1 9.8 Tf  [(regression derived age-at-onset for the onset of functional impact of Huntington disease when patients are in mid- to late-stage.)] TJ ET
BT 26.250 413.369 Td /F4 12.0 Tf  [(Formal Correction)] TJ ET
BT 26.250 393.415 Td /F1 9.8 Tf  [(This article has been formally corrected to address the following. All reference to and analysis of thePREDICT-HD dataset has )] TJ ET
BT 26.250 381.510 Td /F1 9.8 Tf  [(been removed from the original version of this article at the request of the PREDICT-HD Statistics Team.)] TJ ET
BT 26.250 344.908 Td /F4 12.0 Tf  [(INTRODUCTION)] TJ ET
BT 26.250 324.954 Td /F1 9.8 Tf  [(Age-at-onset \(AAO\) in Huntington disease \(HD\) describes the point in time when a carrier of the mutated gene develops )] TJ ET
BT 26.250 313.049 Td /F1 9.8 Tf  [(unequivocal HD signs. The accurate determination of AAO is critical to find factors that modify AAO and to develop and )] TJ ET
BT 26.250 301.144 Td /F1 9.8 Tf  [(evaluate therapies that aim to delay it. In manifest HD, an autosomal dominant disease with a highly penetrant CAG repeat )] TJ ET
BT 26.250 289.239 Td /F1 9.8 Tf  [(expansion mutation in the )] TJ ET
BT 140.062 289.239 Td /F5 9.8 Tf  [(HTT)] TJ ET
BT 159.016 289.239 Td /F1 9.8 Tf  [( gene, )] TJ ET
0.267 0.267 0.267 rg
BT 188.831 289.239 Td /F1 8.7 Tf  [([1])] TJ ET
0.271 0.267 0.267 rg
BT 198.469 289.239 Td /F1 9.8 Tf  [( a clinician estimates AAO retrospectively based on information from manifest patients, )] TJ ET
BT 26.250 277.335 Td /F1 9.8 Tf  [(relatives, and carers. For AAO predictions in the prodromal phase the formula of Langbehn and colleagues uses CAG repeat )] TJ ET
BT 26.250 265.430 Td /F1 9.8 Tf  [(length and age because of their well known influences on AAO and calculates the time to a predefined degree of probability of )] TJ ET
BT 26.250 253.525 Td /F1 9.8 Tf  [(manifesting signs of HD. )] TJ ET
0.267 0.267 0.267 rg
BT 134.621 253.525 Td /F1 8.7 Tf  [([2])] TJ ET
0.271 0.267 0.267 rg
BT 144.259 253.525 Td /F1 9.8 Tf  [( However, CAG repeat length accounts for only about 50-60% of the variability, so other factors not )] TJ ET
BT 26.250 241.620 Td /F1 9.8 Tf  [(modelled in this formula likely influence AAO. )] TJ ET
0.267 0.267 0.267 rg
BT 224.029 241.620 Td /F1 8.7 Tf  [([3])] TJ ET
0.271 0.267 0.267 rg
BT 233.666 241.620 Td /F1 9.8 Tf  [( Another formula published by Ranen and colleagues uses CAG repeat length )] TJ ET
BT 26.250 229.716 Td /F1 9.8 Tf  [(and parental onset age to estimate AAO. )] TJ ET
0.267 0.267 0.267 rg
BT 205.104 229.716 Td /F1 8.7 Tf  [([4] , )] TJ ET
BT 221.969 229.716 Td /F1 8.7 Tf  [([5)] TJ ET
BT 229.197 229.716 Td /F1 8.7 Tf  [(])] TJ ET
0.271 0.267 0.267 rg
BT 231.607 229.716 Td /F1 9.8 Tf  [( This may accommodate for some other inherited factors as an advantage over )] TJ ET
BT 26.250 217.811 Td /F1 9.8 Tf  [(the Langbehn formula. However, it was derived from a small sample of affected parent-child pairs and needs to be validated in )] TJ ET
BT 26.250 205.906 Td /F1 9.8 Tf  [(larger numbers of patients. )] TJ ET
0.267 0.267 0.267 rg
BT 144.927 205.906 Td /F1 8.7 Tf  [([5])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 186.501 Td /F1 9.8 Tf  [(The aim of this study is to compare clinicians� estimates with data-based extrapolations of AAO, and predictions using the )] TJ ET
BT 26.250 174.597 Td /F1 9.8 Tf  [(Langbehn, or Ranen formula. To this end we used data from the European Huntington�s Disease Network�s \(EHDN\) )] TJ ET
BT 26.250 162.692 Td /F1 9.8 Tf  [(REGISTRY, a longitudinal observational study of HD for preparing statistical models. )] TJ ET
0.267 0.267 0.267 rg
BT 393.640 162.692 Td /F1 8.7 Tf  [([6] , [7])] TJ ET
0.271 0.267 0.267 rg
BT 420.142 162.692 Td /F1 9.8 Tf  [( REGISTRY enrols participants at )] TJ ET
BT 26.250 150.787 Td /F1 9.8 Tf  [(any stage of HD including the prodromal phase. )] TJ ET
0.267 0.267 0.267 rg
BT 234.890 150.787 Td /F1 8.7 Tf  [([6] , [7])] TJ ET
0.271 0.267 0.267 rg
BT 261.393 150.787 Td /F1 9.8 Tf  [( We hypothesized that in the REGISTRY data agreement rates between )] TJ ET
BT 26.250 138.882 Td /F1 9.8 Tf  [(the clinicians� estimates of AAO and data based AAO would be low since we expected that the retrospective estimate of AAO in )] TJ ET
BT 26.250 126.978 Td /F1 9.8 Tf  [(REGISTRY was imprecise. We further expected that data-based calculations of a motor onset is possible and less variable than )] TJ ET
BT 26.250 115.073 Td /F1 9.8 Tf  [(clinicians� estimates of AAO, and, similarly, that it is possible to calculate an onset of functional impairment.)] TJ ET
BT 26.250 78.470 Td /F4 12.0 Tf  [(METHODS)] TJ ET
BT 26.250 58.516 Td /F4 9.8 Tf  [(Participants)] TJ ET
BT 26.250 39.111 Td /F1 9.8 Tf  [(Retrospective data from an ongoing multicentre, longitudinal observational research study, EHDN�s REGISTRY, was used. )] TJ ET
Q
q
0.000 0.000 0.000 rg
BT 291.710 19.825 Td /F1 11.0 Tf  [(1)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Huntington Disease)] TJ ET

Q
endstream
endobj
8 0 obj
<< /Type /Font
/Subtype /Type1
/Name /F1
/BaseFont /Helvetica
/Encoding /WinAnsiEncoding
>>
endobj
9 0 obj
<< /Type /Font
/Subtype /Type1
/Name /F2
/BaseFont /Times-Bold
/Encoding /WinAnsiEncoding
>>
endobj
10 0 obj
<< /Type /Font
/Subtype /Type1
/Name /F3
/BaseFont /Times-Italic
/Encoding /WinAnsiEncoding
>>
endobj
11 0 obj
<< /Type /Font
/Subtype /Type1
/Name /F4
/BaseFont /Helvetica-Bold
/Encoding /WinAnsiEncoding
>>
endobj
12 0 obj
<< /Type /Font
/Subtype /Type1
/Name /F5
/BaseFont /Helvetica-Oblique
/Encoding /WinAnsiEncoding
>>
endobj
13 0 obj
<<
/Type /XObject
/Subtype /Image
/Width 500
/Height 52
/Filter /FlateDecode
/DecodeParms << /Predictor 15 /Colors 1 /Columns 500 /BitsPerComponent 8>>
/ColorSpace /DeviceGray
/BitsPerComponent 8
/Length 144>>
stream
x���1
0���'ݲ؎�"e����{��dz��A��dz��A��dz��A��dz��A��dz��A��dz��A��dz��A��dz��A��dz��A��dz��A��dz��A��dz��A��tlM0\
endstream
endobj
14 0 obj
<<
/Type /XObject
/Subtype /Image
/Width 500
/Height 52
/SMask 13 0 R
/Filter /FlateDecode
/DecodeParms << /Predictor 15 /Colors 3 /Columns 500 /BitsPerComponent 8>>
/ColorSpace /DeviceRGB
/BitsPerComponent 8
/Length 4223>>
stream
x��ە�8��=���,��8C�#h�!�hG�
v�#0���=���j$q1�u��aN�ĥT*�J���&�a���_�Z�a��a��0�	a��0�	a��0�	�H�^UUUUX!�03�S�Y�����|^�G��0Ì�Ô{]����w�a�_��>�"��O��eYa��G!��8�e}��a�6̖{�4��M&��d���:�"�qʲ��\Q�UUM�S��<ϛN�l���d2�l6�Z
�a�<��=�2��B�(���2��vK�7M�\.GW�0���r����rW�W��a������v��ߖe9�C?Eq8��G�q�y~~�}_��q�d�Ͻ(�n��eY��ʒ��Gj�����K�4EQ�N�����j�ͷm{�X��?|�7��m۶m�qP��:Ȳ�p8�K�m����u]���lN��z����u�Z�,���N���T�eY��"jlUUQ�W\,aR��iV��bȗ�</I��-�˦i�4�m�(��n��˲�4Mq��(��=.���,��0��[y�����|��n��5����ɲ�8��׫\�\ MS�Z��e���m�y�נ�4^����:D_Ap�\��*�Ҷ��VO�q�ؤ�e�,�*WR�%��c
���s��X/`Y�
�N�!ry:(�(˲����;�2̗�5Z��}����Z.��X��������tʲL�l6��v0Q���~���f���eY¬v]רG��j�^.�A�i�[r`�B�,ˢ(R϶�EQ�q�62Ȳl�Z�ʶZ�v�]��mc��x���뺋�B����~��*��B���7˲���,S�	%����e���y�ZX�)1K_������A~j
è�����x<�v���|~zտ�F��7�8����U1W���mv_A�5��
^� .������-[wC��(e`�ᖻl��R������,ˢ

���������+��Nv�m۾��������EQ����eY��:�"۶-˪�
'�S��dY6���9�eV��#B(=_�ͮ0d����pBض��K�G�i�F�m�V��3F1�~��c���x\�Vu]A���bF�N��|>�L�k�Hk��E�s�����jd��.L6���=I�ו	�P�]�1��t7�S�����c2�uIu�MM�;
�K��5>A�$Ǒ$I����׋��n��Y��0�_H�at��;�a�q䃰U�$��n���R���,��z�O7bT
�m��h��h���ԫܻu1F*q���m'�P��}ܙ<ϕAL�O�6L�w�3nB�.T��4c���<�L���4�C��M���	U��F�n787lۖ�F(q˲�����rV���/�+�R�rW>o�{�߽���.l�V�
$l����aԀ��I��u�!�gwChx����J�]Ne� (�+�M�"d�-�E��qc��=P�
!�
��"n�f��(���7���>�c�e�,Ř�m�[�!ʝD�!�m����)Bs@)��t�a�3���}�g�˲�}�Z���b���շ�O�N�KF�p����倫�R��g�(��,I���2C�%��5y�
B	���vo����9�϶m+
�ІX�cT�w�V�5;��8�d�H��F{��7Qm6�'N۠�%$���H�SM���k!D�4�i:���ŕS�*�bS�̹"�2=�ԓ�H51$�Uf�Z�V��t��l�i<��0]�n���DZlc��W���v;LQr��x����hk����+},C����V�e��D�8�]���ې���/.�m[n��c)�2�X��AOM��o&�}�"&��ڨv�宇EqX$�tcGc,�|`��5�)y���O(U\��͠&���ԭ��C&~�1ynKo�����C�~��k��q�qltV\��4M�8N�T�r��e����#��s�T�|>+GJ
�W]�$I�i	EMH�dD7�0_
�r��E�Ѐa:�c4�u�U��0.RH=��S�N4�/z2�p�Ȥ�fx$�]�1�w��t<]׭����U�$%�=��w�i���~ܮ{��=�×�w\Բ�!�s^__=��A�x�a1|�=(��l��´�����i�4ME��UUm6y)���~����E����5�UU�~g��ѥ��J'+��WT���N'!�H>�{�=��n����
yt���H{{xzo���<��8�a�����O�w0l���N]?���g�NR�2�Ɍ6Z��摤��Ww�(����eYv̲�	�b�\�a�������Hɟ�,�J�6	�ܺ�=
��^'ҵ�4^.˲�rIa�J'����RC]�Qѯ����r��洱�l���f�?>ȩ_��Y�e�=�3ʆ�:Fy0D&y��%0z��U^�5�ἧԯ���g�F��eY�q����������ƈ���hz#m��s[o�$�+�0��Q���z��2�-Z�\"#f��2�9��:��WGVzl�B�PD��;�CW�+�D��y��e�$	6HQ"\�&_$��Tp]A�h���e����H�y���R��1��'� p'�sD�)�ZDpB�/�Y_S����V����G����ӌ;Oo[A��m+�����(U�ܮ����+U�ʽ���N=PJ/�>�^���;?�9�o���g����mY�Ѳ=k�@�._������ (��V{�#��z/�,@��Y���,��1�e`&i$�<=�EQl6��|���A4b��%'X��[Ѷa���S��h��/QM&$�����N��gSٲ,奭�ֻ�DH�>E�e�SFo�[�'��ķ��r�i��V���a��߶���ї5�,�lj��*�
Q��=T�qE�MD��4�N���6MC��
����L(P�Ư%���n�^�� w�~�oSrDf�e�0�^��F�]��������G$IY������?��v�+���r�EQ�-��WU��m������pP^� ���:v��z�֝�2q#3D�ƾ�t:�
���~�Gv�(��,��$�j�:�NpC�ˏ�S�)���=ϛL&xlۆ+�i�8��}CH,t�%���z\�MD����������0�^t��C>�(��4;ن�����]螞�P�t:5���f�[��@�o��q��g�{L�̷gY���D��"ma�I�����4co�����KE�����殂 �'��ٲ��t���2_��,�����m�[|Qa����fL���u��DZ(
�W���
5o�Oi����y{0�<�s꺰��^�x<�}�#�:///����t@.�q�hј@������n���굮k�~�P��A�}H�`Y�f�	�F��r�E],mm��v��V�4EQІ'�[���F���1�Y����i�B���\׵l�a��i��#��������=�P�D��$���/ֈ��xp�7 4�[m��}�?���C����7�h�v��???���7��}���1)�8���ۺ���#	?��l�nk�m�y�s�#C|�s7&]��<�"
���}�(�(���O��iz��0||����r��kb�d�^��p8��\��9V��8�i|8:������V+�q�K�%�w�+�}�\*-y
��O�5+��!C� �V�!j�#�����rIqVMӴ�0tv���ض��ni4�e�~����>���o�������q�NF�;��r���j%��z�wuo�10)Bw�ܮ�C!��}�Έ3��H(�.E��'�	��h�]j�D�A �6����.�M
T�8z��q��y~o����eO�#�]�PWp���0�<�;F������܆b+�ɽ��nKQy�\�8n�ڶ��d����/��خ^���^o��|�N�.�[�vO�z<MS��M�T�,F�P�x9rsQWd)ö�����
z��ｏsK��>`'E�f̈��+"�"/�cL��<�" �����Ƅ_���~�W|��¿�Tt"fi���Y�_��uW��x<Š�M(�0�L�8�91�a��>��ao\
|��[�C~mX�33�;�o6�����|>�ϻ#ChR�����0Ì`�r�뚢�����#�~�#���N*�0�Fk�
%ʪ�rO�d6��u͊�A�kdfw�ܧ�)���,Y�0���ܡܛ��4��ۈa���
�0����-�0��)�rg����rg����rg����rg����zm��
endstream
endobj
15 0 obj
<< /Type /Annot
/Subtype /Link
/A 16 0 R
/Border [0 0 0]
/H /I
/Rect [ 15.0000 716.1516 328.2570 736.9416 ]
>>
endobj
16 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/article/age-at-onset-in-huntington-disease/)
>>
endobj
17 0 obj
<< /Type /Annot
/Subtype /Link
/A 18 0 R
/Border [0 0 0]
/H /I
/Rect [ 77.5560 699.1581 131.7173 708.8106 ]
>>
endobj
18 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/article_category/epidemiology/)
>>
endobj
19 0 obj
<< /Type /Annot
/Subtype /Link
/A 20 0 R
/Border [0 0 0]
/H /I
/Rect [ 26.2500 687.2933 81.5130 697.2140 ]
>>
endobj
20 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/author/michaelorth/)
>>
endobj
21 0 obj
<< /Type /Annot
/Subtype /Link
/A 22 0 R
/Border [0 0 0]
/H /I
/Rect [ 86.9340 687.2933 168.7560 697.2140 ]
>>
endobj
22 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/author/carstenschwenke/)
>>
endobj
23 0 obj
<< /Type /Annot
/Subtype /Link
/A 24 0 R
/Border [0 0 0]
/H /I
/Rect [ 188.8313 288.4378 198.4686 297.2561 ]
>>
endobj
24 0 obj
<< /Type /Action
>>
endobj
25 0 obj
<< /Type /Annot
/Subtype /Link
/A 26 0 R
/Border [0 0 0]
/H /I
/Rect [ 134.6213 252.7235 144.2586 261.5419 ]
>>
endobj
26 0 obj
<< /Type /Action
>>
endobj
27 0 obj
<< /Type /Annot
/Subtype /Link
/A 28 0 R
/Border [0 0 0]
/H /I
/Rect [ 224.0288 240.8188 233.6661 249.6371 ]
>>
endobj
28 0 obj
<< /Type /Action
>>
endobj
29 0 obj
<< /Type /Annot
/Subtype /Link
/A 30 0 R
/Border [0 0 0]
/H /I
/Rect [ 205.1040 228.9140 221.9693 237.7324 ]
>>
endobj
30 0 obj
<< /Type /Action
>>
endobj
31 0 obj
<< /Type /Annot
/Subtype /Link
/A 32 0 R
/Border [0 0 0]
/H /I
/Rect [ 221.9693 228.9140 229.1973 237.7324 ]
>>
endobj
32 0 obj
<< /Type /Action
>>
endobj
33 0 obj
<< /Type /Annot
/Subtype /Link
/A 34 0 R
/Border [0 0 0]
/H /I
/Rect [ 229.1973 228.9140 231.6067 237.7324 ]
>>
endobj
34 0 obj
<< /Type /Action
>>
endobj
35 0 obj
<< /Type /Annot
/Subtype /Link
/A 36 0 R
/Border [0 0 0]
/H /I
/Rect [ 144.9270 205.1045 154.5643 213.9229 ]
>>
endobj
36 0 obj
<< /Type /Action
>>
endobj
37 0 obj
<< /Type /Annot
/Subtype /Link
/A 38 0 R
/Border [0 0 0]
/H /I
/Rect [ 393.6397 161.8903 420.1424 170.7086 ]
>>
endobj
38 0 obj
<< /Type /Action
>>
endobj
39 0 obj
<< /Type /Annot
/Subtype /Link
/A 40 0 R
/Border [0 0 0]
/H /I
/Rect [ 234.8903 149.9855 261.3929 158.8039 ]
>>
endobj
40 0 obj
<< /Type /Action
>>
endobj
41 0 obj
<< /Type /Annot
/Subtype /Link
/A 42 0 R
/Border [0 0 0]
/H /I
/Rect [ 15.0000 716.1516 328.2570 736.9416 ]
>>
endobj
42 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/article/age-at-onset-in-huntington-disease/)
>>
endobj
43 0 obj
<< /Type /Annot
/Subtype /Link
/A 44 0 R
/Border [0 0 0]
/H /I
/Rect [ 77.5560 699.1581 131.7173 708.8106 ]
>>
endobj
44 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/article_category/epidemiology/)
>>
endobj
45 0 obj
<< /Type /Annot
/Subtype /Link
/A 46 0 R
/Border [0 0 0]
/H /I
/Rect [ 26.2500 687.2933 81.5130 697.2140 ]
>>
endobj
46 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/author/michaelorth/)
>>
endobj
47 0 obj
<< /Type /Annot
/Subtype /Link
/A 48 0 R
/Border [0 0 0]
/H /I
/Rect [ 86.9340 687.2933 168.7560 697.2140 ]
>>
endobj
48 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/author/carstenschwenke/)
>>
endobj
49 0 obj
<< /Type /Annot
/Subtype /Link
/A 50 0 R
/Border [0 0 0]
/H /I
/Rect [ 188.8313 288.4378 198.4686 297.2561 ]
>>
endobj
50 0 obj
<< /Type /Action
>>
endobj
51 0 obj
<< /Type /Annot
/Subtype /Link
/A 52 0 R
/Border [0 0 0]
/H /I
/Rect [ 134.6213 252.7235 144.2586 261.5419 ]
>>
endobj
52 0 obj
<< /Type /Action
>>
endobj
53 0 obj
<< /Type /Annot
/Subtype /Link
/A 54 0 R
/Border [0 0 0]
/H /I
/Rect [ 224.0288 240.8188 233.6661 249.6371 ]
>>
endobj
54 0 obj
<< /Type /Action
>>
endobj
55 0 obj
<< /Type /Annot
/Subtype /Link
/A 56 0 R
/Border [0 0 0]
/H /I
/Rect [ 205.1040 228.9140 221.9693 237.7324 ]
>>
endobj
56 0 obj
<< /Type /Action
>>
endobj
57 0 obj
<< /Type /Annot
/Subtype /Link
/A 58 0 R
/Border [0 0 0]
/H /I
/Rect [ 221.9693 228.9140 229.1973 237.7324 ]
>>
endobj
58 0 obj
<< /Type /Action
>>
endobj
59 0 obj
<< /Type /Annot
/Subtype /Link
/A 60 0 R
/Border [0 0 0]
/H /I
/Rect [ 229.1973 228.9140 231.6067 237.7324 ]
>>
endobj
60 0 obj
<< /Type /Action
>>
endobj
61 0 obj
<< /Type /Annot
/Subtype /Link
/A 62 0 R
/Border [0 0 0]
/H /I
/Rect [ 144.9270 205.1045 154.5643 213.9229 ]
>>
endobj
62 0 obj
<< /Type /Action
>>
endobj
63 0 obj
<< /Type /Annot
/Subtype /Link
/A 64 0 R
/Border [0 0 0]
/H /I
/Rect [ 393.6397 161.8903 420.1424 170.7086 ]
>>
endobj
64 0 obj
<< /Type /Action
>>
endobj
65 0 obj
<< /Type /Annot
/Subtype /Link
/A 66 0 R
/Border [0 0 0]
/H /I
/Rect [ 234.8903 149.9855 261.3929 158.8039 ]
>>
endobj
66 0 obj
<< /Type /Action
>>
endobj
67 0 obj
<< /Type /Annot
/Subtype /Link
/A 68 0 R
/Border [0 0 0]
/H /I
/Rect [ 15.0000 716.1516 328.2570 736.9416 ]
>>
endobj
68 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/article/age-at-onset-in-huntington-disease/)
>>
endobj
69 0 obj
<< /Type /Annot
/Subtype /Link
/A 70 0 R
/Border [0 0 0]
/H /I
/Rect [ 77.5560 699.1581 131.7173 708.8106 ]
>>
endobj
70 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/article_category/epidemiology/)
>>
endobj
71 0 obj
<< /Type /Annot
/Subtype /Link
/A 72 0 R
/Border [0 0 0]
/H /I
/Rect [ 26.2500 687.2933 81.5130 697.2140 ]
>>
endobj
72 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/author/michaelorth/)
>>
endobj
73 0 obj
<< /Type /Annot
/Subtype /Link
/A 74 0 R
/Border [0 0 0]
/H /I
/Rect [ 86.9340 687.2933 168.7560 697.2140 ]
>>
endobj
74 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/author/carstenschwenke/)
>>
endobj
75 0 obj
<< /Type /Annot
/Subtype /Link
/A 76 0 R
/Border [0 0 0]
/H /I
/Rect [ 188.8313 288.4378 198.4686 297.2561 ]
>>
endobj
76 0 obj
<< /Type /Action
>>
endobj
77 0 obj
<< /Type /Annot
/Subtype /Link
/A 78 0 R
/Border [0 0 0]
/H /I
/Rect [ 134.6213 252.7235 144.2586 261.5419 ]
>>
endobj
78 0 obj
<< /Type /Action
>>
endobj
79 0 obj
<< /Type /Annot
/Subtype /Link
/A 80 0 R
/Border [0 0 0]
/H /I
/Rect [ 224.0288 240.8188 233.6661 249.6371 ]
>>
endobj
80 0 obj
<< /Type /Action
>>
endobj
81 0 obj
<< /Type /Annot
/Subtype /Link
/A 82 0 R
/Border [0 0 0]
/H /I
/Rect [ 205.1040 228.9140 221.9693 237.7324 ]
>>
endobj
82 0 obj
<< /Type /Action
>>
endobj
83 0 obj
<< /Type /Annot
/Subtype /Link
/A 84 0 R
/Border [0 0 0]
/H /I
/Rect [ 221.9693 228.9140 229.1973 237.7324 ]
>>
endobj
84 0 obj
<< /Type /Action
>>
endobj
85 0 obj
<< /Type /Annot
/Subtype /Link
/A 86 0 R
/Border [0 0 0]
/H /I
/Rect [ 229.1973 228.9140 231.6067 237.7324 ]
>>
endobj
86 0 obj
<< /Type /Action
>>
endobj
87 0 obj
<< /Type /Annot
/Subtype /Link
/A 88 0 R
/Border [0 0 0]
/H /I
/Rect [ 144.9270 205.1045 154.5643 213.9229 ]
>>
endobj
88 0 obj
<< /Type /Action
>>
endobj
89 0 obj
<< /Type /Annot
/Subtype /Link
/A 90 0 R
/Border [0 0 0]
/H /I
/Rect [ 393.6397 161.8903 420.1424 170.7086 ]
>>
endobj
90 0 obj
<< /Type /Action
>>
endobj
91 0 obj
<< /Type /Annot
/Subtype /Link
/A 92 0 R
/Border [0 0 0]
/H /I
/Rect [ 234.8903 149.9855 261.3929 158.8039 ]
>>
endobj
92 0 obj
<< /Type /Action
>>
endobj
93 0 obj
<< /Type /Page
/Parent 3 0 R
/Annots [ 95 0 R 97 0 R 99 0 R 101 0 R 103 0 R 105 0 R 107 0 R 110 0 R 112 0 R 114 0 R 116 0 R 118 0 R 120 0 R 122 0 R 124 0 R 126 0 R 128 0 R 130 0 R 132 0 R 134 0 R 136 0 R ]
/Contents 94 0 R
>>
endobj
94 0 obj
<<
/Length 20958 >>
stream

0.271 0.267 0.267 rg
q
15.000 30.391 577.500 746.609 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(REGISTRY is collecting data in Europe from symptomatic and pre-HD )] TJ ET
BT 330.762 767.476 Td /F5 9.8 Tf  [(HTT)] TJ ET
BT 349.716 767.476 Td /F1 9.8 Tf  [(mutation expansion carriers \(with known CAG repeat )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(length?36\).)] TJ ET
0.267 0.267 0.267 rg
BT 75.029 755.571 Td /F1 8.7 Tf  [([6] , [7])] TJ ET
0.271 0.267 0.267 rg
BT 101.532 755.571 Td /F1 9.8 Tf  [(Participants had at least three visits where age, gender, CAG repeat length, parent affected, and clinical data )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(\(Unified Huntington�s Disease Rating Scale motor score, total functional capacity\) were available. )] TJ ET
0.267 0.267 0.267 rg
BT 447.284 743.667 Td /F1 8.7 Tf  [([8])] TJ ET
0.271 0.267 0.267 rg
BT 456.922 743.667 Td /F1 9.8 Tf  [(All REGISTRY data were )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(from participants with manifest HD. This was defined as carrying the HD gene mutation and having a motor phenotype that with )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(? 99% certainty was unequivocal for HD \(diagnostic confidence of 4 on motor UHDRS\). )] TJ ET
0.267 0.267 0.267 rg
BT 405.018 719.857 Td /F1 8.7 Tf  [([8])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 700.452 Td /F1 9.8 Tf  [(Participants gave informed written consent according to the International Conference on Harmonisation-Good Clinical Practice )] TJ ET
BT 26.250 688.548 Td /F1 9.8 Tf  [(\(ICH-GCP\) guidelines \()] TJ ET
0.267 0.267 0.267 rg
BT 126.470 688.548 Td /F1 9.8 Tf  [(https://www.ich.org/LOB/media/MEDIA482.pdf)] TJ ET
0.271 0.267 0.267 rg
BT 321.548 688.548 Td /F1 9.8 Tf  [(\). Ethical approval was obtained from the local ethics )] TJ ET
BT 26.250 676.643 Td /F1 9.8 Tf  [(committee for each study site contributing to REGISTRY.)] TJ ET
BT 26.250 657.238 Td /F4 9.8 Tf  [(Data analysis and statistics)] TJ ET
BT 26.250 637.833 Td /F1 9.8 Tf  [(AAO was calculated using generalized linear mixed models based on individual slopes of motor or TFC scores. This means for )] TJ ET
BT 26.250 625.929 Td /F1 9.8 Tf  [(each participant a linear regression was calculated including intercept and slope of the independent factor across visit dates )] TJ ET
BT 26.250 614.024 Td /F1 9.8 Tf  [(\(Figure 1\). Visit was included as random factor. Dependent variables were the date of examination of the motorscore, or TFC, )] TJ ET
BT 26.250 602.119 Td /F1 9.8 Tf  [(independent variables were �motorscore� or �TFC.� The estimates of the regression were then used to extrapolate the AAO by )] TJ ET
BT 26.250 590.214 Td /F1 9.8 Tf  [(calculating the age for a motorscore of 5, or a TFC of 12, our definitions of manifest disease \(Figure 1\).)] TJ ET
BT 26.250 570.810 Td /F1 9.8 Tf  [(For AAO predictions, the formula of Langbehn with the predicted probability of signs exceeding 0.6, 0.4 and 0.2 \(i.e., �Langb )] TJ ET
BT 26.250 558.905 Td /F1 9.8 Tf  [(0.6,� �Langb 0.4,� and �Langb 0.2�\), or the formula of Ranen and colleagues \(�Ranen�\), was used. )] TJ ET
0.267 0.267 0.267 rg
BT 448.415 558.905 Td /F1 8.7 Tf  [([5])] TJ ET
0.271 0.267 0.267 rg
BT 458.053 558.905 Td /F1 9.8 Tf  [( We emulated the )] TJ ET
BT 26.250 547.000 Td /F1 9.8 Tf  [(prodromal stage in our manifest participants by going back in time to when each participant was pre-manifest. We arbitrarily )] TJ ET
BT 26.250 535.095 Td /F1 9.8 Tf  [(chose an age of 10 years. Secondly, we calculated the disease burden from a participant�s age and CAG repeat length \(\(CAG )] TJ ET
BT 570.895 533.031 Td /F1 8.7 Tf  [(n)] TJ ET
BT 26.250 523.191 Td /F1 9.8 Tf  [(-35.5\) X age = disease burden\) and using the Langbehn formula predicted AAO at an age that corresponded to a disease )] TJ ET
BT 26.250 511.286 Td /F1 9.8 Tf  [(burden of 200 \(�LB DB 0.6�\). )] TJ ET
0.267 0.267 0.267 rg
BT 151.976 511.286 Td /F1 8.7 Tf  [([9])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 491.881 Td /F1 9.8 Tf  [(One additional model was based on the CAG repeats, age of affected parent, the motorscore \(population-slope\) and gender as )] TJ ET
BT 26.250 479.976 Td /F1 9.8 Tf  [(independent variables and the rater estimate as dependent variable \(�Ranen extended�\). A second model was estimated )] TJ ET
BT 26.250 468.072 Td /F1 9.8 Tf  [(analogous to the Ranen formula \(�Ranen analog�\) based on CAG repeats and age of affected parent. Linear regression was )] TJ ET
BT 26.250 456.167 Td /F1 9.8 Tf  [(used to assess the importance of these factors for the rater estimate. The regression estimates were used to populate the )] TJ ET
BT 26.250 444.262 Td /F1 9.8 Tf  [(formula.)] TJ ET
BT 26.250 424.857 Td /F1 9.8 Tf  [(The pairwise Pearson correlation coefficients were estimated to investigate the linear correlation of each pair of formulae on )] TJ ET
BT 26.250 412.953 Td /F1 9.8 Tf  [(�AAO.� We compared the different models for predicting AAO by calculating agreement rates with Clopper-Pearson 95% )] TJ ET
BT 26.250 401.048 Td /F1 9.8 Tf  [(confidence intervals between pairs of estimates. If both methods arrived at the same result within a �5 year bracket the )] TJ ET
BT 26.250 389.143 Td /F1 9.8 Tf  [(agreement was defined as �1�. If the results were more than 5 years different the agreement was defined as �0�. For all )] TJ ET
BT 26.250 377.238 Td /F1 9.8 Tf  [(participants, the agreement rate was expressed as % agreement within accepted range.)] TJ ET
0.965 0.965 0.965 rg
26.250 130.162 555.000 237.195 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 367.357 m 581.250 367.357 l 581.250 366.607 l 26.250 366.607 l  f
26.250 130.162 m 581.250 130.162 l 581.250 130.912 l 26.250 130.912 l  f
q
225.000 0 0 147.750 35.250 209.857 cm /I3 Do
Q 
q
35.250 141.412 537.000 62.445 re W n
0.271 0.267 0.267 rg
BT 35.250 192.868 Td /F4 9.8 Tf  [(Figure 1.)] TJ ET
BT 75.888 192.868 Td /F1 9.8 Tf  [( Illustration of age-at-onset extrapolation from longitudinal UHDRS motor, or total functional capacity \(TFC\), )] TJ ET
BT 35.250 179.132 Td /F1 9.8 Tf  [(scores. Linear regression analysis calculates the age for a motorscore of 5 \(motor score threshold\), or a TFC of 12 \(TFC )] TJ ET
BT 35.250 165.396 Td /F1 9.8 Tf  [(threshold\). The vertical lines illustrate the age of the participant at threshold \(motor estimate, TFC estimate\) and how these )] TJ ET
BT 35.250 151.660 Td /F1 9.8 Tf  [(calculated onsets compare to the rater estimate.)] TJ ET
Q
BT 26.250 95.941 Td /F4 12.0 Tf  [(RESULTS)] TJ ET
BT 26.250 75.987 Td /F4 9.8 Tf  [(REGISTRY participants)] TJ ET
BT 26.250 56.582 Td /F1 9.8 Tf  [(Data from 423 REGISTRY participants were included \(205 male\). The mean CAG repeat expansion was 44 \(SD 4\), this was )] TJ ET
BT 26.250 44.677 Td /F1 9.8 Tf  [(similar in men and women. In 193 participants \(46%\) the gene was inherited from the mother and in 177 \(42%\) from the father, )] TJ ET
Q
q
15.000 30.391 577.500 746.609 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(REGISTRY is collecting data in Europe from symptomatic and pre-HD )] TJ ET
BT 330.762 767.476 Td /F5 9.8 Tf  [(HTT)] TJ ET
BT 349.716 767.476 Td /F1 9.8 Tf  [(mutation expansion carriers \(with known CAG repeat )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(length?36\).)] TJ ET
0.267 0.267 0.267 rg
BT 75.029 755.571 Td /F1 8.7 Tf  [([6] , [7])] TJ ET
0.271 0.267 0.267 rg
BT 101.532 755.571 Td /F1 9.8 Tf  [(Participants had at least three visits where age, gender, CAG repeat length, parent affected, and clinical data )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(\(Unified Huntington�s Disease Rating Scale motor score, total functional capacity\) were available. )] TJ ET
0.267 0.267 0.267 rg
BT 447.284 743.667 Td /F1 8.7 Tf  [([8])] TJ ET
0.271 0.267 0.267 rg
BT 456.922 743.667 Td /F1 9.8 Tf  [(All REGISTRY data were )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(from participants with manifest HD. This was defined as carrying the HD gene mutation and having a motor phenotype that with )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(? 99% certainty was unequivocal for HD \(diagnostic confidence of 4 on motor UHDRS\). )] TJ ET
0.267 0.267 0.267 rg
BT 405.018 719.857 Td /F1 8.7 Tf  [([8])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 700.452 Td /F1 9.8 Tf  [(Participants gave informed written consent according to the International Conference on Harmonisation-Good Clinical Practice )] TJ ET
BT 26.250 688.548 Td /F1 9.8 Tf  [(\(ICH-GCP\) guidelines \()] TJ ET
0.267 0.267 0.267 rg
BT 126.470 688.548 Td /F1 9.8 Tf  [(https://www.ich.org/LOB/media/MEDIA482.pdf)] TJ ET
0.271 0.267 0.267 rg
BT 321.548 688.548 Td /F1 9.8 Tf  [(\). Ethical approval was obtained from the local ethics )] TJ ET
BT 26.250 676.643 Td /F1 9.8 Tf  [(committee for each study site contributing to REGISTRY.)] TJ ET
BT 26.250 657.238 Td /F4 9.8 Tf  [(Data analysis and statistics)] TJ ET
BT 26.250 637.833 Td /F1 9.8 Tf  [(AAO was calculated using generalized linear mixed models based on individual slopes of motor or TFC scores. This means for )] TJ ET
BT 26.250 625.929 Td /F1 9.8 Tf  [(each participant a linear regression was calculated including intercept and slope of the independent factor across visit dates )] TJ ET
BT 26.250 614.024 Td /F1 9.8 Tf  [(\(Figure 1\). Visit was included as random factor. Dependent variables were the date of examination of the motorscore, or TFC, )] TJ ET
BT 26.250 602.119 Td /F1 9.8 Tf  [(independent variables were �motorscore� or �TFC.� The estimates of the regression were then used to extrapolate the AAO by )] TJ ET
BT 26.250 590.214 Td /F1 9.8 Tf  [(calculating the age for a motorscore of 5, or a TFC of 12, our definitions of manifest disease \(Figure 1\).)] TJ ET
BT 26.250 570.810 Td /F1 9.8 Tf  [(For AAO predictions, the formula of Langbehn with the predicted probability of signs exceeding 0.6, 0.4 and 0.2 \(i.e., �Langb )] TJ ET
BT 26.250 558.905 Td /F1 9.8 Tf  [(0.6,� �Langb 0.4,� and �Langb 0.2�\), or the formula of Ranen and colleagues \(�Ranen�\), was used. )] TJ ET
0.267 0.267 0.267 rg
BT 448.415 558.905 Td /F1 8.7 Tf  [([5])] TJ ET
0.271 0.267 0.267 rg
BT 458.053 558.905 Td /F1 9.8 Tf  [( We emulated the )] TJ ET
BT 26.250 547.000 Td /F1 9.8 Tf  [(prodromal stage in our manifest participants by going back in time to when each participant was pre-manifest. We arbitrarily )] TJ ET
BT 26.250 535.095 Td /F1 9.8 Tf  [(chose an age of 10 years. Secondly, we calculated the disease burden from a participant�s age and CAG repeat length \(\(CAG )] TJ ET
BT 570.895 533.031 Td /F1 8.7 Tf  [(n)] TJ ET
BT 26.250 523.191 Td /F1 9.8 Tf  [(-35.5\) X age = disease burden\) and using the Langbehn formula predicted AAO at an age that corresponded to a disease )] TJ ET
BT 26.250 511.286 Td /F1 9.8 Tf  [(burden of 200 \(�LB DB 0.6�\). )] TJ ET
0.267 0.267 0.267 rg
BT 151.976 511.286 Td /F1 8.7 Tf  [([9])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 491.881 Td /F1 9.8 Tf  [(One additional model was based on the CAG repeats, age of affected parent, the motorscore \(population-slope\) and gender as )] TJ ET
BT 26.250 479.976 Td /F1 9.8 Tf  [(independent variables and the rater estimate as dependent variable \(�Ranen extended�\). A second model was estimated )] TJ ET
BT 26.250 468.072 Td /F1 9.8 Tf  [(analogous to the Ranen formula \(�Ranen analog�\) based on CAG repeats and age of affected parent. Linear regression was )] TJ ET
BT 26.250 456.167 Td /F1 9.8 Tf  [(used to assess the importance of these factors for the rater estimate. The regression estimates were used to populate the )] TJ ET
BT 26.250 444.262 Td /F1 9.8 Tf  [(formula.)] TJ ET
BT 26.250 424.857 Td /F1 9.8 Tf  [(The pairwise Pearson correlation coefficients were estimated to investigate the linear correlation of each pair of formulae on )] TJ ET
BT 26.250 412.953 Td /F1 9.8 Tf  [(�AAO.� We compared the different models for predicting AAO by calculating agreement rates with Clopper-Pearson 95% )] TJ ET
BT 26.250 401.048 Td /F1 9.8 Tf  [(confidence intervals between pairs of estimates. If both methods arrived at the same result within a �5 year bracket the )] TJ ET
BT 26.250 389.143 Td /F1 9.8 Tf  [(agreement was defined as �1�. If the results were more than 5 years different the agreement was defined as �0�. For all )] TJ ET
BT 26.250 377.238 Td /F1 9.8 Tf  [(participants, the agreement rate was expressed as % agreement within accepted range.)] TJ ET
0.965 0.965 0.965 rg
26.250 130.162 555.000 237.195 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 367.357 m 581.250 367.357 l 581.250 366.607 l 26.250 366.607 l  f
26.250 130.162 m 581.250 130.162 l 581.250 130.912 l 26.250 130.912 l  f
q
225.000 0 0 147.750 35.250 209.857 cm /I3 Do
Q 
q
35.250 141.412 537.000 62.445 re W n
0.271 0.267 0.267 rg
BT 35.250 192.868 Td /F4 9.8 Tf  [(Figure 1.)] TJ ET
BT 75.888 192.868 Td /F1 9.8 Tf  [( Illustration of age-at-onset extrapolation from longitudinal UHDRS motor, or total functional capacity \(TFC\), )] TJ ET
BT 35.250 179.132 Td /F1 9.8 Tf  [(scores. Linear regression analysis calculates the age for a motorscore of 5 \(motor score threshold\), or a TFC of 12 \(TFC )] TJ ET
BT 35.250 165.396 Td /F1 9.8 Tf  [(threshold\). The vertical lines illustrate the age of the participant at threshold \(motor estimate, TFC estimate\) and how these )] TJ ET
BT 35.250 151.660 Td /F1 9.8 Tf  [(calculated onsets compare to the rater estimate.)] TJ ET
Q
BT 26.250 95.941 Td /F4 12.0 Tf  [(RESULTS)] TJ ET
BT 26.250 75.987 Td /F4 9.8 Tf  [(REGISTRY participants)] TJ ET
BT 26.250 56.582 Td /F1 9.8 Tf  [(Data from 423 REGISTRY participants were included \(205 male\). The mean CAG repeat expansion was 44 \(SD 4\), this was )] TJ ET
BT 26.250 44.677 Td /F1 9.8 Tf  [(similar in men and women. In 193 participants \(46%\) the gene was inherited from the mother and in 177 \(42%\) from the father, )] TJ ET
Q
q
15.000 30.391 577.500 746.609 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(REGISTRY is collecting data in Europe from symptomatic and pre-HD )] TJ ET
BT 330.762 767.476 Td /F5 9.8 Tf  [(HTT)] TJ ET
BT 349.716 767.476 Td /F1 9.8 Tf  [(mutation expansion carriers \(with known CAG repeat )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(length?36\).)] TJ ET
0.267 0.267 0.267 rg
BT 75.029 755.571 Td /F1 8.7 Tf  [([6] , [7])] TJ ET
0.271 0.267 0.267 rg
BT 101.532 755.571 Td /F1 9.8 Tf  [(Participants had at least three visits where age, gender, CAG repeat length, parent affected, and clinical data )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(\(Unified Huntington�s Disease Rating Scale motor score, total functional capacity\) were available. )] TJ ET
0.267 0.267 0.267 rg
BT 447.284 743.667 Td /F1 8.7 Tf  [([8])] TJ ET
0.271 0.267 0.267 rg
BT 456.922 743.667 Td /F1 9.8 Tf  [(All REGISTRY data were )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(from participants with manifest HD. This was defined as carrying the HD gene mutation and having a motor phenotype that with )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(? 99% certainty was unequivocal for HD \(diagnostic confidence of 4 on motor UHDRS\). )] TJ ET
0.267 0.267 0.267 rg
BT 405.018 719.857 Td /F1 8.7 Tf  [([8])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 700.452 Td /F1 9.8 Tf  [(Participants gave informed written consent according to the International Conference on Harmonisation-Good Clinical Practice )] TJ ET
BT 26.250 688.548 Td /F1 9.8 Tf  [(\(ICH-GCP\) guidelines \()] TJ ET
0.267 0.267 0.267 rg
BT 126.470 688.548 Td /F1 9.8 Tf  [(https://www.ich.org/LOB/media/MEDIA482.pdf)] TJ ET
0.271 0.267 0.267 rg
BT 321.548 688.548 Td /F1 9.8 Tf  [(\). Ethical approval was obtained from the local ethics )] TJ ET
BT 26.250 676.643 Td /F1 9.8 Tf  [(committee for each study site contributing to REGISTRY.)] TJ ET
BT 26.250 657.238 Td /F4 9.8 Tf  [(Data analysis and statistics)] TJ ET
BT 26.250 637.833 Td /F1 9.8 Tf  [(AAO was calculated using generalized linear mixed models based on individual slopes of motor or TFC scores. This means for )] TJ ET
BT 26.250 625.929 Td /F1 9.8 Tf  [(each participant a linear regression was calculated including intercept and slope of the independent factor across visit dates )] TJ ET
BT 26.250 614.024 Td /F1 9.8 Tf  [(\(Figure 1\). Visit was included as random factor. Dependent variables were the date of examination of the motorscore, or TFC, )] TJ ET
BT 26.250 602.119 Td /F1 9.8 Tf  [(independent variables were �motorscore� or �TFC.� The estimates of the regression were then used to extrapolate the AAO by )] TJ ET
BT 26.250 590.214 Td /F1 9.8 Tf  [(calculating the age for a motorscore of 5, or a TFC of 12, our definitions of manifest disease \(Figure 1\).)] TJ ET
BT 26.250 570.810 Td /F1 9.8 Tf  [(For AAO predictions, the formula of Langbehn with the predicted probability of signs exceeding 0.6, 0.4 and 0.2 \(i.e., �Langb )] TJ ET
BT 26.250 558.905 Td /F1 9.8 Tf  [(0.6,� �Langb 0.4,� and �Langb 0.2�\), or the formula of Ranen and colleagues \(�Ranen�\), was used. )] TJ ET
0.267 0.267 0.267 rg
BT 448.415 558.905 Td /F1 8.7 Tf  [([5])] TJ ET
0.271 0.267 0.267 rg
BT 458.053 558.905 Td /F1 9.8 Tf  [( We emulated the )] TJ ET
BT 26.250 547.000 Td /F1 9.8 Tf  [(prodromal stage in our manifest participants by going back in time to when each participant was pre-manifest. We arbitrarily )] TJ ET
BT 26.250 535.095 Td /F1 9.8 Tf  [(chose an age of 10 years. Secondly, we calculated the disease burden from a participant�s age and CAG repeat length \(\(CAG )] TJ ET
BT 570.895 533.031 Td /F1 8.7 Tf  [(n)] TJ ET
BT 26.250 523.191 Td /F1 9.8 Tf  [(-35.5\) X age = disease burden\) and using the Langbehn formula predicted AAO at an age that corresponded to a disease )] TJ ET
BT 26.250 511.286 Td /F1 9.8 Tf  [(burden of 200 \(�LB DB 0.6�\). )] TJ ET
0.267 0.267 0.267 rg
BT 151.976 511.286 Td /F1 8.7 Tf  [([9])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 491.881 Td /F1 9.8 Tf  [(One additional model was based on the CAG repeats, age of affected parent, the motorscore \(population-slope\) and gender as )] TJ ET
BT 26.250 479.976 Td /F1 9.8 Tf  [(independent variables and the rater estimate as dependent variable \(�Ranen extended�\). A second model was estimated )] TJ ET
BT 26.250 468.072 Td /F1 9.8 Tf  [(analogous to the Ranen formula \(�Ranen analog�\) based on CAG repeats and age of affected parent. Linear regression was )] TJ ET
BT 26.250 456.167 Td /F1 9.8 Tf  [(used to assess the importance of these factors for the rater estimate. The regression estimates were used to populate the )] TJ ET
BT 26.250 444.262 Td /F1 9.8 Tf  [(formula.)] TJ ET
BT 26.250 424.857 Td /F1 9.8 Tf  [(The pairwise Pearson correlation coefficients were estimated to investigate the linear correlation of each pair of formulae on )] TJ ET
BT 26.250 412.953 Td /F1 9.8 Tf  [(�AAO.� We compared the different models for predicting AAO by calculating agreement rates with Clopper-Pearson 95% )] TJ ET
BT 26.250 401.048 Td /F1 9.8 Tf  [(confidence intervals between pairs of estimates. If both methods arrived at the same result within a �5 year bracket the )] TJ ET
BT 26.250 389.143 Td /F1 9.8 Tf  [(agreement was defined as �1�. If the results were more than 5 years different the agreement was defined as �0�. For all )] TJ ET
BT 26.250 377.238 Td /F1 9.8 Tf  [(participants, the agreement rate was expressed as % agreement within accepted range.)] TJ ET
0.965 0.965 0.965 rg
26.250 130.162 555.000 237.195 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 367.357 m 581.250 367.357 l 581.250 366.607 l 26.250 366.607 l  f
26.250 130.162 m 581.250 130.162 l 581.250 130.912 l 26.250 130.912 l  f
q
225.000 0 0 147.750 35.250 209.857 cm /I3 Do
Q 
q
35.250 141.412 537.000 62.445 re W n
0.271 0.267 0.267 rg
BT 35.250 192.868 Td /F4 9.8 Tf  [(Figure 1.)] TJ ET
BT 75.888 192.868 Td /F1 9.8 Tf  [( Illustration of age-at-onset extrapolation from longitudinal UHDRS motor, or total functional capacity \(TFC\), )] TJ ET
BT 35.250 179.132 Td /F1 9.8 Tf  [(scores. Linear regression analysis calculates the age for a motorscore of 5 \(motor score threshold\), or a TFC of 12 \(TFC )] TJ ET
BT 35.250 165.396 Td /F1 9.8 Tf  [(threshold\). The vertical lines illustrate the age of the participant at threshold \(motor estimate, TFC estimate\) and how these )] TJ ET
BT 35.250 151.660 Td /F1 9.8 Tf  [(calculated onsets compare to the rater estimate.)] TJ ET
Q
BT 26.250 95.941 Td /F4 12.0 Tf  [(RESULTS)] TJ ET
BT 26.250 75.987 Td /F4 9.8 Tf  [(REGISTRY participants)] TJ ET
BT 26.250 56.582 Td /F1 9.8 Tf  [(Data from 423 REGISTRY participants were included \(205 male\). The mean CAG repeat expansion was 44 \(SD 4\), this was )] TJ ET
BT 26.250 44.677 Td /F1 9.8 Tf  [(similar in men and women. In 193 participants \(46%\) the gene was inherited from the mother and in 177 \(42%\) from the father, )] TJ ET
Q
q
225.000 0 0 147.750 35.250 209.857 cm /I3 Do
Q 
q
0.000 0.000 0.000 rg
BT 291.710 19.825 Td /F1 11.0 Tf  [(2)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Huntington Disease)] TJ ET

Q
endstream
endobj
95 0 obj
<< /Type /Annot
/Subtype /Link
/A 96 0 R
/Border [0 0 0]
/H /I
/Rect [ 75.0292 754.7698 101.5319 763.5881 ]
>>
endobj
96 0 obj
<< /Type /Action
>>
endobj
97 0 obj
<< /Type /Annot
/Subtype /Link
/A 98 0 R
/Border [0 0 0]
/H /I
/Rect [ 447.2842 742.8650 456.9216 751.6834 ]
>>
endobj
98 0 obj
<< /Type /Action
>>
endobj
99 0 obj
<< /Type /Annot
/Subtype /Link
/A 100 0 R
/Border [0 0 0]
/H /I
/Rect [ 405.0180 719.0555 414.6553 727.8739 ]
>>
endobj
100 0 obj
<< /Type /Action
>>
endobj
101 0 obj
<< /Type /Annot
/Subtype /Link
/A 102 0 R
/Border [0 0 0]
/H /I
/Rect [ 126.4702 687.6458 321.5482 697.5665 ]
>>
endobj
102 0 obj
<< /Type /Action
/S /URI
/URI (https://www.ich.org/LOB/media/MEDIA482.pdf)
>>
endobj
103 0 obj
<< /Type /Annot
/Subtype /Link
/A 104 0 R
/Border [0 0 0]
/H /I
/Rect [ 448.4153 558.1033 458.0526 566.9216 ]
>>
endobj
104 0 obj
<< /Type /Action
>>
endobj
105 0 obj
<< /Type /Annot
/Subtype /Link
/A 106 0 R
/Border [0 0 0]
/H /I
/Rect [ 151.9762 510.4843 161.6136 519.3026 ]
>>
endobj
106 0 obj
<< /Type /Action
>>
endobj
107 0 obj
<< /Type /Annot
/Subtype /Link
/A 108 0 R
/Border [0 0 0]
/H /I
/Rect [ 35.2500 209.8575 260.2500 357.6075 ]
>>
endobj
108 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/files/2011/07/Figure-1.jpg)
>>
endobj
109 0 obj
<<
/Type /XObject
/Subtype /Image
/Width 300
/Height 197
/ColorSpace /DeviceRGB
/Filter /DCTDecode
/BitsPerComponent 8
/Length 9629>>
stream
����JFIF



��;CREATOR: gd-jpeg v1.0 (using IJG JPEG v62), quality = 90
��C




��C
		

���
,
"

��







	
���

}
!1AQa"q2���#B��R��$3br�	
%&'()*456789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz���������������������������������������������������������������������������










	
���

w
!1AQaq"2�B����	#3R�br�
$4�%�&'()*56789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz��������������������������������������������������������������������������
?�R�f��@�~��vS�5����K��2E,>`����܊�����n����~���P��,a��"�@���b�҂N3.��z��u����i�����h�u_�����G�㵋㏈v^k&������洄�!h���`8�r�’Nb�ﭘJ�~���v��B9��w�N��?�����v�'U���O��;\L��=��}�G�5�����>v�!@UO,
����h?
i�)�~rQa);I66���Ҁ;�'U���O��;G������?����&�s��a��
?4
�����i�����j������?���ǣ��=}�^�]��ů�t��Z�!�u_�����G��U���K�\����k[5Z��[��S@��W�-?����N��?v����v�sEgy:�����#��ڎ�uhm��vyE-ͣ��Z��W�?�������
��T�Z�#���_'U���O��;Z	�җ4
�����i�����h�u_�����G�㵣�3@�N��?�����v�'U���O��;Z9�4
�����i�����h�u_�����G�㵣��}�[i�
ĞZ��%I�=��������
�������i�����jv�-U��@(�;����i��1a��w�������W�-?����N��?�����v��z��8�I�I2����2���gq*�M�7M�W<g���@������?��������
��Ӧ�,��~�%�q͸.�l�X~�O�O:͚̑���v�Üu���W�-?����N��?�����v��y
�&T�a������`h;������
���M7]O��c{{h/�̑D��iUX�q��{V�k���k�j��{He���q[�@�OQ�h��E��8��h���5�Ww�K��˥��Z[�\B��r��9c���c�;�����
/�Ss�K�u�/N��"��i�0]4�N2yt*�c���
s����ٷ_O��+"f�\�H%Nc�����K�m}5<M�	d�&�u�U+�g9�I���P���c_�Q�x�]��JGr7L.q�H��7uχ:���Y��I�ٽ�i��T<���
����½~4
Q
�<�����K���x���V�F(��w�<b�������ou�Z�*/���Z��5���K��������+P���1�����{G���"��c�C��֏j�g���h�.��_����4y�_��/�����F8�
�e������&��E�Z#5��oud ����K��j�+���$WMU��A���m��7�����g�Y䶹�H��z�6�A���Ze������&��#�W��̍�.�#Mlz,��$I.?�W��T֬�[	/on��������^qɠ	<˯����?�Me������&��|y��N�km^�[��X�
�}���jZ�\����L����2q�(
���_����4y���/����Sl��s�2~q�E�c?���@�6*�diA��O2��x���Uol�EI��eS�4���BkB9RPLn�
��s�?�
���{+���R�l�8'>�y5+�J�?�QX���`��:�+�P�^dk@�%�b	枀?�эCd�Z8R%�I�L�6�?*���sR�:�Ѹ���B������Z��h�l���A�WQ����6��9c��$}�4��wگ��_��/�����EU�.��_����5��_k1x���O�m6k�~�u��5�G� n�r8��1Y.�y�d�������
���^(�P{QE!�W��{/\�� �Pѧ�����؈��d��K�܁һ�
�"oGa⻍Yu}F�[˛p�]�c��s���;�J)M�3E~t�Թ�5V��}��t��Z��U.^{R�ޑ���@꽗Y�롤���tՈ�\�l%q\&�=d�}�l���]
Y���@W�?��������ځ�A���m��;�^��ZƟ+�,�4S�߆U;�E�V��x��Y�]Ώ<���P����>r�I����찮�~��W���;�6�(O��`�z�y>T���l1��~��W�}7B���O���@hbe	pU�����Af�Fs�k�տg_
k7�wsO~�]�I#ó���]��O��Ǩ+����>�<�ً�6�2F����Y��#*1+����TV,gYGo{��E�$�!æp�ܟS����(��?��|�Oe��q$3N��� �](���(��(��QEW3�h6W�!��愵��ċ��ma��p:���W!m��Xx���7wV��34��!|�R�F@�����㱠�QHis@u���
�E��\u)4�,���qk���#4�����'
q��zS~u�M�K�]i0iW�����=����0�.>|t>����RQڀ񢎔w��Ǝ�Ps�ȓi�ҹ/@�XD�0Z��<��?�u��$
F���\���/a
2ܲ��#���>i��x^{���P�E��Б���7J��0��������q�����&[��.S��P�� �3�������������CҼ~�P�$��wh�ݦ��S2�%>C��J�-��j���^7�%��mf�TU7Z~��1�X� ���#9���=�>��E}g������L����e#�>��R��<y.�=߅o�i.4��iZ�̜FĞ��(��	�»0s���C�������'����H�������(z:��[^�����-��֏n�ĭ��\pX������GZJZ?(����h��
(��~4
(�4Qފ+#E#�z�#�>���V�sN�$�(�5}r�F�
�<�%c;��w``��LԸ����h4V��ˏ�3^խ!V3�E!�#,�����?��j^<�g����6����Y����)�@ۻ��z�9�ָ��SW���eq��4�n-�
D\����c�F��v$dW��'�w>��
��쑤N.U��s��L
�E%-�>��Pf���l��n�W7�˛[�h^��m�XH�ņ��<���!����
�HE��t�o�V�ia
ȥK]1
������L�4
��SX�I�E7:=��n��|wX�CǐAa�u9�5�X�Vc�y�����ҝS�vf�+�{��|��U,�f�|��:���t�^��7�t4
c4Q�(��Y!����I�t7C\\i�y��-w6W;��q�;��Q�k�4/�:o��A�\�WBe@ң�������x.xc��d���N���Jw�@� �ᴣ�W�e�����{�8���Mѹ�G���+��?xq|O��f$�=�e���}�&C�7F��#��
�r)s\��<F�#ф�mF������3����VS޺Pf�^)�����(��
(��
8��+��u�h�O�i$���]�Tym�b�j~lm�Xq��MY:.
ެq�/^���(W�K���
�~*@n~���̚U҅!�t�a~c�s\��!��w�	������tet�H��@�=r<0+�����ះ~%�!�����N�XnedU�@�a%�_���Vg������f��j��Ϩ�$�t�#l.VF\�� ���;�r{��u��B����sk���Ww0,Z[�b\pJ���O'&�S^z�7��<u{g�����Ÿ��mE�a|�C�����C��f�
SE%-����K�������ej�Un�����O����Py"���?�t5f�Y�����KI�A"�
�����L��U�������*�>��)y��
��Ի�:�����K�Mg
:�=h�|�E�]���E���k-�y�?��ᔟ�^���q�z�������]�[˒�k�A"���������Mq���K��
^h��Kw��%J��yg���H#�,�v,�J��*������_���S�Y�- �ۣ) �pr85�@	KEQEQ@��QFh5��V�_�ڍ�ݕ�I]�"ᜬd9n�F=����sI���^��ƺ�j+N�ۆ�X�lu�H��+��t�x�T�,munt�y���x�;�x�P�9�f�3��m_��|S�}OJ�,\�t��5�,�gP���1�NY�;��H�@w�A]����SYٛ��,�
n��+8��aGrp�S��x�f~�q]C�/���\�*�����������@�=
ҽX��@�8�::��&�����o^'������+���fM�7���⸻�K}�t��j6���[�ԥ����p��'oC��;R'z)h�%P
A���J�w������V�����_�����Z��}g����U{>���C@~>�5�S@x����#�)�wr��1���lm>���x_�v�
�?��]-�n��pZbH*Ę��9�rq�1�P�A�|Q��M��\����F/���,�u��pNG������=H����Oc'�#�.��;s�2�~�z=A�Dž��so�@N4O��Epm�}<I$��] X�W����8'�"�t_��
���M,�f�agq��mۓ�9��J ���
��q�+��]��?�<S��.4S4��}�

|��@u�NKo��e��<K�YY�ڼ�wN�>\��UU=>�6�A��څ����%�s�m�
>�b�]]�"a�A����˒ڗ��%�ŝ�_�CL��� ��F>���e�ݏ�<1��7A��4Kt�&�%����v���s_��?|)'�|8��Mk���\�F�UI裰ş6�����rIwk�K\�H14 �x�2���ؚ�h �yo�|i�i�)o��O�����R�8/Ɋ>bU���2@�[�_R�������-���-DFUˣ�[�T䂢T�ײ�3��>?𥦤"�Ǖu
0a��A9�s�ހ:ޔb�JZ(��
);R�
E%-�M���K���1�J��J! d�q[u�i
��O�*���7�w%��6���:m���
Ӏ(ǵ��QE#�Wy{�	<N���m�:w6���.�M+�=�.NNEv��W}a�E�v��բ�E���mt��
�a���99>�PcKIF3@E��h擵�R��}��t��Z��K�������ej�ګ�u����U����]
Y��JZ�������ʧ�+Ǿ6�[�Ð
@t���m�%J�j��Al�
�I�
I��=K�kO�v
������W�g����{Wg`~!�>Gؼ��W�:�g;��琿����7%��Ʃm��g�:uğh0�X��gr���o(�Q�,If�׷*�ڀ�bP��T8S���RR���9�	&��C ��������gNQ�����Xw���<K{�����
�E�k�څ�\K�v��p��pU�:�}<@5�~<�
�z��m�M�Ǒz �k{�B"�r2����
v�=*ѫ��
�S�����ݎ�-��l�<��X��$�B��pI<��Q�(��(��1@+F��UF`�IА9�U�\�I�
KS6��hG+[���,d�}	U�����1@Q@FEqW~K?ɫ�_P�{�����\�o^7"v'��v���K_	E��km��R�k��3�S��I���ր=���f�
N��Pf��(����k�]?�V�UV��}��t��Z�-
�g���jȪ�]g����,�('�6���[�^��{y�X�խI�&÷y���^>�����i��h~E����pAj��̥s�����Nr
���4�wD�^��~!�
��:V�z��߈���V��IeF �76N{8�u�U.�&H��l�:O8���O�l��}WV�,.d]B{+y��b�`�x���0�b2��u�
8��Q�N4��W�N4�����
3K�;Pf�Z(���f�
(��
=(��
(��+��o.c��j�l��+�����p��z�N���b�4V�KղrׯO�(^�(�QE%q7���<g&��=���i�
g�)��
|��#o#���W%�j���(M>MX��^�X�C:��0h���<�s�@mR�
E�R�ڒ�5R��>-����n����ů�t��Z�,�[V���z��^C������<k�]Ea��q���e)<d�B��WR˵p۶���?��)t�\F�csu���TJ�#p1�y�A� T�~}��Z�`#8�'Rl�d��p��ٜ��!�	~Zh���X�oi�l�Y��� o�*v�^Q��(�*
@����6�U=A�Ǎ��so�@'�JRi��:��;Q@�3E(
(�S�54����Q�=�O�2Fj��%�P7�)<a�9���@���+�Y#qt�>y�g�\����id��w�O���
z+is��� x�ߜ�����J�<O�J2�����j�����I��Α[�$��6sP��
6��KY��Fdb�@'�O�~��
�Eb��k!F��x���:���pj��m�Ib��G#�@��t��������#��	�C,d�_�|���KX:E�MkR���$�(�a�6�C�����P�J
~tQEW-��[[�"K1�y��aь�v���q�n�w�]Er�!���V�S�U�=9Z͛*Ճ��X���g���e��������*����������	��?��b�x�K.���}��0dP��������6]��X���⪫x�J@I���dR��dg�����A@v]��X�����w�=a��g������Pp����$0g��J|G������
����z��~��U���ϵ̑g�?���u����T�ufSЉ
^��Zg�k��o���z~V�
-��������|)u�iumB�+����_(���i��Hy�2I���������
�g�=,�nzzH(DGt��~��K���z��~��U_ĺTc-nq� ����L���?�@v���X������7�/�m�,ϧ���6�X��-��"��<G�����>�~���=(���щa��3��R�����߳��UT�������z
?�%��m����y�8�[.��������*���������|G��~���
D�.��uvR2�h�˿����?�Un��?����UP��JVU:��'����$z_����}��{I��1��H����Tf�ս�&K{W'$���������JpH�-�ӉQC��K@7_ۨ'2�
xj݊�S��<0?���7�㸎8����J,m+��۽�o�H���������m)��ܑ�y�����|����G�z��t��>����Z�s�a���;��JE,���I2
�w�$zg��A�A���t�(���@�Dt��qM����<��k,����rz���:��](���}��<��R�i��_�����+�����[�79���U�-5���V�g�<�j�q��ꚾ%ҝC.�n�FA���ʧP�z ɠ[.��?����U��+�[� ��������S������+A���������i۞/�����	��둴��}(��8��(����<g�뺎��x~�����V2�[�(:���zs�N��A�����8R��5�aa�E�=B{��Yt���v�e��3��w�#����
��+MB�D��H���Rx�`��/64sв�2=�Rh������O����v�>9*A�У�s�v��+��+�E��Z��3��D��N�1�'�xغ�G��`*�!�pV���b������a������_jj[̞����a	l``u�<A��Z��.�}gka��a���$ˑ���!����Q@�1�V���z�u/���+����6v�
Q�c��v�]
(�i�ƣcZ-���p&Fynm��Pud`�������6����>��9�'N�m�K��_��O���v�Z��{{�;��k�VZ���.ml�W�m����F�� ##�[�f�����@�`���R����y�)�HV`9 P�\w0閩$3�,J'�ڍ&��
9���-��,��
��>���&zt����)�����[�-�
�_i���x��A��Et��ߗg;�u���G��.�?�e���b���s7�'E�" 9*K��\�����u��t�x�1��Ir�c�Gpj��-B�F��U���R$��/)�0���xg�*ߍ�_�y�.��4�46���4#w����|�p��޽�������X��^�oeWs��2P�;g�H<��5�;]�����8t������I
�67���[� �s��ъ�#�kv��^�_NҖ��-������<�|_�뺄K��Y���r�pז�xx�9U�6q�j���?*�?�k���>�gw���l`����Al�l��y�����񖟬j����ݮ�����:%�grdg##�i��4vP-�$�+�]j��`Oj�Es�i���|ג^۝ۈ�[q�s�=:�Z:յ�Ɠw�,v��,K�G#�b��=��
��{-N�C��Y����P,֐�Q�'W'`U-cM��*��t��(tH���Y���)#�(��y�k��EE$d�lpH��� �t�b����|ffIl-�イ�s��޺:(��(�A��NԦ�(
(�E���PiqE�
袀
\sE��1AQ@	��QE��P
���J\QE�QE��Q@�(�h��:
(��
1E
��
endstream
endobj
110 0 obj
<< /Type /Annot
/Subtype /Link
/A 111 0 R
/Border [0 0 0]
/H /I
/Rect [ 75.0292 754.7698 101.5319 763.5881 ]
>>
endobj
111 0 obj
<< /Type /Action
>>
endobj
112 0 obj
<< /Type /Annot
/Subtype /Link
/A 113 0 R
/Border [0 0 0]
/H /I
/Rect [ 447.2842 742.8650 456.9216 751.6834 ]
>>
endobj
113 0 obj
<< /Type /Action
>>
endobj
114 0 obj
<< /Type /Annot
/Subtype /Link
/A 115 0 R
/Border [0 0 0]
/H /I
/Rect [ 405.0180 719.0555 414.6553 727.8739 ]
>>
endobj
115 0 obj
<< /Type /Action
>>
endobj
116 0 obj
<< /Type /Annot
/Subtype /Link
/A 117 0 R
/Border [0 0 0]
/H /I
/Rect [ 126.4702 687.6458 321.5482 697.5665 ]
>>
endobj
117 0 obj
<< /Type /Action
/S /URI
/URI (https://www.ich.org/LOB/media/MEDIA482.pdf)
>>
endobj
118 0 obj
<< /Type /Annot
/Subtype /Link
/A 119 0 R
/Border [0 0 0]
/H /I
/Rect [ 448.4153 558.1033 458.0526 566.9216 ]
>>
endobj
119 0 obj
<< /Type /Action
>>
endobj
120 0 obj
<< /Type /Annot
/Subtype /Link
/A 121 0 R
/Border [0 0 0]
/H /I
/Rect [ 151.9762 510.4843 161.6136 519.3026 ]
>>
endobj
121 0 obj
<< /Type /Action
>>
endobj
122 0 obj
<< /Type /Annot
/Subtype /Link
/A 123 0 R
/Border [0 0 0]
/H /I
/Rect [ 35.2500 209.8575 260.2500 357.6075 ]
>>
endobj
123 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/files/2011/07/Figure-1.jpg)
>>
endobj
124 0 obj
<< /Type /Annot
/Subtype /Link
/A 125 0 R
/Border [0 0 0]
/H /I
/Rect [ 75.0292 754.7698 101.5319 763.5881 ]
>>
endobj
125 0 obj
<< /Type /Action
>>
endobj
126 0 obj
<< /Type /Annot
/Subtype /Link
/A 127 0 R
/Border [0 0 0]
/H /I
/Rect [ 447.2842 742.8650 456.9216 751.6834 ]
>>
endobj
127 0 obj
<< /Type /Action
>>
endobj
128 0 obj
<< /Type /Annot
/Subtype /Link
/A 129 0 R
/Border [0 0 0]
/H /I
/Rect [ 405.0180 719.0555 414.6553 727.8739 ]
>>
endobj
129 0 obj
<< /Type /Action
>>
endobj
130 0 obj
<< /Type /Annot
/Subtype /Link
/A 131 0 R
/Border [0 0 0]
/H /I
/Rect [ 126.4702 687.6458 321.5482 697.5665 ]
>>
endobj
131 0 obj
<< /Type /Action
/S /URI
/URI (https://www.ich.org/LOB/media/MEDIA482.pdf)
>>
endobj
132 0 obj
<< /Type /Annot
/Subtype /Link
/A 133 0 R
/Border [0 0 0]
/H /I
/Rect [ 448.4153 558.1033 458.0526 566.9216 ]
>>
endobj
133 0 obj
<< /Type /Action
>>
endobj
134 0 obj
<< /Type /Annot
/Subtype /Link
/A 135 0 R
/Border [0 0 0]
/H /I
/Rect [ 151.9762 510.4843 161.6136 519.3026 ]
>>
endobj
135 0 obj
<< /Type /Action
>>
endobj
136 0 obj
<< /Type /Annot
/Subtype /Link
/A 137 0 R
/Border [0 0 0]
/H /I
/Rect [ 35.2500 209.8575 260.2500 357.6075 ]
>>
endobj
137 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/files/2011/07/Figure-1.jpg)
>>
endobj
138 0 obj
<< /Type /Page
/Parent 3 0 R
/Annots [ 140 0 R 143 0 R 145 0 R ]
/Contents 139 0 R
>>
endobj
139 0 obj
<<
/Length 53052 >>
stream

0.271 0.267 0.267 rg
q
15.000 44.124 577.500 732.876 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(in 30 \(7%\) no signs of HD were reported in either parent, and in 23 \(5%\) the inheritance was unknown for both parents or for at )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(least one parent, where the other parent was not affected. Eight participants \(2%\) had a juvenile onset \(before the age of 20\), )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(and 24 \(6%\) had a late onset of HD above age 60. A motor onset was present in 303, other onset types in 120. The average )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(motor score at enrolment was 35 \(out of a possible 124\), 158 \(37%\) participants were in stage 1, 120 \(28%\) in stage 2, 111 )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(\(26%\) in stage 3, 30 \(7%\) in stage 4 and 4 \(1%\) in stage 5. Patients were first seen by investigators a median of 6 years after )] TJ ET
BT 26.250 707.952 Td /F1 9.8 Tf  [(the estimated onset. The medium number of visits was 3 \(range 3-18\).)] TJ ET
BT 26.250 688.548 Td /F4 9.8 Tf  [(AAO extrapolation from longitudinal data)] TJ ET
BT 26.250 669.143 Td /F1 9.8 Tf  [(Sixty-six participants with a negative slope of the motor score were excluded because no individual AAO could be calculated. In )] TJ ET
BT 26.250 657.238 Td /F1 9.8 Tf  [(the remaining 357 participants, on average the motor score increased linearly by 2.57 points per year. The mean AAO of data )] TJ ET
BT 26.250 645.333 Td /F1 9.8 Tf  [(based extrapolated motor signs was 47 \(range 13-81, SD 11.67\).)] TJ ET
BT 26.250 625.929 Td /F1 9.8 Tf  [(Forty-four participants were excluded because the slope of the TFC was positive. This meant no individual TFC onset could be )] TJ ET
BT 26.250 614.024 Td /F1 9.8 Tf  [(extrapolated based on longitudinal data. In the remaining 379 participants, on average the TFC score decreased linearly by 0.52 )] TJ ET
BT 26.250 602.119 Td /F1 9.8 Tf  [(points per year. The TFC of the 251 patients in disease stages 1 or 2 decreased by 0.75 points per year compared to 128 )] TJ ET
BT 26.250 590.214 Td /F1 9.8 Tf  [(patients in disease stages 3, 4, or 5 who on average lost 0.26 points per year. The mean extrapolated AAO was 48 \(range 14-)] TJ ET
BT 26.250 578.310 Td /F1 9.8 Tf  [(81, SD 12, Figure 2\).)] TJ ET
BT 26.250 558.905 Td /F1 9.8 Tf  [(The investigator estimated AAO was 3 years before the motorscore calculated AAO \(Table 1, Figure 2\) with an agreement rate )] TJ ET
BT 26.250 547.000 Td /F1 9.8 Tf  [(of 0.57 \(Table 2\). The calculated TFC onset was 4 years later than the investigator�s estimate \(Table 1, Figure 2\) with an )] TJ ET
BT 26.250 535.095 Td /F1 9.8 Tf  [(agreement rate of 0.52 \(Table 2\).)] TJ ET
0.965 0.965 0.965 rg
26.250 284.269 555.000 240.945 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 525.214 m 581.250 525.214 l 581.250 524.464 l 26.250 524.464 l  f
26.250 284.269 m 581.250 284.269 l 581.250 285.019 l 26.250 285.019 l  f
q
225.000 0 0 151.500 35.250 363.964 cm /I4 Do
Q 
q
35.250 295.519 537.000 62.445 re W n
0.271 0.267 0.267 rg
BT 35.250 346.975 Td /F4 9.8 Tf  [(Figure 2.)] TJ ET
BT 75.888 346.975 Td /F1 9.8 Tf  [( REGISTRY data: difference to rater estimate. The boxes of the boxplots contain 50% of the data and the median )] TJ ET
BT 35.250 333.239 Td /F1 9.8 Tf  [(\(vertical solid line\), the bars indicate the 25%tile and the empty dots outliers. Abbreviations: TFC ind: regression derived )] TJ ET
BT 35.250 319.503 Td /F1 9.8 Tf  [(TFC age-at-onset. TFC ind � 4 ys: regression derived TFC age-at-onset minus 4 years. Motorscore ind: regression derived )] TJ ET
BT 35.250 305.767 Td /F1 9.8 Tf  [(motor age-at-onset. R. analog: Ranen analogous. R. extended: Ranen extended.)] TJ ET
Q
BT 26.250 267.246 Td /F4 9.8 Tf  [(Table 1.)] TJ ET
1.000 1.000 1.000 rg
26.250 112.933 555.000 144.431 re f
0.267 0.267 0.267 rg
26.625 256.240 148.908 0.750 re f
26.625 240.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 246.385 Td /F4 9.8 Tf  [(Model)] TJ ET
0.267 0.267 0.267 rg
174.783 256.240 42.418 0.750 re f
174.783 240.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 180.033 246.385 Td /F4 9.8 Tf  [(N)] TJ ET
0.267 0.267 0.267 rg
216.451 256.240 57.161 0.750 re f
216.451 240.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 221.701 246.385 Td /F4 9.8 Tf  [(mean)] TJ ET
0.267 0.267 0.267 rg
272.862 256.240 55.443 0.750 re f
272.862 240.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 278.112 246.385 Td /F4 9.8 Tf  [(SD)] TJ ET
0.267 0.267 0.267 rg
327.556 256.240 44.136 0.750 re f
327.556 240.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 332.806 246.385 Td /F4 9.8 Tf  [(min)] TJ ET
0.267 0.267 0.267 rg
370.942 256.240 46.760 0.750 re f
370.942 240.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 376.192 246.385 Td /F4 9.8 Tf  [(Q25)] TJ ET
0.267 0.267 0.267 rg
416.951 256.240 71.045 0.750 re f
416.951 240.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 422.201 246.385 Td /F4 9.8 Tf  [(median)] TJ ET
0.267 0.267 0.267 rg
487.247 256.240 46.760 0.750 re f
487.247 240.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 492.497 246.385 Td /F4 9.8 Tf  [(Q75)] TJ ET
0.267 0.267 0.267 rg
533.256 256.240 47.619 0.750 re f
533.256 240.358 0.750 16.631 re f
580.125 240.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 538.506 246.385 Td /F4 9.8 Tf  [(max)] TJ ET
0.267 0.267 0.267 rg
26.625 240.358 148.908 0.750 re f
26.625 224.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 230.503 Td /F4 9.8 Tf  [(investigator \(rater estimate\))] TJ ET
0.267 0.267 0.267 rg
174.783 240.358 42.418 0.750 re f
174.783 224.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 180.033 230.503 Td /F1 9.8 Tf  [(423)] TJ ET
0.267 0.267 0.267 rg
216.451 240.358 57.161 0.750 re f
216.451 224.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 221.701 230.503 Td /F1 9.8 Tf  [(44.08)] TJ ET
0.267 0.267 0.267 rg
272.862 240.358 55.443 0.750 re f
272.862 224.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 278.112 230.503 Td /F1 9.8 Tf  [(11.32)] TJ ET
0.267 0.267 0.267 rg
327.556 240.358 44.136 0.750 re f
327.556 224.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 332.806 230.503 Td /F1 9.8 Tf  [(10)] TJ ET
0.267 0.267 0.267 rg
370.942 240.358 46.760 0.750 re f
370.942 224.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 376.192 230.503 Td /F1 9.8 Tf  [(35.5)] TJ ET
0.267 0.267 0.267 rg
416.951 240.358 71.045 0.750 re f
416.951 224.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 422.201 230.503 Td /F1 9.8 Tf  [(44)] TJ ET
0.267 0.267 0.267 rg
487.247 240.358 46.760 0.750 re f
487.247 224.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 492.497 230.503 Td /F1 9.8 Tf  [(51.5)] TJ ET
0.267 0.267 0.267 rg
533.256 240.358 47.619 0.750 re f
533.256 224.477 0.750 16.631 re f
580.125 224.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 538.506 230.503 Td /F1 9.8 Tf  [(77)] TJ ET
0.267 0.267 0.267 rg
26.625 224.477 148.908 0.750 re f
26.625 208.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 214.622 Td /F4 9.8 Tf  [(Motor score)] TJ ET
0.267 0.267 0.267 rg
174.783 224.477 42.418 0.750 re f
174.783 208.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 180.033 214.622 Td /F1 9.8 Tf  [(357)] TJ ET
0.267 0.267 0.267 rg
216.451 224.477 57.161 0.750 re f
216.451 208.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 221.701 214.622 Td /F1 9.8 Tf  [(47.06)] TJ ET
0.267 0.267 0.267 rg
272.862 224.477 55.443 0.750 re f
272.862 208.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 278.112 214.622 Td /F1 9.8 Tf  [(11.7)] TJ ET
0.267 0.267 0.267 rg
327.556 224.477 44.136 0.750 re f
327.556 208.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 332.806 214.622 Td /F1 9.8 Tf  [(13)] TJ ET
0.267 0.267 0.267 rg
370.942 224.477 46.760 0.750 re f
370.942 208.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 376.192 214.622 Td /F1 9.8 Tf  [(38)] TJ ET
0.267 0.267 0.267 rg
416.951 224.477 71.045 0.750 re f
416.951 208.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 422.201 214.622 Td /F1 9.8 Tf  [(47)] TJ ET
0.267 0.267 0.267 rg
487.247 224.477 46.760 0.750 re f
487.247 208.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 492.497 214.622 Td /F1 9.8 Tf  [(56)] TJ ET
0.267 0.267 0.267 rg
533.256 224.477 47.619 0.750 re f
533.256 208.596 0.750 16.631 re f
580.125 208.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 538.506 214.622 Td /F1 9.8 Tf  [(81)] TJ ET
0.267 0.267 0.267 rg
26.625 208.596 148.908 0.750 re f
26.625 192.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 198.741 Td /F4 9.8 Tf  [(TFC score)] TJ ET
0.267 0.267 0.267 rg
174.783 208.596 42.418 0.750 re f
174.783 192.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 180.033 198.741 Td /F1 9.8 Tf  [(379)] TJ ET
0.267 0.267 0.267 rg
216.451 208.596 57.161 0.750 re f
216.451 192.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 221.701 198.741 Td /F1 9.8 Tf  [(48)] TJ ET
0.267 0.267 0.267 rg
272.862 208.596 55.443 0.750 re f
272.862 192.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 278.112 198.741 Td /F1 9.8 Tf  [(12)] TJ ET
0.267 0.267 0.267 rg
327.556 208.596 44.136 0.750 re f
327.556 192.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 332.806 198.741 Td /F1 9.8 Tf  [(14)] TJ ET
0.267 0.267 0.267 rg
370.942 208.596 46.760 0.750 re f
370.942 192.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 376.192 198.741 Td /F1 9.8 Tf  [(40)] TJ ET
0.267 0.267 0.267 rg
416.951 208.596 71.045 0.750 re f
416.951 192.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 422.201 198.741 Td /F1 9.8 Tf  [(49)] TJ ET
0.267 0.267 0.267 rg
487.247 208.596 46.760 0.750 re f
487.247 192.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 492.497 198.741 Td /F1 9.8 Tf  [(56.5)] TJ ET
0.267 0.267 0.267 rg
533.256 208.596 47.619 0.750 re f
533.256 192.715 0.750 16.631 re f
580.125 192.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 538.506 198.741 Td /F1 9.8 Tf  [(81)] TJ ET
0.267 0.267 0.267 rg
26.625 192.715 148.908 0.750 re f
26.625 176.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 182.860 Td /F4 9.8 Tf  [(Langbehn age 10)] TJ ET
0.267 0.267 0.267 rg
174.783 192.715 42.418 0.750 re f
174.783 176.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 180.033 182.860 Td /F1 9.8 Tf  [(423)] TJ ET
0.267 0.267 0.267 rg
216.451 192.715 57.161 0.750 re f
216.451 176.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 221.701 182.860 Td /F1 9.8 Tf  [(46.82)] TJ ET
0.267 0.267 0.267 rg
272.862 192.715 55.443 0.750 re f
272.862 176.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 278.112 182.860 Td /F1 9.8 Tf  [(10.5)] TJ ET
0.267 0.267 0.267 rg
327.556 192.715 44.136 0.750 re f
327.556 176.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 332.806 182.860 Td /F1 9.8 Tf  [(23)] TJ ET
0.267 0.267 0.267 rg
370.942 192.715 46.760 0.750 re f
370.942 176.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 376.192 182.860 Td /F1 9.8 Tf  [(40)] TJ ET
0.267 0.267 0.267 rg
416.951 192.715 71.045 0.750 re f
416.951 176.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 422.201 182.860 Td /F1 9.8 Tf  [(46)] TJ ET
0.267 0.267 0.267 rg
487.247 192.715 46.760 0.750 re f
487.247 176.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 492.497 182.860 Td /F1 9.8 Tf  [(54)] TJ ET
0.267 0.267 0.267 rg
533.256 192.715 47.619 0.750 re f
533.256 176.833 0.750 16.631 re f
580.125 176.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 538.506 182.860 Td /F1 9.8 Tf  [(89)] TJ ET
0.267 0.267 0.267 rg
26.625 176.833 148.908 0.750 re f
26.625 160.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 166.978 Td /F4 9.8 Tf  [(Langbehn db 200)] TJ ET
0.267 0.267 0.267 rg
174.783 176.833 42.418 0.750 re f
174.783 160.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 180.033 166.978 Td /F1 9.8 Tf  [(417)] TJ ET
0.267 0.267 0.267 rg
216.451 176.833 57.161 0.750 re f
216.451 160.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 221.701 166.978 Td /F1 9.8 Tf  [(46.65)] TJ ET
0.267 0.267 0.267 rg
272.862 176.833 55.443 0.750 re f
272.862 160.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 278.112 166.978 Td /F1 9.8 Tf  [(10.1)] TJ ET
0.267 0.267 0.267 rg
327.556 176.833 44.136 0.750 re f
327.556 160.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 332.806 166.978 Td /F1 9.8 Tf  [(23)] TJ ET
0.267 0.267 0.267 rg
370.942 176.833 46.760 0.750 re f
370.942 160.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 376.192 166.978 Td /F1 9.8 Tf  [(40)] TJ ET
0.267 0.267 0.267 rg
416.951 176.833 71.045 0.750 re f
416.951 160.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 422.201 166.978 Td /F1 9.8 Tf  [(46)] TJ ET
0.267 0.267 0.267 rg
487.247 176.833 46.760 0.750 re f
487.247 160.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 492.497 166.978 Td /F1 9.8 Tf  [(55)] TJ ET
0.267 0.267 0.267 rg
533.256 176.833 47.619 0.750 re f
533.256 160.952 0.750 16.631 re f
580.125 160.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 538.506 166.978 Td /F1 9.8 Tf  [(74)] TJ ET
0.267 0.267 0.267 rg
26.625 160.952 148.908 0.750 re f
26.625 145.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 151.097 Td /F4 9.8 Tf  [(Ranen)] TJ ET
0.267 0.267 0.267 rg
174.783 160.952 42.418 0.750 re f
174.783 145.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 180.033 151.097 Td /F1 9.8 Tf  [(280)] TJ ET
0.267 0.267 0.267 rg
216.451 160.952 57.161 0.750 re f
216.451 145.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 221.701 151.097 Td /F1 9.8 Tf  [(41.94)] TJ ET
0.267 0.267 0.267 rg
272.862 160.952 55.443 0.750 re f
272.862 145.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 278.112 151.097 Td /F1 9.8 Tf  [(7.9)] TJ ET
0.267 0.267 0.267 rg
327.556 160.952 44.136 0.750 re f
327.556 145.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 332.806 151.097 Td /F1 9.8 Tf  [(8)] TJ ET
0.267 0.267 0.267 rg
370.942 160.952 46.760 0.750 re f
370.942 145.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 376.192 151.097 Td /F1 9.8 Tf  [(38)] TJ ET
0.267 0.267 0.267 rg
416.951 160.952 71.045 0.750 re f
416.951 145.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 422.201 151.097 Td /F1 9.8 Tf  [(43)] TJ ET
0.267 0.267 0.267 rg
487.247 160.952 46.760 0.750 re f
487.247 145.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 492.497 151.097 Td /F1 9.8 Tf  [(47)] TJ ET
0.267 0.267 0.267 rg
533.256 160.952 47.619 0.750 re f
533.256 145.071 0.750 16.631 re f
580.125 145.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 538.506 151.097 Td /F1 9.8 Tf  [(61)] TJ ET
0.267 0.267 0.267 rg
26.625 145.071 148.908 0.750 re f
26.625 129.190 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 135.216 Td /F4 9.8 Tf  [(Ranen analogous)] TJ ET
0.267 0.267 0.267 rg
174.783 145.071 42.418 0.750 re f
174.783 129.190 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 180.033 135.216 Td /F1 9.8 Tf  [(280)] TJ ET
0.267 0.267 0.267 rg
216.451 145.071 57.161 0.750 re f
216.451 129.190 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 221.701 135.216 Td /F1 9.8 Tf  [(42.44)] TJ ET
0.267 0.267 0.267 rg
272.862 145.071 55.443 0.750 re f
272.862 129.190 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 278.112 135.216 Td /F1 9.8 Tf  [(8.4)] TJ ET
0.267 0.267 0.267 rg
327.556 145.071 44.136 0.750 re f
327.556 129.190 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 332.806 135.216 Td /F1 9.8 Tf  [(-6)] TJ ET
0.267 0.267 0.267 rg
370.942 145.071 46.760 0.750 re f
370.942 129.190 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 376.192 135.216 Td /F1 9.8 Tf  [(38)] TJ ET
0.267 0.267 0.267 rg
416.951 145.071 71.045 0.750 re f
416.951 129.190 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 422.201 135.216 Td /F1 9.8 Tf  [(44)] TJ ET
0.267 0.267 0.267 rg
487.247 145.071 46.760 0.750 re f
487.247 129.190 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 492.497 135.216 Td /F1 9.8 Tf  [(48)] TJ ET
0.267 0.267 0.267 rg
533.256 145.071 47.619 0.750 re f
533.256 129.190 0.750 16.631 re f
580.125 129.190 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 538.506 135.216 Td /F1 9.8 Tf  [(59)] TJ ET
0.267 0.267 0.267 rg
26.625 129.190 148.908 0.750 re f
26.625 113.308 148.908 0.750 re f
26.625 113.308 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 119.335 Td /F4 9.8 Tf  [(Ranen extended)] TJ ET
0.267 0.267 0.267 rg
174.783 129.190 42.418 0.750 re f
174.783 113.308 42.418 0.750 re f
174.783 113.308 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 180.033 119.335 Td /F1 9.8 Tf  [(280)] TJ ET
0.267 0.267 0.267 rg
216.451 129.190 57.161 0.750 re f
216.451 113.308 57.161 0.750 re f
216.451 113.308 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 221.701 119.335 Td /F1 9.8 Tf  [(42.58)] TJ ET
0.267 0.267 0.267 rg
272.862 129.190 55.443 0.750 re f
272.862 113.308 55.443 0.750 re f
272.862 113.308 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 278.112 119.335 Td /F1 9.8 Tf  [(8.7)] TJ ET
0.267 0.267 0.267 rg
327.556 129.190 44.136 0.750 re f
327.556 113.308 44.136 0.750 re f
327.556 113.308 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 332.806 119.335 Td /F1 9.8 Tf  [(0)] TJ ET
0.267 0.267 0.267 rg
370.942 129.190 46.760 0.750 re f
370.942 113.308 46.760 0.750 re f
370.942 113.308 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 376.192 119.335 Td /F1 9.8 Tf  [(38)] TJ ET
0.267 0.267 0.267 rg
416.951 129.190 71.045 0.750 re f
416.951 113.308 71.045 0.750 re f
416.951 113.308 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 422.201 119.335 Td /F1 9.8 Tf  [(44)] TJ ET
0.267 0.267 0.267 rg
487.247 129.190 46.760 0.750 re f
487.247 113.308 46.760 0.750 re f
487.247 113.308 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 492.497 119.335 Td /F1 9.8 Tf  [(49)] TJ ET
0.267 0.267 0.267 rg
533.256 129.190 47.619 0.750 re f
533.256 113.308 47.619 0.750 re f
533.256 113.308 0.750 16.631 re f
580.125 113.308 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 538.506 119.335 Td /F1 9.8 Tf  [(60)] TJ ET
BT 26.250 65.910 Td /F4 9.8 Tf  [(Table 1.)] TJ ET
BT 62.559 65.910 Td /F1 9.8 Tf  [( REGISTRY data. AAO estimates and data based calculations. Abbreviations: TFC total functional capacity. Langbehn )] TJ ET
BT 26.250 54.005 Td /F1 9.8 Tf  [(db: Langbehn disease burden.)] TJ ET
Q
q
15.000 44.124 577.500 732.876 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(in 30 \(7%\) no signs of HD were reported in either parent, and in 23 \(5%\) the inheritance was unknown for both parents or for at )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(least one parent, where the other parent was not affected. Eight participants \(2%\) had a juvenile onset \(before the age of 20\), )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(and 24 \(6%\) had a late onset of HD above age 60. A motor onset was present in 303, other onset types in 120. The average )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(motor score at enrolment was 35 \(out of a possible 124\), 158 \(37%\) participants were in stage 1, 120 \(28%\) in stage 2, 111 )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(\(26%\) in stage 3, 30 \(7%\) in stage 4 and 4 \(1%\) in stage 5. Patients were first seen by investigators a median of 6 years after )] TJ ET
BT 26.250 707.952 Td /F1 9.8 Tf  [(the estimated onset. The medium number of visits was 3 \(range 3-18\).)] TJ ET
BT 26.250 688.548 Td /F4 9.8 Tf  [(AAO extrapolation from longitudinal data)] TJ ET
BT 26.250 669.143 Td /F1 9.8 Tf  [(Sixty-six participants with a negative slope of the motor score were excluded because no individual AAO could be calculated. In )] TJ ET
BT 26.250 657.238 Td /F1 9.8 Tf  [(the remaining 357 participants, on average the motor score increased linearly by 2.57 points per year. The mean AAO of data )] TJ ET
BT 26.250 645.333 Td /F1 9.8 Tf  [(based extrapolated motor signs was 47 \(range 13-81, SD 11.67\).)] TJ ET
BT 26.250 625.929 Td /F1 9.8 Tf  [(Forty-four participants were excluded because the slope of the TFC was positive. This meant no individual TFC onset could be )] TJ ET
BT 26.250 614.024 Td /F1 9.8 Tf  [(extrapolated based on longitudinal data. In the remaining 379 participants, on average the TFC score decreased linearly by 0.52 )] TJ ET
BT 26.250 602.119 Td /F1 9.8 Tf  [(points per year. The TFC of the 251 patients in disease stages 1 or 2 decreased by 0.75 points per year compared to 128 )] TJ ET
BT 26.250 590.214 Td /F1 9.8 Tf  [(patients in disease stages 3, 4, or 5 who on average lost 0.26 points per year. The mean extrapolated AAO was 48 \(range 14-)] TJ ET
BT 26.250 578.310 Td /F1 9.8 Tf  [(81, SD 12, Figure 2\).)] TJ ET
BT 26.250 558.905 Td /F1 9.8 Tf  [(The investigator estimated AAO was 3 years before the motorscore calculated AAO \(Table 1, Figure 2\) with an agreement rate )] TJ ET
BT 26.250 547.000 Td /F1 9.8 Tf  [(of 0.57 \(Table 2\). The calculated TFC onset was 4 years later than the investigator�s estimate \(Table 1, Figure 2\) with an )] TJ ET
BT 26.250 535.095 Td /F1 9.8 Tf  [(agreement rate of 0.52 \(Table 2\).)] TJ ET
0.965 0.965 0.965 rg
26.250 284.269 555.000 240.945 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 525.214 m 581.250 525.214 l 581.250 524.464 l 26.250 524.464 l  f
26.250 284.269 m 581.250 284.269 l 581.250 285.019 l 26.250 285.019 l  f
q
225.000 0 0 151.500 35.250 363.964 cm /I4 Do
Q 
q
35.250 295.519 537.000 62.445 re W n
0.271 0.267 0.267 rg
BT 35.250 346.975 Td /F4 9.8 Tf  [(Figure 2.)] TJ ET
BT 75.888 346.975 Td /F1 9.8 Tf  [( REGISTRY data: difference to rater estimate. The boxes of the boxplots contain 50% of the data and the median )] TJ ET
BT 35.250 333.239 Td /F1 9.8 Tf  [(\(vertical solid line\), the bars indicate the 25%tile and the empty dots outliers. Abbreviations: TFC ind: regression derived )] TJ ET
BT 35.250 319.503 Td /F1 9.8 Tf  [(TFC age-at-onset. TFC ind � 4 ys: regression derived TFC age-at-onset minus 4 years. Motorscore ind: regression derived )] TJ ET
BT 35.250 305.767 Td /F1 9.8 Tf  [(motor age-at-onset. R. analog: Ranen analogous. R. extended: Ranen extended.)] TJ ET
Q
BT 26.250 267.246 Td /F4 9.8 Tf  [(Table 1.)] TJ ET
1.000 1.000 1.000 rg
26.250 112.933 555.000 144.431 re f
0.267 0.267 0.267 rg
26.625 256.240 148.908 0.750 re f
26.625 240.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 246.385 Td /F4 9.8 Tf  [(Model)] TJ ET
0.267 0.267 0.267 rg
174.783 256.240 42.418 0.750 re f
174.783 240.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 180.033 246.385 Td /F4 9.8 Tf  [(N)] TJ ET
0.267 0.267 0.267 rg
216.451 256.240 57.161 0.750 re f
216.451 240.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 221.701 246.385 Td /F4 9.8 Tf  [(mean)] TJ ET
0.267 0.267 0.267 rg
272.862 256.240 55.443 0.750 re f
272.862 240.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 278.112 246.385 Td /F4 9.8 Tf  [(SD)] TJ ET
0.267 0.267 0.267 rg
327.556 256.240 44.136 0.750 re f
327.556 240.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 332.806 246.385 Td /F4 9.8 Tf  [(min)] TJ ET
0.267 0.267 0.267 rg
370.942 256.240 46.760 0.750 re f
370.942 240.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 376.192 246.385 Td /F4 9.8 Tf  [(Q25)] TJ ET
0.267 0.267 0.267 rg
416.951 256.240 71.045 0.750 re f
416.951 240.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 422.201 246.385 Td /F4 9.8 Tf  [(median)] TJ ET
0.267 0.267 0.267 rg
487.247 256.240 46.760 0.750 re f
487.247 240.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 492.497 246.385 Td /F4 9.8 Tf  [(Q75)] TJ ET
0.267 0.267 0.267 rg
533.256 256.240 47.619 0.750 re f
533.256 240.358 0.750 16.631 re f
580.125 240.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 538.506 246.385 Td /F4 9.8 Tf  [(max)] TJ ET
0.267 0.267 0.267 rg
26.625 240.358 148.908 0.750 re f
26.625 224.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 230.503 Td /F4 9.8 Tf  [(investigator \(rater estimate\))] TJ ET
0.267 0.267 0.267 rg
174.783 240.358 42.418 0.750 re f
174.783 224.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 180.033 230.503 Td /F1 9.8 Tf  [(423)] TJ ET
0.267 0.267 0.267 rg
216.451 240.358 57.161 0.750 re f
216.451 224.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 221.701 230.503 Td /F1 9.8 Tf  [(44.08)] TJ ET
0.267 0.267 0.267 rg
272.862 240.358 55.443 0.750 re f
272.862 224.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 278.112 230.503 Td /F1 9.8 Tf  [(11.32)] TJ ET
0.267 0.267 0.267 rg
327.556 240.358 44.136 0.750 re f
327.556 224.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 332.806 230.503 Td /F1 9.8 Tf  [(10)] TJ ET
0.267 0.267 0.267 rg
370.942 240.358 46.760 0.750 re f
370.942 224.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 376.192 230.503 Td /F1 9.8 Tf  [(35.5)] TJ ET
0.267 0.267 0.267 rg
416.951 240.358 71.045 0.750 re f
416.951 224.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 422.201 230.503 Td /F1 9.8 Tf  [(44)] TJ ET
0.267 0.267 0.267 rg
487.247 240.358 46.760 0.750 re f
487.247 224.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 492.497 230.503 Td /F1 9.8 Tf  [(51.5)] TJ ET
0.267 0.267 0.267 rg
533.256 240.358 47.619 0.750 re f
533.256 224.477 0.750 16.631 re f
580.125 224.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 538.506 230.503 Td /F1 9.8 Tf  [(77)] TJ ET
0.267 0.267 0.267 rg
26.625 224.477 148.908 0.750 re f
26.625 208.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 214.622 Td /F4 9.8 Tf  [(Motor score)] TJ ET
0.267 0.267 0.267 rg
174.783 224.477 42.418 0.750 re f
174.783 208.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 180.033 214.622 Td /F1 9.8 Tf  [(357)] TJ ET
0.267 0.267 0.267 rg
216.451 224.477 57.161 0.750 re f
216.451 208.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 221.701 214.622 Td /F1 9.8 Tf  [(47.06)] TJ ET
0.267 0.267 0.267 rg
272.862 224.477 55.443 0.750 re f
272.862 208.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 278.112 214.622 Td /F1 9.8 Tf  [(11.7)] TJ ET
0.267 0.267 0.267 rg
327.556 224.477 44.136 0.750 re f
327.556 208.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 332.806 214.622 Td /F1 9.8 Tf  [(13)] TJ ET
0.267 0.267 0.267 rg
370.942 224.477 46.760 0.750 re f
370.942 208.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 376.192 214.622 Td /F1 9.8 Tf  [(38)] TJ ET
0.267 0.267 0.267 rg
416.951 224.477 71.045 0.750 re f
416.951 208.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 422.201 214.622 Td /F1 9.8 Tf  [(47)] TJ ET
0.267 0.267 0.267 rg
487.247 224.477 46.760 0.750 re f
487.247 208.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 492.497 214.622 Td /F1 9.8 Tf  [(56)] TJ ET
0.267 0.267 0.267 rg
533.256 224.477 47.619 0.750 re f
533.256 208.596 0.750 16.631 re f
580.125 208.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 538.506 214.622 Td /F1 9.8 Tf  [(81)] TJ ET
0.267 0.267 0.267 rg
26.625 208.596 148.908 0.750 re f
26.625 192.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 198.741 Td /F4 9.8 Tf  [(TFC score)] TJ ET
0.267 0.267 0.267 rg
174.783 208.596 42.418 0.750 re f
174.783 192.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 180.033 198.741 Td /F1 9.8 Tf  [(379)] TJ ET
0.267 0.267 0.267 rg
216.451 208.596 57.161 0.750 re f
216.451 192.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 221.701 198.741 Td /F1 9.8 Tf  [(48)] TJ ET
0.267 0.267 0.267 rg
272.862 208.596 55.443 0.750 re f
272.862 192.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 278.112 198.741 Td /F1 9.8 Tf  [(12)] TJ ET
0.267 0.267 0.267 rg
327.556 208.596 44.136 0.750 re f
327.556 192.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 332.806 198.741 Td /F1 9.8 Tf  [(14)] TJ ET
0.267 0.267 0.267 rg
370.942 208.596 46.760 0.750 re f
370.942 192.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 376.192 198.741 Td /F1 9.8 Tf  [(40)] TJ ET
0.267 0.267 0.267 rg
416.951 208.596 71.045 0.750 re f
416.951 192.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 422.201 198.741 Td /F1 9.8 Tf  [(49)] TJ ET
0.267 0.267 0.267 rg
487.247 208.596 46.760 0.750 re f
487.247 192.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 492.497 198.741 Td /F1 9.8 Tf  [(56.5)] TJ ET
0.267 0.267 0.267 rg
533.256 208.596 47.619 0.750 re f
533.256 192.715 0.750 16.631 re f
580.125 192.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 538.506 198.741 Td /F1 9.8 Tf  [(81)] TJ ET
0.267 0.267 0.267 rg
26.625 192.715 148.908 0.750 re f
26.625 176.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 182.860 Td /F4 9.8 Tf  [(Langbehn age 10)] TJ ET
0.267 0.267 0.267 rg
174.783 192.715 42.418 0.750 re f
174.783 176.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 180.033 182.860 Td /F1 9.8 Tf  [(423)] TJ ET
0.267 0.267 0.267 rg
216.451 192.715 57.161 0.750 re f
216.451 176.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 221.701 182.860 Td /F1 9.8 Tf  [(46.82)] TJ ET
0.267 0.267 0.267 rg
272.862 192.715 55.443 0.750 re f
272.862 176.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 278.112 182.860 Td /F1 9.8 Tf  [(10.5)] TJ ET
0.267 0.267 0.267 rg
327.556 192.715 44.136 0.750 re f
327.556 176.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 332.806 182.860 Td /F1 9.8 Tf  [(23)] TJ ET
0.267 0.267 0.267 rg
370.942 192.715 46.760 0.750 re f
370.942 176.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 376.192 182.860 Td /F1 9.8 Tf  [(40)] TJ ET
0.267 0.267 0.267 rg
416.951 192.715 71.045 0.750 re f
416.951 176.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 422.201 182.860 Td /F1 9.8 Tf  [(46)] TJ ET
0.267 0.267 0.267 rg
487.247 192.715 46.760 0.750 re f
487.247 176.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 492.497 182.860 Td /F1 9.8 Tf  [(54)] TJ ET
0.267 0.267 0.267 rg
533.256 192.715 47.619 0.750 re f
533.256 176.833 0.750 16.631 re f
580.125 176.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 538.506 182.860 Td /F1 9.8 Tf  [(89)] TJ ET
0.267 0.267 0.267 rg
26.625 176.833 148.908 0.750 re f
26.625 160.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 166.978 Td /F4 9.8 Tf  [(Langbehn db 200)] TJ ET
0.267 0.267 0.267 rg
174.783 176.833 42.418 0.750 re f
174.783 160.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 180.033 166.978 Td /F1 9.8 Tf  [(417)] TJ ET
0.267 0.267 0.267 rg
216.451 176.833 57.161 0.750 re f
216.451 160.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 221.701 166.978 Td /F1 9.8 Tf  [(46.65)] TJ ET
0.267 0.267 0.267 rg
272.862 176.833 55.443 0.750 re f
272.862 160.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 278.112 166.978 Td /F1 9.8 Tf  [(10.1)] TJ ET
0.267 0.267 0.267 rg
327.556 176.833 44.136 0.750 re f
327.556 160.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 332.806 166.978 Td /F1 9.8 Tf  [(23)] TJ ET
0.267 0.267 0.267 rg
370.942 176.833 46.760 0.750 re f
370.942 160.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 376.192 166.978 Td /F1 9.8 Tf  [(40)] TJ ET
0.267 0.267 0.267 rg
416.951 176.833 71.045 0.750 re f
416.951 160.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 422.201 166.978 Td /F1 9.8 Tf  [(46)] TJ ET
0.267 0.267 0.267 rg
487.247 176.833 46.760 0.750 re f
487.247 160.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 492.497 166.978 Td /F1 9.8 Tf  [(55)] TJ ET
0.267 0.267 0.267 rg
533.256 176.833 47.619 0.750 re f
533.256 160.952 0.750 16.631 re f
580.125 160.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 538.506 166.978 Td /F1 9.8 Tf  [(74)] TJ ET
0.267 0.267 0.267 rg
26.625 160.952 148.908 0.750 re f
26.625 145.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 151.097 Td /F4 9.8 Tf  [(Ranen)] TJ ET
0.267 0.267 0.267 rg
174.783 160.952 42.418 0.750 re f
174.783 145.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 180.033 151.097 Td /F1 9.8 Tf  [(280)] TJ ET
0.267 0.267 0.267 rg
216.451 160.952 57.161 0.750 re f
216.451 145.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 221.701 151.097 Td /F1 9.8 Tf  [(41.94)] TJ ET
0.267 0.267 0.267 rg
272.862 160.952 55.443 0.750 re f
272.862 145.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 278.112 151.097 Td /F1 9.8 Tf  [(7.9)] TJ ET
0.267 0.267 0.267 rg
327.556 160.952 44.136 0.750 re f
327.556 145.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 332.806 151.097 Td /F1 9.8 Tf  [(8)] TJ ET
0.267 0.267 0.267 rg
370.942 160.952 46.760 0.750 re f
370.942 145.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 376.192 151.097 Td /F1 9.8 Tf  [(38)] TJ ET
0.267 0.267 0.267 rg
416.951 160.952 71.045 0.750 re f
416.951 145.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 422.201 151.097 Td /F1 9.8 Tf  [(43)] TJ ET
0.267 0.267 0.267 rg
487.247 160.952 46.760 0.750 re f
487.247 145.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 492.497 151.097 Td /F1 9.8 Tf  [(47)] TJ ET
0.267 0.267 0.267 rg
533.256 160.952 47.619 0.750 re f
533.256 145.071 0.750 16.631 re f
580.125 145.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 538.506 151.097 Td /F1 9.8 Tf  [(61)] TJ ET
0.267 0.267 0.267 rg
26.625 145.071 148.908 0.750 re f
26.625 129.190 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 135.216 Td /F4 9.8 Tf  [(Ranen analogous)] TJ ET
0.267 0.267 0.267 rg
174.783 145.071 42.418 0.750 re f
174.783 129.190 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 180.033 135.216 Td /F1 9.8 Tf  [(280)] TJ ET
0.267 0.267 0.267 rg
216.451 145.071 57.161 0.750 re f
216.451 129.190 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 221.701 135.216 Td /F1 9.8 Tf  [(42.44)] TJ ET
0.267 0.267 0.267 rg
272.862 145.071 55.443 0.750 re f
272.862 129.190 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 278.112 135.216 Td /F1 9.8 Tf  [(8.4)] TJ ET
0.267 0.267 0.267 rg
327.556 145.071 44.136 0.750 re f
327.556 129.190 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 332.806 135.216 Td /F1 9.8 Tf  [(-6)] TJ ET
0.267 0.267 0.267 rg
370.942 145.071 46.760 0.750 re f
370.942 129.190 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 376.192 135.216 Td /F1 9.8 Tf  [(38)] TJ ET
0.267 0.267 0.267 rg
416.951 145.071 71.045 0.750 re f
416.951 129.190 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 422.201 135.216 Td /F1 9.8 Tf  [(44)] TJ ET
0.267 0.267 0.267 rg
487.247 145.071 46.760 0.750 re f
487.247 129.190 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 492.497 135.216 Td /F1 9.8 Tf  [(48)] TJ ET
0.267 0.267 0.267 rg
533.256 145.071 47.619 0.750 re f
533.256 129.190 0.750 16.631 re f
580.125 129.190 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 538.506 135.216 Td /F1 9.8 Tf  [(59)] TJ ET
0.267 0.267 0.267 rg
26.625 129.190 148.908 0.750 re f
26.625 113.308 148.908 0.750 re f
26.625 113.308 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 119.335 Td /F4 9.8 Tf  [(Ranen extended)] TJ ET
0.267 0.267 0.267 rg
174.783 129.190 42.418 0.750 re f
174.783 113.308 42.418 0.750 re f
174.783 113.308 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 180.033 119.335 Td /F1 9.8 Tf  [(280)] TJ ET
0.267 0.267 0.267 rg
216.451 129.190 57.161 0.750 re f
216.451 113.308 57.161 0.750 re f
216.451 113.308 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 221.701 119.335 Td /F1 9.8 Tf  [(42.58)] TJ ET
0.267 0.267 0.267 rg
272.862 129.190 55.443 0.750 re f
272.862 113.308 55.443 0.750 re f
272.862 113.308 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 278.112 119.335 Td /F1 9.8 Tf  [(8.7)] TJ ET
0.267 0.267 0.267 rg
327.556 129.190 44.136 0.750 re f
327.556 113.308 44.136 0.750 re f
327.556 113.308 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 332.806 119.335 Td /F1 9.8 Tf  [(0)] TJ ET
0.267 0.267 0.267 rg
370.942 129.190 46.760 0.750 re f
370.942 113.308 46.760 0.750 re f
370.942 113.308 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 376.192 119.335 Td /F1 9.8 Tf  [(38)] TJ ET
0.267 0.267 0.267 rg
416.951 129.190 71.045 0.750 re f
416.951 113.308 71.045 0.750 re f
416.951 113.308 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 422.201 119.335 Td /F1 9.8 Tf  [(44)] TJ ET
0.267 0.267 0.267 rg
487.247 129.190 46.760 0.750 re f
487.247 113.308 46.760 0.750 re f
487.247 113.308 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 492.497 119.335 Td /F1 9.8 Tf  [(49)] TJ ET
0.267 0.267 0.267 rg
533.256 129.190 47.619 0.750 re f
533.256 113.308 47.619 0.750 re f
533.256 113.308 0.750 16.631 re f
580.125 113.308 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 538.506 119.335 Td /F1 9.8 Tf  [(60)] TJ ET
BT 26.250 65.910 Td /F4 9.8 Tf  [(Table 1.)] TJ ET
BT 62.559 65.910 Td /F1 9.8 Tf  [( REGISTRY data. AAO estimates and data based calculations. Abbreviations: TFC total functional capacity. Langbehn )] TJ ET
BT 26.250 54.005 Td /F1 9.8 Tf  [(db: Langbehn disease burden.)] TJ ET
Q
q
15.000 44.124 577.500 732.876 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(in 30 \(7%\) no signs of HD were reported in either parent, and in 23 \(5%\) the inheritance was unknown for both parents or for at )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(least one parent, where the other parent was not affected. Eight participants \(2%\) had a juvenile onset \(before the age of 20\), )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(and 24 \(6%\) had a late onset of HD above age 60. A motor onset was present in 303, other onset types in 120. The average )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(motor score at enrolment was 35 \(out of a possible 124\), 158 \(37%\) participants were in stage 1, 120 \(28%\) in stage 2, 111 )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(\(26%\) in stage 3, 30 \(7%\) in stage 4 and 4 \(1%\) in stage 5. Patients were first seen by investigators a median of 6 years after )] TJ ET
BT 26.250 707.952 Td /F1 9.8 Tf  [(the estimated onset. The medium number of visits was 3 \(range 3-18\).)] TJ ET
BT 26.250 688.548 Td /F4 9.8 Tf  [(AAO extrapolation from longitudinal data)] TJ ET
BT 26.250 669.143 Td /F1 9.8 Tf  [(Sixty-six participants with a negative slope of the motor score were excluded because no individual AAO could be calculated. In )] TJ ET
BT 26.250 657.238 Td /F1 9.8 Tf  [(the remaining 357 participants, on average the motor score increased linearly by 2.57 points per year. The mean AAO of data )] TJ ET
BT 26.250 645.333 Td /F1 9.8 Tf  [(based extrapolated motor signs was 47 \(range 13-81, SD 11.67\).)] TJ ET
BT 26.250 625.929 Td /F1 9.8 Tf  [(Forty-four participants were excluded because the slope of the TFC was positive. This meant no individual TFC onset could be )] TJ ET
BT 26.250 614.024 Td /F1 9.8 Tf  [(extrapolated based on longitudinal data. In the remaining 379 participants, on average the TFC score decreased linearly by 0.52 )] TJ ET
BT 26.250 602.119 Td /F1 9.8 Tf  [(points per year. The TFC of the 251 patients in disease stages 1 or 2 decreased by 0.75 points per year compared to 128 )] TJ ET
BT 26.250 590.214 Td /F1 9.8 Tf  [(patients in disease stages 3, 4, or 5 who on average lost 0.26 points per year. The mean extrapolated AAO was 48 \(range 14-)] TJ ET
BT 26.250 578.310 Td /F1 9.8 Tf  [(81, SD 12, Figure 2\).)] TJ ET
BT 26.250 558.905 Td /F1 9.8 Tf  [(The investigator estimated AAO was 3 years before the motorscore calculated AAO \(Table 1, Figure 2\) with an agreement rate )] TJ ET
BT 26.250 547.000 Td /F1 9.8 Tf  [(of 0.57 \(Table 2\). The calculated TFC onset was 4 years later than the investigator�s estimate \(Table 1, Figure 2\) with an )] TJ ET
BT 26.250 535.095 Td /F1 9.8 Tf  [(agreement rate of 0.52 \(Table 2\).)] TJ ET
0.965 0.965 0.965 rg
26.250 284.269 555.000 240.945 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 525.214 m 581.250 525.214 l 581.250 524.464 l 26.250 524.464 l  f
26.250 284.269 m 581.250 284.269 l 581.250 285.019 l 26.250 285.019 l  f
q
225.000 0 0 151.500 35.250 363.964 cm /I4 Do
Q 
q
35.250 295.519 537.000 62.445 re W n
0.271 0.267 0.267 rg
BT 35.250 346.975 Td /F4 9.8 Tf  [(Figure 2.)] TJ ET
BT 75.888 346.975 Td /F1 9.8 Tf  [( REGISTRY data: difference to rater estimate. The boxes of the boxplots contain 50% of the data and the median )] TJ ET
BT 35.250 333.239 Td /F1 9.8 Tf  [(\(vertical solid line\), the bars indicate the 25%tile and the empty dots outliers. Abbreviations: TFC ind: regression derived )] TJ ET
BT 35.250 319.503 Td /F1 9.8 Tf  [(TFC age-at-onset. TFC ind � 4 ys: regression derived TFC age-at-onset minus 4 years. Motorscore ind: regression derived )] TJ ET
BT 35.250 305.767 Td /F1 9.8 Tf  [(motor age-at-onset. R. analog: Ranen analogous. R. extended: Ranen extended.)] TJ ET
Q
BT 26.250 267.246 Td /F4 9.8 Tf  [(Table 1.)] TJ ET
1.000 1.000 1.000 rg
26.250 112.933 555.000 144.431 re f
0.267 0.267 0.267 rg
26.625 256.240 148.908 0.750 re f
26.625 240.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 246.385 Td /F4 9.8 Tf  [(Model)] TJ ET
0.267 0.267 0.267 rg
174.783 256.240 42.418 0.750 re f
174.783 240.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 180.033 246.385 Td /F4 9.8 Tf  [(N)] TJ ET
0.267 0.267 0.267 rg
216.451 256.240 57.161 0.750 re f
216.451 240.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 221.701 246.385 Td /F4 9.8 Tf  [(mean)] TJ ET
0.267 0.267 0.267 rg
272.862 256.240 55.443 0.750 re f
272.862 240.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 278.112 246.385 Td /F4 9.8 Tf  [(SD)] TJ ET
0.267 0.267 0.267 rg
327.556 256.240 44.136 0.750 re f
327.556 240.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 332.806 246.385 Td /F4 9.8 Tf  [(min)] TJ ET
0.267 0.267 0.267 rg
370.942 256.240 46.760 0.750 re f
370.942 240.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 376.192 246.385 Td /F4 9.8 Tf  [(Q25)] TJ ET
0.267 0.267 0.267 rg
416.951 256.240 71.045 0.750 re f
416.951 240.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 422.201 246.385 Td /F4 9.8 Tf  [(median)] TJ ET
0.267 0.267 0.267 rg
487.247 256.240 46.760 0.750 re f
487.247 240.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 492.497 246.385 Td /F4 9.8 Tf  [(Q75)] TJ ET
0.267 0.267 0.267 rg
533.256 256.240 47.619 0.750 re f
533.256 240.358 0.750 16.631 re f
580.125 240.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 538.506 246.385 Td /F4 9.8 Tf  [(max)] TJ ET
0.267 0.267 0.267 rg
26.625 240.358 148.908 0.750 re f
26.625 224.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 230.503 Td /F4 9.8 Tf  [(investigator \(rater estimate\))] TJ ET
0.267 0.267 0.267 rg
174.783 240.358 42.418 0.750 re f
174.783 224.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 180.033 230.503 Td /F1 9.8 Tf  [(423)] TJ ET
0.267 0.267 0.267 rg
216.451 240.358 57.161 0.750 re f
216.451 224.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 221.701 230.503 Td /F1 9.8 Tf  [(44.08)] TJ ET
0.267 0.267 0.267 rg
272.862 240.358 55.443 0.750 re f
272.862 224.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 278.112 230.503 Td /F1 9.8 Tf  [(11.32)] TJ ET
0.267 0.267 0.267 rg
327.556 240.358 44.136 0.750 re f
327.556 224.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 332.806 230.503 Td /F1 9.8 Tf  [(10)] TJ ET
0.267 0.267 0.267 rg
370.942 240.358 46.760 0.750 re f
370.942 224.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 376.192 230.503 Td /F1 9.8 Tf  [(35.5)] TJ ET
0.267 0.267 0.267 rg
416.951 240.358 71.045 0.750 re f
416.951 224.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 422.201 230.503 Td /F1 9.8 Tf  [(44)] TJ ET
0.267 0.267 0.267 rg
487.247 240.358 46.760 0.750 re f
487.247 224.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 492.497 230.503 Td /F1 9.8 Tf  [(51.5)] TJ ET
0.267 0.267 0.267 rg
533.256 240.358 47.619 0.750 re f
533.256 224.477 0.750 16.631 re f
580.125 224.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 538.506 230.503 Td /F1 9.8 Tf  [(77)] TJ ET
0.267 0.267 0.267 rg
26.625 224.477 148.908 0.750 re f
26.625 208.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 214.622 Td /F4 9.8 Tf  [(Motor score)] TJ ET
0.267 0.267 0.267 rg
174.783 224.477 42.418 0.750 re f
174.783 208.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 180.033 214.622 Td /F1 9.8 Tf  [(357)] TJ ET
0.267 0.267 0.267 rg
216.451 224.477 57.161 0.750 re f
216.451 208.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 221.701 214.622 Td /F1 9.8 Tf  [(47.06)] TJ ET
0.267 0.267 0.267 rg
272.862 224.477 55.443 0.750 re f
272.862 208.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 278.112 214.622 Td /F1 9.8 Tf  [(11.7)] TJ ET
0.267 0.267 0.267 rg
327.556 224.477 44.136 0.750 re f
327.556 208.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 332.806 214.622 Td /F1 9.8 Tf  [(13)] TJ ET
0.267 0.267 0.267 rg
370.942 224.477 46.760 0.750 re f
370.942 208.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 376.192 214.622 Td /F1 9.8 Tf  [(38)] TJ ET
0.267 0.267 0.267 rg
416.951 224.477 71.045 0.750 re f
416.951 208.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 422.201 214.622 Td /F1 9.8 Tf  [(47)] TJ ET
0.267 0.267 0.267 rg
487.247 224.477 46.760 0.750 re f
487.247 208.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 492.497 214.622 Td /F1 9.8 Tf  [(56)] TJ ET
0.267 0.267 0.267 rg
533.256 224.477 47.619 0.750 re f
533.256 208.596 0.750 16.631 re f
580.125 208.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 538.506 214.622 Td /F1 9.8 Tf  [(81)] TJ ET
0.267 0.267 0.267 rg
26.625 208.596 148.908 0.750 re f
26.625 192.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 198.741 Td /F4 9.8 Tf  [(TFC score)] TJ ET
0.267 0.267 0.267 rg
174.783 208.596 42.418 0.750 re f
174.783 192.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 180.033 198.741 Td /F1 9.8 Tf  [(379)] TJ ET
0.267 0.267 0.267 rg
216.451 208.596 57.161 0.750 re f
216.451 192.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 221.701 198.741 Td /F1 9.8 Tf  [(48)] TJ ET
0.267 0.267 0.267 rg
272.862 208.596 55.443 0.750 re f
272.862 192.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 278.112 198.741 Td /F1 9.8 Tf  [(12)] TJ ET
0.267 0.267 0.267 rg
327.556 208.596 44.136 0.750 re f
327.556 192.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 332.806 198.741 Td /F1 9.8 Tf  [(14)] TJ ET
0.267 0.267 0.267 rg
370.942 208.596 46.760 0.750 re f
370.942 192.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 376.192 198.741 Td /F1 9.8 Tf  [(40)] TJ ET
0.267 0.267 0.267 rg
416.951 208.596 71.045 0.750 re f
416.951 192.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 422.201 198.741 Td /F1 9.8 Tf  [(49)] TJ ET
0.267 0.267 0.267 rg
487.247 208.596 46.760 0.750 re f
487.247 192.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 492.497 198.741 Td /F1 9.8 Tf  [(56.5)] TJ ET
0.267 0.267 0.267 rg
533.256 208.596 47.619 0.750 re f
533.256 192.715 0.750 16.631 re f
580.125 192.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 538.506 198.741 Td /F1 9.8 Tf  [(81)] TJ ET
0.267 0.267 0.267 rg
26.625 192.715 148.908 0.750 re f
26.625 176.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 182.860 Td /F4 9.8 Tf  [(Langbehn age 10)] TJ ET
0.267 0.267 0.267 rg
174.783 192.715 42.418 0.750 re f
174.783 176.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 180.033 182.860 Td /F1 9.8 Tf  [(423)] TJ ET
0.267 0.267 0.267 rg
216.451 192.715 57.161 0.750 re f
216.451 176.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 221.701 182.860 Td /F1 9.8 Tf  [(46.82)] TJ ET
0.267 0.267 0.267 rg
272.862 192.715 55.443 0.750 re f
272.862 176.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 278.112 182.860 Td /F1 9.8 Tf  [(10.5)] TJ ET
0.267 0.267 0.267 rg
327.556 192.715 44.136 0.750 re f
327.556 176.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 332.806 182.860 Td /F1 9.8 Tf  [(23)] TJ ET
0.267 0.267 0.267 rg
370.942 192.715 46.760 0.750 re f
370.942 176.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 376.192 182.860 Td /F1 9.8 Tf  [(40)] TJ ET
0.267 0.267 0.267 rg
416.951 192.715 71.045 0.750 re f
416.951 176.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 422.201 182.860 Td /F1 9.8 Tf  [(46)] TJ ET
0.267 0.267 0.267 rg
487.247 192.715 46.760 0.750 re f
487.247 176.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 492.497 182.860 Td /F1 9.8 Tf  [(54)] TJ ET
0.267 0.267 0.267 rg
533.256 192.715 47.619 0.750 re f
533.256 176.833 0.750 16.631 re f
580.125 176.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 538.506 182.860 Td /F1 9.8 Tf  [(89)] TJ ET
0.267 0.267 0.267 rg
26.625 176.833 148.908 0.750 re f
26.625 160.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 166.978 Td /F4 9.8 Tf  [(Langbehn db 200)] TJ ET
0.267 0.267 0.267 rg
174.783 176.833 42.418 0.750 re f
174.783 160.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 180.033 166.978 Td /F1 9.8 Tf  [(417)] TJ ET
0.267 0.267 0.267 rg
216.451 176.833 57.161 0.750 re f
216.451 160.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 221.701 166.978 Td /F1 9.8 Tf  [(46.65)] TJ ET
0.267 0.267 0.267 rg
272.862 176.833 55.443 0.750 re f
272.862 160.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 278.112 166.978 Td /F1 9.8 Tf  [(10.1)] TJ ET
0.267 0.267 0.267 rg
327.556 176.833 44.136 0.750 re f
327.556 160.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 332.806 166.978 Td /F1 9.8 Tf  [(23)] TJ ET
0.267 0.267 0.267 rg
370.942 176.833 46.760 0.750 re f
370.942 160.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 376.192 166.978 Td /F1 9.8 Tf  [(40)] TJ ET
0.267 0.267 0.267 rg
416.951 176.833 71.045 0.750 re f
416.951 160.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 422.201 166.978 Td /F1 9.8 Tf  [(46)] TJ ET
0.267 0.267 0.267 rg
487.247 176.833 46.760 0.750 re f
487.247 160.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 492.497 166.978 Td /F1 9.8 Tf  [(55)] TJ ET
0.267 0.267 0.267 rg
533.256 176.833 47.619 0.750 re f
533.256 160.952 0.750 16.631 re f
580.125 160.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 538.506 166.978 Td /F1 9.8 Tf  [(74)] TJ ET
0.267 0.267 0.267 rg
26.625 160.952 148.908 0.750 re f
26.625 145.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 151.097 Td /F4 9.8 Tf  [(Ranen)] TJ ET
0.267 0.267 0.267 rg
174.783 160.952 42.418 0.750 re f
174.783 145.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 180.033 151.097 Td /F1 9.8 Tf  [(280)] TJ ET
0.267 0.267 0.267 rg
216.451 160.952 57.161 0.750 re f
216.451 145.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 221.701 151.097 Td /F1 9.8 Tf  [(41.94)] TJ ET
0.267 0.267 0.267 rg
272.862 160.952 55.443 0.750 re f
272.862 145.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 278.112 151.097 Td /F1 9.8 Tf  [(7.9)] TJ ET
0.267 0.267 0.267 rg
327.556 160.952 44.136 0.750 re f
327.556 145.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 332.806 151.097 Td /F1 9.8 Tf  [(8)] TJ ET
0.267 0.267 0.267 rg
370.942 160.952 46.760 0.750 re f
370.942 145.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 376.192 151.097 Td /F1 9.8 Tf  [(38)] TJ ET
0.267 0.267 0.267 rg
416.951 160.952 71.045 0.750 re f
416.951 145.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 422.201 151.097 Td /F1 9.8 Tf  [(43)] TJ ET
0.267 0.267 0.267 rg
487.247 160.952 46.760 0.750 re f
487.247 145.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 492.497 151.097 Td /F1 9.8 Tf  [(47)] TJ ET
0.267 0.267 0.267 rg
533.256 160.952 47.619 0.750 re f
533.256 145.071 0.750 16.631 re f
580.125 145.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 538.506 151.097 Td /F1 9.8 Tf  [(61)] TJ ET
0.267 0.267 0.267 rg
26.625 145.071 148.908 0.750 re f
26.625 129.190 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 135.216 Td /F4 9.8 Tf  [(Ranen analogous)] TJ ET
0.267 0.267 0.267 rg
174.783 145.071 42.418 0.750 re f
174.783 129.190 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 180.033 135.216 Td /F1 9.8 Tf  [(280)] TJ ET
0.267 0.267 0.267 rg
216.451 145.071 57.161 0.750 re f
216.451 129.190 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 221.701 135.216 Td /F1 9.8 Tf  [(42.44)] TJ ET
0.267 0.267 0.267 rg
272.862 145.071 55.443 0.750 re f
272.862 129.190 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 278.112 135.216 Td /F1 9.8 Tf  [(8.4)] TJ ET
0.267 0.267 0.267 rg
327.556 145.071 44.136 0.750 re f
327.556 129.190 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 332.806 135.216 Td /F1 9.8 Tf  [(-6)] TJ ET
0.267 0.267 0.267 rg
370.942 145.071 46.760 0.750 re f
370.942 129.190 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 376.192 135.216 Td /F1 9.8 Tf  [(38)] TJ ET
0.267 0.267 0.267 rg
416.951 145.071 71.045 0.750 re f
416.951 129.190 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 422.201 135.216 Td /F1 9.8 Tf  [(44)] TJ ET
0.267 0.267 0.267 rg
487.247 145.071 46.760 0.750 re f
487.247 129.190 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 492.497 135.216 Td /F1 9.8 Tf  [(48)] TJ ET
0.267 0.267 0.267 rg
533.256 145.071 47.619 0.750 re f
533.256 129.190 0.750 16.631 re f
580.125 129.190 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 538.506 135.216 Td /F1 9.8 Tf  [(59)] TJ ET
0.267 0.267 0.267 rg
26.625 129.190 148.908 0.750 re f
26.625 113.308 148.908 0.750 re f
26.625 113.308 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 119.335 Td /F4 9.8 Tf  [(Ranen extended)] TJ ET
0.267 0.267 0.267 rg
174.783 129.190 42.418 0.750 re f
174.783 113.308 42.418 0.750 re f
174.783 113.308 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 180.033 119.335 Td /F1 9.8 Tf  [(280)] TJ ET
0.267 0.267 0.267 rg
216.451 129.190 57.161 0.750 re f
216.451 113.308 57.161 0.750 re f
216.451 113.308 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 221.701 119.335 Td /F1 9.8 Tf  [(42.58)] TJ ET
0.267 0.267 0.267 rg
272.862 129.190 55.443 0.750 re f
272.862 113.308 55.443 0.750 re f
272.862 113.308 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 278.112 119.335 Td /F1 9.8 Tf  [(8.7)] TJ ET
0.267 0.267 0.267 rg
327.556 129.190 44.136 0.750 re f
327.556 113.308 44.136 0.750 re f
327.556 113.308 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 332.806 119.335 Td /F1 9.8 Tf  [(0)] TJ ET
0.267 0.267 0.267 rg
370.942 129.190 46.760 0.750 re f
370.942 113.308 46.760 0.750 re f
370.942 113.308 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 376.192 119.335 Td /F1 9.8 Tf  [(38)] TJ ET
0.267 0.267 0.267 rg
416.951 129.190 71.045 0.750 re f
416.951 113.308 71.045 0.750 re f
416.951 113.308 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 422.201 119.335 Td /F1 9.8 Tf  [(44)] TJ ET
0.267 0.267 0.267 rg
487.247 129.190 46.760 0.750 re f
487.247 113.308 46.760 0.750 re f
487.247 113.308 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 492.497 119.335 Td /F1 9.8 Tf  [(49)] TJ ET
0.267 0.267 0.267 rg
533.256 129.190 47.619 0.750 re f
533.256 113.308 47.619 0.750 re f
533.256 113.308 0.750 16.631 re f
580.125 113.308 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 538.506 119.335 Td /F1 9.8 Tf  [(60)] TJ ET
BT 26.250 65.910 Td /F4 9.8 Tf  [(Table 1.)] TJ ET
BT 62.559 65.910 Td /F1 9.8 Tf  [( REGISTRY data. AAO estimates and data based calculations. Abbreviations: TFC total functional capacity. Langbehn )] TJ ET
BT 26.250 54.005 Td /F1 9.8 Tf  [(db: Langbehn disease burden.)] TJ ET
Q
q
225.000 0 0 151.500 35.250 363.964 cm /I4 Do
Q 
q
0.000 0.000 0.000 rg
BT 291.710 19.825 Td /F1 11.0 Tf  [(3)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Huntington Disease)] TJ ET

Q
endstream
endobj
140 0 obj
<< /Type /Annot
/Subtype /Link
/A 141 0 R
/Border [0 0 0]
/H /I
/Rect [ 35.2500 363.9645 260.2500 515.4645 ]
>>
endobj
141 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/files/2011/07/Figure-2.jpg)
>>
endobj
142 0 obj
<<
/Type /XObject
/Subtype /Image
/Width 300
/Height 202
/ColorSpace /DeviceRGB
/Filter /DCTDecode
/BitsPerComponent 8
/Length 15608>>
stream
����JFIF



��;CREATOR: gd-jpeg v1.0 (using IJG JPEG v62), quality = 90
��C




��C
		

���
,
"

��







	
���

}
!1AQa"q2���#B��R��$3br�	
%&'()*456789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz���������������������������������������������������������������������������










	
���

w
!1AQaq"2�B����	#3R�br�
$4�%�&'()*56789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz��������������������������������������������������������������������������
?�R��ih��(�h�j9��d`pB�?*�߇���Q�
k7��F�z��my0�;��]��jp2N(�x��ָ��W���?���"��
�V������O��Z���'�ޭ�E���Ɵ�ȴ¼�����������;SK���
�W������O��ZO�W���?���"�oG�\O�+�[�����?��h��y���C�?����-vԟ�q_�5o�(~'��4��E����E���Ɵ�ȴ
��4��¼��������������E���Ɵ�ȴ
�Q\G�+�[�����?��j
C�zŭ������㍜e,1�3�>�
�q�Ep��>��5c��� ����-;���E���Ɵ�ȴ
�qI�q?�5o�(~'��4��E����E���Ɵ�ȴ
��4f���W���?���"��
�W������O��Z���k���y���C�?����-��o�(~'��4��E�ڊ��^j��P�O�|i���G�+�[�����?��h��h⸏�W���?���"��¼�����������;j+���y��C�?����-�5o�(~'��4��E����(�������g��Mu��Ows�`cfD,
l	�pGֽX
ZN)i1@1\���cÞ�Γ�Owo{�GS��f�]�,�6��ߡ�i�u��Yw��u
R=F��9��Y'VE^:p%�t�/�RO��b�&�VR�"�{����,6��2��5kM�~��O{��otl�ᡐ2Fv2Ï�n�c��>h��լZX-n���y˕�,H
8�@�P�|1�cqe�m%��%��g����
�>w�ݏ�Ig���6v�i�Z�ױ�	$�\����8�j�����������t�m~�[H��V�\q=����U dM�Ad�I�����Z�
��IҀ;1I�1@F9����I�\Q���4oCy.�z���Nm�`��\p7
�A0� �[����{K��\&��Z��q3\L���BI[�;,p2O&��8/|s�O�5��5�d��(
0%��q�F��y��?}s��
�]�[G�Fe����´]�#
J�!��6#~>S���/��Pk�kº.�z��o��f����I����7@����=O�����v�%�a���*��=������}w���v������Z<����<�&eL��
��Ys���f�χm�5Iu�2;�:/>���=�x|�NQpA�`r+/O�E�Wӵ@Ӵ;�9ZPt�H�Ĥ��a������5�yk�@Q���3�����J��\���w���|߼���k翋V����įY������O֮�n��n�(�)nEb�{T"�6㎕�	�qҾj�����U���#�
�����X���-��Hg�v��5�`�H�����

h�g�g��ƹ�	5���G世�]��9M�Ūͺ'��$q������°��S��4��L�C}+_D�B�BJw|�H#
����
����K�/�x+Z��������[?"/��l�6V�D�’x��yx�G>�
��7����.����������x1�5W9)�N��Z��;����n<An#���,w�����"]��+(�x'8�S��Uع�\u��ꚞ��x{M��n~��jvq\�ˎ<!e%W)ǮMv(�E�*FA��h�3��M�^���[LB2�H����0� �Mm�CG�����]/N��V�f��m!X���ޑ���=��hB��#�]�zcj辴W�́9ڮ8`
�08�VR25����x{K�ՙ��4�M.ԻH`��bM��j�2}h@QIڊ^�RqF(
zQ�J8�+�p��;���薭I~ �r'�1���<M,m��Yw�3"\�e�gڲ�7����o?�KV�|5�\.�n.�y$7 9Y󼤙܄���(��ŏ
_]���w8{���y,�H�Yq����J���+��\��y��k���Z\%� ����W<��^��g�5�b��1I��bx����[.�O�QYn��)��2ȱ��ne�9�|W�Ƒ�I��YGss��ē��f�����v��kx�P,���02?P@?�U�.-�V�{T1A/���B0U2���*���c���k����$Km ��Ar������/�?�H<
�`+�'Jڟ�::Į�]�x�[�c#$�==Mb���?�o�
X��:PcIǽR�P
GzCE-��Z:�-�?��w�u�iv�p�hs,7p���ZE�p����)�F��=O�H��yWŏ�/ÿ��}7Wӵ{���J��L�q!��"�r���h��H�ީ�!E=h��?�@���&
?UO�I����|Q��6�A' ǿ�X�G(ߵ���y4�?G־�oy��bl��lR8�,<���e8ee�j����j�—p�����1?,����� ���d�-�����\[�����L��DZ���6p1�++T���I�oE��!�/n�t+�(m���ý��
}��֨k��i�j3M"�v�;��U
I$���<�H�{�o�~;��oiz��5;��]�rJ�����+¿f�xv��	�����B�����������%ߘ�M�Ę.Xm9��M�,�xn�Ė��(�uq�귳O�����9@
ыg#�9�߀�ּ;�;i?�5���!�-���&��|Q$�����,�$(�q��Q���_��y�Z5��e��ϔ��tѲ�F�=��#匳u��q��O����ڸ��ϑ�G�]�8��b����۞�+|tq�@'�/ڏD�7�5
7P�uym ��ˑl��d�h�&�VA�u$c�l�F+�֡�&��j��4V����Ɨ	�EWP�2�8<�|Z=�:�Φ����+yf���r����C����9_�FӼU�h�ב]�o\I:(�ˆ��1?�~�RAdk�<SB�9�K�r�������]������{ױ��"�gV*J�c�T��lH
�z�@�:qK���z�q�@/�Q�q_���������%�6��ᶿ�O��k�Ee���m$�}�R�A�@9���>7����o?�KWT4�&x���q�:?,m�9��s����g�����$�/෼x#�ἲ˷�e
�e.�\d�ƽ�TW@�[��퀷`�����
����v�q@��/]x.�N��ҥՅ����w�R2����0��<U���y���j��W�Q��C89;��#����
�I�}(����l����"�)BA.�!q��>�A�5gE��������V��-��2)��W.P�H�zW��Z6-ye�Ʃ55ӭ�Ú��ׯo�@��<�[7��1��ў��|�h<
�`+�'J��U~�/��r��x��V?�N�
��qKGQE��֎)x�
:���^�yog&�qo�Gi7�ʤ�\�b0>���o�x��z���͢]M�}���ɵ�C|ʍ�
nU8a��Ec��Y��J�N�W�������%'��y��~7x�@���Z��l���C�f��d&&�r
*��NfL���=�ќ�'�_jz'�<7��xv�S��As�[vc~�w�2���
�<�sĞ&��.�}��SJ�X�'�<�I�9̆6*rS�2�Aa�>�������8�<�<ͣv����j��)cy8�����0�;a%��p�����/��[ڰ�(�wr��M�_�o��w/���N�!�w�!}��wok��?�t���[���K��#A��qy#*m��aG 
��|¸_��<'Ï6�����2�no�<3��v�4�L
�$t�1������'��<=���׷x�C�/��>e�ʘ��{1�G���k�~%��~�u��W~.�<w�~�kw�|7��1��h��+���A����	izό/�5���iz�����G��Y<�h��[�O�*z���<W����������7���KO2���D�J��Ž�i|I}ꊾ�$�]^���f`F?��ޣ���O��|q
�>k:�f}ڄK(��j��	���f��y{�ĝ~���Z���֦�e��_ɨ��iR<ԌǼ�t���7��]��H�PƐ�	!@''��RPFzW+������t��<;w᫕��w���
�w̪z�S�2����WE'�8��'�^(��ZJ�7����o?�KU��q=�ݽ��5���5���`�ٔ6�8�
^���$w������-]�U��0����x����Afkue���<�p�������f�C�֓j�Ҝ1@�AQ�
�xWS�z��F�b$�Ie})`�L��f�p6�������v�?~!�=.$�y���n
Yp����R9�z�q@Gk��6������ޘ�P��@“&s�|�A5����A�n?�c���]e҃o/��r�x��V?�N�
����/P
�Q�j1E!�R���(=�xJ�ŷ> �~ ����b�F�-���t�/�~Q��g!C7YI@w�Q���
���v�%'̆,���Ԇ��r�rH�����d�$�N�ڋ�b�T�jǴ|፾Y��J���v�;R� c��v�n�L$��z^�Ѣ���dc�|��/�^�
׉
֜%�tĶx�|�H��?,K�
"��C��h�Ҁ<�g�'���s�YYYN4�TF�7op���Ih� ��=����G��������z�����M����k���۶�%�0�0y����c&c�lד�s���~6��p|F��k�\�V5��2��[y���}��ӟJ��?�C�ؽ���4u��r�__��Ht�=�������3��.���������\��5�|���_��[M�:z5օ����w��6��ֽ�KX?�O���Q�M�6�|T�#���!_�v:��
b;��}4ɤ�;�E�)Xc�#�pdld�����x�b��zN��F�X+jR�2n��~�|��(|�2:�GI@G�oV��gw���F���K�����>_�WE�h�F�`��Ҧ]P�Goq��G<������;Z�?g�W��������zV�g�.}���> �𵜾(�����
��
��p	M���
$d�/�׾-��O�Y�����b�?�������
� )!I*:�8��=)i
�.=�(�����P��H���y��Z���/�Zk��[[d�U�'��P|�D.�f�NG#�h�n��;�~?�y��Z�Q@I�x��<��	{����K|H-�1��8'�K�{���ڗ�L�q\W�4_��E�4�E`�l���2:����t�pHNv��K��o���u=Yt-KL��f�c�2G��IL3�!�`�8*F���vz�u,�:��"��a0���>l��$��z����8�"�to���c��i���%�����2&�0*w
�Ǯ�+��5��S�������u�,>�/���W'�h�Š�7�����(��"��f��N(�.h
8��7��Ƞ=+���?�"��5��=.�em2�!T6�BA!A?+F���2����#4��O�:?�5K��9�G��o|��(����}���lddq����>&��|o)������d��9�Y�X���F�ʷ˅?�W��^���M�Mw<v� �0P]�".Or̠�@�i�$S�y�݋���v�5��y�����8�}F�_�Z��4���y�[Lt�+y������ W�]&ih�o��(�5�Y�o���躊��u�Ig���9��c��푏�e���+��!��|O�����K���$֛�3As-���h�N���>Q�^G�?��^'�5���~
SO�ʆk����\�p��f!�Y@��w]��w��������?�I��߃vZ�|7�궑�ϡ۬6�b�$r�K�i<�s�;G���Z��{���K���=�+
;jq��V l�U��vW��j�0�c�i�����F�,�-���pXC���]�&�;8���������4R�q��	�����2Kz�,�o��QS\�I%plX�E���;���2
`�Һ h�<�F��K��>��dzm���}Ve?�/#�N�/".ͤ��X���[�:�\x#Ƕ��>�#6�YC7�'���䌴g�Dexݸz���k�$�m<s�R4.c`v��2�px"�2<�k�W���|I������:�T8.�ʨ	
Urs��f�|6��Q�h/o��r=S33-�p�@&�aUG��8-�q��Z@�R=h�'ހ�2(�(Ƞ�8���~7����o?�KVl�G�	f��]V�KQ%Ɇ�ج/4l��Y(G0�$�ⴾ7����o?�KWj1��=�� � ��W�,|�ra{��6��N�
�]��XI���I���P;�U�n4ˍ*�i-ev�N��F��H,��ן��?��g�F-�f���Ύyh���dNc9�wҽzK���U�$"��2q��8�
����ƍekf�>�[h-��c�<a���w�;�3�A5�/����-ky�W��:�]��FG��B��{eEw�n�0G0�3�vHmm��z拭B��Q�."�Wq�\(f<�Oa@o�
�X�ij��k�H^��4�J��?�s�h�yp����k�H����c���]
��c���pGs *���;��S�'�5����A�o�
X��:PcJ3IFh
h���)��K^cM��=�>�
��^�P�����k���vPN��Z͑ ���̜��8�Fӕ�<&���oć\Ԯ�ԣDd���ڨ��3����]��қ�V� 2�����H�@�@���d�9%D�C�V`��s-�i�@�W��"?b�������8��3��9�]]�Esu
�M,�$1�Wv���g���W:�뚖���|��4��b�)�W&ʞ�9'�D���{�xM�����lf��¼i�R�) ��Q��y�oj�ݖ���{}q��H�31�K����=��W֐\�ۡ�Dl�# �T
��%��M�뚣�8����M�'�l�n{8Us��Θ��ka�?�^t^r�c������}��(�=�_
M-����樋s
�@�G��p�ِ�g$��x�/B����M~�Q�øд����k,���S��Ҵ5����4M'Z�G�����=��yYn��B�����3W�g�<E�N�S�������ۉ������)�g����C�&�*~��'����1�j�7�NV+�b^�I�={Ɵ�w��am�bf�J�D�F_&2ў����?^x:�O�$�@�`:��g-�xv��=�P66A! ����
���ih�AV[(��m$>�)t����\Y)VG�<]{��r��P��g}:��x�ZV�8\	b�b��O�����]��(�=��7+�7_�Z����
n�'��b���rI�+�n�j:�/|7?�u�i5����t˿.�㑤۹�(����pq��:?���v����E��Y��!�O�pz�v�ZWpڨi�H��(.�OA�s@w�|��u	�7�5���-�hf�s�X�4;�o†�@D�k�.�!q���w���6�����կh�ϔ7I��D珚iOF
��%�1L�����	H��\�
Ʊci/�=ݼ2`� S�q�����|R�%s�+�:�^6����!��o�Ǚ�0V��?X�=��4K�x�]�k���z�D�N������U�jNv�9f�s�Kg�[_�ki�PpLN�S��'��X�.����Gj��xW��xkľ"՟\Ե$��I��b��m,q����q�GQ�����E��'�w�������D�S��7�����-�ۨBR%��Wp�g�ޮ|n��;���薮�x��)�>kza�V�X�g�6Y���L {2�����I'�8�wz��f��]&y�(�;9%vUTYԱ,��
�I�Q�h�T
��7��Ӧ�P�O��W�^F,6FS��y�����y�*;]?�Z�s�p�]0�4nrWh��9)��x�z�ީkcqm�R�X�U, 	�*�񯇙�wM*1aw0N
�О(�?ᛴV�d�5�a��u��
X�]H�(PI@X��^kz�0�r؍OPt���G�Y�<m�+�*Ǒ�<�[��?���u���Q�V�@*��ne���u�M�=�($�\Vh�P	em�۴Nq�	8
�I�~�?�x��z���2I4n�Q�:��r�ӿE�Ҵ�
��7�����*�ߎ�H�t��d�?'��H:���n6��wg�\犣�h�ş�7�����(����Ҁ
�k��B���9��Z��&�5]�2m�~�8##�֧��I�xSI�S��#�����Ҟ
f
�Ԓ�sT�������g�Z��f�o�O�0��8�t?GS�Pk����7��ڻ�|&yČ�$^W88J?�g�`�/Ýž!е�Nէ�4I[)��c����s~��5��-4	�"�n�͆ɛ���s�=�r;��t�c4W?�h�<5q�k��s������u�#�A�%�~���[{�kQ�M��ao���K`�U��
I�W?7�	E��|;��ho��I7L�����%���y��U4
ď����-'P�8�T�=Ďڄ�F�0��*���AӼ=�i-g�A���0%�~�}���I�'��X����{{�Z�
��q����,~)ѥ��լ�k��-�[�-:�y~a��zPI|
�O&�#ٖmH�>k����)��+G��N�KM�i�y6����c�=O\ӏ�|<,^��h�I|���\~ZɌ�-��n���C�S���Vԯ|I�G'�ƣn��j
IWr�����E�h���¿�zý�Յ���fRH��.IV{��r�`��Ǹ�$��|]c��|
����MB�D�;��K�tV��`�4�|�>����s@����"��>#�þ ����B�ߖi$�H�D9�ۀy�^��]O]�v�/k2[��Mmu�~e���
ԇpn59���W�<=��
�h6b�P��Xҷ@4�
�ۼ���
�9ף'�tt�`�[\]Ao�X���m�qОzӭ�]�Io���:{%��j���`@">~b��a��䭭i����\�F'
\��9`��
I�����Z�-�-mg�D1��|�z�vO��SK�]y57{2[R]5�xO����]_i
w��l�Ԑ�� 	���w��J���l|b�i:έs����:e�PiU�����ʲ����ml�3@W��d��֛�\�=ֿa7��\J��$n�&�8�-��P�l�'�>�_��K~ծ��nV�$YZ<H�9R26�{�և��Y�x�G�U������I	q
ʒ5~���K�����-�m�if�C�cE��	�
g�ƅ���D�E��I���"��%`:�l�8<1��\o�_�s���OK���H��P�o"]�#��`9��|S�����da����g~�q���Yq�*è8�k[��m��	XeP�"�)���>| ���+�?�Ig��y��<���s�'�Ʈ��4-�Z׊l�Z=gXT[���C�UQ�'�^��Z�)s@z)3Fh

(�h����$w������-T�ঈ�W�2���qq-ĢQ>ք�}�88AW>7����o?�KV��&Z
��mi�z��b�Rn�.��r��;w�CE�)g�ŧ�5[��{�,
�B����8,��1��lz@�{?���kA�\]�&0JA/���0�3�<u�|�����|Jm
��5��H����T�P�AV#�k����94��-�4�I%2�ደ��T�'��q��s�j�趉q8r�q
�2wK*ƿ����s7?�#i�ͧɫb�d�H�����\��~`�����)����1уΰ�n%y�g�� ƻ�g����Z�|.��
g�Gn�&�g�n��F�ݒ
�
� �*-/⮃�h���e,���@�S#4AK@�g!H�#N���?��g���Ԅa�Y�"��:�)#d����#�	�
�7�}o���.����o��W��cƇoL�8��5�$�������t���[L��M���ɩ;D�ѡ���`�|��'.3�V>
��7�����(���3@5�M�6�.��X��Vm�-��F�!�T���qU�<!�i��խ��;}O��i���U���{��ѵx�����3@w�n��mjm6�]^�P�<*f�r���3�G�֥rڏčK�ޛ�	�kz�&x"�B�����Ȇ_��\���#Dּm�xN�y[Yґ$���`�Q��$Oό��S^�Ɠ� �X�mu8`�n"���R@
F}ϭb���OE�(t�[mDy�f�hg���q�a�����֦o��"|B
3����_o�-���W;��+��
�J�f��X	��I�fO��K�G���Ѝ���e����X>3���x�D�X�H_X�KA,��b��??c��A�x�/���� �|�	-�p�aA$�����@غy���
��[y��]��q����^��`մۿk����\����$O�r�+oJ� �=֛l�����e6Ҁ�rI\/C�`�o�X���Q�T�dI����9��c8۳v1�����#��W��6~��{��^�k3[F��\$B ɖ�F�+�<a�^x���p��j�;�n�g��H�H��u'y�ZD�z���
���� ����΢�B<�v��}����|5�C�f�ua�a��5������/���
\�\����(�aҬD�Z@<�k���+��8�6eSinVc�Pb\9��ƾP��<��|"�/�&�G��Ś-��b�S�R^"Ȅ��RA�Y�������a�V���7�:l��[�H��u#�A�=g�2�J��hD��Z��2�Oj�?�W�r��Z���-�-;U���^@�B$G��b%<�}j�>9��K�.%/�)kQ�iF�=I_�����#h)�\�5�����H�c�"O@�2G���
?�kJ����ֺV�&;[8V(�''
�
W.�a�����$��d1��]H�RPGjʓ�zTz�͋O(����T��y0#�9
���
ϵpW��o��5�;�k�Kc�G��i����3L��M����c�I�l�>�4-��/����L�9�s�z���{�� �-�H�E�$
U`(p_>:xO�ڤ^�����r&�x��Θ��7zddN͟č����
�yN�ik��b0�A�������3��Q���B����0��5�䷱�V�D���}���$�zEp�t<�w4Q�3@	ޗ�3Fh����$w������-W�w��vϣ[��M+���3�`��v�1֩�n��;���薢������m\E4/<n$��B�A2|�q���pq�4
6��ú:���],0P5��y �R���t�=I��q\6��kO�t�v��\�zmv0X�j���wH2�-�v6�3��3@�=.�Y������Y1��ã`�2��q���3��[��(�VY,lC}�@ �Ps]h�ai���b�v=����-���av�s����9�Y�'��u�V�&�msn�\SEj��'
@�3�Gֶ]�!lt׏h_�Lw6�r���,5+����,�JH3y{s�#�EzG�"z5��b
*�m��ۢ�������y���k?�<
�`+�'J�Ҿ<h�!�[]/XW��if�X�=�5���eA�>�9���_�H<
�`+�'J�9�斓4����F�F�52(!\��Q��4��X�H�pN:dԔf�#�<~w�寛���7c�>�'4SY��=p:Pd�9�H��6�,��}G�U�4[Mz�mo��Y��	��<R,��=�בk�u�O���C�-~���im��֏���H�r�N(�b6��t/���_F�e�ưn/,�(�T+;9�I���`���X���9u5�d@�<�]��,�������[�n��O��H��/2I���jpN�q.wq�
�#��^�V��X�}kX���%c{���9@,FOҼ�\����{Ǻ�����쯴�K@���yH$�r�dN�籮��7��/=ލw�yz~��DDY��_:�n�� �Ҽ��ȳ�?��
`�w|E�9g��1�iMn�㯀4��T�6�-���j�5ϋ�ed��YY0#�H\
�_]���'�5-6�úH��,����|��H�
���<k�Z��������_����xV�t=FX�Э�[���&R"_ݮd
���@��L۞Իk��ŗ�[��k�r䍾Ϻ����lm=~B��jY|WwZ��
j�l�$h�g�y���.0:��N;g��v�}����6�`�A�2]ȯ�+��ns�N}�����?�L�H����o;���j,���N$,$
d�+���֏��]x�
VK�Q�
���h��M�W�2T������<�Gq�-���o��#Q)
K��:י[�f�g��||�Gh$h����O��#6��6`����%�H�
G4�&�cY �p�9&1Ҋ(�h��h�4Q@O���#�7��-���j�m�kE�Ag"v-(H�y�s����ֹo���G|o�`[���A�2[�o��E��[I."���!�~P9y%R��pJ珻@�����y?g����
#��U�J�aIؑWy�%�~:�j��6-�E
K%�-�߇Y< �
2Xn��ܪ���`�J_��sF=���Gp1o/��r��x��V?�N��ȁї�^y���^(�փ���>8ae��Gi�J��ˍB�Ny8��J_¸��E|e�C����*��E|e�C����*�;\�FkͼO�|BӼ=���>-MCS�{kV�aY�T�é��A�o���
!����Q�����+�����?���+������h���+�_���(�����_���(�����{x����Ya�J::�YH��Ӣ� �#�F�*��@y��'�-夞-Dң��HnƓd��Q"cwEU���3Z����������<_�Uv���q_���������D_�U���������D?�UX�w���O�Z6���66z|6̗�oq�1��6KGs�ט�a�#�?����/�W�ZI��i<Co��1G��ɺ�Hs���o�E|e�C���/�*�<O���Y�<^���i)��:L K&õ3���ƀ4�����������@���[�ܞ�f���p��i�qZ��G�J R�rv���'���|-�V����eI

�����R��+�/�W���T
��~��+�/�W���T�+�/�W��T
�\YAu,Mr���!gPLo������f���>=����W�_�<��
"��-�/�C����t�fҵ��L9P�,zv�I���渟�E|e�C����*��E|e�C����/�*�;\�渟�E|e�C����*��E|e�C����*�;lњ���d
#���C��Vo���Z�����[�������Iwh�L$C1@]
�r:��
�9��+�_���(�����_���(�����w�������D�v��^y��8�7��;�Q�Ia�\,Z\(�7X���<�h���$R�(

��J)h�%���襣4
��C���h�'�|?6�~J�+F#E�7n
"���\���sZ��I.5�Agv$�[Io��|�K|�]7g
�p���h���Z(��H��f����]x����?b�Ѥ_�ln4�æ���YL�o4|�P� שJ[h��X�x�@��;���>Ky�I��2����s�q�(j�@������%dx�R�Ҽ?su���]�@����R���!�j�m�Al`u�X��u,���+� ���?�N�Su�W<�s����T
C÷������j}��kh�
�|�
�˂I$�Z]i
�Gmw
�BXeIc=@�ڙ���Պ�
�S�p}8 �4��Gq����ʲ�Aƀ^c/��\<r�th�F[���}�6#zB�6�ga.0Lev��O��qP3�2OARq�@�����斊�~#�z燼���oGmwZ�"m����H.���[��������7��"�h�Lq��x~]�H��ߵ�/��V�@�utP
E-%%-����挚(���I֖����A�֒�
:њ;P����ހ�҅�@��=h����R���,����=�G���u{�6�a04�P��B� }�Ͻz��
�k�5x|X�k����<~a�;�0a�q�7�3�}Nu#��Ǩ�ݦ�� ��K��eE�폅�
�Rp��2s�#� �h�l>	��t��Cqv"�~��C��t�W�n�79��N���>o$�:��'�����P���*�.�2��װ�v�9־��ެ5	/�+y X���H�WT��~��95�c�9�wM��������U�
6��
���9�V4�
�>�
�x;^�V�����2�d�c��E�
�8UP?�����cw�=4�#���ˉchV2��y����`W�z�h�t���^�q��i�j
%��k�����y�	c�(�zwJ;�
P(QE'a@�h�!������{Qڊ
����?��
endstream
endobj
143 0 obj
<< /Type /Annot
/Subtype /Link
/A 144 0 R
/Border [0 0 0]
/H /I
/Rect [ 35.2500 363.9645 260.2500 515.4645 ]
>>
endobj
144 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/files/2011/07/Figure-2.jpg)
>>
endobj
145 0 obj
<< /Type /Annot
/Subtype /Link
/A 146 0 R
/Border [0 0 0]
/H /I
/Rect [ 35.2500 363.9645 260.2500 515.4645 ]
>>
endobj
146 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/files/2011/07/Figure-2.jpg)
>>
endobj
147 0 obj
<< /Type /Page
/Parent 3 0 R
/Contents 148 0 R
>>
endobj
148 0 obj
<<
/Length 118429 >>
stream

0.271 0.267 0.267 rg
q
15.000 67.484 577.500 709.516 re W n
0.271 0.267 0.267 rg
BT 26.250 750.278 Td /F4 12.0 Tf  [(Predicting AAO)] TJ ET
BT 26.250 730.324 Td /F1 9.8 Tf  [(The Langbehn formula \(LB 06\) predicted an AAO of 46.82 \(SD 10.5, range 23-89\) when 10 years of age; with age at a disease )] TJ ET
BT 26.250 718.419 Td /F1 9.8 Tf  [(burden of 200, the predicted average AAO was 46.65 \(SD 10.14, range 23-74\). The agreement rate with the investigator�s )] TJ ET
BT 26.250 706.515 Td /F1 9.8 Tf  [(estimate was 0.46 \(Table 2\). In 280 participants \(140 women\) with the necessary data the Ranen formula predicted an AAO of )] TJ ET
BT 26.250 694.610 Td /F1 9.8 Tf  [(41.9 years \(SD 7.9, range 8-61\). In that group of participants this is similar to the investigator�s estimates of 42 years. The )] TJ ET
BT 26.250 682.705 Td /F1 9.8 Tf  [(agreement rate was 0.46 \(Table 2\).)] TJ ET
BT 26.250 663.300 Td /F4 9.8 Tf  [(Comparing formulae derived AAO)] TJ ET
BT 26.250 643.896 Td /F1 9.8 Tf  [(In a total of 206 REGISTRY patients \(109 women\) with complete data the best agreement rate was between the extrapolated )] TJ ET
BT 26.250 631.991 Td /F1 9.8 Tf  [(AAOs on the longitudinal TFC and motor score data \(0.76, Table 2\). Using parent AAO and CAG repeats resulted in the )] TJ ET
BT 26.250 620.086 Td /F1 9.8 Tf  [(following formula that best predicted the investigator�s AAO estimate \(Ranen analog\):)] TJ ET
BT 26.250 600.681 Td /F1 9.8 Tf  [(AAO=90.3918+0.3293*parent AAO-1.3996*CAG repeats)] TJ ET
BT 26.250 581.277 Td /F1 9.8 Tf  [(In a next step we entered all available data into a regression model for the prediction of the investigator�s estimate of AAO )] TJ ET
BT 26.250 569.372 Td /F1 9.8 Tf  [(\(Ranen extended\). Motor score, parent AAO, CAG repeats, and gender significantly contributed to the regression model )] TJ ET
BT 26.250 557.467 Td /F1 9.8 Tf  [(resulting in the following formula:)] TJ ET
BT 26.250 538.062 Td /F1 9.8 Tf  [(AAO=88.7546+0.0430*motorscore+0.3546*parent AAO-1.4311*CAG repeats+1.0124*gender \(male=1, female=0\). We then )] TJ ET
BT 26.250 526.158 Td /F1 9.8 Tf  [(entered the dataset of each participant into this formula to arrive at the calculated AAO.)] TJ ET
BT 26.250 506.753 Td /F1 9.8 Tf  [(The data driven formula resembles the Ranen and Ranen analogous formula with high agreement rates \(0.97, Table 2\) while )] TJ ET
BT 26.250 494.848 Td /F1 9.8 Tf  [(the agreement rates with other AAO calculations was much lower \(Table 2\).)] TJ ET
BT 26.250 475.443 Td /F1 9.8 Tf  [(We then assessed 145 participants with a motor onset. The findings were similar to the analyses including all participants )] TJ ET
BT 26.250 463.539 Td /F1 9.8 Tf  [(regardless of major symptom at onset \(Table 2\); the rater estimated an earlier onset than the AAO from the regression analyses.)] TJ ET
BT 26.250 444.134 Td /F4 9.8 Tf  [(Table 2.)] TJ ET
1.000 1.000 1.000 rg
26.250 67.484 555.000 366.769 re f
0.267 0.267 0.267 rg
26.625 433.128 72.770 0.750 re f
26.625 417.247 0.750 16.631 re f
98.645 433.128 72.770 0.750 re f
98.645 417.247 0.750 16.631 re f
170.665 433.128 35.400 0.750 re f
206.065 433.128 86.649 0.750 re f
292.715 433.128 38.675 0.750 re f
331.389 433.128 39.050 0.750 re f
170.665 417.247 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 423.273 Td /F4 9.8 Tf  [(All participants)] TJ ET
0.267 0.267 0.267 rg
369.689 433.128 39.104 0.750 re f
408.793 433.128 88.829 0.750 re f
497.621 433.128 41.439 0.750 re f
539.061 433.128 41.814 0.750 re f
369.689 417.247 0.750 16.631 re f
580.125 417.247 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 423.273 Td /F4 9.8 Tf  [(Participants with motor onset)] TJ ET
0.267 0.267 0.267 rg
26.625 417.247 72.770 0.750 re f
26.625 401.366 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 407.392 Td /F4 9.8 Tf  [(Formula 1)] TJ ET
0.267 0.267 0.267 rg
98.645 417.247 72.770 0.750 re f
98.645 401.366 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 407.392 Td /F4 9.8 Tf  [(Formula 2)] TJ ET
0.267 0.267 0.267 rg
170.665 417.247 35.775 0.750 re f
170.665 401.366 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 407.392 Td /F4 9.8 Tf  [(N)] TJ ET
0.267 0.267 0.267 rg
205.690 417.247 87.399 0.750 re f
205.690 401.366 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 407.392 Td /F4 9.8 Tf  [(agreement rate)] TJ ET
0.267 0.267 0.267 rg
292.340 417.247 39.050 0.750 re f
331.389 417.247 39.050 0.750 re f
292.340 401.366 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 407.392 Td /F4 9.8 Tf  [(95% CI)] TJ ET
0.267 0.267 0.267 rg
369.689 417.247 39.479 0.750 re f
369.689 401.366 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 407.392 Td /F4 9.8 Tf  [(N)] TJ ET
0.267 0.267 0.267 rg
408.418 417.247 89.579 0.750 re f
408.418 401.366 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 407.392 Td /F4 9.8 Tf  [(Agreement rate)] TJ ET
0.267 0.267 0.267 rg
497.246 417.247 41.814 0.750 re f
539.061 417.247 41.814 0.750 re f
497.246 401.366 0.750 16.631 re f
580.125 401.366 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 407.392 Td /F4 9.8 Tf  [(95% CI)] TJ ET
0.267 0.267 0.267 rg
26.625 401.366 72.770 0.750 re f
26.625 385.484 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 391.511 Td /F1 9.8 Tf  [(Ranen)] TJ ET
0.267 0.267 0.267 rg
98.645 401.366 72.770 0.750 re f
98.645 385.484 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 391.511 Td /F1 9.8 Tf  [(Langb 06)] TJ ET
0.267 0.267 0.267 rg
170.665 401.366 35.775 0.750 re f
170.665 385.484 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 391.511 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 401.366 87.399 0.750 re f
205.690 385.484 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 391.511 Td /F1 9.8 Tf  [(0.50)] TJ ET
0.267 0.267 0.267 rg
292.340 401.366 39.425 0.750 re f
292.340 385.484 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 391.511 Td /F1 9.8 Tf  [(0.43)] TJ ET
0.267 0.267 0.267 rg
331.014 401.366 39.425 0.750 re f
331.014 385.484 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 391.511 Td /F1 9.8 Tf  [(0.58)] TJ ET
0.267 0.267 0.267 rg
369.689 401.366 39.479 0.750 re f
369.689 385.484 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 391.511 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 401.366 89.579 0.750 re f
408.418 385.484 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 391.511 Td /F1 9.8 Tf  [(0.49)] TJ ET
0.267 0.267 0.267 rg
497.246 401.366 42.189 0.750 re f
497.246 385.484 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 391.511 Td /F1 9.8 Tf  [(0.41)] TJ ET
0.267 0.267 0.267 rg
538.686 401.366 42.189 0.750 re f
538.686 385.484 0.750 16.631 re f
580.125 385.484 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 391.511 Td /F1 9.8 Tf  [(0.57)] TJ ET
0.267 0.267 0.267 rg
26.625 385.484 72.770 0.750 re f
26.625 369.603 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 375.629 Td /F1 9.8 Tf  [(Ranen)] TJ ET
0.267 0.267 0.267 rg
98.645 385.484 72.770 0.750 re f
98.645 369.603 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 375.629 Td /F1 9.8 Tf  [(Langb db 06)] TJ ET
0.267 0.267 0.267 rg
170.665 385.484 35.775 0.750 re f
170.665 369.603 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 375.629 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 385.484 87.399 0.750 re f
205.690 369.603 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 375.629 Td /F1 9.8 Tf  [(0.50)] TJ ET
0.267 0.267 0.267 rg
292.340 385.484 39.425 0.750 re f
292.340 369.603 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 375.629 Td /F1 9.8 Tf  [(0.43)] TJ ET
0.267 0.267 0.267 rg
331.014 385.484 39.425 0.750 re f
331.014 369.603 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 375.629 Td /F1 9.8 Tf  [(0.58)] TJ ET
0.267 0.267 0.267 rg
369.689 385.484 39.479 0.750 re f
369.689 369.603 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 375.629 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 385.484 89.579 0.750 re f
408.418 369.603 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 375.629 Td /F1 9.8 Tf  [(0.49)] TJ ET
0.267 0.267 0.267 rg
497.246 385.484 42.189 0.750 re f
497.246 369.603 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 375.629 Td /F1 9.8 Tf  [(0.41)] TJ ET
0.267 0.267 0.267 rg
538.686 385.484 42.189 0.750 re f
538.686 369.603 0.750 16.631 re f
580.125 369.603 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 375.629 Td /F1 9.8 Tf  [(0.57)] TJ ET
0.267 0.267 0.267 rg
26.625 369.603 72.770 0.750 re f
26.625 353.722 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 359.748 Td /F1 9.8 Tf  [(Ranen)] TJ ET
0.267 0.267 0.267 rg
98.645 369.603 72.770 0.750 re f
98.645 353.722 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 359.748 Td /F1 9.8 Tf  [(R. extended)] TJ ET
0.267 0.267 0.267 rg
170.665 369.603 35.775 0.750 re f
170.665 353.722 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 359.748 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 369.603 87.399 0.750 re f
205.690 353.722 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 359.748 Td /F1 9.8 Tf  [(0.97)] TJ ET
0.267 0.267 0.267 rg
292.340 369.603 39.425 0.750 re f
292.340 353.722 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 359.748 Td /F1 9.8 Tf  [(0.94)] TJ ET
0.267 0.267 0.267 rg
331.014 369.603 39.425 0.750 re f
331.014 353.722 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 359.748 Td /F1 9.8 Tf  [(0.99)] TJ ET
0.267 0.267 0.267 rg
369.689 369.603 39.479 0.750 re f
369.689 353.722 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 359.748 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 369.603 89.579 0.750 re f
408.418 353.722 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 359.748 Td /F1 9.8 Tf  [(0.96)] TJ ET
0.267 0.267 0.267 rg
497.246 369.603 42.189 0.750 re f
497.246 353.722 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 359.748 Td /F1 9.8 Tf  [(0.91)] TJ ET
0.267 0.267 0.267 rg
538.686 369.603 42.189 0.750 re f
538.686 353.722 0.750 16.631 re f
580.125 353.722 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 359.748 Td /F1 9.8 Tf  [(0.98)] TJ ET
0.267 0.267 0.267 rg
26.625 353.722 72.770 0.750 re f
26.625 337.840 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 343.867 Td /F1 9.8 Tf  [(Ranen)] TJ ET
0.267 0.267 0.267 rg
98.645 353.722 72.770 0.750 re f
98.645 337.840 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 343.867 Td /F1 9.8 Tf  [(R. analog)] TJ ET
0.267 0.267 0.267 rg
170.665 353.722 35.775 0.750 re f
170.665 337.840 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 343.867 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 353.722 87.399 0.750 re f
205.690 337.840 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 343.867 Td /F1 9.8 Tf  [(0.97)] TJ ET
0.267 0.267 0.267 rg
292.340 353.722 39.425 0.750 re f
292.340 337.840 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 343.867 Td /F1 9.8 Tf  [(0.94)] TJ ET
0.267 0.267 0.267 rg
331.014 353.722 39.425 0.750 re f
331.014 337.840 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 343.867 Td /F1 9.8 Tf  [(0.99)] TJ ET
0.267 0.267 0.267 rg
369.689 353.722 39.479 0.750 re f
369.689 337.840 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 343.867 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 353.722 89.579 0.750 re f
408.418 337.840 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 343.867 Td /F1 9.8 Tf  [(0.97)] TJ ET
0.267 0.267 0.267 rg
497.246 353.722 42.189 0.750 re f
497.246 337.840 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 343.867 Td /F1 9.8 Tf  [(0.92)] TJ ET
0.267 0.267 0.267 rg
538.686 353.722 42.189 0.750 re f
538.686 337.840 0.750 16.631 re f
580.125 337.840 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 343.867 Td /F1 9.8 Tf  [(0.99)] TJ ET
0.267 0.267 0.267 rg
26.625 337.840 72.770 0.750 re f
26.625 321.959 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 327.985 Td /F1 9.8 Tf  [(Ranen)] TJ ET
0.267 0.267 0.267 rg
98.645 337.840 72.770 0.750 re f
98.645 321.959 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 327.985 Td /F1 9.8 Tf  [(Motor)] TJ ET
0.267 0.267 0.267 rg
170.665 337.840 35.775 0.750 re f
170.665 321.959 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 327.985 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 337.840 87.399 0.750 re f
205.690 321.959 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 327.985 Td /F1 9.8 Tf  [(0.35)] TJ ET
0.267 0.267 0.267 rg
292.340 337.840 39.425 0.750 re f
292.340 321.959 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 327.985 Td /F1 9.8 Tf  [(0.29)] TJ ET
0.267 0.267 0.267 rg
331.014 337.840 39.425 0.750 re f
331.014 321.959 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 327.985 Td /F1 9.8 Tf  [(0.42)] TJ ET
0.267 0.267 0.267 rg
369.689 337.840 39.479 0.750 re f
369.689 321.959 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 327.985 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 337.840 89.579 0.750 re f
408.418 321.959 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 327.985 Td /F1 9.8 Tf  [(0.35)] TJ ET
0.267 0.267 0.267 rg
497.246 337.840 42.189 0.750 re f
497.246 321.959 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 327.985 Td /F1 9.8 Tf  [(0.27)] TJ ET
0.267 0.267 0.267 rg
538.686 337.840 42.189 0.750 re f
538.686 321.959 0.750 16.631 re f
580.125 321.959 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 327.985 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
26.625 321.959 72.770 0.750 re f
26.625 306.078 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 312.104 Td /F1 9.8 Tf  [(Ranen)] TJ ET
0.267 0.267 0.267 rg
98.645 321.959 72.770 0.750 re f
98.645 306.078 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 312.104 Td /F1 9.8 Tf  [(Rater)] TJ ET
0.267 0.267 0.267 rg
170.665 321.959 35.775 0.750 re f
170.665 306.078 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 312.104 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 321.959 87.399 0.750 re f
205.690 306.078 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 312.104 Td /F1 9.8 Tf  [(0.45)] TJ ET
0.267 0.267 0.267 rg
292.340 321.959 39.425 0.750 re f
292.340 306.078 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 312.104 Td /F1 9.8 Tf  [(0.38)] TJ ET
0.267 0.267 0.267 rg
331.014 321.959 39.425 0.750 re f
331.014 306.078 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 312.104 Td /F1 9.8 Tf  [(0.52)] TJ ET
0.267 0.267 0.267 rg
369.689 321.959 39.479 0.750 re f
369.689 306.078 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 312.104 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 321.959 89.579 0.750 re f
408.418 306.078 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 312.104 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
497.246 321.959 42.189 0.750 re f
497.246 306.078 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 312.104 Td /F1 9.8 Tf  [(0.36)] TJ ET
0.267 0.267 0.267 rg
538.686 321.959 42.189 0.750 re f
538.686 306.078 0.750 16.631 re f
580.125 306.078 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 312.104 Td /F1 9.8 Tf  [(0.53)] TJ ET
0.267 0.267 0.267 rg
26.625 306.078 72.770 0.750 re f
26.625 290.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 296.223 Td /F1 9.8 Tf  [(Ranen)] TJ ET
0.267 0.267 0.267 rg
98.645 306.078 72.770 0.750 re f
98.645 290.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 296.223 Td /F1 9.8 Tf  [(TFC)] TJ ET
0.267 0.267 0.267 rg
170.665 306.078 35.775 0.750 re f
170.665 290.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 296.223 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 306.078 87.399 0.750 re f
205.690 290.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 296.223 Td /F1 9.8 Tf  [(0.37)] TJ ET
0.267 0.267 0.267 rg
292.340 306.078 39.425 0.750 re f
292.340 290.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 296.223 Td /F1 9.8 Tf  [(0.31)] TJ ET
0.267 0.267 0.267 rg
331.014 306.078 39.425 0.750 re f
331.014 290.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 296.223 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
369.689 306.078 39.479 0.750 re f
369.689 290.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 296.223 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 306.078 89.579 0.750 re f
408.418 290.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 296.223 Td /F1 9.8 Tf  [(0.32)] TJ ET
0.267 0.267 0.267 rg
497.246 306.078 42.189 0.750 re f
497.246 290.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 296.223 Td /F1 9.8 Tf  [(0.25)] TJ ET
0.267 0.267 0.267 rg
538.686 306.078 42.189 0.750 re f
538.686 290.197 0.750 16.631 re f
580.125 290.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 296.223 Td /F1 9.8 Tf  [(0.41)] TJ ET
0.267 0.267 0.267 rg
26.625 290.197 72.770 0.750 re f
26.625 274.315 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 280.342 Td /F1 9.8 Tf  [(Langb 06)] TJ ET
0.267 0.267 0.267 rg
98.645 290.197 72.770 0.750 re f
98.645 274.315 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 280.342 Td /F1 9.8 Tf  [(R. extended)] TJ ET
0.267 0.267 0.267 rg
170.665 290.197 35.775 0.750 re f
170.665 274.315 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 280.342 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 290.197 87.399 0.750 re f
205.690 274.315 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 280.342 Td /F1 9.8 Tf  [(0.63)] TJ ET
0.267 0.267 0.267 rg
292.340 290.197 39.425 0.750 re f
292.340 274.315 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 280.342 Td /F1 9.8 Tf  [(0.56)] TJ ET
0.267 0.267 0.267 rg
331.014 290.197 39.425 0.750 re f
331.014 274.315 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 280.342 Td /F1 9.8 Tf  [(0.69)] TJ ET
0.267 0.267 0.267 rg
369.689 290.197 39.479 0.750 re f
369.689 274.315 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 280.342 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 290.197 89.579 0.750 re f
408.418 274.315 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 280.342 Td /F1 9.8 Tf  [(0.59)] TJ ET
0.267 0.267 0.267 rg
497.246 290.197 42.189 0.750 re f
497.246 274.315 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 280.342 Td /F1 9.8 Tf  [(0.50)] TJ ET
0.267 0.267 0.267 rg
538.686 290.197 42.189 0.750 re f
538.686 274.315 0.750 16.631 re f
580.125 274.315 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 280.342 Td /F1 9.8 Tf  [(0.67)] TJ ET
0.267 0.267 0.267 rg
26.625 274.315 72.770 0.750 re f
26.625 258.434 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 264.460 Td /F1 9.8 Tf  [(Langb 06)] TJ ET
0.267 0.267 0.267 rg
98.645 274.315 72.770 0.750 re f
98.645 258.434 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 264.460 Td /F1 9.8 Tf  [(R. Analog)] TJ ET
0.267 0.267 0.267 rg
170.665 274.315 35.775 0.750 re f
170.665 258.434 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 264.460 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 274.315 87.399 0.750 re f
205.690 258.434 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 264.460 Td /F1 9.8 Tf  [(0.65)] TJ ET
0.267 0.267 0.267 rg
292.340 274.315 39.425 0.750 re f
292.340 258.434 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 264.460 Td /F1 9.8 Tf  [(0.58)] TJ ET
0.267 0.267 0.267 rg
331.014 274.315 39.425 0.750 re f
331.014 258.434 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 264.460 Td /F1 9.8 Tf  [(0.72)] TJ ET
0.267 0.267 0.267 rg
369.689 274.315 39.479 0.750 re f
369.689 258.434 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 264.460 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 274.315 89.579 0.750 re f
408.418 258.434 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 264.460 Td /F1 9.8 Tf  [(0.60)] TJ ET
0.267 0.267 0.267 rg
497.246 274.315 42.189 0.750 re f
497.246 258.434 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 264.460 Td /F1 9.8 Tf  [(0.52)] TJ ET
0.267 0.267 0.267 rg
538.686 274.315 42.189 0.750 re f
538.686 258.434 0.750 16.631 re f
580.125 258.434 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 264.460 Td /F1 9.8 Tf  [(0.68)] TJ ET
0.267 0.267 0.267 rg
26.625 258.434 72.770 0.750 re f
26.625 242.553 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 248.579 Td /F1 9.8 Tf  [(Langb 06)] TJ ET
0.267 0.267 0.267 rg
98.645 258.434 72.770 0.750 re f
98.645 242.553 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 248.579 Td /F1 9.8 Tf  [(Motor)] TJ ET
0.267 0.267 0.267 rg
170.665 258.434 35.775 0.750 re f
170.665 242.553 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 248.579 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 258.434 87.399 0.750 re f
205.690 242.553 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 248.579 Td /F1 9.8 Tf  [(0.50)] TJ ET
0.267 0.267 0.267 rg
292.340 258.434 39.425 0.750 re f
292.340 242.553 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 248.579 Td /F1 9.8 Tf  [(0.43)] TJ ET
0.267 0.267 0.267 rg
331.014 258.434 39.425 0.750 re f
331.014 242.553 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 248.579 Td /F1 9.8 Tf  [(0.57)] TJ ET
0.267 0.267 0.267 rg
369.689 258.434 39.479 0.750 re f
369.689 242.553 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 248.579 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 258.434 89.579 0.750 re f
408.418 242.553 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 248.579 Td /F1 9.8 Tf  [(0.57)] TJ ET
0.267 0.267 0.267 rg
497.246 258.434 42.189 0.750 re f
497.246 242.553 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 248.579 Td /F1 9.8 Tf  [(0.48)] TJ ET
0.267 0.267 0.267 rg
538.686 258.434 42.189 0.750 re f
538.686 242.553 0.750 16.631 re f
580.125 242.553 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 248.579 Td /F1 9.8 Tf  [(0.65)] TJ ET
0.267 0.267 0.267 rg
26.625 242.553 72.770 0.750 re f
26.625 226.672 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 232.698 Td /F1 9.8 Tf  [(Langb 06)] TJ ET
0.267 0.267 0.267 rg
98.645 242.553 72.770 0.750 re f
98.645 226.672 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 232.698 Td /F1 9.8 Tf  [(TFC)] TJ ET
0.267 0.267 0.267 rg
170.665 242.553 35.775 0.750 re f
170.665 226.672 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 232.698 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 242.553 87.399 0.750 re f
205.690 226.672 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 232.698 Td /F1 9.8 Tf  [(0.51)] TJ ET
0.267 0.267 0.267 rg
292.340 242.553 39.425 0.750 re f
292.340 226.672 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 232.698 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
331.014 242.553 39.425 0.750 re f
331.014 226.672 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 232.698 Td /F1 9.8 Tf  [(0.58)] TJ ET
0.267 0.267 0.267 rg
369.689 242.553 39.479 0.750 re f
369.689 226.672 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 232.698 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 242.553 89.579 0.750 re f
408.418 226.672 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 232.698 Td /F1 9.8 Tf  [(0.55)] TJ ET
0.267 0.267 0.267 rg
497.246 242.553 42.189 0.750 re f
497.246 226.672 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 232.698 Td /F1 9.8 Tf  [(0.47)] TJ ET
0.267 0.267 0.267 rg
538.686 242.553 42.189 0.750 re f
538.686 226.672 0.750 16.631 re f
580.125 226.672 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 232.698 Td /F1 9.8 Tf  [(0.63)] TJ ET
0.267 0.267 0.267 rg
26.625 226.672 72.770 0.750 re f
26.625 210.790 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 216.817 Td /F1 9.8 Tf  [(Langb db 06)] TJ ET
0.267 0.267 0.267 rg
98.645 226.672 72.770 0.750 re f
98.645 210.790 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 216.817 Td /F1 9.8 Tf  [(Langb 06)] TJ ET
0.267 0.267 0.267 rg
170.665 226.672 35.775 0.750 re f
170.665 210.790 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 216.817 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 226.672 87.399 0.750 re f
205.690 210.790 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 216.817 Td /F1 9.8 Tf  [(1.00)] TJ ET
0.267 0.267 0.267 rg
292.340 226.672 39.425 0.750 re f
292.340 210.790 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 216.817 Td /F1 9.8 Tf  [(0.98)] TJ ET
0.267 0.267 0.267 rg
331.014 226.672 39.425 0.750 re f
331.014 210.790 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 216.817 Td /F1 9.8 Tf  [(1.00)] TJ ET
0.267 0.267 0.267 rg
369.689 226.672 39.479 0.750 re f
369.689 210.790 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 216.817 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 226.672 89.579 0.750 re f
408.418 210.790 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 216.817 Td /F1 9.8 Tf  [(1.00)] TJ ET
0.267 0.267 0.267 rg
497.246 226.672 42.189 0.750 re f
497.246 210.790 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 216.817 Td /F1 9.8 Tf  [(0.97)] TJ ET
0.267 0.267 0.267 rg
538.686 226.672 42.189 0.750 re f
538.686 210.790 0.750 16.631 re f
580.125 210.790 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 216.817 Td /F1 9.8 Tf  [(1.00)] TJ ET
0.267 0.267 0.267 rg
26.625 210.790 72.770 0.750 re f
26.625 194.909 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 200.935 Td /F1 9.8 Tf  [(Langb db 06)] TJ ET
0.267 0.267 0.267 rg
98.645 210.790 72.770 0.750 re f
98.645 194.909 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 200.935 Td /F1 9.8 Tf  [(R. extended)] TJ ET
0.267 0.267 0.267 rg
170.665 210.790 35.775 0.750 re f
170.665 194.909 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 200.935 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 210.790 87.399 0.750 re f
205.690 194.909 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 200.935 Td /F1 9.8 Tf  [(0.60)] TJ ET
0.267 0.267 0.267 rg
292.340 210.790 39.425 0.750 re f
292.340 194.909 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 200.935 Td /F1 9.8 Tf  [(0.53)] TJ ET
0.267 0.267 0.267 rg
331.014 210.790 39.425 0.750 re f
331.014 194.909 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 200.935 Td /F1 9.8 Tf  [(0.67)] TJ ET
0.267 0.267 0.267 rg
369.689 210.790 39.479 0.750 re f
369.689 194.909 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 200.935 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 210.790 89.579 0.750 re f
408.418 194.909 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 200.935 Td /F1 9.8 Tf  [(0.55)] TJ ET
0.267 0.267 0.267 rg
497.246 210.790 42.189 0.750 re f
497.246 194.909 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 200.935 Td /F1 9.8 Tf  [(0.47)] TJ ET
0.267 0.267 0.267 rg
538.686 210.790 42.189 0.750 re f
538.686 194.909 0.750 16.631 re f
580.125 194.909 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 200.935 Td /F1 9.8 Tf  [(0.63)] TJ ET
0.267 0.267 0.267 rg
26.625 194.909 72.770 0.750 re f
26.625 179.028 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 185.054 Td /F1 9.8 Tf  [(Langb db 06)] TJ ET
0.267 0.267 0.267 rg
98.645 194.909 72.770 0.750 re f
98.645 179.028 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 185.054 Td /F1 9.8 Tf  [(R. Analog)] TJ ET
0.267 0.267 0.267 rg
170.665 194.909 35.775 0.750 re f
170.665 179.028 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 185.054 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 194.909 87.399 0.750 re f
205.690 179.028 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 185.054 Td /F1 9.8 Tf  [(0.64)] TJ ET
0.267 0.267 0.267 rg
292.340 194.909 39.425 0.750 re f
292.340 179.028 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 185.054 Td /F1 9.8 Tf  [(0.57)] TJ ET
0.267 0.267 0.267 rg
331.014 194.909 39.425 0.750 re f
331.014 179.028 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 185.054 Td /F1 9.8 Tf  [(0.70)] TJ ET
0.267 0.267 0.267 rg
369.689 194.909 39.479 0.750 re f
369.689 179.028 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 185.054 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 194.909 89.579 0.750 re f
408.418 179.028 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 185.054 Td /F1 9.8 Tf  [(0.59)] TJ ET
0.267 0.267 0.267 rg
497.246 194.909 42.189 0.750 re f
497.246 179.028 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 185.054 Td /F1 9.8 Tf  [(0.50)] TJ ET
0.267 0.267 0.267 rg
538.686 194.909 42.189 0.750 re f
538.686 179.028 0.750 16.631 re f
580.125 179.028 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 185.054 Td /F1 9.8 Tf  [(0.67)] TJ ET
0.267 0.267 0.267 rg
26.625 179.028 72.770 0.750 re f
26.625 163.147 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 169.173 Td /F1 9.8 Tf  [(Langb db 06)] TJ ET
0.267 0.267 0.267 rg
98.645 179.028 72.770 0.750 re f
98.645 163.147 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 169.173 Td /F1 9.8 Tf  [(Motor)] TJ ET
0.267 0.267 0.267 rg
170.665 179.028 35.775 0.750 re f
170.665 163.147 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 169.173 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 179.028 87.399 0.750 re f
205.690 163.147 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 169.173 Td /F1 9.8 Tf  [(0.51)] TJ ET
0.267 0.267 0.267 rg
292.340 179.028 39.425 0.750 re f
292.340 163.147 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 169.173 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
331.014 179.028 39.425 0.750 re f
331.014 163.147 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 169.173 Td /F1 9.8 Tf  [(0.58)] TJ ET
0.267 0.267 0.267 rg
369.689 179.028 39.479 0.750 re f
369.689 163.147 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 169.173 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 179.028 89.579 0.750 re f
408.418 163.147 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 169.173 Td /F1 9.8 Tf  [(0.59)] TJ ET
0.267 0.267 0.267 rg
497.246 179.028 42.189 0.750 re f
497.246 163.147 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 169.173 Td /F1 9.8 Tf  [(0.50)] TJ ET
0.267 0.267 0.267 rg
538.686 179.028 42.189 0.750 re f
538.686 163.147 0.750 16.631 re f
580.125 163.147 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 169.173 Td /F1 9.8 Tf  [(0.67)] TJ ET
0.267 0.267 0.267 rg
26.625 163.147 72.770 0.750 re f
26.625 147.265 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 153.292 Td /F1 9.8 Tf  [(Langb db 06)] TJ ET
0.267 0.267 0.267 rg
98.645 163.147 72.770 0.750 re f
98.645 147.265 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 153.292 Td /F1 9.8 Tf  [(TFC)] TJ ET
0.267 0.267 0.267 rg
170.665 163.147 35.775 0.750 re f
170.665 147.265 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 153.292 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 163.147 87.399 0.750 re f
205.690 147.265 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 153.292 Td /F1 9.8 Tf  [(0.51)] TJ ET
0.267 0.267 0.267 rg
292.340 163.147 39.425 0.750 re f
292.340 147.265 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 153.292 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
331.014 163.147 39.425 0.750 re f
331.014 147.265 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 153.292 Td /F1 9.8 Tf  [(0.58)] TJ ET
0.267 0.267 0.267 rg
369.689 163.147 39.479 0.750 re f
369.689 147.265 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 153.292 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 163.147 89.579 0.750 re f
408.418 147.265 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 153.292 Td /F1 9.8 Tf  [(0.55)] TJ ET
0.267 0.267 0.267 rg
497.246 163.147 42.189 0.750 re f
497.246 147.265 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 153.292 Td /F1 9.8 Tf  [(0.47)] TJ ET
0.267 0.267 0.267 rg
538.686 163.147 42.189 0.750 re f
538.686 147.265 0.750 16.631 re f
580.125 147.265 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 153.292 Td /F1 9.8 Tf  [(0.63)] TJ ET
0.267 0.267 0.267 rg
26.625 147.265 72.770 0.750 re f
26.625 131.384 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 137.410 Td /F1 9.8 Tf  [(R. extended)] TJ ET
0.267 0.267 0.267 rg
98.645 147.265 72.770 0.750 re f
98.645 131.384 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 137.410 Td /F1 9.8 Tf  [(R. analog)] TJ ET
0.267 0.267 0.267 rg
170.665 147.265 35.775 0.750 re f
170.665 131.384 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 137.410 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 147.265 87.399 0.750 re f
205.690 131.384 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 137.410 Td /F1 9.8 Tf  [(1.00)] TJ ET
0.267 0.267 0.267 rg
292.340 147.265 39.425 0.750 re f
292.340 131.384 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 137.410 Td /F1 9.8 Tf  [(0.98)] TJ ET
0.267 0.267 0.267 rg
331.014 147.265 39.425 0.750 re f
331.014 131.384 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 137.410 Td /F1 9.8 Tf  [(1.00)] TJ ET
0.267 0.267 0.267 rg
369.689 147.265 39.479 0.750 re f
369.689 131.384 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 137.410 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 147.265 89.579 0.750 re f
408.418 131.384 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 137.410 Td /F1 9.8 Tf  [(1.00)] TJ ET
0.267 0.267 0.267 rg
497.246 147.265 42.189 0.750 re f
497.246 131.384 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 137.410 Td /F1 9.8 Tf  [(0.97)] TJ ET
0.267 0.267 0.267 rg
538.686 147.265 42.189 0.750 re f
538.686 131.384 0.750 16.631 re f
580.125 131.384 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 137.410 Td /F1 9.8 Tf  [(1.00)] TJ ET
0.267 0.267 0.267 rg
26.625 131.384 72.770 0.750 re f
26.625 115.503 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 121.529 Td /F1 9.8 Tf  [(R. extended)] TJ ET
0.267 0.267 0.267 rg
98.645 131.384 72.770 0.750 re f
98.645 115.503 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 121.529 Td /F1 9.8 Tf  [(Motor)] TJ ET
0.267 0.267 0.267 rg
170.665 131.384 35.775 0.750 re f
170.665 115.503 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 121.529 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 131.384 87.399 0.750 re f
205.690 115.503 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 121.529 Td /F1 9.8 Tf  [(0.41)] TJ ET
0.267 0.267 0.267 rg
292.340 131.384 39.425 0.750 re f
292.340 115.503 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 121.529 Td /F1 9.8 Tf  [(0.34)] TJ ET
0.267 0.267 0.267 rg
331.014 131.384 39.425 0.750 re f
331.014 115.503 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 121.529 Td /F1 9.8 Tf  [(0.48)] TJ ET
0.267 0.267 0.267 rg
369.689 131.384 39.479 0.750 re f
369.689 115.503 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 121.529 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 131.384 89.579 0.750 re f
408.418 115.503 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 121.529 Td /F1 9.8 Tf  [(0.43)] TJ ET
0.267 0.267 0.267 rg
497.246 131.384 42.189 0.750 re f
497.246 115.503 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 121.529 Td /F1 9.8 Tf  [(0.35)] TJ ET
0.267 0.267 0.267 rg
538.686 131.384 42.189 0.750 re f
538.686 115.503 0.750 16.631 re f
580.125 115.503 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 121.529 Td /F1 9.8 Tf  [(0.52)] TJ ET
0.267 0.267 0.267 rg
26.625 115.503 72.770 0.750 re f
26.625 99.622 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 105.648 Td /F1 9.8 Tf  [(R. extended)] TJ ET
0.267 0.267 0.267 rg
98.645 115.503 72.770 0.750 re f
98.645 99.622 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 105.648 Td /F1 9.8 Tf  [(TFC)] TJ ET
0.267 0.267 0.267 rg
170.665 115.503 35.775 0.750 re f
170.665 99.622 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 105.648 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 115.503 87.399 0.750 re f
205.690 99.622 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 105.648 Td /F1 9.8 Tf  [(0.43)] TJ ET
0.267 0.267 0.267 rg
292.340 115.503 39.425 0.750 re f
292.340 99.622 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 105.648 Td /F1 9.8 Tf  [(0.36)] TJ ET
0.267 0.267 0.267 rg
331.014 115.503 39.425 0.750 re f
331.014 99.622 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 105.648 Td /F1 9.8 Tf  [(0.50)] TJ ET
0.267 0.267 0.267 rg
369.689 115.503 39.479 0.750 re f
369.689 99.622 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 105.648 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 115.503 89.579 0.750 re f
408.418 99.622 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 105.648 Td /F1 9.8 Tf  [(0.40)] TJ ET
0.267 0.267 0.267 rg
497.246 115.503 42.189 0.750 re f
497.246 99.622 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 105.648 Td /F1 9.8 Tf  [(0.32)] TJ ET
0.267 0.267 0.267 rg
538.686 115.503 42.189 0.750 re f
538.686 99.622 0.750 16.631 re f
580.125 99.622 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 105.648 Td /F1 9.8 Tf  [(0.48)] TJ ET
0.267 0.267 0.267 rg
26.625 99.622 72.770 0.750 re f
26.625 83.740 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 89.767 Td /F1 9.8 Tf  [(R. analog)] TJ ET
0.267 0.267 0.267 rg
98.645 99.622 72.770 0.750 re f
98.645 83.740 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 89.767 Td /F1 9.8 Tf  [(Motor)] TJ ET
0.267 0.267 0.267 rg
170.665 99.622 35.775 0.750 re f
170.665 83.740 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 89.767 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 99.622 87.399 0.750 re f
205.690 83.740 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 89.767 Td /F1 9.8 Tf  [(0.41)] TJ ET
0.267 0.267 0.267 rg
292.340 99.622 39.425 0.750 re f
292.340 83.740 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 89.767 Td /F1 9.8 Tf  [(0.34)] TJ ET
0.267 0.267 0.267 rg
331.014 99.622 39.425 0.750 re f
331.014 83.740 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 89.767 Td /F1 9.8 Tf  [(0.48)] TJ ET
0.267 0.267 0.267 rg
369.689 99.622 39.479 0.750 re f
369.689 83.740 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 89.767 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 99.622 89.579 0.750 re f
408.418 83.740 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 89.767 Td /F1 9.8 Tf  [(0.43)] TJ ET
0.267 0.267 0.267 rg
497.246 99.622 42.189 0.750 re f
497.246 83.740 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 89.767 Td /F1 9.8 Tf  [(0.35)] TJ ET
0.267 0.267 0.267 rg
538.686 99.622 42.189 0.750 re f
538.686 83.740 0.750 16.631 re f
580.125 83.740 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 89.767 Td /F1 9.8 Tf  [(0.51)] TJ ET
0.267 0.267 0.267 rg
26.625 83.740 72.770 0.750 re f
26.625 67.859 72.770 0.750 re f
26.625 67.859 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 73.885 Td /F1 9.8 Tf  [(R. analog)] TJ ET
0.267 0.267 0.267 rg
98.645 83.740 72.770 0.750 re f
98.645 67.859 72.770 0.750 re f
98.645 67.859 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 73.885 Td /F1 9.8 Tf  [(TFC)] TJ ET
0.267 0.267 0.267 rg
170.665 83.740 35.775 0.750 re f
170.665 67.859 35.775 0.750 re f
170.665 67.859 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 73.885 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 83.740 87.399 0.750 re f
205.690 67.859 87.399 0.750 re f
205.690 67.859 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 73.885 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
292.340 83.740 39.425 0.750 re f
292.340 67.859 39.425 0.750 re f
292.340 67.859 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 73.885 Td /F1 9.8 Tf  [(0.37)] TJ ET
0.267 0.267 0.267 rg
331.014 83.740 39.425 0.750 re f
331.014 67.859 39.425 0.750 re f
331.014 67.859 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 73.885 Td /F1 9.8 Tf  [(0.51)] TJ ET
0.267 0.267 0.267 rg
369.689 83.740 39.479 0.750 re f
369.689 67.859 39.479 0.750 re f
369.689 67.859 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 73.885 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 83.740 89.579 0.750 re f
408.418 67.859 89.579 0.750 re f
408.418 67.859 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 73.885 Td /F1 9.8 Tf  [(0.41)] TJ ET
0.267 0.267 0.267 rg
497.246 83.740 42.189 0.750 re f
497.246 67.859 42.189 0.750 re f
497.246 67.859 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 73.885 Td /F1 9.8 Tf  [(0.33)] TJ ET
0.267 0.267 0.267 rg
538.686 83.740 42.189 0.750 re f
538.686 67.859 42.189 0.750 re f
538.686 67.859 0.750 16.631 re f
580.125 67.859 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 73.885 Td /F1 9.8 Tf  [(0.49)] TJ ET
Q
q
15.000 67.484 577.500 709.516 re W n
0.271 0.267 0.267 rg
BT 26.250 750.278 Td /F4 12.0 Tf  [(Predicting AAO)] TJ ET
BT 26.250 730.324 Td /F1 9.8 Tf  [(The Langbehn formula \(LB 06\) predicted an AAO of 46.82 \(SD 10.5, range 23-89\) when 10 years of age; with age at a disease )] TJ ET
BT 26.250 718.419 Td /F1 9.8 Tf  [(burden of 200, the predicted average AAO was 46.65 \(SD 10.14, range 23-74\). The agreement rate with the investigator�s )] TJ ET
BT 26.250 706.515 Td /F1 9.8 Tf  [(estimate was 0.46 \(Table 2\). In 280 participants \(140 women\) with the necessary data the Ranen formula predicted an AAO of )] TJ ET
BT 26.250 694.610 Td /F1 9.8 Tf  [(41.9 years \(SD 7.9, range 8-61\). In that group of participants this is similar to the investigator�s estimates of 42 years. The )] TJ ET
BT 26.250 682.705 Td /F1 9.8 Tf  [(agreement rate was 0.46 \(Table 2\).)] TJ ET
BT 26.250 663.300 Td /F4 9.8 Tf  [(Comparing formulae derived AAO)] TJ ET
BT 26.250 643.896 Td /F1 9.8 Tf  [(In a total of 206 REGISTRY patients \(109 women\) with complete data the best agreement rate was between the extrapolated )] TJ ET
BT 26.250 631.991 Td /F1 9.8 Tf  [(AAOs on the longitudinal TFC and motor score data \(0.76, Table 2\). Using parent AAO and CAG repeats resulted in the )] TJ ET
BT 26.250 620.086 Td /F1 9.8 Tf  [(following formula that best predicted the investigator�s AAO estimate \(Ranen analog\):)] TJ ET
BT 26.250 600.681 Td /F1 9.8 Tf  [(AAO=90.3918+0.3293*parent AAO-1.3996*CAG repeats)] TJ ET
BT 26.250 581.277 Td /F1 9.8 Tf  [(In a next step we entered all available data into a regression model for the prediction of the investigator�s estimate of AAO )] TJ ET
BT 26.250 569.372 Td /F1 9.8 Tf  [(\(Ranen extended\). Motor score, parent AAO, CAG repeats, and gender significantly contributed to the regression model )] TJ ET
BT 26.250 557.467 Td /F1 9.8 Tf  [(resulting in the following formula:)] TJ ET
BT 26.250 538.062 Td /F1 9.8 Tf  [(AAO=88.7546+0.0430*motorscore+0.3546*parent AAO-1.4311*CAG repeats+1.0124*gender \(male=1, female=0\). We then )] TJ ET
BT 26.250 526.158 Td /F1 9.8 Tf  [(entered the dataset of each participant into this formula to arrive at the calculated AAO.)] TJ ET
BT 26.250 506.753 Td /F1 9.8 Tf  [(The data driven formula resembles the Ranen and Ranen analogous formula with high agreement rates \(0.97, Table 2\) while )] TJ ET
BT 26.250 494.848 Td /F1 9.8 Tf  [(the agreement rates with other AAO calculations was much lower \(Table 2\).)] TJ ET
BT 26.250 475.443 Td /F1 9.8 Tf  [(We then assessed 145 participants with a motor onset. The findings were similar to the analyses including all participants )] TJ ET
BT 26.250 463.539 Td /F1 9.8 Tf  [(regardless of major symptom at onset \(Table 2\); the rater estimated an earlier onset than the AAO from the regression analyses.)] TJ ET
BT 26.250 444.134 Td /F4 9.8 Tf  [(Table 2.)] TJ ET
1.000 1.000 1.000 rg
26.250 67.484 555.000 366.769 re f
0.267 0.267 0.267 rg
26.625 433.128 72.770 0.750 re f
26.625 417.247 0.750 16.631 re f
98.645 433.128 72.770 0.750 re f
98.645 417.247 0.750 16.631 re f
170.665 433.128 35.400 0.750 re f
206.065 433.128 86.649 0.750 re f
292.715 433.128 38.675 0.750 re f
331.389 433.128 39.050 0.750 re f
170.665 417.247 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 423.273 Td /F4 9.8 Tf  [(All participants)] TJ ET
0.267 0.267 0.267 rg
369.689 433.128 39.104 0.750 re f
408.793 433.128 88.829 0.750 re f
497.621 433.128 41.439 0.750 re f
539.061 433.128 41.814 0.750 re f
369.689 417.247 0.750 16.631 re f
580.125 417.247 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 423.273 Td /F4 9.8 Tf  [(Participants with motor onset)] TJ ET
0.267 0.267 0.267 rg
26.625 417.247 72.770 0.750 re f
26.625 401.366 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 407.392 Td /F4 9.8 Tf  [(Formula 1)] TJ ET
0.267 0.267 0.267 rg
98.645 417.247 72.770 0.750 re f
98.645 401.366 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 407.392 Td /F4 9.8 Tf  [(Formula 2)] TJ ET
0.267 0.267 0.267 rg
170.665 417.247 35.775 0.750 re f
170.665 401.366 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 407.392 Td /F4 9.8 Tf  [(N)] TJ ET
0.267 0.267 0.267 rg
205.690 417.247 87.399 0.750 re f
205.690 401.366 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 407.392 Td /F4 9.8 Tf  [(agreement rate)] TJ ET
0.267 0.267 0.267 rg
292.340 417.247 39.050 0.750 re f
331.389 417.247 39.050 0.750 re f
292.340 401.366 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 407.392 Td /F4 9.8 Tf  [(95% CI)] TJ ET
0.267 0.267 0.267 rg
369.689 417.247 39.479 0.750 re f
369.689 401.366 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 407.392 Td /F4 9.8 Tf  [(N)] TJ ET
0.267 0.267 0.267 rg
408.418 417.247 89.579 0.750 re f
408.418 401.366 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 407.392 Td /F4 9.8 Tf  [(Agreement rate)] TJ ET
0.267 0.267 0.267 rg
497.246 417.247 41.814 0.750 re f
539.061 417.247 41.814 0.750 re f
497.246 401.366 0.750 16.631 re f
580.125 401.366 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 407.392 Td /F4 9.8 Tf  [(95% CI)] TJ ET
0.267 0.267 0.267 rg
26.625 401.366 72.770 0.750 re f
26.625 385.484 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 391.511 Td /F1 9.8 Tf  [(Ranen)] TJ ET
0.267 0.267 0.267 rg
98.645 401.366 72.770 0.750 re f
98.645 385.484 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 391.511 Td /F1 9.8 Tf  [(Langb 06)] TJ ET
0.267 0.267 0.267 rg
170.665 401.366 35.775 0.750 re f
170.665 385.484 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 391.511 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 401.366 87.399 0.750 re f
205.690 385.484 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 391.511 Td /F1 9.8 Tf  [(0.50)] TJ ET
0.267 0.267 0.267 rg
292.340 401.366 39.425 0.750 re f
292.340 385.484 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 391.511 Td /F1 9.8 Tf  [(0.43)] TJ ET
0.267 0.267 0.267 rg
331.014 401.366 39.425 0.750 re f
331.014 385.484 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 391.511 Td /F1 9.8 Tf  [(0.58)] TJ ET
0.267 0.267 0.267 rg
369.689 401.366 39.479 0.750 re f
369.689 385.484 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 391.511 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 401.366 89.579 0.750 re f
408.418 385.484 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 391.511 Td /F1 9.8 Tf  [(0.49)] TJ ET
0.267 0.267 0.267 rg
497.246 401.366 42.189 0.750 re f
497.246 385.484 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 391.511 Td /F1 9.8 Tf  [(0.41)] TJ ET
0.267 0.267 0.267 rg
538.686 401.366 42.189 0.750 re f
538.686 385.484 0.750 16.631 re f
580.125 385.484 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 391.511 Td /F1 9.8 Tf  [(0.57)] TJ ET
0.267 0.267 0.267 rg
26.625 385.484 72.770 0.750 re f
26.625 369.603 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 375.629 Td /F1 9.8 Tf  [(Ranen)] TJ ET
0.267 0.267 0.267 rg
98.645 385.484 72.770 0.750 re f
98.645 369.603 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 375.629 Td /F1 9.8 Tf  [(Langb db 06)] TJ ET
0.267 0.267 0.267 rg
170.665 385.484 35.775 0.750 re f
170.665 369.603 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 375.629 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 385.484 87.399 0.750 re f
205.690 369.603 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 375.629 Td /F1 9.8 Tf  [(0.50)] TJ ET
0.267 0.267 0.267 rg
292.340 385.484 39.425 0.750 re f
292.340 369.603 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 375.629 Td /F1 9.8 Tf  [(0.43)] TJ ET
0.267 0.267 0.267 rg
331.014 385.484 39.425 0.750 re f
331.014 369.603 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 375.629 Td /F1 9.8 Tf  [(0.58)] TJ ET
0.267 0.267 0.267 rg
369.689 385.484 39.479 0.750 re f
369.689 369.603 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 375.629 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 385.484 89.579 0.750 re f
408.418 369.603 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 375.629 Td /F1 9.8 Tf  [(0.49)] TJ ET
0.267 0.267 0.267 rg
497.246 385.484 42.189 0.750 re f
497.246 369.603 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 375.629 Td /F1 9.8 Tf  [(0.41)] TJ ET
0.267 0.267 0.267 rg
538.686 385.484 42.189 0.750 re f
538.686 369.603 0.750 16.631 re f
580.125 369.603 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 375.629 Td /F1 9.8 Tf  [(0.57)] TJ ET
0.267 0.267 0.267 rg
26.625 369.603 72.770 0.750 re f
26.625 353.722 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 359.748 Td /F1 9.8 Tf  [(Ranen)] TJ ET
0.267 0.267 0.267 rg
98.645 369.603 72.770 0.750 re f
98.645 353.722 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 359.748 Td /F1 9.8 Tf  [(R. extended)] TJ ET
0.267 0.267 0.267 rg
170.665 369.603 35.775 0.750 re f
170.665 353.722 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 359.748 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 369.603 87.399 0.750 re f
205.690 353.722 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 359.748 Td /F1 9.8 Tf  [(0.97)] TJ ET
0.267 0.267 0.267 rg
292.340 369.603 39.425 0.750 re f
292.340 353.722 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 359.748 Td /F1 9.8 Tf  [(0.94)] TJ ET
0.267 0.267 0.267 rg
331.014 369.603 39.425 0.750 re f
331.014 353.722 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 359.748 Td /F1 9.8 Tf  [(0.99)] TJ ET
0.267 0.267 0.267 rg
369.689 369.603 39.479 0.750 re f
369.689 353.722 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 359.748 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 369.603 89.579 0.750 re f
408.418 353.722 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 359.748 Td /F1 9.8 Tf  [(0.96)] TJ ET
0.267 0.267 0.267 rg
497.246 369.603 42.189 0.750 re f
497.246 353.722 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 359.748 Td /F1 9.8 Tf  [(0.91)] TJ ET
0.267 0.267 0.267 rg
538.686 369.603 42.189 0.750 re f
538.686 353.722 0.750 16.631 re f
580.125 353.722 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 359.748 Td /F1 9.8 Tf  [(0.98)] TJ ET
0.267 0.267 0.267 rg
26.625 353.722 72.770 0.750 re f
26.625 337.840 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 343.867 Td /F1 9.8 Tf  [(Ranen)] TJ ET
0.267 0.267 0.267 rg
98.645 353.722 72.770 0.750 re f
98.645 337.840 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 343.867 Td /F1 9.8 Tf  [(R. analog)] TJ ET
0.267 0.267 0.267 rg
170.665 353.722 35.775 0.750 re f
170.665 337.840 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 343.867 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 353.722 87.399 0.750 re f
205.690 337.840 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 343.867 Td /F1 9.8 Tf  [(0.97)] TJ ET
0.267 0.267 0.267 rg
292.340 353.722 39.425 0.750 re f
292.340 337.840 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 343.867 Td /F1 9.8 Tf  [(0.94)] TJ ET
0.267 0.267 0.267 rg
331.014 353.722 39.425 0.750 re f
331.014 337.840 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 343.867 Td /F1 9.8 Tf  [(0.99)] TJ ET
0.267 0.267 0.267 rg
369.689 353.722 39.479 0.750 re f
369.689 337.840 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 343.867 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 353.722 89.579 0.750 re f
408.418 337.840 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 343.867 Td /F1 9.8 Tf  [(0.97)] TJ ET
0.267 0.267 0.267 rg
497.246 353.722 42.189 0.750 re f
497.246 337.840 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 343.867 Td /F1 9.8 Tf  [(0.92)] TJ ET
0.267 0.267 0.267 rg
538.686 353.722 42.189 0.750 re f
538.686 337.840 0.750 16.631 re f
580.125 337.840 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 343.867 Td /F1 9.8 Tf  [(0.99)] TJ ET
0.267 0.267 0.267 rg
26.625 337.840 72.770 0.750 re f
26.625 321.959 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 327.985 Td /F1 9.8 Tf  [(Ranen)] TJ ET
0.267 0.267 0.267 rg
98.645 337.840 72.770 0.750 re f
98.645 321.959 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 327.985 Td /F1 9.8 Tf  [(Motor)] TJ ET
0.267 0.267 0.267 rg
170.665 337.840 35.775 0.750 re f
170.665 321.959 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 327.985 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 337.840 87.399 0.750 re f
205.690 321.959 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 327.985 Td /F1 9.8 Tf  [(0.35)] TJ ET
0.267 0.267 0.267 rg
292.340 337.840 39.425 0.750 re f
292.340 321.959 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 327.985 Td /F1 9.8 Tf  [(0.29)] TJ ET
0.267 0.267 0.267 rg
331.014 337.840 39.425 0.750 re f
331.014 321.959 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 327.985 Td /F1 9.8 Tf  [(0.42)] TJ ET
0.267 0.267 0.267 rg
369.689 337.840 39.479 0.750 re f
369.689 321.959 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 327.985 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 337.840 89.579 0.750 re f
408.418 321.959 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 327.985 Td /F1 9.8 Tf  [(0.35)] TJ ET
0.267 0.267 0.267 rg
497.246 337.840 42.189 0.750 re f
497.246 321.959 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 327.985 Td /F1 9.8 Tf  [(0.27)] TJ ET
0.267 0.267 0.267 rg
538.686 337.840 42.189 0.750 re f
538.686 321.959 0.750 16.631 re f
580.125 321.959 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 327.985 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
26.625 321.959 72.770 0.750 re f
26.625 306.078 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 312.104 Td /F1 9.8 Tf  [(Ranen)] TJ ET
0.267 0.267 0.267 rg
98.645 321.959 72.770 0.750 re f
98.645 306.078 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 312.104 Td /F1 9.8 Tf  [(Rater)] TJ ET
0.267 0.267 0.267 rg
170.665 321.959 35.775 0.750 re f
170.665 306.078 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 312.104 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 321.959 87.399 0.750 re f
205.690 306.078 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 312.104 Td /F1 9.8 Tf  [(0.45)] TJ ET
0.267 0.267 0.267 rg
292.340 321.959 39.425 0.750 re f
292.340 306.078 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 312.104 Td /F1 9.8 Tf  [(0.38)] TJ ET
0.267 0.267 0.267 rg
331.014 321.959 39.425 0.750 re f
331.014 306.078 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 312.104 Td /F1 9.8 Tf  [(0.52)] TJ ET
0.267 0.267 0.267 rg
369.689 321.959 39.479 0.750 re f
369.689 306.078 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 312.104 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 321.959 89.579 0.750 re f
408.418 306.078 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 312.104 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
497.246 321.959 42.189 0.750 re f
497.246 306.078 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 312.104 Td /F1 9.8 Tf  [(0.36)] TJ ET
0.267 0.267 0.267 rg
538.686 321.959 42.189 0.750 re f
538.686 306.078 0.750 16.631 re f
580.125 306.078 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 312.104 Td /F1 9.8 Tf  [(0.53)] TJ ET
0.267 0.267 0.267 rg
26.625 306.078 72.770 0.750 re f
26.625 290.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 296.223 Td /F1 9.8 Tf  [(Ranen)] TJ ET
0.267 0.267 0.267 rg
98.645 306.078 72.770 0.750 re f
98.645 290.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 296.223 Td /F1 9.8 Tf  [(TFC)] TJ ET
0.267 0.267 0.267 rg
170.665 306.078 35.775 0.750 re f
170.665 290.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 296.223 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 306.078 87.399 0.750 re f
205.690 290.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 296.223 Td /F1 9.8 Tf  [(0.37)] TJ ET
0.267 0.267 0.267 rg
292.340 306.078 39.425 0.750 re f
292.340 290.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 296.223 Td /F1 9.8 Tf  [(0.31)] TJ ET
0.267 0.267 0.267 rg
331.014 306.078 39.425 0.750 re f
331.014 290.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 296.223 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
369.689 306.078 39.479 0.750 re f
369.689 290.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 296.223 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 306.078 89.579 0.750 re f
408.418 290.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 296.223 Td /F1 9.8 Tf  [(0.32)] TJ ET
0.267 0.267 0.267 rg
497.246 306.078 42.189 0.750 re f
497.246 290.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 296.223 Td /F1 9.8 Tf  [(0.25)] TJ ET
0.267 0.267 0.267 rg
538.686 306.078 42.189 0.750 re f
538.686 290.197 0.750 16.631 re f
580.125 290.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 296.223 Td /F1 9.8 Tf  [(0.41)] TJ ET
0.267 0.267 0.267 rg
26.625 290.197 72.770 0.750 re f
26.625 274.315 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 280.342 Td /F1 9.8 Tf  [(Langb 06)] TJ ET
0.267 0.267 0.267 rg
98.645 290.197 72.770 0.750 re f
98.645 274.315 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 280.342 Td /F1 9.8 Tf  [(R. extended)] TJ ET
0.267 0.267 0.267 rg
170.665 290.197 35.775 0.750 re f
170.665 274.315 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 280.342 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 290.197 87.399 0.750 re f
205.690 274.315 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 280.342 Td /F1 9.8 Tf  [(0.63)] TJ ET
0.267 0.267 0.267 rg
292.340 290.197 39.425 0.750 re f
292.340 274.315 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 280.342 Td /F1 9.8 Tf  [(0.56)] TJ ET
0.267 0.267 0.267 rg
331.014 290.197 39.425 0.750 re f
331.014 274.315 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 280.342 Td /F1 9.8 Tf  [(0.69)] TJ ET
0.267 0.267 0.267 rg
369.689 290.197 39.479 0.750 re f
369.689 274.315 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 280.342 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 290.197 89.579 0.750 re f
408.418 274.315 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 280.342 Td /F1 9.8 Tf  [(0.59)] TJ ET
0.267 0.267 0.267 rg
497.246 290.197 42.189 0.750 re f
497.246 274.315 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 280.342 Td /F1 9.8 Tf  [(0.50)] TJ ET
0.267 0.267 0.267 rg
538.686 290.197 42.189 0.750 re f
538.686 274.315 0.750 16.631 re f
580.125 274.315 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 280.342 Td /F1 9.8 Tf  [(0.67)] TJ ET
0.267 0.267 0.267 rg
26.625 274.315 72.770 0.750 re f
26.625 258.434 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 264.460 Td /F1 9.8 Tf  [(Langb 06)] TJ ET
0.267 0.267 0.267 rg
98.645 274.315 72.770 0.750 re f
98.645 258.434 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 264.460 Td /F1 9.8 Tf  [(R. Analog)] TJ ET
0.267 0.267 0.267 rg
170.665 274.315 35.775 0.750 re f
170.665 258.434 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 264.460 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 274.315 87.399 0.750 re f
205.690 258.434 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 264.460 Td /F1 9.8 Tf  [(0.65)] TJ ET
0.267 0.267 0.267 rg
292.340 274.315 39.425 0.750 re f
292.340 258.434 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 264.460 Td /F1 9.8 Tf  [(0.58)] TJ ET
0.267 0.267 0.267 rg
331.014 274.315 39.425 0.750 re f
331.014 258.434 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 264.460 Td /F1 9.8 Tf  [(0.72)] TJ ET
0.267 0.267 0.267 rg
369.689 274.315 39.479 0.750 re f
369.689 258.434 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 264.460 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 274.315 89.579 0.750 re f
408.418 258.434 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 264.460 Td /F1 9.8 Tf  [(0.60)] TJ ET
0.267 0.267 0.267 rg
497.246 274.315 42.189 0.750 re f
497.246 258.434 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 264.460 Td /F1 9.8 Tf  [(0.52)] TJ ET
0.267 0.267 0.267 rg
538.686 274.315 42.189 0.750 re f
538.686 258.434 0.750 16.631 re f
580.125 258.434 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 264.460 Td /F1 9.8 Tf  [(0.68)] TJ ET
0.267 0.267 0.267 rg
26.625 258.434 72.770 0.750 re f
26.625 242.553 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 248.579 Td /F1 9.8 Tf  [(Langb 06)] TJ ET
0.267 0.267 0.267 rg
98.645 258.434 72.770 0.750 re f
98.645 242.553 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 248.579 Td /F1 9.8 Tf  [(Motor)] TJ ET
0.267 0.267 0.267 rg
170.665 258.434 35.775 0.750 re f
170.665 242.553 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 248.579 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 258.434 87.399 0.750 re f
205.690 242.553 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 248.579 Td /F1 9.8 Tf  [(0.50)] TJ ET
0.267 0.267 0.267 rg
292.340 258.434 39.425 0.750 re f
292.340 242.553 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 248.579 Td /F1 9.8 Tf  [(0.43)] TJ ET
0.267 0.267 0.267 rg
331.014 258.434 39.425 0.750 re f
331.014 242.553 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 248.579 Td /F1 9.8 Tf  [(0.57)] TJ ET
0.267 0.267 0.267 rg
369.689 258.434 39.479 0.750 re f
369.689 242.553 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 248.579 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 258.434 89.579 0.750 re f
408.418 242.553 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 248.579 Td /F1 9.8 Tf  [(0.57)] TJ ET
0.267 0.267 0.267 rg
497.246 258.434 42.189 0.750 re f
497.246 242.553 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 248.579 Td /F1 9.8 Tf  [(0.48)] TJ ET
0.267 0.267 0.267 rg
538.686 258.434 42.189 0.750 re f
538.686 242.553 0.750 16.631 re f
580.125 242.553 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 248.579 Td /F1 9.8 Tf  [(0.65)] TJ ET
0.267 0.267 0.267 rg
26.625 242.553 72.770 0.750 re f
26.625 226.672 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 232.698 Td /F1 9.8 Tf  [(Langb 06)] TJ ET
0.267 0.267 0.267 rg
98.645 242.553 72.770 0.750 re f
98.645 226.672 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 232.698 Td /F1 9.8 Tf  [(TFC)] TJ ET
0.267 0.267 0.267 rg
170.665 242.553 35.775 0.750 re f
170.665 226.672 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 232.698 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 242.553 87.399 0.750 re f
205.690 226.672 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 232.698 Td /F1 9.8 Tf  [(0.51)] TJ ET
0.267 0.267 0.267 rg
292.340 242.553 39.425 0.750 re f
292.340 226.672 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 232.698 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
331.014 242.553 39.425 0.750 re f
331.014 226.672 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 232.698 Td /F1 9.8 Tf  [(0.58)] TJ ET
0.267 0.267 0.267 rg
369.689 242.553 39.479 0.750 re f
369.689 226.672 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 232.698 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 242.553 89.579 0.750 re f
408.418 226.672 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 232.698 Td /F1 9.8 Tf  [(0.55)] TJ ET
0.267 0.267 0.267 rg
497.246 242.553 42.189 0.750 re f
497.246 226.672 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 232.698 Td /F1 9.8 Tf  [(0.47)] TJ ET
0.267 0.267 0.267 rg
538.686 242.553 42.189 0.750 re f
538.686 226.672 0.750 16.631 re f
580.125 226.672 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 232.698 Td /F1 9.8 Tf  [(0.63)] TJ ET
0.267 0.267 0.267 rg
26.625 226.672 72.770 0.750 re f
26.625 210.790 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 216.817 Td /F1 9.8 Tf  [(Langb db 06)] TJ ET
0.267 0.267 0.267 rg
98.645 226.672 72.770 0.750 re f
98.645 210.790 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 216.817 Td /F1 9.8 Tf  [(Langb 06)] TJ ET
0.267 0.267 0.267 rg
170.665 226.672 35.775 0.750 re f
170.665 210.790 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 216.817 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 226.672 87.399 0.750 re f
205.690 210.790 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 216.817 Td /F1 9.8 Tf  [(1.00)] TJ ET
0.267 0.267 0.267 rg
292.340 226.672 39.425 0.750 re f
292.340 210.790 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 216.817 Td /F1 9.8 Tf  [(0.98)] TJ ET
0.267 0.267 0.267 rg
331.014 226.672 39.425 0.750 re f
331.014 210.790 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 216.817 Td /F1 9.8 Tf  [(1.00)] TJ ET
0.267 0.267 0.267 rg
369.689 226.672 39.479 0.750 re f
369.689 210.790 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 216.817 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 226.672 89.579 0.750 re f
408.418 210.790 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 216.817 Td /F1 9.8 Tf  [(1.00)] TJ ET
0.267 0.267 0.267 rg
497.246 226.672 42.189 0.750 re f
497.246 210.790 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 216.817 Td /F1 9.8 Tf  [(0.97)] TJ ET
0.267 0.267 0.267 rg
538.686 226.672 42.189 0.750 re f
538.686 210.790 0.750 16.631 re f
580.125 210.790 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 216.817 Td /F1 9.8 Tf  [(1.00)] TJ ET
0.267 0.267 0.267 rg
26.625 210.790 72.770 0.750 re f
26.625 194.909 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 200.935 Td /F1 9.8 Tf  [(Langb db 06)] TJ ET
0.267 0.267 0.267 rg
98.645 210.790 72.770 0.750 re f
98.645 194.909 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 200.935 Td /F1 9.8 Tf  [(R. extended)] TJ ET
0.267 0.267 0.267 rg
170.665 210.790 35.775 0.750 re f
170.665 194.909 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 200.935 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 210.790 87.399 0.750 re f
205.690 194.909 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 200.935 Td /F1 9.8 Tf  [(0.60)] TJ ET
0.267 0.267 0.267 rg
292.340 210.790 39.425 0.750 re f
292.340 194.909 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 200.935 Td /F1 9.8 Tf  [(0.53)] TJ ET
0.267 0.267 0.267 rg
331.014 210.790 39.425 0.750 re f
331.014 194.909 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 200.935 Td /F1 9.8 Tf  [(0.67)] TJ ET
0.267 0.267 0.267 rg
369.689 210.790 39.479 0.750 re f
369.689 194.909 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 200.935 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 210.790 89.579 0.750 re f
408.418 194.909 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 200.935 Td /F1 9.8 Tf  [(0.55)] TJ ET
0.267 0.267 0.267 rg
497.246 210.790 42.189 0.750 re f
497.246 194.909 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 200.935 Td /F1 9.8 Tf  [(0.47)] TJ ET
0.267 0.267 0.267 rg
538.686 210.790 42.189 0.750 re f
538.686 194.909 0.750 16.631 re f
580.125 194.909 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 200.935 Td /F1 9.8 Tf  [(0.63)] TJ ET
0.267 0.267 0.267 rg
26.625 194.909 72.770 0.750 re f
26.625 179.028 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 185.054 Td /F1 9.8 Tf  [(Langb db 06)] TJ ET
0.267 0.267 0.267 rg
98.645 194.909 72.770 0.750 re f
98.645 179.028 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 185.054 Td /F1 9.8 Tf  [(R. Analog)] TJ ET
0.267 0.267 0.267 rg
170.665 194.909 35.775 0.750 re f
170.665 179.028 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 185.054 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 194.909 87.399 0.750 re f
205.690 179.028 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 185.054 Td /F1 9.8 Tf  [(0.64)] TJ ET
0.267 0.267 0.267 rg
292.340 194.909 39.425 0.750 re f
292.340 179.028 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 185.054 Td /F1 9.8 Tf  [(0.57)] TJ ET
0.267 0.267 0.267 rg
331.014 194.909 39.425 0.750 re f
331.014 179.028 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 185.054 Td /F1 9.8 Tf  [(0.70)] TJ ET
0.267 0.267 0.267 rg
369.689 194.909 39.479 0.750 re f
369.689 179.028 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 185.054 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 194.909 89.579 0.750 re f
408.418 179.028 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 185.054 Td /F1 9.8 Tf  [(0.59)] TJ ET
0.267 0.267 0.267 rg
497.246 194.909 42.189 0.750 re f
497.246 179.028 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 185.054 Td /F1 9.8 Tf  [(0.50)] TJ ET
0.267 0.267 0.267 rg
538.686 194.909 42.189 0.750 re f
538.686 179.028 0.750 16.631 re f
580.125 179.028 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 185.054 Td /F1 9.8 Tf  [(0.67)] TJ ET
0.267 0.267 0.267 rg
26.625 179.028 72.770 0.750 re f
26.625 163.147 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 169.173 Td /F1 9.8 Tf  [(Langb db 06)] TJ ET
0.267 0.267 0.267 rg
98.645 179.028 72.770 0.750 re f
98.645 163.147 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 169.173 Td /F1 9.8 Tf  [(Motor)] TJ ET
0.267 0.267 0.267 rg
170.665 179.028 35.775 0.750 re f
170.665 163.147 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 169.173 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 179.028 87.399 0.750 re f
205.690 163.147 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 169.173 Td /F1 9.8 Tf  [(0.51)] TJ ET
0.267 0.267 0.267 rg
292.340 179.028 39.425 0.750 re f
292.340 163.147 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 169.173 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
331.014 179.028 39.425 0.750 re f
331.014 163.147 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 169.173 Td /F1 9.8 Tf  [(0.58)] TJ ET
0.267 0.267 0.267 rg
369.689 179.028 39.479 0.750 re f
369.689 163.147 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 169.173 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 179.028 89.579 0.750 re f
408.418 163.147 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 169.173 Td /F1 9.8 Tf  [(0.59)] TJ ET
0.267 0.267 0.267 rg
497.246 179.028 42.189 0.750 re f
497.246 163.147 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 169.173 Td /F1 9.8 Tf  [(0.50)] TJ ET
0.267 0.267 0.267 rg
538.686 179.028 42.189 0.750 re f
538.686 163.147 0.750 16.631 re f
580.125 163.147 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 169.173 Td /F1 9.8 Tf  [(0.67)] TJ ET
0.267 0.267 0.267 rg
26.625 163.147 72.770 0.750 re f
26.625 147.265 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 153.292 Td /F1 9.8 Tf  [(Langb db 06)] TJ ET
0.267 0.267 0.267 rg
98.645 163.147 72.770 0.750 re f
98.645 147.265 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 153.292 Td /F1 9.8 Tf  [(TFC)] TJ ET
0.267 0.267 0.267 rg
170.665 163.147 35.775 0.750 re f
170.665 147.265 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 153.292 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 163.147 87.399 0.750 re f
205.690 147.265 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 153.292 Td /F1 9.8 Tf  [(0.51)] TJ ET
0.267 0.267 0.267 rg
292.340 163.147 39.425 0.750 re f
292.340 147.265 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 153.292 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
331.014 163.147 39.425 0.750 re f
331.014 147.265 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 153.292 Td /F1 9.8 Tf  [(0.58)] TJ ET
0.267 0.267 0.267 rg
369.689 163.147 39.479 0.750 re f
369.689 147.265 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 153.292 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 163.147 89.579 0.750 re f
408.418 147.265 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 153.292 Td /F1 9.8 Tf  [(0.55)] TJ ET
0.267 0.267 0.267 rg
497.246 163.147 42.189 0.750 re f
497.246 147.265 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 153.292 Td /F1 9.8 Tf  [(0.47)] TJ ET
0.267 0.267 0.267 rg
538.686 163.147 42.189 0.750 re f
538.686 147.265 0.750 16.631 re f
580.125 147.265 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 153.292 Td /F1 9.8 Tf  [(0.63)] TJ ET
0.267 0.267 0.267 rg
26.625 147.265 72.770 0.750 re f
26.625 131.384 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 137.410 Td /F1 9.8 Tf  [(R. extended)] TJ ET
0.267 0.267 0.267 rg
98.645 147.265 72.770 0.750 re f
98.645 131.384 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 137.410 Td /F1 9.8 Tf  [(R. analog)] TJ ET
0.267 0.267 0.267 rg
170.665 147.265 35.775 0.750 re f
170.665 131.384 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 137.410 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 147.265 87.399 0.750 re f
205.690 131.384 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 137.410 Td /F1 9.8 Tf  [(1.00)] TJ ET
0.267 0.267 0.267 rg
292.340 147.265 39.425 0.750 re f
292.340 131.384 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 137.410 Td /F1 9.8 Tf  [(0.98)] TJ ET
0.267 0.267 0.267 rg
331.014 147.265 39.425 0.750 re f
331.014 131.384 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 137.410 Td /F1 9.8 Tf  [(1.00)] TJ ET
0.267 0.267 0.267 rg
369.689 147.265 39.479 0.750 re f
369.689 131.384 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 137.410 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 147.265 89.579 0.750 re f
408.418 131.384 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 137.410 Td /F1 9.8 Tf  [(1.00)] TJ ET
0.267 0.267 0.267 rg
497.246 147.265 42.189 0.750 re f
497.246 131.384 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 137.410 Td /F1 9.8 Tf  [(0.97)] TJ ET
0.267 0.267 0.267 rg
538.686 147.265 42.189 0.750 re f
538.686 131.384 0.750 16.631 re f
580.125 131.384 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 137.410 Td /F1 9.8 Tf  [(1.00)] TJ ET
0.267 0.267 0.267 rg
26.625 131.384 72.770 0.750 re f
26.625 115.503 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 121.529 Td /F1 9.8 Tf  [(R. extended)] TJ ET
0.267 0.267 0.267 rg
98.645 131.384 72.770 0.750 re f
98.645 115.503 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 121.529 Td /F1 9.8 Tf  [(Motor)] TJ ET
0.267 0.267 0.267 rg
170.665 131.384 35.775 0.750 re f
170.665 115.503 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 121.529 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 131.384 87.399 0.750 re f
205.690 115.503 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 121.529 Td /F1 9.8 Tf  [(0.41)] TJ ET
0.267 0.267 0.267 rg
292.340 131.384 39.425 0.750 re f
292.340 115.503 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 121.529 Td /F1 9.8 Tf  [(0.34)] TJ ET
0.267 0.267 0.267 rg
331.014 131.384 39.425 0.750 re f
331.014 115.503 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 121.529 Td /F1 9.8 Tf  [(0.48)] TJ ET
0.267 0.267 0.267 rg
369.689 131.384 39.479 0.750 re f
369.689 115.503 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 121.529 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 131.384 89.579 0.750 re f
408.418 115.503 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 121.529 Td /F1 9.8 Tf  [(0.43)] TJ ET
0.267 0.267 0.267 rg
497.246 131.384 42.189 0.750 re f
497.246 115.503 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 121.529 Td /F1 9.8 Tf  [(0.35)] TJ ET
0.267 0.267 0.267 rg
538.686 131.384 42.189 0.750 re f
538.686 115.503 0.750 16.631 re f
580.125 115.503 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 121.529 Td /F1 9.8 Tf  [(0.52)] TJ ET
0.267 0.267 0.267 rg
26.625 115.503 72.770 0.750 re f
26.625 99.622 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 105.648 Td /F1 9.8 Tf  [(R. extended)] TJ ET
0.267 0.267 0.267 rg
98.645 115.503 72.770 0.750 re f
98.645 99.622 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 105.648 Td /F1 9.8 Tf  [(TFC)] TJ ET
0.267 0.267 0.267 rg
170.665 115.503 35.775 0.750 re f
170.665 99.622 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 105.648 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 115.503 87.399 0.750 re f
205.690 99.622 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 105.648 Td /F1 9.8 Tf  [(0.43)] TJ ET
0.267 0.267 0.267 rg
292.340 115.503 39.425 0.750 re f
292.340 99.622 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 105.648 Td /F1 9.8 Tf  [(0.36)] TJ ET
0.267 0.267 0.267 rg
331.014 115.503 39.425 0.750 re f
331.014 99.622 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 105.648 Td /F1 9.8 Tf  [(0.50)] TJ ET
0.267 0.267 0.267 rg
369.689 115.503 39.479 0.750 re f
369.689 99.622 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 105.648 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 115.503 89.579 0.750 re f
408.418 99.622 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 105.648 Td /F1 9.8 Tf  [(0.40)] TJ ET
0.267 0.267 0.267 rg
497.246 115.503 42.189 0.750 re f
497.246 99.622 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 105.648 Td /F1 9.8 Tf  [(0.32)] TJ ET
0.267 0.267 0.267 rg
538.686 115.503 42.189 0.750 re f
538.686 99.622 0.750 16.631 re f
580.125 99.622 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 105.648 Td /F1 9.8 Tf  [(0.48)] TJ ET
0.267 0.267 0.267 rg
26.625 99.622 72.770 0.750 re f
26.625 83.740 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 89.767 Td /F1 9.8 Tf  [(R. analog)] TJ ET
0.267 0.267 0.267 rg
98.645 99.622 72.770 0.750 re f
98.645 83.740 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 89.767 Td /F1 9.8 Tf  [(Motor)] TJ ET
0.267 0.267 0.267 rg
170.665 99.622 35.775 0.750 re f
170.665 83.740 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 89.767 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 99.622 87.399 0.750 re f
205.690 83.740 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 89.767 Td /F1 9.8 Tf  [(0.41)] TJ ET
0.267 0.267 0.267 rg
292.340 99.622 39.425 0.750 re f
292.340 83.740 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 89.767 Td /F1 9.8 Tf  [(0.34)] TJ ET
0.267 0.267 0.267 rg
331.014 99.622 39.425 0.750 re f
331.014 83.740 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 89.767 Td /F1 9.8 Tf  [(0.48)] TJ ET
0.267 0.267 0.267 rg
369.689 99.622 39.479 0.750 re f
369.689 83.740 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 89.767 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 99.622 89.579 0.750 re f
408.418 83.740 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 89.767 Td /F1 9.8 Tf  [(0.43)] TJ ET
0.267 0.267 0.267 rg
497.246 99.622 42.189 0.750 re f
497.246 83.740 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 89.767 Td /F1 9.8 Tf  [(0.35)] TJ ET
0.267 0.267 0.267 rg
538.686 99.622 42.189 0.750 re f
538.686 83.740 0.750 16.631 re f
580.125 83.740 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 89.767 Td /F1 9.8 Tf  [(0.51)] TJ ET
0.267 0.267 0.267 rg
26.625 83.740 72.770 0.750 re f
26.625 67.859 72.770 0.750 re f
26.625 67.859 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 73.885 Td /F1 9.8 Tf  [(R. analog)] TJ ET
0.267 0.267 0.267 rg
98.645 83.740 72.770 0.750 re f
98.645 67.859 72.770 0.750 re f
98.645 67.859 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 73.885 Td /F1 9.8 Tf  [(TFC)] TJ ET
0.267 0.267 0.267 rg
170.665 83.740 35.775 0.750 re f
170.665 67.859 35.775 0.750 re f
170.665 67.859 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 73.885 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 83.740 87.399 0.750 re f
205.690 67.859 87.399 0.750 re f
205.690 67.859 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 73.885 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
292.340 83.740 39.425 0.750 re f
292.340 67.859 39.425 0.750 re f
292.340 67.859 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 73.885 Td /F1 9.8 Tf  [(0.37)] TJ ET
0.267 0.267 0.267 rg
331.014 83.740 39.425 0.750 re f
331.014 67.859 39.425 0.750 re f
331.014 67.859 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 73.885 Td /F1 9.8 Tf  [(0.51)] TJ ET
0.267 0.267 0.267 rg
369.689 83.740 39.479 0.750 re f
369.689 67.859 39.479 0.750 re f
369.689 67.859 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 73.885 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 83.740 89.579 0.750 re f
408.418 67.859 89.579 0.750 re f
408.418 67.859 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 73.885 Td /F1 9.8 Tf  [(0.41)] TJ ET
0.267 0.267 0.267 rg
497.246 83.740 42.189 0.750 re f
497.246 67.859 42.189 0.750 re f
497.246 67.859 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 73.885 Td /F1 9.8 Tf  [(0.33)] TJ ET
0.267 0.267 0.267 rg
538.686 83.740 42.189 0.750 re f
538.686 67.859 42.189 0.750 re f
538.686 67.859 0.750 16.631 re f
580.125 67.859 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 73.885 Td /F1 9.8 Tf  [(0.49)] TJ ET
Q
q
15.000 67.484 577.500 709.516 re W n
0.271 0.267 0.267 rg
BT 26.250 750.278 Td /F4 12.0 Tf  [(Predicting AAO)] TJ ET
BT 26.250 730.324 Td /F1 9.8 Tf  [(The Langbehn formula \(LB 06\) predicted an AAO of 46.82 \(SD 10.5, range 23-89\) when 10 years of age; with age at a disease )] TJ ET
BT 26.250 718.419 Td /F1 9.8 Tf  [(burden of 200, the predicted average AAO was 46.65 \(SD 10.14, range 23-74\). The agreement rate with the investigator�s )] TJ ET
BT 26.250 706.515 Td /F1 9.8 Tf  [(estimate was 0.46 \(Table 2\). In 280 participants \(140 women\) with the necessary data the Ranen formula predicted an AAO of )] TJ ET
BT 26.250 694.610 Td /F1 9.8 Tf  [(41.9 years \(SD 7.9, range 8-61\). In that group of participants this is similar to the investigator�s estimates of 42 years. The )] TJ ET
BT 26.250 682.705 Td /F1 9.8 Tf  [(agreement rate was 0.46 \(Table 2\).)] TJ ET
BT 26.250 663.300 Td /F4 9.8 Tf  [(Comparing formulae derived AAO)] TJ ET
BT 26.250 643.896 Td /F1 9.8 Tf  [(In a total of 206 REGISTRY patients \(109 women\) with complete data the best agreement rate was between the extrapolated )] TJ ET
BT 26.250 631.991 Td /F1 9.8 Tf  [(AAOs on the longitudinal TFC and motor score data \(0.76, Table 2\). Using parent AAO and CAG repeats resulted in the )] TJ ET
BT 26.250 620.086 Td /F1 9.8 Tf  [(following formula that best predicted the investigator�s AAO estimate \(Ranen analog\):)] TJ ET
BT 26.250 600.681 Td /F1 9.8 Tf  [(AAO=90.3918+0.3293*parent AAO-1.3996*CAG repeats)] TJ ET
BT 26.250 581.277 Td /F1 9.8 Tf  [(In a next step we entered all available data into a regression model for the prediction of the investigator�s estimate of AAO )] TJ ET
BT 26.250 569.372 Td /F1 9.8 Tf  [(\(Ranen extended\). Motor score, parent AAO, CAG repeats, and gender significantly contributed to the regression model )] TJ ET
BT 26.250 557.467 Td /F1 9.8 Tf  [(resulting in the following formula:)] TJ ET
BT 26.250 538.062 Td /F1 9.8 Tf  [(AAO=88.7546+0.0430*motorscore+0.3546*parent AAO-1.4311*CAG repeats+1.0124*gender \(male=1, female=0\). We then )] TJ ET
BT 26.250 526.158 Td /F1 9.8 Tf  [(entered the dataset of each participant into this formula to arrive at the calculated AAO.)] TJ ET
BT 26.250 506.753 Td /F1 9.8 Tf  [(The data driven formula resembles the Ranen and Ranen analogous formula with high agreement rates \(0.97, Table 2\) while )] TJ ET
BT 26.250 494.848 Td /F1 9.8 Tf  [(the agreement rates with other AAO calculations was much lower \(Table 2\).)] TJ ET
BT 26.250 475.443 Td /F1 9.8 Tf  [(We then assessed 145 participants with a motor onset. The findings were similar to the analyses including all participants )] TJ ET
BT 26.250 463.539 Td /F1 9.8 Tf  [(regardless of major symptom at onset \(Table 2\); the rater estimated an earlier onset than the AAO from the regression analyses.)] TJ ET
BT 26.250 444.134 Td /F4 9.8 Tf  [(Table 2.)] TJ ET
1.000 1.000 1.000 rg
26.250 67.484 555.000 366.769 re f
0.267 0.267 0.267 rg
26.625 433.128 72.770 0.750 re f
26.625 417.247 0.750 16.631 re f
98.645 433.128 72.770 0.750 re f
98.645 417.247 0.750 16.631 re f
170.665 433.128 35.400 0.750 re f
206.065 433.128 86.649 0.750 re f
292.715 433.128 38.675 0.750 re f
331.389 433.128 39.050 0.750 re f
170.665 417.247 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 423.273 Td /F4 9.8 Tf  [(All participants)] TJ ET
0.267 0.267 0.267 rg
369.689 433.128 39.104 0.750 re f
408.793 433.128 88.829 0.750 re f
497.621 433.128 41.439 0.750 re f
539.061 433.128 41.814 0.750 re f
369.689 417.247 0.750 16.631 re f
580.125 417.247 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 423.273 Td /F4 9.8 Tf  [(Participants with motor onset)] TJ ET
0.267 0.267 0.267 rg
26.625 417.247 72.770 0.750 re f
26.625 401.366 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 407.392 Td /F4 9.8 Tf  [(Formula 1)] TJ ET
0.267 0.267 0.267 rg
98.645 417.247 72.770 0.750 re f
98.645 401.366 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 407.392 Td /F4 9.8 Tf  [(Formula 2)] TJ ET
0.267 0.267 0.267 rg
170.665 417.247 35.775 0.750 re f
170.665 401.366 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 407.392 Td /F4 9.8 Tf  [(N)] TJ ET
0.267 0.267 0.267 rg
205.690 417.247 87.399 0.750 re f
205.690 401.366 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 407.392 Td /F4 9.8 Tf  [(agreement rate)] TJ ET
0.267 0.267 0.267 rg
292.340 417.247 39.050 0.750 re f
331.389 417.247 39.050 0.750 re f
292.340 401.366 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 407.392 Td /F4 9.8 Tf  [(95% CI)] TJ ET
0.267 0.267 0.267 rg
369.689 417.247 39.479 0.750 re f
369.689 401.366 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 407.392 Td /F4 9.8 Tf  [(N)] TJ ET
0.267 0.267 0.267 rg
408.418 417.247 89.579 0.750 re f
408.418 401.366 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 407.392 Td /F4 9.8 Tf  [(Agreement rate)] TJ ET
0.267 0.267 0.267 rg
497.246 417.247 41.814 0.750 re f
539.061 417.247 41.814 0.750 re f
497.246 401.366 0.750 16.631 re f
580.125 401.366 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 407.392 Td /F4 9.8 Tf  [(95% CI)] TJ ET
0.267 0.267 0.267 rg
26.625 401.366 72.770 0.750 re f
26.625 385.484 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 391.511 Td /F1 9.8 Tf  [(Ranen)] TJ ET
0.267 0.267 0.267 rg
98.645 401.366 72.770 0.750 re f
98.645 385.484 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 391.511 Td /F1 9.8 Tf  [(Langb 06)] TJ ET
0.267 0.267 0.267 rg
170.665 401.366 35.775 0.750 re f
170.665 385.484 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 391.511 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 401.366 87.399 0.750 re f
205.690 385.484 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 391.511 Td /F1 9.8 Tf  [(0.50)] TJ ET
0.267 0.267 0.267 rg
292.340 401.366 39.425 0.750 re f
292.340 385.484 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 391.511 Td /F1 9.8 Tf  [(0.43)] TJ ET
0.267 0.267 0.267 rg
331.014 401.366 39.425 0.750 re f
331.014 385.484 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 391.511 Td /F1 9.8 Tf  [(0.58)] TJ ET
0.267 0.267 0.267 rg
369.689 401.366 39.479 0.750 re f
369.689 385.484 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 391.511 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 401.366 89.579 0.750 re f
408.418 385.484 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 391.511 Td /F1 9.8 Tf  [(0.49)] TJ ET
0.267 0.267 0.267 rg
497.246 401.366 42.189 0.750 re f
497.246 385.484 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 391.511 Td /F1 9.8 Tf  [(0.41)] TJ ET
0.267 0.267 0.267 rg
538.686 401.366 42.189 0.750 re f
538.686 385.484 0.750 16.631 re f
580.125 385.484 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 391.511 Td /F1 9.8 Tf  [(0.57)] TJ ET
0.267 0.267 0.267 rg
26.625 385.484 72.770 0.750 re f
26.625 369.603 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 375.629 Td /F1 9.8 Tf  [(Ranen)] TJ ET
0.267 0.267 0.267 rg
98.645 385.484 72.770 0.750 re f
98.645 369.603 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 375.629 Td /F1 9.8 Tf  [(Langb db 06)] TJ ET
0.267 0.267 0.267 rg
170.665 385.484 35.775 0.750 re f
170.665 369.603 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 375.629 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 385.484 87.399 0.750 re f
205.690 369.603 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 375.629 Td /F1 9.8 Tf  [(0.50)] TJ ET
0.267 0.267 0.267 rg
292.340 385.484 39.425 0.750 re f
292.340 369.603 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 375.629 Td /F1 9.8 Tf  [(0.43)] TJ ET
0.267 0.267 0.267 rg
331.014 385.484 39.425 0.750 re f
331.014 369.603 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 375.629 Td /F1 9.8 Tf  [(0.58)] TJ ET
0.267 0.267 0.267 rg
369.689 385.484 39.479 0.750 re f
369.689 369.603 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 375.629 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 385.484 89.579 0.750 re f
408.418 369.603 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 375.629 Td /F1 9.8 Tf  [(0.49)] TJ ET
0.267 0.267 0.267 rg
497.246 385.484 42.189 0.750 re f
497.246 369.603 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 375.629 Td /F1 9.8 Tf  [(0.41)] TJ ET
0.267 0.267 0.267 rg
538.686 385.484 42.189 0.750 re f
538.686 369.603 0.750 16.631 re f
580.125 369.603 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 375.629 Td /F1 9.8 Tf  [(0.57)] TJ ET
0.267 0.267 0.267 rg
26.625 369.603 72.770 0.750 re f
26.625 353.722 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 359.748 Td /F1 9.8 Tf  [(Ranen)] TJ ET
0.267 0.267 0.267 rg
98.645 369.603 72.770 0.750 re f
98.645 353.722 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 359.748 Td /F1 9.8 Tf  [(R. extended)] TJ ET
0.267 0.267 0.267 rg
170.665 369.603 35.775 0.750 re f
170.665 353.722 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 359.748 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 369.603 87.399 0.750 re f
205.690 353.722 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 359.748 Td /F1 9.8 Tf  [(0.97)] TJ ET
0.267 0.267 0.267 rg
292.340 369.603 39.425 0.750 re f
292.340 353.722 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 359.748 Td /F1 9.8 Tf  [(0.94)] TJ ET
0.267 0.267 0.267 rg
331.014 369.603 39.425 0.750 re f
331.014 353.722 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 359.748 Td /F1 9.8 Tf  [(0.99)] TJ ET
0.267 0.267 0.267 rg
369.689 369.603 39.479 0.750 re f
369.689 353.722 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 359.748 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 369.603 89.579 0.750 re f
408.418 353.722 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 359.748 Td /F1 9.8 Tf  [(0.96)] TJ ET
0.267 0.267 0.267 rg
497.246 369.603 42.189 0.750 re f
497.246 353.722 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 359.748 Td /F1 9.8 Tf  [(0.91)] TJ ET
0.267 0.267 0.267 rg
538.686 369.603 42.189 0.750 re f
538.686 353.722 0.750 16.631 re f
580.125 353.722 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 359.748 Td /F1 9.8 Tf  [(0.98)] TJ ET
0.267 0.267 0.267 rg
26.625 353.722 72.770 0.750 re f
26.625 337.840 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 343.867 Td /F1 9.8 Tf  [(Ranen)] TJ ET
0.267 0.267 0.267 rg
98.645 353.722 72.770 0.750 re f
98.645 337.840 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 343.867 Td /F1 9.8 Tf  [(R. analog)] TJ ET
0.267 0.267 0.267 rg
170.665 353.722 35.775 0.750 re f
170.665 337.840 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 343.867 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 353.722 87.399 0.750 re f
205.690 337.840 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 343.867 Td /F1 9.8 Tf  [(0.97)] TJ ET
0.267 0.267 0.267 rg
292.340 353.722 39.425 0.750 re f
292.340 337.840 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 343.867 Td /F1 9.8 Tf  [(0.94)] TJ ET
0.267 0.267 0.267 rg
331.014 353.722 39.425 0.750 re f
331.014 337.840 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 343.867 Td /F1 9.8 Tf  [(0.99)] TJ ET
0.267 0.267 0.267 rg
369.689 353.722 39.479 0.750 re f
369.689 337.840 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 343.867 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 353.722 89.579 0.750 re f
408.418 337.840 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 343.867 Td /F1 9.8 Tf  [(0.97)] TJ ET
0.267 0.267 0.267 rg
497.246 353.722 42.189 0.750 re f
497.246 337.840 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 343.867 Td /F1 9.8 Tf  [(0.92)] TJ ET
0.267 0.267 0.267 rg
538.686 353.722 42.189 0.750 re f
538.686 337.840 0.750 16.631 re f
580.125 337.840 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 343.867 Td /F1 9.8 Tf  [(0.99)] TJ ET
0.267 0.267 0.267 rg
26.625 337.840 72.770 0.750 re f
26.625 321.959 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 327.985 Td /F1 9.8 Tf  [(Ranen)] TJ ET
0.267 0.267 0.267 rg
98.645 337.840 72.770 0.750 re f
98.645 321.959 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 327.985 Td /F1 9.8 Tf  [(Motor)] TJ ET
0.267 0.267 0.267 rg
170.665 337.840 35.775 0.750 re f
170.665 321.959 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 327.985 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 337.840 87.399 0.750 re f
205.690 321.959 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 327.985 Td /F1 9.8 Tf  [(0.35)] TJ ET
0.267 0.267 0.267 rg
292.340 337.840 39.425 0.750 re f
292.340 321.959 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 327.985 Td /F1 9.8 Tf  [(0.29)] TJ ET
0.267 0.267 0.267 rg
331.014 337.840 39.425 0.750 re f
331.014 321.959 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 327.985 Td /F1 9.8 Tf  [(0.42)] TJ ET
0.267 0.267 0.267 rg
369.689 337.840 39.479 0.750 re f
369.689 321.959 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 327.985 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 337.840 89.579 0.750 re f
408.418 321.959 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 327.985 Td /F1 9.8 Tf  [(0.35)] TJ ET
0.267 0.267 0.267 rg
497.246 337.840 42.189 0.750 re f
497.246 321.959 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 327.985 Td /F1 9.8 Tf  [(0.27)] TJ ET
0.267 0.267 0.267 rg
538.686 337.840 42.189 0.750 re f
538.686 321.959 0.750 16.631 re f
580.125 321.959 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 327.985 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
26.625 321.959 72.770 0.750 re f
26.625 306.078 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 312.104 Td /F1 9.8 Tf  [(Ranen)] TJ ET
0.267 0.267 0.267 rg
98.645 321.959 72.770 0.750 re f
98.645 306.078 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 312.104 Td /F1 9.8 Tf  [(Rater)] TJ ET
0.267 0.267 0.267 rg
170.665 321.959 35.775 0.750 re f
170.665 306.078 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 312.104 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 321.959 87.399 0.750 re f
205.690 306.078 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 312.104 Td /F1 9.8 Tf  [(0.45)] TJ ET
0.267 0.267 0.267 rg
292.340 321.959 39.425 0.750 re f
292.340 306.078 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 312.104 Td /F1 9.8 Tf  [(0.38)] TJ ET
0.267 0.267 0.267 rg
331.014 321.959 39.425 0.750 re f
331.014 306.078 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 312.104 Td /F1 9.8 Tf  [(0.52)] TJ ET
0.267 0.267 0.267 rg
369.689 321.959 39.479 0.750 re f
369.689 306.078 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 312.104 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 321.959 89.579 0.750 re f
408.418 306.078 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 312.104 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
497.246 321.959 42.189 0.750 re f
497.246 306.078 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 312.104 Td /F1 9.8 Tf  [(0.36)] TJ ET
0.267 0.267 0.267 rg
538.686 321.959 42.189 0.750 re f
538.686 306.078 0.750 16.631 re f
580.125 306.078 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 312.104 Td /F1 9.8 Tf  [(0.53)] TJ ET
0.267 0.267 0.267 rg
26.625 306.078 72.770 0.750 re f
26.625 290.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 296.223 Td /F1 9.8 Tf  [(Ranen)] TJ ET
0.267 0.267 0.267 rg
98.645 306.078 72.770 0.750 re f
98.645 290.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 296.223 Td /F1 9.8 Tf  [(TFC)] TJ ET
0.267 0.267 0.267 rg
170.665 306.078 35.775 0.750 re f
170.665 290.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 296.223 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 306.078 87.399 0.750 re f
205.690 290.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 296.223 Td /F1 9.8 Tf  [(0.37)] TJ ET
0.267 0.267 0.267 rg
292.340 306.078 39.425 0.750 re f
292.340 290.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 296.223 Td /F1 9.8 Tf  [(0.31)] TJ ET
0.267 0.267 0.267 rg
331.014 306.078 39.425 0.750 re f
331.014 290.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 296.223 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
369.689 306.078 39.479 0.750 re f
369.689 290.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 296.223 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 306.078 89.579 0.750 re f
408.418 290.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 296.223 Td /F1 9.8 Tf  [(0.32)] TJ ET
0.267 0.267 0.267 rg
497.246 306.078 42.189 0.750 re f
497.246 290.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 296.223 Td /F1 9.8 Tf  [(0.25)] TJ ET
0.267 0.267 0.267 rg
538.686 306.078 42.189 0.750 re f
538.686 290.197 0.750 16.631 re f
580.125 290.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 296.223 Td /F1 9.8 Tf  [(0.41)] TJ ET
0.267 0.267 0.267 rg
26.625 290.197 72.770 0.750 re f
26.625 274.315 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 280.342 Td /F1 9.8 Tf  [(Langb 06)] TJ ET
0.267 0.267 0.267 rg
98.645 290.197 72.770 0.750 re f
98.645 274.315 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 280.342 Td /F1 9.8 Tf  [(R. extended)] TJ ET
0.267 0.267 0.267 rg
170.665 290.197 35.775 0.750 re f
170.665 274.315 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 280.342 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 290.197 87.399 0.750 re f
205.690 274.315 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 280.342 Td /F1 9.8 Tf  [(0.63)] TJ ET
0.267 0.267 0.267 rg
292.340 290.197 39.425 0.750 re f
292.340 274.315 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 280.342 Td /F1 9.8 Tf  [(0.56)] TJ ET
0.267 0.267 0.267 rg
331.014 290.197 39.425 0.750 re f
331.014 274.315 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 280.342 Td /F1 9.8 Tf  [(0.69)] TJ ET
0.267 0.267 0.267 rg
369.689 290.197 39.479 0.750 re f
369.689 274.315 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 280.342 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 290.197 89.579 0.750 re f
408.418 274.315 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 280.342 Td /F1 9.8 Tf  [(0.59)] TJ ET
0.267 0.267 0.267 rg
497.246 290.197 42.189 0.750 re f
497.246 274.315 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 280.342 Td /F1 9.8 Tf  [(0.50)] TJ ET
0.267 0.267 0.267 rg
538.686 290.197 42.189 0.750 re f
538.686 274.315 0.750 16.631 re f
580.125 274.315 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 280.342 Td /F1 9.8 Tf  [(0.67)] TJ ET
0.267 0.267 0.267 rg
26.625 274.315 72.770 0.750 re f
26.625 258.434 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 264.460 Td /F1 9.8 Tf  [(Langb 06)] TJ ET
0.267 0.267 0.267 rg
98.645 274.315 72.770 0.750 re f
98.645 258.434 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 264.460 Td /F1 9.8 Tf  [(R. Analog)] TJ ET
0.267 0.267 0.267 rg
170.665 274.315 35.775 0.750 re f
170.665 258.434 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 264.460 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 274.315 87.399 0.750 re f
205.690 258.434 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 264.460 Td /F1 9.8 Tf  [(0.65)] TJ ET
0.267 0.267 0.267 rg
292.340 274.315 39.425 0.750 re f
292.340 258.434 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 264.460 Td /F1 9.8 Tf  [(0.58)] TJ ET
0.267 0.267 0.267 rg
331.014 274.315 39.425 0.750 re f
331.014 258.434 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 264.460 Td /F1 9.8 Tf  [(0.72)] TJ ET
0.267 0.267 0.267 rg
369.689 274.315 39.479 0.750 re f
369.689 258.434 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 264.460 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 274.315 89.579 0.750 re f
408.418 258.434 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 264.460 Td /F1 9.8 Tf  [(0.60)] TJ ET
0.267 0.267 0.267 rg
497.246 274.315 42.189 0.750 re f
497.246 258.434 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 264.460 Td /F1 9.8 Tf  [(0.52)] TJ ET
0.267 0.267 0.267 rg
538.686 274.315 42.189 0.750 re f
538.686 258.434 0.750 16.631 re f
580.125 258.434 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 264.460 Td /F1 9.8 Tf  [(0.68)] TJ ET
0.267 0.267 0.267 rg
26.625 258.434 72.770 0.750 re f
26.625 242.553 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 248.579 Td /F1 9.8 Tf  [(Langb 06)] TJ ET
0.267 0.267 0.267 rg
98.645 258.434 72.770 0.750 re f
98.645 242.553 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 248.579 Td /F1 9.8 Tf  [(Motor)] TJ ET
0.267 0.267 0.267 rg
170.665 258.434 35.775 0.750 re f
170.665 242.553 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 248.579 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 258.434 87.399 0.750 re f
205.690 242.553 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 248.579 Td /F1 9.8 Tf  [(0.50)] TJ ET
0.267 0.267 0.267 rg
292.340 258.434 39.425 0.750 re f
292.340 242.553 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 248.579 Td /F1 9.8 Tf  [(0.43)] TJ ET
0.267 0.267 0.267 rg
331.014 258.434 39.425 0.750 re f
331.014 242.553 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 248.579 Td /F1 9.8 Tf  [(0.57)] TJ ET
0.267 0.267 0.267 rg
369.689 258.434 39.479 0.750 re f
369.689 242.553 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 248.579 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 258.434 89.579 0.750 re f
408.418 242.553 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 248.579 Td /F1 9.8 Tf  [(0.57)] TJ ET
0.267 0.267 0.267 rg
497.246 258.434 42.189 0.750 re f
497.246 242.553 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 248.579 Td /F1 9.8 Tf  [(0.48)] TJ ET
0.267 0.267 0.267 rg
538.686 258.434 42.189 0.750 re f
538.686 242.553 0.750 16.631 re f
580.125 242.553 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 248.579 Td /F1 9.8 Tf  [(0.65)] TJ ET
0.267 0.267 0.267 rg
26.625 242.553 72.770 0.750 re f
26.625 226.672 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 232.698 Td /F1 9.8 Tf  [(Langb 06)] TJ ET
0.267 0.267 0.267 rg
98.645 242.553 72.770 0.750 re f
98.645 226.672 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 232.698 Td /F1 9.8 Tf  [(TFC)] TJ ET
0.267 0.267 0.267 rg
170.665 242.553 35.775 0.750 re f
170.665 226.672 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 232.698 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 242.553 87.399 0.750 re f
205.690 226.672 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 232.698 Td /F1 9.8 Tf  [(0.51)] TJ ET
0.267 0.267 0.267 rg
292.340 242.553 39.425 0.750 re f
292.340 226.672 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 232.698 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
331.014 242.553 39.425 0.750 re f
331.014 226.672 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 232.698 Td /F1 9.8 Tf  [(0.58)] TJ ET
0.267 0.267 0.267 rg
369.689 242.553 39.479 0.750 re f
369.689 226.672 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 232.698 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 242.553 89.579 0.750 re f
408.418 226.672 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 232.698 Td /F1 9.8 Tf  [(0.55)] TJ ET
0.267 0.267 0.267 rg
497.246 242.553 42.189 0.750 re f
497.246 226.672 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 232.698 Td /F1 9.8 Tf  [(0.47)] TJ ET
0.267 0.267 0.267 rg
538.686 242.553 42.189 0.750 re f
538.686 226.672 0.750 16.631 re f
580.125 226.672 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 232.698 Td /F1 9.8 Tf  [(0.63)] TJ ET
0.267 0.267 0.267 rg
26.625 226.672 72.770 0.750 re f
26.625 210.790 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 216.817 Td /F1 9.8 Tf  [(Langb db 06)] TJ ET
0.267 0.267 0.267 rg
98.645 226.672 72.770 0.750 re f
98.645 210.790 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 216.817 Td /F1 9.8 Tf  [(Langb 06)] TJ ET
0.267 0.267 0.267 rg
170.665 226.672 35.775 0.750 re f
170.665 210.790 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 216.817 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 226.672 87.399 0.750 re f
205.690 210.790 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 216.817 Td /F1 9.8 Tf  [(1.00)] TJ ET
0.267 0.267 0.267 rg
292.340 226.672 39.425 0.750 re f
292.340 210.790 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 216.817 Td /F1 9.8 Tf  [(0.98)] TJ ET
0.267 0.267 0.267 rg
331.014 226.672 39.425 0.750 re f
331.014 210.790 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 216.817 Td /F1 9.8 Tf  [(1.00)] TJ ET
0.267 0.267 0.267 rg
369.689 226.672 39.479 0.750 re f
369.689 210.790 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 216.817 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 226.672 89.579 0.750 re f
408.418 210.790 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 216.817 Td /F1 9.8 Tf  [(1.00)] TJ ET
0.267 0.267 0.267 rg
497.246 226.672 42.189 0.750 re f
497.246 210.790 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 216.817 Td /F1 9.8 Tf  [(0.97)] TJ ET
0.267 0.267 0.267 rg
538.686 226.672 42.189 0.750 re f
538.686 210.790 0.750 16.631 re f
580.125 210.790 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 216.817 Td /F1 9.8 Tf  [(1.00)] TJ ET
0.267 0.267 0.267 rg
26.625 210.790 72.770 0.750 re f
26.625 194.909 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 200.935 Td /F1 9.8 Tf  [(Langb db 06)] TJ ET
0.267 0.267 0.267 rg
98.645 210.790 72.770 0.750 re f
98.645 194.909 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 200.935 Td /F1 9.8 Tf  [(R. extended)] TJ ET
0.267 0.267 0.267 rg
170.665 210.790 35.775 0.750 re f
170.665 194.909 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 200.935 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 210.790 87.399 0.750 re f
205.690 194.909 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 200.935 Td /F1 9.8 Tf  [(0.60)] TJ ET
0.267 0.267 0.267 rg
292.340 210.790 39.425 0.750 re f
292.340 194.909 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 200.935 Td /F1 9.8 Tf  [(0.53)] TJ ET
0.267 0.267 0.267 rg
331.014 210.790 39.425 0.750 re f
331.014 194.909 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 200.935 Td /F1 9.8 Tf  [(0.67)] TJ ET
0.267 0.267 0.267 rg
369.689 210.790 39.479 0.750 re f
369.689 194.909 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 200.935 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 210.790 89.579 0.750 re f
408.418 194.909 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 200.935 Td /F1 9.8 Tf  [(0.55)] TJ ET
0.267 0.267 0.267 rg
497.246 210.790 42.189 0.750 re f
497.246 194.909 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 200.935 Td /F1 9.8 Tf  [(0.47)] TJ ET
0.267 0.267 0.267 rg
538.686 210.790 42.189 0.750 re f
538.686 194.909 0.750 16.631 re f
580.125 194.909 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 200.935 Td /F1 9.8 Tf  [(0.63)] TJ ET
0.267 0.267 0.267 rg
26.625 194.909 72.770 0.750 re f
26.625 179.028 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 185.054 Td /F1 9.8 Tf  [(Langb db 06)] TJ ET
0.267 0.267 0.267 rg
98.645 194.909 72.770 0.750 re f
98.645 179.028 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 185.054 Td /F1 9.8 Tf  [(R. Analog)] TJ ET
0.267 0.267 0.267 rg
170.665 194.909 35.775 0.750 re f
170.665 179.028 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 185.054 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 194.909 87.399 0.750 re f
205.690 179.028 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 185.054 Td /F1 9.8 Tf  [(0.64)] TJ ET
0.267 0.267 0.267 rg
292.340 194.909 39.425 0.750 re f
292.340 179.028 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 185.054 Td /F1 9.8 Tf  [(0.57)] TJ ET
0.267 0.267 0.267 rg
331.014 194.909 39.425 0.750 re f
331.014 179.028 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 185.054 Td /F1 9.8 Tf  [(0.70)] TJ ET
0.267 0.267 0.267 rg
369.689 194.909 39.479 0.750 re f
369.689 179.028 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 185.054 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 194.909 89.579 0.750 re f
408.418 179.028 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 185.054 Td /F1 9.8 Tf  [(0.59)] TJ ET
0.267 0.267 0.267 rg
497.246 194.909 42.189 0.750 re f
497.246 179.028 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 185.054 Td /F1 9.8 Tf  [(0.50)] TJ ET
0.267 0.267 0.267 rg
538.686 194.909 42.189 0.750 re f
538.686 179.028 0.750 16.631 re f
580.125 179.028 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 185.054 Td /F1 9.8 Tf  [(0.67)] TJ ET
0.267 0.267 0.267 rg
26.625 179.028 72.770 0.750 re f
26.625 163.147 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 169.173 Td /F1 9.8 Tf  [(Langb db 06)] TJ ET
0.267 0.267 0.267 rg
98.645 179.028 72.770 0.750 re f
98.645 163.147 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 169.173 Td /F1 9.8 Tf  [(Motor)] TJ ET
0.267 0.267 0.267 rg
170.665 179.028 35.775 0.750 re f
170.665 163.147 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 169.173 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 179.028 87.399 0.750 re f
205.690 163.147 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 169.173 Td /F1 9.8 Tf  [(0.51)] TJ ET
0.267 0.267 0.267 rg
292.340 179.028 39.425 0.750 re f
292.340 163.147 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 169.173 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
331.014 179.028 39.425 0.750 re f
331.014 163.147 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 169.173 Td /F1 9.8 Tf  [(0.58)] TJ ET
0.267 0.267 0.267 rg
369.689 179.028 39.479 0.750 re f
369.689 163.147 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 169.173 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 179.028 89.579 0.750 re f
408.418 163.147 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 169.173 Td /F1 9.8 Tf  [(0.59)] TJ ET
0.267 0.267 0.267 rg
497.246 179.028 42.189 0.750 re f
497.246 163.147 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 169.173 Td /F1 9.8 Tf  [(0.50)] TJ ET
0.267 0.267 0.267 rg
538.686 179.028 42.189 0.750 re f
538.686 163.147 0.750 16.631 re f
580.125 163.147 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 169.173 Td /F1 9.8 Tf  [(0.67)] TJ ET
0.267 0.267 0.267 rg
26.625 163.147 72.770 0.750 re f
26.625 147.265 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 153.292 Td /F1 9.8 Tf  [(Langb db 06)] TJ ET
0.267 0.267 0.267 rg
98.645 163.147 72.770 0.750 re f
98.645 147.265 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 153.292 Td /F1 9.8 Tf  [(TFC)] TJ ET
0.267 0.267 0.267 rg
170.665 163.147 35.775 0.750 re f
170.665 147.265 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 153.292 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 163.147 87.399 0.750 re f
205.690 147.265 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 153.292 Td /F1 9.8 Tf  [(0.51)] TJ ET
0.267 0.267 0.267 rg
292.340 163.147 39.425 0.750 re f
292.340 147.265 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 153.292 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
331.014 163.147 39.425 0.750 re f
331.014 147.265 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 153.292 Td /F1 9.8 Tf  [(0.58)] TJ ET
0.267 0.267 0.267 rg
369.689 163.147 39.479 0.750 re f
369.689 147.265 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 153.292 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 163.147 89.579 0.750 re f
408.418 147.265 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 153.292 Td /F1 9.8 Tf  [(0.55)] TJ ET
0.267 0.267 0.267 rg
497.246 163.147 42.189 0.750 re f
497.246 147.265 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 153.292 Td /F1 9.8 Tf  [(0.47)] TJ ET
0.267 0.267 0.267 rg
538.686 163.147 42.189 0.750 re f
538.686 147.265 0.750 16.631 re f
580.125 147.265 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 153.292 Td /F1 9.8 Tf  [(0.63)] TJ ET
0.267 0.267 0.267 rg
26.625 147.265 72.770 0.750 re f
26.625 131.384 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 137.410 Td /F1 9.8 Tf  [(R. extended)] TJ ET
0.267 0.267 0.267 rg
98.645 147.265 72.770 0.750 re f
98.645 131.384 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 137.410 Td /F1 9.8 Tf  [(R. analog)] TJ ET
0.267 0.267 0.267 rg
170.665 147.265 35.775 0.750 re f
170.665 131.384 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 137.410 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 147.265 87.399 0.750 re f
205.690 131.384 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 137.410 Td /F1 9.8 Tf  [(1.00)] TJ ET
0.267 0.267 0.267 rg
292.340 147.265 39.425 0.750 re f
292.340 131.384 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 137.410 Td /F1 9.8 Tf  [(0.98)] TJ ET
0.267 0.267 0.267 rg
331.014 147.265 39.425 0.750 re f
331.014 131.384 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 137.410 Td /F1 9.8 Tf  [(1.00)] TJ ET
0.267 0.267 0.267 rg
369.689 147.265 39.479 0.750 re f
369.689 131.384 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 137.410 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 147.265 89.579 0.750 re f
408.418 131.384 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 137.410 Td /F1 9.8 Tf  [(1.00)] TJ ET
0.267 0.267 0.267 rg
497.246 147.265 42.189 0.750 re f
497.246 131.384 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 137.410 Td /F1 9.8 Tf  [(0.97)] TJ ET
0.267 0.267 0.267 rg
538.686 147.265 42.189 0.750 re f
538.686 131.384 0.750 16.631 re f
580.125 131.384 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 137.410 Td /F1 9.8 Tf  [(1.00)] TJ ET
0.267 0.267 0.267 rg
26.625 131.384 72.770 0.750 re f
26.625 115.503 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 121.529 Td /F1 9.8 Tf  [(R. extended)] TJ ET
0.267 0.267 0.267 rg
98.645 131.384 72.770 0.750 re f
98.645 115.503 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 121.529 Td /F1 9.8 Tf  [(Motor)] TJ ET
0.267 0.267 0.267 rg
170.665 131.384 35.775 0.750 re f
170.665 115.503 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 121.529 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 131.384 87.399 0.750 re f
205.690 115.503 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 121.529 Td /F1 9.8 Tf  [(0.41)] TJ ET
0.267 0.267 0.267 rg
292.340 131.384 39.425 0.750 re f
292.340 115.503 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 121.529 Td /F1 9.8 Tf  [(0.34)] TJ ET
0.267 0.267 0.267 rg
331.014 131.384 39.425 0.750 re f
331.014 115.503 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 121.529 Td /F1 9.8 Tf  [(0.48)] TJ ET
0.267 0.267 0.267 rg
369.689 131.384 39.479 0.750 re f
369.689 115.503 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 121.529 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 131.384 89.579 0.750 re f
408.418 115.503 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 121.529 Td /F1 9.8 Tf  [(0.43)] TJ ET
0.267 0.267 0.267 rg
497.246 131.384 42.189 0.750 re f
497.246 115.503 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 121.529 Td /F1 9.8 Tf  [(0.35)] TJ ET
0.267 0.267 0.267 rg
538.686 131.384 42.189 0.750 re f
538.686 115.503 0.750 16.631 re f
580.125 115.503 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 121.529 Td /F1 9.8 Tf  [(0.52)] TJ ET
0.267 0.267 0.267 rg
26.625 115.503 72.770 0.750 re f
26.625 99.622 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 105.648 Td /F1 9.8 Tf  [(R. extended)] TJ ET
0.267 0.267 0.267 rg
98.645 115.503 72.770 0.750 re f
98.645 99.622 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 105.648 Td /F1 9.8 Tf  [(TFC)] TJ ET
0.267 0.267 0.267 rg
170.665 115.503 35.775 0.750 re f
170.665 99.622 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 105.648 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 115.503 87.399 0.750 re f
205.690 99.622 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 105.648 Td /F1 9.8 Tf  [(0.43)] TJ ET
0.267 0.267 0.267 rg
292.340 115.503 39.425 0.750 re f
292.340 99.622 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 105.648 Td /F1 9.8 Tf  [(0.36)] TJ ET
0.267 0.267 0.267 rg
331.014 115.503 39.425 0.750 re f
331.014 99.622 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 105.648 Td /F1 9.8 Tf  [(0.50)] TJ ET
0.267 0.267 0.267 rg
369.689 115.503 39.479 0.750 re f
369.689 99.622 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 105.648 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 115.503 89.579 0.750 re f
408.418 99.622 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 105.648 Td /F1 9.8 Tf  [(0.40)] TJ ET
0.267 0.267 0.267 rg
497.246 115.503 42.189 0.750 re f
497.246 99.622 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 105.648 Td /F1 9.8 Tf  [(0.32)] TJ ET
0.267 0.267 0.267 rg
538.686 115.503 42.189 0.750 re f
538.686 99.622 0.750 16.631 re f
580.125 99.622 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 105.648 Td /F1 9.8 Tf  [(0.48)] TJ ET
0.267 0.267 0.267 rg
26.625 99.622 72.770 0.750 re f
26.625 83.740 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 89.767 Td /F1 9.8 Tf  [(R. analog)] TJ ET
0.267 0.267 0.267 rg
98.645 99.622 72.770 0.750 re f
98.645 83.740 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 89.767 Td /F1 9.8 Tf  [(Motor)] TJ ET
0.267 0.267 0.267 rg
170.665 99.622 35.775 0.750 re f
170.665 83.740 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 89.767 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 99.622 87.399 0.750 re f
205.690 83.740 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 89.767 Td /F1 9.8 Tf  [(0.41)] TJ ET
0.267 0.267 0.267 rg
292.340 99.622 39.425 0.750 re f
292.340 83.740 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 89.767 Td /F1 9.8 Tf  [(0.34)] TJ ET
0.267 0.267 0.267 rg
331.014 99.622 39.425 0.750 re f
331.014 83.740 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 89.767 Td /F1 9.8 Tf  [(0.48)] TJ ET
0.267 0.267 0.267 rg
369.689 99.622 39.479 0.750 re f
369.689 83.740 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 89.767 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 99.622 89.579 0.750 re f
408.418 83.740 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 89.767 Td /F1 9.8 Tf  [(0.43)] TJ ET
0.267 0.267 0.267 rg
497.246 99.622 42.189 0.750 re f
497.246 83.740 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 89.767 Td /F1 9.8 Tf  [(0.35)] TJ ET
0.267 0.267 0.267 rg
538.686 99.622 42.189 0.750 re f
538.686 83.740 0.750 16.631 re f
580.125 83.740 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 89.767 Td /F1 9.8 Tf  [(0.51)] TJ ET
0.267 0.267 0.267 rg
26.625 83.740 72.770 0.750 re f
26.625 67.859 72.770 0.750 re f
26.625 67.859 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 73.885 Td /F1 9.8 Tf  [(R. analog)] TJ ET
0.267 0.267 0.267 rg
98.645 83.740 72.770 0.750 re f
98.645 67.859 72.770 0.750 re f
98.645 67.859 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 73.885 Td /F1 9.8 Tf  [(TFC)] TJ ET
0.267 0.267 0.267 rg
170.665 83.740 35.775 0.750 re f
170.665 67.859 35.775 0.750 re f
170.665 67.859 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 73.885 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 83.740 87.399 0.750 re f
205.690 67.859 87.399 0.750 re f
205.690 67.859 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 73.885 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
292.340 83.740 39.425 0.750 re f
292.340 67.859 39.425 0.750 re f
292.340 67.859 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 73.885 Td /F1 9.8 Tf  [(0.37)] TJ ET
0.267 0.267 0.267 rg
331.014 83.740 39.425 0.750 re f
331.014 67.859 39.425 0.750 re f
331.014 67.859 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 73.885 Td /F1 9.8 Tf  [(0.51)] TJ ET
0.267 0.267 0.267 rg
369.689 83.740 39.479 0.750 re f
369.689 67.859 39.479 0.750 re f
369.689 67.859 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 73.885 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 83.740 89.579 0.750 re f
408.418 67.859 89.579 0.750 re f
408.418 67.859 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 73.885 Td /F1 9.8 Tf  [(0.41)] TJ ET
0.267 0.267 0.267 rg
497.246 83.740 42.189 0.750 re f
497.246 67.859 42.189 0.750 re f
497.246 67.859 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 73.885 Td /F1 9.8 Tf  [(0.33)] TJ ET
0.267 0.267 0.267 rg
538.686 83.740 42.189 0.750 re f
538.686 67.859 42.189 0.750 re f
538.686 67.859 0.750 16.631 re f
580.125 67.859 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 73.885 Td /F1 9.8 Tf  [(0.49)] TJ ET
Q
q
0.000 0.000 0.000 rg
BT 291.710 19.825 Td /F1 11.0 Tf  [(4)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Huntington Disease)] TJ ET

Q
endstream
endobj
149 0 obj
<< /Type /Page
/Parent 3 0 R
/Annots [ 151 0 R 153 0 R 155 0 R 157 0 R 159 0 R 161 0 R 163 0 R 165 0 R 167 0 R ]
/Contents 150 0 R
>>
endobj
150 0 obj
<<
/Length 55243 >>
stream

0.271 0.267 0.267 rg
q
15.000 38.864 577.500 738.136 re W n
1.000 1.000 1.000 rg
26.250 649.706 555.000 127.294 re f
0.267 0.267 0.267 rg
26.625 776.625 72.770 0.750 re f
26.625 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 31.875 766.770 Td /F1 9.8 Tf  [(Motor)] TJ ET
0.267 0.267 0.267 rg
98.645 776.625 72.770 0.750 re f
98.645 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 103.895 766.770 Td /F1 9.8 Tf  [(TFC)] TJ ET
0.267 0.267 0.267 rg
170.665 776.625 35.775 0.750 re f
170.665 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 175.915 766.770 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 776.625 87.399 0.750 re f
205.690 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 210.940 766.770 Td /F1 9.8 Tf  [(0.76)] TJ ET
0.267 0.267 0.267 rg
292.340 776.625 39.425 0.750 re f
292.340 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 297.590 766.770 Td /F1 9.8 Tf  [(0.69)] TJ ET
0.267 0.267 0.267 rg
331.014 776.625 39.425 0.750 re f
331.014 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 336.264 766.770 Td /F1 9.8 Tf  [(0.81)] TJ ET
0.267 0.267 0.267 rg
369.689 776.625 39.479 0.750 re f
369.689 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 374.939 766.770 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 776.625 89.579 0.750 re f
408.418 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 413.668 766.770 Td /F1 9.8 Tf  [(0.73)] TJ ET
0.267 0.267 0.267 rg
497.246 776.625 42.189 0.750 re f
497.246 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 502.496 766.770 Td /F1 9.8 Tf  [(0.65)] TJ ET
0.267 0.267 0.267 rg
538.686 776.625 42.189 0.750 re f
538.686 745.369 0.750 32.006 re f
580.125 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 543.936 766.770 Td /F1 9.8 Tf  [(0.80)] TJ ET
0.267 0.267 0.267 rg
26.625 745.369 72.770 0.750 re f
26.625 729.487 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 735.514 Td /F1 9.8 Tf  [(Rater)] TJ ET
0.267 0.267 0.267 rg
98.645 745.369 72.770 0.750 re f
98.645 729.487 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 735.514 Td /F1 9.8 Tf  [(Langb 06)] TJ ET
0.267 0.267 0.267 rg
170.665 745.369 35.775 0.750 re f
170.665 729.487 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 735.514 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 745.369 87.399 0.750 re f
205.690 729.487 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 735.514 Td /F1 9.8 Tf  [(0.51)] TJ ET
0.267 0.267 0.267 rg
292.340 745.369 39.425 0.750 re f
292.340 729.487 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 735.514 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
331.014 745.369 39.425 0.750 re f
331.014 729.487 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 735.514 Td /F1 9.8 Tf  [(0.58)] TJ ET
0.267 0.267 0.267 rg
369.689 745.369 39.479 0.750 re f
369.689 729.487 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 735.514 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 745.369 89.579 0.750 re f
408.418 729.487 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 735.514 Td /F1 9.8 Tf  [(0.53)] TJ ET
0.267 0.267 0.267 rg
497.246 745.369 42.189 0.750 re f
497.246 729.487 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 735.514 Td /F1 9.8 Tf  [(0.45)] TJ ET
0.267 0.267 0.267 rg
538.686 745.369 42.189 0.750 re f
538.686 729.487 0.750 16.631 re f
580.125 729.487 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 735.514 Td /F1 9.8 Tf  [(0.61)] TJ ET
0.267 0.267 0.267 rg
26.625 729.487 72.770 0.750 re f
26.625 713.606 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 719.633 Td /F1 9.8 Tf  [(Rater)] TJ ET
0.267 0.267 0.267 rg
98.645 729.487 72.770 0.750 re f
98.645 713.606 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 719.633 Td /F1 9.8 Tf  [(Langb db 06)] TJ ET
0.267 0.267 0.267 rg
170.665 729.487 35.775 0.750 re f
170.665 713.606 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 719.633 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 729.487 87.399 0.750 re f
205.690 713.606 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 719.633 Td /F1 9.8 Tf  [(0.50)] TJ ET
0.267 0.267 0.267 rg
292.340 729.487 39.425 0.750 re f
292.340 713.606 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 719.633 Td /F1 9.8 Tf  [(0.43)] TJ ET
0.267 0.267 0.267 rg
331.014 729.487 39.425 0.750 re f
331.014 713.606 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 719.633 Td /F1 9.8 Tf  [(0.57)] TJ ET
0.267 0.267 0.267 rg
369.689 729.487 39.479 0.750 re f
369.689 713.606 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 719.633 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 729.487 89.579 0.750 re f
408.418 713.606 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 719.633 Td /F1 9.8 Tf  [(0.52)] TJ ET
0.267 0.267 0.267 rg
497.246 729.487 42.189 0.750 re f
497.246 713.606 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 719.633 Td /F1 9.8 Tf  [(0.43)] TJ ET
0.267 0.267 0.267 rg
538.686 729.487 42.189 0.750 re f
538.686 713.606 0.750 16.631 re f
580.125 713.606 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 719.633 Td /F1 9.8 Tf  [(0.60)] TJ ET
0.267 0.267 0.267 rg
26.625 713.606 72.770 0.750 re f
26.625 697.725 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 703.751 Td /F1 9.8 Tf  [(Rater)] TJ ET
0.267 0.267 0.267 rg
98.645 713.606 72.770 0.750 re f
98.645 697.725 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 703.751 Td /F1 9.8 Tf  [(R. extended)] TJ ET
0.267 0.267 0.267 rg
170.665 713.606 35.775 0.750 re f
170.665 697.725 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 703.751 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 713.606 87.399 0.750 re f
205.690 697.725 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 703.751 Td /F1 9.8 Tf  [(0.49)] TJ ET
0.267 0.267 0.267 rg
292.340 713.606 39.425 0.750 re f
292.340 697.725 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 703.751 Td /F1 9.8 Tf  [(0.42)] TJ ET
0.267 0.267 0.267 rg
331.014 713.606 39.425 0.750 re f
331.014 697.725 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 703.751 Td /F1 9.8 Tf  [(0.56)] TJ ET
0.267 0.267 0.267 rg
369.689 713.606 39.479 0.750 re f
369.689 697.725 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 703.751 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 713.606 89.579 0.750 re f
408.418 697.725 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 703.751 Td /F1 9.8 Tf  [(0.52)] TJ ET
0.267 0.267 0.267 rg
497.246 713.606 42.189 0.750 re f
497.246 697.725 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 703.751 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
538.686 713.606 42.189 0.750 re f
538.686 697.725 0.750 16.631 re f
580.125 697.725 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 703.751 Td /F1 9.8 Tf  [(0.61)] TJ ET
0.267 0.267 0.267 rg
26.625 697.725 72.770 0.750 re f
26.625 681.844 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 687.870 Td /F1 9.8 Tf  [(Rater)] TJ ET
0.267 0.267 0.267 rg
98.645 697.725 72.770 0.750 re f
98.645 681.844 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 687.870 Td /F1 9.8 Tf  [(R. analog)] TJ ET
0.267 0.267 0.267 rg
170.665 697.725 35.775 0.750 re f
170.665 681.844 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 687.870 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 697.725 87.399 0.750 re f
205.690 681.844 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 687.870 Td /F1 9.8 Tf  [(0.52)] TJ ET
0.267 0.267 0.267 rg
292.340 697.725 39.425 0.750 re f
292.340 681.844 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 687.870 Td /F1 9.8 Tf  [(0.45)] TJ ET
0.267 0.267 0.267 rg
331.014 697.725 39.425 0.750 re f
331.014 681.844 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 687.870 Td /F1 9.8 Tf  [(0.59)] TJ ET
0.267 0.267 0.267 rg
369.689 697.725 39.479 0.750 re f
369.689 681.844 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 687.870 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 697.725 89.579 0.750 re f
408.418 681.844 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 687.870 Td /F1 9.8 Tf  [(0.54)] TJ ET
0.267 0.267 0.267 rg
497.246 697.725 42.189 0.750 re f
497.246 681.844 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 687.870 Td /F1 9.8 Tf  [(0.45)] TJ ET
0.267 0.267 0.267 rg
538.686 697.725 42.189 0.750 re f
538.686 681.844 0.750 16.631 re f
580.125 681.844 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 687.870 Td /F1 9.8 Tf  [(0.62)] TJ ET
0.267 0.267 0.267 rg
26.625 681.844 72.770 0.750 re f
26.625 665.962 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 671.989 Td /F1 9.8 Tf  [(Rater)] TJ ET
0.267 0.267 0.267 rg
98.645 681.844 72.770 0.750 re f
98.645 665.962 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 671.989 Td /F1 9.8 Tf  [(Motor)] TJ ET
0.267 0.267 0.267 rg
170.665 681.844 35.775 0.750 re f
170.665 665.962 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 671.989 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 681.844 87.399 0.750 re f
205.690 665.962 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 671.989 Td /F1 9.8 Tf  [(0.58)] TJ ET
0.267 0.267 0.267 rg
292.340 681.844 39.425 0.750 re f
292.340 665.962 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 671.989 Td /F1 9.8 Tf  [(0.51)] TJ ET
0.267 0.267 0.267 rg
331.014 681.844 39.425 0.750 re f
331.014 665.962 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 671.989 Td /F1 9.8 Tf  [(0.65)] TJ ET
0.267 0.267 0.267 rg
369.689 681.844 39.479 0.750 re f
369.689 665.962 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 671.989 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 681.844 89.579 0.750 re f
408.418 665.962 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 671.989 Td /F1 9.8 Tf  [(0.61)] TJ ET
0.267 0.267 0.267 rg
497.246 681.844 42.189 0.750 re f
497.246 665.962 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 671.989 Td /F1 9.8 Tf  [(0.52)] TJ ET
0.267 0.267 0.267 rg
538.686 681.844 42.189 0.750 re f
538.686 665.962 0.750 16.631 re f
580.125 665.962 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 671.989 Td /F1 9.8 Tf  [(0.69)] TJ ET
0.267 0.267 0.267 rg
26.625 665.962 72.770 0.750 re f
26.625 650.081 72.770 0.750 re f
26.625 650.081 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 656.108 Td /F1 9.8 Tf  [(Rater)] TJ ET
0.267 0.267 0.267 rg
98.645 665.962 72.770 0.750 re f
98.645 650.081 72.770 0.750 re f
98.645 650.081 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 656.108 Td /F1 9.8 Tf  [(TFC)] TJ ET
0.267 0.267 0.267 rg
170.665 665.962 35.775 0.750 re f
170.665 650.081 35.775 0.750 re f
170.665 650.081 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 656.108 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 665.962 87.399 0.750 re f
205.690 650.081 87.399 0.750 re f
205.690 650.081 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 656.108 Td /F1 9.8 Tf  [(0.52)] TJ ET
0.267 0.267 0.267 rg
292.340 665.962 39.425 0.750 re f
292.340 650.081 39.425 0.750 re f
292.340 650.081 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 656.108 Td /F1 9.8 Tf  [(0.45)] TJ ET
0.267 0.267 0.267 rg
331.014 665.962 39.425 0.750 re f
331.014 650.081 39.425 0.750 re f
331.014 650.081 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 656.108 Td /F1 9.8 Tf  [(0.59)] TJ ET
0.267 0.267 0.267 rg
369.689 665.962 39.479 0.750 re f
369.689 650.081 39.479 0.750 re f
369.689 650.081 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 656.108 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 665.962 89.579 0.750 re f
408.418 650.081 89.579 0.750 re f
408.418 650.081 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 656.108 Td /F1 9.8 Tf  [(0.52)] TJ ET
0.267 0.267 0.267 rg
497.246 665.962 42.189 0.750 re f
497.246 650.081 42.189 0.750 re f
497.246 650.081 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 656.108 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
538.686 665.962 42.189 0.750 re f
538.686 650.081 42.189 0.750 re f
538.686 650.081 0.750 16.631 re f
580.125 650.081 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 656.108 Td /F1 9.8 Tf  [(0.61)] TJ ET
BT 26.250 602.682 Td /F4 9.8 Tf  [(Table 2.)] TJ ET
BT 62.559 602.682 Td /F1 9.8 Tf  [( Agreement rates \(� 5years\) between different formulae. Agreement rates between pairs of estimates were calculated )] TJ ET
BT 26.250 590.778 Td /F1 9.8 Tf  [(with Clopper-Pearson 95% confidence intervals. If both methods arrived at the same result within a �5 year bracket the )] TJ ET
BT 26.250 578.873 Td /F1 9.8 Tf  [(agreement was defined as �1�. If the results were more than 5 years different the agreement was defined as �0�. For all )] TJ ET
BT 26.250 566.968 Td /F1 9.8 Tf  [(participants, the agreement rate was expressed as % agreement within accepted range. Abbreviations: Langb db 06: calculated )] TJ ET
BT 26.250 555.063 Td /F1 9.8 Tf  [(at an age corresponding to disease burden of 200, age when the predicted probability of signs exceeds 0.6. R. analog: Ranen )] TJ ET
BT 26.250 543.159 Td /F1 9.8 Tf  [(analogous. R. extended: Ranen extended.)] TJ ET
BT 26.250 506.556 Td /F4 12.0 Tf  [(DISCUSSION)] TJ ET
BT 26.250 486.602 Td /F1 9.8 Tf  [(The present study assessed how a data derived age-at-onset compares to the rater�s estimate, the commonly used definition of )] TJ ET
BT 26.250 474.697 Td /F1 9.8 Tf  [(AAO. Using longitudinal data from the REGISTRY large observational study, our results suggest that it can be useful to 1\) add )] TJ ET
BT 26.250 462.792 Td /F1 9.8 Tf  [(in the manifest population motor score regression derived AAO as additional motor onset; 2\) when patients are in mid- to late-)] TJ ET
BT 26.250 450.888 Td /F1 9.8 Tf  [(stage HD add TFC regression derived AAO for the onset of functional impact of HD; 3\) predictions of AAO suggest a later onset )] TJ ET
BT 26.250 438.983 Td /F1 9.8 Tf  [(than the actual emergence of unequivocal motor signs of HD.)] TJ ET
BT 26.250 419.578 Td /F4 9.8 Tf  [(Calculate age-at-onset in manifest HD)] TJ ET
BT 26.250 400.173 Td /F1 9.8 Tf  [(The current gold standard of AAO is a clinician�s estimate integrating data from the patient�s history, collateral history of family )] TJ ET
BT 26.250 388.269 Td /F1 9.8 Tf  [(or carers and the examination of the patient. We compared a data derived AAO with the estimated AAO. We first used a simple )] TJ ET
BT 26.250 376.364 Td /F1 9.8 Tf  [(regression analysis of longitudinal UHDRS motor score data and calculated the patient�s age when the motor score was 5 or )] TJ ET
BT 26.250 364.459 Td /F1 9.8 Tf  [(greater, a cut-off used in TRACK-HD, a large longitudinal multi-centre study. )] TJ ET
0.267 0.267 0.267 rg
BT 357.331 364.459 Td /F1 8.7 Tf  [([10], [11])] TJ ET
0.271 0.267 0.267 rg
BT 391.061 364.459 Td /F1 9.8 Tf  [( The AAO from regressing motor scores )] TJ ET
BT 26.250 352.554 Td /F1 9.8 Tf  [(was 3 years later than the median AAO estimated by REGISTRY investigators. The agreement rates between onset in )] TJ ET
BT 26.250 340.650 Td /F1 9.8 Tf  [(REGISTRY data and the calculated motor onset revealed a difference of about 20 years in the 25%tile. REGISTRY participants )] TJ ET
BT 26.250 328.745 Td /F1 9.8 Tf  [(were enrolled when they already had manifest HD. This means that at the REGISTRY enrolment visit the investigator may have )] TJ ET
BT 26.250 316.840 Td /F1 9.8 Tf  [(had to judge AAO after many years of manifest disease. This AAO estimate would be less accurate than AAO observation. )] TJ ET
BT 26.250 304.935 Td /F1 9.8 Tf  [(However, in REGISTRY an earlier estimated onset than that calculated from longitudinal motor scores may also suggest that )] TJ ET
BT 26.250 293.031 Td /F1 9.8 Tf  [(investigators are not guided by motor signs alone.)] TJ ET
BT 26.250 273.626 Td /F1 9.8 Tf  [(Many studies of genetic modifiers relate their effect to a general onset of HD. It is possible that there are domain specific onset )] TJ ET
BT 26.250 261.721 Td /F1 9.8 Tf  [(modifiers. Such domain specific modifying effects may be overlooked unless domain specific onsets are defined. Our data )] TJ ET
BT 26.250 249.816 Td /F1 9.8 Tf  [(suggest that it is possible to use longitudinal motor score data to extrapolate a motor domain onset even in patients with a non-)] TJ ET
BT 26.250 237.912 Td /F1 9.8 Tf  [(motor onset. This approach has the added advantage that it is based on data collected by certified UHDRS motor scale raters )] TJ ET
BT 26.250 226.007 Td /F1 9.8 Tf  [(directly examining the patient. This removes some of the variability introduced by judging an onset retrospectively.)] TJ ET
BT 26.250 206.602 Td /F1 9.8 Tf  [(The UHDRS TFC reflects a general impact on the ability to work, handle finances, and the activities of daily living. )] TJ ET
0.267 0.267 0.267 rg
BT 518.274 206.602 Td /F1 8.7 Tf  [([12])] TJ ET
0.271 0.267 0.267 rg
BT 532.730 206.602 Td /F1 9.8 Tf  [( The )] TJ ET
BT 26.250 194.697 Td /F1 9.8 Tf  [(calculated TFC onset was about 4 years later than the rater estimate indicating that it may take a number of years before HD )] TJ ET
BT 26.250 182.793 Td /F1 9.8 Tf  [(manifestations have a substantial impact on daily life. The good agreement rate between the rater estimate and the calculated )] TJ ET
BT 26.250 170.888 Td /F1 9.8 Tf  [(�TFC onset minus 4 years� suggests this interval of 4 years is fairly robust and does not depend on the major sign at onset. A )] TJ ET
BT 26.250 158.983 Td /F1 9.8 Tf  [(�TCF onset� may add an important endpoint based on function. While in the prodromal phase new scales may have to be )] TJ ET
BT 26.250 147.078 Td /F1 9.8 Tf  [(devised, in midstage HD patients the calculation of an onset of functional impairment using the TFC may help identify the )] TJ ET
BT 26.250 135.174 Td /F1 9.8 Tf  [(factors that are most relevant to maintain function. )] TJ ET
0.267 0.267 0.267 rg
BT 245.186 135.174 Td /F1 8.7 Tf  [([13])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 115.769 Td /F4 9.8 Tf  [(Predicting age-at-onset in prodromal HD)] TJ ET
BT 26.250 96.364 Td /F1 9.8 Tf  [(Assuming our manifest participants were prodromal we compared AAO estimations in the REGISTRY data using the Langbehn, )] TJ ET
BT 26.250 84.459 Td /F1 9.8 Tf  [(or Ranen, formula with the rater estimates of AAO. While the medians agree well, in a substantial proportion of cases the )] TJ ET
BT 26.250 72.555 Td /F1 9.8 Tf  [(difference was as large as �20 years. Overall, however, the Langbehn formula estimates the AAO later than the raters� )] TJ ET
BT 26.250 60.650 Td /F1 9.8 Tf  [(observed AAO. This suggests that unequivocal motor signs of HD manifest earlier, sometimes many years, than predicted using )] TJ ET
BT 26.250 48.745 Td /F1 9.8 Tf  [(the Langbehn formula.)] TJ ET
Q
q
15.000 38.864 577.500 738.136 re W n
1.000 1.000 1.000 rg
26.250 649.706 555.000 127.294 re f
0.267 0.267 0.267 rg
26.625 776.625 72.770 0.750 re f
26.625 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 31.875 766.770 Td /F1 9.8 Tf  [(Motor)] TJ ET
0.267 0.267 0.267 rg
98.645 776.625 72.770 0.750 re f
98.645 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 103.895 766.770 Td /F1 9.8 Tf  [(TFC)] TJ ET
0.267 0.267 0.267 rg
170.665 776.625 35.775 0.750 re f
170.665 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 175.915 766.770 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 776.625 87.399 0.750 re f
205.690 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 210.940 766.770 Td /F1 9.8 Tf  [(0.76)] TJ ET
0.267 0.267 0.267 rg
292.340 776.625 39.425 0.750 re f
292.340 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 297.590 766.770 Td /F1 9.8 Tf  [(0.69)] TJ ET
0.267 0.267 0.267 rg
331.014 776.625 39.425 0.750 re f
331.014 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 336.264 766.770 Td /F1 9.8 Tf  [(0.81)] TJ ET
0.267 0.267 0.267 rg
369.689 776.625 39.479 0.750 re f
369.689 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 374.939 766.770 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 776.625 89.579 0.750 re f
408.418 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 413.668 766.770 Td /F1 9.8 Tf  [(0.73)] TJ ET
0.267 0.267 0.267 rg
497.246 776.625 42.189 0.750 re f
497.246 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 502.496 766.770 Td /F1 9.8 Tf  [(0.65)] TJ ET
0.267 0.267 0.267 rg
538.686 776.625 42.189 0.750 re f
538.686 745.369 0.750 32.006 re f
580.125 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 543.936 766.770 Td /F1 9.8 Tf  [(0.80)] TJ ET
0.267 0.267 0.267 rg
26.625 745.369 72.770 0.750 re f
26.625 729.487 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 735.514 Td /F1 9.8 Tf  [(Rater)] TJ ET
0.267 0.267 0.267 rg
98.645 745.369 72.770 0.750 re f
98.645 729.487 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 735.514 Td /F1 9.8 Tf  [(Langb 06)] TJ ET
0.267 0.267 0.267 rg
170.665 745.369 35.775 0.750 re f
170.665 729.487 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 735.514 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 745.369 87.399 0.750 re f
205.690 729.487 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 735.514 Td /F1 9.8 Tf  [(0.51)] TJ ET
0.267 0.267 0.267 rg
292.340 745.369 39.425 0.750 re f
292.340 729.487 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 735.514 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
331.014 745.369 39.425 0.750 re f
331.014 729.487 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 735.514 Td /F1 9.8 Tf  [(0.58)] TJ ET
0.267 0.267 0.267 rg
369.689 745.369 39.479 0.750 re f
369.689 729.487 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 735.514 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 745.369 89.579 0.750 re f
408.418 729.487 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 735.514 Td /F1 9.8 Tf  [(0.53)] TJ ET
0.267 0.267 0.267 rg
497.246 745.369 42.189 0.750 re f
497.246 729.487 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 735.514 Td /F1 9.8 Tf  [(0.45)] TJ ET
0.267 0.267 0.267 rg
538.686 745.369 42.189 0.750 re f
538.686 729.487 0.750 16.631 re f
580.125 729.487 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 735.514 Td /F1 9.8 Tf  [(0.61)] TJ ET
0.267 0.267 0.267 rg
26.625 729.487 72.770 0.750 re f
26.625 713.606 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 719.633 Td /F1 9.8 Tf  [(Rater)] TJ ET
0.267 0.267 0.267 rg
98.645 729.487 72.770 0.750 re f
98.645 713.606 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 719.633 Td /F1 9.8 Tf  [(Langb db 06)] TJ ET
0.267 0.267 0.267 rg
170.665 729.487 35.775 0.750 re f
170.665 713.606 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 719.633 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 729.487 87.399 0.750 re f
205.690 713.606 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 719.633 Td /F1 9.8 Tf  [(0.50)] TJ ET
0.267 0.267 0.267 rg
292.340 729.487 39.425 0.750 re f
292.340 713.606 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 719.633 Td /F1 9.8 Tf  [(0.43)] TJ ET
0.267 0.267 0.267 rg
331.014 729.487 39.425 0.750 re f
331.014 713.606 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 719.633 Td /F1 9.8 Tf  [(0.57)] TJ ET
0.267 0.267 0.267 rg
369.689 729.487 39.479 0.750 re f
369.689 713.606 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 719.633 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 729.487 89.579 0.750 re f
408.418 713.606 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 719.633 Td /F1 9.8 Tf  [(0.52)] TJ ET
0.267 0.267 0.267 rg
497.246 729.487 42.189 0.750 re f
497.246 713.606 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 719.633 Td /F1 9.8 Tf  [(0.43)] TJ ET
0.267 0.267 0.267 rg
538.686 729.487 42.189 0.750 re f
538.686 713.606 0.750 16.631 re f
580.125 713.606 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 719.633 Td /F1 9.8 Tf  [(0.60)] TJ ET
0.267 0.267 0.267 rg
26.625 713.606 72.770 0.750 re f
26.625 697.725 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 703.751 Td /F1 9.8 Tf  [(Rater)] TJ ET
0.267 0.267 0.267 rg
98.645 713.606 72.770 0.750 re f
98.645 697.725 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 703.751 Td /F1 9.8 Tf  [(R. extended)] TJ ET
0.267 0.267 0.267 rg
170.665 713.606 35.775 0.750 re f
170.665 697.725 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 703.751 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 713.606 87.399 0.750 re f
205.690 697.725 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 703.751 Td /F1 9.8 Tf  [(0.49)] TJ ET
0.267 0.267 0.267 rg
292.340 713.606 39.425 0.750 re f
292.340 697.725 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 703.751 Td /F1 9.8 Tf  [(0.42)] TJ ET
0.267 0.267 0.267 rg
331.014 713.606 39.425 0.750 re f
331.014 697.725 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 703.751 Td /F1 9.8 Tf  [(0.56)] TJ ET
0.267 0.267 0.267 rg
369.689 713.606 39.479 0.750 re f
369.689 697.725 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 703.751 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 713.606 89.579 0.750 re f
408.418 697.725 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 703.751 Td /F1 9.8 Tf  [(0.52)] TJ ET
0.267 0.267 0.267 rg
497.246 713.606 42.189 0.750 re f
497.246 697.725 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 703.751 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
538.686 713.606 42.189 0.750 re f
538.686 697.725 0.750 16.631 re f
580.125 697.725 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 703.751 Td /F1 9.8 Tf  [(0.61)] TJ ET
0.267 0.267 0.267 rg
26.625 697.725 72.770 0.750 re f
26.625 681.844 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 687.870 Td /F1 9.8 Tf  [(Rater)] TJ ET
0.267 0.267 0.267 rg
98.645 697.725 72.770 0.750 re f
98.645 681.844 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 687.870 Td /F1 9.8 Tf  [(R. analog)] TJ ET
0.267 0.267 0.267 rg
170.665 697.725 35.775 0.750 re f
170.665 681.844 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 687.870 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 697.725 87.399 0.750 re f
205.690 681.844 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 687.870 Td /F1 9.8 Tf  [(0.52)] TJ ET
0.267 0.267 0.267 rg
292.340 697.725 39.425 0.750 re f
292.340 681.844 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 687.870 Td /F1 9.8 Tf  [(0.45)] TJ ET
0.267 0.267 0.267 rg
331.014 697.725 39.425 0.750 re f
331.014 681.844 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 687.870 Td /F1 9.8 Tf  [(0.59)] TJ ET
0.267 0.267 0.267 rg
369.689 697.725 39.479 0.750 re f
369.689 681.844 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 687.870 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 697.725 89.579 0.750 re f
408.418 681.844 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 687.870 Td /F1 9.8 Tf  [(0.54)] TJ ET
0.267 0.267 0.267 rg
497.246 697.725 42.189 0.750 re f
497.246 681.844 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 687.870 Td /F1 9.8 Tf  [(0.45)] TJ ET
0.267 0.267 0.267 rg
538.686 697.725 42.189 0.750 re f
538.686 681.844 0.750 16.631 re f
580.125 681.844 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 687.870 Td /F1 9.8 Tf  [(0.62)] TJ ET
0.267 0.267 0.267 rg
26.625 681.844 72.770 0.750 re f
26.625 665.962 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 671.989 Td /F1 9.8 Tf  [(Rater)] TJ ET
0.267 0.267 0.267 rg
98.645 681.844 72.770 0.750 re f
98.645 665.962 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 671.989 Td /F1 9.8 Tf  [(Motor)] TJ ET
0.267 0.267 0.267 rg
170.665 681.844 35.775 0.750 re f
170.665 665.962 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 671.989 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 681.844 87.399 0.750 re f
205.690 665.962 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 671.989 Td /F1 9.8 Tf  [(0.58)] TJ ET
0.267 0.267 0.267 rg
292.340 681.844 39.425 0.750 re f
292.340 665.962 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 671.989 Td /F1 9.8 Tf  [(0.51)] TJ ET
0.267 0.267 0.267 rg
331.014 681.844 39.425 0.750 re f
331.014 665.962 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 671.989 Td /F1 9.8 Tf  [(0.65)] TJ ET
0.267 0.267 0.267 rg
369.689 681.844 39.479 0.750 re f
369.689 665.962 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 671.989 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 681.844 89.579 0.750 re f
408.418 665.962 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 671.989 Td /F1 9.8 Tf  [(0.61)] TJ ET
0.267 0.267 0.267 rg
497.246 681.844 42.189 0.750 re f
497.246 665.962 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 671.989 Td /F1 9.8 Tf  [(0.52)] TJ ET
0.267 0.267 0.267 rg
538.686 681.844 42.189 0.750 re f
538.686 665.962 0.750 16.631 re f
580.125 665.962 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 671.989 Td /F1 9.8 Tf  [(0.69)] TJ ET
0.267 0.267 0.267 rg
26.625 665.962 72.770 0.750 re f
26.625 650.081 72.770 0.750 re f
26.625 650.081 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 656.108 Td /F1 9.8 Tf  [(Rater)] TJ ET
0.267 0.267 0.267 rg
98.645 665.962 72.770 0.750 re f
98.645 650.081 72.770 0.750 re f
98.645 650.081 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 656.108 Td /F1 9.8 Tf  [(TFC)] TJ ET
0.267 0.267 0.267 rg
170.665 665.962 35.775 0.750 re f
170.665 650.081 35.775 0.750 re f
170.665 650.081 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 656.108 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 665.962 87.399 0.750 re f
205.690 650.081 87.399 0.750 re f
205.690 650.081 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 656.108 Td /F1 9.8 Tf  [(0.52)] TJ ET
0.267 0.267 0.267 rg
292.340 665.962 39.425 0.750 re f
292.340 650.081 39.425 0.750 re f
292.340 650.081 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 656.108 Td /F1 9.8 Tf  [(0.45)] TJ ET
0.267 0.267 0.267 rg
331.014 665.962 39.425 0.750 re f
331.014 650.081 39.425 0.750 re f
331.014 650.081 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 656.108 Td /F1 9.8 Tf  [(0.59)] TJ ET
0.267 0.267 0.267 rg
369.689 665.962 39.479 0.750 re f
369.689 650.081 39.479 0.750 re f
369.689 650.081 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 656.108 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 665.962 89.579 0.750 re f
408.418 650.081 89.579 0.750 re f
408.418 650.081 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 656.108 Td /F1 9.8 Tf  [(0.52)] TJ ET
0.267 0.267 0.267 rg
497.246 665.962 42.189 0.750 re f
497.246 650.081 42.189 0.750 re f
497.246 650.081 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 656.108 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
538.686 665.962 42.189 0.750 re f
538.686 650.081 42.189 0.750 re f
538.686 650.081 0.750 16.631 re f
580.125 650.081 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 656.108 Td /F1 9.8 Tf  [(0.61)] TJ ET
BT 26.250 602.682 Td /F4 9.8 Tf  [(Table 2.)] TJ ET
BT 62.559 602.682 Td /F1 9.8 Tf  [( Agreement rates \(� 5years\) between different formulae. Agreement rates between pairs of estimates were calculated )] TJ ET
BT 26.250 590.778 Td /F1 9.8 Tf  [(with Clopper-Pearson 95% confidence intervals. If both methods arrived at the same result within a �5 year bracket the )] TJ ET
BT 26.250 578.873 Td /F1 9.8 Tf  [(agreement was defined as �1�. If the results were more than 5 years different the agreement was defined as �0�. For all )] TJ ET
BT 26.250 566.968 Td /F1 9.8 Tf  [(participants, the agreement rate was expressed as % agreement within accepted range. Abbreviations: Langb db 06: calculated )] TJ ET
BT 26.250 555.063 Td /F1 9.8 Tf  [(at an age corresponding to disease burden of 200, age when the predicted probability of signs exceeds 0.6. R. analog: Ranen )] TJ ET
BT 26.250 543.159 Td /F1 9.8 Tf  [(analogous. R. extended: Ranen extended.)] TJ ET
BT 26.250 506.556 Td /F4 12.0 Tf  [(DISCUSSION)] TJ ET
BT 26.250 486.602 Td /F1 9.8 Tf  [(The present study assessed how a data derived age-at-onset compares to the rater�s estimate, the commonly used definition of )] TJ ET
BT 26.250 474.697 Td /F1 9.8 Tf  [(AAO. Using longitudinal data from the REGISTRY large observational study, our results suggest that it can be useful to 1\) add )] TJ ET
BT 26.250 462.792 Td /F1 9.8 Tf  [(in the manifest population motor score regression derived AAO as additional motor onset; 2\) when patients are in mid- to late-)] TJ ET
BT 26.250 450.888 Td /F1 9.8 Tf  [(stage HD add TFC regression derived AAO for the onset of functional impact of HD; 3\) predictions of AAO suggest a later onset )] TJ ET
BT 26.250 438.983 Td /F1 9.8 Tf  [(than the actual emergence of unequivocal motor signs of HD.)] TJ ET
BT 26.250 419.578 Td /F4 9.8 Tf  [(Calculate age-at-onset in manifest HD)] TJ ET
BT 26.250 400.173 Td /F1 9.8 Tf  [(The current gold standard of AAO is a clinician�s estimate integrating data from the patient�s history, collateral history of family )] TJ ET
BT 26.250 388.269 Td /F1 9.8 Tf  [(or carers and the examination of the patient. We compared a data derived AAO with the estimated AAO. We first used a simple )] TJ ET
BT 26.250 376.364 Td /F1 9.8 Tf  [(regression analysis of longitudinal UHDRS motor score data and calculated the patient�s age when the motor score was 5 or )] TJ ET
BT 26.250 364.459 Td /F1 9.8 Tf  [(greater, a cut-off used in TRACK-HD, a large longitudinal multi-centre study. )] TJ ET
0.267 0.267 0.267 rg
BT 357.331 364.459 Td /F1 8.7 Tf  [([10], [11])] TJ ET
0.271 0.267 0.267 rg
BT 391.061 364.459 Td /F1 9.8 Tf  [( The AAO from regressing motor scores )] TJ ET
BT 26.250 352.554 Td /F1 9.8 Tf  [(was 3 years later than the median AAO estimated by REGISTRY investigators. The agreement rates between onset in )] TJ ET
BT 26.250 340.650 Td /F1 9.8 Tf  [(REGISTRY data and the calculated motor onset revealed a difference of about 20 years in the 25%tile. REGISTRY participants )] TJ ET
BT 26.250 328.745 Td /F1 9.8 Tf  [(were enrolled when they already had manifest HD. This means that at the REGISTRY enrolment visit the investigator may have )] TJ ET
BT 26.250 316.840 Td /F1 9.8 Tf  [(had to judge AAO after many years of manifest disease. This AAO estimate would be less accurate than AAO observation. )] TJ ET
BT 26.250 304.935 Td /F1 9.8 Tf  [(However, in REGISTRY an earlier estimated onset than that calculated from longitudinal motor scores may also suggest that )] TJ ET
BT 26.250 293.031 Td /F1 9.8 Tf  [(investigators are not guided by motor signs alone.)] TJ ET
BT 26.250 273.626 Td /F1 9.8 Tf  [(Many studies of genetic modifiers relate their effect to a general onset of HD. It is possible that there are domain specific onset )] TJ ET
BT 26.250 261.721 Td /F1 9.8 Tf  [(modifiers. Such domain specific modifying effects may be overlooked unless domain specific onsets are defined. Our data )] TJ ET
BT 26.250 249.816 Td /F1 9.8 Tf  [(suggest that it is possible to use longitudinal motor score data to extrapolate a motor domain onset even in patients with a non-)] TJ ET
BT 26.250 237.912 Td /F1 9.8 Tf  [(motor onset. This approach has the added advantage that it is based on data collected by certified UHDRS motor scale raters )] TJ ET
BT 26.250 226.007 Td /F1 9.8 Tf  [(directly examining the patient. This removes some of the variability introduced by judging an onset retrospectively.)] TJ ET
BT 26.250 206.602 Td /F1 9.8 Tf  [(The UHDRS TFC reflects a general impact on the ability to work, handle finances, and the activities of daily living. )] TJ ET
0.267 0.267 0.267 rg
BT 518.274 206.602 Td /F1 8.7 Tf  [([12])] TJ ET
0.271 0.267 0.267 rg
BT 532.730 206.602 Td /F1 9.8 Tf  [( The )] TJ ET
BT 26.250 194.697 Td /F1 9.8 Tf  [(calculated TFC onset was about 4 years later than the rater estimate indicating that it may take a number of years before HD )] TJ ET
BT 26.250 182.793 Td /F1 9.8 Tf  [(manifestations have a substantial impact on daily life. The good agreement rate between the rater estimate and the calculated )] TJ ET
BT 26.250 170.888 Td /F1 9.8 Tf  [(�TFC onset minus 4 years� suggests this interval of 4 years is fairly robust and does not depend on the major sign at onset. A )] TJ ET
BT 26.250 158.983 Td /F1 9.8 Tf  [(�TCF onset� may add an important endpoint based on function. While in the prodromal phase new scales may have to be )] TJ ET
BT 26.250 147.078 Td /F1 9.8 Tf  [(devised, in midstage HD patients the calculation of an onset of functional impairment using the TFC may help identify the )] TJ ET
BT 26.250 135.174 Td /F1 9.8 Tf  [(factors that are most relevant to maintain function. )] TJ ET
0.267 0.267 0.267 rg
BT 245.186 135.174 Td /F1 8.7 Tf  [([13])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 115.769 Td /F4 9.8 Tf  [(Predicting age-at-onset in prodromal HD)] TJ ET
BT 26.250 96.364 Td /F1 9.8 Tf  [(Assuming our manifest participants were prodromal we compared AAO estimations in the REGISTRY data using the Langbehn, )] TJ ET
BT 26.250 84.459 Td /F1 9.8 Tf  [(or Ranen, formula with the rater estimates of AAO. While the medians agree well, in a substantial proportion of cases the )] TJ ET
BT 26.250 72.555 Td /F1 9.8 Tf  [(difference was as large as �20 years. Overall, however, the Langbehn formula estimates the AAO later than the raters� )] TJ ET
BT 26.250 60.650 Td /F1 9.8 Tf  [(observed AAO. This suggests that unequivocal motor signs of HD manifest earlier, sometimes many years, than predicted using )] TJ ET
BT 26.250 48.745 Td /F1 9.8 Tf  [(the Langbehn formula.)] TJ ET
Q
q
15.000 38.864 577.500 738.136 re W n
1.000 1.000 1.000 rg
26.250 649.706 555.000 127.294 re f
0.267 0.267 0.267 rg
26.625 776.625 72.770 0.750 re f
26.625 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 31.875 766.770 Td /F1 9.8 Tf  [(Motor)] TJ ET
0.267 0.267 0.267 rg
98.645 776.625 72.770 0.750 re f
98.645 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 103.895 766.770 Td /F1 9.8 Tf  [(TFC)] TJ ET
0.267 0.267 0.267 rg
170.665 776.625 35.775 0.750 re f
170.665 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 175.915 766.770 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 776.625 87.399 0.750 re f
205.690 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 210.940 766.770 Td /F1 9.8 Tf  [(0.76)] TJ ET
0.267 0.267 0.267 rg
292.340 776.625 39.425 0.750 re f
292.340 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 297.590 766.770 Td /F1 9.8 Tf  [(0.69)] TJ ET
0.267 0.267 0.267 rg
331.014 776.625 39.425 0.750 re f
331.014 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 336.264 766.770 Td /F1 9.8 Tf  [(0.81)] TJ ET
0.267 0.267 0.267 rg
369.689 776.625 39.479 0.750 re f
369.689 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 374.939 766.770 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 776.625 89.579 0.750 re f
408.418 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 413.668 766.770 Td /F1 9.8 Tf  [(0.73)] TJ ET
0.267 0.267 0.267 rg
497.246 776.625 42.189 0.750 re f
497.246 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 502.496 766.770 Td /F1 9.8 Tf  [(0.65)] TJ ET
0.267 0.267 0.267 rg
538.686 776.625 42.189 0.750 re f
538.686 745.369 0.750 32.006 re f
580.125 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 543.936 766.770 Td /F1 9.8 Tf  [(0.80)] TJ ET
0.267 0.267 0.267 rg
26.625 745.369 72.770 0.750 re f
26.625 729.487 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 735.514 Td /F1 9.8 Tf  [(Rater)] TJ ET
0.267 0.267 0.267 rg
98.645 745.369 72.770 0.750 re f
98.645 729.487 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 735.514 Td /F1 9.8 Tf  [(Langb 06)] TJ ET
0.267 0.267 0.267 rg
170.665 745.369 35.775 0.750 re f
170.665 729.487 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 735.514 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 745.369 87.399 0.750 re f
205.690 729.487 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 735.514 Td /F1 9.8 Tf  [(0.51)] TJ ET
0.267 0.267 0.267 rg
292.340 745.369 39.425 0.750 re f
292.340 729.487 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 735.514 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
331.014 745.369 39.425 0.750 re f
331.014 729.487 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 735.514 Td /F1 9.8 Tf  [(0.58)] TJ ET
0.267 0.267 0.267 rg
369.689 745.369 39.479 0.750 re f
369.689 729.487 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 735.514 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 745.369 89.579 0.750 re f
408.418 729.487 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 735.514 Td /F1 9.8 Tf  [(0.53)] TJ ET
0.267 0.267 0.267 rg
497.246 745.369 42.189 0.750 re f
497.246 729.487 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 735.514 Td /F1 9.8 Tf  [(0.45)] TJ ET
0.267 0.267 0.267 rg
538.686 745.369 42.189 0.750 re f
538.686 729.487 0.750 16.631 re f
580.125 729.487 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 735.514 Td /F1 9.8 Tf  [(0.61)] TJ ET
0.267 0.267 0.267 rg
26.625 729.487 72.770 0.750 re f
26.625 713.606 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 719.633 Td /F1 9.8 Tf  [(Rater)] TJ ET
0.267 0.267 0.267 rg
98.645 729.487 72.770 0.750 re f
98.645 713.606 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 719.633 Td /F1 9.8 Tf  [(Langb db 06)] TJ ET
0.267 0.267 0.267 rg
170.665 729.487 35.775 0.750 re f
170.665 713.606 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 719.633 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 729.487 87.399 0.750 re f
205.690 713.606 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 719.633 Td /F1 9.8 Tf  [(0.50)] TJ ET
0.267 0.267 0.267 rg
292.340 729.487 39.425 0.750 re f
292.340 713.606 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 719.633 Td /F1 9.8 Tf  [(0.43)] TJ ET
0.267 0.267 0.267 rg
331.014 729.487 39.425 0.750 re f
331.014 713.606 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 719.633 Td /F1 9.8 Tf  [(0.57)] TJ ET
0.267 0.267 0.267 rg
369.689 729.487 39.479 0.750 re f
369.689 713.606 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 719.633 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 729.487 89.579 0.750 re f
408.418 713.606 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 719.633 Td /F1 9.8 Tf  [(0.52)] TJ ET
0.267 0.267 0.267 rg
497.246 729.487 42.189 0.750 re f
497.246 713.606 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 719.633 Td /F1 9.8 Tf  [(0.43)] TJ ET
0.267 0.267 0.267 rg
538.686 729.487 42.189 0.750 re f
538.686 713.606 0.750 16.631 re f
580.125 713.606 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 719.633 Td /F1 9.8 Tf  [(0.60)] TJ ET
0.267 0.267 0.267 rg
26.625 713.606 72.770 0.750 re f
26.625 697.725 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 703.751 Td /F1 9.8 Tf  [(Rater)] TJ ET
0.267 0.267 0.267 rg
98.645 713.606 72.770 0.750 re f
98.645 697.725 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 703.751 Td /F1 9.8 Tf  [(R. extended)] TJ ET
0.267 0.267 0.267 rg
170.665 713.606 35.775 0.750 re f
170.665 697.725 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 703.751 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 713.606 87.399 0.750 re f
205.690 697.725 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 703.751 Td /F1 9.8 Tf  [(0.49)] TJ ET
0.267 0.267 0.267 rg
292.340 713.606 39.425 0.750 re f
292.340 697.725 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 703.751 Td /F1 9.8 Tf  [(0.42)] TJ ET
0.267 0.267 0.267 rg
331.014 713.606 39.425 0.750 re f
331.014 697.725 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 703.751 Td /F1 9.8 Tf  [(0.56)] TJ ET
0.267 0.267 0.267 rg
369.689 713.606 39.479 0.750 re f
369.689 697.725 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 703.751 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 713.606 89.579 0.750 re f
408.418 697.725 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 703.751 Td /F1 9.8 Tf  [(0.52)] TJ ET
0.267 0.267 0.267 rg
497.246 713.606 42.189 0.750 re f
497.246 697.725 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 703.751 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
538.686 713.606 42.189 0.750 re f
538.686 697.725 0.750 16.631 re f
580.125 697.725 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 703.751 Td /F1 9.8 Tf  [(0.61)] TJ ET
0.267 0.267 0.267 rg
26.625 697.725 72.770 0.750 re f
26.625 681.844 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 687.870 Td /F1 9.8 Tf  [(Rater)] TJ ET
0.267 0.267 0.267 rg
98.645 697.725 72.770 0.750 re f
98.645 681.844 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 687.870 Td /F1 9.8 Tf  [(R. analog)] TJ ET
0.267 0.267 0.267 rg
170.665 697.725 35.775 0.750 re f
170.665 681.844 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 687.870 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 697.725 87.399 0.750 re f
205.690 681.844 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 687.870 Td /F1 9.8 Tf  [(0.52)] TJ ET
0.267 0.267 0.267 rg
292.340 697.725 39.425 0.750 re f
292.340 681.844 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 687.870 Td /F1 9.8 Tf  [(0.45)] TJ ET
0.267 0.267 0.267 rg
331.014 697.725 39.425 0.750 re f
331.014 681.844 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 687.870 Td /F1 9.8 Tf  [(0.59)] TJ ET
0.267 0.267 0.267 rg
369.689 697.725 39.479 0.750 re f
369.689 681.844 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 687.870 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 697.725 89.579 0.750 re f
408.418 681.844 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 687.870 Td /F1 9.8 Tf  [(0.54)] TJ ET
0.267 0.267 0.267 rg
497.246 697.725 42.189 0.750 re f
497.246 681.844 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 687.870 Td /F1 9.8 Tf  [(0.45)] TJ ET
0.267 0.267 0.267 rg
538.686 697.725 42.189 0.750 re f
538.686 681.844 0.750 16.631 re f
580.125 681.844 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 687.870 Td /F1 9.8 Tf  [(0.62)] TJ ET
0.267 0.267 0.267 rg
26.625 681.844 72.770 0.750 re f
26.625 665.962 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 671.989 Td /F1 9.8 Tf  [(Rater)] TJ ET
0.267 0.267 0.267 rg
98.645 681.844 72.770 0.750 re f
98.645 665.962 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 671.989 Td /F1 9.8 Tf  [(Motor)] TJ ET
0.267 0.267 0.267 rg
170.665 681.844 35.775 0.750 re f
170.665 665.962 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 671.989 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 681.844 87.399 0.750 re f
205.690 665.962 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 671.989 Td /F1 9.8 Tf  [(0.58)] TJ ET
0.267 0.267 0.267 rg
292.340 681.844 39.425 0.750 re f
292.340 665.962 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 671.989 Td /F1 9.8 Tf  [(0.51)] TJ ET
0.267 0.267 0.267 rg
331.014 681.844 39.425 0.750 re f
331.014 665.962 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 671.989 Td /F1 9.8 Tf  [(0.65)] TJ ET
0.267 0.267 0.267 rg
369.689 681.844 39.479 0.750 re f
369.689 665.962 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 671.989 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 681.844 89.579 0.750 re f
408.418 665.962 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 671.989 Td /F1 9.8 Tf  [(0.61)] TJ ET
0.267 0.267 0.267 rg
497.246 681.844 42.189 0.750 re f
497.246 665.962 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 671.989 Td /F1 9.8 Tf  [(0.52)] TJ ET
0.267 0.267 0.267 rg
538.686 681.844 42.189 0.750 re f
538.686 665.962 0.750 16.631 re f
580.125 665.962 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 671.989 Td /F1 9.8 Tf  [(0.69)] TJ ET
0.267 0.267 0.267 rg
26.625 665.962 72.770 0.750 re f
26.625 650.081 72.770 0.750 re f
26.625 650.081 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 656.108 Td /F1 9.8 Tf  [(Rater)] TJ ET
0.267 0.267 0.267 rg
98.645 665.962 72.770 0.750 re f
98.645 650.081 72.770 0.750 re f
98.645 650.081 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 103.895 656.108 Td /F1 9.8 Tf  [(TFC)] TJ ET
0.267 0.267 0.267 rg
170.665 665.962 35.775 0.750 re f
170.665 650.081 35.775 0.750 re f
170.665 650.081 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 175.915 656.108 Td /F1 9.8 Tf  [(206)] TJ ET
0.267 0.267 0.267 rg
205.690 665.962 87.399 0.750 re f
205.690 650.081 87.399 0.750 re f
205.690 650.081 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.940 656.108 Td /F1 9.8 Tf  [(0.52)] TJ ET
0.267 0.267 0.267 rg
292.340 665.962 39.425 0.750 re f
292.340 650.081 39.425 0.750 re f
292.340 650.081 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 297.590 656.108 Td /F1 9.8 Tf  [(0.45)] TJ ET
0.267 0.267 0.267 rg
331.014 665.962 39.425 0.750 re f
331.014 650.081 39.425 0.750 re f
331.014 650.081 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 336.264 656.108 Td /F1 9.8 Tf  [(0.59)] TJ ET
0.267 0.267 0.267 rg
369.689 665.962 39.479 0.750 re f
369.689 650.081 39.479 0.750 re f
369.689 650.081 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 374.939 656.108 Td /F1 9.8 Tf  [(145)] TJ ET
0.267 0.267 0.267 rg
408.418 665.962 89.579 0.750 re f
408.418 650.081 89.579 0.750 re f
408.418 650.081 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.668 656.108 Td /F1 9.8 Tf  [(0.52)] TJ ET
0.267 0.267 0.267 rg
497.246 665.962 42.189 0.750 re f
497.246 650.081 42.189 0.750 re f
497.246 650.081 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 502.496 656.108 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
538.686 665.962 42.189 0.750 re f
538.686 650.081 42.189 0.750 re f
538.686 650.081 0.750 16.631 re f
580.125 650.081 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 543.936 656.108 Td /F1 9.8 Tf  [(0.61)] TJ ET
BT 26.250 602.682 Td /F4 9.8 Tf  [(Table 2.)] TJ ET
BT 62.559 602.682 Td /F1 9.8 Tf  [( Agreement rates \(� 5years\) between different formulae. Agreement rates between pairs of estimates were calculated )] TJ ET
BT 26.250 590.778 Td /F1 9.8 Tf  [(with Clopper-Pearson 95% confidence intervals. If both methods arrived at the same result within a �5 year bracket the )] TJ ET
BT 26.250 578.873 Td /F1 9.8 Tf  [(agreement was defined as �1�. If the results were more than 5 years different the agreement was defined as �0�. For all )] TJ ET
BT 26.250 566.968 Td /F1 9.8 Tf  [(participants, the agreement rate was expressed as % agreement within accepted range. Abbreviations: Langb db 06: calculated )] TJ ET
BT 26.250 555.063 Td /F1 9.8 Tf  [(at an age corresponding to disease burden of 200, age when the predicted probability of signs exceeds 0.6. R. analog: Ranen )] TJ ET
BT 26.250 543.159 Td /F1 9.8 Tf  [(analogous. R. extended: Ranen extended.)] TJ ET
BT 26.250 506.556 Td /F4 12.0 Tf  [(DISCUSSION)] TJ ET
BT 26.250 486.602 Td /F1 9.8 Tf  [(The present study assessed how a data derived age-at-onset compares to the rater�s estimate, the commonly used definition of )] TJ ET
BT 26.250 474.697 Td /F1 9.8 Tf  [(AAO. Using longitudinal data from the REGISTRY large observational study, our results suggest that it can be useful to 1\) add )] TJ ET
BT 26.250 462.792 Td /F1 9.8 Tf  [(in the manifest population motor score regression derived AAO as additional motor onset; 2\) when patients are in mid- to late-)] TJ ET
BT 26.250 450.888 Td /F1 9.8 Tf  [(stage HD add TFC regression derived AAO for the onset of functional impact of HD; 3\) predictions of AAO suggest a later onset )] TJ ET
BT 26.250 438.983 Td /F1 9.8 Tf  [(than the actual emergence of unequivocal motor signs of HD.)] TJ ET
BT 26.250 419.578 Td /F4 9.8 Tf  [(Calculate age-at-onset in manifest HD)] TJ ET
BT 26.250 400.173 Td /F1 9.8 Tf  [(The current gold standard of AAO is a clinician�s estimate integrating data from the patient�s history, collateral history of family )] TJ ET
BT 26.250 388.269 Td /F1 9.8 Tf  [(or carers and the examination of the patient. We compared a data derived AAO with the estimated AAO. We first used a simple )] TJ ET
BT 26.250 376.364 Td /F1 9.8 Tf  [(regression analysis of longitudinal UHDRS motor score data and calculated the patient�s age when the motor score was 5 or )] TJ ET
BT 26.250 364.459 Td /F1 9.8 Tf  [(greater, a cut-off used in TRACK-HD, a large longitudinal multi-centre study. )] TJ ET
0.267 0.267 0.267 rg
BT 357.331 364.459 Td /F1 8.7 Tf  [([10], [11])] TJ ET
0.271 0.267 0.267 rg
BT 391.061 364.459 Td /F1 9.8 Tf  [( The AAO from regressing motor scores )] TJ ET
BT 26.250 352.554 Td /F1 9.8 Tf  [(was 3 years later than the median AAO estimated by REGISTRY investigators. The agreement rates between onset in )] TJ ET
BT 26.250 340.650 Td /F1 9.8 Tf  [(REGISTRY data and the calculated motor onset revealed a difference of about 20 years in the 25%tile. REGISTRY participants )] TJ ET
BT 26.250 328.745 Td /F1 9.8 Tf  [(were enrolled when they already had manifest HD. This means that at the REGISTRY enrolment visit the investigator may have )] TJ ET
BT 26.250 316.840 Td /F1 9.8 Tf  [(had to judge AAO after many years of manifest disease. This AAO estimate would be less accurate than AAO observation. )] TJ ET
BT 26.250 304.935 Td /F1 9.8 Tf  [(However, in REGISTRY an earlier estimated onset than that calculated from longitudinal motor scores may also suggest that )] TJ ET
BT 26.250 293.031 Td /F1 9.8 Tf  [(investigators are not guided by motor signs alone.)] TJ ET
BT 26.250 273.626 Td /F1 9.8 Tf  [(Many studies of genetic modifiers relate their effect to a general onset of HD. It is possible that there are domain specific onset )] TJ ET
BT 26.250 261.721 Td /F1 9.8 Tf  [(modifiers. Such domain specific modifying effects may be overlooked unless domain specific onsets are defined. Our data )] TJ ET
BT 26.250 249.816 Td /F1 9.8 Tf  [(suggest that it is possible to use longitudinal motor score data to extrapolate a motor domain onset even in patients with a non-)] TJ ET
BT 26.250 237.912 Td /F1 9.8 Tf  [(motor onset. This approach has the added advantage that it is based on data collected by certified UHDRS motor scale raters )] TJ ET
BT 26.250 226.007 Td /F1 9.8 Tf  [(directly examining the patient. This removes some of the variability introduced by judging an onset retrospectively.)] TJ ET
BT 26.250 206.602 Td /F1 9.8 Tf  [(The UHDRS TFC reflects a general impact on the ability to work, handle finances, and the activities of daily living. )] TJ ET
0.267 0.267 0.267 rg
BT 518.274 206.602 Td /F1 8.7 Tf  [([12])] TJ ET
0.271 0.267 0.267 rg
BT 532.730 206.602 Td /F1 9.8 Tf  [( The )] TJ ET
BT 26.250 194.697 Td /F1 9.8 Tf  [(calculated TFC onset was about 4 years later than the rater estimate indicating that it may take a number of years before HD )] TJ ET
BT 26.250 182.793 Td /F1 9.8 Tf  [(manifestations have a substantial impact on daily life. The good agreement rate between the rater estimate and the calculated )] TJ ET
BT 26.250 170.888 Td /F1 9.8 Tf  [(�TFC onset minus 4 years� suggests this interval of 4 years is fairly robust and does not depend on the major sign at onset. A )] TJ ET
BT 26.250 158.983 Td /F1 9.8 Tf  [(�TCF onset� may add an important endpoint based on function. While in the prodromal phase new scales may have to be )] TJ ET
BT 26.250 147.078 Td /F1 9.8 Tf  [(devised, in midstage HD patients the calculation of an onset of functional impairment using the TFC may help identify the )] TJ ET
BT 26.250 135.174 Td /F1 9.8 Tf  [(factors that are most relevant to maintain function. )] TJ ET
0.267 0.267 0.267 rg
BT 245.186 135.174 Td /F1 8.7 Tf  [([13])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 115.769 Td /F4 9.8 Tf  [(Predicting age-at-onset in prodromal HD)] TJ ET
BT 26.250 96.364 Td /F1 9.8 Tf  [(Assuming our manifest participants were prodromal we compared AAO estimations in the REGISTRY data using the Langbehn, )] TJ ET
BT 26.250 84.459 Td /F1 9.8 Tf  [(or Ranen, formula with the rater estimates of AAO. While the medians agree well, in a substantial proportion of cases the )] TJ ET
BT 26.250 72.555 Td /F1 9.8 Tf  [(difference was as large as �20 years. Overall, however, the Langbehn formula estimates the AAO later than the raters� )] TJ ET
BT 26.250 60.650 Td /F1 9.8 Tf  [(observed AAO. This suggests that unequivocal motor signs of HD manifest earlier, sometimes many years, than predicted using )] TJ ET
BT 26.250 48.745 Td /F1 9.8 Tf  [(the Langbehn formula.)] TJ ET
Q
q
0.000 0.000 0.000 rg
BT 291.710 19.825 Td /F1 11.0 Tf  [(5)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Huntington Disease)] TJ ET

Q
endstream
endobj
151 0 obj
<< /Type /Annot
/Subtype /Link
/A 152 0 R
/Border [0 0 0]
/H /I
/Rect [ 357.3308 363.6575 391.0614 372.4759 ]
>>
endobj
152 0 obj
<< /Type /Action
>>
endobj
153 0 obj
<< /Type /Annot
/Subtype /Link
/A 154 0 R
/Border [0 0 0]
/H /I
/Rect [ 518.2740 205.8005 532.7300 214.6189 ]
>>
endobj
154 0 obj
<< /Type /Action
>>
endobj
155 0 obj
<< /Type /Annot
/Subtype /Link
/A 156 0 R
/Border [0 0 0]
/H /I
/Rect [ 245.1863 134.3720 259.6423 143.1904 ]
>>
endobj
156 0 obj
<< /Type /Action
>>
endobj
157 0 obj
<< /Type /Annot
/Subtype /Link
/A 158 0 R
/Border [0 0 0]
/H /I
/Rect [ 357.3308 363.6575 391.0614 372.4759 ]
>>
endobj
158 0 obj
<< /Type /Action
>>
endobj
159 0 obj
<< /Type /Annot
/Subtype /Link
/A 160 0 R
/Border [0 0 0]
/H /I
/Rect [ 518.2740 205.8005 532.7300 214.6189 ]
>>
endobj
160 0 obj
<< /Type /Action
>>
endobj
161 0 obj
<< /Type /Annot
/Subtype /Link
/A 162 0 R
/Border [0 0 0]
/H /I
/Rect [ 245.1863 134.3720 259.6423 143.1904 ]
>>
endobj
162 0 obj
<< /Type /Action
>>
endobj
163 0 obj
<< /Type /Annot
/Subtype /Link
/A 164 0 R
/Border [0 0 0]
/H /I
/Rect [ 357.3308 363.6575 391.0614 372.4759 ]
>>
endobj
164 0 obj
<< /Type /Action
>>
endobj
165 0 obj
<< /Type /Annot
/Subtype /Link
/A 166 0 R
/Border [0 0 0]
/H /I
/Rect [ 518.2740 205.8005 532.7300 214.6189 ]
>>
endobj
166 0 obj
<< /Type /Action
>>
endobj
167 0 obj
<< /Type /Annot
/Subtype /Link
/A 168 0 R
/Border [0 0 0]
/H /I
/Rect [ 245.1863 134.3720 259.6423 143.1904 ]
>>
endobj
168 0 obj
<< /Type /Action
>>
endobj
169 0 obj
<< /Type /Page
/Parent 3 0 R
/Annots [ 171 0 R 173 0 R 175 0 R 177 0 R 179 0 R 181 0 R ]
/Contents 170 0 R
>>
endobj
170 0 obj
<<
/Length 27445 >>
stream

0.271 0.267 0.267 rg
q
15.000 16.277 577.500 760.723 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(We next used the data to model predictions of the rater estimate of AAO. Integrating the parent AAO and the individual CAG )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(repeat length resulted in a formula in very good agreement with the Ranen formula. The agreement rates of the Ranen, or )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(Ranen analogous, formula with the rater estimate or the extrapolated AAO revealed a large window of �20 years. Overall, the )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(difference of the population based analyses, i.e. median, is unbiased, but on individual levels high deviances from the rater )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(estimate were found. This suggests that other factors may also influence the AAO on an individual level that average out on a )] TJ ET
BT 26.250 707.952 Td /F1 9.8 Tf  [(group level.)] TJ ET
BT 26.250 688.548 Td /F4 9.8 Tf  [(Conclusions and limitations)] TJ ET
BT 26.250 669.143 Td /F1 9.8 Tf  [(A methodological limitation relates to the assumption of linear progression. Rates of decline of TFC in our study agree )] TJ ET
BT 26.250 657.238 Td /F1 9.8 Tf  [(reasonably well with previous data in documenting the rate of decline is slower in the later stages of the disease than in the )] TJ ET
BT 26.250 645.333 Td /F1 9.8 Tf  [(earlier stages probably reflecting a floor effect. )] TJ ET
0.267 0.267 0.267 rg
BT 228.923 645.333 Td /F1 8.7 Tf  [([12])] TJ ET
0.271 0.267 0.267 rg
BT 243.379 645.333 Td /F1 9.8 Tf  [( Progression of HD may not be linear in all stages. Since the population was )] TJ ET
BT 26.250 633.429 Td /F1 9.8 Tf  [(too small further studies need to investigate rates of progression of HD in large data sets using for example non-linear statistical )] TJ ET
BT 26.250 621.524 Td /F1 9.8 Tf  [(models. We had to exclude a substantial proportion of participants from the data based extrapolations because the slopes were )] TJ ET
BT 26.250 609.619 Td /F1 9.8 Tf  [(in the wrong direction. Such individuals present a challenge for the proposed technique of estimating individual onset by )] TJ ET
BT 26.250 597.714 Td /F1 9.8 Tf  [(extrapolating backwards.)] TJ ET
BT 26.250 578.310 Td /F1 9.8 Tf  [(Our results suggest inaccuracies of the concept of a rater estimated AAO. Observing the onset may result in a more accurate )] TJ ET
BT 26.250 566.405 Td /F1 9.8 Tf  [(AAO than estimating the AAO from a distance of many years even if experienced HD clinicians use all available information )] TJ ET
BT 26.250 554.500 Td /F1 9.8 Tf  [(from patients, relatives, and carers. We do not have an objective measure of AAO, or the truth, so we cannot reliably say which )] TJ ET
BT 26.250 542.595 Td /F1 9.8 Tf  [(of the AAOs we have evaluated is the best. AAO implies it is possible to identify a point in time when HD signs manifest while )] TJ ET
BT 26.250 530.691 Td /F1 9.8 Tf  [(clinically it would be more appropriate to refer to a transition period of sometimes several years from the prodromal to the )] TJ ET
BT 26.250 518.786 Td /F1 9.8 Tf  [(manifest stage of HD. Based on our results we suggest to add in manifest HD cohorts a data derived AAO, especially for the )] TJ ET
BT 26.250 506.881 Td /F1 9.8 Tf  [(motor domain. This may be particularly important when using REGISTRY data where the rater estimate of AAO seems less )] TJ ET
BT 26.250 494.976 Td /F1 9.8 Tf  [(reliable. For predictions of AAO in the prodromal phase of HD, our data suggest that the Langbehn formula works better than )] TJ ET
BT 26.250 483.072 Td /F1 9.8 Tf  [(the formula integrating parental AAO. The challenge for the future is to find objective means to define AAO, both predicted and )] TJ ET
BT 26.250 471.167 Td /F1 9.8 Tf  [(retrospective. REGISTRY and PREDICT-HD, and also TRACK-HD, offer large collections of longitudinal data that can be used )] TJ ET
BT 26.250 459.262 Td /F1 9.8 Tf  [(to meet this challenge. )] TJ ET
0.267 0.267 0.267 rg
BT 126.509 459.262 Td /F1 8.7 Tf  [([10])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 422.660 Td /F4 12.0 Tf  [(Acknowledgements)] TJ ET
BT 26.250 402.705 Td /F4 9.8 Tf  [(Expansion of Collaborator List)] TJ ET
BT 26.250 383.301 Td /F4 9.8 Tf  [(European Huntington�s Disease Registry Contributors)] TJ ET
BT 26.250 363.896 Td /F1 9.8 Tf  [(A-C Bachoud-L�vi,Registry Steering committee AR Bentivoglio, Registry Steering committee I Biunno, R Bonelli, Registry )] TJ ET
BT 26.250 351.991 Td /F1 9.8 Tf  [(Steering committee J-M Burgunder, Registry Steering committee SB Dunnett, Registry Steering committee JJ Ferreira, Registry )] TJ ET
BT 26.250 340.086 Td /F1 9.8 Tf  [(Steering committee OJ Handley, Registry Steering committee A Heiberg, Registry Steering committee T Illmann, Registry )] TJ ET
BT 26.250 328.182 Td /F1 9.8 Tf  [(Steering committee GB Landwehrmeyer, Registry Steering committee J Levey, Registry Steering committee JE Nielsen, )] TJ ET
BT 26.250 316.277 Td /F1 9.8 Tf  [(Registry Steering committee M P�iv�rinta, Registry Steering committee RAC Roos, Registry Steering committee A Rojo )] TJ ET
BT 26.250 304.372 Td /F1 9.8 Tf  [(Sebasti�n, Registry Steering committee SJ Tabrizi, Registry Steering committee W Vandenberghe, Registry Steering committee )] TJ ET
BT 26.250 292.467 Td /F1 9.8 Tf  [(C Verellen-Dumoulin, Registry Steering committee J Zaremba, Registry Steering committee T Uhrova, Registry Steering )] TJ ET
BT 26.250 280.563 Td /F1 9.8 Tf  [(committee J Wahlstr�m, Registry Steering committee T Illmann,Information technology M Wallner, Information technology )] TJ ET
BT 26.250 268.658 Td /F1 9.8 Tf  [(Katrin Barth,Central coordination and Language coordinator Leonor Correia-Guedes, Central coordination and Language )] TJ ET
BT 26.250 256.753 Td /F1 9.8 Tf  [(coordinator Ana Maria Finisterra,Central coordination and Language coordinator Monica Bascu�ana Garde, Central )] TJ ET
BT 26.250 244.848 Td /F1 9.8 Tf  [(coordination and Language coordinator Reineke Bos, Central coordination and Language coordinator Sabrina Burg, Central )] TJ ET
BT 26.250 232.944 Td /F1 9.8 Tf  [(coordination and Language coordinator Daniel Ecker, Central coordination and Language coordinator Olivia J Handley, Central )] TJ ET
BT 26.250 221.039 Td /F1 9.8 Tf  [(coordination and Language coordinator Christine Held, Central coordination and Language coordinator Kerstin Koppers, Central )] TJ ET
BT 26.250 209.134 Td /F1 9.8 Tf  [(coordination and Language coordinator Mathilde Laur�, Central coordination and Language coordinator Asunci�n Mart�nez )] TJ ET
BT 26.250 197.229 Td /F1 9.8 Tf  [(Descals, Central coordination and Language coordinator Tim McLean, Central coordination and Language coordinator Tiago )] TJ ET
BT 26.250 185.325 Td /F1 9.8 Tf  [(Mestre,Central coordination and Language coordinator Sara Minster,Central coordination and Language coordinator Daniela )] TJ ET
BT 26.250 173.420 Td /F1 9.8 Tf  [(Monza, Central coordination and Language coordinator Jenny Townhill \(formerly Naji\), Central coordination and Language )] TJ ET
BT 26.250 161.515 Td /F1 9.8 Tf  [(coordinator Michael Orth, Central coordination and Language coordinator Helene Padieu, Central coordination and Language )] TJ ET
BT 26.250 149.610 Td /F1 9.8 Tf  [(coordinator Laurent Paterski, Central coordination and Language coordinator Nadia Peppa, Central coordination and Language )] TJ ET
BT 26.250 137.706 Td /F1 9.8 Tf  [(coordinator Susana Pro Koivisto, Central coordination and Language coordinator Amandine Rialland, Central coordination and )] TJ ET
BT 26.250 125.801 Td /F1 9.8 Tf  [(Language coordinator Niini R�ren \(formerly Heinonen\), Central coordination and Language coordinator Pavla �a�inkov�, )] TJ ET
BT 26.250 113.896 Td /F1 9.8 Tf  [(Central coordination and Language coordinator Patricia Trigo Cubillo, Central coordination and Language coordinator Christine )] TJ ET
BT 26.250 101.991 Td /F1 9.8 Tf  [(Tritsch, Central coordination and Language coordinator Marlene R van Walsem, Central coordination and Language coordinator )] TJ ET
BT 26.250 90.087 Td /F1 9.8 Tf  [(Marie-Noelle Witjes-An�,Central coordination and Language coordinator Elizaveta Yudina \(formerly Tarasova\),Central )] TJ ET
BT 26.250 78.182 Td /F1 9.8 Tf  [(coordination and Language coordinator Daniel Zielonka, Central coordination and Language coordinator Eugeniusz Zielonka, )] TJ ET
BT 26.250 66.277 Td /F1 9.8 Tf  [(Central coordination and Language coordinator Paola Zinzi, Central coordination and Language coordinator Raphael M. Bonelli, )] TJ ET
BT 26.250 54.372 Td /F1 9.8 Tf  [(Graz \(LKH Graz, Abteilung f�r Psychiatrie\), Austria Brigitte Herranhof, Graz \(LKH Graz, Abteilung f�r Psychiatrie\), Austria Anna )] TJ ET
BT 26.250 42.468 Td /F1 9.8 Tf  [(Holl \(formerly H�dl\), Graz \(LKH Graz, Abteilung f�r Psychiatrie\), Austria Markus Magnet, Graz \(LKH Graz, Abteilung f�r )] TJ ET
BT 26.250 30.563 Td /F1 9.8 Tf  [(Psychiatrie\), Austria Daniela Otti, Graz \(LKH Graz, Abteilung f�r Psychiatrie\), Austria Annamaria Painold, Graz \(LKH Graz, )] TJ ET
Q
q
15.000 16.277 577.500 760.723 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(We next used the data to model predictions of the rater estimate of AAO. Integrating the parent AAO and the individual CAG )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(repeat length resulted in a formula in very good agreement with the Ranen formula. The agreement rates of the Ranen, or )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(Ranen analogous, formula with the rater estimate or the extrapolated AAO revealed a large window of �20 years. Overall, the )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(difference of the population based analyses, i.e. median, is unbiased, but on individual levels high deviances from the rater )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(estimate were found. This suggests that other factors may also influence the AAO on an individual level that average out on a )] TJ ET
BT 26.250 707.952 Td /F1 9.8 Tf  [(group level.)] TJ ET
BT 26.250 688.548 Td /F4 9.8 Tf  [(Conclusions and limitations)] TJ ET
BT 26.250 669.143 Td /F1 9.8 Tf  [(A methodological limitation relates to the assumption of linear progression. Rates of decline of TFC in our study agree )] TJ ET
BT 26.250 657.238 Td /F1 9.8 Tf  [(reasonably well with previous data in documenting the rate of decline is slower in the later stages of the disease than in the )] TJ ET
BT 26.250 645.333 Td /F1 9.8 Tf  [(earlier stages probably reflecting a floor effect. )] TJ ET
0.267 0.267 0.267 rg
BT 228.923 645.333 Td /F1 8.7 Tf  [([12])] TJ ET
0.271 0.267 0.267 rg
BT 243.379 645.333 Td /F1 9.8 Tf  [( Progression of HD may not be linear in all stages. Since the population was )] TJ ET
BT 26.250 633.429 Td /F1 9.8 Tf  [(too small further studies need to investigate rates of progression of HD in large data sets using for example non-linear statistical )] TJ ET
BT 26.250 621.524 Td /F1 9.8 Tf  [(models. We had to exclude a substantial proportion of participants from the data based extrapolations because the slopes were )] TJ ET
BT 26.250 609.619 Td /F1 9.8 Tf  [(in the wrong direction. Such individuals present a challenge for the proposed technique of estimating individual onset by )] TJ ET
BT 26.250 597.714 Td /F1 9.8 Tf  [(extrapolating backwards.)] TJ ET
BT 26.250 578.310 Td /F1 9.8 Tf  [(Our results suggest inaccuracies of the concept of a rater estimated AAO. Observing the onset may result in a more accurate )] TJ ET
BT 26.250 566.405 Td /F1 9.8 Tf  [(AAO than estimating the AAO from a distance of many years even if experienced HD clinicians use all available information )] TJ ET
BT 26.250 554.500 Td /F1 9.8 Tf  [(from patients, relatives, and carers. We do not have an objective measure of AAO, or the truth, so we cannot reliably say which )] TJ ET
BT 26.250 542.595 Td /F1 9.8 Tf  [(of the AAOs we have evaluated is the best. AAO implies it is possible to identify a point in time when HD signs manifest while )] TJ ET
BT 26.250 530.691 Td /F1 9.8 Tf  [(clinically it would be more appropriate to refer to a transition period of sometimes several years from the prodromal to the )] TJ ET
BT 26.250 518.786 Td /F1 9.8 Tf  [(manifest stage of HD. Based on our results we suggest to add in manifest HD cohorts a data derived AAO, especially for the )] TJ ET
BT 26.250 506.881 Td /F1 9.8 Tf  [(motor domain. This may be particularly important when using REGISTRY data where the rater estimate of AAO seems less )] TJ ET
BT 26.250 494.976 Td /F1 9.8 Tf  [(reliable. For predictions of AAO in the prodromal phase of HD, our data suggest that the Langbehn formula works better than )] TJ ET
BT 26.250 483.072 Td /F1 9.8 Tf  [(the formula integrating parental AAO. The challenge for the future is to find objective means to define AAO, both predicted and )] TJ ET
BT 26.250 471.167 Td /F1 9.8 Tf  [(retrospective. REGISTRY and PREDICT-HD, and also TRACK-HD, offer large collections of longitudinal data that can be used )] TJ ET
BT 26.250 459.262 Td /F1 9.8 Tf  [(to meet this challenge. )] TJ ET
0.267 0.267 0.267 rg
BT 126.509 459.262 Td /F1 8.7 Tf  [([10])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 422.660 Td /F4 12.0 Tf  [(Acknowledgements)] TJ ET
BT 26.250 402.705 Td /F4 9.8 Tf  [(Expansion of Collaborator List)] TJ ET
BT 26.250 383.301 Td /F4 9.8 Tf  [(European Huntington�s Disease Registry Contributors)] TJ ET
BT 26.250 363.896 Td /F1 9.8 Tf  [(A-C Bachoud-L�vi,Registry Steering committee AR Bentivoglio, Registry Steering committee I Biunno, R Bonelli, Registry )] TJ ET
BT 26.250 351.991 Td /F1 9.8 Tf  [(Steering committee J-M Burgunder, Registry Steering committee SB Dunnett, Registry Steering committee JJ Ferreira, Registry )] TJ ET
BT 26.250 340.086 Td /F1 9.8 Tf  [(Steering committee OJ Handley, Registry Steering committee A Heiberg, Registry Steering committee T Illmann, Registry )] TJ ET
BT 26.250 328.182 Td /F1 9.8 Tf  [(Steering committee GB Landwehrmeyer, Registry Steering committee J Levey, Registry Steering committee JE Nielsen, )] TJ ET
BT 26.250 316.277 Td /F1 9.8 Tf  [(Registry Steering committee M P�iv�rinta, Registry Steering committee RAC Roos, Registry Steering committee A Rojo )] TJ ET
BT 26.250 304.372 Td /F1 9.8 Tf  [(Sebasti�n, Registry Steering committee SJ Tabrizi, Registry Steering committee W Vandenberghe, Registry Steering committee )] TJ ET
BT 26.250 292.467 Td /F1 9.8 Tf  [(C Verellen-Dumoulin, Registry Steering committee J Zaremba, Registry Steering committee T Uhrova, Registry Steering )] TJ ET
BT 26.250 280.563 Td /F1 9.8 Tf  [(committee J Wahlstr�m, Registry Steering committee T Illmann,Information technology M Wallner, Information technology )] TJ ET
BT 26.250 268.658 Td /F1 9.8 Tf  [(Katrin Barth,Central coordination and Language coordinator Leonor Correia-Guedes, Central coordination and Language )] TJ ET
BT 26.250 256.753 Td /F1 9.8 Tf  [(coordinator Ana Maria Finisterra,Central coordination and Language coordinator Monica Bascu�ana Garde, Central )] TJ ET
BT 26.250 244.848 Td /F1 9.8 Tf  [(coordination and Language coordinator Reineke Bos, Central coordination and Language coordinator Sabrina Burg, Central )] TJ ET
BT 26.250 232.944 Td /F1 9.8 Tf  [(coordination and Language coordinator Daniel Ecker, Central coordination and Language coordinator Olivia J Handley, Central )] TJ ET
BT 26.250 221.039 Td /F1 9.8 Tf  [(coordination and Language coordinator Christine Held, Central coordination and Language coordinator Kerstin Koppers, Central )] TJ ET
BT 26.250 209.134 Td /F1 9.8 Tf  [(coordination and Language coordinator Mathilde Laur�, Central coordination and Language coordinator Asunci�n Mart�nez )] TJ ET
BT 26.250 197.229 Td /F1 9.8 Tf  [(Descals, Central coordination and Language coordinator Tim McLean, Central coordination and Language coordinator Tiago )] TJ ET
BT 26.250 185.325 Td /F1 9.8 Tf  [(Mestre,Central coordination and Language coordinator Sara Minster,Central coordination and Language coordinator Daniela )] TJ ET
BT 26.250 173.420 Td /F1 9.8 Tf  [(Monza, Central coordination and Language coordinator Jenny Townhill \(formerly Naji\), Central coordination and Language )] TJ ET
BT 26.250 161.515 Td /F1 9.8 Tf  [(coordinator Michael Orth, Central coordination and Language coordinator Helene Padieu, Central coordination and Language )] TJ ET
BT 26.250 149.610 Td /F1 9.8 Tf  [(coordinator Laurent Paterski, Central coordination and Language coordinator Nadia Peppa, Central coordination and Language )] TJ ET
BT 26.250 137.706 Td /F1 9.8 Tf  [(coordinator Susana Pro Koivisto, Central coordination and Language coordinator Amandine Rialland, Central coordination and )] TJ ET
BT 26.250 125.801 Td /F1 9.8 Tf  [(Language coordinator Niini R�ren \(formerly Heinonen\), Central coordination and Language coordinator Pavla �a�inkov�, )] TJ ET
BT 26.250 113.896 Td /F1 9.8 Tf  [(Central coordination and Language coordinator Patricia Trigo Cubillo, Central coordination and Language coordinator Christine )] TJ ET
BT 26.250 101.991 Td /F1 9.8 Tf  [(Tritsch, Central coordination and Language coordinator Marlene R van Walsem, Central coordination and Language coordinator )] TJ ET
BT 26.250 90.087 Td /F1 9.8 Tf  [(Marie-Noelle Witjes-An�,Central coordination and Language coordinator Elizaveta Yudina \(formerly Tarasova\),Central )] TJ ET
BT 26.250 78.182 Td /F1 9.8 Tf  [(coordination and Language coordinator Daniel Zielonka, Central coordination and Language coordinator Eugeniusz Zielonka, )] TJ ET
BT 26.250 66.277 Td /F1 9.8 Tf  [(Central coordination and Language coordinator Paola Zinzi, Central coordination and Language coordinator Raphael M. Bonelli, )] TJ ET
BT 26.250 54.372 Td /F1 9.8 Tf  [(Graz \(LKH Graz, Abteilung f�r Psychiatrie\), Austria Brigitte Herranhof, Graz \(LKH Graz, Abteilung f�r Psychiatrie\), Austria Anna )] TJ ET
BT 26.250 42.468 Td /F1 9.8 Tf  [(Holl \(formerly H�dl\), Graz \(LKH Graz, Abteilung f�r Psychiatrie\), Austria Markus Magnet, Graz \(LKH Graz, Abteilung f�r )] TJ ET
BT 26.250 30.563 Td /F1 9.8 Tf  [(Psychiatrie\), Austria Daniela Otti, Graz \(LKH Graz, Abteilung f�r Psychiatrie\), Austria Annamaria Painold, Graz \(LKH Graz, )] TJ ET
Q
q
15.000 16.277 577.500 760.723 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(We next used the data to model predictions of the rater estimate of AAO. Integrating the parent AAO and the individual CAG )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(repeat length resulted in a formula in very good agreement with the Ranen formula. The agreement rates of the Ranen, or )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(Ranen analogous, formula with the rater estimate or the extrapolated AAO revealed a large window of �20 years. Overall, the )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(difference of the population based analyses, i.e. median, is unbiased, but on individual levels high deviances from the rater )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(estimate were found. This suggests that other factors may also influence the AAO on an individual level that average out on a )] TJ ET
BT 26.250 707.952 Td /F1 9.8 Tf  [(group level.)] TJ ET
BT 26.250 688.548 Td /F4 9.8 Tf  [(Conclusions and limitations)] TJ ET
BT 26.250 669.143 Td /F1 9.8 Tf  [(A methodological limitation relates to the assumption of linear progression. Rates of decline of TFC in our study agree )] TJ ET
BT 26.250 657.238 Td /F1 9.8 Tf  [(reasonably well with previous data in documenting the rate of decline is slower in the later stages of the disease than in the )] TJ ET
BT 26.250 645.333 Td /F1 9.8 Tf  [(earlier stages probably reflecting a floor effect. )] TJ ET
0.267 0.267 0.267 rg
BT 228.923 645.333 Td /F1 8.7 Tf  [([12])] TJ ET
0.271 0.267 0.267 rg
BT 243.379 645.333 Td /F1 9.8 Tf  [( Progression of HD may not be linear in all stages. Since the population was )] TJ ET
BT 26.250 633.429 Td /F1 9.8 Tf  [(too small further studies need to investigate rates of progression of HD in large data sets using for example non-linear statistical )] TJ ET
BT 26.250 621.524 Td /F1 9.8 Tf  [(models. We had to exclude a substantial proportion of participants from the data based extrapolations because the slopes were )] TJ ET
BT 26.250 609.619 Td /F1 9.8 Tf  [(in the wrong direction. Such individuals present a challenge for the proposed technique of estimating individual onset by )] TJ ET
BT 26.250 597.714 Td /F1 9.8 Tf  [(extrapolating backwards.)] TJ ET
BT 26.250 578.310 Td /F1 9.8 Tf  [(Our results suggest inaccuracies of the concept of a rater estimated AAO. Observing the onset may result in a more accurate )] TJ ET
BT 26.250 566.405 Td /F1 9.8 Tf  [(AAO than estimating the AAO from a distance of many years even if experienced HD clinicians use all available information )] TJ ET
BT 26.250 554.500 Td /F1 9.8 Tf  [(from patients, relatives, and carers. We do not have an objective measure of AAO, or the truth, so we cannot reliably say which )] TJ ET
BT 26.250 542.595 Td /F1 9.8 Tf  [(of the AAOs we have evaluated is the best. AAO implies it is possible to identify a point in time when HD signs manifest while )] TJ ET
BT 26.250 530.691 Td /F1 9.8 Tf  [(clinically it would be more appropriate to refer to a transition period of sometimes several years from the prodromal to the )] TJ ET
BT 26.250 518.786 Td /F1 9.8 Tf  [(manifest stage of HD. Based on our results we suggest to add in manifest HD cohorts a data derived AAO, especially for the )] TJ ET
BT 26.250 506.881 Td /F1 9.8 Tf  [(motor domain. This may be particularly important when using REGISTRY data where the rater estimate of AAO seems less )] TJ ET
BT 26.250 494.976 Td /F1 9.8 Tf  [(reliable. For predictions of AAO in the prodromal phase of HD, our data suggest that the Langbehn formula works better than )] TJ ET
BT 26.250 483.072 Td /F1 9.8 Tf  [(the formula integrating parental AAO. The challenge for the future is to find objective means to define AAO, both predicted and )] TJ ET
BT 26.250 471.167 Td /F1 9.8 Tf  [(retrospective. REGISTRY and PREDICT-HD, and also TRACK-HD, offer large collections of longitudinal data that can be used )] TJ ET
BT 26.250 459.262 Td /F1 9.8 Tf  [(to meet this challenge. )] TJ ET
0.267 0.267 0.267 rg
BT 126.509 459.262 Td /F1 8.7 Tf  [([10])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 422.660 Td /F4 12.0 Tf  [(Acknowledgements)] TJ ET
BT 26.250 402.705 Td /F4 9.8 Tf  [(Expansion of Collaborator List)] TJ ET
BT 26.250 383.301 Td /F4 9.8 Tf  [(European Huntington�s Disease Registry Contributors)] TJ ET
BT 26.250 363.896 Td /F1 9.8 Tf  [(A-C Bachoud-L�vi,Registry Steering committee AR Bentivoglio, Registry Steering committee I Biunno, R Bonelli, Registry )] TJ ET
BT 26.250 351.991 Td /F1 9.8 Tf  [(Steering committee J-M Burgunder, Registry Steering committee SB Dunnett, Registry Steering committee JJ Ferreira, Registry )] TJ ET
BT 26.250 340.086 Td /F1 9.8 Tf  [(Steering committee OJ Handley, Registry Steering committee A Heiberg, Registry Steering committee T Illmann, Registry )] TJ ET
BT 26.250 328.182 Td /F1 9.8 Tf  [(Steering committee GB Landwehrmeyer, Registry Steering committee J Levey, Registry Steering committee JE Nielsen, )] TJ ET
BT 26.250 316.277 Td /F1 9.8 Tf  [(Registry Steering committee M P�iv�rinta, Registry Steering committee RAC Roos, Registry Steering committee A Rojo )] TJ ET
BT 26.250 304.372 Td /F1 9.8 Tf  [(Sebasti�n, Registry Steering committee SJ Tabrizi, Registry Steering committee W Vandenberghe, Registry Steering committee )] TJ ET
BT 26.250 292.467 Td /F1 9.8 Tf  [(C Verellen-Dumoulin, Registry Steering committee J Zaremba, Registry Steering committee T Uhrova, Registry Steering )] TJ ET
BT 26.250 280.563 Td /F1 9.8 Tf  [(committee J Wahlstr�m, Registry Steering committee T Illmann,Information technology M Wallner, Information technology )] TJ ET
BT 26.250 268.658 Td /F1 9.8 Tf  [(Katrin Barth,Central coordination and Language coordinator Leonor Correia-Guedes, Central coordination and Language )] TJ ET
BT 26.250 256.753 Td /F1 9.8 Tf  [(coordinator Ana Maria Finisterra,Central coordination and Language coordinator Monica Bascu�ana Garde, Central )] TJ ET
BT 26.250 244.848 Td /F1 9.8 Tf  [(coordination and Language coordinator Reineke Bos, Central coordination and Language coordinator Sabrina Burg, Central )] TJ ET
BT 26.250 232.944 Td /F1 9.8 Tf  [(coordination and Language coordinator Daniel Ecker, Central coordination and Language coordinator Olivia J Handley, Central )] TJ ET
BT 26.250 221.039 Td /F1 9.8 Tf  [(coordination and Language coordinator Christine Held, Central coordination and Language coordinator Kerstin Koppers, Central )] TJ ET
BT 26.250 209.134 Td /F1 9.8 Tf  [(coordination and Language coordinator Mathilde Laur�, Central coordination and Language coordinator Asunci�n Mart�nez )] TJ ET
BT 26.250 197.229 Td /F1 9.8 Tf  [(Descals, Central coordination and Language coordinator Tim McLean, Central coordination and Language coordinator Tiago )] TJ ET
BT 26.250 185.325 Td /F1 9.8 Tf  [(Mestre,Central coordination and Language coordinator Sara Minster,Central coordination and Language coordinator Daniela )] TJ ET
BT 26.250 173.420 Td /F1 9.8 Tf  [(Monza, Central coordination and Language coordinator Jenny Townhill \(formerly Naji\), Central coordination and Language )] TJ ET
BT 26.250 161.515 Td /F1 9.8 Tf  [(coordinator Michael Orth, Central coordination and Language coordinator Helene Padieu, Central coordination and Language )] TJ ET
BT 26.250 149.610 Td /F1 9.8 Tf  [(coordinator Laurent Paterski, Central coordination and Language coordinator Nadia Peppa, Central coordination and Language )] TJ ET
BT 26.250 137.706 Td /F1 9.8 Tf  [(coordinator Susana Pro Koivisto, Central coordination and Language coordinator Amandine Rialland, Central coordination and )] TJ ET
BT 26.250 125.801 Td /F1 9.8 Tf  [(Language coordinator Niini R�ren \(formerly Heinonen\), Central coordination and Language coordinator Pavla �a�inkov�, )] TJ ET
BT 26.250 113.896 Td /F1 9.8 Tf  [(Central coordination and Language coordinator Patricia Trigo Cubillo, Central coordination and Language coordinator Christine )] TJ ET
BT 26.250 101.991 Td /F1 9.8 Tf  [(Tritsch, Central coordination and Language coordinator Marlene R van Walsem, Central coordination and Language coordinator )] TJ ET
BT 26.250 90.087 Td /F1 9.8 Tf  [(Marie-Noelle Witjes-An�,Central coordination and Language coordinator Elizaveta Yudina \(formerly Tarasova\),Central )] TJ ET
BT 26.250 78.182 Td /F1 9.8 Tf  [(coordination and Language coordinator Daniel Zielonka, Central coordination and Language coordinator Eugeniusz Zielonka, )] TJ ET
BT 26.250 66.277 Td /F1 9.8 Tf  [(Central coordination and Language coordinator Paola Zinzi, Central coordination and Language coordinator Raphael M. Bonelli, )] TJ ET
BT 26.250 54.372 Td /F1 9.8 Tf  [(Graz \(LKH Graz, Abteilung f�r Psychiatrie\), Austria Brigitte Herranhof, Graz \(LKH Graz, Abteilung f�r Psychiatrie\), Austria Anna )] TJ ET
BT 26.250 42.468 Td /F1 9.8 Tf  [(Holl \(formerly H�dl\), Graz \(LKH Graz, Abteilung f�r Psychiatrie\), Austria Markus Magnet, Graz \(LKH Graz, Abteilung f�r )] TJ ET
BT 26.250 30.563 Td /F1 9.8 Tf  [(Psychiatrie\), Austria Daniela Otti, Graz \(LKH Graz, Abteilung f�r Psychiatrie\), Austria Annamaria Painold, Graz \(LKH Graz, )] TJ ET
Q
q
0.000 0.000 0.000 rg
BT 291.710 19.825 Td /F1 11.0 Tf  [(6)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Huntington Disease)] TJ ET

Q
endstream
endobj
171 0 obj
<< /Type /Annot
/Subtype /Link
/A 172 0 R
/Border [0 0 0]
/H /I
/Rect [ 228.9232 644.5318 243.3793 653.3501 ]
>>
endobj
172 0 obj
<< /Type /Action
>>
endobj
173 0 obj
<< /Type /Annot
/Subtype /Link
/A 174 0 R
/Border [0 0 0]
/H /I
/Rect [ 126.5092 458.4605 140.9653 467.2789 ]
>>
endobj
174 0 obj
<< /Type /Action
>>
endobj
175 0 obj
<< /Type /Annot
/Subtype /Link
/A 176 0 R
/Border [0 0 0]
/H /I
/Rect [ 228.9232 644.5318 243.3793 653.3501 ]
>>
endobj
176 0 obj
<< /Type /Action
>>
endobj
177 0 obj
<< /Type /Annot
/Subtype /Link
/A 178 0 R
/Border [0 0 0]
/H /I
/Rect [ 126.5092 458.4605 140.9653 467.2789 ]
>>
endobj
178 0 obj
<< /Type /Action
>>
endobj
179 0 obj
<< /Type /Annot
/Subtype /Link
/A 180 0 R
/Border [0 0 0]
/H /I
/Rect [ 228.9232 644.5318 243.3793 653.3501 ]
>>
endobj
180 0 obj
<< /Type /Action
>>
endobj
181 0 obj
<< /Type /Annot
/Subtype /Link
/A 182 0 R
/Border [0 0 0]
/H /I
/Rect [ 126.5092 458.4605 140.9653 467.2789 ]
>>
endobj
182 0 obj
<< /Type /Action
>>
endobj
183 0 obj
<< /Type /Page
/Parent 3 0 R
/Contents 184 0 R
>>
endobj
184 0 obj
<<
/Length 31648 >>
stream

0.271 0.267 0.267 rg
q
15.000 15.096 577.500 761.904 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(Abteilung f�r Psychiatrie\), Austria Karin Reisinger, Graz \(LKH Graz, Abteilung f�r Psychiatrie\), Austria Monika Scheibl, Graz )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(\(LKH Graz, Abteilung f�r Psychiatrie\), Austria Helmut Sch�ggl, Graz \(LKH Graz, Abteilung f�r Psychiatrie\), Austria Pascale )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(Riba�, Charleroi, Institut de Pathologie et de G�n�tique \(IPG\), Belgium Christine Verellen-Dumoulin, Charleroi, Institut de )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(Pathologie et de G�n�tique \(IPG\), Belgium Andrea Boogaerts, Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium Wim )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(Vandenberghe, Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium Dimphna van Reijen, Universitair Ziekenhuis )] TJ ET
BT 26.250 707.952 Td /F1 9.8 Tf  [(Gasthuisberg, Leuven, Belgium Ji?� Klemp�?; Extrapyramidov� centrum, Neurologick� klinika, 1. LF UK a VFN, Prague, Czech )] TJ ET
BT 26.250 696.048 Td /F1 9.8 Tf  [(Republic Jan Roth, Extrapyramidov� centrum, Neurologick� klinika, 1. LF UK a VFN, Prague, Czech Republic J�rgen E. )] TJ ET
BT 26.250 684.143 Td /F1 9.8 Tf  [(Nielsen, Hukommelsesklinikken, Rigshospitalet; Panum Instituttet, Copenhage, Denmark Lena E. Hjermind, )] TJ ET
BT 26.250 672.238 Td /F1 9.8 Tf  [(Hukommelsesklinikken, Rigshospitalet; Panum Instituttet, Copenhage, Denmark Oda Jakobsen, Hukommelsesklinikken, )] TJ ET
BT 26.250 660.333 Td /F1 9.8 Tf  [(Rigshospitalet; Panum Instituttet, Copenhage, Denmark Jette Stokholm, Hukommelsesklinikken, Rigshospitalet; Panum )] TJ ET
BT 26.250 648.429 Td /F1 9.8 Tf  [(Instituttet, Copenhage, Denmark Lis Hasholt, Hukommelsesklinikken, Rigshospitalet; Panum Instituttet, Copenhage, Denmark )] TJ ET
BT 26.250 636.524 Td /F1 9.8 Tf  [(Anne N�rrem�lle, Hukommelsesklinikken, Rigshospitalet; Panum Instituttet, Copenhage, Denmark Sven Asger S�rensen, )] TJ ET
BT 26.250 624.619 Td /F1 9.8 Tf  [(Hukommelsesklinikken, Rigshospitalet; Panum Instituttet, Copenhage, Denmark Heli Hiivola, Rehabilitation Centre Suvituuli, )] TJ ET
BT 26.250 612.714 Td /F1 9.8 Tf  [(Turku-Suvituuli, Finland Kirsti Martikainen, Rehabilitation Centre Suvituuli, Turku-Suvituuli, Finland Katri Tuuha, Rehabilitation )] TJ ET
BT 26.250 600.810 Td /F1 9.8 Tf  [(Centre Suvituuli, Turku-Suvituuli, Finland Maire Santala, Terveystalo Healthcare Service Centre, Tamper, Finland Christoph )] TJ ET
BT 26.250 588.905 Td /F1 9.8 Tf  [(Michael Kosinski, Universit�tsklinikum Aachen, Neurologische Klinik, Aachen, Germany Eva Milkereit, Universit�tsklinikum )] TJ ET
BT 26.250 577.000 Td /F1 9.8 Tf  [(Aachen, Neurologische Klinik, Aachen, Germany Daniela Probst, Universit�tsklinikum Aachen, Neurologische Klinik, Aachen, )] TJ ET
BT 26.250 565.095 Td /F1 9.8 Tf  [(Germany Christian Sass, Universit�tsklinikum Aachen, Neurologische Klinik, Aachen, Germany JohannesSchiefer, )] TJ ET
BT 26.250 553.191 Td /F1 9.8 Tf  [(Universit�tsklinikum Aachen, Neurologische Klinik, Aachen, Germany Christiane Schlangen, Universit�tsklinikum Aachen, )] TJ ET
BT 26.250 541.286 Td /F1 9.8 Tf  [(Neurologische Klinik, Aachen, Germany Cornelius J. Werner, Universit�tsklinikum Aachen, Neurologische Klinik, Aachen, )] TJ ET
BT 26.250 529.381 Td /F1 9.8 Tf  [(Germany Harald Gelderblom, Klinik und Poliklinik f�r Neurologie � Charit� � Universit�tsmedizin Berlin, Berlin, Germany Josef )] TJ ET
BT 26.250 517.476 Td /F1 9.8 Tf  [(Priller, Klinik und Poliklinik f�r Neurologie � Charit� � Universit�tsmedizin Berlin, Berlin, Germany Harald Pr��, Klinik und )] TJ ET
BT 26.250 505.572 Td /F1 9.8 Tf  [(Poliklinik f�r Neurologie � Charit� � Universit�tsmedizin Berlin, Berlin, Germany Eike Jakob Spruth, Klinik und Poliklinik f�r )] TJ ET
BT 26.250 493.667 Td /F1 9.8 Tf  [(Neurologie � Charit� � Universit�tsmedizin Berlin, Berlin, Germany J�rgen Andrich)] TJ ET
BT 382.778 493.667 Td /F4 9.8 Tf  [(, )] TJ ET
BT 388.199 493.667 Td /F1 9.8 Tf  [(Huntington-Zentrum \(NRW\) Bochum im St. )] TJ ET
BT 26.250 481.762 Td /F1 9.8 Tf  [(Josef-Hospital, Bochum, Germany Gisa Ellrichmann, Huntington-Zentrum \(NRW\) Bochum im St. Josef-Hospital, Bochum, )] TJ ET
BT 26.250 469.857 Td /F1 9.8 Tf  [(Germany Rainer Hoffmann, Huntington-Zentrum \(NRW\) Bochum im St. Josef-Hospital, Bochum, Germany Christian Prehn, )] TJ ET
BT 26.250 457.953 Td /F1 9.8 Tf  [(Huntington-Zentrum \(NRW\) Bochum im St. Josef-Hospital, Bochum, Germany Carsten Saft, Huntington-Zentrum \(NRW\) )] TJ ET
BT 26.250 446.048 Td /F1 9.8 Tf  [(Bochum im St. Josef-Hospital, Bochum, Germany Stephan Salmen, Huntington-Zentrum \(NRW\) Bochum im St. Josef-Hospital, )] TJ ET
BT 26.250 434.143 Td /F1 9.8 Tf  [(Bochum, Germany Christiane Stamm, Huntington-Zentrum \(NRW\) Bochum im St. Josef-Hospital, Bochum, Germany Tanja )] TJ ET
BT 26.250 422.238 Td /F1 9.8 Tf  [(Steiner, Huntington-Zentrum \(NRW\) Bochum im St. Josef-Hospital, Bochum, Germany Katrin Stra�burge, Huntington-Zentrum )] TJ ET
BT 26.250 410.334 Td /F1 9.8 Tf  [(\(NRW\) Bochum im St. Josef-Hospital, Bochum, Germany Herwig Lange, Reha Zentrum in Dinslaken im Gesundheitszentrums )] TJ ET
BT 26.250 398.429 Td /F1 9.8 Tf  [(Lang, Dinslake, German Matthias L�hle, Universit�tsklinikum Carl Gustav Carus an der Technischen Universit�t Dresden, Klinik )] TJ ET
BT 26.250 386.524 Td /F1 9.8 Tf  [(und Poliklinik f�r Neurologie, Dresden, Germany Simone Schmidt, Universit�tsklinikum Carl Gustav Carus an der Technischen )] TJ ET
BT 26.250 374.619 Td /F1 9.8 Tf  [(Universit�t Dresden, Klinik und Poliklinik f�r Neurologie, Dresden, Germany Alexander Storch, Universit�tsklinikum Carl Gustav )] TJ ET
BT 26.250 362.715 Td /F1 9.8 Tf  [(Carus an der Technischen Universit�t Dresden, Klinik und Poliklinik f�r Neurologie, Dresden, Germany Annett Wolz, )] TJ ET
BT 26.250 350.810 Td /F1 9.8 Tf  [(Universit�tsklinikum Carl Gustav Carus an der Technischen Universit�t Dresden, Klinik und Poliklinik f�r Neurologie, Dresden, )] TJ ET
BT 26.250 338.905 Td /F1 9.8 Tf  [(Germany Martin Wolz, Universit�tsklinikum Carl Gustav Carus an der Technischen Universit�t Dresden, Klinik und Poliklinik f�r )] TJ ET
BT 26.250 327.000 Td /F1 9.8 Tf  [(Neurologie, Dresden, Germany Johann Lambeck, Universit�tsklinik Freiburg, Neurologie, Freiburg, Germany Birgit Zucker, )] TJ ET
BT 26.250 315.096 Td /F1 9.8 Tf  [(Universit�tsklinik Freiburg, Neurologie, Freiburg, Germany Ute Hidding, Universit�tsklinikum Hamburg-Eppendorf, Klinik und )] TJ ET
BT 26.250 303.191 Td /F1 9.8 Tf  [(Poliklinik f�r Neurologie, Hamburg, Germany Jan Lewerenz, Universit�tsklinikum Hamburg-Eppendorf, Klinik und Poliklinik f�r )] TJ ET
BT 26.250 291.286 Td /F1 9.8 Tf  [(Neurologie, Hamburg, Germany Alexander M�nchau, Universit�tsklinikum Hamburg-Eppendorf, Klinik und Poliklinik f�r )] TJ ET
BT 26.250 279.381 Td /F1 9.8 Tf  [(Neurologie, Hamburg, Germany Michael Orth, Universit�tsklinikum Hamburg-Eppendorf, Klinik und Poliklinik f�r Neurologie, )] TJ ET
BT 26.250 267.477 Td /F1 9.8 Tf  [(Hamburg, Germany Jenny Schmalfeld, Universit�tsklinikum Hamburg-Eppendorf, Klinik und Poliklinik f�r Neurologie, Hamburg, )] TJ ET
BT 26.250 255.572 Td /F1 9.8 Tf  [(Germany Lars Stubbe, Universit�tsklinikum Hamburg-Eppendorf, Klinik und Poliklinik f�r Neurologie, Hamburg, Germany )] TJ ET
BT 26.250 243.667 Td /F1 9.8 Tf  [(Simone Zittel, Universit�tsklinikum Hamburg-Eppendorf, Klinik und Poliklinik f�r Neurologie, Hamburg, Germany Walburgis )] TJ ET
BT 26.250 231.762 Td /F1 9.8 Tf  [(Heinicke, Psychatrium Heiligenhafen, Heiligenhafe, Germany Bernhard Longinus, Klinik f�r Psychiatrie und Psychotherapie )] TJ ET
BT 26.250 219.858 Td /F1 9.8 Tf  [(Marburg-S�d, Marburg KP, Germany Jens Carsten M�ller, Universit�t Marburg, Neurologie, Marburg Uni, Germany Ida )] TJ ET
BT 26.250 207.953 Td /F1 9.8 Tf  [(Rissling, Universit�t Marburg, Neurologie, Marburg Uni, Germany Alexander Peinemann, Huntington-Ambulanz im Neuro-)] TJ ET
BT 26.250 196.048 Td /F1 9.8 Tf  [(Kopfzentrum � Klinikum rechts der Isar der Neurologischen Klinik und Poliklinik der Technischen Universit�t M�nchen, )] TJ ET
BT 26.250 184.143 Td /F1 9.8 Tf  [(M�nchen, Germany Michael St�dtler, Huntington-Ambulanz im Neuro-Kopfzentrum � Klinikum rechts der Isar der )] TJ ET
BT 26.250 172.239 Td /F1 9.8 Tf  [(Neurologischen Klinik und Poliklinik der Technischen Universit�t M�nchen, M�nchen, Germany Adolf Weindl, Huntington-)] TJ ET
BT 26.250 160.334 Td /F1 9.8 Tf  [(Ambulanz im Neuro-Kopfzentrum � Klinikum rechts der Isar der Neurologischen Klinik und Poliklinik der Technischen )] TJ ET
BT 26.250 148.429 Td /F1 9.8 Tf  [(Universit�t M�nchen, M�nchen, Germany Stefan Bohlen, Universit�tsklinikum M�nster, Klinik und Poliklinik f�r Neurologie, )] TJ ET
BT 26.250 136.524 Td /F1 9.8 Tf  [(M�nste, Germany Eva H�lzner, Universit�tsklinikum M�nster, Klinik und Poliklinik f�r Neurologie, M�nste, Germany Herwig )] TJ ET
BT 26.250 124.620 Td /F1 9.8 Tf  [(Lange, Universit�tsklinikum M�nster, Klinik und Poliklinik f�r Neurologie, M�nste, Germany Ralf Reilmann, Universit�tsklinikum )] TJ ET
BT 26.250 112.715 Td /F1 9.8 Tf  [(M�nster, Klinik und Poliklinik f�r Neurologie, M�nste, German Antonie Beister, Isar-Amper-Klinikum � Klinik Taufkirchen \(Vils\), )] TJ ET
BT 26.250 100.810 Td /F1 9.8 Tf  [(Taufkirchen, Germany Matthias Dose, Isar-Amper-Klinikum � Klinik Taufkirchen \(Vils\), Taufkirchen, Germany Kathrin Hammer, )] TJ ET
BT 26.250 88.905 Td /F1 9.8 Tf  [(Isar-Amper-Klinikum � Klinik Taufkirchen \(Vils\), Taufkirchen, Germany Janina Kieni, Isar-Amper-Klinikum � Klinik Taufkirchen )] TJ ET
BT 26.250 77.001 Td /F1 9.8 Tf  [(\(Vils\), Taufkirchen, Germany Gabriele Leythaeuser, Isar-Amper-Klinikum � Klinik Taufkirchen \(Vils\), Taufkirchen, Germany Ralf )] TJ ET
BT 26.250 65.096 Td /F1 9.8 Tf  [(Marquard, Isar-Amper-Klinikum � Klinik Taufkirchen \(Vils\), Taufkirchen, Germany Tina Raab, Isar-Amper-Klinikum � Klinik )] TJ ET
BT 26.250 53.191 Td /F1 9.8 Tf  [(Taufkirchen \(Vils\), Taufkirchen, Germany Sven Richter, Isar-Amper-Klinikum � Klinik Taufkirchen \(Vils\), Taufkirchen, Germany )] TJ ET
BT 26.250 41.286 Td /F1 9.8 Tf  [(Amina Selimbegovic-Turkovic, Isar-Amper-Klinikum � Klinik Taufkirchen \(Vils\), Taufkirchen, Germany Caroline Schrenk, Isar-)] TJ ET
BT 26.250 29.382 Td /F1 9.8 Tf  [(Amper-Klinikum � Klinik Taufkirchen \(Vils\), Taufkirchen, Germany Michele Schuierer;, Isar-Amper-Klinikum � Klinik Taufkirchen )] TJ ET
Q
q
15.000 15.096 577.500 761.904 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(Abteilung f�r Psychiatrie\), Austria Karin Reisinger, Graz \(LKH Graz, Abteilung f�r Psychiatrie\), Austria Monika Scheibl, Graz )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(\(LKH Graz, Abteilung f�r Psychiatrie\), Austria Helmut Sch�ggl, Graz \(LKH Graz, Abteilung f�r Psychiatrie\), Austria Pascale )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(Riba�, Charleroi, Institut de Pathologie et de G�n�tique \(IPG\), Belgium Christine Verellen-Dumoulin, Charleroi, Institut de )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(Pathologie et de G�n�tique \(IPG\), Belgium Andrea Boogaerts, Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium Wim )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(Vandenberghe, Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium Dimphna van Reijen, Universitair Ziekenhuis )] TJ ET
BT 26.250 707.952 Td /F1 9.8 Tf  [(Gasthuisberg, Leuven, Belgium Ji?� Klemp�?; Extrapyramidov� centrum, Neurologick� klinika, 1. LF UK a VFN, Prague, Czech )] TJ ET
BT 26.250 696.048 Td /F1 9.8 Tf  [(Republic Jan Roth, Extrapyramidov� centrum, Neurologick� klinika, 1. LF UK a VFN, Prague, Czech Republic J�rgen E. )] TJ ET
BT 26.250 684.143 Td /F1 9.8 Tf  [(Nielsen, Hukommelsesklinikken, Rigshospitalet; Panum Instituttet, Copenhage, Denmark Lena E. Hjermind, )] TJ ET
BT 26.250 672.238 Td /F1 9.8 Tf  [(Hukommelsesklinikken, Rigshospitalet; Panum Instituttet, Copenhage, Denmark Oda Jakobsen, Hukommelsesklinikken, )] TJ ET
BT 26.250 660.333 Td /F1 9.8 Tf  [(Rigshospitalet; Panum Instituttet, Copenhage, Denmark Jette Stokholm, Hukommelsesklinikken, Rigshospitalet; Panum )] TJ ET
BT 26.250 648.429 Td /F1 9.8 Tf  [(Instituttet, Copenhage, Denmark Lis Hasholt, Hukommelsesklinikken, Rigshospitalet; Panum Instituttet, Copenhage, Denmark )] TJ ET
BT 26.250 636.524 Td /F1 9.8 Tf  [(Anne N�rrem�lle, Hukommelsesklinikken, Rigshospitalet; Panum Instituttet, Copenhage, Denmark Sven Asger S�rensen, )] TJ ET
BT 26.250 624.619 Td /F1 9.8 Tf  [(Hukommelsesklinikken, Rigshospitalet; Panum Instituttet, Copenhage, Denmark Heli Hiivola, Rehabilitation Centre Suvituuli, )] TJ ET
BT 26.250 612.714 Td /F1 9.8 Tf  [(Turku-Suvituuli, Finland Kirsti Martikainen, Rehabilitation Centre Suvituuli, Turku-Suvituuli, Finland Katri Tuuha, Rehabilitation )] TJ ET
BT 26.250 600.810 Td /F1 9.8 Tf  [(Centre Suvituuli, Turku-Suvituuli, Finland Maire Santala, Terveystalo Healthcare Service Centre, Tamper, Finland Christoph )] TJ ET
BT 26.250 588.905 Td /F1 9.8 Tf  [(Michael Kosinski, Universit�tsklinikum Aachen, Neurologische Klinik, Aachen, Germany Eva Milkereit, Universit�tsklinikum )] TJ ET
BT 26.250 577.000 Td /F1 9.8 Tf  [(Aachen, Neurologische Klinik, Aachen, Germany Daniela Probst, Universit�tsklinikum Aachen, Neurologische Klinik, Aachen, )] TJ ET
BT 26.250 565.095 Td /F1 9.8 Tf  [(Germany Christian Sass, Universit�tsklinikum Aachen, Neurologische Klinik, Aachen, Germany JohannesSchiefer, )] TJ ET
BT 26.250 553.191 Td /F1 9.8 Tf  [(Universit�tsklinikum Aachen, Neurologische Klinik, Aachen, Germany Christiane Schlangen, Universit�tsklinikum Aachen, )] TJ ET
BT 26.250 541.286 Td /F1 9.8 Tf  [(Neurologische Klinik, Aachen, Germany Cornelius J. Werner, Universit�tsklinikum Aachen, Neurologische Klinik, Aachen, )] TJ ET
BT 26.250 529.381 Td /F1 9.8 Tf  [(Germany Harald Gelderblom, Klinik und Poliklinik f�r Neurologie � Charit� � Universit�tsmedizin Berlin, Berlin, Germany Josef )] TJ ET
BT 26.250 517.476 Td /F1 9.8 Tf  [(Priller, Klinik und Poliklinik f�r Neurologie � Charit� � Universit�tsmedizin Berlin, Berlin, Germany Harald Pr��, Klinik und )] TJ ET
BT 26.250 505.572 Td /F1 9.8 Tf  [(Poliklinik f�r Neurologie � Charit� � Universit�tsmedizin Berlin, Berlin, Germany Eike Jakob Spruth, Klinik und Poliklinik f�r )] TJ ET
BT 26.250 493.667 Td /F1 9.8 Tf  [(Neurologie � Charit� � Universit�tsmedizin Berlin, Berlin, Germany J�rgen Andrich)] TJ ET
BT 382.778 493.667 Td /F4 9.8 Tf  [(, )] TJ ET
BT 388.199 493.667 Td /F1 9.8 Tf  [(Huntington-Zentrum \(NRW\) Bochum im St. )] TJ ET
BT 26.250 481.762 Td /F1 9.8 Tf  [(Josef-Hospital, Bochum, Germany Gisa Ellrichmann, Huntington-Zentrum \(NRW\) Bochum im St. Josef-Hospital, Bochum, )] TJ ET
BT 26.250 469.857 Td /F1 9.8 Tf  [(Germany Rainer Hoffmann, Huntington-Zentrum \(NRW\) Bochum im St. Josef-Hospital, Bochum, Germany Christian Prehn, )] TJ ET
BT 26.250 457.953 Td /F1 9.8 Tf  [(Huntington-Zentrum \(NRW\) Bochum im St. Josef-Hospital, Bochum, Germany Carsten Saft, Huntington-Zentrum \(NRW\) )] TJ ET
BT 26.250 446.048 Td /F1 9.8 Tf  [(Bochum im St. Josef-Hospital, Bochum, Germany Stephan Salmen, Huntington-Zentrum \(NRW\) Bochum im St. Josef-Hospital, )] TJ ET
BT 26.250 434.143 Td /F1 9.8 Tf  [(Bochum, Germany Christiane Stamm, Huntington-Zentrum \(NRW\) Bochum im St. Josef-Hospital, Bochum, Germany Tanja )] TJ ET
BT 26.250 422.238 Td /F1 9.8 Tf  [(Steiner, Huntington-Zentrum \(NRW\) Bochum im St. Josef-Hospital, Bochum, Germany Katrin Stra�burge, Huntington-Zentrum )] TJ ET
BT 26.250 410.334 Td /F1 9.8 Tf  [(\(NRW\) Bochum im St. Josef-Hospital, Bochum, Germany Herwig Lange, Reha Zentrum in Dinslaken im Gesundheitszentrums )] TJ ET
BT 26.250 398.429 Td /F1 9.8 Tf  [(Lang, Dinslake, German Matthias L�hle, Universit�tsklinikum Carl Gustav Carus an der Technischen Universit�t Dresden, Klinik )] TJ ET
BT 26.250 386.524 Td /F1 9.8 Tf  [(und Poliklinik f�r Neurologie, Dresden, Germany Simone Schmidt, Universit�tsklinikum Carl Gustav Carus an der Technischen )] TJ ET
BT 26.250 374.619 Td /F1 9.8 Tf  [(Universit�t Dresden, Klinik und Poliklinik f�r Neurologie, Dresden, Germany Alexander Storch, Universit�tsklinikum Carl Gustav )] TJ ET
BT 26.250 362.715 Td /F1 9.8 Tf  [(Carus an der Technischen Universit�t Dresden, Klinik und Poliklinik f�r Neurologie, Dresden, Germany Annett Wolz, )] TJ ET
BT 26.250 350.810 Td /F1 9.8 Tf  [(Universit�tsklinikum Carl Gustav Carus an der Technischen Universit�t Dresden, Klinik und Poliklinik f�r Neurologie, Dresden, )] TJ ET
BT 26.250 338.905 Td /F1 9.8 Tf  [(Germany Martin Wolz, Universit�tsklinikum Carl Gustav Carus an der Technischen Universit�t Dresden, Klinik und Poliklinik f�r )] TJ ET
BT 26.250 327.000 Td /F1 9.8 Tf  [(Neurologie, Dresden, Germany Johann Lambeck, Universit�tsklinik Freiburg, Neurologie, Freiburg, Germany Birgit Zucker, )] TJ ET
BT 26.250 315.096 Td /F1 9.8 Tf  [(Universit�tsklinik Freiburg, Neurologie, Freiburg, Germany Ute Hidding, Universit�tsklinikum Hamburg-Eppendorf, Klinik und )] TJ ET
BT 26.250 303.191 Td /F1 9.8 Tf  [(Poliklinik f�r Neurologie, Hamburg, Germany Jan Lewerenz, Universit�tsklinikum Hamburg-Eppendorf, Klinik und Poliklinik f�r )] TJ ET
BT 26.250 291.286 Td /F1 9.8 Tf  [(Neurologie, Hamburg, Germany Alexander M�nchau, Universit�tsklinikum Hamburg-Eppendorf, Klinik und Poliklinik f�r )] TJ ET
BT 26.250 279.381 Td /F1 9.8 Tf  [(Neurologie, Hamburg, Germany Michael Orth, Universit�tsklinikum Hamburg-Eppendorf, Klinik und Poliklinik f�r Neurologie, )] TJ ET
BT 26.250 267.477 Td /F1 9.8 Tf  [(Hamburg, Germany Jenny Schmalfeld, Universit�tsklinikum Hamburg-Eppendorf, Klinik und Poliklinik f�r Neurologie, Hamburg, )] TJ ET
BT 26.250 255.572 Td /F1 9.8 Tf  [(Germany Lars Stubbe, Universit�tsklinikum Hamburg-Eppendorf, Klinik und Poliklinik f�r Neurologie, Hamburg, Germany )] TJ ET
BT 26.250 243.667 Td /F1 9.8 Tf  [(Simone Zittel, Universit�tsklinikum Hamburg-Eppendorf, Klinik und Poliklinik f�r Neurologie, Hamburg, Germany Walburgis )] TJ ET
BT 26.250 231.762 Td /F1 9.8 Tf  [(Heinicke, Psychatrium Heiligenhafen, Heiligenhafe, Germany Bernhard Longinus, Klinik f�r Psychiatrie und Psychotherapie )] TJ ET
BT 26.250 219.858 Td /F1 9.8 Tf  [(Marburg-S�d, Marburg KP, Germany Jens Carsten M�ller, Universit�t Marburg, Neurologie, Marburg Uni, Germany Ida )] TJ ET
BT 26.250 207.953 Td /F1 9.8 Tf  [(Rissling, Universit�t Marburg, Neurologie, Marburg Uni, Germany Alexander Peinemann, Huntington-Ambulanz im Neuro-)] TJ ET
BT 26.250 196.048 Td /F1 9.8 Tf  [(Kopfzentrum � Klinikum rechts der Isar der Neurologischen Klinik und Poliklinik der Technischen Universit�t M�nchen, )] TJ ET
BT 26.250 184.143 Td /F1 9.8 Tf  [(M�nchen, Germany Michael St�dtler, Huntington-Ambulanz im Neuro-Kopfzentrum � Klinikum rechts der Isar der )] TJ ET
BT 26.250 172.239 Td /F1 9.8 Tf  [(Neurologischen Klinik und Poliklinik der Technischen Universit�t M�nchen, M�nchen, Germany Adolf Weindl, Huntington-)] TJ ET
BT 26.250 160.334 Td /F1 9.8 Tf  [(Ambulanz im Neuro-Kopfzentrum � Klinikum rechts der Isar der Neurologischen Klinik und Poliklinik der Technischen )] TJ ET
BT 26.250 148.429 Td /F1 9.8 Tf  [(Universit�t M�nchen, M�nchen, Germany Stefan Bohlen, Universit�tsklinikum M�nster, Klinik und Poliklinik f�r Neurologie, )] TJ ET
BT 26.250 136.524 Td /F1 9.8 Tf  [(M�nste, Germany Eva H�lzner, Universit�tsklinikum M�nster, Klinik und Poliklinik f�r Neurologie, M�nste, Germany Herwig )] TJ ET
BT 26.250 124.620 Td /F1 9.8 Tf  [(Lange, Universit�tsklinikum M�nster, Klinik und Poliklinik f�r Neurologie, M�nste, Germany Ralf Reilmann, Universit�tsklinikum )] TJ ET
BT 26.250 112.715 Td /F1 9.8 Tf  [(M�nster, Klinik und Poliklinik f�r Neurologie, M�nste, German Antonie Beister, Isar-Amper-Klinikum � Klinik Taufkirchen \(Vils\), )] TJ ET
BT 26.250 100.810 Td /F1 9.8 Tf  [(Taufkirchen, Germany Matthias Dose, Isar-Amper-Klinikum � Klinik Taufkirchen \(Vils\), Taufkirchen, Germany Kathrin Hammer, )] TJ ET
BT 26.250 88.905 Td /F1 9.8 Tf  [(Isar-Amper-Klinikum � Klinik Taufkirchen \(Vils\), Taufkirchen, Germany Janina Kieni, Isar-Amper-Klinikum � Klinik Taufkirchen )] TJ ET
BT 26.250 77.001 Td /F1 9.8 Tf  [(\(Vils\), Taufkirchen, Germany Gabriele Leythaeuser, Isar-Amper-Klinikum � Klinik Taufkirchen \(Vils\), Taufkirchen, Germany Ralf )] TJ ET
BT 26.250 65.096 Td /F1 9.8 Tf  [(Marquard, Isar-Amper-Klinikum � Klinik Taufkirchen \(Vils\), Taufkirchen, Germany Tina Raab, Isar-Amper-Klinikum � Klinik )] TJ ET
BT 26.250 53.191 Td /F1 9.8 Tf  [(Taufkirchen \(Vils\), Taufkirchen, Germany Sven Richter, Isar-Amper-Klinikum � Klinik Taufkirchen \(Vils\), Taufkirchen, Germany )] TJ ET
BT 26.250 41.286 Td /F1 9.8 Tf  [(Amina Selimbegovic-Turkovic, Isar-Amper-Klinikum � Klinik Taufkirchen \(Vils\), Taufkirchen, Germany Caroline Schrenk, Isar-)] TJ ET
BT 26.250 29.382 Td /F1 9.8 Tf  [(Amper-Klinikum � Klinik Taufkirchen \(Vils\), Taufkirchen, Germany Michele Schuierer;, Isar-Amper-Klinikum � Klinik Taufkirchen )] TJ ET
Q
q
15.000 15.096 577.500 761.904 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(Abteilung f�r Psychiatrie\), Austria Karin Reisinger, Graz \(LKH Graz, Abteilung f�r Psychiatrie\), Austria Monika Scheibl, Graz )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(\(LKH Graz, Abteilung f�r Psychiatrie\), Austria Helmut Sch�ggl, Graz \(LKH Graz, Abteilung f�r Psychiatrie\), Austria Pascale )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(Riba�, Charleroi, Institut de Pathologie et de G�n�tique \(IPG\), Belgium Christine Verellen-Dumoulin, Charleroi, Institut de )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(Pathologie et de G�n�tique \(IPG\), Belgium Andrea Boogaerts, Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium Wim )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(Vandenberghe, Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium Dimphna van Reijen, Universitair Ziekenhuis )] TJ ET
BT 26.250 707.952 Td /F1 9.8 Tf  [(Gasthuisberg, Leuven, Belgium Ji?� Klemp�?; Extrapyramidov� centrum, Neurologick� klinika, 1. LF UK a VFN, Prague, Czech )] TJ ET
BT 26.250 696.048 Td /F1 9.8 Tf  [(Republic Jan Roth, Extrapyramidov� centrum, Neurologick� klinika, 1. LF UK a VFN, Prague, Czech Republic J�rgen E. )] TJ ET
BT 26.250 684.143 Td /F1 9.8 Tf  [(Nielsen, Hukommelsesklinikken, Rigshospitalet; Panum Instituttet, Copenhage, Denmark Lena E. Hjermind, )] TJ ET
BT 26.250 672.238 Td /F1 9.8 Tf  [(Hukommelsesklinikken, Rigshospitalet; Panum Instituttet, Copenhage, Denmark Oda Jakobsen, Hukommelsesklinikken, )] TJ ET
BT 26.250 660.333 Td /F1 9.8 Tf  [(Rigshospitalet; Panum Instituttet, Copenhage, Denmark Jette Stokholm, Hukommelsesklinikken, Rigshospitalet; Panum )] TJ ET
BT 26.250 648.429 Td /F1 9.8 Tf  [(Instituttet, Copenhage, Denmark Lis Hasholt, Hukommelsesklinikken, Rigshospitalet; Panum Instituttet, Copenhage, Denmark )] TJ ET
BT 26.250 636.524 Td /F1 9.8 Tf  [(Anne N�rrem�lle, Hukommelsesklinikken, Rigshospitalet; Panum Instituttet, Copenhage, Denmark Sven Asger S�rensen, )] TJ ET
BT 26.250 624.619 Td /F1 9.8 Tf  [(Hukommelsesklinikken, Rigshospitalet; Panum Instituttet, Copenhage, Denmark Heli Hiivola, Rehabilitation Centre Suvituuli, )] TJ ET
BT 26.250 612.714 Td /F1 9.8 Tf  [(Turku-Suvituuli, Finland Kirsti Martikainen, Rehabilitation Centre Suvituuli, Turku-Suvituuli, Finland Katri Tuuha, Rehabilitation )] TJ ET
BT 26.250 600.810 Td /F1 9.8 Tf  [(Centre Suvituuli, Turku-Suvituuli, Finland Maire Santala, Terveystalo Healthcare Service Centre, Tamper, Finland Christoph )] TJ ET
BT 26.250 588.905 Td /F1 9.8 Tf  [(Michael Kosinski, Universit�tsklinikum Aachen, Neurologische Klinik, Aachen, Germany Eva Milkereit, Universit�tsklinikum )] TJ ET
BT 26.250 577.000 Td /F1 9.8 Tf  [(Aachen, Neurologische Klinik, Aachen, Germany Daniela Probst, Universit�tsklinikum Aachen, Neurologische Klinik, Aachen, )] TJ ET
BT 26.250 565.095 Td /F1 9.8 Tf  [(Germany Christian Sass, Universit�tsklinikum Aachen, Neurologische Klinik, Aachen, Germany JohannesSchiefer, )] TJ ET
BT 26.250 553.191 Td /F1 9.8 Tf  [(Universit�tsklinikum Aachen, Neurologische Klinik, Aachen, Germany Christiane Schlangen, Universit�tsklinikum Aachen, )] TJ ET
BT 26.250 541.286 Td /F1 9.8 Tf  [(Neurologische Klinik, Aachen, Germany Cornelius J. Werner, Universit�tsklinikum Aachen, Neurologische Klinik, Aachen, )] TJ ET
BT 26.250 529.381 Td /F1 9.8 Tf  [(Germany Harald Gelderblom, Klinik und Poliklinik f�r Neurologie � Charit� � Universit�tsmedizin Berlin, Berlin, Germany Josef )] TJ ET
BT 26.250 517.476 Td /F1 9.8 Tf  [(Priller, Klinik und Poliklinik f�r Neurologie � Charit� � Universit�tsmedizin Berlin, Berlin, Germany Harald Pr��, Klinik und )] TJ ET
BT 26.250 505.572 Td /F1 9.8 Tf  [(Poliklinik f�r Neurologie � Charit� � Universit�tsmedizin Berlin, Berlin, Germany Eike Jakob Spruth, Klinik und Poliklinik f�r )] TJ ET
BT 26.250 493.667 Td /F1 9.8 Tf  [(Neurologie � Charit� � Universit�tsmedizin Berlin, Berlin, Germany J�rgen Andrich)] TJ ET
BT 382.778 493.667 Td /F4 9.8 Tf  [(, )] TJ ET
BT 388.199 493.667 Td /F1 9.8 Tf  [(Huntington-Zentrum \(NRW\) Bochum im St. )] TJ ET
BT 26.250 481.762 Td /F1 9.8 Tf  [(Josef-Hospital, Bochum, Germany Gisa Ellrichmann, Huntington-Zentrum \(NRW\) Bochum im St. Josef-Hospital, Bochum, )] TJ ET
BT 26.250 469.857 Td /F1 9.8 Tf  [(Germany Rainer Hoffmann, Huntington-Zentrum \(NRW\) Bochum im St. Josef-Hospital, Bochum, Germany Christian Prehn, )] TJ ET
BT 26.250 457.953 Td /F1 9.8 Tf  [(Huntington-Zentrum \(NRW\) Bochum im St. Josef-Hospital, Bochum, Germany Carsten Saft, Huntington-Zentrum \(NRW\) )] TJ ET
BT 26.250 446.048 Td /F1 9.8 Tf  [(Bochum im St. Josef-Hospital, Bochum, Germany Stephan Salmen, Huntington-Zentrum \(NRW\) Bochum im St. Josef-Hospital, )] TJ ET
BT 26.250 434.143 Td /F1 9.8 Tf  [(Bochum, Germany Christiane Stamm, Huntington-Zentrum \(NRW\) Bochum im St. Josef-Hospital, Bochum, Germany Tanja )] TJ ET
BT 26.250 422.238 Td /F1 9.8 Tf  [(Steiner, Huntington-Zentrum \(NRW\) Bochum im St. Josef-Hospital, Bochum, Germany Katrin Stra�burge, Huntington-Zentrum )] TJ ET
BT 26.250 410.334 Td /F1 9.8 Tf  [(\(NRW\) Bochum im St. Josef-Hospital, Bochum, Germany Herwig Lange, Reha Zentrum in Dinslaken im Gesundheitszentrums )] TJ ET
BT 26.250 398.429 Td /F1 9.8 Tf  [(Lang, Dinslake, German Matthias L�hle, Universit�tsklinikum Carl Gustav Carus an der Technischen Universit�t Dresden, Klinik )] TJ ET
BT 26.250 386.524 Td /F1 9.8 Tf  [(und Poliklinik f�r Neurologie, Dresden, Germany Simone Schmidt, Universit�tsklinikum Carl Gustav Carus an der Technischen )] TJ ET
BT 26.250 374.619 Td /F1 9.8 Tf  [(Universit�t Dresden, Klinik und Poliklinik f�r Neurologie, Dresden, Germany Alexander Storch, Universit�tsklinikum Carl Gustav )] TJ ET
BT 26.250 362.715 Td /F1 9.8 Tf  [(Carus an der Technischen Universit�t Dresden, Klinik und Poliklinik f�r Neurologie, Dresden, Germany Annett Wolz, )] TJ ET
BT 26.250 350.810 Td /F1 9.8 Tf  [(Universit�tsklinikum Carl Gustav Carus an der Technischen Universit�t Dresden, Klinik und Poliklinik f�r Neurologie, Dresden, )] TJ ET
BT 26.250 338.905 Td /F1 9.8 Tf  [(Germany Martin Wolz, Universit�tsklinikum Carl Gustav Carus an der Technischen Universit�t Dresden, Klinik und Poliklinik f�r )] TJ ET
BT 26.250 327.000 Td /F1 9.8 Tf  [(Neurologie, Dresden, Germany Johann Lambeck, Universit�tsklinik Freiburg, Neurologie, Freiburg, Germany Birgit Zucker, )] TJ ET
BT 26.250 315.096 Td /F1 9.8 Tf  [(Universit�tsklinik Freiburg, Neurologie, Freiburg, Germany Ute Hidding, Universit�tsklinikum Hamburg-Eppendorf, Klinik und )] TJ ET
BT 26.250 303.191 Td /F1 9.8 Tf  [(Poliklinik f�r Neurologie, Hamburg, Germany Jan Lewerenz, Universit�tsklinikum Hamburg-Eppendorf, Klinik und Poliklinik f�r )] TJ ET
BT 26.250 291.286 Td /F1 9.8 Tf  [(Neurologie, Hamburg, Germany Alexander M�nchau, Universit�tsklinikum Hamburg-Eppendorf, Klinik und Poliklinik f�r )] TJ ET
BT 26.250 279.381 Td /F1 9.8 Tf  [(Neurologie, Hamburg, Germany Michael Orth, Universit�tsklinikum Hamburg-Eppendorf, Klinik und Poliklinik f�r Neurologie, )] TJ ET
BT 26.250 267.477 Td /F1 9.8 Tf  [(Hamburg, Germany Jenny Schmalfeld, Universit�tsklinikum Hamburg-Eppendorf, Klinik und Poliklinik f�r Neurologie, Hamburg, )] TJ ET
BT 26.250 255.572 Td /F1 9.8 Tf  [(Germany Lars Stubbe, Universit�tsklinikum Hamburg-Eppendorf, Klinik und Poliklinik f�r Neurologie, Hamburg, Germany )] TJ ET
BT 26.250 243.667 Td /F1 9.8 Tf  [(Simone Zittel, Universit�tsklinikum Hamburg-Eppendorf, Klinik und Poliklinik f�r Neurologie, Hamburg, Germany Walburgis )] TJ ET
BT 26.250 231.762 Td /F1 9.8 Tf  [(Heinicke, Psychatrium Heiligenhafen, Heiligenhafe, Germany Bernhard Longinus, Klinik f�r Psychiatrie und Psychotherapie )] TJ ET
BT 26.250 219.858 Td /F1 9.8 Tf  [(Marburg-S�d, Marburg KP, Germany Jens Carsten M�ller, Universit�t Marburg, Neurologie, Marburg Uni, Germany Ida )] TJ ET
BT 26.250 207.953 Td /F1 9.8 Tf  [(Rissling, Universit�t Marburg, Neurologie, Marburg Uni, Germany Alexander Peinemann, Huntington-Ambulanz im Neuro-)] TJ ET
BT 26.250 196.048 Td /F1 9.8 Tf  [(Kopfzentrum � Klinikum rechts der Isar der Neurologischen Klinik und Poliklinik der Technischen Universit�t M�nchen, )] TJ ET
BT 26.250 184.143 Td /F1 9.8 Tf  [(M�nchen, Germany Michael St�dtler, Huntington-Ambulanz im Neuro-Kopfzentrum � Klinikum rechts der Isar der )] TJ ET
BT 26.250 172.239 Td /F1 9.8 Tf  [(Neurologischen Klinik und Poliklinik der Technischen Universit�t M�nchen, M�nchen, Germany Adolf Weindl, Huntington-)] TJ ET
BT 26.250 160.334 Td /F1 9.8 Tf  [(Ambulanz im Neuro-Kopfzentrum � Klinikum rechts der Isar der Neurologischen Klinik und Poliklinik der Technischen )] TJ ET
BT 26.250 148.429 Td /F1 9.8 Tf  [(Universit�t M�nchen, M�nchen, Germany Stefan Bohlen, Universit�tsklinikum M�nster, Klinik und Poliklinik f�r Neurologie, )] TJ ET
BT 26.250 136.524 Td /F1 9.8 Tf  [(M�nste, Germany Eva H�lzner, Universit�tsklinikum M�nster, Klinik und Poliklinik f�r Neurologie, M�nste, Germany Herwig )] TJ ET
BT 26.250 124.620 Td /F1 9.8 Tf  [(Lange, Universit�tsklinikum M�nster, Klinik und Poliklinik f�r Neurologie, M�nste, Germany Ralf Reilmann, Universit�tsklinikum )] TJ ET
BT 26.250 112.715 Td /F1 9.8 Tf  [(M�nster, Klinik und Poliklinik f�r Neurologie, M�nste, German Antonie Beister, Isar-Amper-Klinikum � Klinik Taufkirchen \(Vils\), )] TJ ET
BT 26.250 100.810 Td /F1 9.8 Tf  [(Taufkirchen, Germany Matthias Dose, Isar-Amper-Klinikum � Klinik Taufkirchen \(Vils\), Taufkirchen, Germany Kathrin Hammer, )] TJ ET
BT 26.250 88.905 Td /F1 9.8 Tf  [(Isar-Amper-Klinikum � Klinik Taufkirchen \(Vils\), Taufkirchen, Germany Janina Kieni, Isar-Amper-Klinikum � Klinik Taufkirchen )] TJ ET
BT 26.250 77.001 Td /F1 9.8 Tf  [(\(Vils\), Taufkirchen, Germany Gabriele Leythaeuser, Isar-Amper-Klinikum � Klinik Taufkirchen \(Vils\), Taufkirchen, Germany Ralf )] TJ ET
BT 26.250 65.096 Td /F1 9.8 Tf  [(Marquard, Isar-Amper-Klinikum � Klinik Taufkirchen \(Vils\), Taufkirchen, Germany Tina Raab, Isar-Amper-Klinikum � Klinik )] TJ ET
BT 26.250 53.191 Td /F1 9.8 Tf  [(Taufkirchen \(Vils\), Taufkirchen, Germany Sven Richter, Isar-Amper-Klinikum � Klinik Taufkirchen \(Vils\), Taufkirchen, Germany )] TJ ET
BT 26.250 41.286 Td /F1 9.8 Tf  [(Amina Selimbegovic-Turkovic, Isar-Amper-Klinikum � Klinik Taufkirchen \(Vils\), Taufkirchen, Germany Caroline Schrenk, Isar-)] TJ ET
BT 26.250 29.382 Td /F1 9.8 Tf  [(Amper-Klinikum � Klinik Taufkirchen \(Vils\), Taufkirchen, Germany Michele Schuierer;, Isar-Amper-Klinikum � Klinik Taufkirchen )] TJ ET
Q
q
0.000 0.000 0.000 rg
BT 291.710 19.825 Td /F1 11.0 Tf  [(7)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Huntington Disease)] TJ ET

Q
endstream
endobj
185 0 obj
<< /Type /Page
/Parent 3 0 R
/Contents 186 0 R
>>
endobj
186 0 obj
<<
/Length 26338 >>
stream

0.271 0.267 0.267 rg
q
15.000 27.834 577.500 749.166 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(\(Vils\), Taufkirchen, Germany Alexandra Wiedemann, Isar-Amper-Klinikum � Klinik Taufkirchen \(Vils\), Taufkirchen, Germany )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(Katrin Barth, Universit�tsklinikum Ulm, Neurologie, Ulm, Germany Andrea Buck, Universit�tsklinikum Ulm, Neurologie, Ulm, )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(Germany Julia Connemann, Universit�tsklinikum Ulm, Neurologie, Ulm, Germany Daniel Ecker, Universit�tsklinikum Ulm, )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(Neurologie, Ulm, Germany Carolin Eschenbach, Universit�tsklinikum Ulm, Neurologie, Ulm, Germany Christine Held, )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(Universit�tsklinikum Ulm, Neurologie, Ulm, Germany Bernhard Landwehrmeyer, Universit�tsklinikum Ulm, Neurologie, Ulm, )] TJ ET
BT 26.250 707.952 Td /F1 9.8 Tf  [(Germany Franziska Lezius, Universit�tsklinikum Ulm, Neurologie, Ulm, Germany Anke Niess, Universit�tsklinikum Ulm, )] TJ ET
BT 26.250 696.048 Td /F1 9.8 Tf  [(Neurologie, Ulm, Germany Michael Orth, Universit�tsklinikum Ulm, Neurologie, Ulm, Germany Sigurd S��muth, )] TJ ET
BT 26.250 684.143 Td /F1 9.8 Tf  [(Universit�tsklinikum Ulm, Neurologie, Ulm, Germany Sonja Trautmann, Universit�tsklinikum Ulm, Neurologie, Ulm, Germany )] TJ ET
BT 26.250 672.238 Td /F1 9.8 Tf  [(Patrick Weydt, Universit�tsklinikum Ulm, Neurologie, Ulm, Germany Claudia Cormio, Dipartimento di Scienze Neurologiche e )] TJ ET
BT 26.250 660.333 Td /F1 9.8 Tf  [(Psichiatriche Universita� di Bari, Bari, Italy Olimpia Difruscolo, Dipartimento di Scienze Neurologiche e Psichiatriche Universita� )] TJ ET
BT 26.250 648.429 Td /F1 9.8 Tf  [(di Bari, Bari, Italy Vittorio Sciruicchio, Dipartimento di Scienze Neurologiche e Psichiatriche Universita� di Bari, Bari, Italy Claudia )] TJ ET
BT 26.250 636.524 Td /F1 9.8 Tf  [(Serpino, Dipartimento di Scienze Neurologiche e Psichiatriche Universita� di Bari, Bari, Italy Marina de Tommaso, Dipartimento )] TJ ET
BT 26.250 624.619 Td /F1 9.8 Tf  [(di Scienze Neurologiche e Psichiatriche Universita� di Bari, Bari, Italy Elisabetta Bertini, Dipartimento di Scienze Neurologiche e )] TJ ET
BT 26.250 612.714 Td /F1 9.8 Tf  [(Psichiatriche Universita� degli Studi di Firenze-Azienda Ospedaliera Universitaria Careggi, Florence, Italy Elena Ghelli, )] TJ ET
BT 26.250 600.810 Td /F1 9.8 Tf  [(Dipartimento di Scienze Neurologiche e Psichiatriche Universita� degli Studi di Firenze-Azienda Ospedaliera Universitaria )] TJ ET
BT 26.250 588.905 Td /F1 9.8 Tf  [(Careggi, Florence, Italy Andrea Ginestroni, Dipartimento di Scienze Neurologiche e Psichiatriche Universita� degli Studi di )] TJ ET
BT 26.250 577.000 Td /F1 9.8 Tf  [(Firenze-Azienda Ospedaliera Universitaria Careggi, Florence, Italy Francesca Massaro, Dipartimento di Scienze Neurologiche e )] TJ ET
BT 26.250 565.095 Td /F1 9.8 Tf  [(Psichiatriche Universita� degli Studi di Firenze-Azienda Ospedaliera Universitaria Careggi, Florence, Italy Claudia Mechi, )] TJ ET
BT 26.250 553.191 Td /F1 9.8 Tf  [(Dipartimento di Scienze Neurologiche e Psichiatriche Universita� degli Studi di Firenze-Azienda Ospedaliera Universitaria )] TJ ET
BT 26.250 541.286 Td /F1 9.8 Tf  [(Careggi, Florence, Italy Marco Paganini, Dipartimento di Scienze Neurologiche e Psichiatriche Universita� degli Studi di Firenze-)] TJ ET
BT 26.250 529.381 Td /F1 9.8 Tf  [(Azienda Ospedaliera Universitaria Careggi, Florence, Italy Silvia Piacentini, Dipartimento di Scienze Neurologiche e )] TJ ET
BT 26.250 517.476 Td /F1 9.8 Tf  [(Psichiatriche Universita� degli Studi di Firenze-Azienda Ospedaliera Universitaria Careggi, Florence, Italy Silvia Pradella, )] TJ ET
BT 26.250 505.572 Td /F1 9.8 Tf  [(Dipartimento di Scienze Neurologiche e Psichiatriche Universita� degli Studi di Firenze-Azienda Ospedaliera Universitaria )] TJ ET
BT 26.250 493.667 Td /F1 9.8 Tf  [(Careggi, Florence, Italy Anna Maria Romoli, Dipartimento di Scienze Neurologiche e Psichiatriche Universita� degli Studi di )] TJ ET
BT 26.250 481.762 Td /F1 9.8 Tf  [(Firenze-Azienda Ospedaliera Universitaria Careggi, Florence, Italy Sandro Sorbi, Dipartimento di Scienze Neurologiche e )] TJ ET
BT 26.250 469.857 Td /F1 9.8 Tf  [(Psichiatriche Universita� degli Studi di Firenze-Azienda Ospedaliera Universitaria Careggi, Florence, Italy Giovanni Abbruzzese, )] TJ ET
BT 26.250 457.953 Td /F1 9.8 Tf  [(Dipartimento di Neuroscienze, Oftalmologia e Genetica \(DiNOG\), Universit� di Genova, Genoa, Italy Monica Bandettini di )] TJ ET
BT 26.250 446.048 Td /F1 9.8 Tf  [(Poggio, Dipartimento di Neuroscienze, Oftalmologia e Genetica \(DiNOG\), Universit� di Genova, Genoa, Italy Giovanna )] TJ ET
BT 26.250 434.143 Td /F1 9.8 Tf  [(Ferrandes, Dipartimento di Neuroscienze, Oftalmologia e Genetica \(DiNOG\), Universit� di Genova, Genoa, Italy Paola Mandich, )] TJ ET
BT 26.250 422.238 Td /F1 9.8 Tf  [(Dipartimento di Neuroscienze, Oftalmologia e Genetica \(DiNOG\), Universit� di Genova, Genoa, Italy Roberta Marchese, )] TJ ET
BT 26.250 410.334 Td /F1 9.8 Tf  [(Dipartimento di Neuroscienze, Oftalmologia e Genetica \(DiNOG\),Universit� di Genova, Genoa, Italy)] TJ ET
BT 26.250 398.429 Td /F1 9.8 Tf  [(Alberto Albanese, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 379.024 Td /F1 9.8 Tf  [(Daniela Di Bella, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 359.619 Td /F1 9.8 Tf  [(Stefano Di Donato, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 340.215 Td /F1 9.8 Tf  [(Cinzia Gellera, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 320.810 Td /F1 9.8 Tf  [(Silvia Genitrini, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 301.405 Td /F1 9.8 Tf  [(Caterina Mariotti, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 282.000 Td /F1 9.8 Tf  [(Daniela Monza, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 262.596 Td /F1 9.8 Tf  [(Lorenzo Nanetti, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 243.191 Td /F1 9.8 Tf  [(Dominga Paridi, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 223.786 Td /F1 9.8 Tf  [(Paola Soliveri, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 204.381 Td /F1 9.8 Tf  [(Chiara Tomasello, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 184.977 Td /F1 9.8 Tf  [(Giuseppe De Michele, Dipartimento di Scienze NeurologicheAzienda Ospedaliera Universitaria Federico II, Naples, Italy Luigi Di )] TJ ET
BT 26.250 173.072 Td /F1 9.8 Tf  [(Maio, Dipartimento di Scienze NeurologicheAzienda Ospedaliera Universitaria Federico II, Naples, Italy Carlo Rinaldi, )] TJ ET
BT 26.250 161.167 Td /F1 9.8 Tf  [(Dipartimento di Scienze NeurologicheAzienda Ospedaliera Universitaria Federico II, Naples, Italy Cinzia Valeria Russo, )] TJ ET
BT 26.250 149.262 Td /F1 9.8 Tf  [(Dipartimento di Scienze NeurologicheAzienda Ospedaliera Universitaria Federico II, Naples, Italy Elena Salvatore, Dipartimento )] TJ ET
BT 26.250 137.358 Td /F1 9.8 Tf  [(di Scienze NeurologicheAzienda Ospedaliera Universitaria Federico II, Naples, Italy Tecla Tucci, Dipartimento di Scienze )] TJ ET
BT 26.250 125.453 Td /F1 9.8 Tf  [(NeurologicheAzienda Ospedaliera Universitaria Federico II, Naples, Italy Francesca Elifani, Centro di Neurogenetica e Malattie )] TJ ET
BT 26.250 113.548 Td /F1 9.8 Tf  [(Rare � IRCCS Neuromed, Pozzilli \(IS\), Italy Sara Orobello, Centro di Neurogenetica e Malattie Rare � IRCCS Neuromed, )] TJ ET
BT 26.250 101.643 Td /F1 9.8 Tf  [(Pozzilli \(IS\), Italy Silvia Alberti, Centro di Neurogenetica e Malattie Rare � IRCCS Neuromed, Pozzilli \(IS\), Italy Annamaria )] TJ ET
BT 26.250 89.739 Td /F1 9.8 Tf  [(Griguoli, Centro di Neurogenetica e Malattie Rare � IRCCS Neuromed, Pozzilli \(IS\), Italy Enrico Amico, Centro di Neurogenetica )] TJ ET
BT 26.250 77.834 Td /F1 9.8 Tf  [(e Malattie Rare � IRCCS Neuromed, Pozzilli \(IS\), Italy Annunziata De Nicola, Centro di Neurogenetica e Malattie Rare � IRCCS )] TJ ET
BT 26.250 65.929 Td /F1 9.8 Tf  [(Neuromed, Pozzilli \(IS\), Italy Tiziana Martino, Centro di Neurogenetica e Malattie Rare � IRCCS Neuromed, Pozzilli \(IS\), Italy )] TJ ET
BT 26.250 54.024 Td /F1 9.8 Tf  [(Ferdinando Squitier, Centro di Neurogenetica e Malattie Rare � IRCCS Neuromed, Pozzilli \(IS\), Italy)] TJ ET
BT 26.250 42.120 Td /F1 9.8 Tf  [(Anna Rita Bentivoglio, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione )] TJ ET
Q
q
15.000 27.834 577.500 749.166 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(\(Vils\), Taufkirchen, Germany Alexandra Wiedemann, Isar-Amper-Klinikum � Klinik Taufkirchen \(Vils\), Taufkirchen, Germany )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(Katrin Barth, Universit�tsklinikum Ulm, Neurologie, Ulm, Germany Andrea Buck, Universit�tsklinikum Ulm, Neurologie, Ulm, )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(Germany Julia Connemann, Universit�tsklinikum Ulm, Neurologie, Ulm, Germany Daniel Ecker, Universit�tsklinikum Ulm, )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(Neurologie, Ulm, Germany Carolin Eschenbach, Universit�tsklinikum Ulm, Neurologie, Ulm, Germany Christine Held, )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(Universit�tsklinikum Ulm, Neurologie, Ulm, Germany Bernhard Landwehrmeyer, Universit�tsklinikum Ulm, Neurologie, Ulm, )] TJ ET
BT 26.250 707.952 Td /F1 9.8 Tf  [(Germany Franziska Lezius, Universit�tsklinikum Ulm, Neurologie, Ulm, Germany Anke Niess, Universit�tsklinikum Ulm, )] TJ ET
BT 26.250 696.048 Td /F1 9.8 Tf  [(Neurologie, Ulm, Germany Michael Orth, Universit�tsklinikum Ulm, Neurologie, Ulm, Germany Sigurd S��muth, )] TJ ET
BT 26.250 684.143 Td /F1 9.8 Tf  [(Universit�tsklinikum Ulm, Neurologie, Ulm, Germany Sonja Trautmann, Universit�tsklinikum Ulm, Neurologie, Ulm, Germany )] TJ ET
BT 26.250 672.238 Td /F1 9.8 Tf  [(Patrick Weydt, Universit�tsklinikum Ulm, Neurologie, Ulm, Germany Claudia Cormio, Dipartimento di Scienze Neurologiche e )] TJ ET
BT 26.250 660.333 Td /F1 9.8 Tf  [(Psichiatriche Universita� di Bari, Bari, Italy Olimpia Difruscolo, Dipartimento di Scienze Neurologiche e Psichiatriche Universita� )] TJ ET
BT 26.250 648.429 Td /F1 9.8 Tf  [(di Bari, Bari, Italy Vittorio Sciruicchio, Dipartimento di Scienze Neurologiche e Psichiatriche Universita� di Bari, Bari, Italy Claudia )] TJ ET
BT 26.250 636.524 Td /F1 9.8 Tf  [(Serpino, Dipartimento di Scienze Neurologiche e Psichiatriche Universita� di Bari, Bari, Italy Marina de Tommaso, Dipartimento )] TJ ET
BT 26.250 624.619 Td /F1 9.8 Tf  [(di Scienze Neurologiche e Psichiatriche Universita� di Bari, Bari, Italy Elisabetta Bertini, Dipartimento di Scienze Neurologiche e )] TJ ET
BT 26.250 612.714 Td /F1 9.8 Tf  [(Psichiatriche Universita� degli Studi di Firenze-Azienda Ospedaliera Universitaria Careggi, Florence, Italy Elena Ghelli, )] TJ ET
BT 26.250 600.810 Td /F1 9.8 Tf  [(Dipartimento di Scienze Neurologiche e Psichiatriche Universita� degli Studi di Firenze-Azienda Ospedaliera Universitaria )] TJ ET
BT 26.250 588.905 Td /F1 9.8 Tf  [(Careggi, Florence, Italy Andrea Ginestroni, Dipartimento di Scienze Neurologiche e Psichiatriche Universita� degli Studi di )] TJ ET
BT 26.250 577.000 Td /F1 9.8 Tf  [(Firenze-Azienda Ospedaliera Universitaria Careggi, Florence, Italy Francesca Massaro, Dipartimento di Scienze Neurologiche e )] TJ ET
BT 26.250 565.095 Td /F1 9.8 Tf  [(Psichiatriche Universita� degli Studi di Firenze-Azienda Ospedaliera Universitaria Careggi, Florence, Italy Claudia Mechi, )] TJ ET
BT 26.250 553.191 Td /F1 9.8 Tf  [(Dipartimento di Scienze Neurologiche e Psichiatriche Universita� degli Studi di Firenze-Azienda Ospedaliera Universitaria )] TJ ET
BT 26.250 541.286 Td /F1 9.8 Tf  [(Careggi, Florence, Italy Marco Paganini, Dipartimento di Scienze Neurologiche e Psichiatriche Universita� degli Studi di Firenze-)] TJ ET
BT 26.250 529.381 Td /F1 9.8 Tf  [(Azienda Ospedaliera Universitaria Careggi, Florence, Italy Silvia Piacentini, Dipartimento di Scienze Neurologiche e )] TJ ET
BT 26.250 517.476 Td /F1 9.8 Tf  [(Psichiatriche Universita� degli Studi di Firenze-Azienda Ospedaliera Universitaria Careggi, Florence, Italy Silvia Pradella, )] TJ ET
BT 26.250 505.572 Td /F1 9.8 Tf  [(Dipartimento di Scienze Neurologiche e Psichiatriche Universita� degli Studi di Firenze-Azienda Ospedaliera Universitaria )] TJ ET
BT 26.250 493.667 Td /F1 9.8 Tf  [(Careggi, Florence, Italy Anna Maria Romoli, Dipartimento di Scienze Neurologiche e Psichiatriche Universita� degli Studi di )] TJ ET
BT 26.250 481.762 Td /F1 9.8 Tf  [(Firenze-Azienda Ospedaliera Universitaria Careggi, Florence, Italy Sandro Sorbi, Dipartimento di Scienze Neurologiche e )] TJ ET
BT 26.250 469.857 Td /F1 9.8 Tf  [(Psichiatriche Universita� degli Studi di Firenze-Azienda Ospedaliera Universitaria Careggi, Florence, Italy Giovanni Abbruzzese, )] TJ ET
BT 26.250 457.953 Td /F1 9.8 Tf  [(Dipartimento di Neuroscienze, Oftalmologia e Genetica \(DiNOG\), Universit� di Genova, Genoa, Italy Monica Bandettini di )] TJ ET
BT 26.250 446.048 Td /F1 9.8 Tf  [(Poggio, Dipartimento di Neuroscienze, Oftalmologia e Genetica \(DiNOG\), Universit� di Genova, Genoa, Italy Giovanna )] TJ ET
BT 26.250 434.143 Td /F1 9.8 Tf  [(Ferrandes, Dipartimento di Neuroscienze, Oftalmologia e Genetica \(DiNOG\), Universit� di Genova, Genoa, Italy Paola Mandich, )] TJ ET
BT 26.250 422.238 Td /F1 9.8 Tf  [(Dipartimento di Neuroscienze, Oftalmologia e Genetica \(DiNOG\), Universit� di Genova, Genoa, Italy Roberta Marchese, )] TJ ET
BT 26.250 410.334 Td /F1 9.8 Tf  [(Dipartimento di Neuroscienze, Oftalmologia e Genetica \(DiNOG\),Universit� di Genova, Genoa, Italy)] TJ ET
BT 26.250 398.429 Td /F1 9.8 Tf  [(Alberto Albanese, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 379.024 Td /F1 9.8 Tf  [(Daniela Di Bella, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 359.619 Td /F1 9.8 Tf  [(Stefano Di Donato, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 340.215 Td /F1 9.8 Tf  [(Cinzia Gellera, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 320.810 Td /F1 9.8 Tf  [(Silvia Genitrini, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 301.405 Td /F1 9.8 Tf  [(Caterina Mariotti, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 282.000 Td /F1 9.8 Tf  [(Daniela Monza, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 262.596 Td /F1 9.8 Tf  [(Lorenzo Nanetti, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 243.191 Td /F1 9.8 Tf  [(Dominga Paridi, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 223.786 Td /F1 9.8 Tf  [(Paola Soliveri, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 204.381 Td /F1 9.8 Tf  [(Chiara Tomasello, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 184.977 Td /F1 9.8 Tf  [(Giuseppe De Michele, Dipartimento di Scienze NeurologicheAzienda Ospedaliera Universitaria Federico II, Naples, Italy Luigi Di )] TJ ET
BT 26.250 173.072 Td /F1 9.8 Tf  [(Maio, Dipartimento di Scienze NeurologicheAzienda Ospedaliera Universitaria Federico II, Naples, Italy Carlo Rinaldi, )] TJ ET
BT 26.250 161.167 Td /F1 9.8 Tf  [(Dipartimento di Scienze NeurologicheAzienda Ospedaliera Universitaria Federico II, Naples, Italy Cinzia Valeria Russo, )] TJ ET
BT 26.250 149.262 Td /F1 9.8 Tf  [(Dipartimento di Scienze NeurologicheAzienda Ospedaliera Universitaria Federico II, Naples, Italy Elena Salvatore, Dipartimento )] TJ ET
BT 26.250 137.358 Td /F1 9.8 Tf  [(di Scienze NeurologicheAzienda Ospedaliera Universitaria Federico II, Naples, Italy Tecla Tucci, Dipartimento di Scienze )] TJ ET
BT 26.250 125.453 Td /F1 9.8 Tf  [(NeurologicheAzienda Ospedaliera Universitaria Federico II, Naples, Italy Francesca Elifani, Centro di Neurogenetica e Malattie )] TJ ET
BT 26.250 113.548 Td /F1 9.8 Tf  [(Rare � IRCCS Neuromed, Pozzilli \(IS\), Italy Sara Orobello, Centro di Neurogenetica e Malattie Rare � IRCCS Neuromed, )] TJ ET
BT 26.250 101.643 Td /F1 9.8 Tf  [(Pozzilli \(IS\), Italy Silvia Alberti, Centro di Neurogenetica e Malattie Rare � IRCCS Neuromed, Pozzilli \(IS\), Italy Annamaria )] TJ ET
BT 26.250 89.739 Td /F1 9.8 Tf  [(Griguoli, Centro di Neurogenetica e Malattie Rare � IRCCS Neuromed, Pozzilli \(IS\), Italy Enrico Amico, Centro di Neurogenetica )] TJ ET
BT 26.250 77.834 Td /F1 9.8 Tf  [(e Malattie Rare � IRCCS Neuromed, Pozzilli \(IS\), Italy Annunziata De Nicola, Centro di Neurogenetica e Malattie Rare � IRCCS )] TJ ET
BT 26.250 65.929 Td /F1 9.8 Tf  [(Neuromed, Pozzilli \(IS\), Italy Tiziana Martino, Centro di Neurogenetica e Malattie Rare � IRCCS Neuromed, Pozzilli \(IS\), Italy )] TJ ET
BT 26.250 54.024 Td /F1 9.8 Tf  [(Ferdinando Squitier, Centro di Neurogenetica e Malattie Rare � IRCCS Neuromed, Pozzilli \(IS\), Italy)] TJ ET
BT 26.250 42.120 Td /F1 9.8 Tf  [(Anna Rita Bentivoglio, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione )] TJ ET
Q
q
15.000 27.834 577.500 749.166 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(\(Vils\), Taufkirchen, Germany Alexandra Wiedemann, Isar-Amper-Klinikum � Klinik Taufkirchen \(Vils\), Taufkirchen, Germany )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(Katrin Barth, Universit�tsklinikum Ulm, Neurologie, Ulm, Germany Andrea Buck, Universit�tsklinikum Ulm, Neurologie, Ulm, )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(Germany Julia Connemann, Universit�tsklinikum Ulm, Neurologie, Ulm, Germany Daniel Ecker, Universit�tsklinikum Ulm, )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(Neurologie, Ulm, Germany Carolin Eschenbach, Universit�tsklinikum Ulm, Neurologie, Ulm, Germany Christine Held, )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(Universit�tsklinikum Ulm, Neurologie, Ulm, Germany Bernhard Landwehrmeyer, Universit�tsklinikum Ulm, Neurologie, Ulm, )] TJ ET
BT 26.250 707.952 Td /F1 9.8 Tf  [(Germany Franziska Lezius, Universit�tsklinikum Ulm, Neurologie, Ulm, Germany Anke Niess, Universit�tsklinikum Ulm, )] TJ ET
BT 26.250 696.048 Td /F1 9.8 Tf  [(Neurologie, Ulm, Germany Michael Orth, Universit�tsklinikum Ulm, Neurologie, Ulm, Germany Sigurd S��muth, )] TJ ET
BT 26.250 684.143 Td /F1 9.8 Tf  [(Universit�tsklinikum Ulm, Neurologie, Ulm, Germany Sonja Trautmann, Universit�tsklinikum Ulm, Neurologie, Ulm, Germany )] TJ ET
BT 26.250 672.238 Td /F1 9.8 Tf  [(Patrick Weydt, Universit�tsklinikum Ulm, Neurologie, Ulm, Germany Claudia Cormio, Dipartimento di Scienze Neurologiche e )] TJ ET
BT 26.250 660.333 Td /F1 9.8 Tf  [(Psichiatriche Universita� di Bari, Bari, Italy Olimpia Difruscolo, Dipartimento di Scienze Neurologiche e Psichiatriche Universita� )] TJ ET
BT 26.250 648.429 Td /F1 9.8 Tf  [(di Bari, Bari, Italy Vittorio Sciruicchio, Dipartimento di Scienze Neurologiche e Psichiatriche Universita� di Bari, Bari, Italy Claudia )] TJ ET
BT 26.250 636.524 Td /F1 9.8 Tf  [(Serpino, Dipartimento di Scienze Neurologiche e Psichiatriche Universita� di Bari, Bari, Italy Marina de Tommaso, Dipartimento )] TJ ET
BT 26.250 624.619 Td /F1 9.8 Tf  [(di Scienze Neurologiche e Psichiatriche Universita� di Bari, Bari, Italy Elisabetta Bertini, Dipartimento di Scienze Neurologiche e )] TJ ET
BT 26.250 612.714 Td /F1 9.8 Tf  [(Psichiatriche Universita� degli Studi di Firenze-Azienda Ospedaliera Universitaria Careggi, Florence, Italy Elena Ghelli, )] TJ ET
BT 26.250 600.810 Td /F1 9.8 Tf  [(Dipartimento di Scienze Neurologiche e Psichiatriche Universita� degli Studi di Firenze-Azienda Ospedaliera Universitaria )] TJ ET
BT 26.250 588.905 Td /F1 9.8 Tf  [(Careggi, Florence, Italy Andrea Ginestroni, Dipartimento di Scienze Neurologiche e Psichiatriche Universita� degli Studi di )] TJ ET
BT 26.250 577.000 Td /F1 9.8 Tf  [(Firenze-Azienda Ospedaliera Universitaria Careggi, Florence, Italy Francesca Massaro, Dipartimento di Scienze Neurologiche e )] TJ ET
BT 26.250 565.095 Td /F1 9.8 Tf  [(Psichiatriche Universita� degli Studi di Firenze-Azienda Ospedaliera Universitaria Careggi, Florence, Italy Claudia Mechi, )] TJ ET
BT 26.250 553.191 Td /F1 9.8 Tf  [(Dipartimento di Scienze Neurologiche e Psichiatriche Universita� degli Studi di Firenze-Azienda Ospedaliera Universitaria )] TJ ET
BT 26.250 541.286 Td /F1 9.8 Tf  [(Careggi, Florence, Italy Marco Paganini, Dipartimento di Scienze Neurologiche e Psichiatriche Universita� degli Studi di Firenze-)] TJ ET
BT 26.250 529.381 Td /F1 9.8 Tf  [(Azienda Ospedaliera Universitaria Careggi, Florence, Italy Silvia Piacentini, Dipartimento di Scienze Neurologiche e )] TJ ET
BT 26.250 517.476 Td /F1 9.8 Tf  [(Psichiatriche Universita� degli Studi di Firenze-Azienda Ospedaliera Universitaria Careggi, Florence, Italy Silvia Pradella, )] TJ ET
BT 26.250 505.572 Td /F1 9.8 Tf  [(Dipartimento di Scienze Neurologiche e Psichiatriche Universita� degli Studi di Firenze-Azienda Ospedaliera Universitaria )] TJ ET
BT 26.250 493.667 Td /F1 9.8 Tf  [(Careggi, Florence, Italy Anna Maria Romoli, Dipartimento di Scienze Neurologiche e Psichiatriche Universita� degli Studi di )] TJ ET
BT 26.250 481.762 Td /F1 9.8 Tf  [(Firenze-Azienda Ospedaliera Universitaria Careggi, Florence, Italy Sandro Sorbi, Dipartimento di Scienze Neurologiche e )] TJ ET
BT 26.250 469.857 Td /F1 9.8 Tf  [(Psichiatriche Universita� degli Studi di Firenze-Azienda Ospedaliera Universitaria Careggi, Florence, Italy Giovanni Abbruzzese, )] TJ ET
BT 26.250 457.953 Td /F1 9.8 Tf  [(Dipartimento di Neuroscienze, Oftalmologia e Genetica \(DiNOG\), Universit� di Genova, Genoa, Italy Monica Bandettini di )] TJ ET
BT 26.250 446.048 Td /F1 9.8 Tf  [(Poggio, Dipartimento di Neuroscienze, Oftalmologia e Genetica \(DiNOG\), Universit� di Genova, Genoa, Italy Giovanna )] TJ ET
BT 26.250 434.143 Td /F1 9.8 Tf  [(Ferrandes, Dipartimento di Neuroscienze, Oftalmologia e Genetica \(DiNOG\), Universit� di Genova, Genoa, Italy Paola Mandich, )] TJ ET
BT 26.250 422.238 Td /F1 9.8 Tf  [(Dipartimento di Neuroscienze, Oftalmologia e Genetica \(DiNOG\), Universit� di Genova, Genoa, Italy Roberta Marchese, )] TJ ET
BT 26.250 410.334 Td /F1 9.8 Tf  [(Dipartimento di Neuroscienze, Oftalmologia e Genetica \(DiNOG\),Universit� di Genova, Genoa, Italy)] TJ ET
BT 26.250 398.429 Td /F1 9.8 Tf  [(Alberto Albanese, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 379.024 Td /F1 9.8 Tf  [(Daniela Di Bella, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 359.619 Td /F1 9.8 Tf  [(Stefano Di Donato, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 340.215 Td /F1 9.8 Tf  [(Cinzia Gellera, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 320.810 Td /F1 9.8 Tf  [(Silvia Genitrini, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 301.405 Td /F1 9.8 Tf  [(Caterina Mariotti, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 282.000 Td /F1 9.8 Tf  [(Daniela Monza, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 262.596 Td /F1 9.8 Tf  [(Lorenzo Nanetti, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 243.191 Td /F1 9.8 Tf  [(Dominga Paridi, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 223.786 Td /F1 9.8 Tf  [(Paola Soliveri, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 204.381 Td /F1 9.8 Tf  [(Chiara Tomasello, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy)] TJ ET
BT 26.250 184.977 Td /F1 9.8 Tf  [(Giuseppe De Michele, Dipartimento di Scienze NeurologicheAzienda Ospedaliera Universitaria Federico II, Naples, Italy Luigi Di )] TJ ET
BT 26.250 173.072 Td /F1 9.8 Tf  [(Maio, Dipartimento di Scienze NeurologicheAzienda Ospedaliera Universitaria Federico II, Naples, Italy Carlo Rinaldi, )] TJ ET
BT 26.250 161.167 Td /F1 9.8 Tf  [(Dipartimento di Scienze NeurologicheAzienda Ospedaliera Universitaria Federico II, Naples, Italy Cinzia Valeria Russo, )] TJ ET
BT 26.250 149.262 Td /F1 9.8 Tf  [(Dipartimento di Scienze NeurologicheAzienda Ospedaliera Universitaria Federico II, Naples, Italy Elena Salvatore, Dipartimento )] TJ ET
BT 26.250 137.358 Td /F1 9.8 Tf  [(di Scienze NeurologicheAzienda Ospedaliera Universitaria Federico II, Naples, Italy Tecla Tucci, Dipartimento di Scienze )] TJ ET
BT 26.250 125.453 Td /F1 9.8 Tf  [(NeurologicheAzienda Ospedaliera Universitaria Federico II, Naples, Italy Francesca Elifani, Centro di Neurogenetica e Malattie )] TJ ET
BT 26.250 113.548 Td /F1 9.8 Tf  [(Rare � IRCCS Neuromed, Pozzilli \(IS\), Italy Sara Orobello, Centro di Neurogenetica e Malattie Rare � IRCCS Neuromed, )] TJ ET
BT 26.250 101.643 Td /F1 9.8 Tf  [(Pozzilli \(IS\), Italy Silvia Alberti, Centro di Neurogenetica e Malattie Rare � IRCCS Neuromed, Pozzilli \(IS\), Italy Annamaria )] TJ ET
BT 26.250 89.739 Td /F1 9.8 Tf  [(Griguoli, Centro di Neurogenetica e Malattie Rare � IRCCS Neuromed, Pozzilli \(IS\), Italy Enrico Amico, Centro di Neurogenetica )] TJ ET
BT 26.250 77.834 Td /F1 9.8 Tf  [(e Malattie Rare � IRCCS Neuromed, Pozzilli \(IS\), Italy Annunziata De Nicola, Centro di Neurogenetica e Malattie Rare � IRCCS )] TJ ET
BT 26.250 65.929 Td /F1 9.8 Tf  [(Neuromed, Pozzilli \(IS\), Italy Tiziana Martino, Centro di Neurogenetica e Malattie Rare � IRCCS Neuromed, Pozzilli \(IS\), Italy )] TJ ET
BT 26.250 54.024 Td /F1 9.8 Tf  [(Ferdinando Squitier, Centro di Neurogenetica e Malattie Rare � IRCCS Neuromed, Pozzilli \(IS\), Italy)] TJ ET
BT 26.250 42.120 Td /F1 9.8 Tf  [(Anna Rita Bentivoglio, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione )] TJ ET
Q
q
0.000 0.000 0.000 rg
BT 291.710 19.825 Td /F1 11.0 Tf  [(8)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Huntington Disease)] TJ ET

Q
endstream
endobj
187 0 obj
<< /Type /Page
/Parent 3 0 R
/Contents 188 0 R
>>
endobj
188 0 obj
<<
/Length 23716 >>
stream

0.271 0.267 0.267 rg
q
15.000 26.048 577.500 750.952 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(/CNR;Istituto di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 748.071 Td /F1 9.8 Tf  [(Claudio Catalli, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione /CNR;Istituto )] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 716.762 Td /F1 9.8 Tf  [(Raffaella Di Giacopo, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione )] TJ ET
BT 26.250 704.857 Td /F1 9.8 Tf  [(/CNR;Istituto di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 685.452 Td /F1 9.8 Tf  [(Alfonso Fasano, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione )] TJ ET
BT 26.250 673.548 Td /F1 9.8 Tf  [(/CNR;Istituto di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 654.143 Td /F1 9.8 Tf  [(Marina Frontali, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione /CNR;Istituto )] TJ ET
BT 26.250 642.238 Td /F1 9.8 Tf  [(di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 622.833 Td /F1 9.8 Tf  [(Arianna Guidubaldi, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione )] TJ ET
BT 26.250 610.929 Td /F1 9.8 Tf  [(/CNR;Istituto di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 591.524 Td /F1 9.8 Tf  [(Tamara Ialongo, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione )] TJ ET
BT 26.250 579.619 Td /F1 9.8 Tf  [(/CNR;Istituto di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 560.214 Td /F1 9.8 Tf  [(Gioia Jacopini, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione /CNR;Istituto )] TJ ET
BT 26.250 548.310 Td /F1 9.8 Tf  [(di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 528.905 Td /F1 9.8 Tf  [(Giovanna Loria, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione )] TJ ET
BT 26.250 517.000 Td /F1 9.8 Tf  [(/CNR;Istituto di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 497.595 Td /F1 9.8 Tf  [(Carla Piano, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione /CNR;Istituto di )] TJ ET
BT 26.250 485.691 Td /F1 9.8 Tf  [(Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 466.286 Td /F1 9.8 Tf  [(Piccininni Chiara, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione )] TJ ET
BT 26.250 454.381 Td /F1 9.8 Tf  [(/CNR;Istituto di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 434.976 Td /F1 9.8 Tf  [(Davide Quaranta, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione )] TJ ET
BT 26.250 423.072 Td /F1 9.8 Tf  [(/CNR;Istituto di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 403.667 Td /F1 9.8 Tf  [(Silvia Romano, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione /CNR;Istituto )] TJ ET
BT 26.250 391.762 Td /F1 9.8 Tf  [(di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 372.357 Td /F1 9.8 Tf  [(Francesco Soleti, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione )] TJ ET
BT 26.250 360.453 Td /F1 9.8 Tf  [(/CNR;Istituto di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 341.048 Td /F1 9.8 Tf  [(Maria Spadaro, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione /CNR;Istituto )] TJ ET
BT 26.250 329.143 Td /F1 9.8 Tf  [(di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 309.738 Td /F1 9.8 Tf  [(Paola Zinzi, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione /CNR;Istituto di )] TJ ET
BT 26.250 297.834 Td /F1 9.8 Tf  [(Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 278.429 Td /F1 9.8 Tf  [(Monique S.E. van Hout, Medisch Spectrum Twente, Ensched, Netherlands Jeroen P.P. van Vugt, Medisch Spectrum Twente, )] TJ ET
BT 26.250 266.524 Td /F1 9.8 Tf  [(Ensched, Netherlands A. Marit de Weert, Medisch Spectrum Twente, Ensched, Netherlands J.J.W. Bolwijn, Polikliniek )] TJ ET
BT 26.250 254.619 Td /F1 9.8 Tf  [(Neurologie, Groningen, Netherlands M. Dekker, Polikliniek Neurologie, Groningen, Netherlands K.L. Leenders, Polikliniek )] TJ ET
BT 26.250 242.715 Td /F1 9.8 Tf  [(Neurologie, Groningen, Netherlands J.C.H. van Oostrom, Polikliniek Neurologie, Groningen, Netherlands Reineke Bos, Leiden )] TJ ET
BT 26.250 230.810 Td /F1 9.8 Tf  [(University Medical Centre \(LUMC\), Leide, Netherlands Eve M. Dumas, Leiden University Medical Centre \(LUMC\), Leide, )] TJ ET
BT 26.250 218.905 Td /F1 9.8 Tf  [(Netherlands Caroline K. Jurgens, Leiden University Medical Centre \(LUMC\), Leide, Netherlands Simon J. A. van den Bogaard, )] TJ ET
BT 26.250 207.000 Td /F1 9.8 Tf  [(Leiden University Medical Centre \(LUMC\), Leide, Netherlands Raymund A.C. Roos, Leiden University Medical Centre \(LUMC\), )] TJ ET
BT 26.250 195.096 Td /F1 9.8 Tf  [(Leide, Netherlands Ellen P. �t Hart, Leiden University Medical Centre \(LUMC\), Leide, Netherlands Marie-No�lle Witjes-An�, )] TJ ET
BT 26.250 183.191 Td /F1 9.8 Tf  [(Leiden University Medical Centre \(LUMC\), Leide, Netherlands Berry Kremer, Universitair Medisch Centrum St. Radboud, )] TJ ET
BT 26.250 171.286 Td /F1 9.8 Tf  [(Neurology, Nijmege, Netherlands C.C.P. Verstappen, Universitair Medisch Centrum St. Radboud, Neurology, Nijmege, )] TJ ET
BT 26.250 159.381 Td /F1 9.8 Tf  [(Netherland Arvid Heiberg, Rikshospitalet, Dept. of Medical Genetics and Dep. of Neurology, Oslo University Hospital, Norway )] TJ ET
BT 26.250 147.477 Td /F1 9.8 Tf  [(Marleen R van Walsem, Rikshospitalet, Dept. of Medical Genetics and Dep. of Neurology, Oslo University Hospital, Norway Jan )] TJ ET
BT 26.250 135.572 Td /F1 9.8 Tf  [(Frich, Rikshospitalet, Dept. of Medical Genetics and Dep. of Neurology, Oslo University Hospital, Norway Olaf Aaserud, )] TJ ET
BT 26.250 123.667 Td /F1 9.8 Tf  [(Rikshospitalet, Dept. of Medical Genetics and Dep. of Neurology, Oslo University Hospital, Norway Raghild Wehu, )] TJ ET
BT 26.250 111.762 Td /F1 9.8 Tf  [(Rikshospitalet, Dept. of Medical Genetics and Dep. of Neurology, Oslo University Hospital, Norway Kathrine Bj�rgo, Ulleval, )] TJ ET
BT 26.250 99.858 Td /F1 9.8 Tf  [(Dept of Medical Genetics and Department, Oslo University Hospital, Norway Madelein Fannemel, Ulleval, Dept of Medical )] TJ ET
BT 26.250 87.953 Td /F1 9.8 Tf  [(Genetics and Department, Oslo University Hospital, Norway Per G�rvell, Ulleval, Dept of Medical Genetics and Department, )] TJ ET
BT 26.250 76.048 Td /F1 9.8 Tf  [(Oslo University Hospital, Norway Eirin Lorentzen, Ulleval, Dept of Medical Genetics and Department, Oslo University Hospital, )] TJ ET
BT 26.250 64.143 Td /F1 9.8 Tf  [(Norway Susana Pro Koivisto, Ulleval, Dept of Medical Genetics and Department, Oslo University Hospital, Norway Lars )] TJ ET
BT 26.250 52.239 Td /F1 9.8 Tf  [(Retterst�l, Ulleval, Dept of Medical Genetics and Department, Oslo University Hospital, Norway Inga Bj�rnevoll, St. Olavs )] TJ ET
BT 26.250 40.334 Td /F1 9.8 Tf  [(Hospital, Trondheim, Norway Sigrid Botne Sando, St. Olavs Hospital, Trondheim, Norway Emilia Sitek, St. Adalbert Hospital, )] TJ ET
Q
q
15.000 26.048 577.500 750.952 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(/CNR;Istituto di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 748.071 Td /F1 9.8 Tf  [(Claudio Catalli, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione /CNR;Istituto )] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 716.762 Td /F1 9.8 Tf  [(Raffaella Di Giacopo, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione )] TJ ET
BT 26.250 704.857 Td /F1 9.8 Tf  [(/CNR;Istituto di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 685.452 Td /F1 9.8 Tf  [(Alfonso Fasano, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione )] TJ ET
BT 26.250 673.548 Td /F1 9.8 Tf  [(/CNR;Istituto di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 654.143 Td /F1 9.8 Tf  [(Marina Frontali, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione /CNR;Istituto )] TJ ET
BT 26.250 642.238 Td /F1 9.8 Tf  [(di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 622.833 Td /F1 9.8 Tf  [(Arianna Guidubaldi, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione )] TJ ET
BT 26.250 610.929 Td /F1 9.8 Tf  [(/CNR;Istituto di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 591.524 Td /F1 9.8 Tf  [(Tamara Ialongo, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione )] TJ ET
BT 26.250 579.619 Td /F1 9.8 Tf  [(/CNR;Istituto di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 560.214 Td /F1 9.8 Tf  [(Gioia Jacopini, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione /CNR;Istituto )] TJ ET
BT 26.250 548.310 Td /F1 9.8 Tf  [(di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 528.905 Td /F1 9.8 Tf  [(Giovanna Loria, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione )] TJ ET
BT 26.250 517.000 Td /F1 9.8 Tf  [(/CNR;Istituto di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 497.595 Td /F1 9.8 Tf  [(Carla Piano, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione /CNR;Istituto di )] TJ ET
BT 26.250 485.691 Td /F1 9.8 Tf  [(Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 466.286 Td /F1 9.8 Tf  [(Piccininni Chiara, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione )] TJ ET
BT 26.250 454.381 Td /F1 9.8 Tf  [(/CNR;Istituto di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 434.976 Td /F1 9.8 Tf  [(Davide Quaranta, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione )] TJ ET
BT 26.250 423.072 Td /F1 9.8 Tf  [(/CNR;Istituto di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 403.667 Td /F1 9.8 Tf  [(Silvia Romano, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione /CNR;Istituto )] TJ ET
BT 26.250 391.762 Td /F1 9.8 Tf  [(di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 372.357 Td /F1 9.8 Tf  [(Francesco Soleti, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione )] TJ ET
BT 26.250 360.453 Td /F1 9.8 Tf  [(/CNR;Istituto di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 341.048 Td /F1 9.8 Tf  [(Maria Spadaro, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione /CNR;Istituto )] TJ ET
BT 26.250 329.143 Td /F1 9.8 Tf  [(di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 309.738 Td /F1 9.8 Tf  [(Paola Zinzi, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione /CNR;Istituto di )] TJ ET
BT 26.250 297.834 Td /F1 9.8 Tf  [(Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 278.429 Td /F1 9.8 Tf  [(Monique S.E. van Hout, Medisch Spectrum Twente, Ensched, Netherlands Jeroen P.P. van Vugt, Medisch Spectrum Twente, )] TJ ET
BT 26.250 266.524 Td /F1 9.8 Tf  [(Ensched, Netherlands A. Marit de Weert, Medisch Spectrum Twente, Ensched, Netherlands J.J.W. Bolwijn, Polikliniek )] TJ ET
BT 26.250 254.619 Td /F1 9.8 Tf  [(Neurologie, Groningen, Netherlands M. Dekker, Polikliniek Neurologie, Groningen, Netherlands K.L. Leenders, Polikliniek )] TJ ET
BT 26.250 242.715 Td /F1 9.8 Tf  [(Neurologie, Groningen, Netherlands J.C.H. van Oostrom, Polikliniek Neurologie, Groningen, Netherlands Reineke Bos, Leiden )] TJ ET
BT 26.250 230.810 Td /F1 9.8 Tf  [(University Medical Centre \(LUMC\), Leide, Netherlands Eve M. Dumas, Leiden University Medical Centre \(LUMC\), Leide, )] TJ ET
BT 26.250 218.905 Td /F1 9.8 Tf  [(Netherlands Caroline K. Jurgens, Leiden University Medical Centre \(LUMC\), Leide, Netherlands Simon J. A. van den Bogaard, )] TJ ET
BT 26.250 207.000 Td /F1 9.8 Tf  [(Leiden University Medical Centre \(LUMC\), Leide, Netherlands Raymund A.C. Roos, Leiden University Medical Centre \(LUMC\), )] TJ ET
BT 26.250 195.096 Td /F1 9.8 Tf  [(Leide, Netherlands Ellen P. �t Hart, Leiden University Medical Centre \(LUMC\), Leide, Netherlands Marie-No�lle Witjes-An�, )] TJ ET
BT 26.250 183.191 Td /F1 9.8 Tf  [(Leiden University Medical Centre \(LUMC\), Leide, Netherlands Berry Kremer, Universitair Medisch Centrum St. Radboud, )] TJ ET
BT 26.250 171.286 Td /F1 9.8 Tf  [(Neurology, Nijmege, Netherlands C.C.P. Verstappen, Universitair Medisch Centrum St. Radboud, Neurology, Nijmege, )] TJ ET
BT 26.250 159.381 Td /F1 9.8 Tf  [(Netherland Arvid Heiberg, Rikshospitalet, Dept. of Medical Genetics and Dep. of Neurology, Oslo University Hospital, Norway )] TJ ET
BT 26.250 147.477 Td /F1 9.8 Tf  [(Marleen R van Walsem, Rikshospitalet, Dept. of Medical Genetics and Dep. of Neurology, Oslo University Hospital, Norway Jan )] TJ ET
BT 26.250 135.572 Td /F1 9.8 Tf  [(Frich, Rikshospitalet, Dept. of Medical Genetics and Dep. of Neurology, Oslo University Hospital, Norway Olaf Aaserud, )] TJ ET
BT 26.250 123.667 Td /F1 9.8 Tf  [(Rikshospitalet, Dept. of Medical Genetics and Dep. of Neurology, Oslo University Hospital, Norway Raghild Wehu, )] TJ ET
BT 26.250 111.762 Td /F1 9.8 Tf  [(Rikshospitalet, Dept. of Medical Genetics and Dep. of Neurology, Oslo University Hospital, Norway Kathrine Bj�rgo, Ulleval, )] TJ ET
BT 26.250 99.858 Td /F1 9.8 Tf  [(Dept of Medical Genetics and Department, Oslo University Hospital, Norway Madelein Fannemel, Ulleval, Dept of Medical )] TJ ET
BT 26.250 87.953 Td /F1 9.8 Tf  [(Genetics and Department, Oslo University Hospital, Norway Per G�rvell, Ulleval, Dept of Medical Genetics and Department, )] TJ ET
BT 26.250 76.048 Td /F1 9.8 Tf  [(Oslo University Hospital, Norway Eirin Lorentzen, Ulleval, Dept of Medical Genetics and Department, Oslo University Hospital, )] TJ ET
BT 26.250 64.143 Td /F1 9.8 Tf  [(Norway Susana Pro Koivisto, Ulleval, Dept of Medical Genetics and Department, Oslo University Hospital, Norway Lars )] TJ ET
BT 26.250 52.239 Td /F1 9.8 Tf  [(Retterst�l, Ulleval, Dept of Medical Genetics and Department, Oslo University Hospital, Norway Inga Bj�rnevoll, St. Olavs )] TJ ET
BT 26.250 40.334 Td /F1 9.8 Tf  [(Hospital, Trondheim, Norway Sigrid Botne Sando, St. Olavs Hospital, Trondheim, Norway Emilia Sitek, St. Adalbert Hospital, )] TJ ET
Q
q
15.000 26.048 577.500 750.952 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(/CNR;Istituto di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 748.071 Td /F1 9.8 Tf  [(Claudio Catalli, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione /CNR;Istituto )] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 716.762 Td /F1 9.8 Tf  [(Raffaella Di Giacopo, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione )] TJ ET
BT 26.250 704.857 Td /F1 9.8 Tf  [(/CNR;Istituto di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 685.452 Td /F1 9.8 Tf  [(Alfonso Fasano, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione )] TJ ET
BT 26.250 673.548 Td /F1 9.8 Tf  [(/CNR;Istituto di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 654.143 Td /F1 9.8 Tf  [(Marina Frontali, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione /CNR;Istituto )] TJ ET
BT 26.250 642.238 Td /F1 9.8 Tf  [(di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 622.833 Td /F1 9.8 Tf  [(Arianna Guidubaldi, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione )] TJ ET
BT 26.250 610.929 Td /F1 9.8 Tf  [(/CNR;Istituto di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 591.524 Td /F1 9.8 Tf  [(Tamara Ialongo, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione )] TJ ET
BT 26.250 579.619 Td /F1 9.8 Tf  [(/CNR;Istituto di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 560.214 Td /F1 9.8 Tf  [(Gioia Jacopini, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione /CNR;Istituto )] TJ ET
BT 26.250 548.310 Td /F1 9.8 Tf  [(di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 528.905 Td /F1 9.8 Tf  [(Giovanna Loria, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione )] TJ ET
BT 26.250 517.000 Td /F1 9.8 Tf  [(/CNR;Istituto di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 497.595 Td /F1 9.8 Tf  [(Carla Piano, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione /CNR;Istituto di )] TJ ET
BT 26.250 485.691 Td /F1 9.8 Tf  [(Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 466.286 Td /F1 9.8 Tf  [(Piccininni Chiara, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione )] TJ ET
BT 26.250 454.381 Td /F1 9.8 Tf  [(/CNR;Istituto di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 434.976 Td /F1 9.8 Tf  [(Davide Quaranta, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione )] TJ ET
BT 26.250 423.072 Td /F1 9.8 Tf  [(/CNR;Istituto di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 403.667 Td /F1 9.8 Tf  [(Silvia Romano, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione /CNR;Istituto )] TJ ET
BT 26.250 391.762 Td /F1 9.8 Tf  [(di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 372.357 Td /F1 9.8 Tf  [(Francesco Soleti, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione )] TJ ET
BT 26.250 360.453 Td /F1 9.8 Tf  [(/CNR;Istituto di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 341.048 Td /F1 9.8 Tf  [(Maria Spadaro, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione /CNR;Istituto )] TJ ET
BT 26.250 329.143 Td /F1 9.8 Tf  [(di Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 309.738 Td /F1 9.8 Tf  [(Paola Zinzi, Istituto di Neurobiologia e Medicina Molecolare & Istituto di Scienze e Tecnologie della Cognizione /CNR;Istituto di )] TJ ET
BT 26.250 297.834 Td /F1 9.8 Tf  [(Neurologia Universit� Cattolica del Sacro Cuore, Rome, Italy)] TJ ET
BT 26.250 278.429 Td /F1 9.8 Tf  [(Monique S.E. van Hout, Medisch Spectrum Twente, Ensched, Netherlands Jeroen P.P. van Vugt, Medisch Spectrum Twente, )] TJ ET
BT 26.250 266.524 Td /F1 9.8 Tf  [(Ensched, Netherlands A. Marit de Weert, Medisch Spectrum Twente, Ensched, Netherlands J.J.W. Bolwijn, Polikliniek )] TJ ET
BT 26.250 254.619 Td /F1 9.8 Tf  [(Neurologie, Groningen, Netherlands M. Dekker, Polikliniek Neurologie, Groningen, Netherlands K.L. Leenders, Polikliniek )] TJ ET
BT 26.250 242.715 Td /F1 9.8 Tf  [(Neurologie, Groningen, Netherlands J.C.H. van Oostrom, Polikliniek Neurologie, Groningen, Netherlands Reineke Bos, Leiden )] TJ ET
BT 26.250 230.810 Td /F1 9.8 Tf  [(University Medical Centre \(LUMC\), Leide, Netherlands Eve M. Dumas, Leiden University Medical Centre \(LUMC\), Leide, )] TJ ET
BT 26.250 218.905 Td /F1 9.8 Tf  [(Netherlands Caroline K. Jurgens, Leiden University Medical Centre \(LUMC\), Leide, Netherlands Simon J. A. van den Bogaard, )] TJ ET
BT 26.250 207.000 Td /F1 9.8 Tf  [(Leiden University Medical Centre \(LUMC\), Leide, Netherlands Raymund A.C. Roos, Leiden University Medical Centre \(LUMC\), )] TJ ET
BT 26.250 195.096 Td /F1 9.8 Tf  [(Leide, Netherlands Ellen P. �t Hart, Leiden University Medical Centre \(LUMC\), Leide, Netherlands Marie-No�lle Witjes-An�, )] TJ ET
BT 26.250 183.191 Td /F1 9.8 Tf  [(Leiden University Medical Centre \(LUMC\), Leide, Netherlands Berry Kremer, Universitair Medisch Centrum St. Radboud, )] TJ ET
BT 26.250 171.286 Td /F1 9.8 Tf  [(Neurology, Nijmege, Netherlands C.C.P. Verstappen, Universitair Medisch Centrum St. Radboud, Neurology, Nijmege, )] TJ ET
BT 26.250 159.381 Td /F1 9.8 Tf  [(Netherland Arvid Heiberg, Rikshospitalet, Dept. of Medical Genetics and Dep. of Neurology, Oslo University Hospital, Norway )] TJ ET
BT 26.250 147.477 Td /F1 9.8 Tf  [(Marleen R van Walsem, Rikshospitalet, Dept. of Medical Genetics and Dep. of Neurology, Oslo University Hospital, Norway Jan )] TJ ET
BT 26.250 135.572 Td /F1 9.8 Tf  [(Frich, Rikshospitalet, Dept. of Medical Genetics and Dep. of Neurology, Oslo University Hospital, Norway Olaf Aaserud, )] TJ ET
BT 26.250 123.667 Td /F1 9.8 Tf  [(Rikshospitalet, Dept. of Medical Genetics and Dep. of Neurology, Oslo University Hospital, Norway Raghild Wehu, )] TJ ET
BT 26.250 111.762 Td /F1 9.8 Tf  [(Rikshospitalet, Dept. of Medical Genetics and Dep. of Neurology, Oslo University Hospital, Norway Kathrine Bj�rgo, Ulleval, )] TJ ET
BT 26.250 99.858 Td /F1 9.8 Tf  [(Dept of Medical Genetics and Department, Oslo University Hospital, Norway Madelein Fannemel, Ulleval, Dept of Medical )] TJ ET
BT 26.250 87.953 Td /F1 9.8 Tf  [(Genetics and Department, Oslo University Hospital, Norway Per G�rvell, Ulleval, Dept of Medical Genetics and Department, )] TJ ET
BT 26.250 76.048 Td /F1 9.8 Tf  [(Oslo University Hospital, Norway Eirin Lorentzen, Ulleval, Dept of Medical Genetics and Department, Oslo University Hospital, )] TJ ET
BT 26.250 64.143 Td /F1 9.8 Tf  [(Norway Susana Pro Koivisto, Ulleval, Dept of Medical Genetics and Department, Oslo University Hospital, Norway Lars )] TJ ET
BT 26.250 52.239 Td /F1 9.8 Tf  [(Retterst�l, Ulleval, Dept of Medical Genetics and Department, Oslo University Hospital, Norway Inga Bj�rnevoll, St. Olavs )] TJ ET
BT 26.250 40.334 Td /F1 9.8 Tf  [(Hospital, Trondheim, Norway Sigrid Botne Sando, St. Olavs Hospital, Trondheim, Norway Emilia Sitek, St. Adalbert Hospital, )] TJ ET
Q
q
0.000 0.000 0.000 rg
BT 291.710 19.825 Td /F1 11.0 Tf  [(9)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Huntington Disease)] TJ ET

Q
endstream
endobj
189 0 obj
<< /Type /Page
/Parent 3 0 R
/Contents 190 0 R
>>
endobj
190 0 obj
<<
/Length 31496 >>
stream

0.271 0.267 0.267 rg
q
15.000 15.096 577.500 761.904 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(Gdansk; Medical University of Gdansk, Neurological and Psychiatric Nursing Dpt., Gdansk, Poland Jaroslaw Slawek, St. )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(Adalbert Hospital, Gdansk; Medical University of Gdansk, Neurological and Psychiatric Nursing Dpt., Gdansk, Poland Witold )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(Soltan, St. Adalbert Hospital, Gdansk; Medical University of Gdansk, Neurological and Psychiatric Nursing Dpt., Gdansk, )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(Poland Magdalena Boczarska-Jedynak, Silesian Medical University Katowice, Katowice, Poland Barbara Jasinska-Myga, )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(Silesian Medical University Katowice, Katowice, Poland Gregorz Opala, Silesian Medical University Katowice, Katowice, Poland )] TJ ET
BT 26.250 707.952 Td /F1 9.8 Tf  [(Gabriela K?odowska � Duda, Silesian Medical University Katowice, Katowice, Poland Krzysztof Banaszkiewicz, Krakowska )] TJ ET
BT 26.250 696.048 Td /F1 9.8 Tf  [(Akademia Neurologii, Krako, Poland Andrzej Szczudlik, Krakowska Akademia Neurologii, Krako, Poland Monika Rudzi?ska, )] TJ ET
BT 26.250 684.143 Td /F1 9.8 Tf  [(Krakowska Akademia Neurologii, Krako, Poland Magdalena W�jcik, Krakowska Akademia Neurologii, Krako, Poland )] TJ ET
BT 26.250 672.238 Td /F1 9.8 Tf  [(Ma?gorzata Dec, Krakowska Akademia Neurologii, Krako, Poland Malgorzata Krawczyk, Krakowska Akademia Neurologii, )] TJ ET
BT 26.250 660.333 Td /F1 9.8 Tf  [(Krako, Poland Anna Bryl, Medical University of Pozna?, Poznan, Poland Anna Ciesielska, Medical University of Pozna?, )] TJ ET
BT 26.250 648.429 Td /F1 9.8 Tf  [(Poznan, Poland Aneta Klimberg, Medical University of Pozna?, Poznan, Poland Jerzy Marcinkowski, Medical University of )] TJ ET
BT 26.250 636.524 Td /F1 9.8 Tf  [(Pozna?, Poznan, Poland Justyna Sempo?owicz, Medical University of Pozna?, Poznan, Poland Daniel Zielonka, Medical )] TJ ET
BT 26.250 624.619 Td /F1 9.8 Tf  [(University of Pozna?, Poznan, Poland Husam Samara, Medical University of Pozna?, Poznan, Poland Piotr Janik, Medical )] TJ ET
BT 26.250 612.714 Td /F1 9.8 Tf  [(University of Warsaw, Neurology, Warsaw-MU, Poland Anna Gogol, Medical University of Warsaw, Neurology, Warsaw-MU, )] TJ ET
BT 26.250 600.810 Td /F1 9.8 Tf  [(Poland Hubert Kwiecinski, Medical University of Warsaw, Neurology, Warsaw-MU, Poland Zygmunt Jamrozik, Medical )] TJ ET
BT 26.250 588.905 Td /F1 9.8 Tf  [(University of Warsaw, Neurology, Warsaw-MU, Poland Jakub Antczak, Institute of Psychiatry and Neurology Dep. of Genetics, )] TJ ET
BT 26.250 577.000 Td /F1 9.8 Tf  [(Dep. of Neurology, Warsaw-IPiN, Poland Katarzyna Jachinska, Institute of Psychiatry and Neurology Dep. of Genetics, Dep. of )] TJ ET
BT 26.250 565.095 Td /F1 9.8 Tf  [(Neurology, Warsaw-IPiN, Poland Maria Rakowicz, Institute of Psychiatry and Neurology Dep. of Genetics, Dep. of Neurology, )] TJ ET
BT 26.250 553.191 Td /F1 9.8 Tf  [(Warsaw-IPiN, Poland Przemyslaw Richter, Institute of Psychiatry and Neurology Dep. of Genetics, Dep. of Neurology, Warsaw-)] TJ ET
BT 26.250 541.286 Td /F1 9.8 Tf  [(IPiN, Poland Danuta Ryglewicz, Institute of Psychiatry and Neurology Dep. of Genetics, Dep. of Neurology, Warsaw-IPiN, )] TJ ET
BT 26.250 529.381 Td /F1 9.8 Tf  [(Poland Grzegorz Witkowski, Institute of Psychiatry and Neurology Dep. of Genetics, Dep. of Neurology, Warsaw-IPiN, Poland )] TJ ET
BT 26.250 517.476 Td /F1 9.8 Tf  [(Elzbieta Zdzienicka, Institute of Psychiatry and Neurology Dep. of Genetics, Dep. of Neurology, Warsaw-IPiN, Poland Jacek )] TJ ET
BT 26.250 505.572 Td /F1 9.8 Tf  [(Zaremba, Institute of Psychiatry and Neurology Dep. of Genetics, Dep. of Neurology, Warsaw-IPiN, Poland Anna Su?ek, )] TJ ET
BT 26.250 493.667 Td /F1 9.8 Tf  [(Institute of Psychiatry and Neurology Dep. of Genetics, Dep. of Neurology, Warsaw-IPiN, Poland Wioletta Krysa, Institute of )] TJ ET
BT 26.250 481.762 Td /F1 9.8 Tf  [(Psychiatry and Neurology Dep. of Genetics, Dep. of Neurology, Warsaw-IPiN, Poland Tiago Mestre)] TJ ET
BT 454.324 481.762 Td /F4 9.8 Tf  [(, )] TJ ET
BT 459.745 481.762 Td /F1 9.8 Tf  [(Hospital de Santa Maria; )] TJ ET
BT 26.250 469.857 Td /F1 9.8 Tf  [(Neurological Clinical Research Unit, Instituto de Medicina Molecular, Lisbon, Portugal Leonor Correia-Guedes, Hospital de )] TJ ET
BT 26.250 457.953 Td /F1 9.8 Tf  [(Santa Maria; Neurological Clinical Research Unit, Instituto de Medicina Molecular, Lisbon, Portugal Miguel Coelho, Hospital de )] TJ ET
BT 26.250 446.048 Td /F1 9.8 Tf  [(Santa Maria; Neurological Clinical Research Unit, Instituto de Medicina Molecular, Lisbon, Portugal Joaquim J Ferreira, Hospital )] TJ ET
BT 26.250 434.143 Td /F1 9.8 Tf  [(de Santa Maria; Neurological Clinical Research Unit, Instituto de Medicina Molecular, Lisbon, Portugal �ngela Tim�teo, Hospital )] TJ ET
BT 26.250 422.238 Td /F1 9.8 Tf  [(Fernando da Fonseca, Lisbon, Portugal Cristina Costa, Hospital Fernando da Fonseca, Lisbon, Portugal Miguel Gago, Hospital )] TJ ET
BT 26.250 410.334 Td /F1 9.8 Tf  [(de S�o Jo�o, Porto, Portugal Carolina Garrett, Hospital de S�o Jo�o, Porto, Portugal Maria Ros�lia Guerra, Hospital de S�o )] TJ ET
BT 26.250 398.429 Td /F1 9.8 Tf  [(Jo�o, Porto, Portugal Carmen Dur�n Herrera, Hospital Infanta Cristina, Badajoz, Spain Patrocinio Moreno Garcia, Hospital )] TJ ET
BT 26.250 386.524 Td /F1 9.8 Tf  [(Infanta Cristina, Badajoz, Spain Francisco Barrero, Hospital Universitario San Cecilio, Neurolog�a, Granada, Spain Blas Morale, )] TJ ET
BT 26.250 374.619 Td /F1 9.8 Tf  [(Hospital Universitario San Cecilio, Neurolog�a, Granada, Spain Esther Cubo, Servicio de Neurolog�a Hospital General Yag�e, )] TJ ET
BT 26.250 362.715 Td /F1 9.8 Tf  [(Burgos, Spain Natividad Mariscal, Servicio de Neurolog�a Hospital General Yag�e, Burgos, Spain Jes�s S�nchez, Servicio de )] TJ ET
BT 26.250 350.810 Td /F1 9.8 Tf  [(Neurolog�a Hospital General Yag�e, Burgos, Spain Fernando Alonso-Frech, Hospital Universitario de Fuenlabrada, )] TJ ET
BT 26.250 338.905 Td /F1 9.8 Tf  [(Fuenlabrada, Spain Maria Rabasa Perez, Hospital Universitario de Fuenlabrada, Fuenlabrada, Spain Mar�a Fenollar, Hospital )] TJ ET
BT 26.250 327.000 Td /F1 9.8 Tf  [(Cl�nico Universitario San Carlos, Madrid-Clinico, Spain Roc�o Garc�a-Ramos Garc�a, Hospital Cl�nico Universitario San Carlos, )] TJ ET
BT 26.250 315.096 Td /F1 9.8 Tf  [(Madrid-Clinico, Spain Purificacion Pin Quiroga, Hospital Cl�nico Universitario San Carlos, Madrid-Clinico, Spain Susana )] TJ ET
BT 26.250 303.191 Td /F1 9.8 Tf  [(V�zquez Rivera, Hospital Cl�nico Universitario San Carlos, Madrid-Clinico, Spain Clara Villanuev, Hospital Cl�nico Universitario )] TJ ET
BT 26.250 291.286 Td /F1 9.8 Tf  [(San Carlos, Madrid-Clinico, Spain M�nica Bascu�ana, Hospital Ram�n y Cajal, Neurolog�a, Madrid RYC, Spain Marta Fat�s )] TJ ET
BT 26.250 279.381 Td /F1 9.8 Tf  [(Ventura, Hospital Ram�n y Cajal, Neurolog�a, Madrid RYC, Spain Guillermo Garc�a Ribas, Garcia Riva, Hospital Ram�n y )] TJ ET
BT 26.250 267.477 Td /F1 9.8 Tf  [(Cajal, Neurolog�a, Madrid RYC, Spain Justo Garc�a de Y�benes, Hospital Ram�n y Cajal, Neurolog�a, Madrid RYC, Spain Jos� )] TJ ET
BT 26.250 255.572 Td /F1 9.8 Tf  [(Luis L�pez � Send�n Moreno, Hospital Ram�n y Cajal, Neurolog�a, Madrid RYC, Spain Patricia Trigo Cubillo, Hospital Ram�n y )] TJ ET
BT 26.250 243.667 Td /F1 9.8 Tf  [(Cajal, Neurolog�a, Madrid RYC, Spain Pedro J Garc�a Ru�z, Madrid-Fundaci�n Jim�nez D�az, Madrid FJD, Spain Asunci�n )] TJ ET
BT 26.250 231.762 Td /F1 9.8 Tf  [(Mart�nez-Descals, Madrid-Fundaci�n Jim�nez D�az, Madrid FJD, Spain Mar�a Jos� Saiz Artiga, Madrid-Fundaci�n Jim�nez )] TJ ET
BT 26.250 219.858 Td /F1 9.8 Tf  [(D�az, Madrid FJD, Spain Vicenta S�nchez, Madrid-Fundaci�n Jim�nez D�az, Madrid FJD, Spain Miquel Aguilar Barbera, )] TJ ET
BT 26.250 207.953 Td /F1 9.8 Tf  [(Barcelona-Hospital M�tua de Terrassa, Spain Dolors Badenes Guia, Barcelona-Hospital M�tua de Terrassa, Spain Laura )] TJ ET
BT 26.250 196.048 Td /F1 9.8 Tf  [(Casas Hernanz, Barcelona-Hospital M�tua de Terrassa, Spain Judit L�pez Catena, Barcelona-Hospital M�tua de Terrassa, )] TJ ET
BT 26.250 184.143 Td /F1 9.8 Tf  [(Spain Ana Rojo Sebasti�n, Barcelona-Hospital M�tua de Terrassa, Spain Pilar Quil�z Ferrer, Barcelona-Hospital M�tua de )] TJ ET
BT 26.250 172.239 Td /F1 9.8 Tf  [(Terrassa, Spain Gemma Tome Carruesco, Barcelona-Hospital M�tua de Terrassa, Spain Jordi Bas, Hospital Universitari de )] TJ ET
BT 26.250 160.334 Td /F1 9.8 Tf  [(Bellvitge, Barcelona-Bellvitge, Spain N�ria Busquets, Hospital Universitari de Bellvitge, Barcelona-Bellvitge, Spain Matilde )] TJ ET
BT 26.250 148.429 Td /F1 9.8 Tf  [(Calopa, Hospital Universitari de Bellvitge, Barcelona-Bellvitge, Spain Maria Teresa Buongiorno, Barcelona- Hospital Clinico, )] TJ ET
BT 26.250 136.524 Td /F1 9.8 Tf  [(Spain Esteban Mu�oz, Barcelona- Hospital Clinico, Spain Marina Dalmau Elorza, Hospital Mare de Deu de La Merced, )] TJ ET
BT 26.250 124.620 Td /F1 9.8 Tf  [(Barcelona-Merced, Spain Crist�bal D�ez-Aja L�pez, Hospital Mare de Deu de La Merced, Barcelona-Merced, Spain Santiago )] TJ ET
BT 26.250 112.715 Td /F1 9.8 Tf  [(Dur�n-Sindreu Terol, Hospital Mare de Deu de La Merced, Barcelona-Merced, Spain Misericordia Floriach Robert, Hospital )] TJ ET
BT 26.250 100.810 Td /F1 9.8 Tf  [(Mare de Deu de La Merced, Barcelona-Merced, Spain Bel�n Garz�n Ru�z, Hospital Mare de Deu de La Merced, Barcelona-)] TJ ET
BT 26.250 88.905 Td /F1 9.8 Tf  [(Merced, Spain Ana Gonz�lez Casado, Hospital Mare de Deu de La Merced, Barcelona-Merced, Spain Isabel Haro Mart�nez, )] TJ ET
BT 26.250 77.001 Td /F1 9.8 Tf  [(Hospital Mare de Deu de La Merced, Barcelona-Merced, Spain Celia Mareca Viladrich, Hospital Mare de Deu de La Merced, )] TJ ET
BT 26.250 65.096 Td /F1 9.8 Tf  [(Barcelona-Merced, Spain Regina Pons i C�rdenas, Hospital Mare de Deu de La Merced, Barcelona-Merced, Spain Elvira Roca, )] TJ ET
BT 26.250 53.191 Td /F1 9.8 Tf  [(Hospital Mare de Deu de La Merced, Barcelona-Merced, Spain Joan Roig Llesoy, Hospital Mare de Deu de La Merced, )] TJ ET
BT 26.250 41.286 Td /F1 9.8 Tf  [(Barcelona-Merced, Spain Jes�s Miguel Ruiz Idiago, Hospital Mare de Deu de La Merced, Barcelona-Merced, Spain Mar Ru�z )] TJ ET
BT 26.250 29.382 Td /F1 9.8 Tf  [(Vergara, Hospital Mare de Deu de La Merced, Barcelona-Merced, Spain Socorro Soriano Garc�a, Hospital Mare de Deu de La )] TJ ET
Q
q
15.000 15.096 577.500 761.904 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(Gdansk; Medical University of Gdansk, Neurological and Psychiatric Nursing Dpt., Gdansk, Poland Jaroslaw Slawek, St. )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(Adalbert Hospital, Gdansk; Medical University of Gdansk, Neurological and Psychiatric Nursing Dpt., Gdansk, Poland Witold )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(Soltan, St. Adalbert Hospital, Gdansk; Medical University of Gdansk, Neurological and Psychiatric Nursing Dpt., Gdansk, )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(Poland Magdalena Boczarska-Jedynak, Silesian Medical University Katowice, Katowice, Poland Barbara Jasinska-Myga, )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(Silesian Medical University Katowice, Katowice, Poland Gregorz Opala, Silesian Medical University Katowice, Katowice, Poland )] TJ ET
BT 26.250 707.952 Td /F1 9.8 Tf  [(Gabriela K?odowska � Duda, Silesian Medical University Katowice, Katowice, Poland Krzysztof Banaszkiewicz, Krakowska )] TJ ET
BT 26.250 696.048 Td /F1 9.8 Tf  [(Akademia Neurologii, Krako, Poland Andrzej Szczudlik, Krakowska Akademia Neurologii, Krako, Poland Monika Rudzi?ska, )] TJ ET
BT 26.250 684.143 Td /F1 9.8 Tf  [(Krakowska Akademia Neurologii, Krako, Poland Magdalena W�jcik, Krakowska Akademia Neurologii, Krako, Poland )] TJ ET
BT 26.250 672.238 Td /F1 9.8 Tf  [(Ma?gorzata Dec, Krakowska Akademia Neurologii, Krako, Poland Malgorzata Krawczyk, Krakowska Akademia Neurologii, )] TJ ET
BT 26.250 660.333 Td /F1 9.8 Tf  [(Krako, Poland Anna Bryl, Medical University of Pozna?, Poznan, Poland Anna Ciesielska, Medical University of Pozna?, )] TJ ET
BT 26.250 648.429 Td /F1 9.8 Tf  [(Poznan, Poland Aneta Klimberg, Medical University of Pozna?, Poznan, Poland Jerzy Marcinkowski, Medical University of )] TJ ET
BT 26.250 636.524 Td /F1 9.8 Tf  [(Pozna?, Poznan, Poland Justyna Sempo?owicz, Medical University of Pozna?, Poznan, Poland Daniel Zielonka, Medical )] TJ ET
BT 26.250 624.619 Td /F1 9.8 Tf  [(University of Pozna?, Poznan, Poland Husam Samara, Medical University of Pozna?, Poznan, Poland Piotr Janik, Medical )] TJ ET
BT 26.250 612.714 Td /F1 9.8 Tf  [(University of Warsaw, Neurology, Warsaw-MU, Poland Anna Gogol, Medical University of Warsaw, Neurology, Warsaw-MU, )] TJ ET
BT 26.250 600.810 Td /F1 9.8 Tf  [(Poland Hubert Kwiecinski, Medical University of Warsaw, Neurology, Warsaw-MU, Poland Zygmunt Jamrozik, Medical )] TJ ET
BT 26.250 588.905 Td /F1 9.8 Tf  [(University of Warsaw, Neurology, Warsaw-MU, Poland Jakub Antczak, Institute of Psychiatry and Neurology Dep. of Genetics, )] TJ ET
BT 26.250 577.000 Td /F1 9.8 Tf  [(Dep. of Neurology, Warsaw-IPiN, Poland Katarzyna Jachinska, Institute of Psychiatry and Neurology Dep. of Genetics, Dep. of )] TJ ET
BT 26.250 565.095 Td /F1 9.8 Tf  [(Neurology, Warsaw-IPiN, Poland Maria Rakowicz, Institute of Psychiatry and Neurology Dep. of Genetics, Dep. of Neurology, )] TJ ET
BT 26.250 553.191 Td /F1 9.8 Tf  [(Warsaw-IPiN, Poland Przemyslaw Richter, Institute of Psychiatry and Neurology Dep. of Genetics, Dep. of Neurology, Warsaw-)] TJ ET
BT 26.250 541.286 Td /F1 9.8 Tf  [(IPiN, Poland Danuta Ryglewicz, Institute of Psychiatry and Neurology Dep. of Genetics, Dep. of Neurology, Warsaw-IPiN, )] TJ ET
BT 26.250 529.381 Td /F1 9.8 Tf  [(Poland Grzegorz Witkowski, Institute of Psychiatry and Neurology Dep. of Genetics, Dep. of Neurology, Warsaw-IPiN, Poland )] TJ ET
BT 26.250 517.476 Td /F1 9.8 Tf  [(Elzbieta Zdzienicka, Institute of Psychiatry and Neurology Dep. of Genetics, Dep. of Neurology, Warsaw-IPiN, Poland Jacek )] TJ ET
BT 26.250 505.572 Td /F1 9.8 Tf  [(Zaremba, Institute of Psychiatry and Neurology Dep. of Genetics, Dep. of Neurology, Warsaw-IPiN, Poland Anna Su?ek, )] TJ ET
BT 26.250 493.667 Td /F1 9.8 Tf  [(Institute of Psychiatry and Neurology Dep. of Genetics, Dep. of Neurology, Warsaw-IPiN, Poland Wioletta Krysa, Institute of )] TJ ET
BT 26.250 481.762 Td /F1 9.8 Tf  [(Psychiatry and Neurology Dep. of Genetics, Dep. of Neurology, Warsaw-IPiN, Poland Tiago Mestre)] TJ ET
BT 454.324 481.762 Td /F4 9.8 Tf  [(, )] TJ ET
BT 459.745 481.762 Td /F1 9.8 Tf  [(Hospital de Santa Maria; )] TJ ET
BT 26.250 469.857 Td /F1 9.8 Tf  [(Neurological Clinical Research Unit, Instituto de Medicina Molecular, Lisbon, Portugal Leonor Correia-Guedes, Hospital de )] TJ ET
BT 26.250 457.953 Td /F1 9.8 Tf  [(Santa Maria; Neurological Clinical Research Unit, Instituto de Medicina Molecular, Lisbon, Portugal Miguel Coelho, Hospital de )] TJ ET
BT 26.250 446.048 Td /F1 9.8 Tf  [(Santa Maria; Neurological Clinical Research Unit, Instituto de Medicina Molecular, Lisbon, Portugal Joaquim J Ferreira, Hospital )] TJ ET
BT 26.250 434.143 Td /F1 9.8 Tf  [(de Santa Maria; Neurological Clinical Research Unit, Instituto de Medicina Molecular, Lisbon, Portugal �ngela Tim�teo, Hospital )] TJ ET
BT 26.250 422.238 Td /F1 9.8 Tf  [(Fernando da Fonseca, Lisbon, Portugal Cristina Costa, Hospital Fernando da Fonseca, Lisbon, Portugal Miguel Gago, Hospital )] TJ ET
BT 26.250 410.334 Td /F1 9.8 Tf  [(de S�o Jo�o, Porto, Portugal Carolina Garrett, Hospital de S�o Jo�o, Porto, Portugal Maria Ros�lia Guerra, Hospital de S�o )] TJ ET
BT 26.250 398.429 Td /F1 9.8 Tf  [(Jo�o, Porto, Portugal Carmen Dur�n Herrera, Hospital Infanta Cristina, Badajoz, Spain Patrocinio Moreno Garcia, Hospital )] TJ ET
BT 26.250 386.524 Td /F1 9.8 Tf  [(Infanta Cristina, Badajoz, Spain Francisco Barrero, Hospital Universitario San Cecilio, Neurolog�a, Granada, Spain Blas Morale, )] TJ ET
BT 26.250 374.619 Td /F1 9.8 Tf  [(Hospital Universitario San Cecilio, Neurolog�a, Granada, Spain Esther Cubo, Servicio de Neurolog�a Hospital General Yag�e, )] TJ ET
BT 26.250 362.715 Td /F1 9.8 Tf  [(Burgos, Spain Natividad Mariscal, Servicio de Neurolog�a Hospital General Yag�e, Burgos, Spain Jes�s S�nchez, Servicio de )] TJ ET
BT 26.250 350.810 Td /F1 9.8 Tf  [(Neurolog�a Hospital General Yag�e, Burgos, Spain Fernando Alonso-Frech, Hospital Universitario de Fuenlabrada, )] TJ ET
BT 26.250 338.905 Td /F1 9.8 Tf  [(Fuenlabrada, Spain Maria Rabasa Perez, Hospital Universitario de Fuenlabrada, Fuenlabrada, Spain Mar�a Fenollar, Hospital )] TJ ET
BT 26.250 327.000 Td /F1 9.8 Tf  [(Cl�nico Universitario San Carlos, Madrid-Clinico, Spain Roc�o Garc�a-Ramos Garc�a, Hospital Cl�nico Universitario San Carlos, )] TJ ET
BT 26.250 315.096 Td /F1 9.8 Tf  [(Madrid-Clinico, Spain Purificacion Pin Quiroga, Hospital Cl�nico Universitario San Carlos, Madrid-Clinico, Spain Susana )] TJ ET
BT 26.250 303.191 Td /F1 9.8 Tf  [(V�zquez Rivera, Hospital Cl�nico Universitario San Carlos, Madrid-Clinico, Spain Clara Villanuev, Hospital Cl�nico Universitario )] TJ ET
BT 26.250 291.286 Td /F1 9.8 Tf  [(San Carlos, Madrid-Clinico, Spain M�nica Bascu�ana, Hospital Ram�n y Cajal, Neurolog�a, Madrid RYC, Spain Marta Fat�s )] TJ ET
BT 26.250 279.381 Td /F1 9.8 Tf  [(Ventura, Hospital Ram�n y Cajal, Neurolog�a, Madrid RYC, Spain Guillermo Garc�a Ribas, Garcia Riva, Hospital Ram�n y )] TJ ET
BT 26.250 267.477 Td /F1 9.8 Tf  [(Cajal, Neurolog�a, Madrid RYC, Spain Justo Garc�a de Y�benes, Hospital Ram�n y Cajal, Neurolog�a, Madrid RYC, Spain Jos� )] TJ ET
BT 26.250 255.572 Td /F1 9.8 Tf  [(Luis L�pez � Send�n Moreno, Hospital Ram�n y Cajal, Neurolog�a, Madrid RYC, Spain Patricia Trigo Cubillo, Hospital Ram�n y )] TJ ET
BT 26.250 243.667 Td /F1 9.8 Tf  [(Cajal, Neurolog�a, Madrid RYC, Spain Pedro J Garc�a Ru�z, Madrid-Fundaci�n Jim�nez D�az, Madrid FJD, Spain Asunci�n )] TJ ET
BT 26.250 231.762 Td /F1 9.8 Tf  [(Mart�nez-Descals, Madrid-Fundaci�n Jim�nez D�az, Madrid FJD, Spain Mar�a Jos� Saiz Artiga, Madrid-Fundaci�n Jim�nez )] TJ ET
BT 26.250 219.858 Td /F1 9.8 Tf  [(D�az, Madrid FJD, Spain Vicenta S�nchez, Madrid-Fundaci�n Jim�nez D�az, Madrid FJD, Spain Miquel Aguilar Barbera, )] TJ ET
BT 26.250 207.953 Td /F1 9.8 Tf  [(Barcelona-Hospital M�tua de Terrassa, Spain Dolors Badenes Guia, Barcelona-Hospital M�tua de Terrassa, Spain Laura )] TJ ET
BT 26.250 196.048 Td /F1 9.8 Tf  [(Casas Hernanz, Barcelona-Hospital M�tua de Terrassa, Spain Judit L�pez Catena, Barcelona-Hospital M�tua de Terrassa, )] TJ ET
BT 26.250 184.143 Td /F1 9.8 Tf  [(Spain Ana Rojo Sebasti�n, Barcelona-Hospital M�tua de Terrassa, Spain Pilar Quil�z Ferrer, Barcelona-Hospital M�tua de )] TJ ET
BT 26.250 172.239 Td /F1 9.8 Tf  [(Terrassa, Spain Gemma Tome Carruesco, Barcelona-Hospital M�tua de Terrassa, Spain Jordi Bas, Hospital Universitari de )] TJ ET
BT 26.250 160.334 Td /F1 9.8 Tf  [(Bellvitge, Barcelona-Bellvitge, Spain N�ria Busquets, Hospital Universitari de Bellvitge, Barcelona-Bellvitge, Spain Matilde )] TJ ET
BT 26.250 148.429 Td /F1 9.8 Tf  [(Calopa, Hospital Universitari de Bellvitge, Barcelona-Bellvitge, Spain Maria Teresa Buongiorno, Barcelona- Hospital Clinico, )] TJ ET
BT 26.250 136.524 Td /F1 9.8 Tf  [(Spain Esteban Mu�oz, Barcelona- Hospital Clinico, Spain Marina Dalmau Elorza, Hospital Mare de Deu de La Merced, )] TJ ET
BT 26.250 124.620 Td /F1 9.8 Tf  [(Barcelona-Merced, Spain Crist�bal D�ez-Aja L�pez, Hospital Mare de Deu de La Merced, Barcelona-Merced, Spain Santiago )] TJ ET
BT 26.250 112.715 Td /F1 9.8 Tf  [(Dur�n-Sindreu Terol, Hospital Mare de Deu de La Merced, Barcelona-Merced, Spain Misericordia Floriach Robert, Hospital )] TJ ET
BT 26.250 100.810 Td /F1 9.8 Tf  [(Mare de Deu de La Merced, Barcelona-Merced, Spain Bel�n Garz�n Ru�z, Hospital Mare de Deu de La Merced, Barcelona-)] TJ ET
BT 26.250 88.905 Td /F1 9.8 Tf  [(Merced, Spain Ana Gonz�lez Casado, Hospital Mare de Deu de La Merced, Barcelona-Merced, Spain Isabel Haro Mart�nez, )] TJ ET
BT 26.250 77.001 Td /F1 9.8 Tf  [(Hospital Mare de Deu de La Merced, Barcelona-Merced, Spain Celia Mareca Viladrich, Hospital Mare de Deu de La Merced, )] TJ ET
BT 26.250 65.096 Td /F1 9.8 Tf  [(Barcelona-Merced, Spain Regina Pons i C�rdenas, Hospital Mare de Deu de La Merced, Barcelona-Merced, Spain Elvira Roca, )] TJ ET
BT 26.250 53.191 Td /F1 9.8 Tf  [(Hospital Mare de Deu de La Merced, Barcelona-Merced, Spain Joan Roig Llesoy, Hospital Mare de Deu de La Merced, )] TJ ET
BT 26.250 41.286 Td /F1 9.8 Tf  [(Barcelona-Merced, Spain Jes�s Miguel Ruiz Idiago, Hospital Mare de Deu de La Merced, Barcelona-Merced, Spain Mar Ru�z )] TJ ET
BT 26.250 29.382 Td /F1 9.8 Tf  [(Vergara, Hospital Mare de Deu de La Merced, Barcelona-Merced, Spain Socorro Soriano Garc�a, Hospital Mare de Deu de La )] TJ ET
Q
q
15.000 15.096 577.500 761.904 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(Gdansk; Medical University of Gdansk, Neurological and Psychiatric Nursing Dpt., Gdansk, Poland Jaroslaw Slawek, St. )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(Adalbert Hospital, Gdansk; Medical University of Gdansk, Neurological and Psychiatric Nursing Dpt., Gdansk, Poland Witold )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(Soltan, St. Adalbert Hospital, Gdansk; Medical University of Gdansk, Neurological and Psychiatric Nursing Dpt., Gdansk, )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(Poland Magdalena Boczarska-Jedynak, Silesian Medical University Katowice, Katowice, Poland Barbara Jasinska-Myga, )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(Silesian Medical University Katowice, Katowice, Poland Gregorz Opala, Silesian Medical University Katowice, Katowice, Poland )] TJ ET
BT 26.250 707.952 Td /F1 9.8 Tf  [(Gabriela K?odowska � Duda, Silesian Medical University Katowice, Katowice, Poland Krzysztof Banaszkiewicz, Krakowska )] TJ ET
BT 26.250 696.048 Td /F1 9.8 Tf  [(Akademia Neurologii, Krako, Poland Andrzej Szczudlik, Krakowska Akademia Neurologii, Krako, Poland Monika Rudzi?ska, )] TJ ET
BT 26.250 684.143 Td /F1 9.8 Tf  [(Krakowska Akademia Neurologii, Krako, Poland Magdalena W�jcik, Krakowska Akademia Neurologii, Krako, Poland )] TJ ET
BT 26.250 672.238 Td /F1 9.8 Tf  [(Ma?gorzata Dec, Krakowska Akademia Neurologii, Krako, Poland Malgorzata Krawczyk, Krakowska Akademia Neurologii, )] TJ ET
BT 26.250 660.333 Td /F1 9.8 Tf  [(Krako, Poland Anna Bryl, Medical University of Pozna?, Poznan, Poland Anna Ciesielska, Medical University of Pozna?, )] TJ ET
BT 26.250 648.429 Td /F1 9.8 Tf  [(Poznan, Poland Aneta Klimberg, Medical University of Pozna?, Poznan, Poland Jerzy Marcinkowski, Medical University of )] TJ ET
BT 26.250 636.524 Td /F1 9.8 Tf  [(Pozna?, Poznan, Poland Justyna Sempo?owicz, Medical University of Pozna?, Poznan, Poland Daniel Zielonka, Medical )] TJ ET
BT 26.250 624.619 Td /F1 9.8 Tf  [(University of Pozna?, Poznan, Poland Husam Samara, Medical University of Pozna?, Poznan, Poland Piotr Janik, Medical )] TJ ET
BT 26.250 612.714 Td /F1 9.8 Tf  [(University of Warsaw, Neurology, Warsaw-MU, Poland Anna Gogol, Medical University of Warsaw, Neurology, Warsaw-MU, )] TJ ET
BT 26.250 600.810 Td /F1 9.8 Tf  [(Poland Hubert Kwiecinski, Medical University of Warsaw, Neurology, Warsaw-MU, Poland Zygmunt Jamrozik, Medical )] TJ ET
BT 26.250 588.905 Td /F1 9.8 Tf  [(University of Warsaw, Neurology, Warsaw-MU, Poland Jakub Antczak, Institute of Psychiatry and Neurology Dep. of Genetics, )] TJ ET
BT 26.250 577.000 Td /F1 9.8 Tf  [(Dep. of Neurology, Warsaw-IPiN, Poland Katarzyna Jachinska, Institute of Psychiatry and Neurology Dep. of Genetics, Dep. of )] TJ ET
BT 26.250 565.095 Td /F1 9.8 Tf  [(Neurology, Warsaw-IPiN, Poland Maria Rakowicz, Institute of Psychiatry and Neurology Dep. of Genetics, Dep. of Neurology, )] TJ ET
BT 26.250 553.191 Td /F1 9.8 Tf  [(Warsaw-IPiN, Poland Przemyslaw Richter, Institute of Psychiatry and Neurology Dep. of Genetics, Dep. of Neurology, Warsaw-)] TJ ET
BT 26.250 541.286 Td /F1 9.8 Tf  [(IPiN, Poland Danuta Ryglewicz, Institute of Psychiatry and Neurology Dep. of Genetics, Dep. of Neurology, Warsaw-IPiN, )] TJ ET
BT 26.250 529.381 Td /F1 9.8 Tf  [(Poland Grzegorz Witkowski, Institute of Psychiatry and Neurology Dep. of Genetics, Dep. of Neurology, Warsaw-IPiN, Poland )] TJ ET
BT 26.250 517.476 Td /F1 9.8 Tf  [(Elzbieta Zdzienicka, Institute of Psychiatry and Neurology Dep. of Genetics, Dep. of Neurology, Warsaw-IPiN, Poland Jacek )] TJ ET
BT 26.250 505.572 Td /F1 9.8 Tf  [(Zaremba, Institute of Psychiatry and Neurology Dep. of Genetics, Dep. of Neurology, Warsaw-IPiN, Poland Anna Su?ek, )] TJ ET
BT 26.250 493.667 Td /F1 9.8 Tf  [(Institute of Psychiatry and Neurology Dep. of Genetics, Dep. of Neurology, Warsaw-IPiN, Poland Wioletta Krysa, Institute of )] TJ ET
BT 26.250 481.762 Td /F1 9.8 Tf  [(Psychiatry and Neurology Dep. of Genetics, Dep. of Neurology, Warsaw-IPiN, Poland Tiago Mestre)] TJ ET
BT 454.324 481.762 Td /F4 9.8 Tf  [(, )] TJ ET
BT 459.745 481.762 Td /F1 9.8 Tf  [(Hospital de Santa Maria; )] TJ ET
BT 26.250 469.857 Td /F1 9.8 Tf  [(Neurological Clinical Research Unit, Instituto de Medicina Molecular, Lisbon, Portugal Leonor Correia-Guedes, Hospital de )] TJ ET
BT 26.250 457.953 Td /F1 9.8 Tf  [(Santa Maria; Neurological Clinical Research Unit, Instituto de Medicina Molecular, Lisbon, Portugal Miguel Coelho, Hospital de )] TJ ET
BT 26.250 446.048 Td /F1 9.8 Tf  [(Santa Maria; Neurological Clinical Research Unit, Instituto de Medicina Molecular, Lisbon, Portugal Joaquim J Ferreira, Hospital )] TJ ET
BT 26.250 434.143 Td /F1 9.8 Tf  [(de Santa Maria; Neurological Clinical Research Unit, Instituto de Medicina Molecular, Lisbon, Portugal �ngela Tim�teo, Hospital )] TJ ET
BT 26.250 422.238 Td /F1 9.8 Tf  [(Fernando da Fonseca, Lisbon, Portugal Cristina Costa, Hospital Fernando da Fonseca, Lisbon, Portugal Miguel Gago, Hospital )] TJ ET
BT 26.250 410.334 Td /F1 9.8 Tf  [(de S�o Jo�o, Porto, Portugal Carolina Garrett, Hospital de S�o Jo�o, Porto, Portugal Maria Ros�lia Guerra, Hospital de S�o )] TJ ET
BT 26.250 398.429 Td /F1 9.8 Tf  [(Jo�o, Porto, Portugal Carmen Dur�n Herrera, Hospital Infanta Cristina, Badajoz, Spain Patrocinio Moreno Garcia, Hospital )] TJ ET
BT 26.250 386.524 Td /F1 9.8 Tf  [(Infanta Cristina, Badajoz, Spain Francisco Barrero, Hospital Universitario San Cecilio, Neurolog�a, Granada, Spain Blas Morale, )] TJ ET
BT 26.250 374.619 Td /F1 9.8 Tf  [(Hospital Universitario San Cecilio, Neurolog�a, Granada, Spain Esther Cubo, Servicio de Neurolog�a Hospital General Yag�e, )] TJ ET
BT 26.250 362.715 Td /F1 9.8 Tf  [(Burgos, Spain Natividad Mariscal, Servicio de Neurolog�a Hospital General Yag�e, Burgos, Spain Jes�s S�nchez, Servicio de )] TJ ET
BT 26.250 350.810 Td /F1 9.8 Tf  [(Neurolog�a Hospital General Yag�e, Burgos, Spain Fernando Alonso-Frech, Hospital Universitario de Fuenlabrada, )] TJ ET
BT 26.250 338.905 Td /F1 9.8 Tf  [(Fuenlabrada, Spain Maria Rabasa Perez, Hospital Universitario de Fuenlabrada, Fuenlabrada, Spain Mar�a Fenollar, Hospital )] TJ ET
BT 26.250 327.000 Td /F1 9.8 Tf  [(Cl�nico Universitario San Carlos, Madrid-Clinico, Spain Roc�o Garc�a-Ramos Garc�a, Hospital Cl�nico Universitario San Carlos, )] TJ ET
BT 26.250 315.096 Td /F1 9.8 Tf  [(Madrid-Clinico, Spain Purificacion Pin Quiroga, Hospital Cl�nico Universitario San Carlos, Madrid-Clinico, Spain Susana )] TJ ET
BT 26.250 303.191 Td /F1 9.8 Tf  [(V�zquez Rivera, Hospital Cl�nico Universitario San Carlos, Madrid-Clinico, Spain Clara Villanuev, Hospital Cl�nico Universitario )] TJ ET
BT 26.250 291.286 Td /F1 9.8 Tf  [(San Carlos, Madrid-Clinico, Spain M�nica Bascu�ana, Hospital Ram�n y Cajal, Neurolog�a, Madrid RYC, Spain Marta Fat�s )] TJ ET
BT 26.250 279.381 Td /F1 9.8 Tf  [(Ventura, Hospital Ram�n y Cajal, Neurolog�a, Madrid RYC, Spain Guillermo Garc�a Ribas, Garcia Riva, Hospital Ram�n y )] TJ ET
BT 26.250 267.477 Td /F1 9.8 Tf  [(Cajal, Neurolog�a, Madrid RYC, Spain Justo Garc�a de Y�benes, Hospital Ram�n y Cajal, Neurolog�a, Madrid RYC, Spain Jos� )] TJ ET
BT 26.250 255.572 Td /F1 9.8 Tf  [(Luis L�pez � Send�n Moreno, Hospital Ram�n y Cajal, Neurolog�a, Madrid RYC, Spain Patricia Trigo Cubillo, Hospital Ram�n y )] TJ ET
BT 26.250 243.667 Td /F1 9.8 Tf  [(Cajal, Neurolog�a, Madrid RYC, Spain Pedro J Garc�a Ru�z, Madrid-Fundaci�n Jim�nez D�az, Madrid FJD, Spain Asunci�n )] TJ ET
BT 26.250 231.762 Td /F1 9.8 Tf  [(Mart�nez-Descals, Madrid-Fundaci�n Jim�nez D�az, Madrid FJD, Spain Mar�a Jos� Saiz Artiga, Madrid-Fundaci�n Jim�nez )] TJ ET
BT 26.250 219.858 Td /F1 9.8 Tf  [(D�az, Madrid FJD, Spain Vicenta S�nchez, Madrid-Fundaci�n Jim�nez D�az, Madrid FJD, Spain Miquel Aguilar Barbera, )] TJ ET
BT 26.250 207.953 Td /F1 9.8 Tf  [(Barcelona-Hospital M�tua de Terrassa, Spain Dolors Badenes Guia, Barcelona-Hospital M�tua de Terrassa, Spain Laura )] TJ ET
BT 26.250 196.048 Td /F1 9.8 Tf  [(Casas Hernanz, Barcelona-Hospital M�tua de Terrassa, Spain Judit L�pez Catena, Barcelona-Hospital M�tua de Terrassa, )] TJ ET
BT 26.250 184.143 Td /F1 9.8 Tf  [(Spain Ana Rojo Sebasti�n, Barcelona-Hospital M�tua de Terrassa, Spain Pilar Quil�z Ferrer, Barcelona-Hospital M�tua de )] TJ ET
BT 26.250 172.239 Td /F1 9.8 Tf  [(Terrassa, Spain Gemma Tome Carruesco, Barcelona-Hospital M�tua de Terrassa, Spain Jordi Bas, Hospital Universitari de )] TJ ET
BT 26.250 160.334 Td /F1 9.8 Tf  [(Bellvitge, Barcelona-Bellvitge, Spain N�ria Busquets, Hospital Universitari de Bellvitge, Barcelona-Bellvitge, Spain Matilde )] TJ ET
BT 26.250 148.429 Td /F1 9.8 Tf  [(Calopa, Hospital Universitari de Bellvitge, Barcelona-Bellvitge, Spain Maria Teresa Buongiorno, Barcelona- Hospital Clinico, )] TJ ET
BT 26.250 136.524 Td /F1 9.8 Tf  [(Spain Esteban Mu�oz, Barcelona- Hospital Clinico, Spain Marina Dalmau Elorza, Hospital Mare de Deu de La Merced, )] TJ ET
BT 26.250 124.620 Td /F1 9.8 Tf  [(Barcelona-Merced, Spain Crist�bal D�ez-Aja L�pez, Hospital Mare de Deu de La Merced, Barcelona-Merced, Spain Santiago )] TJ ET
BT 26.250 112.715 Td /F1 9.8 Tf  [(Dur�n-Sindreu Terol, Hospital Mare de Deu de La Merced, Barcelona-Merced, Spain Misericordia Floriach Robert, Hospital )] TJ ET
BT 26.250 100.810 Td /F1 9.8 Tf  [(Mare de Deu de La Merced, Barcelona-Merced, Spain Bel�n Garz�n Ru�z, Hospital Mare de Deu de La Merced, Barcelona-)] TJ ET
BT 26.250 88.905 Td /F1 9.8 Tf  [(Merced, Spain Ana Gonz�lez Casado, Hospital Mare de Deu de La Merced, Barcelona-Merced, Spain Isabel Haro Mart�nez, )] TJ ET
BT 26.250 77.001 Td /F1 9.8 Tf  [(Hospital Mare de Deu de La Merced, Barcelona-Merced, Spain Celia Mareca Viladrich, Hospital Mare de Deu de La Merced, )] TJ ET
BT 26.250 65.096 Td /F1 9.8 Tf  [(Barcelona-Merced, Spain Regina Pons i C�rdenas, Hospital Mare de Deu de La Merced, Barcelona-Merced, Spain Elvira Roca, )] TJ ET
BT 26.250 53.191 Td /F1 9.8 Tf  [(Hospital Mare de Deu de La Merced, Barcelona-Merced, Spain Joan Roig Llesoy, Hospital Mare de Deu de La Merced, )] TJ ET
BT 26.250 41.286 Td /F1 9.8 Tf  [(Barcelona-Merced, Spain Jes�s Miguel Ruiz Idiago, Hospital Mare de Deu de La Merced, Barcelona-Merced, Spain Mar Ru�z )] TJ ET
BT 26.250 29.382 Td /F1 9.8 Tf  [(Vergara, Hospital Mare de Deu de La Merced, Barcelona-Merced, Spain Socorro Soriano Garc�a, Hospital Mare de Deu de La )] TJ ET
Q
q
0.000 0.000 0.000 rg
BT 291.710 19.825 Td /F1 11.0 Tf  [(10)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Huntington Disease)] TJ ET

Q
endstream
endobj
191 0 obj
<< /Type /Page
/Parent 3 0 R
/Contents 192 0 R
>>
endobj
192 0 obj
<<
/Length 31310 >>
stream

0.271 0.267 0.267 rg
q
15.000 15.096 577.500 761.904 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(Merced, Barcelona-Merced, Spain Antonio Villa Riballo, Hospital Mare de Deu de La Merced, Barcelona-Merced, Spain )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(Aranzaz� Gorospe, Hospital Son Dureta, Palma, Spain In�s Legarda, Hospital Son Dureta, Palma, Spain Penelope Navas )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(Arques, Hospital Son Dureta, Palma, Spain Mar�a Jos� Torres Rodr�guez, Hospital Son Dureta, Palma, Spain Barbara Vives, )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(Hospital Son Dureta, Palma, Spain Itziar Gaston, Hospital Virgen del Camino, Medical Genetic, Pamplona, Spain Maria A. )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(Ramos-Arroyo,Hospital Virgen del Camino, Medical Genetic, Pamplona, Spain Maria Dolores Martinez-Jaurrieta, Hospital )] TJ ET
BT 26.250 707.952 Td /F1 9.8 Tf  [(Virgen del Camino, Medical Genetic, Pamplona, Spain Sven E P�lhagen, Karolinska University Hospital, Stockholm, Sweden )] TJ ET
BT 26.250 696.048 Td /F1 9.8 Tf  [(Martin Paucar, Karolinska University Hospital, Stockholm, Sweden Per Svenningsson, Karolinska University Hospital, )] TJ ET
BT 26.250 684.143 Td /F1 9.8 Tf  [(Stockholm, Sweden Tina Walld�n Reza-Soltani, Karolinska University Hospital, Stockholm, Sweden Arja H�glund, Karolinska )] TJ ET
BT 26.250 672.238 Td /F1 9.8 Tf  [(University Hospital, Stockholm, Sweden Britta Sandstr�, Karolinska University Hospital, Stockholm, Sweden Joakim Tedroff, )] TJ ET
BT 26.250 660.333 Td /F1 9.8 Tf  [(NeuroHealth Consulting Sweden HB, Karolinska Institute, Stockholm-Ersta, Sweden Mona Esmaeilzadeh, NeuroHealth )] TJ ET
BT 26.250 648.429 Td /F1 9.8 Tf  [(Consulting Sweden HB, Karolinska Institute, Stockholm-Ersta, Sweden Elisabeth Winnberg, NeuroHealth Consulting Sweden )] TJ ET
BT 26.250 636.524 Td /F1 9.8 Tf  [(HB, Karolinska Institute, Stockholm-Ersta, Sweden Anders Johansson, Uppsala University Hospital, Uppsal, Sweden Leif )] TJ ET
BT 26.250 624.619 Td /F1 9.8 Tf  [(Wiklund, Uppsala University Hospital, Uppsal, Sweden Camilla Ekwall, Uppsala University Hospital, Uppsal, Sweden Marie-)] TJ ET
BT 26.250 612.714 Td /F1 9.8 Tf  [(Louise G�ller, Uppsala University Hospital, Uppsal, Sweden Yvonne Bj�rn, Uppsala University Hospital, Uppsal, Sweden Jean-)] TJ ET
BT 26.250 600.810 Td /F1 9.8 Tf  [(Marc Burgunder, Neurologische Klinik des Inselspitals, Bern, Switzerland Yvonne Burgunder, Neurologische Klinik des )] TJ ET
BT 26.250 588.905 Td /F1 9.8 Tf  [(Inselspitals, Bern, Switzerland Yanik Stebler, Neurologische Klinik des Inselspitals, Bern, Switzerland Alain Kaelin, Zentrum f�r )] TJ ET
BT 26.250 577.000 Td /F1 9.8 Tf  [(Bewegungsst�rungen, Neurologische Klinik und Poliklinik, Bern, Switzerland Irene Romero, Zentrum f�r Bewegungsst�rungen, )] TJ ET
BT 26.250 565.095 Td /F1 9.8 Tf  [(Neurologische Klinik und Poliklinik, Bern, Switzerland Michael Sch�pbach, Zentrum f�r Bewegungsst�rungen, Neurologische )] TJ ET
BT 26.250 553.191 Td /F1 9.8 Tf  [(Klinik und Poliklinik, Bern, Switzerland Sabine Weber Zaugg, Zentrum f�r Bewegungsst�rungen, Neurologische Klinik und )] TJ ET
BT 26.250 541.286 Td /F1 9.8 Tf  [(Poliklinik, Bern, Switzerland Roisin Jack, NHS Grampian, Clinical Genetics Centre, Aberdeen, UK Kirsty Matheson, NHS )] TJ ET
BT 26.250 529.381 Td /F1 9.8 Tf  [(Grampian, Clinical Genetics Centre, Aberdeen, UK Zosia Miedzybrodzka, NHS Grampian, Clinical Genetics Centre, Aberdeen, )] TJ ET
BT 26.250 517.476 Td /F1 9.8 Tf  [(UK Daniela Rae, NHS Grampian, Clinical Genetics Centre, Aberdeen, UK Sheila Simpson, NHS Grampian, Clinical Genetics )] TJ ET
BT 26.250 505.572 Td /F1 9.8 Tf  [(Centre, Aberdeen, UK Fiona Summers, NHS Grampian, Clinical Genetics Centre, Aberdeen, UK Alexandra Ure, NHS )] TJ ET
BT 26.250 493.667 Td /F1 9.8 Tf  [(Grampian, Clinical Genetics Centre, Aberdeen, UK Adrienne Curtis, The Barberry Centre, Dept of Psychiatry, Birmingham, UK )] TJ ET
BT 26.250 481.762 Td /F1 9.8 Tf  [(Jenny de Souza \(Keylock\), The Barberry Centre, Dept of Psychiatry, Birmingham, UK Hugh Rickards, The Barberry Centre, )] TJ ET
BT 26.250 469.857 Td /F1 9.8 Tf  [(Dept of Psychiatry, Birmingham, UK Jan Wright, The Barberry Centre, Dept of Psychiatry, Birmingham, UK Matthew Armstrong, )] TJ ET
BT 26.250 457.953 Td /F1 9.8 Tf  [(Cambridge Centre for Brain Repair, Forvie Site, Cambridge, UK Roger A. Barker, Cambridge Centre for Brain Repair, Forvie )] TJ ET
BT 26.250 446.048 Td /F1 9.8 Tf  [(Site, Cambridge, UK Deidre O�Keefe, Cambridge Centre for Brain Repair, Forvie Site, Cambridge, UK Anna Di Pietro, )] TJ ET
BT 26.250 434.143 Td /F1 9.8 Tf  [(Cambridge Centre for Brain Repair, Forvie Site, Cambridge, UK Kate Fisher, Cambridge Centre for Brain Repair, Forvie Site, )] TJ ET
BT 26.250 422.238 Td /F1 9.8 Tf  [(Cambridge, UK Anna Goodman, Cambridge Centre for Brain Repair, Forvie Site, Cambridge, UK Susan Hill, Cambridge Centre )] TJ ET
BT 26.250 410.334 Td /F1 9.8 Tf  [(for Brain Repair, Forvie Site, Cambridge, UK Ann Kershaw, Cambridge Centre for Brain Repair, Forvie Site, Cambridge, UK )] TJ ET
BT 26.250 398.429 Td /F1 9.8 Tf  [(Sarah Mason, Cambridge Centre for Brain Repair, Forvie Site, Cambridge, UK Nicole Paterson, Cambridge Centre for Brain )] TJ ET
BT 26.250 386.524 Td /F1 9.8 Tf  [(Repair, Forvie Site, Cambridge, UK Rachel Swain, Cambridge Centre for Brain Repair, Forvie Site, Cambridge, UK Lucy )] TJ ET
BT 26.250 374.619 Td /F1 9.8 Tf  [(Raymon, Cambridge Centre for Brain Repair, Forvie Site, Cambridge, UK Monica Busse, The Institute of Medical Genetics, )] TJ ET
BT 26.250 362.715 Td /F1 9.8 Tf  [(University Hospital of Wales, Cardif, UK Stephen Dunnett, The Institute of Medical Genetics, University Hospital of Wales, )] TJ ET
BT 26.250 350.810 Td /F1 9.8 Tf  [(Cardif, UK Catherine Clenaghan, The Institute of Medical Genetics, University Hospital of Wales, Cardif, UK Ruth Fullham, The )] TJ ET
BT 26.250 338.905 Td /F1 9.8 Tf  [(Institute of Medical Genetics, University Hospital of Wales, Cardif, UK Sarah Hunt, The Institute of Medical Genetics, University )] TJ ET
BT 26.250 327.000 Td /F1 9.8 Tf  [(Hospital of Wales, Cardif, UK Lesley Jones, The Institute of Medical Genetics, University Hospital of Wales, Cardif, UK Una )] TJ ET
BT 26.250 315.096 Td /F1 9.8 Tf  [(Jones, The Institute of Medical Genetics, University Hospital of Wales, Cardif, UK Hanan Khalil, The Institute of Medical )] TJ ET
BT 26.250 303.191 Td /F1 9.8 Tf  [(Genetics, University Hospital of Wales, Cardif, UK Sara Minster, The Institute of Medical Genetics, University Hospital of Wales, )] TJ ET
BT 26.250 291.286 Td /F1 9.8 Tf  [(Cardif, UK Michael Owen, The Institute of Medical Genetics, University Hospital of Wales, Cardif, UK Kathleen Price, The )] TJ ET
BT 26.250 279.381 Td /F1 9.8 Tf  [(Institute of Medical Genetics, University Hospital of Wales, Cardif, UK Jenny Townshill,The Institute of Medical Genetics, )] TJ ET
BT 26.250 267.477 Td /F1 9.8 Tf  [(University Hospital of Wales, Cardif, UK Anne Rosser, The Institute of Medical Genetics, University Hospital of Wales, Cardif, )] TJ ET
BT 26.250 255.572 Td /F1 9.8 Tf  [(UK Maureen Edwards, Molecular Medicine Centre, Western General Hospital, Department of Clinical Genetics, Edinburg, UK )] TJ ET
BT 26.250 243.667 Td /F1 9.8 Tf  [(Teresa Hughes \(Scottish Huntington�s Association\), Molecular Medicine Centre, Western General Hospital, Department of )] TJ ET
BT 26.250 231.762 Td /F1 9.8 Tf  [(Clinical Genetics, Edinburg, UK Marie McGill, Molecular Medicine Centre, Western General Hospital, Department of Clinical )] TJ ET
BT 26.250 219.858 Td /F1 9.8 Tf  [(Genetics, Edinburg, UK Pauline Pearson, Molecular Medicine Centre, Western General Hospital, Department of Clinical )] TJ ET
BT 26.250 207.953 Td /F1 9.8 Tf  [(Genetics, Edinburg, UK Mary Porteous, Molecular Medicine Centre, Western General Hospital, Department of Clinical Genetics, )] TJ ET
BT 26.250 196.048 Td /F1 9.8 Tf  [(Edinburg, UK Paul Smith \(Scottish Huntington�s Association\), Molecular Medicine Centre, Western General Hospital, )] TJ ET
BT 26.250 184.143 Td /F1 9.8 Tf  [(Department of Clinical Genetics, Edinburg, UK Adam Zeman, Molecular Medicine Centre, Western General Hospital, )] TJ ET
BT 26.250 172.239 Td /F1 9.8 Tf  [(Department of Clinical Genetics, Edinburg, UK Peter Brockie, Scottish Huntington�s Association Whyteman�s Brae Hospital, )] TJ ET
BT 26.250 160.334 Td /F1 9.8 Tf  [(Fife, UK Jillian Foster, Scottish Huntington�s Association Whyteman�s Brae Hospital, Fife, UK Nicola Johns, Scottish )] TJ ET
BT 26.250 148.429 Td /F1 9.8 Tf  [(Huntington�s Association Whyteman�s Brae Hospital, Fife, UK Sue McKenzie, Scottish Huntington�s Association Whyteman�s )] TJ ET
BT 26.250 136.524 Td /F1 9.8 Tf  [(Brae Hospital, Fife, UK Jean Rothery, Scottish Huntington�s Association Whyteman�s Brae Hospital, Fife, UK Gareth Thomas, )] TJ ET
BT 26.250 124.620 Td /F1 9.8 Tf  [(Scottish Huntington�s Association Whyteman�s Brae Hospital, Fife, UK Shona Yates, Scottish Huntington�s Association )] TJ ET
BT 26.250 112.715 Td /F1 9.8 Tf  [(Whyteman�s Brae Hospital, Fife, UK Joanne Miller, Abercromby Center, Glasgow, UK Stuart Ritchie, Abercromby Center, )] TJ ET
BT 26.250 100.810 Td /F1 9.8 Tf  [(Glasgow, UK Liz Burrows, Department of Neurology Gloucestershire Royal Hospital, Gloucester, UK Amy Fletcher, Department )] TJ ET
BT 26.250 88.905 Td /F1 9.8 Tf  [(of Neurology Gloucestershire Royal Hospital, Gloucester, UK Alison Harding, Department of Neurology Gloucestershire Royal )] TJ ET
BT 26.250 77.001 Td /F1 9.8 Tf  [(Hospital, Gloucester, UK Fiona Laver, Department of Neurology Gloucestershire Royal Hospital, Gloucester, UK Mark Silva, )] TJ ET
BT 26.250 65.096 Td /F1 9.8 Tf  [(Department of Neurology Gloucestershire Royal Hospital, Gloucester, UK Aileen Thomson, Department of Neurology )] TJ ET
BT 26.250 53.191 Td /F1 9.8 Tf  [(Gloucestershire Royal Hospital, Gloucester, UK Peter Burns, Castle Hill Hospital, Hull, UK Carol Chu, Castle Hill Hospital, Hull, )] TJ ET
BT 26.250 41.286 Td /F1 9.8 Tf  [(UK Carole Evans, Castle Hill Hospital, Hull, UK Stephanie Hamer, Castle Hill Hospital, Hull, UK Ivana Markova, Castle Hill )] TJ ET
BT 26.250 29.382 Td /F1 9.8 Tf  [(Hospital, Hull, UK Julie Miller, Castle Hill Hospital, Hull, UK Ashok Raman, Castle Hill Hospital, Hull, UK Kathy Barnes, Chapel )] TJ ET
Q
q
15.000 15.096 577.500 761.904 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(Merced, Barcelona-Merced, Spain Antonio Villa Riballo, Hospital Mare de Deu de La Merced, Barcelona-Merced, Spain )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(Aranzaz� Gorospe, Hospital Son Dureta, Palma, Spain In�s Legarda, Hospital Son Dureta, Palma, Spain Penelope Navas )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(Arques, Hospital Son Dureta, Palma, Spain Mar�a Jos� Torres Rodr�guez, Hospital Son Dureta, Palma, Spain Barbara Vives, )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(Hospital Son Dureta, Palma, Spain Itziar Gaston, Hospital Virgen del Camino, Medical Genetic, Pamplona, Spain Maria A. )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(Ramos-Arroyo,Hospital Virgen del Camino, Medical Genetic, Pamplona, Spain Maria Dolores Martinez-Jaurrieta, Hospital )] TJ ET
BT 26.250 707.952 Td /F1 9.8 Tf  [(Virgen del Camino, Medical Genetic, Pamplona, Spain Sven E P�lhagen, Karolinska University Hospital, Stockholm, Sweden )] TJ ET
BT 26.250 696.048 Td /F1 9.8 Tf  [(Martin Paucar, Karolinska University Hospital, Stockholm, Sweden Per Svenningsson, Karolinska University Hospital, )] TJ ET
BT 26.250 684.143 Td /F1 9.8 Tf  [(Stockholm, Sweden Tina Walld�n Reza-Soltani, Karolinska University Hospital, Stockholm, Sweden Arja H�glund, Karolinska )] TJ ET
BT 26.250 672.238 Td /F1 9.8 Tf  [(University Hospital, Stockholm, Sweden Britta Sandstr�, Karolinska University Hospital, Stockholm, Sweden Joakim Tedroff, )] TJ ET
BT 26.250 660.333 Td /F1 9.8 Tf  [(NeuroHealth Consulting Sweden HB, Karolinska Institute, Stockholm-Ersta, Sweden Mona Esmaeilzadeh, NeuroHealth )] TJ ET
BT 26.250 648.429 Td /F1 9.8 Tf  [(Consulting Sweden HB, Karolinska Institute, Stockholm-Ersta, Sweden Elisabeth Winnberg, NeuroHealth Consulting Sweden )] TJ ET
BT 26.250 636.524 Td /F1 9.8 Tf  [(HB, Karolinska Institute, Stockholm-Ersta, Sweden Anders Johansson, Uppsala University Hospital, Uppsal, Sweden Leif )] TJ ET
BT 26.250 624.619 Td /F1 9.8 Tf  [(Wiklund, Uppsala University Hospital, Uppsal, Sweden Camilla Ekwall, Uppsala University Hospital, Uppsal, Sweden Marie-)] TJ ET
BT 26.250 612.714 Td /F1 9.8 Tf  [(Louise G�ller, Uppsala University Hospital, Uppsal, Sweden Yvonne Bj�rn, Uppsala University Hospital, Uppsal, Sweden Jean-)] TJ ET
BT 26.250 600.810 Td /F1 9.8 Tf  [(Marc Burgunder, Neurologische Klinik des Inselspitals, Bern, Switzerland Yvonne Burgunder, Neurologische Klinik des )] TJ ET
BT 26.250 588.905 Td /F1 9.8 Tf  [(Inselspitals, Bern, Switzerland Yanik Stebler, Neurologische Klinik des Inselspitals, Bern, Switzerland Alain Kaelin, Zentrum f�r )] TJ ET
BT 26.250 577.000 Td /F1 9.8 Tf  [(Bewegungsst�rungen, Neurologische Klinik und Poliklinik, Bern, Switzerland Irene Romero, Zentrum f�r Bewegungsst�rungen, )] TJ ET
BT 26.250 565.095 Td /F1 9.8 Tf  [(Neurologische Klinik und Poliklinik, Bern, Switzerland Michael Sch�pbach, Zentrum f�r Bewegungsst�rungen, Neurologische )] TJ ET
BT 26.250 553.191 Td /F1 9.8 Tf  [(Klinik und Poliklinik, Bern, Switzerland Sabine Weber Zaugg, Zentrum f�r Bewegungsst�rungen, Neurologische Klinik und )] TJ ET
BT 26.250 541.286 Td /F1 9.8 Tf  [(Poliklinik, Bern, Switzerland Roisin Jack, NHS Grampian, Clinical Genetics Centre, Aberdeen, UK Kirsty Matheson, NHS )] TJ ET
BT 26.250 529.381 Td /F1 9.8 Tf  [(Grampian, Clinical Genetics Centre, Aberdeen, UK Zosia Miedzybrodzka, NHS Grampian, Clinical Genetics Centre, Aberdeen, )] TJ ET
BT 26.250 517.476 Td /F1 9.8 Tf  [(UK Daniela Rae, NHS Grampian, Clinical Genetics Centre, Aberdeen, UK Sheila Simpson, NHS Grampian, Clinical Genetics )] TJ ET
BT 26.250 505.572 Td /F1 9.8 Tf  [(Centre, Aberdeen, UK Fiona Summers, NHS Grampian, Clinical Genetics Centre, Aberdeen, UK Alexandra Ure, NHS )] TJ ET
BT 26.250 493.667 Td /F1 9.8 Tf  [(Grampian, Clinical Genetics Centre, Aberdeen, UK Adrienne Curtis, The Barberry Centre, Dept of Psychiatry, Birmingham, UK )] TJ ET
BT 26.250 481.762 Td /F1 9.8 Tf  [(Jenny de Souza \(Keylock\), The Barberry Centre, Dept of Psychiatry, Birmingham, UK Hugh Rickards, The Barberry Centre, )] TJ ET
BT 26.250 469.857 Td /F1 9.8 Tf  [(Dept of Psychiatry, Birmingham, UK Jan Wright, The Barberry Centre, Dept of Psychiatry, Birmingham, UK Matthew Armstrong, )] TJ ET
BT 26.250 457.953 Td /F1 9.8 Tf  [(Cambridge Centre for Brain Repair, Forvie Site, Cambridge, UK Roger A. Barker, Cambridge Centre for Brain Repair, Forvie )] TJ ET
BT 26.250 446.048 Td /F1 9.8 Tf  [(Site, Cambridge, UK Deidre O�Keefe, Cambridge Centre for Brain Repair, Forvie Site, Cambridge, UK Anna Di Pietro, )] TJ ET
BT 26.250 434.143 Td /F1 9.8 Tf  [(Cambridge Centre for Brain Repair, Forvie Site, Cambridge, UK Kate Fisher, Cambridge Centre for Brain Repair, Forvie Site, )] TJ ET
BT 26.250 422.238 Td /F1 9.8 Tf  [(Cambridge, UK Anna Goodman, Cambridge Centre for Brain Repair, Forvie Site, Cambridge, UK Susan Hill, Cambridge Centre )] TJ ET
BT 26.250 410.334 Td /F1 9.8 Tf  [(for Brain Repair, Forvie Site, Cambridge, UK Ann Kershaw, Cambridge Centre for Brain Repair, Forvie Site, Cambridge, UK )] TJ ET
BT 26.250 398.429 Td /F1 9.8 Tf  [(Sarah Mason, Cambridge Centre for Brain Repair, Forvie Site, Cambridge, UK Nicole Paterson, Cambridge Centre for Brain )] TJ ET
BT 26.250 386.524 Td /F1 9.8 Tf  [(Repair, Forvie Site, Cambridge, UK Rachel Swain, Cambridge Centre for Brain Repair, Forvie Site, Cambridge, UK Lucy )] TJ ET
BT 26.250 374.619 Td /F1 9.8 Tf  [(Raymon, Cambridge Centre for Brain Repair, Forvie Site, Cambridge, UK Monica Busse, The Institute of Medical Genetics, )] TJ ET
BT 26.250 362.715 Td /F1 9.8 Tf  [(University Hospital of Wales, Cardif, UK Stephen Dunnett, The Institute of Medical Genetics, University Hospital of Wales, )] TJ ET
BT 26.250 350.810 Td /F1 9.8 Tf  [(Cardif, UK Catherine Clenaghan, The Institute of Medical Genetics, University Hospital of Wales, Cardif, UK Ruth Fullham, The )] TJ ET
BT 26.250 338.905 Td /F1 9.8 Tf  [(Institute of Medical Genetics, University Hospital of Wales, Cardif, UK Sarah Hunt, The Institute of Medical Genetics, University )] TJ ET
BT 26.250 327.000 Td /F1 9.8 Tf  [(Hospital of Wales, Cardif, UK Lesley Jones, The Institute of Medical Genetics, University Hospital of Wales, Cardif, UK Una )] TJ ET
BT 26.250 315.096 Td /F1 9.8 Tf  [(Jones, The Institute of Medical Genetics, University Hospital of Wales, Cardif, UK Hanan Khalil, The Institute of Medical )] TJ ET
BT 26.250 303.191 Td /F1 9.8 Tf  [(Genetics, University Hospital of Wales, Cardif, UK Sara Minster, The Institute of Medical Genetics, University Hospital of Wales, )] TJ ET
BT 26.250 291.286 Td /F1 9.8 Tf  [(Cardif, UK Michael Owen, The Institute of Medical Genetics, University Hospital of Wales, Cardif, UK Kathleen Price, The )] TJ ET
BT 26.250 279.381 Td /F1 9.8 Tf  [(Institute of Medical Genetics, University Hospital of Wales, Cardif, UK Jenny Townshill,The Institute of Medical Genetics, )] TJ ET
BT 26.250 267.477 Td /F1 9.8 Tf  [(University Hospital of Wales, Cardif, UK Anne Rosser, The Institute of Medical Genetics, University Hospital of Wales, Cardif, )] TJ ET
BT 26.250 255.572 Td /F1 9.8 Tf  [(UK Maureen Edwards, Molecular Medicine Centre, Western General Hospital, Department of Clinical Genetics, Edinburg, UK )] TJ ET
BT 26.250 243.667 Td /F1 9.8 Tf  [(Teresa Hughes \(Scottish Huntington�s Association\), Molecular Medicine Centre, Western General Hospital, Department of )] TJ ET
BT 26.250 231.762 Td /F1 9.8 Tf  [(Clinical Genetics, Edinburg, UK Marie McGill, Molecular Medicine Centre, Western General Hospital, Department of Clinical )] TJ ET
BT 26.250 219.858 Td /F1 9.8 Tf  [(Genetics, Edinburg, UK Pauline Pearson, Molecular Medicine Centre, Western General Hospital, Department of Clinical )] TJ ET
BT 26.250 207.953 Td /F1 9.8 Tf  [(Genetics, Edinburg, UK Mary Porteous, Molecular Medicine Centre, Western General Hospital, Department of Clinical Genetics, )] TJ ET
BT 26.250 196.048 Td /F1 9.8 Tf  [(Edinburg, UK Paul Smith \(Scottish Huntington�s Association\), Molecular Medicine Centre, Western General Hospital, )] TJ ET
BT 26.250 184.143 Td /F1 9.8 Tf  [(Department of Clinical Genetics, Edinburg, UK Adam Zeman, Molecular Medicine Centre, Western General Hospital, )] TJ ET
BT 26.250 172.239 Td /F1 9.8 Tf  [(Department of Clinical Genetics, Edinburg, UK Peter Brockie, Scottish Huntington�s Association Whyteman�s Brae Hospital, )] TJ ET
BT 26.250 160.334 Td /F1 9.8 Tf  [(Fife, UK Jillian Foster, Scottish Huntington�s Association Whyteman�s Brae Hospital, Fife, UK Nicola Johns, Scottish )] TJ ET
BT 26.250 148.429 Td /F1 9.8 Tf  [(Huntington�s Association Whyteman�s Brae Hospital, Fife, UK Sue McKenzie, Scottish Huntington�s Association Whyteman�s )] TJ ET
BT 26.250 136.524 Td /F1 9.8 Tf  [(Brae Hospital, Fife, UK Jean Rothery, Scottish Huntington�s Association Whyteman�s Brae Hospital, Fife, UK Gareth Thomas, )] TJ ET
BT 26.250 124.620 Td /F1 9.8 Tf  [(Scottish Huntington�s Association Whyteman�s Brae Hospital, Fife, UK Shona Yates, Scottish Huntington�s Association )] TJ ET
BT 26.250 112.715 Td /F1 9.8 Tf  [(Whyteman�s Brae Hospital, Fife, UK Joanne Miller, Abercromby Center, Glasgow, UK Stuart Ritchie, Abercromby Center, )] TJ ET
BT 26.250 100.810 Td /F1 9.8 Tf  [(Glasgow, UK Liz Burrows, Department of Neurology Gloucestershire Royal Hospital, Gloucester, UK Amy Fletcher, Department )] TJ ET
BT 26.250 88.905 Td /F1 9.8 Tf  [(of Neurology Gloucestershire Royal Hospital, Gloucester, UK Alison Harding, Department of Neurology Gloucestershire Royal )] TJ ET
BT 26.250 77.001 Td /F1 9.8 Tf  [(Hospital, Gloucester, UK Fiona Laver, Department of Neurology Gloucestershire Royal Hospital, Gloucester, UK Mark Silva, )] TJ ET
BT 26.250 65.096 Td /F1 9.8 Tf  [(Department of Neurology Gloucestershire Royal Hospital, Gloucester, UK Aileen Thomson, Department of Neurology )] TJ ET
BT 26.250 53.191 Td /F1 9.8 Tf  [(Gloucestershire Royal Hospital, Gloucester, UK Peter Burns, Castle Hill Hospital, Hull, UK Carol Chu, Castle Hill Hospital, Hull, )] TJ ET
BT 26.250 41.286 Td /F1 9.8 Tf  [(UK Carole Evans, Castle Hill Hospital, Hull, UK Stephanie Hamer, Castle Hill Hospital, Hull, UK Ivana Markova, Castle Hill )] TJ ET
BT 26.250 29.382 Td /F1 9.8 Tf  [(Hospital, Hull, UK Julie Miller, Castle Hill Hospital, Hull, UK Ashok Raman, Castle Hill Hospital, Hull, UK Kathy Barnes, Chapel )] TJ ET
Q
q
15.000 15.096 577.500 761.904 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(Merced, Barcelona-Merced, Spain Antonio Villa Riballo, Hospital Mare de Deu de La Merced, Barcelona-Merced, Spain )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(Aranzaz� Gorospe, Hospital Son Dureta, Palma, Spain In�s Legarda, Hospital Son Dureta, Palma, Spain Penelope Navas )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(Arques, Hospital Son Dureta, Palma, Spain Mar�a Jos� Torres Rodr�guez, Hospital Son Dureta, Palma, Spain Barbara Vives, )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(Hospital Son Dureta, Palma, Spain Itziar Gaston, Hospital Virgen del Camino, Medical Genetic, Pamplona, Spain Maria A. )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(Ramos-Arroyo,Hospital Virgen del Camino, Medical Genetic, Pamplona, Spain Maria Dolores Martinez-Jaurrieta, Hospital )] TJ ET
BT 26.250 707.952 Td /F1 9.8 Tf  [(Virgen del Camino, Medical Genetic, Pamplona, Spain Sven E P�lhagen, Karolinska University Hospital, Stockholm, Sweden )] TJ ET
BT 26.250 696.048 Td /F1 9.8 Tf  [(Martin Paucar, Karolinska University Hospital, Stockholm, Sweden Per Svenningsson, Karolinska University Hospital, )] TJ ET
BT 26.250 684.143 Td /F1 9.8 Tf  [(Stockholm, Sweden Tina Walld�n Reza-Soltani, Karolinska University Hospital, Stockholm, Sweden Arja H�glund, Karolinska )] TJ ET
BT 26.250 672.238 Td /F1 9.8 Tf  [(University Hospital, Stockholm, Sweden Britta Sandstr�, Karolinska University Hospital, Stockholm, Sweden Joakim Tedroff, )] TJ ET
BT 26.250 660.333 Td /F1 9.8 Tf  [(NeuroHealth Consulting Sweden HB, Karolinska Institute, Stockholm-Ersta, Sweden Mona Esmaeilzadeh, NeuroHealth )] TJ ET
BT 26.250 648.429 Td /F1 9.8 Tf  [(Consulting Sweden HB, Karolinska Institute, Stockholm-Ersta, Sweden Elisabeth Winnberg, NeuroHealth Consulting Sweden )] TJ ET
BT 26.250 636.524 Td /F1 9.8 Tf  [(HB, Karolinska Institute, Stockholm-Ersta, Sweden Anders Johansson, Uppsala University Hospital, Uppsal, Sweden Leif )] TJ ET
BT 26.250 624.619 Td /F1 9.8 Tf  [(Wiklund, Uppsala University Hospital, Uppsal, Sweden Camilla Ekwall, Uppsala University Hospital, Uppsal, Sweden Marie-)] TJ ET
BT 26.250 612.714 Td /F1 9.8 Tf  [(Louise G�ller, Uppsala University Hospital, Uppsal, Sweden Yvonne Bj�rn, Uppsala University Hospital, Uppsal, Sweden Jean-)] TJ ET
BT 26.250 600.810 Td /F1 9.8 Tf  [(Marc Burgunder, Neurologische Klinik des Inselspitals, Bern, Switzerland Yvonne Burgunder, Neurologische Klinik des )] TJ ET
BT 26.250 588.905 Td /F1 9.8 Tf  [(Inselspitals, Bern, Switzerland Yanik Stebler, Neurologische Klinik des Inselspitals, Bern, Switzerland Alain Kaelin, Zentrum f�r )] TJ ET
BT 26.250 577.000 Td /F1 9.8 Tf  [(Bewegungsst�rungen, Neurologische Klinik und Poliklinik, Bern, Switzerland Irene Romero, Zentrum f�r Bewegungsst�rungen, )] TJ ET
BT 26.250 565.095 Td /F1 9.8 Tf  [(Neurologische Klinik und Poliklinik, Bern, Switzerland Michael Sch�pbach, Zentrum f�r Bewegungsst�rungen, Neurologische )] TJ ET
BT 26.250 553.191 Td /F1 9.8 Tf  [(Klinik und Poliklinik, Bern, Switzerland Sabine Weber Zaugg, Zentrum f�r Bewegungsst�rungen, Neurologische Klinik und )] TJ ET
BT 26.250 541.286 Td /F1 9.8 Tf  [(Poliklinik, Bern, Switzerland Roisin Jack, NHS Grampian, Clinical Genetics Centre, Aberdeen, UK Kirsty Matheson, NHS )] TJ ET
BT 26.250 529.381 Td /F1 9.8 Tf  [(Grampian, Clinical Genetics Centre, Aberdeen, UK Zosia Miedzybrodzka, NHS Grampian, Clinical Genetics Centre, Aberdeen, )] TJ ET
BT 26.250 517.476 Td /F1 9.8 Tf  [(UK Daniela Rae, NHS Grampian, Clinical Genetics Centre, Aberdeen, UK Sheila Simpson, NHS Grampian, Clinical Genetics )] TJ ET
BT 26.250 505.572 Td /F1 9.8 Tf  [(Centre, Aberdeen, UK Fiona Summers, NHS Grampian, Clinical Genetics Centre, Aberdeen, UK Alexandra Ure, NHS )] TJ ET
BT 26.250 493.667 Td /F1 9.8 Tf  [(Grampian, Clinical Genetics Centre, Aberdeen, UK Adrienne Curtis, The Barberry Centre, Dept of Psychiatry, Birmingham, UK )] TJ ET
BT 26.250 481.762 Td /F1 9.8 Tf  [(Jenny de Souza \(Keylock\), The Barberry Centre, Dept of Psychiatry, Birmingham, UK Hugh Rickards, The Barberry Centre, )] TJ ET
BT 26.250 469.857 Td /F1 9.8 Tf  [(Dept of Psychiatry, Birmingham, UK Jan Wright, The Barberry Centre, Dept of Psychiatry, Birmingham, UK Matthew Armstrong, )] TJ ET
BT 26.250 457.953 Td /F1 9.8 Tf  [(Cambridge Centre for Brain Repair, Forvie Site, Cambridge, UK Roger A. Barker, Cambridge Centre for Brain Repair, Forvie )] TJ ET
BT 26.250 446.048 Td /F1 9.8 Tf  [(Site, Cambridge, UK Deidre O�Keefe, Cambridge Centre for Brain Repair, Forvie Site, Cambridge, UK Anna Di Pietro, )] TJ ET
BT 26.250 434.143 Td /F1 9.8 Tf  [(Cambridge Centre for Brain Repair, Forvie Site, Cambridge, UK Kate Fisher, Cambridge Centre for Brain Repair, Forvie Site, )] TJ ET
BT 26.250 422.238 Td /F1 9.8 Tf  [(Cambridge, UK Anna Goodman, Cambridge Centre for Brain Repair, Forvie Site, Cambridge, UK Susan Hill, Cambridge Centre )] TJ ET
BT 26.250 410.334 Td /F1 9.8 Tf  [(for Brain Repair, Forvie Site, Cambridge, UK Ann Kershaw, Cambridge Centre for Brain Repair, Forvie Site, Cambridge, UK )] TJ ET
BT 26.250 398.429 Td /F1 9.8 Tf  [(Sarah Mason, Cambridge Centre for Brain Repair, Forvie Site, Cambridge, UK Nicole Paterson, Cambridge Centre for Brain )] TJ ET
BT 26.250 386.524 Td /F1 9.8 Tf  [(Repair, Forvie Site, Cambridge, UK Rachel Swain, Cambridge Centre for Brain Repair, Forvie Site, Cambridge, UK Lucy )] TJ ET
BT 26.250 374.619 Td /F1 9.8 Tf  [(Raymon, Cambridge Centre for Brain Repair, Forvie Site, Cambridge, UK Monica Busse, The Institute of Medical Genetics, )] TJ ET
BT 26.250 362.715 Td /F1 9.8 Tf  [(University Hospital of Wales, Cardif, UK Stephen Dunnett, The Institute of Medical Genetics, University Hospital of Wales, )] TJ ET
BT 26.250 350.810 Td /F1 9.8 Tf  [(Cardif, UK Catherine Clenaghan, The Institute of Medical Genetics, University Hospital of Wales, Cardif, UK Ruth Fullham, The )] TJ ET
BT 26.250 338.905 Td /F1 9.8 Tf  [(Institute of Medical Genetics, University Hospital of Wales, Cardif, UK Sarah Hunt, The Institute of Medical Genetics, University )] TJ ET
BT 26.250 327.000 Td /F1 9.8 Tf  [(Hospital of Wales, Cardif, UK Lesley Jones, The Institute of Medical Genetics, University Hospital of Wales, Cardif, UK Una )] TJ ET
BT 26.250 315.096 Td /F1 9.8 Tf  [(Jones, The Institute of Medical Genetics, University Hospital of Wales, Cardif, UK Hanan Khalil, The Institute of Medical )] TJ ET
BT 26.250 303.191 Td /F1 9.8 Tf  [(Genetics, University Hospital of Wales, Cardif, UK Sara Minster, The Institute of Medical Genetics, University Hospital of Wales, )] TJ ET
BT 26.250 291.286 Td /F1 9.8 Tf  [(Cardif, UK Michael Owen, The Institute of Medical Genetics, University Hospital of Wales, Cardif, UK Kathleen Price, The )] TJ ET
BT 26.250 279.381 Td /F1 9.8 Tf  [(Institute of Medical Genetics, University Hospital of Wales, Cardif, UK Jenny Townshill,The Institute of Medical Genetics, )] TJ ET
BT 26.250 267.477 Td /F1 9.8 Tf  [(University Hospital of Wales, Cardif, UK Anne Rosser, The Institute of Medical Genetics, University Hospital of Wales, Cardif, )] TJ ET
BT 26.250 255.572 Td /F1 9.8 Tf  [(UK Maureen Edwards, Molecular Medicine Centre, Western General Hospital, Department of Clinical Genetics, Edinburg, UK )] TJ ET
BT 26.250 243.667 Td /F1 9.8 Tf  [(Teresa Hughes \(Scottish Huntington�s Association\), Molecular Medicine Centre, Western General Hospital, Department of )] TJ ET
BT 26.250 231.762 Td /F1 9.8 Tf  [(Clinical Genetics, Edinburg, UK Marie McGill, Molecular Medicine Centre, Western General Hospital, Department of Clinical )] TJ ET
BT 26.250 219.858 Td /F1 9.8 Tf  [(Genetics, Edinburg, UK Pauline Pearson, Molecular Medicine Centre, Western General Hospital, Department of Clinical )] TJ ET
BT 26.250 207.953 Td /F1 9.8 Tf  [(Genetics, Edinburg, UK Mary Porteous, Molecular Medicine Centre, Western General Hospital, Department of Clinical Genetics, )] TJ ET
BT 26.250 196.048 Td /F1 9.8 Tf  [(Edinburg, UK Paul Smith \(Scottish Huntington�s Association\), Molecular Medicine Centre, Western General Hospital, )] TJ ET
BT 26.250 184.143 Td /F1 9.8 Tf  [(Department of Clinical Genetics, Edinburg, UK Adam Zeman, Molecular Medicine Centre, Western General Hospital, )] TJ ET
BT 26.250 172.239 Td /F1 9.8 Tf  [(Department of Clinical Genetics, Edinburg, UK Peter Brockie, Scottish Huntington�s Association Whyteman�s Brae Hospital, )] TJ ET
BT 26.250 160.334 Td /F1 9.8 Tf  [(Fife, UK Jillian Foster, Scottish Huntington�s Association Whyteman�s Brae Hospital, Fife, UK Nicola Johns, Scottish )] TJ ET
BT 26.250 148.429 Td /F1 9.8 Tf  [(Huntington�s Association Whyteman�s Brae Hospital, Fife, UK Sue McKenzie, Scottish Huntington�s Association Whyteman�s )] TJ ET
BT 26.250 136.524 Td /F1 9.8 Tf  [(Brae Hospital, Fife, UK Jean Rothery, Scottish Huntington�s Association Whyteman�s Brae Hospital, Fife, UK Gareth Thomas, )] TJ ET
BT 26.250 124.620 Td /F1 9.8 Tf  [(Scottish Huntington�s Association Whyteman�s Brae Hospital, Fife, UK Shona Yates, Scottish Huntington�s Association )] TJ ET
BT 26.250 112.715 Td /F1 9.8 Tf  [(Whyteman�s Brae Hospital, Fife, UK Joanne Miller, Abercromby Center, Glasgow, UK Stuart Ritchie, Abercromby Center, )] TJ ET
BT 26.250 100.810 Td /F1 9.8 Tf  [(Glasgow, UK Liz Burrows, Department of Neurology Gloucestershire Royal Hospital, Gloucester, UK Amy Fletcher, Department )] TJ ET
BT 26.250 88.905 Td /F1 9.8 Tf  [(of Neurology Gloucestershire Royal Hospital, Gloucester, UK Alison Harding, Department of Neurology Gloucestershire Royal )] TJ ET
BT 26.250 77.001 Td /F1 9.8 Tf  [(Hospital, Gloucester, UK Fiona Laver, Department of Neurology Gloucestershire Royal Hospital, Gloucester, UK Mark Silva, )] TJ ET
BT 26.250 65.096 Td /F1 9.8 Tf  [(Department of Neurology Gloucestershire Royal Hospital, Gloucester, UK Aileen Thomson, Department of Neurology )] TJ ET
BT 26.250 53.191 Td /F1 9.8 Tf  [(Gloucestershire Royal Hospital, Gloucester, UK Peter Burns, Castle Hill Hospital, Hull, UK Carol Chu, Castle Hill Hospital, Hull, )] TJ ET
BT 26.250 41.286 Td /F1 9.8 Tf  [(UK Carole Evans, Castle Hill Hospital, Hull, UK Stephanie Hamer, Castle Hill Hospital, Hull, UK Ivana Markova, Castle Hill )] TJ ET
BT 26.250 29.382 Td /F1 9.8 Tf  [(Hospital, Hull, UK Julie Miller, Castle Hill Hospital, Hull, UK Ashok Raman, Castle Hill Hospital, Hull, UK Kathy Barnes, Chapel )] TJ ET
Q
q
0.000 0.000 0.000 rg
BT 291.710 19.825 Td /F1 11.0 Tf  [(11)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Huntington Disease)] TJ ET

Q
endstream
endobj
193 0 obj
<< /Type /Page
/Parent 3 0 R
/Contents 194 0 R
>>
endobj
194 0 obj
<<
/Length 28421 >>
stream

0.271 0.267 0.267 rg
q
15.000 24.125 577.500 752.875 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(Allerton Hospital, Department of Clinical Genetics, Leeds , UK Carol Chu, Chapel Allerton Hospital, Department of Clinical )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(Genetics, Leeds , UK Emma Hobson, Chapel Allerton Hospital, Department of Clinical Genetics, Leeds , UK Stuart Jamieson, )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(Chapel Allerton Hospital, Department of Clinical Genetics, Leeds , UK Ivana Markova, Chapel Allerton Hospital, Department of )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(Clinical Genetics, Leeds , UK Jenny Thomson, Chapel Allerton Hospital, Department of Clinical Genetics, Leeds , UK Jean )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(Toscano, Chapel Allerton Hospital, Department of Clinical Genetics, Leeds , UK Sue Wild, Chapel Allerton Hospital, Department )] TJ ET
BT 26.250 707.952 Td /F1 9.8 Tf  [(of Clinical Genetics, Leeds , UK Pam Yardumian, Chapel Allerton Hospital, Department of Clinical Genetics, Leeds , UK Colin )] TJ ET
BT 26.250 696.048 Td /F1 9.8 Tf  [(Bourne, Leicestershire Partnership Trust, Mill Lodge, Leicester, UK Carole Clayton, Leicestershire Partnership Trust, Mill Lodge, )] TJ ET
BT 26.250 684.143 Td /F1 9.8 Tf  [(Leicester, UK Heather Dipple, Leicestershire Partnership Trust, Mill Lodge, Leicester, UK Jackie Clapton, Leicestershire )] TJ ET
BT 26.250 672.238 Td /F1 9.8 Tf  [(Partnership Trust, Mill Lodge, Leicester, UK Janet Grant, Leicestershire Partnership Trust, Mill Lodge, Leicester, UK Diana )] TJ ET
BT 26.250 660.333 Td /F1 9.8 Tf  [(Gross, Leicestershire Partnership Trust, Mill Lodge, Leicester, UK Caroline Hallam, Leicestershire Partnership Trust, Mill Lodge, )] TJ ET
BT 26.250 648.429 Td /F1 9.8 Tf  [(Leicester, UK Julia Middleton, Leicestershire Partnership Trust, Mill Lodge, Leicester, UK Ann Murch,Leicestershire Partnership )] TJ ET
BT 26.250 636.524 Td /F1 9.8 Tf  [(Trust, Mill Lodge, Leicester, UK Dawn Patino, Leicestershire Partnership Trust, Mill Lodge, Leicester, UK Thomasin Andrews, )] TJ ET
BT 26.250 624.619 Td /F1 9.8 Tf  [(Guy�s Hospital, London, UK Andrew Dougherty, Guy�s Hospital, London, UK Fred Kavalier, Guy�s Hospital, London, UK )] TJ ET
BT 26.250 612.714 Td /F1 9.8 Tf  [(Charlotte Golding, Guy�s Hospital, London, UK Alison Lashwood, Guy�s Hospital, London, UK Dene Robertson, Guy�s Hospital, )] TJ ET
BT 26.250 600.810 Td /F1 9.8 Tf  [(London, UK Deborah Ruddy,Guy�s Hospital, London, UK Anna Whait, Guy�s Hospital, London, UK Michael Patton, St. Georges-)] TJ ET
BT 26.250 588.905 Td /F1 9.8 Tf  [(Hospital, London, UK Maria Peterson, St. Georges-Hospital, London, UK Sarah Rose, St. Georges-Hospital, London, UK )] TJ ET
BT 26.250 577.000 Td /F1 9.8 Tf  [(Thomasin Andrews, The National Hospital for Neurology and Neurosurgery, London, UK Stefania Bruno, The National Hospital )] TJ ET
BT 26.250 565.095 Td /F1 9.8 Tf  [(for Neurology and Neurosurgery, London, UK Charlotte Golding, The National Hospital for Neurology and Neurosurgery, )] TJ ET
BT 26.250 553.191 Td /F1 9.8 Tf  [(London, UK Nayana Lahiri, The National Hospital for Neurology and Neurosurgery, London, UK Marianne Novak, The National )] TJ ET
BT 26.250 541.286 Td /F1 9.8 Tf  [(Hospital for Neurology and Neurosurgery, London, UK Aakta Patel, The National Hospital for Neurology and Neurosurgery, )] TJ ET
BT 26.250 529.381 Td /F1 9.8 Tf  [(London, UK Elisabeth Rosser, The National Hospital for Neurology and Neurosurgery, London, UK Sarah Tabrizi, The National )] TJ ET
BT 26.250 517.476 Td /F1 9.8 Tf  [(Hospital for Neurology and Neurosurgery, London, UK Rachel Taylor, The National Hospital for Neurology and Neurosurgery, )] TJ ET
BT 26.250 505.572 Td /F1 9.8 Tf  [(London, UK Thomas Warner, The National Hospital for Neurology and Neurosurgery, London, UK Edward Wild, The National )] TJ ET
BT 26.250 493.667 Td /F1 9.8 Tf  [(Hospital for Neurology and Neurosurgery, London, UK Natalie Arran, Genetic Medicine, University of Manchester, Manchester )] TJ ET
BT 26.250 481.762 Td /F1 9.8 Tf  [(Academic Health Sciences Centre and Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK Jenny )] TJ ET
BT 26.250 469.857 Td /F1 9.8 Tf  [(Callaghan, Genetic Medicine, University of Manchester, Manchester Academic Health Sciences Centre and Central Manchester )] TJ ET
BT 26.250 457.953 Td /F1 9.8 Tf  [(University Hospitals NHS Foundation Trust, Manchester, UK David Craufurd, Genetic Medicine, University of Manchester, )] TJ ET
BT 26.250 446.048 Td /F1 9.8 Tf  [(Manchester Academic Health Sciences Centre and Central Manchester University Hospitals NHS Foundation Trust, )] TJ ET
BT 26.250 434.143 Td /F1 9.8 Tf  [(Manchester, UK Ruth Fullam, Genetic Medicine, University of Manchester, Manchester Academic Health Sciences Centre and )] TJ ET
BT 26.250 422.238 Td /F1 9.8 Tf  [(Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK Liz Howard, Genetic Medicine, University of )] TJ ET
BT 26.250 410.334 Td /F1 9.8 Tf  [(Manchester, Manchester Academic Health Sciences Centre and Central Manchester University Hospitals NHS Foundation )] TJ ET
BT 26.250 398.429 Td /F1 9.8 Tf  [(Trust, Manchester, UK Susan Huson, Genetic Medicine, University of Manchester, Manchester Academic Health Sciences )] TJ ET
BT 26.250 386.524 Td /F1 9.8 Tf  [(Centre and Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK Lucy Partington-Jones, Genetic )] TJ ET
BT 26.250 374.619 Td /F1 9.8 Tf  [(Medicine, University of Manchester, Manchester Academic Health Sciences Centre and Central Manchester University )] TJ ET
BT 26.250 362.715 Td /F1 9.8 Tf  [(Hospitals NHS Foundation Trust, Manchester, UK Julie Snowden, Genetic Medicine, University of Manchester, Manchester )] TJ ET
BT 26.250 350.810 Td /F1 9.8 Tf  [(Academic Health Sciences Centre and Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK Andrea )] TJ ET
BT 26.250 338.905 Td /F1 9.8 Tf  [(Sollom, Genetic Medicine, University of Manchester, Manchester Academic Health Sciences Centre and Central Manchester )] TJ ET
BT 26.250 327.000 Td /F1 9.8 Tf  [(University Hospitals NHS Foundation Trust, Manchester, UK Jennifer Thompson, Genetic Medicine, University of Manchester, )] TJ ET
BT 26.250 315.096 Td /F1 9.8 Tf  [(Manchester Academic Health Sciences Centre and Central Manchester University Hospitals NHS Foundation Trust, )] TJ ET
BT 26.250 303.191 Td /F1 9.8 Tf  [(Manchester, UK Cheryl Stopford, Genetic Medicine, University of Manchester, Manchester Academic Health Sciences Centre )] TJ ET
BT 26.250 291.286 Td /F1 9.8 Tf  [(and Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK Nichola Verstraelen \(formerly Ritchie\), )] TJ ET
BT 26.250 279.381 Td /F1 9.8 Tf  [(Genetic Medicine, University of Manchester, Manchester Academic Health Sciences Centre and Central Manchester University )] TJ ET
BT 26.250 267.477 Td /F1 9.8 Tf  [(Hospitals NHS Foundation Trust, Manchester, UK Leann Westmoreland, Genetic Medicine, University of Manchester, )] TJ ET
BT 26.250 255.572 Td /F1 9.8 Tf  [(Manchester Academic Health Sciences Centre and Central Manchester University Hospitals NHS Foundation Trust, )] TJ ET
BT 26.250 243.667 Td /F1 9.8 Tf  [(Manchester, UK Andrea H Nemeth, Oxford Radcliffe Hospitals NHS Trust, Oxford, UK Gill Siuda, Oxford Radcliffe Hospitals )] TJ ET
BT 26.250 231.762 Td /F1 9.8 Tf  [(NHS Trust, Oxford, UK David Harrison, Heathleigh Unit, Mount Gould Hospital, Plymouth, UK Max Hughes, Heathleigh Unit, )] TJ ET
BT 26.250 219.858 Td /F1 9.8 Tf  [(Mount Gould Hospital, Plymouth, UK Andrew Parkinson, Heathleigh Unit, Mount Gould Hospital, Plymouth, UK Beverley )] TJ ET
BT 26.250 207.953 Td /F1 9.8 Tf  [(Soltysiak, Heathleigh Unit, Mount Gould Hospital, Plymouth, UK Oliver Bandmann, The Royal Hallamshire Hospital� Sheffield )] TJ ET
BT 26.250 196.048 Td /F1 9.8 Tf  [(Children�s Hospital, Sheffield, UK Alyson Bradbury, The Royal Hallamshire Hospital� Sheffield Children�s Hospital, Sheffield, UK )] TJ ET
BT 26.250 184.143 Td /F1 9.8 Tf  [(Paul Gill, The Royal Hallamshire Hospital� Sheffield Children�s Hospital, Sheffield, UK Helen Fairtlough, The Royal Hallamshire )] TJ ET
BT 26.250 172.239 Td /F1 9.8 Tf  [(Hospital� Sheffield Children�s Hospital, Sheffield, UK Kay Fillingham, The Royal Hallamshire Hospital� Sheffield Children�s )] TJ ET
BT 26.250 160.334 Td /F1 9.8 Tf  [(Hospital, Sheffield, UK Isabella Foustanos, The Royal Hallamshire Hospital� Sheffield Children�s Hospital, Sheffield, UK Kirsty )] TJ ET
BT 26.250 148.429 Td /F1 9.8 Tf  [(O�Donovan, The Royal Hallamshire Hospital� Sheffield Children�s Hospital, Sheffield, UK Nadia Peppa, The Royal Hallamshire )] TJ ET
BT 26.250 136.524 Td /F1 9.8 Tf  [(Hospital� Sheffield Children�s Hospital, Sheffield, UK Katherine Tidswell, The Royal Hallamshire Hospital� Sheffield Children�s )] TJ ET
BT 26.250 124.620 Td /F1 9.8 Tf  [(Hospital, Sheffield, UK Oliver Quarrell, The Royal Hallamshire Hospital� Sheffield Children�s Hospital, Sheffield, UK)] TJ ET
BT 26.250 95.517 Td /F4 12.0 Tf  [(Acknowledgements)] TJ ET
BT 26.250 75.563 Td /F1 9.8 Tf  [(This research is supported by CHDI Foundation, Inc. We thank the REGISTRY sites and the study participants for their time )] TJ ET
BT 562.178 75.563 Td /F1 9.8 Tf  [(and )] TJ ET
BT 26.250 63.658 Td /F1 9.8 Tf  [(effort.)] TJ ET
Q
q
15.000 24.125 577.500 752.875 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(Allerton Hospital, Department of Clinical Genetics, Leeds , UK Carol Chu, Chapel Allerton Hospital, Department of Clinical )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(Genetics, Leeds , UK Emma Hobson, Chapel Allerton Hospital, Department of Clinical Genetics, Leeds , UK Stuart Jamieson, )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(Chapel Allerton Hospital, Department of Clinical Genetics, Leeds , UK Ivana Markova, Chapel Allerton Hospital, Department of )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(Clinical Genetics, Leeds , UK Jenny Thomson, Chapel Allerton Hospital, Department of Clinical Genetics, Leeds , UK Jean )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(Toscano, Chapel Allerton Hospital, Department of Clinical Genetics, Leeds , UK Sue Wild, Chapel Allerton Hospital, Department )] TJ ET
BT 26.250 707.952 Td /F1 9.8 Tf  [(of Clinical Genetics, Leeds , UK Pam Yardumian, Chapel Allerton Hospital, Department of Clinical Genetics, Leeds , UK Colin )] TJ ET
BT 26.250 696.048 Td /F1 9.8 Tf  [(Bourne, Leicestershire Partnership Trust, Mill Lodge, Leicester, UK Carole Clayton, Leicestershire Partnership Trust, Mill Lodge, )] TJ ET
BT 26.250 684.143 Td /F1 9.8 Tf  [(Leicester, UK Heather Dipple, Leicestershire Partnership Trust, Mill Lodge, Leicester, UK Jackie Clapton, Leicestershire )] TJ ET
BT 26.250 672.238 Td /F1 9.8 Tf  [(Partnership Trust, Mill Lodge, Leicester, UK Janet Grant, Leicestershire Partnership Trust, Mill Lodge, Leicester, UK Diana )] TJ ET
BT 26.250 660.333 Td /F1 9.8 Tf  [(Gross, Leicestershire Partnership Trust, Mill Lodge, Leicester, UK Caroline Hallam, Leicestershire Partnership Trust, Mill Lodge, )] TJ ET
BT 26.250 648.429 Td /F1 9.8 Tf  [(Leicester, UK Julia Middleton, Leicestershire Partnership Trust, Mill Lodge, Leicester, UK Ann Murch,Leicestershire Partnership )] TJ ET
BT 26.250 636.524 Td /F1 9.8 Tf  [(Trust, Mill Lodge, Leicester, UK Dawn Patino, Leicestershire Partnership Trust, Mill Lodge, Leicester, UK Thomasin Andrews, )] TJ ET
BT 26.250 624.619 Td /F1 9.8 Tf  [(Guy�s Hospital, London, UK Andrew Dougherty, Guy�s Hospital, London, UK Fred Kavalier, Guy�s Hospital, London, UK )] TJ ET
BT 26.250 612.714 Td /F1 9.8 Tf  [(Charlotte Golding, Guy�s Hospital, London, UK Alison Lashwood, Guy�s Hospital, London, UK Dene Robertson, Guy�s Hospital, )] TJ ET
BT 26.250 600.810 Td /F1 9.8 Tf  [(London, UK Deborah Ruddy,Guy�s Hospital, London, UK Anna Whait, Guy�s Hospital, London, UK Michael Patton, St. Georges-)] TJ ET
BT 26.250 588.905 Td /F1 9.8 Tf  [(Hospital, London, UK Maria Peterson, St. Georges-Hospital, London, UK Sarah Rose, St. Georges-Hospital, London, UK )] TJ ET
BT 26.250 577.000 Td /F1 9.8 Tf  [(Thomasin Andrews, The National Hospital for Neurology and Neurosurgery, London, UK Stefania Bruno, The National Hospital )] TJ ET
BT 26.250 565.095 Td /F1 9.8 Tf  [(for Neurology and Neurosurgery, London, UK Charlotte Golding, The National Hospital for Neurology and Neurosurgery, )] TJ ET
BT 26.250 553.191 Td /F1 9.8 Tf  [(London, UK Nayana Lahiri, The National Hospital for Neurology and Neurosurgery, London, UK Marianne Novak, The National )] TJ ET
BT 26.250 541.286 Td /F1 9.8 Tf  [(Hospital for Neurology and Neurosurgery, London, UK Aakta Patel, The National Hospital for Neurology and Neurosurgery, )] TJ ET
BT 26.250 529.381 Td /F1 9.8 Tf  [(London, UK Elisabeth Rosser, The National Hospital for Neurology and Neurosurgery, London, UK Sarah Tabrizi, The National )] TJ ET
BT 26.250 517.476 Td /F1 9.8 Tf  [(Hospital for Neurology and Neurosurgery, London, UK Rachel Taylor, The National Hospital for Neurology and Neurosurgery, )] TJ ET
BT 26.250 505.572 Td /F1 9.8 Tf  [(London, UK Thomas Warner, The National Hospital for Neurology and Neurosurgery, London, UK Edward Wild, The National )] TJ ET
BT 26.250 493.667 Td /F1 9.8 Tf  [(Hospital for Neurology and Neurosurgery, London, UK Natalie Arran, Genetic Medicine, University of Manchester, Manchester )] TJ ET
BT 26.250 481.762 Td /F1 9.8 Tf  [(Academic Health Sciences Centre and Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK Jenny )] TJ ET
BT 26.250 469.857 Td /F1 9.8 Tf  [(Callaghan, Genetic Medicine, University of Manchester, Manchester Academic Health Sciences Centre and Central Manchester )] TJ ET
BT 26.250 457.953 Td /F1 9.8 Tf  [(University Hospitals NHS Foundation Trust, Manchester, UK David Craufurd, Genetic Medicine, University of Manchester, )] TJ ET
BT 26.250 446.048 Td /F1 9.8 Tf  [(Manchester Academic Health Sciences Centre and Central Manchester University Hospitals NHS Foundation Trust, )] TJ ET
BT 26.250 434.143 Td /F1 9.8 Tf  [(Manchester, UK Ruth Fullam, Genetic Medicine, University of Manchester, Manchester Academic Health Sciences Centre and )] TJ ET
BT 26.250 422.238 Td /F1 9.8 Tf  [(Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK Liz Howard, Genetic Medicine, University of )] TJ ET
BT 26.250 410.334 Td /F1 9.8 Tf  [(Manchester, Manchester Academic Health Sciences Centre and Central Manchester University Hospitals NHS Foundation )] TJ ET
BT 26.250 398.429 Td /F1 9.8 Tf  [(Trust, Manchester, UK Susan Huson, Genetic Medicine, University of Manchester, Manchester Academic Health Sciences )] TJ ET
BT 26.250 386.524 Td /F1 9.8 Tf  [(Centre and Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK Lucy Partington-Jones, Genetic )] TJ ET
BT 26.250 374.619 Td /F1 9.8 Tf  [(Medicine, University of Manchester, Manchester Academic Health Sciences Centre and Central Manchester University )] TJ ET
BT 26.250 362.715 Td /F1 9.8 Tf  [(Hospitals NHS Foundation Trust, Manchester, UK Julie Snowden, Genetic Medicine, University of Manchester, Manchester )] TJ ET
BT 26.250 350.810 Td /F1 9.8 Tf  [(Academic Health Sciences Centre and Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK Andrea )] TJ ET
BT 26.250 338.905 Td /F1 9.8 Tf  [(Sollom, Genetic Medicine, University of Manchester, Manchester Academic Health Sciences Centre and Central Manchester )] TJ ET
BT 26.250 327.000 Td /F1 9.8 Tf  [(University Hospitals NHS Foundation Trust, Manchester, UK Jennifer Thompson, Genetic Medicine, University of Manchester, )] TJ ET
BT 26.250 315.096 Td /F1 9.8 Tf  [(Manchester Academic Health Sciences Centre and Central Manchester University Hospitals NHS Foundation Trust, )] TJ ET
BT 26.250 303.191 Td /F1 9.8 Tf  [(Manchester, UK Cheryl Stopford, Genetic Medicine, University of Manchester, Manchester Academic Health Sciences Centre )] TJ ET
BT 26.250 291.286 Td /F1 9.8 Tf  [(and Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK Nichola Verstraelen \(formerly Ritchie\), )] TJ ET
BT 26.250 279.381 Td /F1 9.8 Tf  [(Genetic Medicine, University of Manchester, Manchester Academic Health Sciences Centre and Central Manchester University )] TJ ET
BT 26.250 267.477 Td /F1 9.8 Tf  [(Hospitals NHS Foundation Trust, Manchester, UK Leann Westmoreland, Genetic Medicine, University of Manchester, )] TJ ET
BT 26.250 255.572 Td /F1 9.8 Tf  [(Manchester Academic Health Sciences Centre and Central Manchester University Hospitals NHS Foundation Trust, )] TJ ET
BT 26.250 243.667 Td /F1 9.8 Tf  [(Manchester, UK Andrea H Nemeth, Oxford Radcliffe Hospitals NHS Trust, Oxford, UK Gill Siuda, Oxford Radcliffe Hospitals )] TJ ET
BT 26.250 231.762 Td /F1 9.8 Tf  [(NHS Trust, Oxford, UK David Harrison, Heathleigh Unit, Mount Gould Hospital, Plymouth, UK Max Hughes, Heathleigh Unit, )] TJ ET
BT 26.250 219.858 Td /F1 9.8 Tf  [(Mount Gould Hospital, Plymouth, UK Andrew Parkinson, Heathleigh Unit, Mount Gould Hospital, Plymouth, UK Beverley )] TJ ET
BT 26.250 207.953 Td /F1 9.8 Tf  [(Soltysiak, Heathleigh Unit, Mount Gould Hospital, Plymouth, UK Oliver Bandmann, The Royal Hallamshire Hospital� Sheffield )] TJ ET
BT 26.250 196.048 Td /F1 9.8 Tf  [(Children�s Hospital, Sheffield, UK Alyson Bradbury, The Royal Hallamshire Hospital� Sheffield Children�s Hospital, Sheffield, UK )] TJ ET
BT 26.250 184.143 Td /F1 9.8 Tf  [(Paul Gill, The Royal Hallamshire Hospital� Sheffield Children�s Hospital, Sheffield, UK Helen Fairtlough, The Royal Hallamshire )] TJ ET
BT 26.250 172.239 Td /F1 9.8 Tf  [(Hospital� Sheffield Children�s Hospital, Sheffield, UK Kay Fillingham, The Royal Hallamshire Hospital� Sheffield Children�s )] TJ ET
BT 26.250 160.334 Td /F1 9.8 Tf  [(Hospital, Sheffield, UK Isabella Foustanos, The Royal Hallamshire Hospital� Sheffield Children�s Hospital, Sheffield, UK Kirsty )] TJ ET
BT 26.250 148.429 Td /F1 9.8 Tf  [(O�Donovan, The Royal Hallamshire Hospital� Sheffield Children�s Hospital, Sheffield, UK Nadia Peppa, The Royal Hallamshire )] TJ ET
BT 26.250 136.524 Td /F1 9.8 Tf  [(Hospital� Sheffield Children�s Hospital, Sheffield, UK Katherine Tidswell, The Royal Hallamshire Hospital� Sheffield Children�s )] TJ ET
BT 26.250 124.620 Td /F1 9.8 Tf  [(Hospital, Sheffield, UK Oliver Quarrell, The Royal Hallamshire Hospital� Sheffield Children�s Hospital, Sheffield, UK)] TJ ET
BT 26.250 95.517 Td /F4 12.0 Tf  [(Acknowledgements)] TJ ET
BT 26.250 75.563 Td /F1 9.8 Tf  [(This research is supported by CHDI Foundation, Inc. We thank the REGISTRY sites and the study participants for their time )] TJ ET
BT 562.178 75.563 Td /F1 9.8 Tf  [(and )] TJ ET
BT 26.250 63.658 Td /F1 9.8 Tf  [(effort.)] TJ ET
Q
q
15.000 24.125 577.500 752.875 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(Allerton Hospital, Department of Clinical Genetics, Leeds , UK Carol Chu, Chapel Allerton Hospital, Department of Clinical )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(Genetics, Leeds , UK Emma Hobson, Chapel Allerton Hospital, Department of Clinical Genetics, Leeds , UK Stuart Jamieson, )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(Chapel Allerton Hospital, Department of Clinical Genetics, Leeds , UK Ivana Markova, Chapel Allerton Hospital, Department of )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(Clinical Genetics, Leeds , UK Jenny Thomson, Chapel Allerton Hospital, Department of Clinical Genetics, Leeds , UK Jean )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(Toscano, Chapel Allerton Hospital, Department of Clinical Genetics, Leeds , UK Sue Wild, Chapel Allerton Hospital, Department )] TJ ET
BT 26.250 707.952 Td /F1 9.8 Tf  [(of Clinical Genetics, Leeds , UK Pam Yardumian, Chapel Allerton Hospital, Department of Clinical Genetics, Leeds , UK Colin )] TJ ET
BT 26.250 696.048 Td /F1 9.8 Tf  [(Bourne, Leicestershire Partnership Trust, Mill Lodge, Leicester, UK Carole Clayton, Leicestershire Partnership Trust, Mill Lodge, )] TJ ET
BT 26.250 684.143 Td /F1 9.8 Tf  [(Leicester, UK Heather Dipple, Leicestershire Partnership Trust, Mill Lodge, Leicester, UK Jackie Clapton, Leicestershire )] TJ ET
BT 26.250 672.238 Td /F1 9.8 Tf  [(Partnership Trust, Mill Lodge, Leicester, UK Janet Grant, Leicestershire Partnership Trust, Mill Lodge, Leicester, UK Diana )] TJ ET
BT 26.250 660.333 Td /F1 9.8 Tf  [(Gross, Leicestershire Partnership Trust, Mill Lodge, Leicester, UK Caroline Hallam, Leicestershire Partnership Trust, Mill Lodge, )] TJ ET
BT 26.250 648.429 Td /F1 9.8 Tf  [(Leicester, UK Julia Middleton, Leicestershire Partnership Trust, Mill Lodge, Leicester, UK Ann Murch,Leicestershire Partnership )] TJ ET
BT 26.250 636.524 Td /F1 9.8 Tf  [(Trust, Mill Lodge, Leicester, UK Dawn Patino, Leicestershire Partnership Trust, Mill Lodge, Leicester, UK Thomasin Andrews, )] TJ ET
BT 26.250 624.619 Td /F1 9.8 Tf  [(Guy�s Hospital, London, UK Andrew Dougherty, Guy�s Hospital, London, UK Fred Kavalier, Guy�s Hospital, London, UK )] TJ ET
BT 26.250 612.714 Td /F1 9.8 Tf  [(Charlotte Golding, Guy�s Hospital, London, UK Alison Lashwood, Guy�s Hospital, London, UK Dene Robertson, Guy�s Hospital, )] TJ ET
BT 26.250 600.810 Td /F1 9.8 Tf  [(London, UK Deborah Ruddy,Guy�s Hospital, London, UK Anna Whait, Guy�s Hospital, London, UK Michael Patton, St. Georges-)] TJ ET
BT 26.250 588.905 Td /F1 9.8 Tf  [(Hospital, London, UK Maria Peterson, St. Georges-Hospital, London, UK Sarah Rose, St. Georges-Hospital, London, UK )] TJ ET
BT 26.250 577.000 Td /F1 9.8 Tf  [(Thomasin Andrews, The National Hospital for Neurology and Neurosurgery, London, UK Stefania Bruno, The National Hospital )] TJ ET
BT 26.250 565.095 Td /F1 9.8 Tf  [(for Neurology and Neurosurgery, London, UK Charlotte Golding, The National Hospital for Neurology and Neurosurgery, )] TJ ET
BT 26.250 553.191 Td /F1 9.8 Tf  [(London, UK Nayana Lahiri, The National Hospital for Neurology and Neurosurgery, London, UK Marianne Novak, The National )] TJ ET
BT 26.250 541.286 Td /F1 9.8 Tf  [(Hospital for Neurology and Neurosurgery, London, UK Aakta Patel, The National Hospital for Neurology and Neurosurgery, )] TJ ET
BT 26.250 529.381 Td /F1 9.8 Tf  [(London, UK Elisabeth Rosser, The National Hospital for Neurology and Neurosurgery, London, UK Sarah Tabrizi, The National )] TJ ET
BT 26.250 517.476 Td /F1 9.8 Tf  [(Hospital for Neurology and Neurosurgery, London, UK Rachel Taylor, The National Hospital for Neurology and Neurosurgery, )] TJ ET
BT 26.250 505.572 Td /F1 9.8 Tf  [(London, UK Thomas Warner, The National Hospital for Neurology and Neurosurgery, London, UK Edward Wild, The National )] TJ ET
BT 26.250 493.667 Td /F1 9.8 Tf  [(Hospital for Neurology and Neurosurgery, London, UK Natalie Arran, Genetic Medicine, University of Manchester, Manchester )] TJ ET
BT 26.250 481.762 Td /F1 9.8 Tf  [(Academic Health Sciences Centre and Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK Jenny )] TJ ET
BT 26.250 469.857 Td /F1 9.8 Tf  [(Callaghan, Genetic Medicine, University of Manchester, Manchester Academic Health Sciences Centre and Central Manchester )] TJ ET
BT 26.250 457.953 Td /F1 9.8 Tf  [(University Hospitals NHS Foundation Trust, Manchester, UK David Craufurd, Genetic Medicine, University of Manchester, )] TJ ET
BT 26.250 446.048 Td /F1 9.8 Tf  [(Manchester Academic Health Sciences Centre and Central Manchester University Hospitals NHS Foundation Trust, )] TJ ET
BT 26.250 434.143 Td /F1 9.8 Tf  [(Manchester, UK Ruth Fullam, Genetic Medicine, University of Manchester, Manchester Academic Health Sciences Centre and )] TJ ET
BT 26.250 422.238 Td /F1 9.8 Tf  [(Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK Liz Howard, Genetic Medicine, University of )] TJ ET
BT 26.250 410.334 Td /F1 9.8 Tf  [(Manchester, Manchester Academic Health Sciences Centre and Central Manchester University Hospitals NHS Foundation )] TJ ET
BT 26.250 398.429 Td /F1 9.8 Tf  [(Trust, Manchester, UK Susan Huson, Genetic Medicine, University of Manchester, Manchester Academic Health Sciences )] TJ ET
BT 26.250 386.524 Td /F1 9.8 Tf  [(Centre and Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK Lucy Partington-Jones, Genetic )] TJ ET
BT 26.250 374.619 Td /F1 9.8 Tf  [(Medicine, University of Manchester, Manchester Academic Health Sciences Centre and Central Manchester University )] TJ ET
BT 26.250 362.715 Td /F1 9.8 Tf  [(Hospitals NHS Foundation Trust, Manchester, UK Julie Snowden, Genetic Medicine, University of Manchester, Manchester )] TJ ET
BT 26.250 350.810 Td /F1 9.8 Tf  [(Academic Health Sciences Centre and Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK Andrea )] TJ ET
BT 26.250 338.905 Td /F1 9.8 Tf  [(Sollom, Genetic Medicine, University of Manchester, Manchester Academic Health Sciences Centre and Central Manchester )] TJ ET
BT 26.250 327.000 Td /F1 9.8 Tf  [(University Hospitals NHS Foundation Trust, Manchester, UK Jennifer Thompson, Genetic Medicine, University of Manchester, )] TJ ET
BT 26.250 315.096 Td /F1 9.8 Tf  [(Manchester Academic Health Sciences Centre and Central Manchester University Hospitals NHS Foundation Trust, )] TJ ET
BT 26.250 303.191 Td /F1 9.8 Tf  [(Manchester, UK Cheryl Stopford, Genetic Medicine, University of Manchester, Manchester Academic Health Sciences Centre )] TJ ET
BT 26.250 291.286 Td /F1 9.8 Tf  [(and Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK Nichola Verstraelen \(formerly Ritchie\), )] TJ ET
BT 26.250 279.381 Td /F1 9.8 Tf  [(Genetic Medicine, University of Manchester, Manchester Academic Health Sciences Centre and Central Manchester University )] TJ ET
BT 26.250 267.477 Td /F1 9.8 Tf  [(Hospitals NHS Foundation Trust, Manchester, UK Leann Westmoreland, Genetic Medicine, University of Manchester, )] TJ ET
BT 26.250 255.572 Td /F1 9.8 Tf  [(Manchester Academic Health Sciences Centre and Central Manchester University Hospitals NHS Foundation Trust, )] TJ ET
BT 26.250 243.667 Td /F1 9.8 Tf  [(Manchester, UK Andrea H Nemeth, Oxford Radcliffe Hospitals NHS Trust, Oxford, UK Gill Siuda, Oxford Radcliffe Hospitals )] TJ ET
BT 26.250 231.762 Td /F1 9.8 Tf  [(NHS Trust, Oxford, UK David Harrison, Heathleigh Unit, Mount Gould Hospital, Plymouth, UK Max Hughes, Heathleigh Unit, )] TJ ET
BT 26.250 219.858 Td /F1 9.8 Tf  [(Mount Gould Hospital, Plymouth, UK Andrew Parkinson, Heathleigh Unit, Mount Gould Hospital, Plymouth, UK Beverley )] TJ ET
BT 26.250 207.953 Td /F1 9.8 Tf  [(Soltysiak, Heathleigh Unit, Mount Gould Hospital, Plymouth, UK Oliver Bandmann, The Royal Hallamshire Hospital� Sheffield )] TJ ET
BT 26.250 196.048 Td /F1 9.8 Tf  [(Children�s Hospital, Sheffield, UK Alyson Bradbury, The Royal Hallamshire Hospital� Sheffield Children�s Hospital, Sheffield, UK )] TJ ET
BT 26.250 184.143 Td /F1 9.8 Tf  [(Paul Gill, The Royal Hallamshire Hospital� Sheffield Children�s Hospital, Sheffield, UK Helen Fairtlough, The Royal Hallamshire )] TJ ET
BT 26.250 172.239 Td /F1 9.8 Tf  [(Hospital� Sheffield Children�s Hospital, Sheffield, UK Kay Fillingham, The Royal Hallamshire Hospital� Sheffield Children�s )] TJ ET
BT 26.250 160.334 Td /F1 9.8 Tf  [(Hospital, Sheffield, UK Isabella Foustanos, The Royal Hallamshire Hospital� Sheffield Children�s Hospital, Sheffield, UK Kirsty )] TJ ET
BT 26.250 148.429 Td /F1 9.8 Tf  [(O�Donovan, The Royal Hallamshire Hospital� Sheffield Children�s Hospital, Sheffield, UK Nadia Peppa, The Royal Hallamshire )] TJ ET
BT 26.250 136.524 Td /F1 9.8 Tf  [(Hospital� Sheffield Children�s Hospital, Sheffield, UK Katherine Tidswell, The Royal Hallamshire Hospital� Sheffield Children�s )] TJ ET
BT 26.250 124.620 Td /F1 9.8 Tf  [(Hospital, Sheffield, UK Oliver Quarrell, The Royal Hallamshire Hospital� Sheffield Children�s Hospital, Sheffield, UK)] TJ ET
BT 26.250 95.517 Td /F4 12.0 Tf  [(Acknowledgements)] TJ ET
BT 26.250 75.563 Td /F1 9.8 Tf  [(This research is supported by CHDI Foundation, Inc. We thank the REGISTRY sites and the study participants for their time )] TJ ET
BT 562.178 75.563 Td /F1 9.8 Tf  [(and )] TJ ET
BT 26.250 63.658 Td /F1 9.8 Tf  [(effort.)] TJ ET
Q
q
0.000 0.000 0.000 rg
BT 291.710 19.825 Td /F1 11.0 Tf  [(12)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Huntington Disease)] TJ ET

Q
endstream
endobj
195 0 obj
<< /Type /Page
/Parent 3 0 R
/Contents 196 0 R
>>
endobj
196 0 obj
<<
/Length 12107 >>
stream

0.271 0.267 0.267 rg
q
15.000 329.729 577.500 447.271 re W n
0.271 0.267 0.267 rg
BT 26.250 750.278 Td /F4 12.0 Tf  [(References)] TJ ET
BT 26.250 722.824 Td /F1 9.8 Tf  [(1.)] TJ ET
BT 38.132 722.824 Td /F1 9.8 Tf  [(The Huntington's Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded )] TJ ET
BT 26.250 710.919 Td /F1 9.8 Tf  [(and unstable on Huntington's disease chromosomes. Cell 1993;72:971-83.)] TJ ET
BT 26.250 691.515 Td /F1 9.8 Tf  [(2.)] TJ ET
BT 38.132 691.515 Td /F1 9.8 Tf  [(Langbehn DR, Brinkman RR, Falush D, Paulsen JS, Hayden MR. A new model for prediction of the age of onset and )] TJ ET
BT 26.250 679.610 Td /F1 9.8 Tf  [(penetrance for Huntington's disease based on CAG length. Clin Genet 2004;65:267-77.)] TJ ET
BT 26.250 660.205 Td /F1 9.8 Tf  [(3.)] TJ ET
BT 38.132 660.205 Td /F1 9.8 Tf  [(Wexler NS, Lorimer J, Porter J, et al. Venezuelan kindreds reveal that genetic and environmental factors modulate )] TJ ET
BT 26.250 648.300 Td /F1 9.8 Tf  [(Huntington's disease age of onset. Proc Natl Acad Sci U S A 2004;101:3498-503.)] TJ ET
BT 26.250 628.896 Td /F1 9.8 Tf  [(4.)] TJ ET
BT 38.132 628.896 Td /F1 9.8 Tf  [(Aylward EH, Codori AM, Barta PE, Pearlson GD, Harris GJ, Brandt J. Basal ganglia volume and proximity to onset in )] TJ ET
BT 26.250 616.991 Td /F1 9.8 Tf  [(presymptomatic Huntington disease. Arch Neurol 1996;53:1293-6.)] TJ ET
BT 26.250 597.586 Td /F1 9.8 Tf  [(5.)] TJ ET
BT 38.132 597.586 Td /F1 9.8 Tf  [(Ranen NG, Stine OC, Abbott MH, et al. Anticipation and instability of IT-15 \(CAG\)n repeats in parent-offspring pairs with )] TJ ET
BT 26.250 585.681 Td /F1 9.8 Tf  [(Huntington disease. Am J Hum Genet 1995;57:593-602.)] TJ ET
BT 26.250 566.277 Td /F1 9.8 Tf  [(6.)] TJ ET
BT 38.132 566.277 Td /F1 9.8 Tf  [(Orth M. Observing Huntington's disease: the European Huntington's Disease Network's REGISTRY. J Neurol Neurosurg )] TJ ET
BT 26.250 554.372 Td /F1 9.8 Tf  [(Psychiatry 2010:19 [Epub ahead of print].)] TJ ET
BT 26.250 534.967 Td /F1 9.8 Tf  [(7.)] TJ ET
BT 38.132 534.967 Td /F1 9.8 Tf  [(Paulsen JS, Hayden M, Stout JC, et al. Preparing for preventive clinical trials: the Predict-HD study. Arch Neurol 2006;63:883-)] TJ ET
BT 26.250 523.062 Td /F1 9.8 Tf  [(90.)] TJ ET
BT 26.250 503.658 Td /F1 9.8 Tf  [(8.)] TJ ET
BT 38.132 503.658 Td /F1 9.8 Tf  [(Huntington Study Group. Unified Huntington's Disease Rating Scale: reliability and consistency. Mov Disord 1996;11:136-42.)] TJ ET
BT 26.250 484.253 Td /F1 9.8 Tf  [(9.)] TJ ET
BT 38.132 484.253 Td /F1 9.8 Tf  [(Penney JB, Jr., Vonsattel JP, MacDonald ME, Gusella JF, Myers RH. CAG repeat number governs the development rate of )] TJ ET
BT 26.250 472.348 Td /F1 9.8 Tf  [(pathology in Huntington's disease. Ann Neurol 1997;41:689-92.)] TJ ET
BT 26.250 452.943 Td /F1 9.8 Tf  [(10.)] TJ ET
BT 43.553 452.943 Td /F1 9.8 Tf  [(Tabrizi SJ, Langbehn DR, Leavitt BR, et al. Biological and clinical manifestations of Huntington's disease in the longitudinal )] TJ ET
BT 26.250 441.039 Td /F1 9.8 Tf  [(TRACK-HD study: cross-sectional analysis of baseline data. Lancet Neurol 2009;8:791-801.)] TJ ET
BT 26.250 421.634 Td /F1 9.8 Tf  [(11.)] TJ ET
BT 43.553 421.634 Td /F1 9.8 Tf  [(Paulsen JS, Langbehn DR, Stout JC, et al. Detection of Huntington's disease decades before diagnosis: the Predict-HD )] TJ ET
BT 26.250 409.729 Td /F1 9.8 Tf  [(study. J Neurol Neurosurg Psychiatry 2008;79:874-80.)] TJ ET
BT 26.250 390.324 Td /F1 9.8 Tf  [(12.)] TJ ET
BT 43.553 390.324 Td /F1 9.8 Tf  [(Marder K, Zhao H, Myers RH, et al. Rate of functional decline in Huntington's disease. Huntington Study Group. Neurology )] TJ ET
BT 26.250 378.420 Td /F1 9.8 Tf  [(2000;54:452-8.)] TJ ET
BT 26.250 359.015 Td /F1 9.8 Tf  [(13.)] TJ ET
BT 43.553 359.015 Td /F1 9.8 Tf  [(Paulsen JS, Wang C, Duff K, et al. Challenges assessing clinical endpoints in early Huntington disease. Mov Disord )] TJ ET
BT 26.250 347.110 Td /F1 9.8 Tf  [(2010;25:2595-603.)] TJ ET
Q
q
15.000 329.729 577.500 447.271 re W n
0.271 0.267 0.267 rg
BT 26.250 750.278 Td /F4 12.0 Tf  [(References)] TJ ET
BT 26.250 722.824 Td /F1 9.8 Tf  [(1.)] TJ ET
BT 38.132 722.824 Td /F1 9.8 Tf  [(The Huntington's Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded )] TJ ET
BT 26.250 710.919 Td /F1 9.8 Tf  [(and unstable on Huntington's disease chromosomes. Cell 1993;72:971-83.)] TJ ET
BT 26.250 691.515 Td /F1 9.8 Tf  [(2.)] TJ ET
BT 38.132 691.515 Td /F1 9.8 Tf  [(Langbehn DR, Brinkman RR, Falush D, Paulsen JS, Hayden MR. A new model for prediction of the age of onset and )] TJ ET
BT 26.250 679.610 Td /F1 9.8 Tf  [(penetrance for Huntington's disease based on CAG length. Clin Genet 2004;65:267-77.)] TJ ET
BT 26.250 660.205 Td /F1 9.8 Tf  [(3.)] TJ ET
BT 38.132 660.205 Td /F1 9.8 Tf  [(Wexler NS, Lorimer J, Porter J, et al. Venezuelan kindreds reveal that genetic and environmental factors modulate )] TJ ET
BT 26.250 648.300 Td /F1 9.8 Tf  [(Huntington's disease age of onset. Proc Natl Acad Sci U S A 2004;101:3498-503.)] TJ ET
BT 26.250 628.896 Td /F1 9.8 Tf  [(4.)] TJ ET
BT 38.132 628.896 Td /F1 9.8 Tf  [(Aylward EH, Codori AM, Barta PE, Pearlson GD, Harris GJ, Brandt J. Basal ganglia volume and proximity to onset in )] TJ ET
BT 26.250 616.991 Td /F1 9.8 Tf  [(presymptomatic Huntington disease. Arch Neurol 1996;53:1293-6.)] TJ ET
BT 26.250 597.586 Td /F1 9.8 Tf  [(5.)] TJ ET
BT 38.132 597.586 Td /F1 9.8 Tf  [(Ranen NG, Stine OC, Abbott MH, et al. Anticipation and instability of IT-15 \(CAG\)n repeats in parent-offspring pairs with )] TJ ET
BT 26.250 585.681 Td /F1 9.8 Tf  [(Huntington disease. Am J Hum Genet 1995;57:593-602.)] TJ ET
BT 26.250 566.277 Td /F1 9.8 Tf  [(6.)] TJ ET
BT 38.132 566.277 Td /F1 9.8 Tf  [(Orth M. Observing Huntington's disease: the European Huntington's Disease Network's REGISTRY. J Neurol Neurosurg )] TJ ET
BT 26.250 554.372 Td /F1 9.8 Tf  [(Psychiatry 2010:19 [Epub ahead of print].)] TJ ET
BT 26.250 534.967 Td /F1 9.8 Tf  [(7.)] TJ ET
BT 38.132 534.967 Td /F1 9.8 Tf  [(Paulsen JS, Hayden M, Stout JC, et al. Preparing for preventive clinical trials: the Predict-HD study. Arch Neurol 2006;63:883-)] TJ ET
BT 26.250 523.062 Td /F1 9.8 Tf  [(90.)] TJ ET
BT 26.250 503.658 Td /F1 9.8 Tf  [(8.)] TJ ET
BT 38.132 503.658 Td /F1 9.8 Tf  [(Huntington Study Group. Unified Huntington's Disease Rating Scale: reliability and consistency. Mov Disord 1996;11:136-42.)] TJ ET
BT 26.250 484.253 Td /F1 9.8 Tf  [(9.)] TJ ET
BT 38.132 484.253 Td /F1 9.8 Tf  [(Penney JB, Jr., Vonsattel JP, MacDonald ME, Gusella JF, Myers RH. CAG repeat number governs the development rate of )] TJ ET
BT 26.250 472.348 Td /F1 9.8 Tf  [(pathology in Huntington's disease. Ann Neurol 1997;41:689-92.)] TJ ET
BT 26.250 452.943 Td /F1 9.8 Tf  [(10.)] TJ ET
BT 43.553 452.943 Td /F1 9.8 Tf  [(Tabrizi SJ, Langbehn DR, Leavitt BR, et al. Biological and clinical manifestations of Huntington's disease in the longitudinal )] TJ ET
BT 26.250 441.039 Td /F1 9.8 Tf  [(TRACK-HD study: cross-sectional analysis of baseline data. Lancet Neurol 2009;8:791-801.)] TJ ET
BT 26.250 421.634 Td /F1 9.8 Tf  [(11.)] TJ ET
BT 43.553 421.634 Td /F1 9.8 Tf  [(Paulsen JS, Langbehn DR, Stout JC, et al. Detection of Huntington's disease decades before diagnosis: the Predict-HD )] TJ ET
BT 26.250 409.729 Td /F1 9.8 Tf  [(study. J Neurol Neurosurg Psychiatry 2008;79:874-80.)] TJ ET
BT 26.250 390.324 Td /F1 9.8 Tf  [(12.)] TJ ET
BT 43.553 390.324 Td /F1 9.8 Tf  [(Marder K, Zhao H, Myers RH, et al. Rate of functional decline in Huntington's disease. Huntington Study Group. Neurology )] TJ ET
BT 26.250 378.420 Td /F1 9.8 Tf  [(2000;54:452-8.)] TJ ET
BT 26.250 359.015 Td /F1 9.8 Tf  [(13.)] TJ ET
BT 43.553 359.015 Td /F1 9.8 Tf  [(Paulsen JS, Wang C, Duff K, et al. Challenges assessing clinical endpoints in early Huntington disease. Mov Disord )] TJ ET
BT 26.250 347.110 Td /F1 9.8 Tf  [(2010;25:2595-603.)] TJ ET
Q
q
15.000 329.729 577.500 447.271 re W n
0.271 0.267 0.267 rg
BT 26.250 750.278 Td /F4 12.0 Tf  [(References)] TJ ET
BT 26.250 722.824 Td /F1 9.8 Tf  [(1.)] TJ ET
BT 38.132 722.824 Td /F1 9.8 Tf  [(The Huntington's Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded )] TJ ET
BT 26.250 710.919 Td /F1 9.8 Tf  [(and unstable on Huntington's disease chromosomes. Cell 1993;72:971-83.)] TJ ET
BT 26.250 691.515 Td /F1 9.8 Tf  [(2.)] TJ ET
BT 38.132 691.515 Td /F1 9.8 Tf  [(Langbehn DR, Brinkman RR, Falush D, Paulsen JS, Hayden MR. A new model for prediction of the age of onset and )] TJ ET
BT 26.250 679.610 Td /F1 9.8 Tf  [(penetrance for Huntington's disease based on CAG length. Clin Genet 2004;65:267-77.)] TJ ET
BT 26.250 660.205 Td /F1 9.8 Tf  [(3.)] TJ ET
BT 38.132 660.205 Td /F1 9.8 Tf  [(Wexler NS, Lorimer J, Porter J, et al. Venezuelan kindreds reveal that genetic and environmental factors modulate )] TJ ET
BT 26.250 648.300 Td /F1 9.8 Tf  [(Huntington's disease age of onset. Proc Natl Acad Sci U S A 2004;101:3498-503.)] TJ ET
BT 26.250 628.896 Td /F1 9.8 Tf  [(4.)] TJ ET
BT 38.132 628.896 Td /F1 9.8 Tf  [(Aylward EH, Codori AM, Barta PE, Pearlson GD, Harris GJ, Brandt J. Basal ganglia volume and proximity to onset in )] TJ ET
BT 26.250 616.991 Td /F1 9.8 Tf  [(presymptomatic Huntington disease. Arch Neurol 1996;53:1293-6.)] TJ ET
BT 26.250 597.586 Td /F1 9.8 Tf  [(5.)] TJ ET
BT 38.132 597.586 Td /F1 9.8 Tf  [(Ranen NG, Stine OC, Abbott MH, et al. Anticipation and instability of IT-15 \(CAG\)n repeats in parent-offspring pairs with )] TJ ET
BT 26.250 585.681 Td /F1 9.8 Tf  [(Huntington disease. Am J Hum Genet 1995;57:593-602.)] TJ ET
BT 26.250 566.277 Td /F1 9.8 Tf  [(6.)] TJ ET
BT 38.132 566.277 Td /F1 9.8 Tf  [(Orth M. Observing Huntington's disease: the European Huntington's Disease Network's REGISTRY. J Neurol Neurosurg )] TJ ET
BT 26.250 554.372 Td /F1 9.8 Tf  [(Psychiatry 2010:19 [Epub ahead of print].)] TJ ET
BT 26.250 534.967 Td /F1 9.8 Tf  [(7.)] TJ ET
BT 38.132 534.967 Td /F1 9.8 Tf  [(Paulsen JS, Hayden M, Stout JC, et al. Preparing for preventive clinical trials: the Predict-HD study. Arch Neurol 2006;63:883-)] TJ ET
BT 26.250 523.062 Td /F1 9.8 Tf  [(90.)] TJ ET
BT 26.250 503.658 Td /F1 9.8 Tf  [(8.)] TJ ET
BT 38.132 503.658 Td /F1 9.8 Tf  [(Huntington Study Group. Unified Huntington's Disease Rating Scale: reliability and consistency. Mov Disord 1996;11:136-42.)] TJ ET
BT 26.250 484.253 Td /F1 9.8 Tf  [(9.)] TJ ET
BT 38.132 484.253 Td /F1 9.8 Tf  [(Penney JB, Jr., Vonsattel JP, MacDonald ME, Gusella JF, Myers RH. CAG repeat number governs the development rate of )] TJ ET
BT 26.250 472.348 Td /F1 9.8 Tf  [(pathology in Huntington's disease. Ann Neurol 1997;41:689-92.)] TJ ET
BT 26.250 452.943 Td /F1 9.8 Tf  [(10.)] TJ ET
BT 43.553 452.943 Td /F1 9.8 Tf  [(Tabrizi SJ, Langbehn DR, Leavitt BR, et al. Biological and clinical manifestations of Huntington's disease in the longitudinal )] TJ ET
BT 26.250 441.039 Td /F1 9.8 Tf  [(TRACK-HD study: cross-sectional analysis of baseline data. Lancet Neurol 2009;8:791-801.)] TJ ET
BT 26.250 421.634 Td /F1 9.8 Tf  [(11.)] TJ ET
BT 43.553 421.634 Td /F1 9.8 Tf  [(Paulsen JS, Langbehn DR, Stout JC, et al. Detection of Huntington's disease decades before diagnosis: the Predict-HD )] TJ ET
BT 26.250 409.729 Td /F1 9.8 Tf  [(study. J Neurol Neurosurg Psychiatry 2008;79:874-80.)] TJ ET
BT 26.250 390.324 Td /F1 9.8 Tf  [(12.)] TJ ET
BT 43.553 390.324 Td /F1 9.8 Tf  [(Marder K, Zhao H, Myers RH, et al. Rate of functional decline in Huntington's disease. Huntington Study Group. Neurology )] TJ ET
BT 26.250 378.420 Td /F1 9.8 Tf  [(2000;54:452-8.)] TJ ET
BT 26.250 359.015 Td /F1 9.8 Tf  [(13.)] TJ ET
BT 43.553 359.015 Td /F1 9.8 Tf  [(Paulsen JS, Wang C, Duff K, et al. Challenges assessing clinical endpoints in early Huntington disease. Mov Disord )] TJ ET
BT 26.250 347.110 Td /F1 9.8 Tf  [(2010;25:2595-603.)] TJ ET
Q
q
0.000 0.000 0.000 rg
BT 291.710 19.825 Td /F1 11.0 Tf  [(13)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Huntington Disease)] TJ ET

Q
endstream
endobj
xref
0 197
0000000000 65535 f 
0000000008 00000 n 
0000000073 00000 n 
0000000119 00000 n 
0000000474 00000 n 
0000000511 00000 n 
0000000704 00000 n 
0000001052 00000 n 
0000024003 00000 n 
0000024110 00000 n 
0000024218 00000 n 
0000024329 00000 n 
0000024442 00000 n 
0000024558 00000 n 
0000024946 00000 n 
0000029427 00000 n 
0000029554 00000 n 
0000029677 00000 n 
0000029804 00000 n 
0000029914 00000 n 
0000030040 00000 n 
0000030139 00000 n 
0000030266 00000 n 
0000030369 00000 n 
0000030497 00000 n 
0000030533 00000 n 
0000030661 00000 n 
0000030697 00000 n 
0000030825 00000 n 
0000030861 00000 n 
0000030989 00000 n 
0000031025 00000 n 
0000031153 00000 n 
0000031189 00000 n 
0000031317 00000 n 
0000031353 00000 n 
0000031481 00000 n 
0000031517 00000 n 
0000031645 00000 n 
0000031681 00000 n 
0000031809 00000 n 
0000031845 00000 n 
0000031972 00000 n 
0000032095 00000 n 
0000032222 00000 n 
0000032332 00000 n 
0000032458 00000 n 
0000032557 00000 n 
0000032684 00000 n 
0000032787 00000 n 
0000032915 00000 n 
0000032951 00000 n 
0000033079 00000 n 
0000033115 00000 n 
0000033243 00000 n 
0000033279 00000 n 
0000033407 00000 n 
0000033443 00000 n 
0000033571 00000 n 
0000033607 00000 n 
0000033735 00000 n 
0000033771 00000 n 
0000033899 00000 n 
0000033935 00000 n 
0000034063 00000 n 
0000034099 00000 n 
0000034227 00000 n 
0000034263 00000 n 
0000034390 00000 n 
0000034513 00000 n 
0000034640 00000 n 
0000034750 00000 n 
0000034876 00000 n 
0000034975 00000 n 
0000035102 00000 n 
0000035205 00000 n 
0000035333 00000 n 
0000035369 00000 n 
0000035497 00000 n 
0000035533 00000 n 
0000035661 00000 n 
0000035697 00000 n 
0000035825 00000 n 
0000035861 00000 n 
0000035989 00000 n 
0000036025 00000 n 
0000036153 00000 n 
0000036189 00000 n 
0000036317 00000 n 
0000036353 00000 n 
0000036481 00000 n 
0000036517 00000 n 
0000036645 00000 n 
0000036681 00000 n 
0000036923 00000 n 
0000057935 00000 n 
0000058062 00000 n 
0000058098 00000 n 
0000058226 00000 n 
0000058262 00000 n 
0000058391 00000 n 
0000058428 00000 n 
0000058558 00000 n 
0000058652 00000 n 
0000058782 00000 n 
0000058819 00000 n 
0000058949 00000 n 
0000058986 00000 n 
0000059115 00000 n 
0000059222 00000 n 
0000069020 00000 n 
0000069149 00000 n 
0000069186 00000 n 
0000069316 00000 n 
0000069353 00000 n 
0000069483 00000 n 
0000069520 00000 n 
0000069650 00000 n 
0000069744 00000 n 
0000069874 00000 n 
0000069911 00000 n 
0000070041 00000 n 
0000070078 00000 n 
0000070207 00000 n 
0000070314 00000 n 
0000070443 00000 n 
0000070480 00000 n 
0000070610 00000 n 
0000070647 00000 n 
0000070777 00000 n 
0000070814 00000 n 
0000070944 00000 n 
0000071038 00000 n 
0000071168 00000 n 
0000071205 00000 n 
0000071335 00000 n 
0000071372 00000 n 
0000071501 00000 n 
0000071608 00000 n 
0000071711 00000 n 
0000124818 00000 n 
0000124947 00000 n 
0000125054 00000 n 
0000140832 00000 n 
0000140961 00000 n 
0000141068 00000 n 
0000141197 00000 n 
0000141304 00000 n 
0000141371 00000 n 
0000259856 00000 n 
0000260007 00000 n 
0000315305 00000 n 
0000315435 00000 n 
0000315472 00000 n 
0000315602 00000 n 
0000315639 00000 n 
0000315769 00000 n 
0000315806 00000 n 
0000315936 00000 n 
0000315973 00000 n 
0000316103 00000 n 
0000316140 00000 n 
0000316270 00000 n 
0000316307 00000 n 
0000316437 00000 n 
0000316474 00000 n 
0000316604 00000 n 
0000316641 00000 n 
0000316771 00000 n 
0000316808 00000 n 
0000316935 00000 n 
0000344435 00000 n 
0000344565 00000 n 
0000344602 00000 n 
0000344732 00000 n 
0000344769 00000 n 
0000344899 00000 n 
0000344936 00000 n 
0000345066 00000 n 
0000345103 00000 n 
0000345233 00000 n 
0000345270 00000 n 
0000345400 00000 n 
0000345437 00000 n 
0000345504 00000 n 
0000377207 00000 n 
0000377274 00000 n 
0000403667 00000 n 
0000403734 00000 n 
0000427505 00000 n 
0000427572 00000 n 
0000459123 00000 n 
0000459190 00000 n 
0000490555 00000 n 
0000490622 00000 n 
0000519098 00000 n 
0000519165 00000 n 
trailer
<<
/Size 197
/Root 1 0 R
/Info 5 0 R
>>
startxref
531327
%%EOF