%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
182 0 R
346 0 R
402 0 R
443 0 R
613 0 R
615 0 R
617 0 R
]
/Count 8
/Resources <<
/ProcSet 4 0 R
/Font << 
/F1 8 0 R
/F2 9 0 R
/F3 10 0 R
/F4 11 0 R
>>
/XObject << 
/I1 12 0 R
/I2 13 0 R
/I3 408 0 R
/I4 415 0 R
/I5 416 0 R
/I6 427 0 R
/I7 428 0 R
/I8 439 0 R
/I9 440 0 R
/I10 441 0 R
/I11 442 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:20170830090729+00'00')
/ModDate (D:20170830090729+00'00')
/Title (No evidence of impaired gastric emptying in early Huntington�s Disease � PLOS Currents Huntington Disease)
>>
endobj
6 0 obj
<< /Type /Page
/Parent 3 0 R
/Annots [ 14 0 R 16 0 R 18 0 R 20 0 R 22 0 R 24 0 R 26 0 R 28 0 R 30 0 R 32 0 R 34 0 R 36 0 R 38 0 R 40 0 R 42 0 R 44 0 R 46 0 R 48 0 R 50 0 R 52 0 R 54 0 R 56 0 R 58 0 R 60 0 R 62 0 R 64 0 R 66 0 R 68 0 R 70 0 R 72 0 R 74 0 R 76 0 R 78 0 R 80 0 R 82 0 R 84 0 R 86 0 R 88 0 R 90 0 R 92 0 R 94 0 R 96 0 R 98 0 R 100 0 R 102 0 R 104 0 R 106 0 R 108 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 138 0 R 140 0 R 142 0 R 144 0 R 146 0 R 148 0 R 150 0 R 152 0 R 154 0 R 156 0 R 158 0 R 160 0 R 162 0 R 164 0 R 166 0 R 168 0 R 170 0 R 172 0 R 174 0 R 176 0 R 178 0 R 180 0 R ]
/Contents 7 0 R
>>
endobj
7 0 obj
<<
/Length 27071 >>
stream

q
375.000 0 0 39.000 222.000 738.000 cm /I2 Do
Q
q
15.000 684.354 577.500 53.646 re W n
0.267 0.267 0.267 rg
BT 15.000 718.042 Td /F2 21.0 Tf  [(No evidence of impaired gastric emptying in early Huntington�s )] TJ ET
BT 15.000 693.094 Td /F2 21.0 Tf  [(Disease)] TJ ET
Q
0.271 0.267 0.267 rg
BT 15.000 675.088 Td /F3 9.8 Tf  [(November 16, 2011)] TJ ET
BT 96.510 675.088 Td /F3 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
BT 101.385 675.088 Td /F3 9.8 Tf  [(Epidemiology)] TJ ET
BT 26.250 663.247 Td /F1 9.8 Tf  [(Carsten Saft)] TJ ET
0.271 0.267 0.267 rg
BT 80.441 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 85.862 663.247 Td /F1 9.8 Tf  [(J�rgen Andrich)] TJ ET
0.271 0.267 0.267 rg
BT 151.430 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 156.851 663.247 Td /F1 9.8 Tf  [(Marc F�lker)] TJ ET
0.271 0.267 0.267 rg
BT 208.312 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 213.733 663.247 Td /F1 9.8 Tf  [(Sarah Gauda)] TJ ET
0.271 0.267 0.267 rg
BT 271.726 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 277.147 663.247 Td /F1 9.8 Tf  [(Sina K�chler)] TJ ET
0.271 0.267 0.267 rg
BT 332.419 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 337.840 663.247 Td /F1 9.8 Tf  [(Dirk Woitalla)] TJ ET
0.271 0.267 0.267 rg
BT 392.548 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 397.969 663.247 Td /F1 9.8 Tf  [(Oliver Goetze)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 651.342 Td /F1 9.8 Tf  [(Saft C, Andrich J, F�lker M, Gauda S, K�chler S, Woitalla D, Goetze O. No evidence of impaired gastric emptying in early )] TJ ET
BT 26.250 639.438 Td /F1 9.8 Tf  [(Huntington�s Disease. PLOS Currents Huntington Disease. 2011 Nov 16 . Edition 1. doi: 10.1371/currents.RRN1284.)] TJ ET
q
15.000 32.625 577.500 604.432 re W n
0.271 0.267 0.267 rg
BT 26.250 610.335 Td /F4 12.0 Tf  [(Abstract)] TJ ET
BT 26.250 590.381 Td /F1 9.8 Tf  [(Background: Several factors, such as dysphagia, an increased motor activity, increased metabolic rate and a hypermetabolic )] TJ ET
BT 26.250 578.476 Td /F1 9.8 Tf  [(state have been discussed as contributing to weight loss even at the early stages of Huntington�s Disease \(HD\). Aim of this pilot )] TJ ET
BT 26.250 566.571 Td /F1 9.8 Tf  [(study was to investigate gastric emptying as a possible reason for weight loss in HD.)] TJ ET
BT 26.250 547.167 Td /F1 9.8 Tf  [(Methods: 11 HD participants at early stages of the disease and matched controls were investigated by using the well-)] TJ ET
BT 26.250 535.262 Td /F1 9.8 Tf  [(established and non-invasive 13C-octanoate breath test. The �Gastroparesis Cardinal Symptom Index� and the �Short-Form )] TJ ET
BT 26.250 523.357 Td /F1 9.8 Tf  [(Leeds Dyspepsia Questionnaire� were used for clinical evaluation of gastroparesis or dyspepsia.)] TJ ET
BT 26.250 503.952 Td /F1 9.8 Tf  [(Results: When compared to standard values ??given in literature and controls all HD patients had normal breath test results. )] TJ ET
BT 26.250 492.048 Td /F1 9.8 Tf  [(There was no evidence of gastroparesis or dyspepsia. There was a correlation of breath test results with the cognitive and )] TJ ET
BT 26.250 480.143 Td /F1 9.8 Tf  [(functional performance of HD participants.)] TJ ET
BT 26.250 460.738 Td /F1 9.8 Tf  [(Conclusion: According to our data, there is no evidence of impaired gastric emptying in early HD. We can not exclude that )] TJ ET
BT 26.250 448.833 Td /F1 9.8 Tf  [(gastric emptying contributes to weight loss at more advanced stages of the disease.)] TJ ET
BT 26.250 429.429 Td /F1 9.8 Tf  [(Corresponding author: PD Dr. med. Carsten Saft, Department of Neurology, Huntington-Center NRW, St. Josef Hospital, )] TJ ET
BT 26.250 417.524 Td /F1 9.8 Tf  [(Gudrunstrasse 56, 44791 Bochum, Germany, E-mail: carsten.saft@ruhr-uni-bochum.de)] TJ ET
BT 26.250 398.119 Td /F1 9.8 Tf  [(� Carsten Saft and J�rgen Andrich contributed equally to this work)] TJ ET
BT 26.250 361.517 Td /F4 12.0 Tf  [(Funding Statement)] TJ ET
BT 26.250 341.562 Td /F1 9.8 Tf  [(The study was supported by a FoRUM grant, University of Bochum \(AZ: F506-2006\). Oliver G�tze was supported by the DFG )] TJ ET
BT 26.250 329.658 Td /F1 9.8 Tf  [(\(G� 13582/1\).)] TJ ET
BT 26.250 300.555 Td /F4 12.0 Tf  [(Introduction)] TJ ET
BT 26.250 280.601 Td /F1 9.8 Tf  [(Weight loss is a main feature in Huntington�s disease \(HD\) and was found to be manifest even at early stages of the disease. )] TJ ET
0.267 0.267 0.267 rg
BT 567.082 280.601 Td /F1 9.8 Tf  [([1])] TJ ET
BT 26.250 268.696 Td /F1 9.8 Tf  [([2])] TJ ET
BT 37.092 268.696 Td /F1 9.8 Tf  [([3])] TJ ET
BT 47.934 268.696 Td /F1 9.8 Tf  [([4])] TJ ET
BT 58.776 268.696 Td /F1 9.8 Tf  [([5])] TJ ET
0.271 0.267 0.267 rg
BT 69.618 268.696 Td /F1 9.8 Tf  [( Multifactorial causes, such as decreased caloric intake due to dysphagia and a higher energy expenditure due to )] TJ ET
BT 26.250 256.791 Td /F1 9.8 Tf  [(increased motor activity have been discussed as being a possible reason for weight loss especially at the advanced stages of )] TJ ET
BT 26.250 244.887 Td /F1 9.8 Tf  [(the disease. )] TJ ET
0.267 0.267 0.267 rg
BT 81.532 244.887 Td /F1 9.8 Tf  [([6])] TJ ET
BT 92.374 244.887 Td /F1 9.8 Tf  [([7])] TJ ET
BT 103.216 244.887 Td /F1 9.8 Tf  [([8])] TJ ET
BT 114.058 244.887 Td /F1 9.8 Tf  [([9])] TJ ET
BT 124.900 244.887 Td /F1 9.8 Tf  [([10])] TJ ET
0.271 0.267 0.267 rg
BT 141.163 244.887 Td /F1 9.8 Tf  [( Using a whole body indirect calorimetry in both early stage HD patients and the R6/2 transgenic )] TJ ET
BT 26.250 232.982 Td /F1 9.8 Tf  [(mouse model of HD, Goodman and colleagues were able to demonstrate that patients with early HD tended to have a negative )] TJ ET
BT 26.250 221.077 Td /F1 9.8 Tf  [(energy balance for reasons not related to their movement disorder, which was paralleled in the transgenic R6/2 mice. )] TJ ET
0.267 0.267 0.267 rg
BT 533.465 221.077 Td /F1 9.8 Tf  [([4])] TJ ET
0.271 0.267 0.267 rg
BT 544.307 221.077 Td /F1 9.8 Tf  [( This )] TJ ET
BT 26.250 209.172 Td /F1 9.8 Tf  [(leads to the assumption of an increased metabolic rate as a main reason for weight loss in HD, which is supported by other )] TJ ET
BT 26.250 197.268 Td /F1 9.8 Tf  [(experiments in the transgenic R6/2 mice. )] TJ ET
0.267 0.267 0.267 rg
BT 205.611 197.268 Td /F1 9.8 Tf  [([4])] TJ ET
BT 216.453 197.268 Td /F1 9.8 Tf  [([11])] TJ ET
BT 232.716 197.268 Td /F1 9.8 Tf  [([12])] TJ ET
0.271 0.267 0.267 rg
BT 248.979 197.268 Td /F1 9.8 Tf  [( In a study investigating the direct relation between the number of CAG )] TJ ET
BT 26.250 185.363 Td /F1 9.8 Tf  [(repeats in the mutant huntingtin gene and weight loss, Aziz and colleagues found a correlation between both of these factors )] TJ ET
BT 26.250 173.458 Td /F1 9.8 Tf  [(and discussed a hypermetabolic state as being a reason for weight loss, occurring even at early stages of the disease. )] TJ ET
0.267 0.267 0.267 rg
BT 538.915 173.458 Td /F1 9.8 Tf  [([13])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 161.553 Td /F1 9.8 Tf  [(They discussed a hypermetabolic state as being likely to stem directly from interference of the mutant protein with cellular )] TJ ET
BT 26.250 149.649 Td /F1 9.8 Tf  [(energy homeostasis and thus reflecting fundamental pathologic mechanisms underlying HD and not to be secondary to )] TJ ET
BT 26.250 137.744 Td /F1 9.8 Tf  [(hyperactivity. Since mutant Huntingtin \(mtHtt\) is not only expressed in the brain of HD patients, but also in the gastrointestinal )] TJ ET
BT 26.250 125.839 Td /F1 9.8 Tf  [(\(GI\) tract, a recently published study investigated the GI tract in the R6/2 mice model for HD. This study describes a loss of )] TJ ET
BT 26.250 113.934 Td /F1 9.8 Tf  [(enteric neuropepitdes, a decreased mucosal thickness and villius length and also an impaired gut motility, diarrhea, and )] TJ ET
BT 26.250 102.030 Td /F1 9.8 Tf  [(malabsorption of food, suggesting that GI dysfunction plays an important role in weight loss in HD mice. )] TJ ET
0.267 0.267 0.267 rg
BT 474.945 102.030 Td /F1 9.8 Tf  [([14])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 82.625 Td /F1 9.8 Tf  [(In addition, gastrointestinal dysfunction is discussed as being the main reason for weight loss in Parkinson�s disease \(PD\). )] TJ ET
0.267 0.267 0.267 rg
BT 555.139 82.625 Td /F1 9.8 Tf  [([15])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 70.720 Td /F1 9.8 Tf  [(In a study using a solid meal and the )] TJ ET
BT 187.213 74.608 Td /F1 8.7 Tf  [(13)] TJ ET
BT 196.850 70.720 Td /F1 9.8 Tf  [( C-sodium octanoate breath test for measurement of gastric emptying in patients with )] TJ ET
BT 26.250 58.815 Td /F1 9.8 Tf  [(PD, Goetze and colleagues found 88% of PD patients suufered from delayed gastric emptying when compared with controls. )] TJ ET
BT 26.250 46.911 Td /F1 9.8 Tf  [(The severity of motor impairment was associated with gastroparesis. )] TJ ET
0.267 0.267 0.267 rg
BT 324.805 46.911 Td /F1 9.8 Tf  [([16])] TJ ET
0.271 0.267 0.267 rg
BT 341.068 46.911 Td /F1 9.8 Tf  [( Several other studies confirm an impaired gastric )] TJ ET
Q
q
15.000 684.354 577.500 53.646 re W n
0.267 0.267 0.267 rg
BT 15.000 718.042 Td /F2 21.0 Tf  [(No evidence of impaired gastric emptying in early Huntington�s )] TJ ET
BT 15.000 693.094 Td /F2 21.0 Tf  [(Disease)] TJ ET
Q
0.271 0.267 0.267 rg
BT 15.000 675.088 Td /F3 9.8 Tf  [(November 16, 2011)] TJ ET
BT 96.510 675.088 Td /F3 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
BT 101.385 675.088 Td /F3 9.8 Tf  [(Epidemiology)] TJ ET
BT 26.250 663.247 Td /F1 9.8 Tf  [(Carsten Saft)] TJ ET
0.271 0.267 0.267 rg
BT 80.441 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 85.862 663.247 Td /F1 9.8 Tf  [(J�rgen Andrich)] TJ ET
0.271 0.267 0.267 rg
BT 151.430 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 156.851 663.247 Td /F1 9.8 Tf  [(Marc F�lker)] TJ ET
0.271 0.267 0.267 rg
BT 208.312 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 213.733 663.247 Td /F1 9.8 Tf  [(Sarah Gauda)] TJ ET
0.271 0.267 0.267 rg
BT 271.726 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 277.147 663.247 Td /F1 9.8 Tf  [(Sina K�chler)] TJ ET
0.271 0.267 0.267 rg
BT 332.419 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 337.840 663.247 Td /F1 9.8 Tf  [(Dirk Woitalla)] TJ ET
0.271 0.267 0.267 rg
BT 392.548 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 397.969 663.247 Td /F1 9.8 Tf  [(Oliver Goetze)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 651.342 Td /F1 9.8 Tf  [(Saft C, Andrich J, F�lker M, Gauda S, K�chler S, Woitalla D, Goetze O. No evidence of impaired gastric emptying in early )] TJ ET
BT 26.250 639.438 Td /F1 9.8 Tf  [(Huntington�s Disease. PLOS Currents Huntington Disease. 2011 Nov 16 . Edition 1. doi: 10.1371/currents.RRN1284.)] TJ ET
q
15.000 32.625 577.500 604.432 re W n
0.271 0.267 0.267 rg
BT 26.250 610.335 Td /F4 12.0 Tf  [(Abstract)] TJ ET
BT 26.250 590.381 Td /F1 9.8 Tf  [(Background: Several factors, such as dysphagia, an increased motor activity, increased metabolic rate and a hypermetabolic )] TJ ET
BT 26.250 578.476 Td /F1 9.8 Tf  [(state have been discussed as contributing to weight loss even at the early stages of Huntington�s Disease \(HD\). Aim of this pilot )] TJ ET
BT 26.250 566.571 Td /F1 9.8 Tf  [(study was to investigate gastric emptying as a possible reason for weight loss in HD.)] TJ ET
BT 26.250 547.167 Td /F1 9.8 Tf  [(Methods: 11 HD participants at early stages of the disease and matched controls were investigated by using the well-)] TJ ET
BT 26.250 535.262 Td /F1 9.8 Tf  [(established and non-invasive 13C-octanoate breath test. The �Gastroparesis Cardinal Symptom Index� and the �Short-Form )] TJ ET
BT 26.250 523.357 Td /F1 9.8 Tf  [(Leeds Dyspepsia Questionnaire� were used for clinical evaluation of gastroparesis or dyspepsia.)] TJ ET
BT 26.250 503.952 Td /F1 9.8 Tf  [(Results: When compared to standard values ??given in literature and controls all HD patients had normal breath test results. )] TJ ET
BT 26.250 492.048 Td /F1 9.8 Tf  [(There was no evidence of gastroparesis or dyspepsia. There was a correlation of breath test results with the cognitive and )] TJ ET
BT 26.250 480.143 Td /F1 9.8 Tf  [(functional performance of HD participants.)] TJ ET
BT 26.250 460.738 Td /F1 9.8 Tf  [(Conclusion: According to our data, there is no evidence of impaired gastric emptying in early HD. We can not exclude that )] TJ ET
BT 26.250 448.833 Td /F1 9.8 Tf  [(gastric emptying contributes to weight loss at more advanced stages of the disease.)] TJ ET
BT 26.250 429.429 Td /F1 9.8 Tf  [(Corresponding author: PD Dr. med. Carsten Saft, Department of Neurology, Huntington-Center NRW, St. Josef Hospital, )] TJ ET
BT 26.250 417.524 Td /F1 9.8 Tf  [(Gudrunstrasse 56, 44791 Bochum, Germany, E-mail: carsten.saft@ruhr-uni-bochum.de)] TJ ET
BT 26.250 398.119 Td /F1 9.8 Tf  [(� Carsten Saft and J�rgen Andrich contributed equally to this work)] TJ ET
BT 26.250 361.517 Td /F4 12.0 Tf  [(Funding Statement)] TJ ET
BT 26.250 341.562 Td /F1 9.8 Tf  [(The study was supported by a FoRUM grant, University of Bochum \(AZ: F506-2006\). Oliver G�tze was supported by the DFG )] TJ ET
BT 26.250 329.658 Td /F1 9.8 Tf  [(\(G� 13582/1\).)] TJ ET
BT 26.250 300.555 Td /F4 12.0 Tf  [(Introduction)] TJ ET
BT 26.250 280.601 Td /F1 9.8 Tf  [(Weight loss is a main feature in Huntington�s disease \(HD\) and was found to be manifest even at early stages of the disease. )] TJ ET
0.267 0.267 0.267 rg
BT 567.082 280.601 Td /F1 9.8 Tf  [([1])] TJ ET
BT 26.250 268.696 Td /F1 9.8 Tf  [([2])] TJ ET
BT 37.092 268.696 Td /F1 9.8 Tf  [([3])] TJ ET
BT 47.934 268.696 Td /F1 9.8 Tf  [([4])] TJ ET
BT 58.776 268.696 Td /F1 9.8 Tf  [([5])] TJ ET
0.271 0.267 0.267 rg
BT 69.618 268.696 Td /F1 9.8 Tf  [( Multifactorial causes, such as decreased caloric intake due to dysphagia and a higher energy expenditure due to )] TJ ET
BT 26.250 256.791 Td /F1 9.8 Tf  [(increased motor activity have been discussed as being a possible reason for weight loss especially at the advanced stages of )] TJ ET
BT 26.250 244.887 Td /F1 9.8 Tf  [(the disease. )] TJ ET
0.267 0.267 0.267 rg
BT 81.532 244.887 Td /F1 9.8 Tf  [([6])] TJ ET
BT 92.374 244.887 Td /F1 9.8 Tf  [([7])] TJ ET
BT 103.216 244.887 Td /F1 9.8 Tf  [([8])] TJ ET
BT 114.058 244.887 Td /F1 9.8 Tf  [([9])] TJ ET
BT 124.900 244.887 Td /F1 9.8 Tf  [([10])] TJ ET
0.271 0.267 0.267 rg
BT 141.163 244.887 Td /F1 9.8 Tf  [( Using a whole body indirect calorimetry in both early stage HD patients and the R6/2 transgenic )] TJ ET
BT 26.250 232.982 Td /F1 9.8 Tf  [(mouse model of HD, Goodman and colleagues were able to demonstrate that patients with early HD tended to have a negative )] TJ ET
BT 26.250 221.077 Td /F1 9.8 Tf  [(energy balance for reasons not related to their movement disorder, which was paralleled in the transgenic R6/2 mice. )] TJ ET
0.267 0.267 0.267 rg
BT 533.465 221.077 Td /F1 9.8 Tf  [([4])] TJ ET
0.271 0.267 0.267 rg
BT 544.307 221.077 Td /F1 9.8 Tf  [( This )] TJ ET
BT 26.250 209.172 Td /F1 9.8 Tf  [(leads to the assumption of an increased metabolic rate as a main reason for weight loss in HD, which is supported by other )] TJ ET
BT 26.250 197.268 Td /F1 9.8 Tf  [(experiments in the transgenic R6/2 mice. )] TJ ET
0.267 0.267 0.267 rg
BT 205.611 197.268 Td /F1 9.8 Tf  [([4])] TJ ET
BT 216.453 197.268 Td /F1 9.8 Tf  [([11])] TJ ET
BT 232.716 197.268 Td /F1 9.8 Tf  [([12])] TJ ET
0.271 0.267 0.267 rg
BT 248.979 197.268 Td /F1 9.8 Tf  [( In a study investigating the direct relation between the number of CAG )] TJ ET
BT 26.250 185.363 Td /F1 9.8 Tf  [(repeats in the mutant huntingtin gene and weight loss, Aziz and colleagues found a correlation between both of these factors )] TJ ET
BT 26.250 173.458 Td /F1 9.8 Tf  [(and discussed a hypermetabolic state as being a reason for weight loss, occurring even at early stages of the disease. )] TJ ET
0.267 0.267 0.267 rg
BT 538.915 173.458 Td /F1 9.8 Tf  [([13])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 161.553 Td /F1 9.8 Tf  [(They discussed a hypermetabolic state as being likely to stem directly from interference of the mutant protein with cellular )] TJ ET
BT 26.250 149.649 Td /F1 9.8 Tf  [(energy homeostasis and thus reflecting fundamental pathologic mechanisms underlying HD and not to be secondary to )] TJ ET
BT 26.250 137.744 Td /F1 9.8 Tf  [(hyperactivity. Since mutant Huntingtin \(mtHtt\) is not only expressed in the brain of HD patients, but also in the gastrointestinal )] TJ ET
BT 26.250 125.839 Td /F1 9.8 Tf  [(\(GI\) tract, a recently published study investigated the GI tract in the R6/2 mice model for HD. This study describes a loss of )] TJ ET
BT 26.250 113.934 Td /F1 9.8 Tf  [(enteric neuropepitdes, a decreased mucosal thickness and villius length and also an impaired gut motility, diarrhea, and )] TJ ET
BT 26.250 102.030 Td /F1 9.8 Tf  [(malabsorption of food, suggesting that GI dysfunction plays an important role in weight loss in HD mice. )] TJ ET
0.267 0.267 0.267 rg
BT 474.945 102.030 Td /F1 9.8 Tf  [([14])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 82.625 Td /F1 9.8 Tf  [(In addition, gastrointestinal dysfunction is discussed as being the main reason for weight loss in Parkinson�s disease \(PD\). )] TJ ET
0.267 0.267 0.267 rg
BT 555.139 82.625 Td /F1 9.8 Tf  [([15])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 70.720 Td /F1 9.8 Tf  [(In a study using a solid meal and the )] TJ ET
BT 187.213 74.608 Td /F1 8.7 Tf  [(13)] TJ ET
BT 196.850 70.720 Td /F1 9.8 Tf  [( C-sodium octanoate breath test for measurement of gastric emptying in patients with )] TJ ET
BT 26.250 58.815 Td /F1 9.8 Tf  [(PD, Goetze and colleagues found 88% of PD patients suufered from delayed gastric emptying when compared with controls. )] TJ ET
BT 26.250 46.911 Td /F1 9.8 Tf  [(The severity of motor impairment was associated with gastroparesis. )] TJ ET
0.267 0.267 0.267 rg
BT 324.805 46.911 Td /F1 9.8 Tf  [([16])] TJ ET
0.271 0.267 0.267 rg
BT 341.068 46.911 Td /F1 9.8 Tf  [( Several other studies confirm an impaired gastric )] TJ ET
Q
q
15.000 684.354 577.500 53.646 re W n
0.267 0.267 0.267 rg
BT 15.000 718.042 Td /F2 21.0 Tf  [(No evidence of impaired gastric emptying in early Huntington�s )] TJ ET
BT 15.000 693.094 Td /F2 21.0 Tf  [(Disease)] TJ ET
Q
0.271 0.267 0.267 rg
BT 15.000 675.088 Td /F3 9.8 Tf  [(November 16, 2011)] TJ ET
BT 96.510 675.088 Td /F3 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
BT 101.385 675.088 Td /F3 9.8 Tf  [(Epidemiology)] TJ ET
BT 26.250 663.247 Td /F1 9.8 Tf  [(Carsten Saft)] TJ ET
0.271 0.267 0.267 rg
BT 80.441 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 85.862 663.247 Td /F1 9.8 Tf  [(J�rgen Andrich)] TJ ET
0.271 0.267 0.267 rg
BT 151.430 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 156.851 663.247 Td /F1 9.8 Tf  [(Marc F�lker)] TJ ET
0.271 0.267 0.267 rg
BT 208.312 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 213.733 663.247 Td /F1 9.8 Tf  [(Sarah Gauda)] TJ ET
0.271 0.267 0.267 rg
BT 271.726 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 277.147 663.247 Td /F1 9.8 Tf  [(Sina K�chler)] TJ ET
0.271 0.267 0.267 rg
BT 332.419 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 337.840 663.247 Td /F1 9.8 Tf  [(Dirk Woitalla)] TJ ET
0.271 0.267 0.267 rg
BT 392.548 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 397.969 663.247 Td /F1 9.8 Tf  [(Oliver Goetze)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 651.342 Td /F1 9.8 Tf  [(Saft C, Andrich J, F�lker M, Gauda S, K�chler S, Woitalla D, Goetze O. No evidence of impaired gastric emptying in early )] TJ ET
BT 26.250 639.438 Td /F1 9.8 Tf  [(Huntington�s Disease. PLOS Currents Huntington Disease. 2011 Nov 16 . Edition 1. doi: 10.1371/currents.RRN1284.)] TJ ET
q
15.000 32.625 577.500 604.432 re W n
0.271 0.267 0.267 rg
BT 26.250 610.335 Td /F4 12.0 Tf  [(Abstract)] TJ ET
BT 26.250 590.381 Td /F1 9.8 Tf  [(Background: Several factors, such as dysphagia, an increased motor activity, increased metabolic rate and a hypermetabolic )] TJ ET
BT 26.250 578.476 Td /F1 9.8 Tf  [(state have been discussed as contributing to weight loss even at the early stages of Huntington�s Disease \(HD\). Aim of this pilot )] TJ ET
BT 26.250 566.571 Td /F1 9.8 Tf  [(study was to investigate gastric emptying as a possible reason for weight loss in HD.)] TJ ET
BT 26.250 547.167 Td /F1 9.8 Tf  [(Methods: 11 HD participants at early stages of the disease and matched controls were investigated by using the well-)] TJ ET
BT 26.250 535.262 Td /F1 9.8 Tf  [(established and non-invasive 13C-octanoate breath test. The �Gastroparesis Cardinal Symptom Index� and the �Short-Form )] TJ ET
BT 26.250 523.357 Td /F1 9.8 Tf  [(Leeds Dyspepsia Questionnaire� were used for clinical evaluation of gastroparesis or dyspepsia.)] TJ ET
BT 26.250 503.952 Td /F1 9.8 Tf  [(Results: When compared to standard values ??given in literature and controls all HD patients had normal breath test results. )] TJ ET
BT 26.250 492.048 Td /F1 9.8 Tf  [(There was no evidence of gastroparesis or dyspepsia. There was a correlation of breath test results with the cognitive and )] TJ ET
BT 26.250 480.143 Td /F1 9.8 Tf  [(functional performance of HD participants.)] TJ ET
BT 26.250 460.738 Td /F1 9.8 Tf  [(Conclusion: According to our data, there is no evidence of impaired gastric emptying in early HD. We can not exclude that )] TJ ET
BT 26.250 448.833 Td /F1 9.8 Tf  [(gastric emptying contributes to weight loss at more advanced stages of the disease.)] TJ ET
BT 26.250 429.429 Td /F1 9.8 Tf  [(Corresponding author: PD Dr. med. Carsten Saft, Department of Neurology, Huntington-Center NRW, St. Josef Hospital, )] TJ ET
BT 26.250 417.524 Td /F1 9.8 Tf  [(Gudrunstrasse 56, 44791 Bochum, Germany, E-mail: carsten.saft@ruhr-uni-bochum.de)] TJ ET
BT 26.250 398.119 Td /F1 9.8 Tf  [(� Carsten Saft and J�rgen Andrich contributed equally to this work)] TJ ET
BT 26.250 361.517 Td /F4 12.0 Tf  [(Funding Statement)] TJ ET
BT 26.250 341.562 Td /F1 9.8 Tf  [(The study was supported by a FoRUM grant, University of Bochum \(AZ: F506-2006\). Oliver G�tze was supported by the DFG )] TJ ET
BT 26.250 329.658 Td /F1 9.8 Tf  [(\(G� 13582/1\).)] TJ ET
BT 26.250 300.555 Td /F4 12.0 Tf  [(Introduction)] TJ ET
BT 26.250 280.601 Td /F1 9.8 Tf  [(Weight loss is a main feature in Huntington�s disease \(HD\) and was found to be manifest even at early stages of the disease. )] TJ ET
0.267 0.267 0.267 rg
BT 567.082 280.601 Td /F1 9.8 Tf  [([1])] TJ ET
BT 26.250 268.696 Td /F1 9.8 Tf  [([2])] TJ ET
BT 37.092 268.696 Td /F1 9.8 Tf  [([3])] TJ ET
BT 47.934 268.696 Td /F1 9.8 Tf  [([4])] TJ ET
BT 58.776 268.696 Td /F1 9.8 Tf  [([5])] TJ ET
0.271 0.267 0.267 rg
BT 69.618 268.696 Td /F1 9.8 Tf  [( Multifactorial causes, such as decreased caloric intake due to dysphagia and a higher energy expenditure due to )] TJ ET
BT 26.250 256.791 Td /F1 9.8 Tf  [(increased motor activity have been discussed as being a possible reason for weight loss especially at the advanced stages of )] TJ ET
BT 26.250 244.887 Td /F1 9.8 Tf  [(the disease. )] TJ ET
0.267 0.267 0.267 rg
BT 81.532 244.887 Td /F1 9.8 Tf  [([6])] TJ ET
BT 92.374 244.887 Td /F1 9.8 Tf  [([7])] TJ ET
BT 103.216 244.887 Td /F1 9.8 Tf  [([8])] TJ ET
BT 114.058 244.887 Td /F1 9.8 Tf  [([9])] TJ ET
BT 124.900 244.887 Td /F1 9.8 Tf  [([10])] TJ ET
0.271 0.267 0.267 rg
BT 141.163 244.887 Td /F1 9.8 Tf  [( Using a whole body indirect calorimetry in both early stage HD patients and the R6/2 transgenic )] TJ ET
BT 26.250 232.982 Td /F1 9.8 Tf  [(mouse model of HD, Goodman and colleagues were able to demonstrate that patients with early HD tended to have a negative )] TJ ET
BT 26.250 221.077 Td /F1 9.8 Tf  [(energy balance for reasons not related to their movement disorder, which was paralleled in the transgenic R6/2 mice. )] TJ ET
0.267 0.267 0.267 rg
BT 533.465 221.077 Td /F1 9.8 Tf  [([4])] TJ ET
0.271 0.267 0.267 rg
BT 544.307 221.077 Td /F1 9.8 Tf  [( This )] TJ ET
BT 26.250 209.172 Td /F1 9.8 Tf  [(leads to the assumption of an increased metabolic rate as a main reason for weight loss in HD, which is supported by other )] TJ ET
BT 26.250 197.268 Td /F1 9.8 Tf  [(experiments in the transgenic R6/2 mice. )] TJ ET
0.267 0.267 0.267 rg
BT 205.611 197.268 Td /F1 9.8 Tf  [([4])] TJ ET
BT 216.453 197.268 Td /F1 9.8 Tf  [([11])] TJ ET
BT 232.716 197.268 Td /F1 9.8 Tf  [([12])] TJ ET
0.271 0.267 0.267 rg
BT 248.979 197.268 Td /F1 9.8 Tf  [( In a study investigating the direct relation between the number of CAG )] TJ ET
BT 26.250 185.363 Td /F1 9.8 Tf  [(repeats in the mutant huntingtin gene and weight loss, Aziz and colleagues found a correlation between both of these factors )] TJ ET
BT 26.250 173.458 Td /F1 9.8 Tf  [(and discussed a hypermetabolic state as being a reason for weight loss, occurring even at early stages of the disease. )] TJ ET
0.267 0.267 0.267 rg
BT 538.915 173.458 Td /F1 9.8 Tf  [([13])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 161.553 Td /F1 9.8 Tf  [(They discussed a hypermetabolic state as being likely to stem directly from interference of the mutant protein with cellular )] TJ ET
BT 26.250 149.649 Td /F1 9.8 Tf  [(energy homeostasis and thus reflecting fundamental pathologic mechanisms underlying HD and not to be secondary to )] TJ ET
BT 26.250 137.744 Td /F1 9.8 Tf  [(hyperactivity. Since mutant Huntingtin \(mtHtt\) is not only expressed in the brain of HD patients, but also in the gastrointestinal )] TJ ET
BT 26.250 125.839 Td /F1 9.8 Tf  [(\(GI\) tract, a recently published study investigated the GI tract in the R6/2 mice model for HD. This study describes a loss of )] TJ ET
BT 26.250 113.934 Td /F1 9.8 Tf  [(enteric neuropepitdes, a decreased mucosal thickness and villius length and also an impaired gut motility, diarrhea, and )] TJ ET
BT 26.250 102.030 Td /F1 9.8 Tf  [(malabsorption of food, suggesting that GI dysfunction plays an important role in weight loss in HD mice. )] TJ ET
0.267 0.267 0.267 rg
BT 474.945 102.030 Td /F1 9.8 Tf  [([14])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 82.625 Td /F1 9.8 Tf  [(In addition, gastrointestinal dysfunction is discussed as being the main reason for weight loss in Parkinson�s disease \(PD\). )] TJ ET
0.267 0.267 0.267 rg
BT 555.139 82.625 Td /F1 9.8 Tf  [([15])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 70.720 Td /F1 9.8 Tf  [(In a study using a solid meal and the )] TJ ET
BT 187.213 74.608 Td /F1 8.7 Tf  [(13)] TJ ET
BT 196.850 70.720 Td /F1 9.8 Tf  [( C-sodium octanoate breath test for measurement of gastric emptying in patients with )] TJ ET
BT 26.250 58.815 Td /F1 9.8 Tf  [(PD, Goetze and colleagues found 88% of PD patients suufered from delayed gastric emptying when compared with controls. )] TJ ET
BT 26.250 46.911 Td /F1 9.8 Tf  [(The severity of motor impairment was associated with gastroparesis. )] TJ ET
0.267 0.267 0.267 rg
BT 324.805 46.911 Td /F1 9.8 Tf  [([16])] TJ ET
0.271 0.267 0.267 rg
BT 341.068 46.911 Td /F1 9.8 Tf  [( Several other studies confirm an impaired gastric )] 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 /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
13 0 obj
<<
/Type /XObject
/Subtype /Image
/Width 500
/Height 52
/SMask 12 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
14 0 obj
<< /Type /Annot
/Subtype /Link
/A 15 0 R
/Border [0 0 0]
/H /I
/Rect [ 15.0000 716.1516 590.7360 736.9416 ]
>>
endobj
15 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/article/no-evidence-of-impaired-gastric-emptying-in-early-huntingtons-disease/)
>>
endobj
16 0 obj
<< /Type /Annot
/Subtype /Link
/A 17 0 R
/Border [0 0 0]
/H /I
/Rect [ 15.0000 691.2036 81.4860 711.9936 ]
>>
endobj
17 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/article/no-evidence-of-impaired-gastric-emptying-in-early-huntingtons-disease/)
>>
endobj
18 0 obj
<< /Type /Annot
/Subtype /Link
/A 19 0 R
/Border [0 0 0]
/H /I
/Rect [ 101.3850 674.2101 155.5463 683.8626 ]
>>
endobj
19 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/article_category/epidemiology/)
>>
endobj
20 0 obj
<< /Type /Annot
/Subtype /Link
/A 21 0 R
/Border [0 0 0]
/H /I
/Rect [ 26.2500 662.3453 80.4405 672.2659 ]
>>
endobj
21 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/author/carstensaft/)
>>
endobj
22 0 obj
<< /Type /Annot
/Subtype /Link
/A 23 0 R
/Border [0 0 0]
/H /I
/Rect [ 85.8615 662.3453 151.4303 672.2659 ]
>>
endobj
23 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/author/jurgenandrich/)
>>
endobj
24 0 obj
<< /Type /Annot
/Subtype /Link
/A 25 0 R
/Border [0 0 0]
/H /I
/Rect [ 156.8512 662.3453 208.3117 672.2659 ]
>>
endobj
25 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/author/marcfalker/)
>>
endobj
26 0 obj
<< /Type /Annot
/Subtype /Link
/A 27 0 R
/Border [0 0 0]
/H /I
/Rect [ 213.7327 662.3453 271.7258 672.2659 ]
>>
endobj
27 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/author/sarahgauda/)
>>
endobj
28 0 obj
<< /Type /Annot
/Subtype /Link
/A 29 0 R
/Border [0 0 0]
/H /I
/Rect [ 277.1467 662.3453 332.4195 672.2659 ]
>>
endobj
29 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/author/sinakuchler/)
>>
endobj
30 0 obj
<< /Type /Annot
/Subtype /Link
/A 31 0 R
/Border [0 0 0]
/H /I
/Rect [ 337.8405 662.3453 392.5477 672.2659 ]
>>
endobj
31 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/author/dirkwoitalla/)
>>
endobj
32 0 obj
<< /Type /Annot
/Subtype /Link
/A 33 0 R
/Border [0 0 0]
/H /I
/Rect [ 397.9687 662.3453 457.5705 672.2659 ]
>>
endobj
33 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/author/olivergoetze/)
>>
endobj
34 0 obj
<< /Type /Annot
/Subtype /Link
/A 35 0 R
/Border [0 0 0]
/H /I
/Rect [ 567.0825 279.6991 577.9245 289.6197 ]
>>
endobj
35 0 obj
<< /Type /Action
>>
endobj
36 0 obj
<< /Type /Annot
/Subtype /Link
/A 37 0 R
/Border [0 0 0]
/H /I
/Rect [ 26.2500 267.7943 37.0920 277.7150 ]
>>
endobj
37 0 obj
<< /Type /Action
>>
endobj
38 0 obj
<< /Type /Annot
/Subtype /Link
/A 39 0 R
/Border [0 0 0]
/H /I
/Rect [ 37.0920 267.7943 47.9340 277.7150 ]
>>
endobj
39 0 obj
<< /Type /Action
>>
endobj
40 0 obj
<< /Type /Annot
/Subtype /Link
/A 41 0 R
/Border [0 0 0]
/H /I
/Rect [ 47.9340 267.7943 58.7760 277.7150 ]
>>
endobj
41 0 obj
<< /Type /Action
>>
endobj
42 0 obj
<< /Type /Annot
/Subtype /Link
/A 43 0 R
/Border [0 0 0]
/H /I
/Rect [ 58.7760 267.7943 69.6180 277.7150 ]
>>
endobj
43 0 obj
<< /Type /Action
>>
endobj
44 0 obj
<< /Type /Annot
/Subtype /Link
/A 45 0 R
/Border [0 0 0]
/H /I
/Rect [ 81.5325 243.9848 92.3745 253.9055 ]
>>
endobj
45 0 obj
<< /Type /Action
>>
endobj
46 0 obj
<< /Type /Annot
/Subtype /Link
/A 47 0 R
/Border [0 0 0]
/H /I
/Rect [ 92.3745 243.9848 103.2165 253.9055 ]
>>
endobj
47 0 obj
<< /Type /Action
>>
endobj
48 0 obj
<< /Type /Annot
/Subtype /Link
/A 49 0 R
/Border [0 0 0]
/H /I
/Rect [ 103.2165 243.9848 114.0585 253.9055 ]
>>
endobj
49 0 obj
<< /Type /Action
>>
endobj
50 0 obj
<< /Type /Annot
/Subtype /Link
/A 51 0 R
/Border [0 0 0]
/H /I
/Rect [ 114.0585 243.9848 124.9005 253.9055 ]
>>
endobj
51 0 obj
<< /Type /Action
>>
endobj
52 0 obj
<< /Type /Annot
/Subtype /Link
/A 53 0 R
/Border [0 0 0]
/H /I
/Rect [ 124.9005 243.9848 141.1635 253.9055 ]
>>
endobj
53 0 obj
<< /Type /Action
>>
endobj
54 0 obj
<< /Type /Annot
/Subtype /Link
/A 55 0 R
/Border [0 0 0]
/H /I
/Rect [ 533.4645 220.1753 544.3065 230.0960 ]
>>
endobj
55 0 obj
<< /Type /Action
>>
endobj
56 0 obj
<< /Type /Annot
/Subtype /Link
/A 57 0 R
/Border [0 0 0]
/H /I
/Rect [ 205.6110 196.3658 216.4530 206.2864 ]
>>
endobj
57 0 obj
<< /Type /Action
>>
endobj
58 0 obj
<< /Type /Annot
/Subtype /Link
/A 59 0 R
/Border [0 0 0]
/H /I
/Rect [ 216.4530 196.3658 232.7160 206.2864 ]
>>
endobj
59 0 obj
<< /Type /Action
>>
endobj
60 0 obj
<< /Type /Annot
/Subtype /Link
/A 61 0 R
/Border [0 0 0]
/H /I
/Rect [ 232.7160 196.3658 248.9790 206.2864 ]
>>
endobj
61 0 obj
<< /Type /Action
>>
endobj
62 0 obj
<< /Type /Annot
/Subtype /Link
/A 63 0 R
/Border [0 0 0]
/H /I
/Rect [ 538.9148 172.5563 555.1778 182.4769 ]
>>
endobj
63 0 obj
<< /Type /Action
>>
endobj
64 0 obj
<< /Type /Annot
/Subtype /Link
/A 65 0 R
/Border [0 0 0]
/H /I
/Rect [ 474.9450 101.1278 491.2080 111.0484 ]
>>
endobj
65 0 obj
<< /Type /Action
>>
endobj
66 0 obj
<< /Type /Annot
/Subtype /Link
/A 67 0 R
/Border [0 0 0]
/H /I
/Rect [ 555.1387 81.7231 571.4017 91.6437 ]
>>
endobj
67 0 obj
<< /Type /Action
>>
endobj
68 0 obj
<< /Type /Annot
/Subtype /Link
/A 69 0 R
/Border [0 0 0]
/H /I
/Rect [ 324.8048 46.0088 341.0677 55.9294 ]
>>
endobj
69 0 obj
<< /Type /Action
>>
endobj
70 0 obj
<< /Type /Annot
/Subtype /Link
/A 71 0 R
/Border [0 0 0]
/H /I
/Rect [ 15.0000 716.1516 590.7360 736.9416 ]
>>
endobj
71 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/article/no-evidence-of-impaired-gastric-emptying-in-early-huntingtons-disease/)
>>
endobj
72 0 obj
<< /Type /Annot
/Subtype /Link
/A 73 0 R
/Border [0 0 0]
/H /I
/Rect [ 15.0000 691.2036 81.4860 711.9936 ]
>>
endobj
73 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/article/no-evidence-of-impaired-gastric-emptying-in-early-huntingtons-disease/)
>>
endobj
74 0 obj
<< /Type /Annot
/Subtype /Link
/A 75 0 R
/Border [0 0 0]
/H /I
/Rect [ 101.3850 674.2101 155.5463 683.8626 ]
>>
endobj
75 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/article_category/epidemiology/)
>>
endobj
76 0 obj
<< /Type /Annot
/Subtype /Link
/A 77 0 R
/Border [0 0 0]
/H /I
/Rect [ 26.2500 662.3453 80.4405 672.2659 ]
>>
endobj
77 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/author/carstensaft/)
>>
endobj
78 0 obj
<< /Type /Annot
/Subtype /Link
/A 79 0 R
/Border [0 0 0]
/H /I
/Rect [ 85.8615 662.3453 151.4303 672.2659 ]
>>
endobj
79 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/author/jurgenandrich/)
>>
endobj
80 0 obj
<< /Type /Annot
/Subtype /Link
/A 81 0 R
/Border [0 0 0]
/H /I
/Rect [ 156.8512 662.3453 208.3117 672.2659 ]
>>
endobj
81 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/author/marcfalker/)
>>
endobj
82 0 obj
<< /Type /Annot
/Subtype /Link
/A 83 0 R
/Border [0 0 0]
/H /I
/Rect [ 213.7327 662.3453 271.7258 672.2659 ]
>>
endobj
83 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/author/sarahgauda/)
>>
endobj
84 0 obj
<< /Type /Annot
/Subtype /Link
/A 85 0 R
/Border [0 0 0]
/H /I
/Rect [ 277.1467 662.3453 332.4195 672.2659 ]
>>
endobj
85 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/author/sinakuchler/)
>>
endobj
86 0 obj
<< /Type /Annot
/Subtype /Link
/A 87 0 R
/Border [0 0 0]
/H /I
/Rect [ 337.8405 662.3453 392.5477 672.2659 ]
>>
endobj
87 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/author/dirkwoitalla/)
>>
endobj
88 0 obj
<< /Type /Annot
/Subtype /Link
/A 89 0 R
/Border [0 0 0]
/H /I
/Rect [ 397.9687 662.3453 457.5705 672.2659 ]
>>
endobj
89 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/author/olivergoetze/)
>>
endobj
90 0 obj
<< /Type /Annot
/Subtype /Link
/A 91 0 R
/Border [0 0 0]
/H /I
/Rect [ 567.0825 279.6991 577.9245 289.6197 ]
>>
endobj
91 0 obj
<< /Type /Action
>>
endobj
92 0 obj
<< /Type /Annot
/Subtype /Link
/A 93 0 R
/Border [0 0 0]
/H /I
/Rect [ 26.2500 267.7943 37.0920 277.7150 ]
>>
endobj
93 0 obj
<< /Type /Action
>>
endobj
94 0 obj
<< /Type /Annot
/Subtype /Link
/A 95 0 R
/Border [0 0 0]
/H /I
/Rect [ 37.0920 267.7943 47.9340 277.7150 ]
>>
endobj
95 0 obj
<< /Type /Action
>>
endobj
96 0 obj
<< /Type /Annot
/Subtype /Link
/A 97 0 R
/Border [0 0 0]
/H /I
/Rect [ 47.9340 267.7943 58.7760 277.7150 ]
>>
endobj
97 0 obj
<< /Type /Action
>>
endobj
98 0 obj
<< /Type /Annot
/Subtype /Link
/A 99 0 R
/Border [0 0 0]
/H /I
/Rect [ 58.7760 267.7943 69.6180 277.7150 ]
>>
endobj
99 0 obj
<< /Type /Action
>>
endobj
100 0 obj
<< /Type /Annot
/Subtype /Link
/A 101 0 R
/Border [0 0 0]
/H /I
/Rect [ 81.5325 243.9848 92.3745 253.9055 ]
>>
endobj
101 0 obj
<< /Type /Action
>>
endobj
102 0 obj
<< /Type /Annot
/Subtype /Link
/A 103 0 R
/Border [0 0 0]
/H /I
/Rect [ 92.3745 243.9848 103.2165 253.9055 ]
>>
endobj
103 0 obj
<< /Type /Action
>>
endobj
104 0 obj
<< /Type /Annot
/Subtype /Link
/A 105 0 R
/Border [0 0 0]
/H /I
/Rect [ 103.2165 243.9848 114.0585 253.9055 ]
>>
endobj
105 0 obj
<< /Type /Action
>>
endobj
106 0 obj
<< /Type /Annot
/Subtype /Link
/A 107 0 R
/Border [0 0 0]
/H /I
/Rect [ 114.0585 243.9848 124.9005 253.9055 ]
>>
endobj
107 0 obj
<< /Type /Action
>>
endobj
108 0 obj
<< /Type /Annot
/Subtype /Link
/A 109 0 R
/Border [0 0 0]
/H /I
/Rect [ 124.9005 243.9848 141.1635 253.9055 ]
>>
endobj
109 0 obj
<< /Type /Action
>>
endobj
110 0 obj
<< /Type /Annot
/Subtype /Link
/A 111 0 R
/Border [0 0 0]
/H /I
/Rect [ 533.4645 220.1753 544.3065 230.0960 ]
>>
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 [ 205.6110 196.3658 216.4530 206.2864 ]
>>
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 [ 216.4530 196.3658 232.7160 206.2864 ]
>>
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 [ 232.7160 196.3658 248.9790 206.2864 ]
>>
endobj
117 0 obj
<< /Type /Action
>>
endobj
118 0 obj
<< /Type /Annot
/Subtype /Link
/A 119 0 R
/Border [0 0 0]
/H /I
/Rect [ 538.9148 172.5563 555.1778 182.4769 ]
>>
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 [ 474.9450 101.1278 491.2080 111.0484 ]
>>
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 [ 555.1387 81.7231 571.4017 91.6437 ]
>>
endobj
123 0 obj
<< /Type /Action
>>
endobj
124 0 obj
<< /Type /Annot
/Subtype /Link
/A 125 0 R
/Border [0 0 0]
/H /I
/Rect [ 324.8048 46.0088 341.0677 55.9294 ]
>>
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 [ 15.0000 716.1516 590.7360 736.9416 ]
>>
endobj
127 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/article/no-evidence-of-impaired-gastric-emptying-in-early-huntingtons-disease/)
>>
endobj
128 0 obj
<< /Type /Annot
/Subtype /Link
/A 129 0 R
/Border [0 0 0]
/H /I
/Rect [ 15.0000 691.2036 81.4860 711.9936 ]
>>
endobj
129 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/article/no-evidence-of-impaired-gastric-emptying-in-early-huntingtons-disease/)
>>
endobj
130 0 obj
<< /Type /Annot
/Subtype /Link
/A 131 0 R
/Border [0 0 0]
/H /I
/Rect [ 101.3850 674.2101 155.5463 683.8626 ]
>>
endobj
131 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/article_category/epidemiology/)
>>
endobj
132 0 obj
<< /Type /Annot
/Subtype /Link
/A 133 0 R
/Border [0 0 0]
/H /I
/Rect [ 26.2500 662.3453 80.4405 672.2659 ]
>>
endobj
133 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/author/carstensaft/)
>>
endobj
134 0 obj
<< /Type /Annot
/Subtype /Link
/A 135 0 R
/Border [0 0 0]
/H /I
/Rect [ 85.8615 662.3453 151.4303 672.2659 ]
>>
endobj
135 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/author/jurgenandrich/)
>>
endobj
136 0 obj
<< /Type /Annot
/Subtype /Link
/A 137 0 R
/Border [0 0 0]
/H /I
/Rect [ 156.8512 662.3453 208.3117 672.2659 ]
>>
endobj
137 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/author/marcfalker/)
>>
endobj
138 0 obj
<< /Type /Annot
/Subtype /Link
/A 139 0 R
/Border [0 0 0]
/H /I
/Rect [ 213.7327 662.3453 271.7258 672.2659 ]
>>
endobj
139 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/author/sarahgauda/)
>>
endobj
140 0 obj
<< /Type /Annot
/Subtype /Link
/A 141 0 R
/Border [0 0 0]
/H /I
/Rect [ 277.1467 662.3453 332.4195 672.2659 ]
>>
endobj
141 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/author/sinakuchler/)
>>
endobj
142 0 obj
<< /Type /Annot
/Subtype /Link
/A 143 0 R
/Border [0 0 0]
/H /I
/Rect [ 337.8405 662.3453 392.5477 672.2659 ]
>>
endobj
143 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/author/dirkwoitalla/)
>>
endobj
144 0 obj
<< /Type /Annot
/Subtype /Link
/A 145 0 R
/Border [0 0 0]
/H /I
/Rect [ 397.9687 662.3453 457.5705 672.2659 ]
>>
endobj
145 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/author/olivergoetze/)
>>
endobj
146 0 obj
<< /Type /Annot
/Subtype /Link
/A 147 0 R
/Border [0 0 0]
/H /I
/Rect [ 567.0825 279.6991 577.9245 289.6197 ]
>>
endobj
147 0 obj
<< /Type /Action
>>
endobj
148 0 obj
<< /Type /Annot
/Subtype /Link
/A 149 0 R
/Border [0 0 0]
/H /I
/Rect [ 26.2500 267.7943 37.0920 277.7150 ]
>>
endobj
149 0 obj
<< /Type /Action
>>
endobj
150 0 obj
<< /Type /Annot
/Subtype /Link
/A 151 0 R
/Border [0 0 0]
/H /I
/Rect [ 37.0920 267.7943 47.9340 277.7150 ]
>>
endobj
151 0 obj
<< /Type /Action
>>
endobj
152 0 obj
<< /Type /Annot
/Subtype /Link
/A 153 0 R
/Border [0 0 0]
/H /I
/Rect [ 47.9340 267.7943 58.7760 277.7150 ]
>>
endobj
153 0 obj
<< /Type /Action
>>
endobj
154 0 obj
<< /Type /Annot
/Subtype /Link
/A 155 0 R
/Border [0 0 0]
/H /I
/Rect [ 58.7760 267.7943 69.6180 277.7150 ]
>>
endobj
155 0 obj
<< /Type /Action
>>
endobj
156 0 obj
<< /Type /Annot
/Subtype /Link
/A 157 0 R
/Border [0 0 0]
/H /I
/Rect [ 81.5325 243.9848 92.3745 253.9055 ]
>>
endobj
157 0 obj
<< /Type /Action
>>
endobj
158 0 obj
<< /Type /Annot
/Subtype /Link
/A 159 0 R
/Border [0 0 0]
/H /I
/Rect [ 92.3745 243.9848 103.2165 253.9055 ]
>>
endobj
159 0 obj
<< /Type /Action
>>
endobj
160 0 obj
<< /Type /Annot
/Subtype /Link
/A 161 0 R
/Border [0 0 0]
/H /I
/Rect [ 103.2165 243.9848 114.0585 253.9055 ]
>>
endobj
161 0 obj
<< /Type /Action
>>
endobj
162 0 obj
<< /Type /Annot
/Subtype /Link
/A 163 0 R
/Border [0 0 0]
/H /I
/Rect [ 114.0585 243.9848 124.9005 253.9055 ]
>>
endobj
163 0 obj
<< /Type /Action
>>
endobj
164 0 obj
<< /Type /Annot
/Subtype /Link
/A 165 0 R
/Border [0 0 0]
/H /I
/Rect [ 124.9005 243.9848 141.1635 253.9055 ]
>>
endobj
165 0 obj
<< /Type /Action
>>
endobj
166 0 obj
<< /Type /Annot
/Subtype /Link
/A 167 0 R
/Border [0 0 0]
/H /I
/Rect [ 533.4645 220.1753 544.3065 230.0960 ]
>>
endobj
167 0 obj
<< /Type /Action
>>
endobj
168 0 obj
<< /Type /Annot
/Subtype /Link
/A 169 0 R
/Border [0 0 0]
/H /I
/Rect [ 205.6110 196.3658 216.4530 206.2864 ]
>>
endobj
169 0 obj
<< /Type /Action
>>
endobj
170 0 obj
<< /Type /Annot
/Subtype /Link
/A 171 0 R
/Border [0 0 0]
/H /I
/Rect [ 216.4530 196.3658 232.7160 206.2864 ]
>>
endobj
171 0 obj
<< /Type /Action
>>
endobj
172 0 obj
<< /Type /Annot
/Subtype /Link
/A 173 0 R
/Border [0 0 0]
/H /I
/Rect [ 232.7160 196.3658 248.9790 206.2864 ]
>>
endobj
173 0 obj
<< /Type /Action
>>
endobj
174 0 obj
<< /Type /Annot
/Subtype /Link
/A 175 0 R
/Border [0 0 0]
/H /I
/Rect [ 538.9148 172.5563 555.1778 182.4769 ]
>>
endobj
175 0 obj
<< /Type /Action
>>
endobj
176 0 obj
<< /Type /Annot
/Subtype /Link
/A 177 0 R
/Border [0 0 0]
/H /I
/Rect [ 474.9450 101.1278 491.2080 111.0484 ]
>>
endobj
177 0 obj
<< /Type /Action
>>
endobj
178 0 obj
<< /Type /Annot
/Subtype /Link
/A 179 0 R
/Border [0 0 0]
/H /I
/Rect [ 555.1387 81.7231 571.4017 91.6437 ]
>>
endobj
179 0 obj
<< /Type /Action
>>
endobj
180 0 obj
<< /Type /Annot
/Subtype /Link
/A 181 0 R
/Border [0 0 0]
/H /I
/Rect [ 324.8048 46.0088 341.0677 55.9294 ]
>>
endobj
181 0 obj
<< /Type /Action
>>
endobj
182 0 obj
<< /Type /Page
/Parent 3 0 R
/Annots [ 184 0 R 186 0 R 188 0 R 190 0 R 192 0 R 194 0 R 196 0 R 198 0 R 200 0 R 202 0 R 204 0 R 206 0 R 208 0 R 210 0 R 212 0 R 214 0 R 216 0 R 218 0 R 220 0 R 222 0 R 224 0 R 226 0 R 228 0 R 230 0 R 232 0 R 234 0 R 236 0 R 238 0 R 240 0 R 242 0 R 244 0 R 246 0 R 248 0 R 250 0 R 252 0 R 254 0 R 256 0 R 258 0 R 260 0 R 262 0 R 264 0 R 266 0 R 268 0 R 270 0 R 272 0 R 274 0 R 276 0 R 278 0 R 280 0 R 282 0 R 284 0 R 286 0 R 288 0 R 290 0 R 292 0 R 294 0 R 296 0 R 298 0 R 300 0 R 302 0 R 304 0 R 306 0 R 308 0 R 310 0 R 312 0 R 314 0 R 316 0 R 318 0 R 320 0 R 322 0 R 324 0 R 326 0 R 328 0 R 330 0 R 332 0 R 334 0 R 336 0 R 338 0 R 340 0 R 342 0 R 344 0 R ]
/Contents 183 0 R
>>
endobj
183 0 obj
<<
/Length 53824 >>
stream

0.271 0.267 0.267 rg
q
15.000 76.473 577.500 700.527 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(emptying in PD, some of them with a rate of 100% of PD patients. )] TJ ET
0.267 0.267 0.267 rg
BT 312.383 767.476 Td /F1 9.8 Tf  [([16])] TJ ET
BT 328.646 767.476 Td /F1 9.8 Tf  [([17])] TJ ET
BT 344.909 767.476 Td /F1 9.8 Tf  [([18])] TJ ET
BT 361.172 767.476 Td /F1 9.8 Tf  [([19])] TJ ET
BT 377.435 767.476 Td /F1 9.8 Tf  [([20])] TJ ET
BT 393.698 767.476 Td /F1 9.8 Tf  [([21])] TJ ET
0.271 0.267 0.267 rg
BT 409.961 767.476 Td /F1 9.8 Tf  [( One study describes a 60% delay in )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(gastric half emptying time in the PD patient group after a solid test meal using the non-invasive )] TJ ET
BT 437.017 759.460 Td /F1 8.7 Tf  [(13)] TJ ET
BT 446.655 755.571 Td /F1 9.8 Tf  [( C-sodium octanoate breath )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(test for evaluation of gastric emptying. )] TJ ET
0.267 0.267 0.267 rg
BT 193.160 743.667 Td /F1 9.8 Tf  [([17])] TJ ET
0.271 0.267 0.267 rg
BT 209.423 743.667 Td /F1 9.8 Tf  [( Neuropathological findings suggest enteric dysfunction to be one of the initial )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(pathophysiological events in PD. )] TJ ET
0.267 0.267 0.267 rg
BT 169.858 731.762 Td /F1 9.8 Tf  [([16])] TJ ET
BT 186.121 731.762 Td /F1 9.8 Tf  [([22])] TJ ET
0.271 0.267 0.267 rg
BT 202.384 731.762 Td /F1 9.8 Tf  [( Central and enteric nervous system involvement in PD is discussed as being a )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(pathophysiologic basis for this dysfunction. )] TJ ET
0.267 0.267 0.267 rg
BT 213.752 719.857 Td /F1 9.8 Tf  [([15])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 700.452 Td /F1 9.8 Tf  [(Autonomic nervous dysfunction was found to be present in HD, too. )] TJ ET
0.267 0.267 0.267 rg
BT 319.978 700.452 Td /F1 9.8 Tf  [([23])] TJ ET
0.271 0.267 0.267 rg
BT 336.241 700.452 Td /F1 9.8 Tf  [( Thus, the aim of the current study was to investigate )] TJ ET
BT 26.250 688.548 Td /F1 9.8 Tf  [(gastric emptying in early HD patients without medication as a possible additional reason for weight loss by using the well-)] TJ ET
BT 26.250 676.643 Td /F1 9.8 Tf  [(established )] TJ ET
BT 78.276 680.531 Td /F1 8.7 Tf  [(13)] TJ ET
BT 87.913 676.643 Td /F1 9.8 Tf  [( C-octanoate breath test. )] TJ ET
0.267 0.267 0.267 rg
BT 197.932 676.643 Td /F1 9.8 Tf  [([16])] TJ ET
BT 214.195 676.643 Td /F1 9.8 Tf  [([17])] TJ ET
BT 230.458 676.643 Td /F1 9.8 Tf  [([18])] TJ ET
BT 246.721 676.643 Td /F1 9.8 Tf  [([19])] TJ ET
BT 262.984 676.643 Td /F1 9.8 Tf  [([20])] TJ ET
BT 279.247 676.643 Td /F1 9.8 Tf  [([21])] TJ ET
BT 295.510 676.643 Td /F1 9.8 Tf  [([24])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 640.040 Td /F4 12.0 Tf  [(Methods)] TJ ET
BT 26.250 620.086 Td /F4 9.8 Tf  [(Participants)] TJ ET
BT 26.250 600.681 Td /F1 9.8 Tf  [(11 manifest HD patients with genetically confirmed diagnosis and without any medication in at clinically early stages of the )] TJ ET
BT 26.250 588.777 Td /F1 9.8 Tf  [(disease \(Shoulson stage I/II\) and 11 controls were recruited from the HD centre Bochum, Germany. )] TJ ET
0.267 0.267 0.267 rg
BT 458.136 588.777 Td /F1 9.8 Tf  [([25])] TJ ET
0.271 0.267 0.267 rg
BT 474.399 588.777 Td /F1 9.8 Tf  [( Participants with )] TJ ET
BT 26.250 576.872 Td /F1 9.8 Tf  [(known concurrent gastrointestinal diseases or previous operations of the gastro-intestinal tract were excluded, as well as )] TJ ET
BT 26.250 564.967 Td /F1 9.8 Tf  [(patients with other severe diseases, diabetes mellitus, severe respiratory dysfunction, and malignancies. Also participants with )] TJ ET
BT 26.250 553.062 Td /F1 9.8 Tf  [(concurrent liver diseases or excessive alcohol consumption \(50 g/d of ethanol\) were excluded. All participants had lab )] TJ ET
BT 26.250 541.158 Td /F1 9.8 Tf  [(parameters for ALT, AST, LDH, cholesterol and triglycerides within the normal range, as well as normal findings for the )] TJ ET
BT 26.250 529.253 Td /F1 9.8 Tf  [(ultrasonography of the upper abdomen. Pregnant and breast-feeding women were excluded. All HD participants underwent )] TJ ET
BT 26.250 517.348 Td /F1 9.8 Tf  [(neurological investigation and were scored according to the UHDRS items �motor scale� \(MS\), �total functional capacity� \(TFC\) )] TJ ET
BT 26.250 505.443 Td /F1 9.8 Tf  [(�independence scale� \(IS\) and the items verbal fluency test, symbol digit test, interference test, color naming and color reading )] TJ ET
BT 26.250 493.539 Td /F1 9.8 Tf  [(which were summarized as �cognitive score� \(CS\). )] TJ ET
0.267 0.267 0.267 rg
BT 246.210 493.539 Td /F1 9.8 Tf  [([26])] TJ ET
0.271 0.267 0.267 rg
BT 262.473 493.539 Td /F1 9.8 Tf  [( Fine motor skills were additionally measured by simple \(tapping; higher )] TJ ET
BT 26.250 481.634 Td /F1 9.8 Tf  [(motor impairment leads to lower test results\) and complex \(pegboard; higher motor impairment leads to higher test results\) )] TJ ET
BT 26.250 469.729 Td /F1 9.8 Tf  [(instrumental movement tests. )] TJ ET
0.267 0.267 0.267 rg
BT 156.296 469.729 Td /F1 9.8 Tf  [([27])] TJ ET
BT 172.559 469.729 Td /F1 9.8 Tf  [([28])] TJ ET
BT 188.822 469.729 Td /F1 9.8 Tf  [([29])] TJ ET
BT 205.085 469.729 Td /F1 9.8 Tf  [([30])] TJ ET
0.271 0.267 0.267 rg
BT 221.348 469.729 Td /F1 9.8 Tf  [( The severity of depressive symptoms was assessed by using the Beck�s )] TJ ET
BT 26.250 457.824 Td /F1 9.8 Tf  [(depression inventory \(BDI\) and Hamilton depression rating scale. )] TJ ET
0.267 0.267 0.267 rg
BT 310.190 457.824 Td /F1 9.8 Tf  [([31])] TJ ET
BT 326.452 457.824 Td /F1 9.8 Tf  [([32])] TJ ET
0.271 0.267 0.267 rg
BT 342.715 457.824 Td /F1 9.8 Tf  [( Clinical characteristics of all HD patients are given in )] TJ ET
BT 26.250 445.920 Td /F1 9.8 Tf  [(table 1. In addition we calculated the disease burden score \(DBS = [CAG repeat � 35.5] x age\) for each subject. )] TJ ET
0.267 0.267 0.267 rg
BT 510.484 445.920 Td /F1 9.8 Tf  [([33])] TJ ET
0.271 0.267 0.267 rg
BT 526.747 445.920 Td /F1 9.8 Tf  [( The study )] TJ ET
BT 26.250 434.015 Td /F1 9.8 Tf  [(was approved by the ethic committee of the Ruhr-University Bochum, Germany \(registration-number 2719\). Participants gave )] TJ ET
BT 26.250 422.110 Td /F1 9.8 Tf  [(informed written consent according to GCP/ICH.)] TJ ET
1.000 1.000 1.000 rg
26.250 76.473 555.000 335.756 re f
0.267 0.267 0.267 rg
26.625 411.104 210.174 0.750 re f
26.625 395.223 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 401.249 Td /F4 9.8 Tf  [(Parameter)] TJ ET
0.267 0.267 0.267 rg
236.049 411.104 188.959 0.750 re f
236.049 395.223 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 401.249 Td /F4 9.8 Tf  [(HD Participants)] TJ ET
0.267 0.267 0.267 rg
424.258 411.104 156.617 0.750 re f
424.258 395.223 0.750 16.631 re f
580.125 395.223 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 401.249 Td /F4 9.8 Tf  [(Controls)] TJ ET
0.267 0.267 0.267 rg
26.625 395.223 210.174 0.750 re f
26.625 379.342 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 385.368 Td /F1 9.8 Tf  [(Age [yr])] TJ ET
0.267 0.267 0.267 rg
236.049 395.223 188.959 0.750 re f
236.049 379.342 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 385.368 Td /F1 9.8 Tf  [(42.4 � 8.4 \(29-57\))] TJ ET
0.267 0.267 0.267 rg
424.258 395.223 156.617 0.750 re f
424.258 379.342 0.750 16.631 re f
580.125 379.342 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 385.368 Td /F1 9.8 Tf  [(48.9 � 9.6 \(38-69\))] TJ ET
0.267 0.267 0.267 rg
26.625 379.342 210.174 0.750 re f
26.625 363.461 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 369.487 Td /F1 9.8 Tf  [(Gender \(male/female\))] TJ ET
0.267 0.267 0.267 rg
236.049 379.342 188.959 0.750 re f
236.049 363.461 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 369.487 Td /F1 9.8 Tf  [(3/8)] TJ ET
0.267 0.267 0.267 rg
424.258 379.342 156.617 0.750 re f
424.258 363.461 0.750 16.631 re f
580.125 363.461 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 369.487 Td /F1 9.8 Tf  [(3/8)] TJ ET
0.267 0.267 0.267 rg
26.625 363.461 210.174 0.750 re f
26.625 347.579 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 353.606 Td /F1 9.8 Tf  [(BMI)] TJ ET
0.267 0.267 0.267 rg
236.049 363.461 188.959 0.750 re f
236.049 347.579 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 353.606 Td /F1 9.8 Tf  [(22.5 � 3.5 \(16-30\))] TJ ET
0.267 0.267 0.267 rg
424.258 363.461 156.617 0.750 re f
424.258 347.579 0.750 16.631 re f
580.125 347.579 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 353.606 Td /F1 9.8 Tf  [(26.5 � 6.4 \(19-42\))] TJ ET
0.267 0.267 0.267 rg
26.625 347.579 210.174 0.750 re f
26.625 331.698 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 337.724 Td /F1 9.8 Tf  [(Weight [kg])] TJ ET
0.267 0.267 0.267 rg
236.049 347.579 188.959 0.750 re f
236.049 331.698 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 337.724 Td /F1 9.8 Tf  [(63.6 � 14.1 \(42-85\))] TJ ET
0.267 0.267 0.267 rg
424.258 347.579 156.617 0.750 re f
424.258 331.698 0.750 16.631 re f
580.125 331.698 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 337.724 Td /F1 9.8 Tf  [(84.5 � 22.5 \(54-128\))] TJ ET
0.267 0.267 0.267 rg
26.625 331.698 210.174 0.750 re f
26.625 315.817 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 321.843 Td /F1 9.8 Tf  [(Height [cm])] TJ ET
0.267 0.267 0.267 rg
236.049 331.698 188.959 0.750 re f
236.049 315.817 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 321.843 Td /F1 9.8 Tf  [(166.8 � 10.1 \(153-183\))] TJ ET
0.267 0.267 0.267 rg
424.258 331.698 156.617 0.750 re f
424.258 315.817 0.750 16.631 re f
580.125 315.817 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 321.843 Td /F1 9.8 Tf  [(178.2 � 9.4 \(164-190\))] TJ ET
0.267 0.267 0.267 rg
26.625 315.817 210.174 0.750 re f
26.625 299.935 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 305.962 Td /F1 9.8 Tf  [(AO motor)] TJ ET
0.267 0.267 0.267 rg
236.049 315.817 188.959 0.750 re f
236.049 299.935 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 305.962 Td /F1 9.8 Tf  [(39 � 8.6 \(25-51\))] TJ ET
0.267 0.267 0.267 rg
424.258 315.817 156.617 0.750 re f
424.258 299.935 0.750 16.631 re f
580.125 299.935 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 305.962 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 299.935 210.174 0.750 re f
26.625 284.054 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 290.080 Td /F1 9.8 Tf  [(AO psychiatric)] TJ ET
0.267 0.267 0.267 rg
236.049 299.935 188.959 0.750 re f
236.049 284.054 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 290.080 Td /F1 9.8 Tf  [(38 � 20.9 \(29-50\)a)] TJ ET
0.267 0.267 0.267 rg
424.258 299.935 156.617 0.750 re f
424.258 284.054 0.750 16.631 re f
580.125 284.054 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 290.080 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 284.054 210.174 0.750 re f
26.625 268.173 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 274.199 Td /F1 9.8 Tf  [(CAG expanded)] TJ ET
0.267 0.267 0.267 rg
236.049 284.054 188.959 0.750 re f
236.049 268.173 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 274.199 Td /F1 9.8 Tf  [(45 � 2.9 \(42-51\))] TJ ET
0.267 0.267 0.267 rg
424.258 284.054 156.617 0.750 re f
424.258 268.173 0.750 16.631 re f
580.125 268.173 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 274.199 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 268.173 210.174 0.750 re f
26.625 252.292 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 258.318 Td /F1 9.8 Tf  [(Disease burden score)] TJ ET
0.267 0.267 0.267 rg
236.049 268.173 188.959 0.750 re f
236.049 252.292 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 258.318 Td /F1 9.8 Tf  [(386.59 � 66.06 \(273-483\))] TJ ET
0.267 0.267 0.267 rg
424.258 268.173 156.617 0.750 re f
424.258 252.292 0.750 16.631 re f
580.125 252.292 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 258.318 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 252.292 210.174 0.750 re f
26.625 236.410 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 242.437 Td /F1 9.8 Tf  [(Disease duration [yr])] TJ ET
0.267 0.267 0.267 rg
236.049 252.292 188.959 0.750 re f
236.049 236.410 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 242.437 Td /F1 9.8 Tf  [(4.2 � 2.5 \(0.1-9\))] TJ ET
0.267 0.267 0.267 rg
424.258 252.292 156.617 0.750 re f
424.258 236.410 0.750 16.631 re f
580.125 236.410 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 242.437 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 236.410 210.174 0.750 re f
26.625 235.660 0.750 1.500 re f
236.049 236.410 188.959 0.750 re f
236.049 235.660 0.750 1.500 re f
424.258 236.410 156.617 0.750 re f
424.258 235.660 0.750 1.500 re f
580.125 235.660 0.750 1.500 re f
26.625 235.660 210.174 0.750 re f
26.625 219.779 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 225.805 Td /F1 9.8 Tf  [(UHDRS MS)] TJ ET
0.267 0.267 0.267 rg
236.049 235.660 188.959 0.750 re f
236.049 219.779 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 225.805 Td /F1 9.8 Tf  [(30.8 � 18.7 \(5-72\))] TJ ET
0.267 0.267 0.267 rg
424.258 235.660 156.617 0.750 re f
424.258 219.779 0.750 16.631 re f
580.125 219.779 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 225.805 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 219.779 210.174 0.750 re f
26.625 203.898 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 209.924 Td /F1 9.8 Tf  [(UHDRS TFC)] TJ ET
0.267 0.267 0.267 rg
236.049 219.779 188.959 0.750 re f
236.049 203.898 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 209.924 Td /F1 9.8 Tf  [(10.2 � 1.9 \(7-12\))] TJ ET
0.267 0.267 0.267 rg
424.258 219.779 156.617 0.750 re f
424.258 203.898 0.750 16.631 re f
580.125 203.898 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 209.924 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 203.898 210.174 0.750 re f
26.625 188.017 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 194.043 Td /F1 9.8 Tf  [(UHDRS IS)] TJ ET
0.267 0.267 0.267 rg
236.049 203.898 188.959 0.750 re f
236.049 188.017 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 194.043 Td /F1 9.8 Tf  [(81.8 � 9.8 \(70-100\))] TJ ET
0.267 0.267 0.267 rg
424.258 203.898 156.617 0.750 re f
424.258 188.017 0.750 16.631 re f
580.125 188.017 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 194.043 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 188.017 210.174 0.750 re f
26.625 172.135 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 178.162 Td /F1 9.8 Tf  [(UHDRS CS)] TJ ET
0.267 0.267 0.267 rg
236.049 188.017 188.959 0.750 re f
236.049 172.135 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 178.162 Td /F1 9.8 Tf  [(195.1 � 79.0 \(98-346\))] TJ ET
0.267 0.267 0.267 rg
424.258 188.017 156.617 0.750 re f
424.258 172.135 0.750 16.631 re f
580.125 172.135 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 178.162 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 172.135 210.174 0.750 re f
26.625 156.254 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 162.280 Td /F1 9.8 Tf  [(Verbal fluency)] TJ ET
0.267 0.267 0.267 rg
236.049 172.135 188.959 0.750 re f
236.049 156.254 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 162.280 Td /F1 9.8 Tf  [(22.5 � 18.2 \(4-69\))] TJ ET
0.267 0.267 0.267 rg
424.258 172.135 156.617 0.750 re f
424.258 156.254 0.750 16.631 re f
580.125 156.254 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 162.280 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 156.254 210.174 0.750 re f
26.625 140.373 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 146.399 Td /F1 9.8 Tf  [(SDMT)] TJ ET
0.267 0.267 0.267 rg
236.049 156.254 188.959 0.750 re f
236.049 140.373 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 146.399 Td /F1 9.8 Tf  [(27.2 � 10.6 \(16-44\))] TJ ET
0.267 0.267 0.267 rg
424.258 156.254 156.617 0.750 re f
424.258 140.373 0.750 16.631 re f
580.125 140.373 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 146.399 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 140.373 210.174 0.750 re f
26.625 124.492 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 130.518 Td /F1 9.8 Tf  [(Stroop color)] TJ ET
0.267 0.267 0.267 rg
236.049 140.373 188.959 0.750 re f
236.049 124.492 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 130.518 Td /F1 9.8 Tf  [(47.1 � 17.1 \(26-74\))] TJ ET
0.267 0.267 0.267 rg
424.258 140.373 156.617 0.750 re f
424.258 124.492 0.750 16.631 re f
580.125 124.492 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 130.518 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 124.492 210.174 0.750 re f
26.625 108.610 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 114.637 Td /F1 9.8 Tf  [(Stroop word)] TJ ET
0.267 0.267 0.267 rg
236.049 124.492 188.959 0.750 re f
236.049 108.610 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 114.637 Td /F1 9.8 Tf  [(68.1 � 22.8 \(32-100\))] TJ ET
0.267 0.267 0.267 rg
424.258 124.492 156.617 0.750 re f
424.258 108.610 0.750 16.631 re f
580.125 108.610 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 114.637 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 108.610 210.174 0.750 re f
26.625 92.729 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 98.755 Td /F1 9.8 Tf  [(Stroop interference)] TJ ET
0.267 0.267 0.267 rg
236.049 108.610 188.959 0.750 re f
236.049 92.729 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 98.755 Td /F1 9.8 Tf  [(29.5 � 16.1 \(10-59\))] TJ ET
0.267 0.267 0.267 rg
424.258 108.610 156.617 0.750 re f
424.258 92.729 0.750 16.631 re f
580.125 92.729 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 98.755 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 92.729 210.174 0.750 re f
26.625 76.848 210.174 0.750 re f
26.625 76.848 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 82.874 Td /F1 9.8 Tf  [(Hamilton)] TJ ET
0.267 0.267 0.267 rg
236.049 92.729 188.959 0.750 re f
236.049 76.848 188.959 0.750 re f
236.049 76.848 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 82.874 Td /F1 9.8 Tf  [(12.8 � 10.0 \(1-26\))] TJ ET
0.267 0.267 0.267 rg
424.258 92.729 156.617 0.750 re f
424.258 76.848 156.617 0.750 re f
424.258 76.848 0.750 16.631 re f
580.125 76.848 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 82.874 Td /F1 9.8 Tf  [(�)] TJ ET
Q
q
15.000 76.473 577.500 700.527 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(emptying in PD, some of them with a rate of 100% of PD patients. )] TJ ET
0.267 0.267 0.267 rg
BT 312.383 767.476 Td /F1 9.8 Tf  [([16])] TJ ET
BT 328.646 767.476 Td /F1 9.8 Tf  [([17])] TJ ET
BT 344.909 767.476 Td /F1 9.8 Tf  [([18])] TJ ET
BT 361.172 767.476 Td /F1 9.8 Tf  [([19])] TJ ET
BT 377.435 767.476 Td /F1 9.8 Tf  [([20])] TJ ET
BT 393.698 767.476 Td /F1 9.8 Tf  [([21])] TJ ET
0.271 0.267 0.267 rg
BT 409.961 767.476 Td /F1 9.8 Tf  [( One study describes a 60% delay in )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(gastric half emptying time in the PD patient group after a solid test meal using the non-invasive )] TJ ET
BT 437.017 759.460 Td /F1 8.7 Tf  [(13)] TJ ET
BT 446.655 755.571 Td /F1 9.8 Tf  [( C-sodium octanoate breath )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(test for evaluation of gastric emptying. )] TJ ET
0.267 0.267 0.267 rg
BT 193.160 743.667 Td /F1 9.8 Tf  [([17])] TJ ET
0.271 0.267 0.267 rg
BT 209.423 743.667 Td /F1 9.8 Tf  [( Neuropathological findings suggest enteric dysfunction to be one of the initial )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(pathophysiological events in PD. )] TJ ET
0.267 0.267 0.267 rg
BT 169.858 731.762 Td /F1 9.8 Tf  [([16])] TJ ET
BT 186.121 731.762 Td /F1 9.8 Tf  [([22])] TJ ET
0.271 0.267 0.267 rg
BT 202.384 731.762 Td /F1 9.8 Tf  [( Central and enteric nervous system involvement in PD is discussed as being a )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(pathophysiologic basis for this dysfunction. )] TJ ET
0.267 0.267 0.267 rg
BT 213.752 719.857 Td /F1 9.8 Tf  [([15])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 700.452 Td /F1 9.8 Tf  [(Autonomic nervous dysfunction was found to be present in HD, too. )] TJ ET
0.267 0.267 0.267 rg
BT 319.978 700.452 Td /F1 9.8 Tf  [([23])] TJ ET
0.271 0.267 0.267 rg
BT 336.241 700.452 Td /F1 9.8 Tf  [( Thus, the aim of the current study was to investigate )] TJ ET
BT 26.250 688.548 Td /F1 9.8 Tf  [(gastric emptying in early HD patients without medication as a possible additional reason for weight loss by using the well-)] TJ ET
BT 26.250 676.643 Td /F1 9.8 Tf  [(established )] TJ ET
BT 78.276 680.531 Td /F1 8.7 Tf  [(13)] TJ ET
BT 87.913 676.643 Td /F1 9.8 Tf  [( C-octanoate breath test. )] TJ ET
0.267 0.267 0.267 rg
BT 197.932 676.643 Td /F1 9.8 Tf  [([16])] TJ ET
BT 214.195 676.643 Td /F1 9.8 Tf  [([17])] TJ ET
BT 230.458 676.643 Td /F1 9.8 Tf  [([18])] TJ ET
BT 246.721 676.643 Td /F1 9.8 Tf  [([19])] TJ ET
BT 262.984 676.643 Td /F1 9.8 Tf  [([20])] TJ ET
BT 279.247 676.643 Td /F1 9.8 Tf  [([21])] TJ ET
BT 295.510 676.643 Td /F1 9.8 Tf  [([24])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 640.040 Td /F4 12.0 Tf  [(Methods)] TJ ET
BT 26.250 620.086 Td /F4 9.8 Tf  [(Participants)] TJ ET
BT 26.250 600.681 Td /F1 9.8 Tf  [(11 manifest HD patients with genetically confirmed diagnosis and without any medication in at clinically early stages of the )] TJ ET
BT 26.250 588.777 Td /F1 9.8 Tf  [(disease \(Shoulson stage I/II\) and 11 controls were recruited from the HD centre Bochum, Germany. )] TJ ET
0.267 0.267 0.267 rg
BT 458.136 588.777 Td /F1 9.8 Tf  [([25])] TJ ET
0.271 0.267 0.267 rg
BT 474.399 588.777 Td /F1 9.8 Tf  [( Participants with )] TJ ET
BT 26.250 576.872 Td /F1 9.8 Tf  [(known concurrent gastrointestinal diseases or previous operations of the gastro-intestinal tract were excluded, as well as )] TJ ET
BT 26.250 564.967 Td /F1 9.8 Tf  [(patients with other severe diseases, diabetes mellitus, severe respiratory dysfunction, and malignancies. Also participants with )] TJ ET
BT 26.250 553.062 Td /F1 9.8 Tf  [(concurrent liver diseases or excessive alcohol consumption \(50 g/d of ethanol\) were excluded. All participants had lab )] TJ ET
BT 26.250 541.158 Td /F1 9.8 Tf  [(parameters for ALT, AST, LDH, cholesterol and triglycerides within the normal range, as well as normal findings for the )] TJ ET
BT 26.250 529.253 Td /F1 9.8 Tf  [(ultrasonography of the upper abdomen. Pregnant and breast-feeding women were excluded. All HD participants underwent )] TJ ET
BT 26.250 517.348 Td /F1 9.8 Tf  [(neurological investigation and were scored according to the UHDRS items �motor scale� \(MS\), �total functional capacity� \(TFC\) )] TJ ET
BT 26.250 505.443 Td /F1 9.8 Tf  [(�independence scale� \(IS\) and the items verbal fluency test, symbol digit test, interference test, color naming and color reading )] TJ ET
BT 26.250 493.539 Td /F1 9.8 Tf  [(which were summarized as �cognitive score� \(CS\). )] TJ ET
0.267 0.267 0.267 rg
BT 246.210 493.539 Td /F1 9.8 Tf  [([26])] TJ ET
0.271 0.267 0.267 rg
BT 262.473 493.539 Td /F1 9.8 Tf  [( Fine motor skills were additionally measured by simple \(tapping; higher )] TJ ET
BT 26.250 481.634 Td /F1 9.8 Tf  [(motor impairment leads to lower test results\) and complex \(pegboard; higher motor impairment leads to higher test results\) )] TJ ET
BT 26.250 469.729 Td /F1 9.8 Tf  [(instrumental movement tests. )] TJ ET
0.267 0.267 0.267 rg
BT 156.296 469.729 Td /F1 9.8 Tf  [([27])] TJ ET
BT 172.559 469.729 Td /F1 9.8 Tf  [([28])] TJ ET
BT 188.822 469.729 Td /F1 9.8 Tf  [([29])] TJ ET
BT 205.085 469.729 Td /F1 9.8 Tf  [([30])] TJ ET
0.271 0.267 0.267 rg
BT 221.348 469.729 Td /F1 9.8 Tf  [( The severity of depressive symptoms was assessed by using the Beck�s )] TJ ET
BT 26.250 457.824 Td /F1 9.8 Tf  [(depression inventory \(BDI\) and Hamilton depression rating scale. )] TJ ET
0.267 0.267 0.267 rg
BT 310.190 457.824 Td /F1 9.8 Tf  [([31])] TJ ET
BT 326.452 457.824 Td /F1 9.8 Tf  [([32])] TJ ET
0.271 0.267 0.267 rg
BT 342.715 457.824 Td /F1 9.8 Tf  [( Clinical characteristics of all HD patients are given in )] TJ ET
BT 26.250 445.920 Td /F1 9.8 Tf  [(table 1. In addition we calculated the disease burden score \(DBS = [CAG repeat � 35.5] x age\) for each subject. )] TJ ET
0.267 0.267 0.267 rg
BT 510.484 445.920 Td /F1 9.8 Tf  [([33])] TJ ET
0.271 0.267 0.267 rg
BT 526.747 445.920 Td /F1 9.8 Tf  [( The study )] TJ ET
BT 26.250 434.015 Td /F1 9.8 Tf  [(was approved by the ethic committee of the Ruhr-University Bochum, Germany \(registration-number 2719\). Participants gave )] TJ ET
BT 26.250 422.110 Td /F1 9.8 Tf  [(informed written consent according to GCP/ICH.)] TJ ET
1.000 1.000 1.000 rg
26.250 76.473 555.000 335.756 re f
0.267 0.267 0.267 rg
26.625 411.104 210.174 0.750 re f
26.625 395.223 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 401.249 Td /F4 9.8 Tf  [(Parameter)] TJ ET
0.267 0.267 0.267 rg
236.049 411.104 188.959 0.750 re f
236.049 395.223 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 401.249 Td /F4 9.8 Tf  [(HD Participants)] TJ ET
0.267 0.267 0.267 rg
424.258 411.104 156.617 0.750 re f
424.258 395.223 0.750 16.631 re f
580.125 395.223 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 401.249 Td /F4 9.8 Tf  [(Controls)] TJ ET
0.267 0.267 0.267 rg
26.625 395.223 210.174 0.750 re f
26.625 379.342 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 385.368 Td /F1 9.8 Tf  [(Age [yr])] TJ ET
0.267 0.267 0.267 rg
236.049 395.223 188.959 0.750 re f
236.049 379.342 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 385.368 Td /F1 9.8 Tf  [(42.4 � 8.4 \(29-57\))] TJ ET
0.267 0.267 0.267 rg
424.258 395.223 156.617 0.750 re f
424.258 379.342 0.750 16.631 re f
580.125 379.342 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 385.368 Td /F1 9.8 Tf  [(48.9 � 9.6 \(38-69\))] TJ ET
0.267 0.267 0.267 rg
26.625 379.342 210.174 0.750 re f
26.625 363.461 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 369.487 Td /F1 9.8 Tf  [(Gender \(male/female\))] TJ ET
0.267 0.267 0.267 rg
236.049 379.342 188.959 0.750 re f
236.049 363.461 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 369.487 Td /F1 9.8 Tf  [(3/8)] TJ ET
0.267 0.267 0.267 rg
424.258 379.342 156.617 0.750 re f
424.258 363.461 0.750 16.631 re f
580.125 363.461 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 369.487 Td /F1 9.8 Tf  [(3/8)] TJ ET
0.267 0.267 0.267 rg
26.625 363.461 210.174 0.750 re f
26.625 347.579 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 353.606 Td /F1 9.8 Tf  [(BMI)] TJ ET
0.267 0.267 0.267 rg
236.049 363.461 188.959 0.750 re f
236.049 347.579 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 353.606 Td /F1 9.8 Tf  [(22.5 � 3.5 \(16-30\))] TJ ET
0.267 0.267 0.267 rg
424.258 363.461 156.617 0.750 re f
424.258 347.579 0.750 16.631 re f
580.125 347.579 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 353.606 Td /F1 9.8 Tf  [(26.5 � 6.4 \(19-42\))] TJ ET
0.267 0.267 0.267 rg
26.625 347.579 210.174 0.750 re f
26.625 331.698 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 337.724 Td /F1 9.8 Tf  [(Weight [kg])] TJ ET
0.267 0.267 0.267 rg
236.049 347.579 188.959 0.750 re f
236.049 331.698 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 337.724 Td /F1 9.8 Tf  [(63.6 � 14.1 \(42-85\))] TJ ET
0.267 0.267 0.267 rg
424.258 347.579 156.617 0.750 re f
424.258 331.698 0.750 16.631 re f
580.125 331.698 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 337.724 Td /F1 9.8 Tf  [(84.5 � 22.5 \(54-128\))] TJ ET
0.267 0.267 0.267 rg
26.625 331.698 210.174 0.750 re f
26.625 315.817 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 321.843 Td /F1 9.8 Tf  [(Height [cm])] TJ ET
0.267 0.267 0.267 rg
236.049 331.698 188.959 0.750 re f
236.049 315.817 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 321.843 Td /F1 9.8 Tf  [(166.8 � 10.1 \(153-183\))] TJ ET
0.267 0.267 0.267 rg
424.258 331.698 156.617 0.750 re f
424.258 315.817 0.750 16.631 re f
580.125 315.817 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 321.843 Td /F1 9.8 Tf  [(178.2 � 9.4 \(164-190\))] TJ ET
0.267 0.267 0.267 rg
26.625 315.817 210.174 0.750 re f
26.625 299.935 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 305.962 Td /F1 9.8 Tf  [(AO motor)] TJ ET
0.267 0.267 0.267 rg
236.049 315.817 188.959 0.750 re f
236.049 299.935 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 305.962 Td /F1 9.8 Tf  [(39 � 8.6 \(25-51\))] TJ ET
0.267 0.267 0.267 rg
424.258 315.817 156.617 0.750 re f
424.258 299.935 0.750 16.631 re f
580.125 299.935 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 305.962 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 299.935 210.174 0.750 re f
26.625 284.054 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 290.080 Td /F1 9.8 Tf  [(AO psychiatric)] TJ ET
0.267 0.267 0.267 rg
236.049 299.935 188.959 0.750 re f
236.049 284.054 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 290.080 Td /F1 9.8 Tf  [(38 � 20.9 \(29-50\)a)] TJ ET
0.267 0.267 0.267 rg
424.258 299.935 156.617 0.750 re f
424.258 284.054 0.750 16.631 re f
580.125 284.054 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 290.080 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 284.054 210.174 0.750 re f
26.625 268.173 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 274.199 Td /F1 9.8 Tf  [(CAG expanded)] TJ ET
0.267 0.267 0.267 rg
236.049 284.054 188.959 0.750 re f
236.049 268.173 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 274.199 Td /F1 9.8 Tf  [(45 � 2.9 \(42-51\))] TJ ET
0.267 0.267 0.267 rg
424.258 284.054 156.617 0.750 re f
424.258 268.173 0.750 16.631 re f
580.125 268.173 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 274.199 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 268.173 210.174 0.750 re f
26.625 252.292 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 258.318 Td /F1 9.8 Tf  [(Disease burden score)] TJ ET
0.267 0.267 0.267 rg
236.049 268.173 188.959 0.750 re f
236.049 252.292 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 258.318 Td /F1 9.8 Tf  [(386.59 � 66.06 \(273-483\))] TJ ET
0.267 0.267 0.267 rg
424.258 268.173 156.617 0.750 re f
424.258 252.292 0.750 16.631 re f
580.125 252.292 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 258.318 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 252.292 210.174 0.750 re f
26.625 236.410 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 242.437 Td /F1 9.8 Tf  [(Disease duration [yr])] TJ ET
0.267 0.267 0.267 rg
236.049 252.292 188.959 0.750 re f
236.049 236.410 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 242.437 Td /F1 9.8 Tf  [(4.2 � 2.5 \(0.1-9\))] TJ ET
0.267 0.267 0.267 rg
424.258 252.292 156.617 0.750 re f
424.258 236.410 0.750 16.631 re f
580.125 236.410 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 242.437 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 236.410 210.174 0.750 re f
26.625 235.660 0.750 1.500 re f
236.049 236.410 188.959 0.750 re f
236.049 235.660 0.750 1.500 re f
424.258 236.410 156.617 0.750 re f
424.258 235.660 0.750 1.500 re f
580.125 235.660 0.750 1.500 re f
26.625 235.660 210.174 0.750 re f
26.625 219.779 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 225.805 Td /F1 9.8 Tf  [(UHDRS MS)] TJ ET
0.267 0.267 0.267 rg
236.049 235.660 188.959 0.750 re f
236.049 219.779 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 225.805 Td /F1 9.8 Tf  [(30.8 � 18.7 \(5-72\))] TJ ET
0.267 0.267 0.267 rg
424.258 235.660 156.617 0.750 re f
424.258 219.779 0.750 16.631 re f
580.125 219.779 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 225.805 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 219.779 210.174 0.750 re f
26.625 203.898 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 209.924 Td /F1 9.8 Tf  [(UHDRS TFC)] TJ ET
0.267 0.267 0.267 rg
236.049 219.779 188.959 0.750 re f
236.049 203.898 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 209.924 Td /F1 9.8 Tf  [(10.2 � 1.9 \(7-12\))] TJ ET
0.267 0.267 0.267 rg
424.258 219.779 156.617 0.750 re f
424.258 203.898 0.750 16.631 re f
580.125 203.898 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 209.924 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 203.898 210.174 0.750 re f
26.625 188.017 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 194.043 Td /F1 9.8 Tf  [(UHDRS IS)] TJ ET
0.267 0.267 0.267 rg
236.049 203.898 188.959 0.750 re f
236.049 188.017 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 194.043 Td /F1 9.8 Tf  [(81.8 � 9.8 \(70-100\))] TJ ET
0.267 0.267 0.267 rg
424.258 203.898 156.617 0.750 re f
424.258 188.017 0.750 16.631 re f
580.125 188.017 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 194.043 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 188.017 210.174 0.750 re f
26.625 172.135 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 178.162 Td /F1 9.8 Tf  [(UHDRS CS)] TJ ET
0.267 0.267 0.267 rg
236.049 188.017 188.959 0.750 re f
236.049 172.135 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 178.162 Td /F1 9.8 Tf  [(195.1 � 79.0 \(98-346\))] TJ ET
0.267 0.267 0.267 rg
424.258 188.017 156.617 0.750 re f
424.258 172.135 0.750 16.631 re f
580.125 172.135 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 178.162 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 172.135 210.174 0.750 re f
26.625 156.254 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 162.280 Td /F1 9.8 Tf  [(Verbal fluency)] TJ ET
0.267 0.267 0.267 rg
236.049 172.135 188.959 0.750 re f
236.049 156.254 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 162.280 Td /F1 9.8 Tf  [(22.5 � 18.2 \(4-69\))] TJ ET
0.267 0.267 0.267 rg
424.258 172.135 156.617 0.750 re f
424.258 156.254 0.750 16.631 re f
580.125 156.254 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 162.280 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 156.254 210.174 0.750 re f
26.625 140.373 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 146.399 Td /F1 9.8 Tf  [(SDMT)] TJ ET
0.267 0.267 0.267 rg
236.049 156.254 188.959 0.750 re f
236.049 140.373 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 146.399 Td /F1 9.8 Tf  [(27.2 � 10.6 \(16-44\))] TJ ET
0.267 0.267 0.267 rg
424.258 156.254 156.617 0.750 re f
424.258 140.373 0.750 16.631 re f
580.125 140.373 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 146.399 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 140.373 210.174 0.750 re f
26.625 124.492 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 130.518 Td /F1 9.8 Tf  [(Stroop color)] TJ ET
0.267 0.267 0.267 rg
236.049 140.373 188.959 0.750 re f
236.049 124.492 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 130.518 Td /F1 9.8 Tf  [(47.1 � 17.1 \(26-74\))] TJ ET
0.267 0.267 0.267 rg
424.258 140.373 156.617 0.750 re f
424.258 124.492 0.750 16.631 re f
580.125 124.492 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 130.518 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 124.492 210.174 0.750 re f
26.625 108.610 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 114.637 Td /F1 9.8 Tf  [(Stroop word)] TJ ET
0.267 0.267 0.267 rg
236.049 124.492 188.959 0.750 re f
236.049 108.610 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 114.637 Td /F1 9.8 Tf  [(68.1 � 22.8 \(32-100\))] TJ ET
0.267 0.267 0.267 rg
424.258 124.492 156.617 0.750 re f
424.258 108.610 0.750 16.631 re f
580.125 108.610 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 114.637 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 108.610 210.174 0.750 re f
26.625 92.729 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 98.755 Td /F1 9.8 Tf  [(Stroop interference)] TJ ET
0.267 0.267 0.267 rg
236.049 108.610 188.959 0.750 re f
236.049 92.729 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 98.755 Td /F1 9.8 Tf  [(29.5 � 16.1 \(10-59\))] TJ ET
0.267 0.267 0.267 rg
424.258 108.610 156.617 0.750 re f
424.258 92.729 0.750 16.631 re f
580.125 92.729 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 98.755 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 92.729 210.174 0.750 re f
26.625 76.848 210.174 0.750 re f
26.625 76.848 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 82.874 Td /F1 9.8 Tf  [(Hamilton)] TJ ET
0.267 0.267 0.267 rg
236.049 92.729 188.959 0.750 re f
236.049 76.848 188.959 0.750 re f
236.049 76.848 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 82.874 Td /F1 9.8 Tf  [(12.8 � 10.0 \(1-26\))] TJ ET
0.267 0.267 0.267 rg
424.258 92.729 156.617 0.750 re f
424.258 76.848 156.617 0.750 re f
424.258 76.848 0.750 16.631 re f
580.125 76.848 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 82.874 Td /F1 9.8 Tf  [(�)] TJ ET
Q
q
15.000 76.473 577.500 700.527 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(emptying in PD, some of them with a rate of 100% of PD patients. )] TJ ET
0.267 0.267 0.267 rg
BT 312.383 767.476 Td /F1 9.8 Tf  [([16])] TJ ET
BT 328.646 767.476 Td /F1 9.8 Tf  [([17])] TJ ET
BT 344.909 767.476 Td /F1 9.8 Tf  [([18])] TJ ET
BT 361.172 767.476 Td /F1 9.8 Tf  [([19])] TJ ET
BT 377.435 767.476 Td /F1 9.8 Tf  [([20])] TJ ET
BT 393.698 767.476 Td /F1 9.8 Tf  [([21])] TJ ET
0.271 0.267 0.267 rg
BT 409.961 767.476 Td /F1 9.8 Tf  [( One study describes a 60% delay in )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(gastric half emptying time in the PD patient group after a solid test meal using the non-invasive )] TJ ET
BT 437.017 759.460 Td /F1 8.7 Tf  [(13)] TJ ET
BT 446.655 755.571 Td /F1 9.8 Tf  [( C-sodium octanoate breath )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(test for evaluation of gastric emptying. )] TJ ET
0.267 0.267 0.267 rg
BT 193.160 743.667 Td /F1 9.8 Tf  [([17])] TJ ET
0.271 0.267 0.267 rg
BT 209.423 743.667 Td /F1 9.8 Tf  [( Neuropathological findings suggest enteric dysfunction to be one of the initial )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(pathophysiological events in PD. )] TJ ET
0.267 0.267 0.267 rg
BT 169.858 731.762 Td /F1 9.8 Tf  [([16])] TJ ET
BT 186.121 731.762 Td /F1 9.8 Tf  [([22])] TJ ET
0.271 0.267 0.267 rg
BT 202.384 731.762 Td /F1 9.8 Tf  [( Central and enteric nervous system involvement in PD is discussed as being a )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(pathophysiologic basis for this dysfunction. )] TJ ET
0.267 0.267 0.267 rg
BT 213.752 719.857 Td /F1 9.8 Tf  [([15])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 700.452 Td /F1 9.8 Tf  [(Autonomic nervous dysfunction was found to be present in HD, too. )] TJ ET
0.267 0.267 0.267 rg
BT 319.978 700.452 Td /F1 9.8 Tf  [([23])] TJ ET
0.271 0.267 0.267 rg
BT 336.241 700.452 Td /F1 9.8 Tf  [( Thus, the aim of the current study was to investigate )] TJ ET
BT 26.250 688.548 Td /F1 9.8 Tf  [(gastric emptying in early HD patients without medication as a possible additional reason for weight loss by using the well-)] TJ ET
BT 26.250 676.643 Td /F1 9.8 Tf  [(established )] TJ ET
BT 78.276 680.531 Td /F1 8.7 Tf  [(13)] TJ ET
BT 87.913 676.643 Td /F1 9.8 Tf  [( C-octanoate breath test. )] TJ ET
0.267 0.267 0.267 rg
BT 197.932 676.643 Td /F1 9.8 Tf  [([16])] TJ ET
BT 214.195 676.643 Td /F1 9.8 Tf  [([17])] TJ ET
BT 230.458 676.643 Td /F1 9.8 Tf  [([18])] TJ ET
BT 246.721 676.643 Td /F1 9.8 Tf  [([19])] TJ ET
BT 262.984 676.643 Td /F1 9.8 Tf  [([20])] TJ ET
BT 279.247 676.643 Td /F1 9.8 Tf  [([21])] TJ ET
BT 295.510 676.643 Td /F1 9.8 Tf  [([24])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 640.040 Td /F4 12.0 Tf  [(Methods)] TJ ET
BT 26.250 620.086 Td /F4 9.8 Tf  [(Participants)] TJ ET
BT 26.250 600.681 Td /F1 9.8 Tf  [(11 manifest HD patients with genetically confirmed diagnosis and without any medication in at clinically early stages of the )] TJ ET
BT 26.250 588.777 Td /F1 9.8 Tf  [(disease \(Shoulson stage I/II\) and 11 controls were recruited from the HD centre Bochum, Germany. )] TJ ET
0.267 0.267 0.267 rg
BT 458.136 588.777 Td /F1 9.8 Tf  [([25])] TJ ET
0.271 0.267 0.267 rg
BT 474.399 588.777 Td /F1 9.8 Tf  [( Participants with )] TJ ET
BT 26.250 576.872 Td /F1 9.8 Tf  [(known concurrent gastrointestinal diseases or previous operations of the gastro-intestinal tract were excluded, as well as )] TJ ET
BT 26.250 564.967 Td /F1 9.8 Tf  [(patients with other severe diseases, diabetes mellitus, severe respiratory dysfunction, and malignancies. Also participants with )] TJ ET
BT 26.250 553.062 Td /F1 9.8 Tf  [(concurrent liver diseases or excessive alcohol consumption \(50 g/d of ethanol\) were excluded. All participants had lab )] TJ ET
BT 26.250 541.158 Td /F1 9.8 Tf  [(parameters for ALT, AST, LDH, cholesterol and triglycerides within the normal range, as well as normal findings for the )] TJ ET
BT 26.250 529.253 Td /F1 9.8 Tf  [(ultrasonography of the upper abdomen. Pregnant and breast-feeding women were excluded. All HD participants underwent )] TJ ET
BT 26.250 517.348 Td /F1 9.8 Tf  [(neurological investigation and were scored according to the UHDRS items �motor scale� \(MS\), �total functional capacity� \(TFC\) )] TJ ET
BT 26.250 505.443 Td /F1 9.8 Tf  [(�independence scale� \(IS\) and the items verbal fluency test, symbol digit test, interference test, color naming and color reading )] TJ ET
BT 26.250 493.539 Td /F1 9.8 Tf  [(which were summarized as �cognitive score� \(CS\). )] TJ ET
0.267 0.267 0.267 rg
BT 246.210 493.539 Td /F1 9.8 Tf  [([26])] TJ ET
0.271 0.267 0.267 rg
BT 262.473 493.539 Td /F1 9.8 Tf  [( Fine motor skills were additionally measured by simple \(tapping; higher )] TJ ET
BT 26.250 481.634 Td /F1 9.8 Tf  [(motor impairment leads to lower test results\) and complex \(pegboard; higher motor impairment leads to higher test results\) )] TJ ET
BT 26.250 469.729 Td /F1 9.8 Tf  [(instrumental movement tests. )] TJ ET
0.267 0.267 0.267 rg
BT 156.296 469.729 Td /F1 9.8 Tf  [([27])] TJ ET
BT 172.559 469.729 Td /F1 9.8 Tf  [([28])] TJ ET
BT 188.822 469.729 Td /F1 9.8 Tf  [([29])] TJ ET
BT 205.085 469.729 Td /F1 9.8 Tf  [([30])] TJ ET
0.271 0.267 0.267 rg
BT 221.348 469.729 Td /F1 9.8 Tf  [( The severity of depressive symptoms was assessed by using the Beck�s )] TJ ET
BT 26.250 457.824 Td /F1 9.8 Tf  [(depression inventory \(BDI\) and Hamilton depression rating scale. )] TJ ET
0.267 0.267 0.267 rg
BT 310.190 457.824 Td /F1 9.8 Tf  [([31])] TJ ET
BT 326.452 457.824 Td /F1 9.8 Tf  [([32])] TJ ET
0.271 0.267 0.267 rg
BT 342.715 457.824 Td /F1 9.8 Tf  [( Clinical characteristics of all HD patients are given in )] TJ ET
BT 26.250 445.920 Td /F1 9.8 Tf  [(table 1. In addition we calculated the disease burden score \(DBS = [CAG repeat � 35.5] x age\) for each subject. )] TJ ET
0.267 0.267 0.267 rg
BT 510.484 445.920 Td /F1 9.8 Tf  [([33])] TJ ET
0.271 0.267 0.267 rg
BT 526.747 445.920 Td /F1 9.8 Tf  [( The study )] TJ ET
BT 26.250 434.015 Td /F1 9.8 Tf  [(was approved by the ethic committee of the Ruhr-University Bochum, Germany \(registration-number 2719\). Participants gave )] TJ ET
BT 26.250 422.110 Td /F1 9.8 Tf  [(informed written consent according to GCP/ICH.)] TJ ET
1.000 1.000 1.000 rg
26.250 76.473 555.000 335.756 re f
0.267 0.267 0.267 rg
26.625 411.104 210.174 0.750 re f
26.625 395.223 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 401.249 Td /F4 9.8 Tf  [(Parameter)] TJ ET
0.267 0.267 0.267 rg
236.049 411.104 188.959 0.750 re f
236.049 395.223 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 401.249 Td /F4 9.8 Tf  [(HD Participants)] TJ ET
0.267 0.267 0.267 rg
424.258 411.104 156.617 0.750 re f
424.258 395.223 0.750 16.631 re f
580.125 395.223 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 401.249 Td /F4 9.8 Tf  [(Controls)] TJ ET
0.267 0.267 0.267 rg
26.625 395.223 210.174 0.750 re f
26.625 379.342 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 385.368 Td /F1 9.8 Tf  [(Age [yr])] TJ ET
0.267 0.267 0.267 rg
236.049 395.223 188.959 0.750 re f
236.049 379.342 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 385.368 Td /F1 9.8 Tf  [(42.4 � 8.4 \(29-57\))] TJ ET
0.267 0.267 0.267 rg
424.258 395.223 156.617 0.750 re f
424.258 379.342 0.750 16.631 re f
580.125 379.342 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 385.368 Td /F1 9.8 Tf  [(48.9 � 9.6 \(38-69\))] TJ ET
0.267 0.267 0.267 rg
26.625 379.342 210.174 0.750 re f
26.625 363.461 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 369.487 Td /F1 9.8 Tf  [(Gender \(male/female\))] TJ ET
0.267 0.267 0.267 rg
236.049 379.342 188.959 0.750 re f
236.049 363.461 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 369.487 Td /F1 9.8 Tf  [(3/8)] TJ ET
0.267 0.267 0.267 rg
424.258 379.342 156.617 0.750 re f
424.258 363.461 0.750 16.631 re f
580.125 363.461 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 369.487 Td /F1 9.8 Tf  [(3/8)] TJ ET
0.267 0.267 0.267 rg
26.625 363.461 210.174 0.750 re f
26.625 347.579 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 353.606 Td /F1 9.8 Tf  [(BMI)] TJ ET
0.267 0.267 0.267 rg
236.049 363.461 188.959 0.750 re f
236.049 347.579 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 353.606 Td /F1 9.8 Tf  [(22.5 � 3.5 \(16-30\))] TJ ET
0.267 0.267 0.267 rg
424.258 363.461 156.617 0.750 re f
424.258 347.579 0.750 16.631 re f
580.125 347.579 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 353.606 Td /F1 9.8 Tf  [(26.5 � 6.4 \(19-42\))] TJ ET
0.267 0.267 0.267 rg
26.625 347.579 210.174 0.750 re f
26.625 331.698 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 337.724 Td /F1 9.8 Tf  [(Weight [kg])] TJ ET
0.267 0.267 0.267 rg
236.049 347.579 188.959 0.750 re f
236.049 331.698 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 337.724 Td /F1 9.8 Tf  [(63.6 � 14.1 \(42-85\))] TJ ET
0.267 0.267 0.267 rg
424.258 347.579 156.617 0.750 re f
424.258 331.698 0.750 16.631 re f
580.125 331.698 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 337.724 Td /F1 9.8 Tf  [(84.5 � 22.5 \(54-128\))] TJ ET
0.267 0.267 0.267 rg
26.625 331.698 210.174 0.750 re f
26.625 315.817 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 321.843 Td /F1 9.8 Tf  [(Height [cm])] TJ ET
0.267 0.267 0.267 rg
236.049 331.698 188.959 0.750 re f
236.049 315.817 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 321.843 Td /F1 9.8 Tf  [(166.8 � 10.1 \(153-183\))] TJ ET
0.267 0.267 0.267 rg
424.258 331.698 156.617 0.750 re f
424.258 315.817 0.750 16.631 re f
580.125 315.817 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 321.843 Td /F1 9.8 Tf  [(178.2 � 9.4 \(164-190\))] TJ ET
0.267 0.267 0.267 rg
26.625 315.817 210.174 0.750 re f
26.625 299.935 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 305.962 Td /F1 9.8 Tf  [(AO motor)] TJ ET
0.267 0.267 0.267 rg
236.049 315.817 188.959 0.750 re f
236.049 299.935 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 305.962 Td /F1 9.8 Tf  [(39 � 8.6 \(25-51\))] TJ ET
0.267 0.267 0.267 rg
424.258 315.817 156.617 0.750 re f
424.258 299.935 0.750 16.631 re f
580.125 299.935 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 305.962 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 299.935 210.174 0.750 re f
26.625 284.054 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 290.080 Td /F1 9.8 Tf  [(AO psychiatric)] TJ ET
0.267 0.267 0.267 rg
236.049 299.935 188.959 0.750 re f
236.049 284.054 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 290.080 Td /F1 9.8 Tf  [(38 � 20.9 \(29-50\)a)] TJ ET
0.267 0.267 0.267 rg
424.258 299.935 156.617 0.750 re f
424.258 284.054 0.750 16.631 re f
580.125 284.054 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 290.080 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 284.054 210.174 0.750 re f
26.625 268.173 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 274.199 Td /F1 9.8 Tf  [(CAG expanded)] TJ ET
0.267 0.267 0.267 rg
236.049 284.054 188.959 0.750 re f
236.049 268.173 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 274.199 Td /F1 9.8 Tf  [(45 � 2.9 \(42-51\))] TJ ET
0.267 0.267 0.267 rg
424.258 284.054 156.617 0.750 re f
424.258 268.173 0.750 16.631 re f
580.125 268.173 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 274.199 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 268.173 210.174 0.750 re f
26.625 252.292 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 258.318 Td /F1 9.8 Tf  [(Disease burden score)] TJ ET
0.267 0.267 0.267 rg
236.049 268.173 188.959 0.750 re f
236.049 252.292 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 258.318 Td /F1 9.8 Tf  [(386.59 � 66.06 \(273-483\))] TJ ET
0.267 0.267 0.267 rg
424.258 268.173 156.617 0.750 re f
424.258 252.292 0.750 16.631 re f
580.125 252.292 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 258.318 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 252.292 210.174 0.750 re f
26.625 236.410 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 242.437 Td /F1 9.8 Tf  [(Disease duration [yr])] TJ ET
0.267 0.267 0.267 rg
236.049 252.292 188.959 0.750 re f
236.049 236.410 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 242.437 Td /F1 9.8 Tf  [(4.2 � 2.5 \(0.1-9\))] TJ ET
0.267 0.267 0.267 rg
424.258 252.292 156.617 0.750 re f
424.258 236.410 0.750 16.631 re f
580.125 236.410 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 242.437 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 236.410 210.174 0.750 re f
26.625 235.660 0.750 1.500 re f
236.049 236.410 188.959 0.750 re f
236.049 235.660 0.750 1.500 re f
424.258 236.410 156.617 0.750 re f
424.258 235.660 0.750 1.500 re f
580.125 235.660 0.750 1.500 re f
26.625 235.660 210.174 0.750 re f
26.625 219.779 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 225.805 Td /F1 9.8 Tf  [(UHDRS MS)] TJ ET
0.267 0.267 0.267 rg
236.049 235.660 188.959 0.750 re f
236.049 219.779 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 225.805 Td /F1 9.8 Tf  [(30.8 � 18.7 \(5-72\))] TJ ET
0.267 0.267 0.267 rg
424.258 235.660 156.617 0.750 re f
424.258 219.779 0.750 16.631 re f
580.125 219.779 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 225.805 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 219.779 210.174 0.750 re f
26.625 203.898 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 209.924 Td /F1 9.8 Tf  [(UHDRS TFC)] TJ ET
0.267 0.267 0.267 rg
236.049 219.779 188.959 0.750 re f
236.049 203.898 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 209.924 Td /F1 9.8 Tf  [(10.2 � 1.9 \(7-12\))] TJ ET
0.267 0.267 0.267 rg
424.258 219.779 156.617 0.750 re f
424.258 203.898 0.750 16.631 re f
580.125 203.898 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 209.924 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 203.898 210.174 0.750 re f
26.625 188.017 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 194.043 Td /F1 9.8 Tf  [(UHDRS IS)] TJ ET
0.267 0.267 0.267 rg
236.049 203.898 188.959 0.750 re f
236.049 188.017 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 194.043 Td /F1 9.8 Tf  [(81.8 � 9.8 \(70-100\))] TJ ET
0.267 0.267 0.267 rg
424.258 203.898 156.617 0.750 re f
424.258 188.017 0.750 16.631 re f
580.125 188.017 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 194.043 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 188.017 210.174 0.750 re f
26.625 172.135 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 178.162 Td /F1 9.8 Tf  [(UHDRS CS)] TJ ET
0.267 0.267 0.267 rg
236.049 188.017 188.959 0.750 re f
236.049 172.135 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 178.162 Td /F1 9.8 Tf  [(195.1 � 79.0 \(98-346\))] TJ ET
0.267 0.267 0.267 rg
424.258 188.017 156.617 0.750 re f
424.258 172.135 0.750 16.631 re f
580.125 172.135 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 178.162 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 172.135 210.174 0.750 re f
26.625 156.254 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 162.280 Td /F1 9.8 Tf  [(Verbal fluency)] TJ ET
0.267 0.267 0.267 rg
236.049 172.135 188.959 0.750 re f
236.049 156.254 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 162.280 Td /F1 9.8 Tf  [(22.5 � 18.2 \(4-69\))] TJ ET
0.267 0.267 0.267 rg
424.258 172.135 156.617 0.750 re f
424.258 156.254 0.750 16.631 re f
580.125 156.254 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 162.280 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 156.254 210.174 0.750 re f
26.625 140.373 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 146.399 Td /F1 9.8 Tf  [(SDMT)] TJ ET
0.267 0.267 0.267 rg
236.049 156.254 188.959 0.750 re f
236.049 140.373 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 146.399 Td /F1 9.8 Tf  [(27.2 � 10.6 \(16-44\))] TJ ET
0.267 0.267 0.267 rg
424.258 156.254 156.617 0.750 re f
424.258 140.373 0.750 16.631 re f
580.125 140.373 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 146.399 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 140.373 210.174 0.750 re f
26.625 124.492 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 130.518 Td /F1 9.8 Tf  [(Stroop color)] TJ ET
0.267 0.267 0.267 rg
236.049 140.373 188.959 0.750 re f
236.049 124.492 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 130.518 Td /F1 9.8 Tf  [(47.1 � 17.1 \(26-74\))] TJ ET
0.267 0.267 0.267 rg
424.258 140.373 156.617 0.750 re f
424.258 124.492 0.750 16.631 re f
580.125 124.492 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 130.518 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 124.492 210.174 0.750 re f
26.625 108.610 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 114.637 Td /F1 9.8 Tf  [(Stroop word)] TJ ET
0.267 0.267 0.267 rg
236.049 124.492 188.959 0.750 re f
236.049 108.610 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 114.637 Td /F1 9.8 Tf  [(68.1 � 22.8 \(32-100\))] TJ ET
0.267 0.267 0.267 rg
424.258 124.492 156.617 0.750 re f
424.258 108.610 0.750 16.631 re f
580.125 108.610 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 114.637 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 108.610 210.174 0.750 re f
26.625 92.729 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 98.755 Td /F1 9.8 Tf  [(Stroop interference)] TJ ET
0.267 0.267 0.267 rg
236.049 108.610 188.959 0.750 re f
236.049 92.729 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 98.755 Td /F1 9.8 Tf  [(29.5 � 16.1 \(10-59\))] TJ ET
0.267 0.267 0.267 rg
424.258 108.610 156.617 0.750 re f
424.258 92.729 0.750 16.631 re f
580.125 92.729 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 98.755 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 92.729 210.174 0.750 re f
26.625 76.848 210.174 0.750 re f
26.625 76.848 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 82.874 Td /F1 9.8 Tf  [(Hamilton)] TJ ET
0.267 0.267 0.267 rg
236.049 92.729 188.959 0.750 re f
236.049 76.848 188.959 0.750 re f
236.049 76.848 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 82.874 Td /F1 9.8 Tf  [(12.8 � 10.0 \(1-26\))] TJ ET
0.267 0.267 0.267 rg
424.258 92.729 156.617 0.750 re f
424.258 76.848 156.617 0.750 re f
424.258 76.848 0.750 16.631 re f
580.125 76.848 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 82.874 Td /F1 9.8 Tf  [(�)] TJ ET
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
184 0 obj
<< /Type /Annot
/Subtype /Link
/A 185 0 R
/Border [0 0 0]
/H /I
/Rect [ 312.3832 766.5743 328.6462 776.4950 ]
>>
endobj
185 0 obj
<< /Type /Action
>>
endobj
186 0 obj
<< /Type /Annot
/Subtype /Link
/A 187 0 R
/Border [0 0 0]
/H /I
/Rect [ 328.6462 766.5743 344.9092 776.4950 ]
>>
endobj
187 0 obj
<< /Type /Action
>>
endobj
188 0 obj
<< /Type /Annot
/Subtype /Link
/A 189 0 R
/Border [0 0 0]
/H /I
/Rect [ 344.9092 766.5743 361.1722 776.4950 ]
>>
endobj
189 0 obj
<< /Type /Action
>>
endobj
190 0 obj
<< /Type /Annot
/Subtype /Link
/A 191 0 R
/Border [0 0 0]
/H /I
/Rect [ 361.1722 766.5743 377.4352 776.4950 ]
>>
endobj
191 0 obj
<< /Type /Action
>>
endobj
192 0 obj
<< /Type /Annot
/Subtype /Link
/A 193 0 R
/Border [0 0 0]
/H /I
/Rect [ 377.4352 766.5743 393.6982 776.4950 ]
>>
endobj
193 0 obj
<< /Type /Action
>>
endobj
194 0 obj
<< /Type /Annot
/Subtype /Link
/A 195 0 R
/Border [0 0 0]
/H /I
/Rect [ 393.6982 766.5743 409.9612 776.4950 ]
>>
endobj
195 0 obj
<< /Type /Action
>>
endobj
196 0 obj
<< /Type /Annot
/Subtype /Link
/A 197 0 R
/Border [0 0 0]
/H /I
/Rect [ 193.1602 742.7648 209.4232 752.6854 ]
>>
endobj
197 0 obj
<< /Type /Action
>>
endobj
198 0 obj
<< /Type /Annot
/Subtype /Link
/A 199 0 R
/Border [0 0 0]
/H /I
/Rect [ 169.8578 730.8601 186.1208 740.7807 ]
>>
endobj
199 0 obj
<< /Type /Action
>>
endobj
200 0 obj
<< /Type /Annot
/Subtype /Link
/A 201 0 R
/Border [0 0 0]
/H /I
/Rect [ 186.1208 730.8601 202.3838 740.7807 ]
>>
endobj
201 0 obj
<< /Type /Action
>>
endobj
202 0 obj
<< /Type /Annot
/Subtype /Link
/A 203 0 R
/Border [0 0 0]
/H /I
/Rect [ 213.7523 718.9553 230.0153 728.8759 ]
>>
endobj
203 0 obj
<< /Type /Action
>>
endobj
204 0 obj
<< /Type /Annot
/Subtype /Link
/A 205 0 R
/Border [0 0 0]
/H /I
/Rect [ 319.9785 699.5506 336.2415 709.4712 ]
>>
endobj
205 0 obj
<< /Type /Action
>>
endobj
206 0 obj
<< /Type /Annot
/Subtype /Link
/A 207 0 R
/Border [0 0 0]
/H /I
/Rect [ 197.9323 675.7411 214.1953 685.6617 ]
>>
endobj
207 0 obj
<< /Type /Action
>>
endobj
208 0 obj
<< /Type /Annot
/Subtype /Link
/A 209 0 R
/Border [0 0 0]
/H /I
/Rect [ 214.1953 675.7411 230.4583 685.6617 ]
>>
endobj
209 0 obj
<< /Type /Action
>>
endobj
210 0 obj
<< /Type /Annot
/Subtype /Link
/A 211 0 R
/Border [0 0 0]
/H /I
/Rect [ 230.4583 675.7411 246.7213 685.6617 ]
>>
endobj
211 0 obj
<< /Type /Action
>>
endobj
212 0 obj
<< /Type /Annot
/Subtype /Link
/A 213 0 R
/Border [0 0 0]
/H /I
/Rect [ 246.7213 675.7411 262.9843 685.6617 ]
>>
endobj
213 0 obj
<< /Type /Action
>>
endobj
214 0 obj
<< /Type /Annot
/Subtype /Link
/A 215 0 R
/Border [0 0 0]
/H /I
/Rect [ 262.9843 675.7411 279.2473 685.6617 ]
>>
endobj
215 0 obj
<< /Type /Action
>>
endobj
216 0 obj
<< /Type /Annot
/Subtype /Link
/A 217 0 R
/Border [0 0 0]
/H /I
/Rect [ 279.2473 675.7411 295.5103 685.6617 ]
>>
endobj
217 0 obj
<< /Type /Action
>>
endobj
218 0 obj
<< /Type /Annot
/Subtype /Link
/A 219 0 R
/Border [0 0 0]
/H /I
/Rect [ 295.5103 675.7411 311.7733 685.6617 ]
>>
endobj
219 0 obj
<< /Type /Action
>>
endobj
220 0 obj
<< /Type /Annot
/Subtype /Link
/A 221 0 R
/Border [0 0 0]
/H /I
/Rect [ 458.1360 587.8748 474.3990 597.7954 ]
>>
endobj
221 0 obj
<< /Type /Action
>>
endobj
222 0 obj
<< /Type /Annot
/Subtype /Link
/A 223 0 R
/Border [0 0 0]
/H /I
/Rect [ 246.2100 492.6368 262.4730 502.5574 ]
>>
endobj
223 0 obj
<< /Type /Action
>>
endobj
224 0 obj
<< /Type /Annot
/Subtype /Link
/A 225 0 R
/Border [0 0 0]
/H /I
/Rect [ 156.2955 468.8273 172.5585 478.7479 ]
>>
endobj
225 0 obj
<< /Type /Action
>>
endobj
226 0 obj
<< /Type /Annot
/Subtype /Link
/A 227 0 R
/Border [0 0 0]
/H /I
/Rect [ 172.5585 468.8273 188.8215 478.7479 ]
>>
endobj
227 0 obj
<< /Type /Action
>>
endobj
228 0 obj
<< /Type /Annot
/Subtype /Link
/A 229 0 R
/Border [0 0 0]
/H /I
/Rect [ 188.8215 468.8273 205.0845 478.7479 ]
>>
endobj
229 0 obj
<< /Type /Action
>>
endobj
230 0 obj
<< /Type /Annot
/Subtype /Link
/A 231 0 R
/Border [0 0 0]
/H /I
/Rect [ 205.0845 468.8273 221.3475 478.7479 ]
>>
endobj
231 0 obj
<< /Type /Action
>>
endobj
232 0 obj
<< /Type /Annot
/Subtype /Link
/A 233 0 R
/Border [0 0 0]
/H /I
/Rect [ 310.1895 456.9226 326.4525 466.8432 ]
>>
endobj
233 0 obj
<< /Type /Action
>>
endobj
234 0 obj
<< /Type /Annot
/Subtype /Link
/A 235 0 R
/Border [0 0 0]
/H /I
/Rect [ 326.4525 456.9226 342.7155 466.8432 ]
>>
endobj
235 0 obj
<< /Type /Action
>>
endobj
236 0 obj
<< /Type /Annot
/Subtype /Link
/A 237 0 R
/Border [0 0 0]
/H /I
/Rect [ 510.4837 445.0178 526.7468 454.9384 ]
>>
endobj
237 0 obj
<< /Type /Action
>>
endobj
238 0 obj
<< /Type /Annot
/Subtype /Link
/A 239 0 R
/Border [0 0 0]
/H /I
/Rect [ 312.3832 766.5743 328.6462 776.4950 ]
>>
endobj
239 0 obj
<< /Type /Action
>>
endobj
240 0 obj
<< /Type /Annot
/Subtype /Link
/A 241 0 R
/Border [0 0 0]
/H /I
/Rect [ 328.6462 766.5743 344.9092 776.4950 ]
>>
endobj
241 0 obj
<< /Type /Action
>>
endobj
242 0 obj
<< /Type /Annot
/Subtype /Link
/A 243 0 R
/Border [0 0 0]
/H /I
/Rect [ 344.9092 766.5743 361.1722 776.4950 ]
>>
endobj
243 0 obj
<< /Type /Action
>>
endobj
244 0 obj
<< /Type /Annot
/Subtype /Link
/A 245 0 R
/Border [0 0 0]
/H /I
/Rect [ 361.1722 766.5743 377.4352 776.4950 ]
>>
endobj
245 0 obj
<< /Type /Action
>>
endobj
246 0 obj
<< /Type /Annot
/Subtype /Link
/A 247 0 R
/Border [0 0 0]
/H /I
/Rect [ 377.4352 766.5743 393.6982 776.4950 ]
>>
endobj
247 0 obj
<< /Type /Action
>>
endobj
248 0 obj
<< /Type /Annot
/Subtype /Link
/A 249 0 R
/Border [0 0 0]
/H /I
/Rect [ 393.6982 766.5743 409.9612 776.4950 ]
>>
endobj
249 0 obj
<< /Type /Action
>>
endobj
250 0 obj
<< /Type /Annot
/Subtype /Link
/A 251 0 R
/Border [0 0 0]
/H /I
/Rect [ 193.1602 742.7648 209.4232 752.6854 ]
>>
endobj
251 0 obj
<< /Type /Action
>>
endobj
252 0 obj
<< /Type /Annot
/Subtype /Link
/A 253 0 R
/Border [0 0 0]
/H /I
/Rect [ 169.8578 730.8601 186.1208 740.7807 ]
>>
endobj
253 0 obj
<< /Type /Action
>>
endobj
254 0 obj
<< /Type /Annot
/Subtype /Link
/A 255 0 R
/Border [0 0 0]
/H /I
/Rect [ 186.1208 730.8601 202.3838 740.7807 ]
>>
endobj
255 0 obj
<< /Type /Action
>>
endobj
256 0 obj
<< /Type /Annot
/Subtype /Link
/A 257 0 R
/Border [0 0 0]
/H /I
/Rect [ 213.7523 718.9553 230.0153 728.8759 ]
>>
endobj
257 0 obj
<< /Type /Action
>>
endobj
258 0 obj
<< /Type /Annot
/Subtype /Link
/A 259 0 R
/Border [0 0 0]
/H /I
/Rect [ 319.9785 699.5506 336.2415 709.4712 ]
>>
endobj
259 0 obj
<< /Type /Action
>>
endobj
260 0 obj
<< /Type /Annot
/Subtype /Link
/A 261 0 R
/Border [0 0 0]
/H /I
/Rect [ 197.9323 675.7411 214.1953 685.6617 ]
>>
endobj
261 0 obj
<< /Type /Action
>>
endobj
262 0 obj
<< /Type /Annot
/Subtype /Link
/A 263 0 R
/Border [0 0 0]
/H /I
/Rect [ 214.1953 675.7411 230.4583 685.6617 ]
>>
endobj
263 0 obj
<< /Type /Action
>>
endobj
264 0 obj
<< /Type /Annot
/Subtype /Link
/A 265 0 R
/Border [0 0 0]
/H /I
/Rect [ 230.4583 675.7411 246.7213 685.6617 ]
>>
endobj
265 0 obj
<< /Type /Action
>>
endobj
266 0 obj
<< /Type /Annot
/Subtype /Link
/A 267 0 R
/Border [0 0 0]
/H /I
/Rect [ 246.7213 675.7411 262.9843 685.6617 ]
>>
endobj
267 0 obj
<< /Type /Action
>>
endobj
268 0 obj
<< /Type /Annot
/Subtype /Link
/A 269 0 R
/Border [0 0 0]
/H /I
/Rect [ 262.9843 675.7411 279.2473 685.6617 ]
>>
endobj
269 0 obj
<< /Type /Action
>>
endobj
270 0 obj
<< /Type /Annot
/Subtype /Link
/A 271 0 R
/Border [0 0 0]
/H /I
/Rect [ 279.2473 675.7411 295.5103 685.6617 ]
>>
endobj
271 0 obj
<< /Type /Action
>>
endobj
272 0 obj
<< /Type /Annot
/Subtype /Link
/A 273 0 R
/Border [0 0 0]
/H /I
/Rect [ 295.5103 675.7411 311.7733 685.6617 ]
>>
endobj
273 0 obj
<< /Type /Action
>>
endobj
274 0 obj
<< /Type /Annot
/Subtype /Link
/A 275 0 R
/Border [0 0 0]
/H /I
/Rect [ 458.1360 587.8748 474.3990 597.7954 ]
>>
endobj
275 0 obj
<< /Type /Action
>>
endobj
276 0 obj
<< /Type /Annot
/Subtype /Link
/A 277 0 R
/Border [0 0 0]
/H /I
/Rect [ 246.2100 492.6368 262.4730 502.5574 ]
>>
endobj
277 0 obj
<< /Type /Action
>>
endobj
278 0 obj
<< /Type /Annot
/Subtype /Link
/A 279 0 R
/Border [0 0 0]
/H /I
/Rect [ 156.2955 468.8273 172.5585 478.7479 ]
>>
endobj
279 0 obj
<< /Type /Action
>>
endobj
280 0 obj
<< /Type /Annot
/Subtype /Link
/A 281 0 R
/Border [0 0 0]
/H /I
/Rect [ 172.5585 468.8273 188.8215 478.7479 ]
>>
endobj
281 0 obj
<< /Type /Action
>>
endobj
282 0 obj
<< /Type /Annot
/Subtype /Link
/A 283 0 R
/Border [0 0 0]
/H /I
/Rect [ 188.8215 468.8273 205.0845 478.7479 ]
>>
endobj
283 0 obj
<< /Type /Action
>>
endobj
284 0 obj
<< /Type /Annot
/Subtype /Link
/A 285 0 R
/Border [0 0 0]
/H /I
/Rect [ 205.0845 468.8273 221.3475 478.7479 ]
>>
endobj
285 0 obj
<< /Type /Action
>>
endobj
286 0 obj
<< /Type /Annot
/Subtype /Link
/A 287 0 R
/Border [0 0 0]
/H /I
/Rect [ 310.1895 456.9226 326.4525 466.8432 ]
>>
endobj
287 0 obj
<< /Type /Action
>>
endobj
288 0 obj
<< /Type /Annot
/Subtype /Link
/A 289 0 R
/Border [0 0 0]
/H /I
/Rect [ 326.4525 456.9226 342.7155 466.8432 ]
>>
endobj
289 0 obj
<< /Type /Action
>>
endobj
290 0 obj
<< /Type /Annot
/Subtype /Link
/A 291 0 R
/Border [0 0 0]
/H /I
/Rect [ 510.4837 445.0178 526.7468 454.9384 ]
>>
endobj
291 0 obj
<< /Type /Action
>>
endobj
292 0 obj
<< /Type /Annot
/Subtype /Link
/A 293 0 R
/Border [0 0 0]
/H /I
/Rect [ 312.3832 766.5743 328.6462 776.4950 ]
>>
endobj
293 0 obj
<< /Type /Action
>>
endobj
294 0 obj
<< /Type /Annot
/Subtype /Link
/A 295 0 R
/Border [0 0 0]
/H /I
/Rect [ 328.6462 766.5743 344.9092 776.4950 ]
>>
endobj
295 0 obj
<< /Type /Action
>>
endobj
296 0 obj
<< /Type /Annot
/Subtype /Link
/A 297 0 R
/Border [0 0 0]
/H /I
/Rect [ 344.9092 766.5743 361.1722 776.4950 ]
>>
endobj
297 0 obj
<< /Type /Action
>>
endobj
298 0 obj
<< /Type /Annot
/Subtype /Link
/A 299 0 R
/Border [0 0 0]
/H /I
/Rect [ 361.1722 766.5743 377.4352 776.4950 ]
>>
endobj
299 0 obj
<< /Type /Action
>>
endobj
300 0 obj
<< /Type /Annot
/Subtype /Link
/A 301 0 R
/Border [0 0 0]
/H /I
/Rect [ 377.4352 766.5743 393.6982 776.4950 ]
>>
endobj
301 0 obj
<< /Type /Action
>>
endobj
302 0 obj
<< /Type /Annot
/Subtype /Link
/A 303 0 R
/Border [0 0 0]
/H /I
/Rect [ 393.6982 766.5743 409.9612 776.4950 ]
>>
endobj
303 0 obj
<< /Type /Action
>>
endobj
304 0 obj
<< /Type /Annot
/Subtype /Link
/A 305 0 R
/Border [0 0 0]
/H /I
/Rect [ 193.1602 742.7648 209.4232 752.6854 ]
>>
endobj
305 0 obj
<< /Type /Action
>>
endobj
306 0 obj
<< /Type /Annot
/Subtype /Link
/A 307 0 R
/Border [0 0 0]
/H /I
/Rect [ 169.8578 730.8601 186.1208 740.7807 ]
>>
endobj
307 0 obj
<< /Type /Action
>>
endobj
308 0 obj
<< /Type /Annot
/Subtype /Link
/A 309 0 R
/Border [0 0 0]
/H /I
/Rect [ 186.1208 730.8601 202.3838 740.7807 ]
>>
endobj
309 0 obj
<< /Type /Action
>>
endobj
310 0 obj
<< /Type /Annot
/Subtype /Link
/A 311 0 R
/Border [0 0 0]
/H /I
/Rect [ 213.7523 718.9553 230.0153 728.8759 ]
>>
endobj
311 0 obj
<< /Type /Action
>>
endobj
312 0 obj
<< /Type /Annot
/Subtype /Link
/A 313 0 R
/Border [0 0 0]
/H /I
/Rect [ 319.9785 699.5506 336.2415 709.4712 ]
>>
endobj
313 0 obj
<< /Type /Action
>>
endobj
314 0 obj
<< /Type /Annot
/Subtype /Link
/A 315 0 R
/Border [0 0 0]
/H /I
/Rect [ 197.9323 675.7411 214.1953 685.6617 ]
>>
endobj
315 0 obj
<< /Type /Action
>>
endobj
316 0 obj
<< /Type /Annot
/Subtype /Link
/A 317 0 R
/Border [0 0 0]
/H /I
/Rect [ 214.1953 675.7411 230.4583 685.6617 ]
>>
endobj
317 0 obj
<< /Type /Action
>>
endobj
318 0 obj
<< /Type /Annot
/Subtype /Link
/A 319 0 R
/Border [0 0 0]
/H /I
/Rect [ 230.4583 675.7411 246.7213 685.6617 ]
>>
endobj
319 0 obj
<< /Type /Action
>>
endobj
320 0 obj
<< /Type /Annot
/Subtype /Link
/A 321 0 R
/Border [0 0 0]
/H /I
/Rect [ 246.7213 675.7411 262.9843 685.6617 ]
>>
endobj
321 0 obj
<< /Type /Action
>>
endobj
322 0 obj
<< /Type /Annot
/Subtype /Link
/A 323 0 R
/Border [0 0 0]
/H /I
/Rect [ 262.9843 675.7411 279.2473 685.6617 ]
>>
endobj
323 0 obj
<< /Type /Action
>>
endobj
324 0 obj
<< /Type /Annot
/Subtype /Link
/A 325 0 R
/Border [0 0 0]
/H /I
/Rect [ 279.2473 675.7411 295.5103 685.6617 ]
>>
endobj
325 0 obj
<< /Type /Action
>>
endobj
326 0 obj
<< /Type /Annot
/Subtype /Link
/A 327 0 R
/Border [0 0 0]
/H /I
/Rect [ 295.5103 675.7411 311.7733 685.6617 ]
>>
endobj
327 0 obj
<< /Type /Action
>>
endobj
328 0 obj
<< /Type /Annot
/Subtype /Link
/A 329 0 R
/Border [0 0 0]
/H /I
/Rect [ 458.1360 587.8748 474.3990 597.7954 ]
>>
endobj
329 0 obj
<< /Type /Action
>>
endobj
330 0 obj
<< /Type /Annot
/Subtype /Link
/A 331 0 R
/Border [0 0 0]
/H /I
/Rect [ 246.2100 492.6368 262.4730 502.5574 ]
>>
endobj
331 0 obj
<< /Type /Action
>>
endobj
332 0 obj
<< /Type /Annot
/Subtype /Link
/A 333 0 R
/Border [0 0 0]
/H /I
/Rect [ 156.2955 468.8273 172.5585 478.7479 ]
>>
endobj
333 0 obj
<< /Type /Action
>>
endobj
334 0 obj
<< /Type /Annot
/Subtype /Link
/A 335 0 R
/Border [0 0 0]
/H /I
/Rect [ 172.5585 468.8273 188.8215 478.7479 ]
>>
endobj
335 0 obj
<< /Type /Action
>>
endobj
336 0 obj
<< /Type /Annot
/Subtype /Link
/A 337 0 R
/Border [0 0 0]
/H /I
/Rect [ 188.8215 468.8273 205.0845 478.7479 ]
>>
endobj
337 0 obj
<< /Type /Action
>>
endobj
338 0 obj
<< /Type /Annot
/Subtype /Link
/A 339 0 R
/Border [0 0 0]
/H /I
/Rect [ 205.0845 468.8273 221.3475 478.7479 ]
>>
endobj
339 0 obj
<< /Type /Action
>>
endobj
340 0 obj
<< /Type /Annot
/Subtype /Link
/A 341 0 R
/Border [0 0 0]
/H /I
/Rect [ 310.1895 456.9226 326.4525 466.8432 ]
>>
endobj
341 0 obj
<< /Type /Action
>>
endobj
342 0 obj
<< /Type /Annot
/Subtype /Link
/A 343 0 R
/Border [0 0 0]
/H /I
/Rect [ 326.4525 456.9226 342.7155 466.8432 ]
>>
endobj
343 0 obj
<< /Type /Action
>>
endobj
344 0 obj
<< /Type /Annot
/Subtype /Link
/A 345 0 R
/Border [0 0 0]
/H /I
/Rect [ 510.4837 445.0178 526.7468 454.9384 ]
>>
endobj
345 0 obj
<< /Type /Action
>>
endobj
346 0 obj
<< /Type /Page
/Parent 3 0 R
/Annots [ 348 0 R 350 0 R 352 0 R 354 0 R 356 0 R 358 0 R 360 0 R 362 0 R 364 0 R 366 0 R 368 0 R 370 0 R 372 0 R 374 0 R 376 0 R 378 0 R 380 0 R 382 0 R 384 0 R 386 0 R 388 0 R 390 0 R 392 0 R 394 0 R 396 0 R 398 0 R 400 0 R ]
/Contents 347 0 R
>>
endobj
347 0 obj
<<
/Length 41194 >>
stream

0.271 0.267 0.267 rg
q
15.000 26.662 577.500 750.338 re W n
1.000 1.000 1.000 rg
26.250 680.719 555.000 96.281 re f
0.267 0.267 0.267 rg
26.625 776.625 210.174 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  [(Beck depression inventory)] TJ ET
0.267 0.267 0.267 rg
236.049 776.625 188.959 0.750 re f
236.049 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 241.299 766.770 Td /F1 9.8 Tf  [(12.3 � 13.4 \(0-39\))] TJ ET
0.267 0.267 0.267 rg
424.258 776.625 156.617 0.750 re f
424.258 745.369 0.750 32.006 re f
580.125 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 429.508 766.770 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 745.369 210.174 0.750 re f
26.625 744.619 0.750 1.500 re f
236.049 745.369 188.959 0.750 re f
236.049 744.619 0.750 1.500 re f
424.258 745.369 156.617 0.750 re f
424.258 744.619 0.750 1.500 re f
580.125 744.619 0.750 1.500 re f
26.625 744.619 210.174 0.750 re f
26.625 728.737 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 734.764 Td /F1 9.8 Tf  [(Tapping dominant)] TJ ET
0.267 0.267 0.267 rg
236.049 744.619 188.959 0.750 re f
236.049 728.737 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 734.764 Td /F1 9.8 Tf  [(129.2 � 44.8 \(47-198\))] TJ ET
0.267 0.267 0.267 rg
424.258 744.619 156.617 0.750 re f
424.258 728.737 0.750 16.631 re f
580.125 728.737 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 734.764 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 728.737 210.174 0.750 re f
26.625 712.856 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 718.883 Td /F1 9.8 Tf  [(Tapping non dominant)] TJ ET
0.267 0.267 0.267 rg
236.049 728.737 188.959 0.750 re f
236.049 712.856 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 718.883 Td /F1 9.8 Tf  [(99.4 � 33 \(38-161\))] TJ ET
0.267 0.267 0.267 rg
424.258 728.737 156.617 0.750 re f
424.258 712.856 0.750 16.631 re f
580.125 712.856 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 718.883 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 712.856 210.174 0.750 re f
26.625 696.975 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 703.001 Td /F1 9.8 Tf  [(Pegboard dominant [sec])] TJ ET
0.267 0.267 0.267 rg
236.049 712.856 188.959 0.750 re f
236.049 696.975 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 703.001 Td /F1 9.8 Tf  [(68.6 � 24.8 \(42.2-120.9\))] TJ ET
0.267 0.267 0.267 rg
424.258 712.856 156.617 0.750 re f
424.258 696.975 0.750 16.631 re f
580.125 696.975 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 703.001 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 696.975 210.174 0.750 re f
26.625 681.094 210.174 0.750 re f
26.625 681.094 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 687.120 Td /F1 9.8 Tf  [(Pegboard non dominant [sec])] TJ ET
0.267 0.267 0.267 rg
236.049 696.975 188.959 0.750 re f
236.049 681.094 188.959 0.750 re f
236.049 681.094 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 687.120 Td /F1 9.8 Tf  [(80.9 � 40.2 \(43.9-184.0\))] TJ ET
0.267 0.267 0.267 rg
424.258 696.975 156.617 0.750 re f
424.258 681.094 156.617 0.750 re f
424.258 681.094 0.750 16.631 re f
580.125 681.094 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 687.120 Td /F1 9.8 Tf  [(�)] TJ ET
BT 26.250 633.695 Td /F4 9.8 Tf  [(Table 1:)] TJ ET
BT 63.095 633.695 Td /F1 9.8 Tf  [( Clinical characteristics of 11 HD patients and 11 matched controls; values are given as mean � SD; range \(min-max\) in )] TJ ET
BT 26.250 621.790 Td /F1 9.8 Tf  [(brackets; Abbreviations: BMI � body mass index, yr � years, AO � age at onset, )] TJ ET
BT 371.995 625.678 Td /F1 8.7 Tf  [(a)] TJ ET
BT 376.813 621.790 Td /F1 9.8 Tf  [( n = 6; UHDRS � unified Huntington�s disease )] TJ ET
BT 26.250 609.885 Td /F1 9.8 Tf  [(rating scale, MS � motor score TFC � total functional capacity, IS � independence scale, CS � cognitive sum score, SDMT � )] TJ ET
BT 26.250 597.981 Td /F1 9.8 Tf  [(symbol digit modalities test; sec � seconds. * � significant differences.)] TJ ET
BT 26.250 578.576 Td /F4 9.8 Tf  [(Test meal and)] TJ ET
BT 91.273 582.464 Td /F4 8.7 Tf  [(13)] TJ ET
BT 100.910 578.576 Td /F4 9.8 Tf  [(C-octanoate breath test technique)] TJ ET
BT 26.250 559.171 Td /F1 9.8 Tf  [(The )] TJ ET
BT 45.760 563.059 Td /F1 8.7 Tf  [(13)] TJ ET
BT 55.397 559.171 Td /F1 9.8 Tf  [( C-octanoate breath test was used in the same way as described earlier. )] TJ ET
0.267 0.267 0.267 rg
BT 370.244 559.171 Td /F1 9.8 Tf  [([16])] TJ ET
BT 386.507 559.171 Td /F1 9.8 Tf  [([17])] TJ ET
BT 402.770 559.171 Td /F1 9.8 Tf  [([18])] TJ ET
BT 419.033 559.171 Td /F1 9.8 Tf  [([34])] TJ ET
0.271 0.267 0.267 rg
BT 435.296 559.171 Td /F1 9.8 Tf  [( In summary: After an overnight )] TJ ET
BT 26.250 547.266 Td /F1 9.8 Tf  [(fasting each participant received a solid test meal consisting of an egg omelet of one egg, 60 g of white bread, 5 g of margarine )] TJ ET
BT 26.250 535.362 Td /F1 9.8 Tf  [(and 150 ml of water \(14 g of proteins, 26 g of carbohydrates and 9 g of fat, 241 kcal\) labeled with 100 mg of 13C-)] TJ ET
BT 26.250 523.457 Td /F1 9.8 Tf  [(sodiumoctanoate \(chemical purity of 99,7 % and an isotopic purity of 99,1 %\) at 8 AM. Breath samples, which were expired in )] TJ ET
BT 26.250 511.552 Td /F1 9.8 Tf  [(close aluminized plastic breath bags of 50 ml content were obtained before substrate administration at baseline and after 10, )] TJ ET
BT 26.250 499.647 Td /F1 9.8 Tf  [(20, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 200, 220 and 240 minutes. The subjects were kept in a relaxed sitting )] TJ ET
BT 26.250 487.743 Td /F1 9.8 Tf  [(position during the octanoate breath test \(OBT\). Physical activity was restricted during the test. All subjects consumed their test )] TJ ET
BT 26.250 475.838 Td /F1 9.8 Tf  [(meal within 10 minutes. The )] TJ ET
BT 150.338 479.726 Td /F1 8.7 Tf  [(13)] TJ ET
BT 159.976 475.838 Td /F1 9.8 Tf  [( C/ )] TJ ET
BT 175.147 479.726 Td /F1 8.7 Tf  [(12)] TJ ET
BT 184.784 475.838 Td /F1 9.8 Tf  [( C isotope ratio of the breath samples was analysed by isotope-selective nondispersive )] TJ ET
BT 26.250 463.933 Td /F1 9.8 Tf  [(infrared spectrometer \(NDIRS\). The results were both expressed as delta \(?\) value per mil \(�\) and delta over baseline \(dob = ? )] TJ ET
BT 26.250 449.964 Td /F1 8.7 Tf  [(s)] TJ ET
BT 30.583 452.028 Td /F1 9.8 Tf  [( � ? )] TJ ET
BT 49.557 449.964 Td /F1 8.7 Tf  [(0)] TJ ET
BT 54.376 452.028 Td /F1 9.8 Tf  [( \). Definition of the ?-value: ? )] TJ ET
BT 181.730 449.964 Td /F1 8.7 Tf  [(s)] TJ ET
BT 186.063 452.028 Td /F1 9.8 Tf  [( = \(R )] TJ ET
BT 210.175 449.964 Td /F1 8.7 Tf  [(S)] TJ ET
BT 215.956 452.028 Td /F1 9.8 Tf  [( /R )] TJ ET
BT 231.127 449.964 Td /F1 8.7 Tf  [(PDB)] TJ ET
BT 248.945 452.028 Td /F1 9.8 Tf  [( -1\) x 1000 [�] with R )] TJ ET
BT 345.938 449.964 Td /F1 8.7 Tf  [(s)] TJ ET
BT 350.272 452.028 Td /F1 9.8 Tf  [( = )] TJ ET
BT 361.387 455.917 Td /F1 8.7 Tf  [(13)] TJ ET
BT 371.024 452.028 Td /F1 9.8 Tf  [( C/ )] TJ ET
BT 386.195 455.917 Td /F1 8.7 Tf  [(12)] TJ ET
BT 395.832 452.028 Td /F1 9.8 Tf  [( C isotope ratio in CO )] TJ ET
BT 491.743 449.964 Td /F1 8.7 Tf  [(2)] TJ ET
BT 496.562 452.028 Td /F1 9.8 Tf  [( in breath and R )] TJ ET
BT 26.250 438.059 Td /F1 8.7 Tf  [(PDB)] TJ ET
BT 44.069 440.124 Td /F1 9.8 Tf  [( = 0.0112372 = isotope ratio in reference \(PDB = PeeDeeBelmnite, South Carolina; ? )] TJ ET
BT 413.408 438.059 Td /F1 8.7 Tf  [(0)] TJ ET
BT 418.227 440.124 Td /F1 9.8 Tf  [( = isotope ratio at baseline\).)] TJ ET
BT 26.250 420.719 Td /F4 9.8 Tf  [(Mathematical analysis of)] TJ ET
BT 141.125 424.607 Td /F4 8.7 Tf  [(13)] TJ ET
BT 150.762 420.719 Td /F4 9.8 Tf  [(CO)] TJ ET
BT 165.387 418.655 Td /F4 8.7 Tf  [(2 )] TJ ET
BT 172.615 420.719 Td /F4 9.8 Tf  [(excretion curves and statistical analysis)] TJ ET
BT 26.250 401.314 Td /F1 9.8 Tf  [(As regards the measuring of the proportion of the )] TJ ET
BT 241.403 405.202 Td /F1 8.7 Tf  [(13)] TJ ET
BT 251.041 401.314 Td /F1 9.8 Tf  [( C-sodium octanoate given by mouth that is metabolised the results were )] TJ ET
BT 26.250 389.409 Td /F1 9.8 Tf  [(expressed as a percentage dose of )] TJ ET
BT 181.256 393.298 Td /F1 8.7 Tf  [(13)] TJ ET
BT 190.893 389.409 Td /F1 9.8 Tf  [( C recovered \(PDR\) over time for each time interval from which the cumulative PDR )] TJ ET
BT 26.250 377.505 Td /F1 9.8 Tf  [(\(cPDR\), obtained by numerical integration from PDR values, was calculated for each time interval. This calculation is based on )] TJ ET
BT 26.250 365.600 Td /F1 9.8 Tf  [(the formula as proposed by Ravussin. )] TJ ET
0.267 0.267 0.267 rg
BT 192.614 365.600 Td /F1 9.8 Tf  [([35])] TJ ET
0.271 0.267 0.267 rg
BT 208.877 365.600 Td /F1 9.8 Tf  [( CO )] TJ ET
BT 228.923 363.536 Td /F1 8.7 Tf  [(2)] TJ ET
BT 233.742 365.600 Td /F1 9.8 Tf  [( production rate was assumed as being 300 mmol per unit of body surface area )] TJ ET
BT 26.250 353.695 Td /F1 9.8 Tf  [(per hour. The body surface area was calculated using the Haycock weight-height formula. )] TJ ET
0.267 0.267 0.267 rg
BT 415.880 353.695 Td /F1 9.8 Tf  [([36])] TJ ET
0.271 0.267 0.267 rg
BT 432.142 353.695 Td /F1 9.8 Tf  [( The evaluation of the OBT for )] TJ ET
BT 26.250 341.790 Td /F1 9.8 Tf  [(gastric emptying was done by non-linear regression analysis of the )] TJ ET
BT 316.702 345.679 Td /F1 8.7 Tf  [(13)] TJ ET
BT 326.340 341.790 Td /F1 9.8 Tf  [( CO )] TJ ET
BT 346.386 339.726 Td /F1 8.7 Tf  [(2)] TJ ET
BT 351.204 341.790 Td /F1 9.8 Tf  [( -excretion curves \(PDR\) with the formula PDR\(t\) = )] TJ ET
BT 26.250 329.886 Td /F1 9.8 Tf  [(at )] TJ ET
BT 37.092 333.774 Td /F1 8.7 Tf  [(b)] TJ ET
BT 41.911 329.886 Td /F1 9.8 Tf  [( e )] TJ ET
BT 52.753 333.774 Td /F1 8.7 Tf  [(-ct)] TJ ET
BT 62.381 329.886 Td /F1 9.8 Tf  [( . The expression ln a, as gastric emptying coefficient \(GEC\) is a reliable parameter to describe the rate at which the )] TJ ET
BT 26.250 317.981 Td /F1 9.8 Tf  [(stomach empties. The percentage of )] TJ ET
BT 187.203 321.869 Td /F1 8.7 Tf  [(13)] TJ ET
BT 196.840 317.981 Td /F1 9.8 Tf  [( CO )] TJ ET
BT 216.886 315.917 Td /F1 8.7 Tf  [(2)] TJ ET
BT 221.705 317.981 Td /F1 9.8 Tf  [( cumulative values was fit using a model given by the formula cPDR\(t\) = m\(1-e )] TJ ET
BT 562.799 321.869 Td /F1 8.7 Tf  [(-kt)] TJ ET
BT 572.428 317.981 Td /F1 9.8 Tf  [( \) )] TJ ET
BT 26.250 309.964 Td /F1 8.7 Tf  [(�)] TJ ET
BT 31.545 306.076 Td /F1 9.8 Tf  [( , where y is cPDR at time t in hours and m, k and � are regression estimated constants, with m being the total amount of )] TJ ET
BT 555.023 309.964 Td /F1 8.7 Tf  [(13)] TJ ET
BT 26.250 294.171 Td /F1 9.8 Tf  [(CO )] TJ ET
BT 43.585 292.107 Td /F1 8.7 Tf  [(2)] TJ ET
BT 48.404 294.171 Td /F1 9.8 Tf  [( when time is infinite. Half gastric emptying time \(t )] TJ ET
BT 265.137 292.107 Td /F1 8.7 Tf  [(50)] TJ ET
BT 274.774 294.171 Td /F1 9.8 Tf  [( \) was calculated by taking PDR\(t\) equal to m/2 in the PDR equation )] TJ ET
BT 26.250 282.267 Td /F1 9.8 Tf  [(which is expressed as t )] TJ ET
BT 129.746 280.202 Td /F1 8.7 Tf  [(50)] TJ ET
BT 139.384 282.267 Td /F1 9.8 Tf  [( = \(-1/k\)ln \(1-2 )] TJ ET
BT 203.587 286.155 Td /F1 8.7 Tf  [(-1/�)] TJ ET
BT 218.997 282.267 Td /F1 9.8 Tf  [( \). The Lag phase is expressed as t )] TJ ET
BT 373.992 280.202 Td /F1 8.7 Tf  [(lag)] TJ ET
BT 385.554 282.267 Td /F1 9.8 Tf  [( = 1/kln�. )] TJ ET
0.267 0.267 0.267 rg
BT 428.639 282.267 Td /F1 9.8 Tf  [([37])] TJ ET
0.271 0.267 0.267 rg
BT 444.902 282.267 Td /F1 9.8 Tf  [( Statistical analysis was )] TJ ET
BT 26.250 270.362 Td /F1 9.8 Tf  [(carried out as a descriptive evaluation of GEC, t )] TJ ET
BT 235.427 268.298 Td /F1 8.7 Tf  [(50)] TJ ET
BT 245.064 270.362 Td /F1 9.8 Tf  [( \(min\), tl )] TJ ET
BT 282.982 268.298 Td /F1 8.7 Tf  [(ag)] TJ ET
BT 292.619 270.362 Td /F1 9.8 Tf  [( \(min\) and t )] TJ ET
BT 344.635 268.298 Td /F1 8.7 Tf  [(peak)] TJ ET
BT 363.425 270.362 Td /F1 9.8 Tf  [( \(min\) and characteristics of participants \(mean � )] TJ ET
BT 26.250 258.457 Td /F1 9.8 Tf  [(SD\).)] TJ ET
BT 26.250 239.052 Td /F4 9.8 Tf  [(Gastroparesis Cardinal Symptom Index \(GCSI\) and Short-Form Leeds Dyspepsia Questionnaire \(SF-LDQ\))] TJ ET
BT 26.250 219.648 Td /F1 9.8 Tf  [(The well-validated Gastroparesis Cardinal Symptom Index \(GCSI\) was used for clinical evaluation of gastroparesis symptoms. )] TJ ET
BT 26.250 207.743 Td /F1 9.8 Tf  [(GCSI quantifies nine symptoms in the three different subscales: nausea and vomiting, postprandial fullness, and bloating. )] TJ ET
0.267 0.267 0.267 rg
BT 551.921 207.743 Td /F1 9.8 Tf  [([38])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 195.838 Td /F1 9.8 Tf  [(In addition patients were asked about the frequency and severity of their stomach complaints, heartburn, burping and nausea )] TJ ET
BT 26.250 183.933 Td /F1 9.8 Tf  [(symptoms according to the Short-Form Leeds Dyspepsia Questionnaire \(SF-LDQ\). )] TJ ET
0.267 0.267 0.267 rg
BT 386.035 183.933 Td /F1 9.8 Tf  [([39])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 164.529 Td /F1 9.8 Tf  [(The data analysis and statistics were performed by using the commercial software program SPSS statistics 19. All measured )] TJ ET
BT 26.250 152.624 Td /F1 9.8 Tf  [(parameters and clinical data were first analysed descriptively and they were when presented as mean � SD. Normality of )] TJ ET
BT 26.250 140.719 Td /F1 9.8 Tf  [(distribution of the data was tested with the one-sample Kolmogorov-Smirnov test. Data were analyzed using the independent t-)] TJ ET
BT 26.250 128.814 Td /F1 9.8 Tf  [(test for comparison between HD participants and controls. Pearson correlation analysis was used for exploratory statistical )] TJ ET
BT 26.250 116.910 Td /F1 9.8 Tf  [(calculations of the normal distributed data.)] TJ ET
BT 26.250 80.307 Td /F4 12.0 Tf  [(Results)] TJ ET
Q
q
15.000 26.662 577.500 750.338 re W n
1.000 1.000 1.000 rg
26.250 680.719 555.000 96.281 re f
0.267 0.267 0.267 rg
26.625 776.625 210.174 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  [(Beck depression inventory)] TJ ET
0.267 0.267 0.267 rg
236.049 776.625 188.959 0.750 re f
236.049 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 241.299 766.770 Td /F1 9.8 Tf  [(12.3 � 13.4 \(0-39\))] TJ ET
0.267 0.267 0.267 rg
424.258 776.625 156.617 0.750 re f
424.258 745.369 0.750 32.006 re f
580.125 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 429.508 766.770 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 745.369 210.174 0.750 re f
26.625 744.619 0.750 1.500 re f
236.049 745.369 188.959 0.750 re f
236.049 744.619 0.750 1.500 re f
424.258 745.369 156.617 0.750 re f
424.258 744.619 0.750 1.500 re f
580.125 744.619 0.750 1.500 re f
26.625 744.619 210.174 0.750 re f
26.625 728.737 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 734.764 Td /F1 9.8 Tf  [(Tapping dominant)] TJ ET
0.267 0.267 0.267 rg
236.049 744.619 188.959 0.750 re f
236.049 728.737 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 734.764 Td /F1 9.8 Tf  [(129.2 � 44.8 \(47-198\))] TJ ET
0.267 0.267 0.267 rg
424.258 744.619 156.617 0.750 re f
424.258 728.737 0.750 16.631 re f
580.125 728.737 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 734.764 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 728.737 210.174 0.750 re f
26.625 712.856 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 718.883 Td /F1 9.8 Tf  [(Tapping non dominant)] TJ ET
0.267 0.267 0.267 rg
236.049 728.737 188.959 0.750 re f
236.049 712.856 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 718.883 Td /F1 9.8 Tf  [(99.4 � 33 \(38-161\))] TJ ET
0.267 0.267 0.267 rg
424.258 728.737 156.617 0.750 re f
424.258 712.856 0.750 16.631 re f
580.125 712.856 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 718.883 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 712.856 210.174 0.750 re f
26.625 696.975 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 703.001 Td /F1 9.8 Tf  [(Pegboard dominant [sec])] TJ ET
0.267 0.267 0.267 rg
236.049 712.856 188.959 0.750 re f
236.049 696.975 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 703.001 Td /F1 9.8 Tf  [(68.6 � 24.8 \(42.2-120.9\))] TJ ET
0.267 0.267 0.267 rg
424.258 712.856 156.617 0.750 re f
424.258 696.975 0.750 16.631 re f
580.125 696.975 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 703.001 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 696.975 210.174 0.750 re f
26.625 681.094 210.174 0.750 re f
26.625 681.094 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 687.120 Td /F1 9.8 Tf  [(Pegboard non dominant [sec])] TJ ET
0.267 0.267 0.267 rg
236.049 696.975 188.959 0.750 re f
236.049 681.094 188.959 0.750 re f
236.049 681.094 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 687.120 Td /F1 9.8 Tf  [(80.9 � 40.2 \(43.9-184.0\))] TJ ET
0.267 0.267 0.267 rg
424.258 696.975 156.617 0.750 re f
424.258 681.094 156.617 0.750 re f
424.258 681.094 0.750 16.631 re f
580.125 681.094 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 687.120 Td /F1 9.8 Tf  [(�)] TJ ET
BT 26.250 633.695 Td /F4 9.8 Tf  [(Table 1:)] TJ ET
BT 63.095 633.695 Td /F1 9.8 Tf  [( Clinical characteristics of 11 HD patients and 11 matched controls; values are given as mean � SD; range \(min-max\) in )] TJ ET
BT 26.250 621.790 Td /F1 9.8 Tf  [(brackets; Abbreviations: BMI � body mass index, yr � years, AO � age at onset, )] TJ ET
BT 371.995 625.678 Td /F1 8.7 Tf  [(a)] TJ ET
BT 376.813 621.790 Td /F1 9.8 Tf  [( n = 6; UHDRS � unified Huntington�s disease )] TJ ET
BT 26.250 609.885 Td /F1 9.8 Tf  [(rating scale, MS � motor score TFC � total functional capacity, IS � independence scale, CS � cognitive sum score, SDMT � )] TJ ET
BT 26.250 597.981 Td /F1 9.8 Tf  [(symbol digit modalities test; sec � seconds. * � significant differences.)] TJ ET
BT 26.250 578.576 Td /F4 9.8 Tf  [(Test meal and)] TJ ET
BT 91.273 582.464 Td /F4 8.7 Tf  [(13)] TJ ET
BT 100.910 578.576 Td /F4 9.8 Tf  [(C-octanoate breath test technique)] TJ ET
BT 26.250 559.171 Td /F1 9.8 Tf  [(The )] TJ ET
BT 45.760 563.059 Td /F1 8.7 Tf  [(13)] TJ ET
BT 55.397 559.171 Td /F1 9.8 Tf  [( C-octanoate breath test was used in the same way as described earlier. )] TJ ET
0.267 0.267 0.267 rg
BT 370.244 559.171 Td /F1 9.8 Tf  [([16])] TJ ET
BT 386.507 559.171 Td /F1 9.8 Tf  [([17])] TJ ET
BT 402.770 559.171 Td /F1 9.8 Tf  [([18])] TJ ET
BT 419.033 559.171 Td /F1 9.8 Tf  [([34])] TJ ET
0.271 0.267 0.267 rg
BT 435.296 559.171 Td /F1 9.8 Tf  [( In summary: After an overnight )] TJ ET
BT 26.250 547.266 Td /F1 9.8 Tf  [(fasting each participant received a solid test meal consisting of an egg omelet of one egg, 60 g of white bread, 5 g of margarine )] TJ ET
BT 26.250 535.362 Td /F1 9.8 Tf  [(and 150 ml of water \(14 g of proteins, 26 g of carbohydrates and 9 g of fat, 241 kcal\) labeled with 100 mg of 13C-)] TJ ET
BT 26.250 523.457 Td /F1 9.8 Tf  [(sodiumoctanoate \(chemical purity of 99,7 % and an isotopic purity of 99,1 %\) at 8 AM. Breath samples, which were expired in )] TJ ET
BT 26.250 511.552 Td /F1 9.8 Tf  [(close aluminized plastic breath bags of 50 ml content were obtained before substrate administration at baseline and after 10, )] TJ ET
BT 26.250 499.647 Td /F1 9.8 Tf  [(20, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 200, 220 and 240 minutes. The subjects were kept in a relaxed sitting )] TJ ET
BT 26.250 487.743 Td /F1 9.8 Tf  [(position during the octanoate breath test \(OBT\). Physical activity was restricted during the test. All subjects consumed their test )] TJ ET
BT 26.250 475.838 Td /F1 9.8 Tf  [(meal within 10 minutes. The )] TJ ET
BT 150.338 479.726 Td /F1 8.7 Tf  [(13)] TJ ET
BT 159.976 475.838 Td /F1 9.8 Tf  [( C/ )] TJ ET
BT 175.147 479.726 Td /F1 8.7 Tf  [(12)] TJ ET
BT 184.784 475.838 Td /F1 9.8 Tf  [( C isotope ratio of the breath samples was analysed by isotope-selective nondispersive )] TJ ET
BT 26.250 463.933 Td /F1 9.8 Tf  [(infrared spectrometer \(NDIRS\). The results were both expressed as delta \(?\) value per mil \(�\) and delta over baseline \(dob = ? )] TJ ET
BT 26.250 449.964 Td /F1 8.7 Tf  [(s)] TJ ET
BT 30.583 452.028 Td /F1 9.8 Tf  [( � ? )] TJ ET
BT 49.557 449.964 Td /F1 8.7 Tf  [(0)] TJ ET
BT 54.376 452.028 Td /F1 9.8 Tf  [( \). Definition of the ?-value: ? )] TJ ET
BT 181.730 449.964 Td /F1 8.7 Tf  [(s)] TJ ET
BT 186.063 452.028 Td /F1 9.8 Tf  [( = \(R )] TJ ET
BT 210.175 449.964 Td /F1 8.7 Tf  [(S)] TJ ET
BT 215.956 452.028 Td /F1 9.8 Tf  [( /R )] TJ ET
BT 231.127 449.964 Td /F1 8.7 Tf  [(PDB)] TJ ET
BT 248.945 452.028 Td /F1 9.8 Tf  [( -1\) x 1000 [�] with R )] TJ ET
BT 345.938 449.964 Td /F1 8.7 Tf  [(s)] TJ ET
BT 350.272 452.028 Td /F1 9.8 Tf  [( = )] TJ ET
BT 361.387 455.917 Td /F1 8.7 Tf  [(13)] TJ ET
BT 371.024 452.028 Td /F1 9.8 Tf  [( C/ )] TJ ET
BT 386.195 455.917 Td /F1 8.7 Tf  [(12)] TJ ET
BT 395.832 452.028 Td /F1 9.8 Tf  [( C isotope ratio in CO )] TJ ET
BT 491.743 449.964 Td /F1 8.7 Tf  [(2)] TJ ET
BT 496.562 452.028 Td /F1 9.8 Tf  [( in breath and R )] TJ ET
BT 26.250 438.059 Td /F1 8.7 Tf  [(PDB)] TJ ET
BT 44.069 440.124 Td /F1 9.8 Tf  [( = 0.0112372 = isotope ratio in reference \(PDB = PeeDeeBelmnite, South Carolina; ? )] TJ ET
BT 413.408 438.059 Td /F1 8.7 Tf  [(0)] TJ ET
BT 418.227 440.124 Td /F1 9.8 Tf  [( = isotope ratio at baseline\).)] TJ ET
BT 26.250 420.719 Td /F4 9.8 Tf  [(Mathematical analysis of)] TJ ET
BT 141.125 424.607 Td /F4 8.7 Tf  [(13)] TJ ET
BT 150.762 420.719 Td /F4 9.8 Tf  [(CO)] TJ ET
BT 165.387 418.655 Td /F4 8.7 Tf  [(2 )] TJ ET
BT 172.615 420.719 Td /F4 9.8 Tf  [(excretion curves and statistical analysis)] TJ ET
BT 26.250 401.314 Td /F1 9.8 Tf  [(As regards the measuring of the proportion of the )] TJ ET
BT 241.403 405.202 Td /F1 8.7 Tf  [(13)] TJ ET
BT 251.041 401.314 Td /F1 9.8 Tf  [( C-sodium octanoate given by mouth that is metabolised the results were )] TJ ET
BT 26.250 389.409 Td /F1 9.8 Tf  [(expressed as a percentage dose of )] TJ ET
BT 181.256 393.298 Td /F1 8.7 Tf  [(13)] TJ ET
BT 190.893 389.409 Td /F1 9.8 Tf  [( C recovered \(PDR\) over time for each time interval from which the cumulative PDR )] TJ ET
BT 26.250 377.505 Td /F1 9.8 Tf  [(\(cPDR\), obtained by numerical integration from PDR values, was calculated for each time interval. This calculation is based on )] TJ ET
BT 26.250 365.600 Td /F1 9.8 Tf  [(the formula as proposed by Ravussin. )] TJ ET
0.267 0.267 0.267 rg
BT 192.614 365.600 Td /F1 9.8 Tf  [([35])] TJ ET
0.271 0.267 0.267 rg
BT 208.877 365.600 Td /F1 9.8 Tf  [( CO )] TJ ET
BT 228.923 363.536 Td /F1 8.7 Tf  [(2)] TJ ET
BT 233.742 365.600 Td /F1 9.8 Tf  [( production rate was assumed as being 300 mmol per unit of body surface area )] TJ ET
BT 26.250 353.695 Td /F1 9.8 Tf  [(per hour. The body surface area was calculated using the Haycock weight-height formula. )] TJ ET
0.267 0.267 0.267 rg
BT 415.880 353.695 Td /F1 9.8 Tf  [([36])] TJ ET
0.271 0.267 0.267 rg
BT 432.142 353.695 Td /F1 9.8 Tf  [( The evaluation of the OBT for )] TJ ET
BT 26.250 341.790 Td /F1 9.8 Tf  [(gastric emptying was done by non-linear regression analysis of the )] TJ ET
BT 316.702 345.679 Td /F1 8.7 Tf  [(13)] TJ ET
BT 326.340 341.790 Td /F1 9.8 Tf  [( CO )] TJ ET
BT 346.386 339.726 Td /F1 8.7 Tf  [(2)] TJ ET
BT 351.204 341.790 Td /F1 9.8 Tf  [( -excretion curves \(PDR\) with the formula PDR\(t\) = )] TJ ET
BT 26.250 329.886 Td /F1 9.8 Tf  [(at )] TJ ET
BT 37.092 333.774 Td /F1 8.7 Tf  [(b)] TJ ET
BT 41.911 329.886 Td /F1 9.8 Tf  [( e )] TJ ET
BT 52.753 333.774 Td /F1 8.7 Tf  [(-ct)] TJ ET
BT 62.381 329.886 Td /F1 9.8 Tf  [( . The expression ln a, as gastric emptying coefficient \(GEC\) is a reliable parameter to describe the rate at which the )] TJ ET
BT 26.250 317.981 Td /F1 9.8 Tf  [(stomach empties. The percentage of )] TJ ET
BT 187.203 321.869 Td /F1 8.7 Tf  [(13)] TJ ET
BT 196.840 317.981 Td /F1 9.8 Tf  [( CO )] TJ ET
BT 216.886 315.917 Td /F1 8.7 Tf  [(2)] TJ ET
BT 221.705 317.981 Td /F1 9.8 Tf  [( cumulative values was fit using a model given by the formula cPDR\(t\) = m\(1-e )] TJ ET
BT 562.799 321.869 Td /F1 8.7 Tf  [(-kt)] TJ ET
BT 572.428 317.981 Td /F1 9.8 Tf  [( \) )] TJ ET
BT 26.250 309.964 Td /F1 8.7 Tf  [(�)] TJ ET
BT 31.545 306.076 Td /F1 9.8 Tf  [( , where y is cPDR at time t in hours and m, k and � are regression estimated constants, with m being the total amount of )] TJ ET
BT 555.023 309.964 Td /F1 8.7 Tf  [(13)] TJ ET
BT 26.250 294.171 Td /F1 9.8 Tf  [(CO )] TJ ET
BT 43.585 292.107 Td /F1 8.7 Tf  [(2)] TJ ET
BT 48.404 294.171 Td /F1 9.8 Tf  [( when time is infinite. Half gastric emptying time \(t )] TJ ET
BT 265.137 292.107 Td /F1 8.7 Tf  [(50)] TJ ET
BT 274.774 294.171 Td /F1 9.8 Tf  [( \) was calculated by taking PDR\(t\) equal to m/2 in the PDR equation )] TJ ET
BT 26.250 282.267 Td /F1 9.8 Tf  [(which is expressed as t )] TJ ET
BT 129.746 280.202 Td /F1 8.7 Tf  [(50)] TJ ET
BT 139.384 282.267 Td /F1 9.8 Tf  [( = \(-1/k\)ln \(1-2 )] TJ ET
BT 203.587 286.155 Td /F1 8.7 Tf  [(-1/�)] TJ ET
BT 218.997 282.267 Td /F1 9.8 Tf  [( \). The Lag phase is expressed as t )] TJ ET
BT 373.992 280.202 Td /F1 8.7 Tf  [(lag)] TJ ET
BT 385.554 282.267 Td /F1 9.8 Tf  [( = 1/kln�. )] TJ ET
0.267 0.267 0.267 rg
BT 428.639 282.267 Td /F1 9.8 Tf  [([37])] TJ ET
0.271 0.267 0.267 rg
BT 444.902 282.267 Td /F1 9.8 Tf  [( Statistical analysis was )] TJ ET
BT 26.250 270.362 Td /F1 9.8 Tf  [(carried out as a descriptive evaluation of GEC, t )] TJ ET
BT 235.427 268.298 Td /F1 8.7 Tf  [(50)] TJ ET
BT 245.064 270.362 Td /F1 9.8 Tf  [( \(min\), tl )] TJ ET
BT 282.982 268.298 Td /F1 8.7 Tf  [(ag)] TJ ET
BT 292.619 270.362 Td /F1 9.8 Tf  [( \(min\) and t )] TJ ET
BT 344.635 268.298 Td /F1 8.7 Tf  [(peak)] TJ ET
BT 363.425 270.362 Td /F1 9.8 Tf  [( \(min\) and characteristics of participants \(mean � )] TJ ET
BT 26.250 258.457 Td /F1 9.8 Tf  [(SD\).)] TJ ET
BT 26.250 239.052 Td /F4 9.8 Tf  [(Gastroparesis Cardinal Symptom Index \(GCSI\) and Short-Form Leeds Dyspepsia Questionnaire \(SF-LDQ\))] TJ ET
BT 26.250 219.648 Td /F1 9.8 Tf  [(The well-validated Gastroparesis Cardinal Symptom Index \(GCSI\) was used for clinical evaluation of gastroparesis symptoms. )] TJ ET
BT 26.250 207.743 Td /F1 9.8 Tf  [(GCSI quantifies nine symptoms in the three different subscales: nausea and vomiting, postprandial fullness, and bloating. )] TJ ET
0.267 0.267 0.267 rg
BT 551.921 207.743 Td /F1 9.8 Tf  [([38])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 195.838 Td /F1 9.8 Tf  [(In addition patients were asked about the frequency and severity of their stomach complaints, heartburn, burping and nausea )] TJ ET
BT 26.250 183.933 Td /F1 9.8 Tf  [(symptoms according to the Short-Form Leeds Dyspepsia Questionnaire \(SF-LDQ\). )] TJ ET
0.267 0.267 0.267 rg
BT 386.035 183.933 Td /F1 9.8 Tf  [([39])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 164.529 Td /F1 9.8 Tf  [(The data analysis and statistics were performed by using the commercial software program SPSS statistics 19. All measured )] TJ ET
BT 26.250 152.624 Td /F1 9.8 Tf  [(parameters and clinical data were first analysed descriptively and they were when presented as mean � SD. Normality of )] TJ ET
BT 26.250 140.719 Td /F1 9.8 Tf  [(distribution of the data was tested with the one-sample Kolmogorov-Smirnov test. Data were analyzed using the independent t-)] TJ ET
BT 26.250 128.814 Td /F1 9.8 Tf  [(test for comparison between HD participants and controls. Pearson correlation analysis was used for exploratory statistical )] TJ ET
BT 26.250 116.910 Td /F1 9.8 Tf  [(calculations of the normal distributed data.)] TJ ET
BT 26.250 80.307 Td /F4 12.0 Tf  [(Results)] TJ ET
Q
q
15.000 26.662 577.500 750.338 re W n
1.000 1.000 1.000 rg
26.250 680.719 555.000 96.281 re f
0.267 0.267 0.267 rg
26.625 776.625 210.174 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  [(Beck depression inventory)] TJ ET
0.267 0.267 0.267 rg
236.049 776.625 188.959 0.750 re f
236.049 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 241.299 766.770 Td /F1 9.8 Tf  [(12.3 � 13.4 \(0-39\))] TJ ET
0.267 0.267 0.267 rg
424.258 776.625 156.617 0.750 re f
424.258 745.369 0.750 32.006 re f
580.125 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 429.508 766.770 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 745.369 210.174 0.750 re f
26.625 744.619 0.750 1.500 re f
236.049 745.369 188.959 0.750 re f
236.049 744.619 0.750 1.500 re f
424.258 745.369 156.617 0.750 re f
424.258 744.619 0.750 1.500 re f
580.125 744.619 0.750 1.500 re f
26.625 744.619 210.174 0.750 re f
26.625 728.737 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 734.764 Td /F1 9.8 Tf  [(Tapping dominant)] TJ ET
0.267 0.267 0.267 rg
236.049 744.619 188.959 0.750 re f
236.049 728.737 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 734.764 Td /F1 9.8 Tf  [(129.2 � 44.8 \(47-198\))] TJ ET
0.267 0.267 0.267 rg
424.258 744.619 156.617 0.750 re f
424.258 728.737 0.750 16.631 re f
580.125 728.737 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 734.764 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 728.737 210.174 0.750 re f
26.625 712.856 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 718.883 Td /F1 9.8 Tf  [(Tapping non dominant)] TJ ET
0.267 0.267 0.267 rg
236.049 728.737 188.959 0.750 re f
236.049 712.856 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 718.883 Td /F1 9.8 Tf  [(99.4 � 33 \(38-161\))] TJ ET
0.267 0.267 0.267 rg
424.258 728.737 156.617 0.750 re f
424.258 712.856 0.750 16.631 re f
580.125 712.856 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 718.883 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 712.856 210.174 0.750 re f
26.625 696.975 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 703.001 Td /F1 9.8 Tf  [(Pegboard dominant [sec])] TJ ET
0.267 0.267 0.267 rg
236.049 712.856 188.959 0.750 re f
236.049 696.975 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 703.001 Td /F1 9.8 Tf  [(68.6 � 24.8 \(42.2-120.9\))] TJ ET
0.267 0.267 0.267 rg
424.258 712.856 156.617 0.750 re f
424.258 696.975 0.750 16.631 re f
580.125 696.975 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 703.001 Td /F1 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
26.625 696.975 210.174 0.750 re f
26.625 681.094 210.174 0.750 re f
26.625 681.094 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 687.120 Td /F1 9.8 Tf  [(Pegboard non dominant [sec])] TJ ET
0.267 0.267 0.267 rg
236.049 696.975 188.959 0.750 re f
236.049 681.094 188.959 0.750 re f
236.049 681.094 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 241.299 687.120 Td /F1 9.8 Tf  [(80.9 � 40.2 \(43.9-184.0\))] TJ ET
0.267 0.267 0.267 rg
424.258 696.975 156.617 0.750 re f
424.258 681.094 156.617 0.750 re f
424.258 681.094 0.750 16.631 re f
580.125 681.094 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 429.508 687.120 Td /F1 9.8 Tf  [(�)] TJ ET
BT 26.250 633.695 Td /F4 9.8 Tf  [(Table 1:)] TJ ET
BT 63.095 633.695 Td /F1 9.8 Tf  [( Clinical characteristics of 11 HD patients and 11 matched controls; values are given as mean � SD; range \(min-max\) in )] TJ ET
BT 26.250 621.790 Td /F1 9.8 Tf  [(brackets; Abbreviations: BMI � body mass index, yr � years, AO � age at onset, )] TJ ET
BT 371.995 625.678 Td /F1 8.7 Tf  [(a)] TJ ET
BT 376.813 621.790 Td /F1 9.8 Tf  [( n = 6; UHDRS � unified Huntington�s disease )] TJ ET
BT 26.250 609.885 Td /F1 9.8 Tf  [(rating scale, MS � motor score TFC � total functional capacity, IS � independence scale, CS � cognitive sum score, SDMT � )] TJ ET
BT 26.250 597.981 Td /F1 9.8 Tf  [(symbol digit modalities test; sec � seconds. * � significant differences.)] TJ ET
BT 26.250 578.576 Td /F4 9.8 Tf  [(Test meal and)] TJ ET
BT 91.273 582.464 Td /F4 8.7 Tf  [(13)] TJ ET
BT 100.910 578.576 Td /F4 9.8 Tf  [(C-octanoate breath test technique)] TJ ET
BT 26.250 559.171 Td /F1 9.8 Tf  [(The )] TJ ET
BT 45.760 563.059 Td /F1 8.7 Tf  [(13)] TJ ET
BT 55.397 559.171 Td /F1 9.8 Tf  [( C-octanoate breath test was used in the same way as described earlier. )] TJ ET
0.267 0.267 0.267 rg
BT 370.244 559.171 Td /F1 9.8 Tf  [([16])] TJ ET
BT 386.507 559.171 Td /F1 9.8 Tf  [([17])] TJ ET
BT 402.770 559.171 Td /F1 9.8 Tf  [([18])] TJ ET
BT 419.033 559.171 Td /F1 9.8 Tf  [([34])] TJ ET
0.271 0.267 0.267 rg
BT 435.296 559.171 Td /F1 9.8 Tf  [( In summary: After an overnight )] TJ ET
BT 26.250 547.266 Td /F1 9.8 Tf  [(fasting each participant received a solid test meal consisting of an egg omelet of one egg, 60 g of white bread, 5 g of margarine )] TJ ET
BT 26.250 535.362 Td /F1 9.8 Tf  [(and 150 ml of water \(14 g of proteins, 26 g of carbohydrates and 9 g of fat, 241 kcal\) labeled with 100 mg of 13C-)] TJ ET
BT 26.250 523.457 Td /F1 9.8 Tf  [(sodiumoctanoate \(chemical purity of 99,7 % and an isotopic purity of 99,1 %\) at 8 AM. Breath samples, which were expired in )] TJ ET
BT 26.250 511.552 Td /F1 9.8 Tf  [(close aluminized plastic breath bags of 50 ml content were obtained before substrate administration at baseline and after 10, )] TJ ET
BT 26.250 499.647 Td /F1 9.8 Tf  [(20, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 200, 220 and 240 minutes. The subjects were kept in a relaxed sitting )] TJ ET
BT 26.250 487.743 Td /F1 9.8 Tf  [(position during the octanoate breath test \(OBT\). Physical activity was restricted during the test. All subjects consumed their test )] TJ ET
BT 26.250 475.838 Td /F1 9.8 Tf  [(meal within 10 minutes. The )] TJ ET
BT 150.338 479.726 Td /F1 8.7 Tf  [(13)] TJ ET
BT 159.976 475.838 Td /F1 9.8 Tf  [( C/ )] TJ ET
BT 175.147 479.726 Td /F1 8.7 Tf  [(12)] TJ ET
BT 184.784 475.838 Td /F1 9.8 Tf  [( C isotope ratio of the breath samples was analysed by isotope-selective nondispersive )] TJ ET
BT 26.250 463.933 Td /F1 9.8 Tf  [(infrared spectrometer \(NDIRS\). The results were both expressed as delta \(?\) value per mil \(�\) and delta over baseline \(dob = ? )] TJ ET
BT 26.250 449.964 Td /F1 8.7 Tf  [(s)] TJ ET
BT 30.583 452.028 Td /F1 9.8 Tf  [( � ? )] TJ ET
BT 49.557 449.964 Td /F1 8.7 Tf  [(0)] TJ ET
BT 54.376 452.028 Td /F1 9.8 Tf  [( \). Definition of the ?-value: ? )] TJ ET
BT 181.730 449.964 Td /F1 8.7 Tf  [(s)] TJ ET
BT 186.063 452.028 Td /F1 9.8 Tf  [( = \(R )] TJ ET
BT 210.175 449.964 Td /F1 8.7 Tf  [(S)] TJ ET
BT 215.956 452.028 Td /F1 9.8 Tf  [( /R )] TJ ET
BT 231.127 449.964 Td /F1 8.7 Tf  [(PDB)] TJ ET
BT 248.945 452.028 Td /F1 9.8 Tf  [( -1\) x 1000 [�] with R )] TJ ET
BT 345.938 449.964 Td /F1 8.7 Tf  [(s)] TJ ET
BT 350.272 452.028 Td /F1 9.8 Tf  [( = )] TJ ET
BT 361.387 455.917 Td /F1 8.7 Tf  [(13)] TJ ET
BT 371.024 452.028 Td /F1 9.8 Tf  [( C/ )] TJ ET
BT 386.195 455.917 Td /F1 8.7 Tf  [(12)] TJ ET
BT 395.832 452.028 Td /F1 9.8 Tf  [( C isotope ratio in CO )] TJ ET
BT 491.743 449.964 Td /F1 8.7 Tf  [(2)] TJ ET
BT 496.562 452.028 Td /F1 9.8 Tf  [( in breath and R )] TJ ET
BT 26.250 438.059 Td /F1 8.7 Tf  [(PDB)] TJ ET
BT 44.069 440.124 Td /F1 9.8 Tf  [( = 0.0112372 = isotope ratio in reference \(PDB = PeeDeeBelmnite, South Carolina; ? )] TJ ET
BT 413.408 438.059 Td /F1 8.7 Tf  [(0)] TJ ET
BT 418.227 440.124 Td /F1 9.8 Tf  [( = isotope ratio at baseline\).)] TJ ET
BT 26.250 420.719 Td /F4 9.8 Tf  [(Mathematical analysis of)] TJ ET
BT 141.125 424.607 Td /F4 8.7 Tf  [(13)] TJ ET
BT 150.762 420.719 Td /F4 9.8 Tf  [(CO)] TJ ET
BT 165.387 418.655 Td /F4 8.7 Tf  [(2 )] TJ ET
BT 172.615 420.719 Td /F4 9.8 Tf  [(excretion curves and statistical analysis)] TJ ET
BT 26.250 401.314 Td /F1 9.8 Tf  [(As regards the measuring of the proportion of the )] TJ ET
BT 241.403 405.202 Td /F1 8.7 Tf  [(13)] TJ ET
BT 251.041 401.314 Td /F1 9.8 Tf  [( C-sodium octanoate given by mouth that is metabolised the results were )] TJ ET
BT 26.250 389.409 Td /F1 9.8 Tf  [(expressed as a percentage dose of )] TJ ET
BT 181.256 393.298 Td /F1 8.7 Tf  [(13)] TJ ET
BT 190.893 389.409 Td /F1 9.8 Tf  [( C recovered \(PDR\) over time for each time interval from which the cumulative PDR )] TJ ET
BT 26.250 377.505 Td /F1 9.8 Tf  [(\(cPDR\), obtained by numerical integration from PDR values, was calculated for each time interval. This calculation is based on )] TJ ET
BT 26.250 365.600 Td /F1 9.8 Tf  [(the formula as proposed by Ravussin. )] TJ ET
0.267 0.267 0.267 rg
BT 192.614 365.600 Td /F1 9.8 Tf  [([35])] TJ ET
0.271 0.267 0.267 rg
BT 208.877 365.600 Td /F1 9.8 Tf  [( CO )] TJ ET
BT 228.923 363.536 Td /F1 8.7 Tf  [(2)] TJ ET
BT 233.742 365.600 Td /F1 9.8 Tf  [( production rate was assumed as being 300 mmol per unit of body surface area )] TJ ET
BT 26.250 353.695 Td /F1 9.8 Tf  [(per hour. The body surface area was calculated using the Haycock weight-height formula. )] TJ ET
0.267 0.267 0.267 rg
BT 415.880 353.695 Td /F1 9.8 Tf  [([36])] TJ ET
0.271 0.267 0.267 rg
BT 432.142 353.695 Td /F1 9.8 Tf  [( The evaluation of the OBT for )] TJ ET
BT 26.250 341.790 Td /F1 9.8 Tf  [(gastric emptying was done by non-linear regression analysis of the )] TJ ET
BT 316.702 345.679 Td /F1 8.7 Tf  [(13)] TJ ET
BT 326.340 341.790 Td /F1 9.8 Tf  [( CO )] TJ ET
BT 346.386 339.726 Td /F1 8.7 Tf  [(2)] TJ ET
BT 351.204 341.790 Td /F1 9.8 Tf  [( -excretion curves \(PDR\) with the formula PDR\(t\) = )] TJ ET
BT 26.250 329.886 Td /F1 9.8 Tf  [(at )] TJ ET
BT 37.092 333.774 Td /F1 8.7 Tf  [(b)] TJ ET
BT 41.911 329.886 Td /F1 9.8 Tf  [( e )] TJ ET
BT 52.753 333.774 Td /F1 8.7 Tf  [(-ct)] TJ ET
BT 62.381 329.886 Td /F1 9.8 Tf  [( . The expression ln a, as gastric emptying coefficient \(GEC\) is a reliable parameter to describe the rate at which the )] TJ ET
BT 26.250 317.981 Td /F1 9.8 Tf  [(stomach empties. The percentage of )] TJ ET
BT 187.203 321.869 Td /F1 8.7 Tf  [(13)] TJ ET
BT 196.840 317.981 Td /F1 9.8 Tf  [( CO )] TJ ET
BT 216.886 315.917 Td /F1 8.7 Tf  [(2)] TJ ET
BT 221.705 317.981 Td /F1 9.8 Tf  [( cumulative values was fit using a model given by the formula cPDR\(t\) = m\(1-e )] TJ ET
BT 562.799 321.869 Td /F1 8.7 Tf  [(-kt)] TJ ET
BT 572.428 317.981 Td /F1 9.8 Tf  [( \) )] TJ ET
BT 26.250 309.964 Td /F1 8.7 Tf  [(�)] TJ ET
BT 31.545 306.076 Td /F1 9.8 Tf  [( , where y is cPDR at time t in hours and m, k and � are regression estimated constants, with m being the total amount of )] TJ ET
BT 555.023 309.964 Td /F1 8.7 Tf  [(13)] TJ ET
BT 26.250 294.171 Td /F1 9.8 Tf  [(CO )] TJ ET
BT 43.585 292.107 Td /F1 8.7 Tf  [(2)] TJ ET
BT 48.404 294.171 Td /F1 9.8 Tf  [( when time is infinite. Half gastric emptying time \(t )] TJ ET
BT 265.137 292.107 Td /F1 8.7 Tf  [(50)] TJ ET
BT 274.774 294.171 Td /F1 9.8 Tf  [( \) was calculated by taking PDR\(t\) equal to m/2 in the PDR equation )] TJ ET
BT 26.250 282.267 Td /F1 9.8 Tf  [(which is expressed as t )] TJ ET
BT 129.746 280.202 Td /F1 8.7 Tf  [(50)] TJ ET
BT 139.384 282.267 Td /F1 9.8 Tf  [( = \(-1/k\)ln \(1-2 )] TJ ET
BT 203.587 286.155 Td /F1 8.7 Tf  [(-1/�)] TJ ET
BT 218.997 282.267 Td /F1 9.8 Tf  [( \). The Lag phase is expressed as t )] TJ ET
BT 373.992 280.202 Td /F1 8.7 Tf  [(lag)] TJ ET
BT 385.554 282.267 Td /F1 9.8 Tf  [( = 1/kln�. )] TJ ET
0.267 0.267 0.267 rg
BT 428.639 282.267 Td /F1 9.8 Tf  [([37])] TJ ET
0.271 0.267 0.267 rg
BT 444.902 282.267 Td /F1 9.8 Tf  [( Statistical analysis was )] TJ ET
BT 26.250 270.362 Td /F1 9.8 Tf  [(carried out as a descriptive evaluation of GEC, t )] TJ ET
BT 235.427 268.298 Td /F1 8.7 Tf  [(50)] TJ ET
BT 245.064 270.362 Td /F1 9.8 Tf  [( \(min\), tl )] TJ ET
BT 282.982 268.298 Td /F1 8.7 Tf  [(ag)] TJ ET
BT 292.619 270.362 Td /F1 9.8 Tf  [( \(min\) and t )] TJ ET
BT 344.635 268.298 Td /F1 8.7 Tf  [(peak)] TJ ET
BT 363.425 270.362 Td /F1 9.8 Tf  [( \(min\) and characteristics of participants \(mean � )] TJ ET
BT 26.250 258.457 Td /F1 9.8 Tf  [(SD\).)] TJ ET
BT 26.250 239.052 Td /F4 9.8 Tf  [(Gastroparesis Cardinal Symptom Index \(GCSI\) and Short-Form Leeds Dyspepsia Questionnaire \(SF-LDQ\))] TJ ET
BT 26.250 219.648 Td /F1 9.8 Tf  [(The well-validated Gastroparesis Cardinal Symptom Index \(GCSI\) was used for clinical evaluation of gastroparesis symptoms. )] TJ ET
BT 26.250 207.743 Td /F1 9.8 Tf  [(GCSI quantifies nine symptoms in the three different subscales: nausea and vomiting, postprandial fullness, and bloating. )] TJ ET
0.267 0.267 0.267 rg
BT 551.921 207.743 Td /F1 9.8 Tf  [([38])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 195.838 Td /F1 9.8 Tf  [(In addition patients were asked about the frequency and severity of their stomach complaints, heartburn, burping and nausea )] TJ ET
BT 26.250 183.933 Td /F1 9.8 Tf  [(symptoms according to the Short-Form Leeds Dyspepsia Questionnaire \(SF-LDQ\). )] TJ ET
0.267 0.267 0.267 rg
BT 386.035 183.933 Td /F1 9.8 Tf  [([39])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 164.529 Td /F1 9.8 Tf  [(The data analysis and statistics were performed by using the commercial software program SPSS statistics 19. All measured )] TJ ET
BT 26.250 152.624 Td /F1 9.8 Tf  [(parameters and clinical data were first analysed descriptively and they were when presented as mean � SD. Normality of )] TJ ET
BT 26.250 140.719 Td /F1 9.8 Tf  [(distribution of the data was tested with the one-sample Kolmogorov-Smirnov test. Data were analyzed using the independent t-)] TJ ET
BT 26.250 128.814 Td /F1 9.8 Tf  [(test for comparison between HD participants and controls. Pearson correlation analysis was used for exploratory statistical )] TJ ET
BT 26.250 116.910 Td /F1 9.8 Tf  [(calculations of the normal distributed data.)] TJ ET
BT 26.250 80.307 Td /F4 12.0 Tf  [(Results)] TJ ET
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
348 0 obj
<< /Type /Annot
/Subtype /Link
/A 349 0 R
/Border [0 0 0]
/H /I
/Rect [ 370.2441 558.2693 386.5071 568.1899 ]
>>
endobj
349 0 obj
<< /Type /Action
>>
endobj
350 0 obj
<< /Type /Annot
/Subtype /Link
/A 351 0 R
/Border [0 0 0]
/H /I
/Rect [ 386.5071 558.2693 402.7701 568.1899 ]
>>
endobj
351 0 obj
<< /Type /Action
>>
endobj
352 0 obj
<< /Type /Annot
/Subtype /Link
/A 353 0 R
/Border [0 0 0]
/H /I
/Rect [ 402.7701 558.2693 419.0331 568.1899 ]
>>
endobj
353 0 obj
<< /Type /Action
>>
endobj
354 0 obj
<< /Type /Annot
/Subtype /Link
/A 355 0 R
/Border [0 0 0]
/H /I
/Rect [ 419.0331 558.2693 435.2961 568.1899 ]
>>
endobj
355 0 obj
<< /Type /Action
>>
endobj
356 0 obj
<< /Type /Annot
/Subtype /Link
/A 357 0 R
/Border [0 0 0]
/H /I
/Rect [ 192.6142 364.6981 208.8773 374.6187 ]
>>
endobj
357 0 obj
<< /Type /Action
>>
endobj
358 0 obj
<< /Type /Annot
/Subtype /Link
/A 359 0 R
/Border [0 0 0]
/H /I
/Rect [ 415.8795 352.7933 432.1425 362.7140 ]
>>
endobj
359 0 obj
<< /Type /Action
>>
endobj
360 0 obj
<< /Type /Annot
/Subtype /Link
/A 361 0 R
/Border [0 0 0]
/H /I
/Rect [ 428.6390 281.3648 444.9020 291.2855 ]
>>
endobj
361 0 obj
<< /Type /Action
>>
endobj
362 0 obj
<< /Type /Annot
/Subtype /Link
/A 363 0 R
/Border [0 0 0]
/H /I
/Rect [ 551.9212 206.8411 568.1843 216.7617 ]
>>
endobj
363 0 obj
<< /Type /Action
>>
endobj
364 0 obj
<< /Type /Annot
/Subtype /Link
/A 365 0 R
/Border [0 0 0]
/H /I
/Rect [ 386.0347 183.0316 402.2977 192.9522 ]
>>
endobj
365 0 obj
<< /Type /Action
>>
endobj
366 0 obj
<< /Type /Annot
/Subtype /Link
/A 367 0 R
/Border [0 0 0]
/H /I
/Rect [ 370.2441 558.2693 386.5071 568.1899 ]
>>
endobj
367 0 obj
<< /Type /Action
>>
endobj
368 0 obj
<< /Type /Annot
/Subtype /Link
/A 369 0 R
/Border [0 0 0]
/H /I
/Rect [ 386.5071 558.2693 402.7701 568.1899 ]
>>
endobj
369 0 obj
<< /Type /Action
>>
endobj
370 0 obj
<< /Type /Annot
/Subtype /Link
/A 371 0 R
/Border [0 0 0]
/H /I
/Rect [ 402.7701 558.2693 419.0331 568.1899 ]
>>
endobj
371 0 obj
<< /Type /Action
>>
endobj
372 0 obj
<< /Type /Annot
/Subtype /Link
/A 373 0 R
/Border [0 0 0]
/H /I
/Rect [ 419.0331 558.2693 435.2961 568.1899 ]
>>
endobj
373 0 obj
<< /Type /Action
>>
endobj
374 0 obj
<< /Type /Annot
/Subtype /Link
/A 375 0 R
/Border [0 0 0]
/H /I
/Rect [ 192.6142 364.6981 208.8773 374.6187 ]
>>
endobj
375 0 obj
<< /Type /Action
>>
endobj
376 0 obj
<< /Type /Annot
/Subtype /Link
/A 377 0 R
/Border [0 0 0]
/H /I
/Rect [ 415.8795 352.7933 432.1425 362.7140 ]
>>
endobj
377 0 obj
<< /Type /Action
>>
endobj
378 0 obj
<< /Type /Annot
/Subtype /Link
/A 379 0 R
/Border [0 0 0]
/H /I
/Rect [ 428.6390 281.3648 444.9020 291.2855 ]
>>
endobj
379 0 obj
<< /Type /Action
>>
endobj
380 0 obj
<< /Type /Annot
/Subtype /Link
/A 381 0 R
/Border [0 0 0]
/H /I
/Rect [ 551.9212 206.8411 568.1843 216.7617 ]
>>
endobj
381 0 obj
<< /Type /Action
>>
endobj
382 0 obj
<< /Type /Annot
/Subtype /Link
/A 383 0 R
/Border [0 0 0]
/H /I
/Rect [ 386.0347 183.0316 402.2977 192.9522 ]
>>
endobj
383 0 obj
<< /Type /Action
>>
endobj
384 0 obj
<< /Type /Annot
/Subtype /Link
/A 385 0 R
/Border [0 0 0]
/H /I
/Rect [ 370.2441 558.2693 386.5071 568.1899 ]
>>
endobj
385 0 obj
<< /Type /Action
>>
endobj
386 0 obj
<< /Type /Annot
/Subtype /Link
/A 387 0 R
/Border [0 0 0]
/H /I
/Rect [ 386.5071 558.2693 402.7701 568.1899 ]
>>
endobj
387 0 obj
<< /Type /Action
>>
endobj
388 0 obj
<< /Type /Annot
/Subtype /Link
/A 389 0 R
/Border [0 0 0]
/H /I
/Rect [ 402.7701 558.2693 419.0331 568.1899 ]
>>
endobj
389 0 obj
<< /Type /Action
>>
endobj
390 0 obj
<< /Type /Annot
/Subtype /Link
/A 391 0 R
/Border [0 0 0]
/H /I
/Rect [ 419.0331 558.2693 435.2961 568.1899 ]
>>
endobj
391 0 obj
<< /Type /Action
>>
endobj
392 0 obj
<< /Type /Annot
/Subtype /Link
/A 393 0 R
/Border [0 0 0]
/H /I
/Rect [ 192.6142 364.6981 208.8773 374.6187 ]
>>
endobj
393 0 obj
<< /Type /Action
>>
endobj
394 0 obj
<< /Type /Annot
/Subtype /Link
/A 395 0 R
/Border [0 0 0]
/H /I
/Rect [ 415.8795 352.7933 432.1425 362.7140 ]
>>
endobj
395 0 obj
<< /Type /Action
>>
endobj
396 0 obj
<< /Type /Annot
/Subtype /Link
/A 397 0 R
/Border [0 0 0]
/H /I
/Rect [ 428.6390 281.3648 444.9020 291.2855 ]
>>
endobj
397 0 obj
<< /Type /Action
>>
endobj
398 0 obj
<< /Type /Annot
/Subtype /Link
/A 399 0 R
/Border [0 0 0]
/H /I
/Rect [ 551.9212 206.8411 568.1843 216.7617 ]
>>
endobj
399 0 obj
<< /Type /Action
>>
endobj
400 0 obj
<< /Type /Annot
/Subtype /Link
/A 401 0 R
/Border [0 0 0]
/H /I
/Rect [ 386.0347 183.0316 402.2977 192.9522 ]
>>
endobj
401 0 obj
<< /Type /Action
>>
endobj
402 0 obj
<< /Type /Page
/Parent 3 0 R
/Annots [ 404 0 R 406 0 R 409 0 R 411 0 R 413 0 R 417 0 R 419 0 R 421 0 R 423 0 R 425 0 R 429 0 R 431 0 R 433 0 R 435 0 R 437 0 R ]
/Contents 403 0 R
>>
endobj
403 0 obj
<<
/Length 34440 >>
stream

0.271 0.267 0.267 rg
q
15.000 46.932 577.500 730.068 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(As expected HD participants had a lower body mass index compared to controls. One HD patient had underweight with a body )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(mass index of 16. There were however, no significant differences between groups concerning any of the clinical data \(table 1\). )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(Breath test results and clinical data showed normal distribution except for gender.)] TJ ET
BT 26.250 724.262 Td /F1 9.8 Tf  [(Results of the )] TJ ET
BT 88.572 728.150 Td /F1 8.7 Tf  [(13)] TJ ET
BT 98.209 724.262 Td /F1 9.8 Tf  [( C-sodium octanoate breath test are given in table 2. )] TJ ET
BT 327.451 728.150 Td /F1 8.7 Tf  [(13)] TJ ET
BT 337.089 724.262 Td /F1 9.8 Tf  [( CO )] TJ ET
BT 357.135 722.198 Td /F1 8.7 Tf  [(2)] TJ ET
BT 361.953 724.262 Td /F1 9.8 Tf  [( -excretion curves \(PDR\) and the percentage of )] TJ ET
BT 568.956 728.150 Td /F1 8.7 Tf  [(13)] TJ ET
BT 26.250 712.357 Td /F1 9.8 Tf  [(CO )] TJ ET
BT 43.585 710.293 Td /F1 8.7 Tf  [(2)] TJ ET
BT 48.404 712.357 Td /F1 9.8 Tf  [( cumulative values \(cPDR\) showed normal excretion of )] TJ ET
BT 287.893 716.245 Td /F1 8.7 Tf  [(13)] TJ ET
BT 297.531 712.357 Td /F1 9.8 Tf  [( C. For PDR only PDR )] TJ ET
BT 397.215 710.293 Td /F1 8.7 Tf  [(max)] TJ ET
BT 413.586 712.357 Td /F1 9.8 Tf  [( for the maximum amount of )] TJ ET
BT 537.674 716.245 Td /F1 8.7 Tf  [(13)] TJ ET
BT 547.312 712.357 Td /F1 9.8 Tf  [( CO )] TJ ET
BT 567.358 710.293 Td /F1 8.7 Tf  [(2)] TJ ET
BT 572.176 712.357 Td /F1 9.8 Tf  [( -)] TJ ET
BT 26.250 700.452 Td /F1 9.8 Tf  [(excretion reached during testing time is listed in table 2. There were no significant differences compared to controls for the )] TJ ET
BT 26.250 688.548 Td /F1 9.8 Tf  [(values decisive for the evaluation of gastric emptying, such as PDR )] TJ ET
BT 319.413 686.483 Td /F1 8.7 Tf  [(max)] TJ ET
BT 335.784 688.548 Td /F1 9.8 Tf  [( , cPDR, GEC, t )] TJ ET
BT 406.764 686.483 Td /F1 8.7 Tf  [(50)] TJ ET
BT 416.402 688.548 Td /F1 9.8 Tf  [( \(min\) and tl )] TJ ET
BT 470.582 686.483 Td /F1 8.7 Tf  [(ag)] TJ ET
BT 480.220 688.548 Td /F1 9.8 Tf  [( \(min; see table 2\). )] TJ ET
BT 26.250 676.643 Td /F1 9.8 Tf  [(Compared to standard values given in literature, the most important parameters t )] TJ ET
BT 377.396 674.579 Td /F1 8.7 Tf  [(50)] TJ ET
BT 387.034 676.643 Td /F1 9.8 Tf  [( and tl )] TJ ET
BT 416.303 674.579 Td /F1 8.7 Tf  [(ag)] TJ ET
BT 425.940 676.643 Td /F1 9.8 Tf  [( were within normal range \(t )] TJ ET
BT 548.937 674.579 Td /F1 8.7 Tf  [(50)] TJ ET
BT 558.574 676.643 Td /F1 9.8 Tf  [( < )] TJ ET
BT 26.250 664.738 Td /F1 9.8 Tf  [(200 min and tl )] TJ ET
BT 90.200 662.674 Td /F1 8.7 Tf  [(ag)] TJ ET
BT 99.838 664.738 Td /F1 9.8 Tf  [( <130 min; no data is available in literature for GEC, cPDR and PDR )] TJ ET
BT 396.520 662.674 Td /F1 8.7 Tf  [(max)] TJ ET
BT 412.892 664.738 Td /F1 9.8 Tf  [( \) and none of the patients had )] TJ ET
BT 26.250 652.833 Td /F1 9.8 Tf  [(abnormal breath test results \(see figure 1\). )] TJ ET
0.267 0.267 0.267 rg
BT 212.660 652.833 Td /F1 9.8 Tf  [([24])] TJ ET
1.000 1.000 1.000 rg
26.250 537.313 555.000 105.640 re f
0.267 0.267 0.267 rg
26.625 641.827 138.598 0.750 re f
26.625 625.946 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 631.972 Td /F4 9.8 Tf  [(OBT Parameter)] TJ ET
0.267 0.267 0.267 rg
164.473 641.827 208.576 0.750 re f
164.473 625.946 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 169.723 631.972 Td /F4 9.8 Tf  [(Results HD)] TJ ET
0.267 0.267 0.267 rg
372.299 641.827 208.576 0.750 re f
372.299 625.946 0.750 16.631 re f
580.125 625.946 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 377.549 631.972 Td /F4 9.8 Tf  [(Results Controls)] TJ ET
0.267 0.267 0.267 rg
26.625 625.946 138.598 0.750 re f
26.625 607.114 0.750 19.582 re f
0.271 0.267 0.267 rg
BT 31.875 613.731 Td /F1 9.8 Tf  [(PDR )] TJ ET
BT 55.168 611.005 Td /F1 8.7 Tf  [(max)] TJ ET
0.267 0.267 0.267 rg
164.473 625.946 208.576 0.750 re f
164.473 607.114 0.750 19.582 re f
0.271 0.267 0.267 rg
BT 169.723 616.091 Td /F1 9.8 Tf  [(9.76 � 2.866.32 � 14.18)] TJ ET
0.267 0.267 0.267 rg
372.299 625.946 208.576 0.750 re f
372.299 607.114 0.750 19.582 re f
580.125 607.114 0.750 19.582 re f
0.271 0.267 0.267 rg
BT 377.549 616.091 Td /F1 9.8 Tf  [(9.85 � 2.615.58 � 14.09)] TJ ET
0.267 0.267 0.267 rg
26.625 607.114 138.598 0.750 re f
26.625 591.233 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 597.259 Td /F1 9.8 Tf  [(cPDR)] TJ ET
0.267 0.267 0.267 rg
164.473 607.114 208.576 0.750 re f
164.473 591.233 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 169.723 597.259 Td /F1 9.8 Tf  [(23.64 � 7.92\(14.72 � 37.0\))] TJ ET
0.267 0.267 0.267 rg
372.299 607.114 208.576 0.750 re f
372.299 591.233 0.750 16.631 re f
580.125 591.233 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 377.549 597.259 Td /F1 9.8 Tf  [(25.38 � 7.92\(15.51 � 34.94\))] TJ ET
0.267 0.267 0.267 rg
26.625 591.233 138.598 0.750 re f
26.625 575.352 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 581.378 Td /F1 9.8 Tf  [(GEC)] TJ ET
0.267 0.267 0.267 rg
164.473 591.233 208.576 0.750 re f
164.473 575.352 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 169.723 581.378 Td /F1 9.8 Tf  [(2.96 � 0.84\(0.95 � 3.77\))] TJ ET
0.267 0.267 0.267 rg
372.299 591.233 208.576 0.750 re f
372.299 575.352 0.750 16.631 re f
580.125 575.352 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 377.549 581.378 Td /F1 9.8 Tf  [(2.89 � 0.36\(2.42 � 3.27\))] TJ ET
0.267 0.267 0.267 rg
26.625 575.352 138.598 0.750 re f
26.625 556.520 0.750 19.582 re f
0.271 0.267 0.267 rg
BT 31.875 563.136 Td /F1 9.8 Tf  [(t )] TJ ET
BT 37.296 560.410 Td /F1 8.7 Tf  [(50)] TJ ET
0.267 0.267 0.267 rg
164.473 575.352 208.576 0.750 re f
164.473 556.520 0.750 19.582 re f
0.271 0.267 0.267 rg
BT 169.723 565.497 Td /F1 9.8 Tf  [(129.26 � 38.84\(77.15 � 197.60\))] TJ ET
0.267 0.267 0.267 rg
372.299 575.352 208.576 0.750 re f
372.299 556.520 0.750 19.582 re f
580.125 556.520 0.750 19.582 re f
0.271 0.267 0.267 rg
BT 377.549 565.497 Td /F1 9.8 Tf  [(135.88 � 22.27\(95.74 � 167.47\))] TJ ET
0.267 0.267 0.267 rg
26.625 556.520 138.598 0.750 re f
26.625 537.688 138.598 0.750 re f
26.625 537.688 0.750 19.582 re f
0.271 0.267 0.267 rg
BT 31.875 544.304 Td /F1 9.8 Tf  [(t )] TJ ET
BT 37.296 541.578 Td /F1 8.7 Tf  [(lag)] TJ ET
0.267 0.267 0.267 rg
164.473 556.520 208.576 0.750 re f
164.473 537.688 208.576 0.750 re f
164.473 537.688 0.750 19.582 re f
0.271 0.267 0.267 rg
BT 169.723 546.665 Td /F1 9.8 Tf  [(85.45 � 25.14\(55.95 � 123.42\))] TJ ET
0.267 0.267 0.267 rg
372.299 556.520 208.576 0.750 re f
372.299 537.688 208.576 0.750 re f
372.299 537.688 0.750 19.582 re f
580.125 537.688 0.750 19.582 re f
0.271 0.267 0.267 rg
BT 377.549 546.665 Td /F1 9.8 Tf  [(80.74 � 17.33\(56.31 � 109.05\))] TJ ET
BT 26.250 490.289 Td /F4 9.8 Tf  [(Table 2)] TJ ET
BT 59.849 490.289 Td /F4 8.7 Tf  [(:)] TJ ET
BT 62.735 494.177 Td /F1 8.7 Tf  [( 13 )] TJ ET
BT 77.191 490.289 Td /F1 9.8 Tf  [( C-sodium octanoate breath test results; values are given as mean � SD; range \(min-max\) in brackets, )] TJ ET
BT 26.250 478.384 Td /F1 9.8 Tf  [(Abbreviations: PDR )] TJ ET
BT 114.029 476.320 Td /F1 8.7 Tf  [(max)] TJ ET
BT 130.401 478.384 Td /F1 9.8 Tf  [( for the maximum amount of )] TJ ET
BT 254.489 482.272 Td /F1 8.7 Tf  [(13)] TJ ET
BT 264.126 478.384 Td /F1 9.8 Tf  [( CO )] TJ ET
BT 284.172 476.320 Td /F1 8.7 Tf  [(2)] TJ ET
BT 288.991 478.384 Td /F1 9.8 Tf  [( -excretion reached during testing time [%]; cPDR � cumulative )] TJ ET
BT 26.250 466.479 Td /F1 9.8 Tf  [(exhaled )] TJ ET
BT 63.105 470.368 Td /F1 8.7 Tf  [(13)] TJ ET
BT 72.742 466.479 Td /F1 9.8 Tf  [( CO )] TJ ET
BT 92.788 464.415 Td /F1 8.7 Tf  [(2)] TJ ET
BT 97.607 466.479 Td /F1 9.8 Tf  [( \(cPDR [%]\) after 240 minutes; GEC � gastric emptying coefficient; t )] TJ ET
BT 392.925 464.415 Td /F1 8.7 Tf  [(peak)] TJ ET
BT 411.714 466.479 Td /F1 9.8 Tf  [( � time to highest exhaled )] TJ ET
BT 525.526 470.368 Td /F1 8.7 Tf  [(13)] TJ ET
BT 535.163 466.479 Td /F1 9.8 Tf  [( CO )] TJ ET
BT 555.209 464.415 Td /F1 8.7 Tf  [(2)] TJ ET
BT 26.250 454.575 Td /F1 9.8 Tf  [(value [min]; t )] TJ ET
BT 84.233 452.510 Td /F1 8.7 Tf  [(50)] TJ ET
BT 93.871 454.575 Td /F1 9.8 Tf  [( � half gastric emptying time [min]; t )] TJ ET
BT 249.929 452.510 Td /F1 8.7 Tf  [(lag)] TJ ET
BT 261.490 454.575 Td /F1 9.8 Tf  [( � Lag phase [min]. * � significant differences.)] TJ ET
0.965 0.965 0.965 rg
26.250 251.575 555.000 193.119 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 444.694 m 581.250 444.694 l 581.250 443.944 l 26.250 443.944 l  f
26.250 251.575 m 581.250 251.575 l 581.250 252.325 l 26.250 252.325 l  f
q
112.500 0 0 112.500 35.250 322.444 cm /I3 Do
Q 
q
35.250 262.825 537.000 53.619 re W n
0.271 0.267 0.267 rg
BT 35.250 306.920 Td /F4 9.8 Tf  [(Fig. 1: Gastric emptying of solids measured by 13 C sodium octanoate breath test presented as individual lag )] TJ ET
BT 35.250 295.015 Td /F4 9.8 Tf  [(phase \(tl ag \) and gastric half emptying time \(t50\) in 11 HD participants \(controls not shown\). The normal t 50 range )] TJ ET
BT 35.250 283.110 Td /F4 9.8 Tf  [(reported from literature \(<200 min\) is shown by the dotted line. A normal t lag range is reported to be below 130 )] TJ ET
BT 35.250 271.206 Td /F4 9.8 Tf  [(min. [24])] TJ ET
Q
BT 26.250 234.551 Td /F1 9.8 Tf  [(Gastroparesis Cardinal Symptom Index \(GCSI\) was 0.3855 \(SEM � 0.48; range 0 � 1.28\) and Short-Form Leeds Dyspepsia )] TJ ET
BT 26.250 222.646 Td /F1 9.8 Tf  [(Questionnaire \(SF-LDQ\) was 0.8182 \(SEM � 1.83; range 0 � 6\) for HD participants. Thus, both questionnaire results were in )] TJ ET
BT 26.250 210.741 Td /F1 9.8 Tf  [(line with published data from healthy controls, without clinical evidence of gastroparesis or dyspepsia. )] TJ ET
0.267 0.267 0.267 rg
BT 466.267 210.741 Td /F1 9.8 Tf  [([38])] TJ ET
BT 482.530 210.741 Td /F1 9.8 Tf  [([39])] TJ ET
0.271 0.267 0.267 rg
BT 498.793 210.741 Td /F1 9.8 Tf  [( GCSI was 0.3027 )] TJ ET
BT 26.250 198.837 Td /F1 9.8 Tf  [(\(SEM � 0.30; range 0 � 0.83\) and SF-LDQ was 2.273 \(SEM � 2.195; range 0 � 7\) for controls. Differences were not significant )] TJ ET
BT 26.250 186.932 Td /F1 9.8 Tf  [(\(data not shown\).)] TJ ET
BT 26.250 167.527 Td /F1 9.8 Tf  [(Explorative correlation analysis of breath test results given in table 2 with clinical symptoms from table 1 showed no significant )] TJ ET
BT 26.250 155.622 Td /F1 9.8 Tf  [(correlation, except for the cognitive sum score and t )] TJ ET
BT 252.226 153.558 Td /F1 8.7 Tf  [(50)] TJ ET
BT 261.863 155.622 Td /F1 9.8 Tf  [( \(p 0.018, r -.692\) and tl )] TJ ET
BT 366.461 153.558 Td /F1 8.7 Tf  [(ag)] TJ ET
BT 376.098 155.622 Td /F1 9.8 Tf  [( \(p 0.019, r -.688\), as well as for PDR )] TJ ET
BT 539.742 153.558 Td /F1 8.7 Tf  [(max)] TJ ET
BT 556.114 155.622 Td /F1 9.8 Tf  [( and )] TJ ET
BT 26.250 143.718 Td /F1 9.8 Tf  [(the total functional capacity \(TFC; p 0.014, r .712; no analysis of the cognitive subtests was done; see figure 2\). Especially no )] TJ ET
BT 26.250 131.813 Td /F1 9.8 Tf  [(correlation to motor symptoms was found.)] TJ ET
0.965 0.965 0.965 rg
26.250 46.932 555.000 75.000 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 121.932 m 581.250 121.932 l 581.250 121.182 l 26.250 121.182 l  f
q
225.000 0 0 59.250 35.250 52.932 cm /I5 Do
Q
q
35.250 46.932 537.000 0.000 re W n
Q
Q
q
15.000 46.932 577.500 730.068 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(As expected HD participants had a lower body mass index compared to controls. One HD patient had underweight with a body )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(mass index of 16. There were however, no significant differences between groups concerning any of the clinical data \(table 1\). )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(Breath test results and clinical data showed normal distribution except for gender.)] TJ ET
BT 26.250 724.262 Td /F1 9.8 Tf  [(Results of the )] TJ ET
BT 88.572 728.150 Td /F1 8.7 Tf  [(13)] TJ ET
BT 98.209 724.262 Td /F1 9.8 Tf  [( C-sodium octanoate breath test are given in table 2. )] TJ ET
BT 327.451 728.150 Td /F1 8.7 Tf  [(13)] TJ ET
BT 337.089 724.262 Td /F1 9.8 Tf  [( CO )] TJ ET
BT 357.135 722.198 Td /F1 8.7 Tf  [(2)] TJ ET
BT 361.953 724.262 Td /F1 9.8 Tf  [( -excretion curves \(PDR\) and the percentage of )] TJ ET
BT 568.956 728.150 Td /F1 8.7 Tf  [(13)] TJ ET
BT 26.250 712.357 Td /F1 9.8 Tf  [(CO )] TJ ET
BT 43.585 710.293 Td /F1 8.7 Tf  [(2)] TJ ET
BT 48.404 712.357 Td /F1 9.8 Tf  [( cumulative values \(cPDR\) showed normal excretion of )] TJ ET
BT 287.893 716.245 Td /F1 8.7 Tf  [(13)] TJ ET
BT 297.531 712.357 Td /F1 9.8 Tf  [( C. For PDR only PDR )] TJ ET
BT 397.215 710.293 Td /F1 8.7 Tf  [(max)] TJ ET
BT 413.586 712.357 Td /F1 9.8 Tf  [( for the maximum amount of )] TJ ET
BT 537.674 716.245 Td /F1 8.7 Tf  [(13)] TJ ET
BT 547.312 712.357 Td /F1 9.8 Tf  [( CO )] TJ ET
BT 567.358 710.293 Td /F1 8.7 Tf  [(2)] TJ ET
BT 572.176 712.357 Td /F1 9.8 Tf  [( -)] TJ ET
BT 26.250 700.452 Td /F1 9.8 Tf  [(excretion reached during testing time is listed in table 2. There were no significant differences compared to controls for the )] TJ ET
BT 26.250 688.548 Td /F1 9.8 Tf  [(values decisive for the evaluation of gastric emptying, such as PDR )] TJ ET
BT 319.413 686.483 Td /F1 8.7 Tf  [(max)] TJ ET
BT 335.784 688.548 Td /F1 9.8 Tf  [( , cPDR, GEC, t )] TJ ET
BT 406.764 686.483 Td /F1 8.7 Tf  [(50)] TJ ET
BT 416.402 688.548 Td /F1 9.8 Tf  [( \(min\) and tl )] TJ ET
BT 470.582 686.483 Td /F1 8.7 Tf  [(ag)] TJ ET
BT 480.220 688.548 Td /F1 9.8 Tf  [( \(min; see table 2\). )] TJ ET
BT 26.250 676.643 Td /F1 9.8 Tf  [(Compared to standard values given in literature, the most important parameters t )] TJ ET
BT 377.396 674.579 Td /F1 8.7 Tf  [(50)] TJ ET
BT 387.034 676.643 Td /F1 9.8 Tf  [( and tl )] TJ ET
BT 416.303 674.579 Td /F1 8.7 Tf  [(ag)] TJ ET
BT 425.940 676.643 Td /F1 9.8 Tf  [( were within normal range \(t )] TJ ET
BT 548.937 674.579 Td /F1 8.7 Tf  [(50)] TJ ET
BT 558.574 676.643 Td /F1 9.8 Tf  [( < )] TJ ET
BT 26.250 664.738 Td /F1 9.8 Tf  [(200 min and tl )] TJ ET
BT 90.200 662.674 Td /F1 8.7 Tf  [(ag)] TJ ET
BT 99.838 664.738 Td /F1 9.8 Tf  [( <130 min; no data is available in literature for GEC, cPDR and PDR )] TJ ET
BT 396.520 662.674 Td /F1 8.7 Tf  [(max)] TJ ET
BT 412.892 664.738 Td /F1 9.8 Tf  [( \) and none of the patients had )] TJ ET
BT 26.250 652.833 Td /F1 9.8 Tf  [(abnormal breath test results \(see figure 1\). )] TJ ET
0.267 0.267 0.267 rg
BT 212.660 652.833 Td /F1 9.8 Tf  [([24])] TJ ET
1.000 1.000 1.000 rg
26.250 537.313 555.000 105.640 re f
0.267 0.267 0.267 rg
26.625 641.827 138.598 0.750 re f
26.625 625.946 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 631.972 Td /F4 9.8 Tf  [(OBT Parameter)] TJ ET
0.267 0.267 0.267 rg
164.473 641.827 208.576 0.750 re f
164.473 625.946 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 169.723 631.972 Td /F4 9.8 Tf  [(Results HD)] TJ ET
0.267 0.267 0.267 rg
372.299 641.827 208.576 0.750 re f
372.299 625.946 0.750 16.631 re f
580.125 625.946 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 377.549 631.972 Td /F4 9.8 Tf  [(Results Controls)] TJ ET
0.267 0.267 0.267 rg
26.625 625.946 138.598 0.750 re f
26.625 607.114 0.750 19.582 re f
0.271 0.267 0.267 rg
BT 31.875 613.731 Td /F1 9.8 Tf  [(PDR )] TJ ET
BT 55.168 611.005 Td /F1 8.7 Tf  [(max)] TJ ET
0.267 0.267 0.267 rg
164.473 625.946 208.576 0.750 re f
164.473 607.114 0.750 19.582 re f
0.271 0.267 0.267 rg
BT 169.723 616.091 Td /F1 9.8 Tf  [(9.76 � 2.866.32 � 14.18)] TJ ET
0.267 0.267 0.267 rg
372.299 625.946 208.576 0.750 re f
372.299 607.114 0.750 19.582 re f
580.125 607.114 0.750 19.582 re f
0.271 0.267 0.267 rg
BT 377.549 616.091 Td /F1 9.8 Tf  [(9.85 � 2.615.58 � 14.09)] TJ ET
0.267 0.267 0.267 rg
26.625 607.114 138.598 0.750 re f
26.625 591.233 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 597.259 Td /F1 9.8 Tf  [(cPDR)] TJ ET
0.267 0.267 0.267 rg
164.473 607.114 208.576 0.750 re f
164.473 591.233 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 169.723 597.259 Td /F1 9.8 Tf  [(23.64 � 7.92\(14.72 � 37.0\))] TJ ET
0.267 0.267 0.267 rg
372.299 607.114 208.576 0.750 re f
372.299 591.233 0.750 16.631 re f
580.125 591.233 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 377.549 597.259 Td /F1 9.8 Tf  [(25.38 � 7.92\(15.51 � 34.94\))] TJ ET
0.267 0.267 0.267 rg
26.625 591.233 138.598 0.750 re f
26.625 575.352 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 581.378 Td /F1 9.8 Tf  [(GEC)] TJ ET
0.267 0.267 0.267 rg
164.473 591.233 208.576 0.750 re f
164.473 575.352 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 169.723 581.378 Td /F1 9.8 Tf  [(2.96 � 0.84\(0.95 � 3.77\))] TJ ET
0.267 0.267 0.267 rg
372.299 591.233 208.576 0.750 re f
372.299 575.352 0.750 16.631 re f
580.125 575.352 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 377.549 581.378 Td /F1 9.8 Tf  [(2.89 � 0.36\(2.42 � 3.27\))] TJ ET
0.267 0.267 0.267 rg
26.625 575.352 138.598 0.750 re f
26.625 556.520 0.750 19.582 re f
0.271 0.267 0.267 rg
BT 31.875 563.136 Td /F1 9.8 Tf  [(t )] TJ ET
BT 37.296 560.410 Td /F1 8.7 Tf  [(50)] TJ ET
0.267 0.267 0.267 rg
164.473 575.352 208.576 0.750 re f
164.473 556.520 0.750 19.582 re f
0.271 0.267 0.267 rg
BT 169.723 565.497 Td /F1 9.8 Tf  [(129.26 � 38.84\(77.15 � 197.60\))] TJ ET
0.267 0.267 0.267 rg
372.299 575.352 208.576 0.750 re f
372.299 556.520 0.750 19.582 re f
580.125 556.520 0.750 19.582 re f
0.271 0.267 0.267 rg
BT 377.549 565.497 Td /F1 9.8 Tf  [(135.88 � 22.27\(95.74 � 167.47\))] TJ ET
0.267 0.267 0.267 rg
26.625 556.520 138.598 0.750 re f
26.625 537.688 138.598 0.750 re f
26.625 537.688 0.750 19.582 re f
0.271 0.267 0.267 rg
BT 31.875 544.304 Td /F1 9.8 Tf  [(t )] TJ ET
BT 37.296 541.578 Td /F1 8.7 Tf  [(lag)] TJ ET
0.267 0.267 0.267 rg
164.473 556.520 208.576 0.750 re f
164.473 537.688 208.576 0.750 re f
164.473 537.688 0.750 19.582 re f
0.271 0.267 0.267 rg
BT 169.723 546.665 Td /F1 9.8 Tf  [(85.45 � 25.14\(55.95 � 123.42\))] TJ ET
0.267 0.267 0.267 rg
372.299 556.520 208.576 0.750 re f
372.299 537.688 208.576 0.750 re f
372.299 537.688 0.750 19.582 re f
580.125 537.688 0.750 19.582 re f
0.271 0.267 0.267 rg
BT 377.549 546.665 Td /F1 9.8 Tf  [(80.74 � 17.33\(56.31 � 109.05\))] TJ ET
BT 26.250 490.289 Td /F4 9.8 Tf  [(Table 2)] TJ ET
BT 59.849 490.289 Td /F4 8.7 Tf  [(:)] TJ ET
BT 62.735 494.177 Td /F1 8.7 Tf  [( 13 )] TJ ET
BT 77.191 490.289 Td /F1 9.8 Tf  [( C-sodium octanoate breath test results; values are given as mean � SD; range \(min-max\) in brackets, )] TJ ET
BT 26.250 478.384 Td /F1 9.8 Tf  [(Abbreviations: PDR )] TJ ET
BT 114.029 476.320 Td /F1 8.7 Tf  [(max)] TJ ET
BT 130.401 478.384 Td /F1 9.8 Tf  [( for the maximum amount of )] TJ ET
BT 254.489 482.272 Td /F1 8.7 Tf  [(13)] TJ ET
BT 264.126 478.384 Td /F1 9.8 Tf  [( CO )] TJ ET
BT 284.172 476.320 Td /F1 8.7 Tf  [(2)] TJ ET
BT 288.991 478.384 Td /F1 9.8 Tf  [( -excretion reached during testing time [%]; cPDR � cumulative )] TJ ET
BT 26.250 466.479 Td /F1 9.8 Tf  [(exhaled )] TJ ET
BT 63.105 470.368 Td /F1 8.7 Tf  [(13)] TJ ET
BT 72.742 466.479 Td /F1 9.8 Tf  [( CO )] TJ ET
BT 92.788 464.415 Td /F1 8.7 Tf  [(2)] TJ ET
BT 97.607 466.479 Td /F1 9.8 Tf  [( \(cPDR [%]\) after 240 minutes; GEC � gastric emptying coefficient; t )] TJ ET
BT 392.925 464.415 Td /F1 8.7 Tf  [(peak)] TJ ET
BT 411.714 466.479 Td /F1 9.8 Tf  [( � time to highest exhaled )] TJ ET
BT 525.526 470.368 Td /F1 8.7 Tf  [(13)] TJ ET
BT 535.163 466.479 Td /F1 9.8 Tf  [( CO )] TJ ET
BT 555.209 464.415 Td /F1 8.7 Tf  [(2)] TJ ET
BT 26.250 454.575 Td /F1 9.8 Tf  [(value [min]; t )] TJ ET
BT 84.233 452.510 Td /F1 8.7 Tf  [(50)] TJ ET
BT 93.871 454.575 Td /F1 9.8 Tf  [( � half gastric emptying time [min]; t )] TJ ET
BT 249.929 452.510 Td /F1 8.7 Tf  [(lag)] TJ ET
BT 261.490 454.575 Td /F1 9.8 Tf  [( � Lag phase [min]. * � significant differences.)] TJ ET
0.965 0.965 0.965 rg
26.250 251.575 555.000 193.119 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 444.694 m 581.250 444.694 l 581.250 443.944 l 26.250 443.944 l  f
26.250 251.575 m 581.250 251.575 l 581.250 252.325 l 26.250 252.325 l  f
q
112.500 0 0 112.500 35.250 322.444 cm /I3 Do
Q 
q
35.250 262.825 537.000 53.619 re W n
0.271 0.267 0.267 rg
BT 35.250 306.920 Td /F4 9.8 Tf  [(Fig. 1: Gastric emptying of solids measured by 13 C sodium octanoate breath test presented as individual lag )] TJ ET
BT 35.250 295.015 Td /F4 9.8 Tf  [(phase \(tl ag \) and gastric half emptying time \(t50\) in 11 HD participants \(controls not shown\). The normal t 50 range )] TJ ET
BT 35.250 283.110 Td /F4 9.8 Tf  [(reported from literature \(<200 min\) is shown by the dotted line. A normal t lag range is reported to be below 130 )] TJ ET
BT 35.250 271.206 Td /F4 9.8 Tf  [(min. [24])] TJ ET
Q
BT 26.250 234.551 Td /F1 9.8 Tf  [(Gastroparesis Cardinal Symptom Index \(GCSI\) was 0.3855 \(SEM � 0.48; range 0 � 1.28\) and Short-Form Leeds Dyspepsia )] TJ ET
BT 26.250 222.646 Td /F1 9.8 Tf  [(Questionnaire \(SF-LDQ\) was 0.8182 \(SEM � 1.83; range 0 � 6\) for HD participants. Thus, both questionnaire results were in )] TJ ET
BT 26.250 210.741 Td /F1 9.8 Tf  [(line with published data from healthy controls, without clinical evidence of gastroparesis or dyspepsia. )] TJ ET
0.267 0.267 0.267 rg
BT 466.267 210.741 Td /F1 9.8 Tf  [([38])] TJ ET
BT 482.530 210.741 Td /F1 9.8 Tf  [([39])] TJ ET
0.271 0.267 0.267 rg
BT 498.793 210.741 Td /F1 9.8 Tf  [( GCSI was 0.3027 )] TJ ET
BT 26.250 198.837 Td /F1 9.8 Tf  [(\(SEM � 0.30; range 0 � 0.83\) and SF-LDQ was 2.273 \(SEM � 2.195; range 0 � 7\) for controls. Differences were not significant )] TJ ET
BT 26.250 186.932 Td /F1 9.8 Tf  [(\(data not shown\).)] TJ ET
BT 26.250 167.527 Td /F1 9.8 Tf  [(Explorative correlation analysis of breath test results given in table 2 with clinical symptoms from table 1 showed no significant )] TJ ET
BT 26.250 155.622 Td /F1 9.8 Tf  [(correlation, except for the cognitive sum score and t )] TJ ET
BT 252.226 153.558 Td /F1 8.7 Tf  [(50)] TJ ET
BT 261.863 155.622 Td /F1 9.8 Tf  [( \(p 0.018, r -.692\) and tl )] TJ ET
BT 366.461 153.558 Td /F1 8.7 Tf  [(ag)] TJ ET
BT 376.098 155.622 Td /F1 9.8 Tf  [( \(p 0.019, r -.688\), as well as for PDR )] TJ ET
BT 539.742 153.558 Td /F1 8.7 Tf  [(max)] TJ ET
BT 556.114 155.622 Td /F1 9.8 Tf  [( and )] TJ ET
BT 26.250 143.718 Td /F1 9.8 Tf  [(the total functional capacity \(TFC; p 0.014, r .712; no analysis of the cognitive subtests was done; see figure 2\). Especially no )] TJ ET
BT 26.250 131.813 Td /F1 9.8 Tf  [(correlation to motor symptoms was found.)] TJ ET
0.965 0.965 0.965 rg
26.250 46.932 555.000 75.000 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 121.932 m 581.250 121.932 l 581.250 121.182 l 26.250 121.182 l  f
q
225.000 0 0 59.250 35.250 52.932 cm /I7 Do
Q
q
35.250 46.932 537.000 0.000 re W n
Q
Q
q
15.000 46.932 577.500 730.068 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(As expected HD participants had a lower body mass index compared to controls. One HD patient had underweight with a body )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(mass index of 16. There were however, no significant differences between groups concerning any of the clinical data \(table 1\). )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(Breath test results and clinical data showed normal distribution except for gender.)] TJ ET
BT 26.250 724.262 Td /F1 9.8 Tf  [(Results of the )] TJ ET
BT 88.572 728.150 Td /F1 8.7 Tf  [(13)] TJ ET
BT 98.209 724.262 Td /F1 9.8 Tf  [( C-sodium octanoate breath test are given in table 2. )] TJ ET
BT 327.451 728.150 Td /F1 8.7 Tf  [(13)] TJ ET
BT 337.089 724.262 Td /F1 9.8 Tf  [( CO )] TJ ET
BT 357.135 722.198 Td /F1 8.7 Tf  [(2)] TJ ET
BT 361.953 724.262 Td /F1 9.8 Tf  [( -excretion curves \(PDR\) and the percentage of )] TJ ET
BT 568.956 728.150 Td /F1 8.7 Tf  [(13)] TJ ET
BT 26.250 712.357 Td /F1 9.8 Tf  [(CO )] TJ ET
BT 43.585 710.293 Td /F1 8.7 Tf  [(2)] TJ ET
BT 48.404 712.357 Td /F1 9.8 Tf  [( cumulative values \(cPDR\) showed normal excretion of )] TJ ET
BT 287.893 716.245 Td /F1 8.7 Tf  [(13)] TJ ET
BT 297.531 712.357 Td /F1 9.8 Tf  [( C. For PDR only PDR )] TJ ET
BT 397.215 710.293 Td /F1 8.7 Tf  [(max)] TJ ET
BT 413.586 712.357 Td /F1 9.8 Tf  [( for the maximum amount of )] TJ ET
BT 537.674 716.245 Td /F1 8.7 Tf  [(13)] TJ ET
BT 547.312 712.357 Td /F1 9.8 Tf  [( CO )] TJ ET
BT 567.358 710.293 Td /F1 8.7 Tf  [(2)] TJ ET
BT 572.176 712.357 Td /F1 9.8 Tf  [( -)] TJ ET
BT 26.250 700.452 Td /F1 9.8 Tf  [(excretion reached during testing time is listed in table 2. There were no significant differences compared to controls for the )] TJ ET
BT 26.250 688.548 Td /F1 9.8 Tf  [(values decisive for the evaluation of gastric emptying, such as PDR )] TJ ET
BT 319.413 686.483 Td /F1 8.7 Tf  [(max)] TJ ET
BT 335.784 688.548 Td /F1 9.8 Tf  [( , cPDR, GEC, t )] TJ ET
BT 406.764 686.483 Td /F1 8.7 Tf  [(50)] TJ ET
BT 416.402 688.548 Td /F1 9.8 Tf  [( \(min\) and tl )] TJ ET
BT 470.582 686.483 Td /F1 8.7 Tf  [(ag)] TJ ET
BT 480.220 688.548 Td /F1 9.8 Tf  [( \(min; see table 2\). )] TJ ET
BT 26.250 676.643 Td /F1 9.8 Tf  [(Compared to standard values given in literature, the most important parameters t )] TJ ET
BT 377.396 674.579 Td /F1 8.7 Tf  [(50)] TJ ET
BT 387.034 676.643 Td /F1 9.8 Tf  [( and tl )] TJ ET
BT 416.303 674.579 Td /F1 8.7 Tf  [(ag)] TJ ET
BT 425.940 676.643 Td /F1 9.8 Tf  [( were within normal range \(t )] TJ ET
BT 548.937 674.579 Td /F1 8.7 Tf  [(50)] TJ ET
BT 558.574 676.643 Td /F1 9.8 Tf  [( < )] TJ ET
BT 26.250 664.738 Td /F1 9.8 Tf  [(200 min and tl )] TJ ET
BT 90.200 662.674 Td /F1 8.7 Tf  [(ag)] TJ ET
BT 99.838 664.738 Td /F1 9.8 Tf  [( <130 min; no data is available in literature for GEC, cPDR and PDR )] TJ ET
BT 396.520 662.674 Td /F1 8.7 Tf  [(max)] TJ ET
BT 412.892 664.738 Td /F1 9.8 Tf  [( \) and none of the patients had )] TJ ET
BT 26.250 652.833 Td /F1 9.8 Tf  [(abnormal breath test results \(see figure 1\). )] TJ ET
0.267 0.267 0.267 rg
BT 212.660 652.833 Td /F1 9.8 Tf  [([24])] TJ ET
1.000 1.000 1.000 rg
26.250 537.313 555.000 105.640 re f
0.267 0.267 0.267 rg
26.625 641.827 138.598 0.750 re f
26.625 625.946 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 631.972 Td /F4 9.8 Tf  [(OBT Parameter)] TJ ET
0.267 0.267 0.267 rg
164.473 641.827 208.576 0.750 re f
164.473 625.946 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 169.723 631.972 Td /F4 9.8 Tf  [(Results HD)] TJ ET
0.267 0.267 0.267 rg
372.299 641.827 208.576 0.750 re f
372.299 625.946 0.750 16.631 re f
580.125 625.946 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 377.549 631.972 Td /F4 9.8 Tf  [(Results Controls)] TJ ET
0.267 0.267 0.267 rg
26.625 625.946 138.598 0.750 re f
26.625 607.114 0.750 19.582 re f
0.271 0.267 0.267 rg
BT 31.875 613.731 Td /F1 9.8 Tf  [(PDR )] TJ ET
BT 55.168 611.005 Td /F1 8.7 Tf  [(max)] TJ ET
0.267 0.267 0.267 rg
164.473 625.946 208.576 0.750 re f
164.473 607.114 0.750 19.582 re f
0.271 0.267 0.267 rg
BT 169.723 616.091 Td /F1 9.8 Tf  [(9.76 � 2.866.32 � 14.18)] TJ ET
0.267 0.267 0.267 rg
372.299 625.946 208.576 0.750 re f
372.299 607.114 0.750 19.582 re f
580.125 607.114 0.750 19.582 re f
0.271 0.267 0.267 rg
BT 377.549 616.091 Td /F1 9.8 Tf  [(9.85 � 2.615.58 � 14.09)] TJ ET
0.267 0.267 0.267 rg
26.625 607.114 138.598 0.750 re f
26.625 591.233 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 597.259 Td /F1 9.8 Tf  [(cPDR)] TJ ET
0.267 0.267 0.267 rg
164.473 607.114 208.576 0.750 re f
164.473 591.233 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 169.723 597.259 Td /F1 9.8 Tf  [(23.64 � 7.92\(14.72 � 37.0\))] TJ ET
0.267 0.267 0.267 rg
372.299 607.114 208.576 0.750 re f
372.299 591.233 0.750 16.631 re f
580.125 591.233 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 377.549 597.259 Td /F1 9.8 Tf  [(25.38 � 7.92\(15.51 � 34.94\))] TJ ET
0.267 0.267 0.267 rg
26.625 591.233 138.598 0.750 re f
26.625 575.352 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 581.378 Td /F1 9.8 Tf  [(GEC)] TJ ET
0.267 0.267 0.267 rg
164.473 591.233 208.576 0.750 re f
164.473 575.352 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 169.723 581.378 Td /F1 9.8 Tf  [(2.96 � 0.84\(0.95 � 3.77\))] TJ ET
0.267 0.267 0.267 rg
372.299 591.233 208.576 0.750 re f
372.299 575.352 0.750 16.631 re f
580.125 575.352 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 377.549 581.378 Td /F1 9.8 Tf  [(2.89 � 0.36\(2.42 � 3.27\))] TJ ET
0.267 0.267 0.267 rg
26.625 575.352 138.598 0.750 re f
26.625 556.520 0.750 19.582 re f
0.271 0.267 0.267 rg
BT 31.875 563.136 Td /F1 9.8 Tf  [(t )] TJ ET
BT 37.296 560.410 Td /F1 8.7 Tf  [(50)] TJ ET
0.267 0.267 0.267 rg
164.473 575.352 208.576 0.750 re f
164.473 556.520 0.750 19.582 re f
0.271 0.267 0.267 rg
BT 169.723 565.497 Td /F1 9.8 Tf  [(129.26 � 38.84\(77.15 � 197.60\))] TJ ET
0.267 0.267 0.267 rg
372.299 575.352 208.576 0.750 re f
372.299 556.520 0.750 19.582 re f
580.125 556.520 0.750 19.582 re f
0.271 0.267 0.267 rg
BT 377.549 565.497 Td /F1 9.8 Tf  [(135.88 � 22.27\(95.74 � 167.47\))] TJ ET
0.267 0.267 0.267 rg
26.625 556.520 138.598 0.750 re f
26.625 537.688 138.598 0.750 re f
26.625 537.688 0.750 19.582 re f
0.271 0.267 0.267 rg
BT 31.875 544.304 Td /F1 9.8 Tf  [(t )] TJ ET
BT 37.296 541.578 Td /F1 8.7 Tf  [(lag)] TJ ET
0.267 0.267 0.267 rg
164.473 556.520 208.576 0.750 re f
164.473 537.688 208.576 0.750 re f
164.473 537.688 0.750 19.582 re f
0.271 0.267 0.267 rg
BT 169.723 546.665 Td /F1 9.8 Tf  [(85.45 � 25.14\(55.95 � 123.42\))] TJ ET
0.267 0.267 0.267 rg
372.299 556.520 208.576 0.750 re f
372.299 537.688 208.576 0.750 re f
372.299 537.688 0.750 19.582 re f
580.125 537.688 0.750 19.582 re f
0.271 0.267 0.267 rg
BT 377.549 546.665 Td /F1 9.8 Tf  [(80.74 � 17.33\(56.31 � 109.05\))] TJ ET
BT 26.250 490.289 Td /F4 9.8 Tf  [(Table 2)] TJ ET
BT 59.849 490.289 Td /F4 8.7 Tf  [(:)] TJ ET
BT 62.735 494.177 Td /F1 8.7 Tf  [( 13 )] TJ ET
BT 77.191 490.289 Td /F1 9.8 Tf  [( C-sodium octanoate breath test results; values are given as mean � SD; range \(min-max\) in brackets, )] TJ ET
BT 26.250 478.384 Td /F1 9.8 Tf  [(Abbreviations: PDR )] TJ ET
BT 114.029 476.320 Td /F1 8.7 Tf  [(max)] TJ ET
BT 130.401 478.384 Td /F1 9.8 Tf  [( for the maximum amount of )] TJ ET
BT 254.489 482.272 Td /F1 8.7 Tf  [(13)] TJ ET
BT 264.126 478.384 Td /F1 9.8 Tf  [( CO )] TJ ET
BT 284.172 476.320 Td /F1 8.7 Tf  [(2)] TJ ET
BT 288.991 478.384 Td /F1 9.8 Tf  [( -excretion reached during testing time [%]; cPDR � cumulative )] TJ ET
BT 26.250 466.479 Td /F1 9.8 Tf  [(exhaled )] TJ ET
BT 63.105 470.368 Td /F1 8.7 Tf  [(13)] TJ ET
BT 72.742 466.479 Td /F1 9.8 Tf  [( CO )] TJ ET
BT 92.788 464.415 Td /F1 8.7 Tf  [(2)] TJ ET
BT 97.607 466.479 Td /F1 9.8 Tf  [( \(cPDR [%]\) after 240 minutes; GEC � gastric emptying coefficient; t )] TJ ET
BT 392.925 464.415 Td /F1 8.7 Tf  [(peak)] TJ ET
BT 411.714 466.479 Td /F1 9.8 Tf  [( � time to highest exhaled )] TJ ET
BT 525.526 470.368 Td /F1 8.7 Tf  [(13)] TJ ET
BT 535.163 466.479 Td /F1 9.8 Tf  [( CO )] TJ ET
BT 555.209 464.415 Td /F1 8.7 Tf  [(2)] TJ ET
BT 26.250 454.575 Td /F1 9.8 Tf  [(value [min]; t )] TJ ET
BT 84.233 452.510 Td /F1 8.7 Tf  [(50)] TJ ET
BT 93.871 454.575 Td /F1 9.8 Tf  [( � half gastric emptying time [min]; t )] TJ ET
BT 249.929 452.510 Td /F1 8.7 Tf  [(lag)] TJ ET
BT 261.490 454.575 Td /F1 9.8 Tf  [( � Lag phase [min]. * � significant differences.)] TJ ET
0.965 0.965 0.965 rg
26.250 251.575 555.000 193.119 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 444.694 m 581.250 444.694 l 581.250 443.944 l 26.250 443.944 l  f
26.250 251.575 m 581.250 251.575 l 581.250 252.325 l 26.250 252.325 l  f
q
112.500 0 0 112.500 35.250 322.444 cm /I3 Do
Q 
q
35.250 262.825 537.000 53.619 re W n
0.271 0.267 0.267 rg
BT 35.250 306.920 Td /F4 9.8 Tf  [(Fig. 1: Gastric emptying of solids measured by 13 C sodium octanoate breath test presented as individual lag )] TJ ET
BT 35.250 295.015 Td /F4 9.8 Tf  [(phase \(tl ag \) and gastric half emptying time \(t50\) in 11 HD participants \(controls not shown\). The normal t 50 range )] TJ ET
BT 35.250 283.110 Td /F4 9.8 Tf  [(reported from literature \(<200 min\) is shown by the dotted line. A normal t lag range is reported to be below 130 )] TJ ET
BT 35.250 271.206 Td /F4 9.8 Tf  [(min. [24])] TJ ET
Q
BT 26.250 234.551 Td /F1 9.8 Tf  [(Gastroparesis Cardinal Symptom Index \(GCSI\) was 0.3855 \(SEM � 0.48; range 0 � 1.28\) and Short-Form Leeds Dyspepsia )] TJ ET
BT 26.250 222.646 Td /F1 9.8 Tf  [(Questionnaire \(SF-LDQ\) was 0.8182 \(SEM � 1.83; range 0 � 6\) for HD participants. Thus, both questionnaire results were in )] TJ ET
BT 26.250 210.741 Td /F1 9.8 Tf  [(line with published data from healthy controls, without clinical evidence of gastroparesis or dyspepsia. )] TJ ET
0.267 0.267 0.267 rg
BT 466.267 210.741 Td /F1 9.8 Tf  [([38])] TJ ET
BT 482.530 210.741 Td /F1 9.8 Tf  [([39])] TJ ET
0.271 0.267 0.267 rg
BT 498.793 210.741 Td /F1 9.8 Tf  [( GCSI was 0.3027 )] TJ ET
BT 26.250 198.837 Td /F1 9.8 Tf  [(\(SEM � 0.30; range 0 � 0.83\) and SF-LDQ was 2.273 \(SEM � 2.195; range 0 � 7\) for controls. Differences were not significant )] TJ ET
BT 26.250 186.932 Td /F1 9.8 Tf  [(\(data not shown\).)] TJ ET
BT 26.250 167.527 Td /F1 9.8 Tf  [(Explorative correlation analysis of breath test results given in table 2 with clinical symptoms from table 1 showed no significant )] TJ ET
BT 26.250 155.622 Td /F1 9.8 Tf  [(correlation, except for the cognitive sum score and t )] TJ ET
BT 252.226 153.558 Td /F1 8.7 Tf  [(50)] TJ ET
BT 261.863 155.622 Td /F1 9.8 Tf  [( \(p 0.018, r -.692\) and tl )] TJ ET
BT 366.461 153.558 Td /F1 8.7 Tf  [(ag)] TJ ET
BT 376.098 155.622 Td /F1 9.8 Tf  [( \(p 0.019, r -.688\), as well as for PDR )] TJ ET
BT 539.742 153.558 Td /F1 8.7 Tf  [(max)] TJ ET
BT 556.114 155.622 Td /F1 9.8 Tf  [( and )] TJ ET
BT 26.250 143.718 Td /F1 9.8 Tf  [(the total functional capacity \(TFC; p 0.014, r .712; no analysis of the cognitive subtests was done; see figure 2\). Especially no )] TJ ET
BT 26.250 131.813 Td /F1 9.8 Tf  [(correlation to motor symptoms was found.)] TJ ET
0.965 0.965 0.965 rg
26.250 46.932 555.000 75.000 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 121.932 m 581.250 121.932 l 581.250 121.182 l 26.250 121.182 l  f
q
225.000 0 0 59.250 35.250 52.932 cm /I9 Do
Q
q
35.250 46.932 537.000 0.000 re W n
Q
Q
q
112.500 0 0 112.500 35.250 322.444 cm /I3 Do
Q 
q
225.000 0 0 59.250 35.250 52.932 cm /I11 Do
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
404 0 obj
<< /Type /Annot
/Subtype /Link
/A 405 0 R
/Border [0 0 0]
/H /I
/Rect [ 212.6602 651.9316 228.9232 661.8522 ]
>>
endobj
405 0 obj
<< /Type /Action
>>
endobj
406 0 obj
<< /Type /Annot
/Subtype /Link
/A 407 0 R
/Border [0 0 0]
/H /I
/Rect [ 35.2500 322.4437 147.7500 434.9437 ]
>>
endobj
407 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/files/2011/11/geparametershd.jpg)
>>
endobj
408 0 obj
<<
/Type /XObject
/Subtype /Image
/Width 150
/Height 150
/ColorSpace /DeviceRGB
/Filter /DCTDecode
/BitsPerComponent 8
/Length 6022>>
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�
$4�%�&'()*56789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz��������������������������������������������������������������������������
?�Q�Q�/�k�?h��~$�e�4�<04Y/��䭾���%܆7�m���
,��#�
�(fr.�sG5�?��k�x?��,��<3�iV0[�w1K'�o@�I�ܤ�vC5�_-K$y
�����h�Դ�>�Ŗ7�Ժ�����JӮL����[Ea)"��J��' ����ޏƀ�9�ǽ�'4sK�z?Nh���4���/�G^��/4~4~4���K��?n
���@	�r��x7�ͅ����9�����o�[���%H��Wz�����Bk��o���=�G��<=�x��/2K��X�&��y��W�H�DT���Y���X
E���o5K��B4#s�Yg^�����ڈb|�T�q�;��9�1�|N����E�4�m#I��f� ���Gy���f,ORI'�XW߶w����Z94�얐�ַ�f�G�\E�a-�
e%V��?z��b�c���㟌���|w�P>5���F��;�y���ʒ2��#a���H4
�7q^
�����o�x���'���oE��o��3�-<	d�Tnh��.�y�����~%�M��7��9�Aw�\{������N�P��g܎c�*��H��	��8����?+I~9��77�L�S��Ί	1w�[�٣�K�VA#;jJ
�@��g�~,E�%�U�D�|9��m}3PXg�� h������*�*�piT��)8���a��Ǻ���[��w�O�tI5�n'��S�x%��7�LQ֚N���K�`��������>�u��zF��iZ�ڋ.�#��ͯ�J�̑
��zR���9��#�
�Wq_-^x�~4����*����x-<I�t�up�i����� ��U@�}��s���[x��'�>+���Ε�kDX��%���lD�F�:�v��v(#/�)+�p��� WqG�߄�%�ϧ�>1�V���u���(�I5,C(��D�q�|ɦ�%�i���x����|N�Ƨ�����0j�n/�kvI�ya7�����
�9*�>��+<g��<����fݛo#;�Hc\s�]JVu�ƾeV��U•"�?�3��79ue��(g�8�3��<�uv�<c�jʞV�k}��b���s+(� ��m��?M��z��f͛o#;�9�q�9ue��(c�+"h�:]�$.�9R̡���8Ϫ���@��_�[|p�����x�\�奝�z�
�\�y1��q�"+a���Rs�W�沼M���zC���k���$q��i��".Ovf���꿱߄��OZ��u�]�h�;GMn�ew1�i�a�>s���-`�P"���������
��W��?�6���յX�{���u<�1DU����UP0W�j_>��$��?}�
�Z��
��e=�$�v�̒�~U�"��=k������
���jVھ�w��$�yg �91v�Gp��GPA�@�<7��cI�������=?��}y�@�ގ1�&�c����|��?��}y�Z9dPh�ގ1�&�c�'>�O��^z�<7��1��`['}���o��Z�ȣ"�3���uۍ&�m��N0��o��S��
��M�ۀ1l�aˌq��[�sִr(��g/��uۍ*�m�\['r�vr[�sօ�ގ�v�VCn��8×㳒�ROZ�ȣ"�3W�z:mۤ�.�mŲq�.1�g%����/��tٷI�]�ۋd×㳒�ROZ�ȣ"�3��z:lۥY.�mŲ
�r�vbX{�z�r�cD02�.�4��t@b�q�%��$��\��~-|H��i��[˝>�R�B�!�tV�#�%��m��@W�/�?|,���!�"���,��*���J��"��<�'�\���i<7�dzf�d�6�Ų
�X��0�$���'�
~��8���
������_'[��!�thB/��ɓ�����k�̌Pt~�!Ǘ�Y&`�n��qӦY�Տ���E��h?�P�i�{&��i�U������P�x��9�����c�29ÑК���3@)���N�_�<s�WL���O�^⼾�u;�k&����b?���!��_Tޣ�r����e���M/����j��^�r�b=��
����<��GMĮ�.@P�^g���K�w���?��-z^�7R�ڌ�n�u���$���/x:�x��/il&[�D�xq%w��M��.A����j��u����gӼ)c�	k7�> �gDڽ�Ⱦ�f�b��;���(-�׸�M�n�ϵ4���K�j�<c��^?����t�/f�Cl�sC�I���}h��Y���4�٭���Yj���U���'@�+3�F}�pR�Ϳd��hs)e#?�Wg��j?��?dO˪�Y�(:�͞�e��"��̍+��.��(�1�@m��}��c���6Vp �{x�qƣ���¬n��<;�|)�WC�k�Z�v�Ki��5�R��]�p���">�s�y�2�%��'ԭ�V�ono
ݙ�[���~u�ؽq�������4��p�{�@)��gw��h�K�����|�x��4����������g��1�IN7�ʂ3�g# �4s@
�H�c�SQ����H�|Bf���k��oJA�i�&�mm-�z�b��

���4봏��A�{���to,��լ�R��M^G���}���B�,��.����3����ۣ��R����Q��Kϥy��:�)ֵ�CP�c�����Z{����If��,��,ĒI'$��,���%x��Ƈm�ɪMe�[��Y��n��:`�0D�۰�G����3OK�s�ǀ4�G�B��x~�C9����I�
|�a� �[���5��O��=��\Y�.�f���|�[����5bco>�J�?|	ዝ��a�we&��F�Ĭ��18�{J��J�j/ٻ�D���ߊ4��('�K�"���M#�r;��~�͎3�����>����O��,�mum+�w�.t��-��6�XAʴA��#�z�O�>��xk�_��0j��}�mV��!��t[ky�ܥ[l���T�py��9����'җ�9����.��X4�p�I�i��umh��e
^}�HLd��.y�R�5/h������&�>���P��6����1۞(���|�{�x�ö�z��q���E`�\�ʌ�CFՉ�9�ڻO��������<����f�ʛ[i��x�Ÿ�~'���X|W�PԭQl��K�]�e�E�Y�F�RT�2
���@Ь�1���:df���C;����2ē�$����E/4PsG4�4`��?ioxC����:�Ķ�N���t�1iptX�zOy{�L��L�;��
�z�;�W��s�?=�
�]9~ (�a���y��,6�yI��H�C�5I$`�
�Ye�"�eP�>���g��ǽy��#��|Q�Q'�4uD@�)��(ӹ��\9�S�?Û��-���]�YGor�Q�b�$��ц0�ڼ�O�~6�<y���߈��t�m$7:��.곙.[��ˆa�
����h�>}�샤�gM���5����,�ell^&�Y�1a#�,�A����ŗ�|?g�i�"YZ)XIJnIbKI$�Z�4`�sG4�4`�sG4�4`�sG4�4`�sG4�4`��)ph����֗cހ8ߋ���U�:��N,�&�G���	��T�%g������p2pq���x��w�|/&����z���H��
6��Q�a�<$���K�ʭ���k��KI�߆�
]�[�&�#
Ż3&���)�e �

C��h��9o�h6�i�B��Y丑�F�Y$�Fg���ٝس$�@��4o���#���P���F���:����1^��z1�@g�
�?��_�"�?��A}�M|;�,����om--�if�}�#�e�����zW��޸�x�����W�om����Ia��xb�Y����FR~Em���
��
�?��_�"�?���Ѿ������-C��W�cތ{����F���:����1G�4o���#���P������
��Ѿ������-C��Q�
�?��_�"�?��zf=�ǽy��4o���#���P���F���:����1^��z��?����w:Ư;���4�/(�Is��laFI h������	M��{p"���Ţ�6�S�S�8 �EO�
�?��_�"�?��u����K�3Z]iz�ϩ���ܼ�sJ�	1烏J�ǽy��4o���#���P��W�cފL{яz\ZLZ6Ѷ�֌ZLQ��Z��[��iW�X����H] �(ɐ�
�O
�����r�~%i�
�%���j�V�$��Z�b�A�Ɍ1 (�A$(�X����i��g�*�]�����_�{Q��6(k	-�������J.Q�$Y��(���g�w�Y�S�
Ė|p��~�@�i�c��WV���$�~�����#����<�Xh�=���� Kkh��q��E�ē�rOP>��
�Z>��j���VV�[�jR&׺tP�V�͌�q�zt��{с�K��@	�1�F��b�{с�F�Cyw�g=����Z�K,ҰT�e���
$���ş<E�ƞ��|Asc�Isq$Z���@�@H��F)q��K�)?�$
���j�u�V���~"��	_�Ay�G}3X�zչ�E>�s{��J���B�6�ݾ�&��gcr��Mc^��5n�./�yX��&�lF�(i6���0��j�����ëo�4�:ݡ���Y���Y��R�I<��dl����0=h���m`z�@qG`Q�Gq@i�Ϗ��ş|<iEƿ��C��G
��R<bG<d1�#�`�ڤן�m���^A�o%�#Ե
��s�<��� �5WF�3Dr%X�"��h�:{G��x��o�=�+��o���7S��7\2H�+�HV��h�n���Vh������~{�����$���f999v���5�B��7�
�~ Z�o����P�l,��V`
 `�cϖ��Q�`Q�P
�FQ�e��Z
�wP���ou��ai#���qr��ƀ�2NIu$MxV��@��_�c�N��?tM]m�G�dI�Z��VM��fO#i
�o�)�a?D�T�C�Z}at�Q����k�
��b�2�ݰ1'nq�Mx�왤��=׋�u
/P��]=5�.�a���Ҍ��N#"�d(�=�qG`Q��8��0(��(�(���
(�`QE��(��'Q@����0(QER`E����\
(��?��
endstream
endobj
409 0 obj
<< /Type /Annot
/Subtype /Link
/A 410 0 R
/Border [0 0 0]
/H /I
/Rect [ 466.2675 209.8396 482.5305 219.7602 ]
>>
endobj
410 0 obj
<< /Type /Action
>>
endobj
411 0 obj
<< /Type /Annot
/Subtype /Link
/A 412 0 R
/Border [0 0 0]
/H /I
/Rect [ 482.5305 209.8396 498.7935 219.7602 ]
>>
endobj
412 0 obj
<< /Type /Action
>>
endobj
413 0 obj
<< /Type /Annot
/Subtype /Link
/A 414 0 R
/Border [0 0 0]
/H /I
/Rect [ 35.2500 52.9320 260.2500 112.1820 ]
>>
endobj
414 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/files/2011/11/abbildungenkorrelationenfinal.png)
>>
endobj
415 0 obj
<<
/Type /XObject
/Subtype /Image
/Width 300
/Height 79
/Filter /FlateDecode
/DecodeParms << /Predictor 15 /Colors 1 /Columns 300 /BitsPerComponent 8>>
/ColorSpace /DeviceGray
/BitsPerComponent 8
/Length 212>>
stream
x���1���@��Cш�`b�+�j����\��Zo3���O<��8���Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�f�a�
endstream
endobj
416 0 obj
<<
/Type /XObject
/Subtype /Image
/Width 300
/Height 79
/SMask 415 0 R
/Filter /FlateDecode
/DecodeParms << /Predictor 15 /Colors 3 /Columns 300 /BitsPerComponent 8>>
/ColorSpace /DeviceRGB
/BitsPerComponent 8
/Length 11973>>
stream
x��]�o���Y�E.���^�KR�x�)Y�h9��
#�$H�?$@��~3�H��-H�H�	�%�AI�u��E���\.w��^�=tܪ����q�3=�u����gv˶mQL�m[��6�8=��#bF��(i|I��M'���w�\
+�)j��ש6H@&A~8dT�dگ���	m@V�(���y��R p��N8�t�����\:��O������H$"�P`���e
6�d���b<���M�������B���xė�bL�	�X�555��xF���r����χ���w�d2GGG������n�[�&��P�T���R���2���6��q{{{dd�db��E�e��/����D"�x���ڶm��R��+�������
A
�Trckk��ٳ.����������455�B������J������~������A.�K&��\�w�Q�hi��
���V9	�ř%��,�	GGGsss|����4����7��t�eY[[[����l6�J]�vmiiɲ����h4Z(Μ9���ס��B�0	�,��eY2����LNN�\���y۶GFFNNN�^o:�N&����;;;{���B��L2�Wq��������nmm}��Q&�y�������r��~�?�H���p8���ɮ]%
�|>_VV���E1n��Z��H=99B�|>�-�NWVV��hc*����tzaa���/��y�^�1�
�����Ϟ=[(jjj.\���d2�L(���H�әL���Ƕm���V�м��\뛿�2������m����O��������̯�}���O`�D"X�uuu	!,�:s�lG'�SSS^�7��F��P(���!Oq�I�U�333�m_�p�2��鉉���~�������l����}}}�pX��wvvFFF�߿��xΟ?o���{�޲�2�����,����P���Ր�+-�
WM�ٔ�'*yy���+�����E+V���'�z3V���uRJ�af���hiiB�������C���jS�Z��ӳ��Y^^>::����G���m�۶+++�\�RSS�vD��x.^�(gH,;::���m{hh�t:��ze5��Y��\��^�S��:���v�OwQ_瑇l�d2�����LJ�����u��uJ̈́�BvB9���7#V,l�կ~���m���7���O%��nUUUOOOWWW{{;<
ã�G^�����2����TW�Κ�˲���s�\ww�l���p��R������I>����ϑ":e�F��R���_>���rB�|>�"��%tJ��u���H�$R��?�����?���p8���S�Ȅ��ei�I+z6H�%#���'s�y�@��u*���׿�ӟ�t�ʕ���oN4��vɠ�At4���(��������v(D������~���������KKK�\��I����rtzzzzz���777�b�������s�Ρ�&����B���
Jӹ
zK�O�n	��
+�*/�mnnڶ-/	��a����������ʆ��������D"���+������r$AI����*Ħ~�.
S�HŎ��}��G�|�ɵkג�$�
3�
j�!k���l1u�m�����---���H�Le���̏~�#�-Ow���N�3	[[[C�P.��,+������P��|���
yE�c�;��	�:6� �P���"'�p�\n��eP#[-��`��>�f�n��������իWʘT*������&/��f>[!Q`A�Eq���y(�$�q�Y`nn��?��������myr��v�i��I�E�
(4[�E���A�ж��O����TTT ]��������>��B�`����d&acc#+��?���!5��a@)��e;�TK�>����F/_���Z�s3�t!INB�YWW����Ɵ�ĩ�e�)����O������ׯ��FD��4������h>������H��

���B�b���>��
k<�X�,��m��Й3g�ܜ��W���{��0<�o<(?���}%���3����m�'''������o��T���x��5�H�lt	p:K�adIt6�C�Xɬ@�vԑ��6�
)��56R�p��?�F򩵬I�k��l�Z��hv���*�Q��:K���j��Yb/�FCh���sss###jꀢ�Q��������Q�.�� ��������S-2�]���I�IF�N�P�N�ŝ�PҭC��l4�u�bqg������R���6۸N3𗬢tD���777���a��Q
�u�C�^�:�`���1r�NZV4�k�4���@�ģsU��A2]V,t��
wj*������Q��nS/JI�$�h/:����
����etB����T*500@-���u�;�Q�K7�-@H
;�����d C�a-A�خ�4��l���
�F�9�چ~�"����S2�pT�P��ŕ�V/ը+چ1Z^^�d2gΜa�׶m���nZT tۍ�����*	��-�lGtȠ�5�����P���_h**��F��6��nS�T���T�E�
t�������\.
��Ѩ��[\\���
�V���+++���=zq��P4??_YY����b�
O�R333������p��A��]l�Cm���!u�3�]cУ0
i �lbS����B\��uݑ=tC�zi_Ԉ
dc�#_��#{H�I)��N���6���%��w60��=UUUUUU3B$ȯh4�D�Ѐ������^�AM+�
�M���H������e����Ҳ����x���ϝ;�sR��ٳ����/B��J�
�:ŋ���$���tbdq�IC��Q��fgg�nwKKK,+//_]]Uw̠�bY�Cg2[	G�lF-,tI%��\�
�V�V(���m�~��
���F"4%P@(��h������R7Uh-�G�n��� E��E=�FR,�
���.�+��UVV�����0R%vuue�Y� �nX��ev�#�l��,Ah& �~�_>
��竪�����3�4#�������������ek���A��R#�(�FM�(+R��R!p�ؔ��
�h4�����xX~ݴ�ۺ�se`{�F7<�������_YY��!Ʌ2MQ���
��k:�N�
��b$H�@Qhq�$���"��R$�<`�϶�@ @��
��i`.����(��T4ة�!�a*�aE���4䨐l6������A� &�S���5B3І(N%���KqARtv�]���U��N�Qɤ��<�f_�ؒ�HTI:-�C~vb�$
�0�䄁
�ԅ"ڕB�����<��#T�CO�m(`tb_�E��&l�ۉDbnn��\ʷ8R�PI�ńuC���ŧ+�#tH�5�:��El��|�R�
œE�zG��G) �x�H{Q|,�,º�0%:��g��FATR��M$kkk�����k��f0�(�Z rvP۵���`prrR�K�>�߿���Du��|M�+ņ�%���� F��V�Kn����;w�PElAl'''<8::ҙj.#��
�Ū��v�2�n�1U�`0�qŘXduC
��j�Z.7677��x__:*4AH'	
K_<�
�i�����Ge��׿��ۖeMLLlooC)�M>+$o�S�
;x�OZ詇,@Nh��k$�
�B��N>��s�N"�p�,��r������ĺ��Ga:p�3쨶
Khpn�1J	�T7�)�5�bY�����ɉ|:�$�H��JN�ڀ�R���k�m��px||<�ߺu�����M����
d2N�Wd��[��A����|	2��l�1�\�recccbb"�Ɉ�!1w�ݣ���*�Ì��u�X�g;T�p���N{�C:���w~~���wtt�
Ǿ��uu[W	�*FS��$�={���wzz:�ˍ��x<Ks���(bC�c[hc�Tjւ��(�]P�
�+Ѕ;����|����n��ܹs2=)-l��:ͽ�;�Q�pHTM"��u�<թ@'*333---uuu��NjlI3J�BG� �q��/
25�ϟ?��d���|>���[Y����@�↺�\E����P�	1'������]�x���prr������MiA�7=ʺÖG4�@�/�c�B�;
Yؗ��p��X��!�l�~��Y$�ǣ\@=�^���`�n�!���;��ZZZ����`P�1���v��9Z��+����_|QWW'�g�rD�B��6"du!�PxX4-ˊ�b333UUU�`pcc���,--���R!���;;;w��moo���L��[�C��h�4'd�޻�����UUU�����唓�ؒ��}����А�����M�R�HD�����%h3�9�L�tZ��Iqrr���$Oi��
�/_����׿����;ʎ]֞�%$�ģ��n�
��NWL��tmmm"��m������^����m��B�Phaa��ݻgϞ�K&�Tj��YA2:M�Eg���	������x<���b�XCC��֖z� ��K�S�!2�L4��'�ɒ_O�E�n=%���^4����B�B� ]���8w�|Y�n���VVV������~u*:NV�,�z�����C�,V�V������%{)
sss{{{���~��`�7�^�z566[t!%4'BB�B�����{�,�z��IWW��%)�N�z�J.�N������q2����u���C�ę�E���������H$2;;����܇N��'9�a�̩ӥ�iΣ��L�\.�ٳgs�����eY###��S��o��
ri��"cY���a_]�[���D"���>22��V��\J��PC١V���O������!����l#Qv�u*;u��q�����-`�n������ѝ;w�ɤ�œ�����'�t���e�w�ʷ�P���������罾
9�;Y���?�%��
چ�A�Hr�\###��ӏ?�����*2X��߸��X;�a������W����߽{wuu�A�7����Ջ\����b]C3mee�ƍ��Q/6Ҡ����quu���D}�E ��u
i�J�I�ԂƋ&/���������/�˿���%c���*B����/���ܺu�ŋH7b���ZdgԱd�C�!��vww����g�h6�#[�О`0��;�d�ى����=ʐS'���)�!�zQ��A�T�8���^\\�����+jH;��1��ϻ�n�w<tD���(�H�Ձ�f"��������6C�RM�1�[RUUշ�����ډ����u�d����΂�\�h�v ������D�$tt�f�vWW������ֽ{����t����'��L(��zE#!�}���VXv��}�fgg���ԃ��������.�H��{G777����Ѩ0.BP���*���*��;*�LV�C��j�!�v�nYV2����~��)�Bv<���tY�u��ً/F��G��H:;uJ�u4�s�gtt��F�Jә7==���੐a��\� �7���o[���_59�|0���?��������


��O
��ɀ�\ꔜ�4�ӾH��oll��w�+�����B�xIn��…GGG7o�lll<{�l�^�
�XD5Gbu�U��
-��l����~�zcc#bcg���B�0==��߯>T����N�)����G�XrQ/]~Q&�~����Un�b�T*�r������xyy���
��++Ԩ옚��x<��N�����|6��p����]��d�g6��
�e���x�BhkkK��
�vvv|>_*���P/�:ּ��u�����x�޽�����6(���R:Ƞ�	k9j�

����	���DFf2���y��!$t�R�����|j������[R<���;99ihh����B��4��^�B$-���/����w����NNN&''������`wv�#�iC᢫<4uI�
ȜL&gff2�L}}���nSS�<�a��.���6��peee0_\\�}���࠼���BG�=�D�ZB�
�� c�	#�h!�����������P�Ȁ�S'bH�B�ԅ
�זP��+�,˒_�*++�{���`f4�I��T*��ٳ���H$��W'�4w�ض�ޡ���dc>��]{����;f�X�
7۶_�x�L&�J��@��=�_�ޛ���D"���d2�\.WQQ������600���P(�{-O���I�;fb��?Y���
�t޳+"�a����;w�tww�Ş��t�zh�nF�<�!u˕᳇4�L*ip__�\�!ԭ�f�uf������_��M�9�w���YXX�B�H�b+���h6����L$��x�&�XYYYXXx��wՃ���H�]��� ��d�e�������Z%R������ͯ^��{�n__����vQn�zYÐ4.��C�c�V>�|�I(>�������{�jjjua��5��:��A�񂌗�����f�����@@]�B�����������C�W�BGGG0���ba7;����2�4�M��m�f��
����8!�B������˱X�Ν;��2��r����766�E�)�D#IW?!'+�@l/����|���񦦦;w��&�����c�jDZأ�0��5�L�����������ٸW�����/Yv����
B�~�R2*XQ(���S�K�-.UL��C��
���z�����:*�t�����=zT(�%�m{�^t.��:�N�0]���X�s��bS���‚�<�y+'��fS(n޼���OG��v{�^(G���,��uG�˒eY���555�{�:�tG
����&;�.����eH��M�եC�x��m$V�-�jkka@�eeeccc�L���UUU���P����&%^��|����%�"fq�x1w΀���CC�S��ew�������g8f1!DGGGGG�����puu���O���t��#��!FD���n�0��ӧO;;;��'#���`���vvdQ0 ���@Q���6h�b���J���jV[R����"lW�l����0�Ё�x<�/_nmm�{���Ғ.����#�~*JK�m��ubрٶ=33#_�OXQEE�\����I.���llL�g#/nmmA�]W��.�8���$8���7===��������K����fÎ{XĐyP~nj�(��%7�����C�8� \l��P�������X,v�֭�����V:���e]�z��9�A�	
Pj��؜*�d2���������J�DPX �+�p��/^<::��~uu�{�'�l�D}YK1*���YN&�y���v�!��t�z��w4�.���bP�pSe�t���(��UUU%��@ ���uÍ��v�n��������۷o

���ڠ�¾0�������%�������kkk�ɤ��SX��������Xi#�P�Q2������ۻ���n������g�B!4�#��Vg3��BG���_�|y��y4�:pAd�t�}
�L��R��
��8�~�^�����T*�����ظ��YWW�J�Ο?O#���b�q���J������F�ϟ?�w� N�?tS�N%P�977wpp�������ɤ<}�9H����54mþ�٨��՛7o˜%��C�M�:�tS԰�J���"��	A�>��*Ս���+�:��]l�CL%�f��mg2�2���ﳞ��%;iٺD��%{�>88X(��<���eYGGG����Z�.��DE+�IJ����l6;66��������ʞ<yB�0�%��D9B! �����p4��lز[
�“'O���Н��j	� �)V>츳��LJ��)�#�Ā�
,�CQ��q��[���
g�Q�`///�G�����1��QW��pQ�.\8<<|��aee���	Y��x***��5.�":'ez_�YFB��hw����$(wr���ԔeY###���˲���eУ� ���,�Z__/
}}}�!��a�1�gH:N���a�8	"�!.E�rT�.��Q�XQ4iѰ��l����|�r<���hnnV/;�z�{�E���	�eM��$����$>��X�8����(���φU-?��Cmв,�c��7��z��H$b
��1�0CP���"��S�%sM���_eR��sN(
;����� 7���իW���'&&�44�d��Ρ
�]�<(	��ϹT]yy��˗���oݺ����#l��C�A��<y���t���/��beeE=@�Z¦	Et!V4s�]#�ƕ�H�N�E.UE�ʫ��
��	a�d$������˗���i
:Q���}���!�Hm��Ru�_��y��.�����z���֭[{{{��T)Ą�E8P�l6����N��^��l[�Z�T�/;I'�5Z�U(E�Ə-_y�SC�P���5�t��|�:�4Bu�mG"�����O�˧�uьdg�Ly�䡻�N��U������JUÌ��ė�l�KbGFF�{驑��y�`���zK����er�v�@Y�l*<������( `Ypt!�tS�Qg��S�r��� ���8�ک{�E1�;w.���k�����sH���t�Baβ�tȔ$:��e555QgUC���P��Q���ϣk6�C
ӵ�L�H�!u]t
nL�D��A;k��D�R�=�y]��$���m��������t*S���pB��#������333�y�#���+pv�$ ����$t�J��ۋ���.�Gh��m�vYYم>|�Fue��ʁG���IK�?��j8ֺ	�|�.�g���v�U�G��Y����|>�E��J������ֶ�6�	B�u[�"������������Dkk+|4�5ϐ�N۶���f���n�ڶ=00�̒���С���K�.���ݼy3���aڑ��힖�TXѹᤸ�4�
1Xn��NB��2ٶ���Cy�o8��ب����ۓ�����
��&!ق�C'��<~����~��v�-�>]__�s�Nooo(�6����l|��������zkk���ZMM��Ύ|�o�e�+��
��vtt�?�[]]ݻﾻ��z��������z
�mA�M�KTk���a#�~*<͜%E����z�sB˲z{{��xKKKYYY0�Bϟ?g����
%vb�f������f�+�̲���ͽ|�R�Z���H3\OOO"��>�������fyyY�(a�YoI_J�E�T]]l�p8������KxQ~ds�!SC��"͉��y�%�9�cI�t�=�����F�3�L.�K=j�l�>s�Lww��|
���@�eUUU����I~�H�����ypp0��OMMٶ-�-b�	n8�3��_s�Q��0CO(U>�'���==5H6��.��U+��u��yucdɸ�Uv�sܹ�:)�:�XK��F��566600 R�.�z�a�Ł� �5[�Ð5��k�n��hV���m�%��D4�m��h݂S����Wg��f	ϰP���y�n�js�QH��K�-���L�nyy�<��١Gcd|�#��5���
��<~h����E��s�B3sjv�I'U@3�U|�
2 QY���s	ȃ���7dc�E���H��y�V	Z(hl��5�,D�e��6��<(�e'5�a:c�@gu�
<C!B��6��v:(%{QG`��/�ҕ9���l#N��A#5�l�9/�|AQ������� �SH��Y���a_]�L���6b[^^.//��W���P�
����Loo��盝�mkk���2�/[x
dY�h��+�4���B_$��K�[��I�A��;͈*[C�teG��j���@2�a�p���R�Ě}4��6�v�9:G�$>�C>����=z�����d��ő�H�R���:E�B/��8��bq8�
4��F�����P�@�#��#;�4C�l��Y��^
�`v��j�uɌ>��F]���rCɅ6��jd�ba�E"O7D��ae :������<99���,K�+����+W��.�.]�),𗚇���@]�ѡ�N*�¨�0�v(�0�vD!fɈ�d��<�X�]�5��N%S�t�"�O�
Ȱ�q����#f4EY�:ՈӲ,u�8��0`�W2&i*���d#��#H!beB��$�q����ASSS,��������LJ�R�33%��S�yZ���X����(4c����݋�㍍�����@`ww>E%�8<<��*�z���T�#���~����3nf�GGG^�W��-��#�+mZ��Q�
÷����������=��OJ�D�����#������̖�厏��_����x<J�}}}��X�	Tb����H$<O6�mjjjnnF@)�ʛ�:�2����S�bJT�Gk<Z������O|��钽Ju�c,�����|�L&�[.���R0��z.������2fAS��G���t/"�m{ffF�Dݜ��Q�Z��hee%�{k � 1�<�m�%���Ƌ���9��#v@��uuu�6B�����x\tI+
����K�S��f�s�
�m������?-�jnn^ZZz뭷�g��!�͛7S�Tkk���z$�a$��w����VKK���q"��v�|g\�I	�?�f����mmmo���z�:�ҠKD4l>ʃ̀���HD����?T�W�,kiiimm-�������677_�t	���ѣ��۶}>����{�WSS��MMM%��t:���)�����V~�b�/^����
���Ǖ�B�p��퍍�������D"��|���ٳg���B�p8���>00��ى�vX� ��1�#����y��Y>�O$~���K�3��}���������ccc���l�ܾ};noog2�o���RhL&�y�������I�R~��|�srrR�t�\�"9@'#�e=z�hmm���kvvvpp���I���e.�@����p8,?i���,�<Ϣ#������D"��z����JI��v�\���>������r
�d 5L�����b1y7�|>�4�`0d�)���H���B!��9!D(��=�����'�ܐ7�{��L&������a����@ �H$\.�rS
v]]]8��ߗ8�兩\���N��a�˥�	�<��Ͳ���Q���܀�^������͇���\V��shh(��tuu��7B9r�����������n��:���xZ[[��t0lllDO~C�]]]���gΜ����������@ P(zzz��U��R�[A��T��cFUYɖ)C�a3�yj�2
�
���Y�.e��j��Oqf��ԁoP�l3N-��y�m���x@���*i'��3ǒnC�R�u�Rx�\��Z�&�.p
0:
R��#���b+++}}}��������KJ3�v�
�~%V%��i���4օ��J��r������e}���gӢC@�iH(�9'd\I���$�)C�����g�����\�T*���4<<���3��������+p�o6�ffJ��E��j��fq�As�(Ɲ���7VVV~��ߵ��tww���?t��d'�Sd�����1���B�!w���?���`0XVVv��u��b���ʤE�B
ca�]�Fe����u�B
���iYV2���b�m{�ޥ���������ccc/^������O~"+���!�d�&fNWb;S�mR�Y�:Jyl�N&��d2��LNN�9sF]��ug���h��D�%���`8��FI̥۠�%y�:��Խ
�L����D�r��r*�iG��2�L6�M&��|>d��\.������}>_cc#���(	��؎.G�D�L�Rg;,
;�5J{3d��B�Lh���RK�S�D�N{I�ufM�3��A:uB,�uґ5F����/�㩴;Tg�
`��粡ق6�6����2P68�
��
��#KPd�
HPj�K-��))���b��u]�/�f*
���`�N��₀:��
�M����1:N��tr�1��3��yVv-
endstream
endobj
417 0 obj
<< /Type /Annot
/Subtype /Link
/A 418 0 R
/Border [0 0 0]
/H /I
/Rect [ 212.6602 651.9316 228.9232 661.8522 ]
>>
endobj
418 0 obj
<< /Type /Action
>>
endobj
419 0 obj
<< /Type /Annot
/Subtype /Link
/A 420 0 R
/Border [0 0 0]
/H /I
/Rect [ 35.2500 322.4437 147.7500 434.9437 ]
>>
endobj
420 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/files/2011/11/geparametershd.jpg)
>>
endobj
421 0 obj
<< /Type /Annot
/Subtype /Link
/A 422 0 R
/Border [0 0 0]
/H /I
/Rect [ 466.2675 209.8396 482.5305 219.7602 ]
>>
endobj
422 0 obj
<< /Type /Action
>>
endobj
423 0 obj
<< /Type /Annot
/Subtype /Link
/A 424 0 R
/Border [0 0 0]
/H /I
/Rect [ 482.5305 209.8396 498.7935 219.7602 ]
>>
endobj
424 0 obj
<< /Type /Action
>>
endobj
425 0 obj
<< /Type /Annot
/Subtype /Link
/A 426 0 R
/Border [0 0 0]
/H /I
/Rect [ 35.2500 52.9320 260.2500 112.1820 ]
>>
endobj
426 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/files/2011/11/abbildungenkorrelationenfinal.png)
>>
endobj
427 0 obj
<<
/Type /XObject
/Subtype /Image
/Width 300
/Height 79
/Filter /FlateDecode
/DecodeParms << /Predictor 15 /Colors 1 /Columns 300 /BitsPerComponent 8>>
/ColorSpace /DeviceGray
/BitsPerComponent 8
/Length 212>>
stream
x���1���@��Cш�`b�+�j����\��Zo3���O<��8���Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�f�a�
endstream
endobj
428 0 obj
<<
/Type /XObject
/Subtype /Image
/Width 300
/Height 79
/SMask 427 0 R
/Filter /FlateDecode
/DecodeParms << /Predictor 15 /Colors 3 /Columns 300 /BitsPerComponent 8>>
/ColorSpace /DeviceRGB
/BitsPerComponent 8
/Length 11973>>
stream
x��]�o���Y�E.���^�KR�x�)Y�h9��
#�$H�?$@��~3�H��-H�H�	�%�AI�u��E���\.w��^�=tܪ����q�3=�u����gv˶mQL�m[��6�8=��#bF��(i|I��M'���w�\
+�)j��ש6H@&A~8dT�dگ���	m@V�(���y��R p��N8�t�����\:��O������H$"�P`���e
6�d���b<���M�������B���xė�bL�	�X�555��xF���r����χ���w�d2GGG������n�[�&��P�T���R���2���6��q{{{dd�db��E�e��/����D"�x���ڶm��R��+�������
A
�Trckk��ٳ.����������455�B������J������~������A.�K&��\�w�Q�hi��
���V9	�ř%��,�	GGGsss|����4����7��t�eY[[[����l6�J]�vmiiɲ����h4Z(Μ9���ס��B�0	�,��eY2����LNN�\���y۶GFFNNN�^o:�N&����;;;{���B��L2�Wq��������nmm}��Q&�y�������r��~�?�H���p8���ɮ]%
�|>_VV���E1n��Z��H=99B�|>�-�NWVV��hc*����tzaa���/��y�^�1�
�����Ϟ=[(jjj.\���d2�L(���H�әL���Ƕm���V�м��\뛿�2������m����O��������̯�}���O`�D"X�uuu	!,�:s�lG'�SSS^�7��F��P(���!Oq�I�U�333�m_�p�2��鉉���~�������l����}}}�pX��wvvFFF�߿��xΟ?o���{�޲�2�����,����P���Ր�+-�
WM�ٔ�'*yy���+�����E+V���'�z3V���uRJ�af���hiiB�������C���jS�Z��ӳ��Y^^>::����G���m�۶+++�\�RSS�vD��x.^�(gH,;::���m{hh�t:��ze5��Y��\��^�S��:���v�OwQ_瑇l�d2�����LJ�����u��uJ̈́�BvB9���7#V,l�կ~���m���7���O%��nUUUOOOWWW{{;<
ã�G^�����2����TW�Κ�˲���s�\ww�l���p��R������I>����ϑ":e�F��R���_>���rB�|>�"��%tJ��u���H�$R��?�����?���p8���S�Ȅ��ei�I+z6H�%#���'s�y�@��u*���׿�ӟ�t�ʕ���oN4��vɠ�At4���(��������v(D������~���������KKK�\��I����rtzzzzz���777�b�������s�Ρ�&����B���
Jӹ
zK�O�n	��
+�*/�mnnڶ-/	��a����������ʆ��������D"���+������r$AI����*Ħ~�.
S�HŎ��}��G�|�ɵkג�$�
3�
j�!k���l1u�m�����---���H�Le���̏~�#�-Ow���N�3	[[[C�P.��,+������P��|���
yE�c�;��	�:6� �P���"'�p�\n��eP#[-��`��>�f�n��������իWʘT*������&/��f>[!Q`A�Eq���y(�$�q�Y`nn��?��������myr��v�i��I�E�
(4[�E���A�ж��O����TTT ]��������>��B�`����d&acc#+��?���!5��a@)��e;�TK�>����F/_���Z�s3�t!INB�YWW����Ɵ�ĩ�e�)����O������ׯ��FD��4������h>������H��

���B�b���>��
k<�X�,��m��Й3g�ܜ��W���{��0<�o<(?���}%���3����m�'''������o��T���x��5�H�lt	p:K�adIt6�C�Xɬ@�vԑ��6�
)��56R�p��?�F򩵬I�k��l�Z��hv���*�Q��:K���j��Yb/�FCh���sss###jꀢ�Q��������Q�.�� ��������S-2�]���I�IF�N�P�N�ŝ�PҭC��l4�u�bqg������R���6۸N3𗬢tD���777���a��Q
�u�C�^�:�`���1r�NZV4�k�4���@�ģsU��A2]V,t��
wj*������Q��nS/JI�$�h/:����
����etB����T*500@-���u�;�Q�K7�-@H
;�����d C�a-A�خ�4��l���
�F�9�چ~�"����S2�pT�P��ŕ�V/ը+چ1Z^^�d2gΜa�׶m���nZT tۍ�����*	��-�lGtȠ�5�����P���_h**��F��6��nS�T���T�E�
t�������\.
��Ѩ��[\\���
�V���+++���=zq��P4??_YY����b�
O�R333������p��A��]l�Cm���!u�3�]cУ0
i �lbS����B\��uݑ=tC�zi_Ԉ
dc�#_��#{H�I)��N���6���%��w60��=UUUUUU3B$ȯh4�D�Ѐ������^�AM+�
�M���H������e����Ҳ����x���ϝ;�sR��ٳ����/B��J�
�:ŋ���$���tbdq�IC��Q��fgg�nwKKK,+//_]]Uw̠�bY�Cg2[	G�lF-,tI%��\�
�V�V(���m�~��
���F"4%P@(��h������R7Uh-�G�n��� E��E=�FR,�
���.�+��UVV�����0R%vuue�Y� �nX��ev�#�l��,Ah& �~�_>
��竪�����3�4#�������������ek���A��R#�(�FM�(+R��R!p�ؔ��
�h4�����xX~ݴ�ۺ�se`{�F7<�������_YY��!Ʌ2MQ���
��k:�N�
��b$H�@Qhq�$���"��R$�<`�϶�@ @��
��i`.����(��T4ة�!�a*�aE���4䨐l6������A� &�S���5B3І(N%���KqARtv�]���U��N�Qɤ��<�f_�ؒ�HTI:-�C~vb�$
�0�䄁
�ԅ"ڕB�����<��#T�CO�m(`tb_�E��&l�ۉDbnn��\ʷ8R�PI�ńuC���ŧ+�#tH�5�:��El��|�R�
œE�zG��G) �x�H{Q|,�,º�0%:��g��FATR��M$kkk�����k��f0�(�Z rvP۵���`prrR�K�>�߿���Du��|M�+ņ�%���� F��V�Kn����;w�PElAl'''<8::ҙj.#��
�Ū��v�2�n�1U�`0�qŘXduC
��j�Z.7677��x__:*4AH'	
K_<�
�i�����Ge��׿��ۖeMLLlooC)�M>+$o�S�
;x�OZ詇,@Nh��k$�
�B��N>��s�N"�p�,��r������ĺ��Ga:p�3쨶
Khpn�1J	�T7�)�5�bY�����ɉ|:�$�H��JN�ڀ�R���k�m��px||<�ߺu�����M����
d2N�Wd��[��A����|	2��l�1�\�recccbb"�Ɉ�!1w�ݣ���*�Ì��u�X�g;T�p���N{�C:���w~~���wtt�
Ǿ��uu[W	�*FS��$�={���wzz:�ˍ��x<Ks���(bC�c[hc�Tjւ��(�]P�
�+Ѕ;����|����n��ܹs2=)-l��:ͽ�;�Q�pHTM"��u�<թ@'*333---uuu��NjlI3J�BG� �q��/
25�ϟ?��d���|>���[Y����@�↺�\E����P�	1'������]�x���prr������MiA�7=ʺÖG4�@�/�c�B�;
Yؗ��p��X��!�l�~��Y$�ǣ\@=�^���`�n�!���;��ZZZ����`P�1���v��9Z��+����_|QWW'�g�rD�B��6"du!�PxX4-ˊ�b333UUU�`pcc���,--���R!���;;;w��moo���L��[�C��h�4'd�޻�����UUU�����唓�ؒ��}����А�����M�R�HD�����%h3�9�L�tZ��Iqrr���$Oi��
�/_����׿����;ʎ]֞�%$�ģ��n�
��NWL��tmmm"��m������^����m��B�Phaa��ݻgϞ�K&�Tj��YA2:M�Eg���	������x<���b�XCC��֖z� ��K�S�!2�L4��'�ɒ_O�E�n=%���^4����B�B� ]���8w�|Y�n���VVV������~u*:NV�,�z�����C�,V�V������%{)
sss{{{���~��`�7�^�z566[t!%4'BB�B�����{�,�z��IWW��%)�N�z�J.�N������q2����u���C�ę�E���������H$2;;����܇N��'9�a�̩ӥ�iΣ��L�\.�ٳgs�����eY###��S��o��
ri��"cY���a_]�[���D"���>22��V��\J��PC١V���O������!����l#Qv�u*;u��q�����-`�n������ѝ;w�ɤ�œ�����'�t���e�w�ʷ�P���������罾
9�;Y���?�%��
چ�A�Hr�\###��ӏ?�����*2X��߸��X;�a������W����߽{wuu�A�7����Ջ\����b]C3mee�ƍ��Q/6Ҡ����quu���D}�E ��u
i�J�I�ԂƋ&/���������/�˿���%c���*B����/���ܺu�ŋH7b���ZdgԱd�C�!��vww����g�h6�#[�О`0��;�d�ى����=ʐS'���)�!�zQ��A�T�8���^\\�����+jH;��1��ϻ�n�w<tD���(�H�Ձ�f"��������6C�RM�1�[RUUշ�����ډ����u�d����΂�\�h�v ������D�$tt�f�vWW������ֽ{����t����'��L(��zE#!�}���VXv��}�fgg���ԃ��������.�H��{G777����Ѩ0.BP���*���*��;*�LV�C��j�!�v�nYV2����~��)�Bv<���tY�u��ً/F��G��H:;uJ�u4�s�gtt��F�Jә7==���੐a��\� �7���o[���_59�|0���?��������


��O
��ɀ�\ꔜ�4�ӾH��oll��w�+�����B�xIn��…GGG7o�lll<{�l�^�
�XD5Gbu�U��
-��l����~�zcc#bcg���B�0==��߯>T����N�)����G�XrQ/]~Q&�~����Un�b�T*�r������xyy���
��++Ԩ옚��x<��N�����|6��p����]��d�g6��
�e���x�BhkkK��
�vvv|>_*���P/�:ּ��u�����x�޽�����6(���R:Ƞ�	k9j�

����	���DFf2���y��!$t�R�����|j������[R<���;99ihh����B��4��^�B$-���/����w����NNN&''������`wv�#�iC᢫<4uI�
ȜL&gff2�L}}���nSS�<�a��.���6��peee0_\\�}���࠼���BG�=�D�ZB�
�� c�	#�h!�����������P�Ȁ�S'bH�B�ԅ
�זP��+�,˒_�*++�{���`f4�I��T*��ٳ���H$��W'�4w�ض�ޡ���dc>��]{����;f�X�
7۶_�x�L&�J��@��=�_�ޛ���D"���d2�\.WQQ������600���P(�{-O���I�;fb��?Y���
�t޳+"�a����;w�tww�Ş��t�zh�nF�<�!u˕᳇4�L*ip__�\�!ԭ�f�uf������_��M�9�w���YXX�B�H�b+���h6����L$��x�&�XYYYXXx��wՃ���H�]��� ��d�e�������Z%R������ͯ^��{�n__����vQn�zYÐ4.��C�c�V>�|�I(>�������{�jjjua��5��:��A�񂌗�����f�����@@]�B�����������C�W�BGGG0���ba7;����2�4�M��m�f��
����8!�B������˱X�Ν;��2��r����766�E�)�D#IW?!'+�@l/����|���񦦦;w��&�����c�jDZأ�0��5�L�����������ٸW�����/Yv����
B�~�R2*XQ(���S�K�-.UL��C��
���z�����:*�t�����=zT(�%�m{�^t.��:�N�0]���X�s��bS���‚�<�y+'��fS(n޼���OG��v{�^(G���,��uG�˒eY���555�{�:�tG
����&;�.����eH��M�եC�x��m$V�-�jkka@�eeeccc�L���UUU���P����&%^��|����%�"fq�x1w΀���CC�S��ew�������g8f1!DGGGGG�����puu���O���t��#��!FD���n�0��ӧO;;;��'#���`���vvdQ0 ���@Q���6h�b���J���jV[R����"lW�l����0�Ё�x<�/_nmm�{���Ғ.����#�~*JK�m��ubрٶ=33#_�OXQEE�\����I.���llL�g#/nmmA�]W��.�8���$8���7===��������K����fÎ{XĐyP~nj�(��%7�����C�8� \l��P�������X,v�֭�����V:���e]�z��9�A�	
Pj��؜*�d2���������J�DPX �+�p��/^<::��~uu�{�'�l�D}YK1*���YN&�y���v�!��t�z��w4�.���bP�pSe�t���(��UUU%��@ ���uÍ��v�n��������۷o

���ڠ�¾0�������%�������kkk�ɤ��SX��������Xi#�P�Q2������ۻ���n������g�B!4�#��Vg3��BG���_�|y��y4�:pAd�t�}
�L��R��
��8�~�^�����T*�����ظ��YWW�J�Ο?O#���b�q���J������F�ϟ?�w� N�?tS�N%P�977wpp�������ɤ<}�9H����54mþ�٨��՛7o˜%��C�M�:�tS԰�J���"��	A�>��*Ս���+�:��]l�CL%�f��mg2�2���ﳞ��%;iٺD��%{�>88X(��<���eYGGG����Z�.��DE+�IJ����l6;66��������ʞ<yB�0�%��D9B! �����p4��lز[
�“'O���Н��j	� �)V>츳��LJ��)�#�Ā�
,�CQ��q��[���
g�Q�`///�G�����1��QW��pQ�.\8<<|��aee���	Y��x***��5.�":'ez_�YFB��hw����$(wr���ԔeY###���˲���eУ� ���,�Z__/
}}}�!��a�1�gH:N���a�8	"�!.E�rT�.��Q�XQ4iѰ��l����|�r<���hnnV/;�z�{�E���	�eM��$����$>��X�8����(���φU-?��Cmв,�c��7��z��H$b
��1�0CP���"��S�%sM���_eR��sN(
;����� 7���իW���'&&�44�d��Ρ
�]�<(	��ϹT]yy��˗���oݺ����#l��C�A��<y���t���/��beeE=@�Z¦	Et!V4s�]#�ƕ�H�N�E.UE�ʫ��
��	a�d$������˗���i
:Q���}���!�Hm��Ru�_��y��.�����z���֭[{{{��T)Ą�E8P�l6����N��^��l[�Z�T�/;I'�5Z�U(E�Ə-_y�SC�P���5�t��|�:�4Bu�mG"�����O�˧�uьdg�Ly�䡻�N��U������JUÌ��ė�l�KbGFF�{驑��y�`���zK����er�v�@Y�l*<������( `Ypt!�tS�Qg��S�r��� ���8�ک{�E1�;w.���k�����sH���t�Baβ�tȔ$:��e555QgUC���P��Q���ϣk6�C
ӵ�L�H�!u]t
nL�D��A;k��D�R�=�y]��$���m��������t*S���pB��#������333�y�#���+pv�$ ����$t�J��ۋ���.�Gh��m�vYYم>|�Fue��ʁG���IK�?��j8ֺ	�|�.�g���v�U�G��Y����|>�E��J������ֶ�6�	B�u[�"������������Dkk+|4�5ϐ�N۶���f���n�ڶ=00�̒���С���K�.���ݼy3���aڑ��힖�TXѹᤸ�4�
1Xn��NB��2ٶ���Cy�o8��ب����ۓ�����
��&!ق�C'��<~����~��v�-�>]__�s�Nooo(�6����l|��������zkk���ZMM��Ύ|�o�e�+��
��vtt�?�[]]ݻﾻ��z��������z
�mA�M�KTk���a#�~*<͜%E����z�sB˲z{{��xKKKYYY0�Bϟ?g����
%vb�f������f�+�̲���ͽ|�R�Z���H3\OOO"��>�������fyyY�(a�YoI_J�E�T]]l�p8������KxQ~ds�!SC��"͉��y�%�9�cI�t�=�����F�3�L.�K=j�l�>s�Lww��|
���@�eUUU����I~�H�����ypp0��OMMٶ-�-b�	n8�3��_s�Q��0CO(U>�'���==5H6��.��U+��u��yucdɸ�Uv�sܹ�:)�:�XK��F��566600 R�.�z�a�Ł� �5[�Ð5��k�n��hV���m�%��D4�m��h݂S����Wg��f	ϰP���y�n�js�QH��K�-���L�nyy�<��١Gcd|�#��5���
��<~h����E��s�B3sjv�I'U@3�U|�
2 QY���s	ȃ���7dc�E���H��y�V	Z(hl��5�,D�e��6��<(�e'5�a:c�@gu�
<C!B��6��v:(%{QG`��/�ҕ9���l#N��A#5�l�9/�|AQ������� �SH��Y���a_]�L���6b[^^.//��W���P�
����Loo��盝�mkk���2�/[x
dY�h��+�4���B_$��K�[��I�A��;͈*[C�teG��j���@2�a�p���R�Ě}4��6�v�9:G�$>�C>����=z�����d��ő�H�R���:E�B/��8��bq8�
4��F�����P�@�#��#;�4C�l��Y��^
�`v��j�uɌ>��F]���rCɅ6��jd�ba�E"O7D��ae :������<99���,K�+����+W��.�.]�),𗚇���@]�ѡ�N*�¨�0�v(�0�vD!fɈ�d��<�X�]�5��N%S�t�"�O�
Ȱ�q����#f4EY�:ՈӲ,u�8��0`�W2&i*���d#��#H!beB��$�q����ASSS,��������LJ�R�33%��S�yZ���X����(4c����݋�㍍�����@`ww>E%�8<<��*�z���T�#���~����3nf�GGG^�W��-��#�+mZ��Q�
÷����������=��OJ�D�����#������̖�厏��_����x<J�}}}��X�	Tb����H$<O6�mjjjnnF@)�ʛ�:�2����S�bJT�Gk<Z������O|��钽Ju�c,�����|�L&�[.���R0��z.������2fAS��G���t/"�m{ffF�Dݜ��Q�Z��hee%�{k � 1�<�m�%���Ƌ���9��#v@��uuu�6B�����x\tI+
����K�S��f�s�
�m������?-�jnn^ZZz뭷�g��!�͛7S�Tkk���z$�a$��w����VKK���q"��v�|g\�I	�?�f����mmmo���z�:�ҠKD4l>ʃ̀���HD����?T�W�,kiiimm-�������677_�t	���ѣ��۶}>����{�WSS��MMM%��t:���)�����V~�b�/^����
���Ǖ�B�p��퍍�������D"��|���ٳg���B�p8���>00��ى�vX� ��1�#����y��Y>�O$~���K�3��}���������ccc���l�ܾ};noog2�o���RhL&�y�������I�R~��|�srrR�t�\�"9@'#�e=z�hmm���kvvvpp���I���e.�@����p8,?i���,�<Ϣ#������D"��z����JI��v�\���>������r
�d 5L�����b1y7�|>�4�`0d�)���H���B!��9!D(��=�����'�ܐ7�{��L&������a����@ �H$\.�rS
v]]]8��ߗ8�兩\���N��a�˥�	�<��Ͳ���Q���܀�^������͇���\V��shh(��tuu��7B9r�����������n��:���xZ[[��t0lllDO~C�]]]���gΜ����������@ P(zzz��U��R�[A��T��cFUYɖ)C�a3�yj�2
�
���Y�.e��j��Oqf��ԁoP�l3N-��y�m���x@���*i'��3ǒnC�R�u�Rx�\��Z�&�.p
0:
R��#���b+++}}}��������KJ3�v�
�~%V%��i���4օ��J��r������e}���gӢC@�iH(�9'd\I���$�)C�����g�����\�T*���4<<���3��������+p�o6�ffJ��E��j��fq�As�(Ɲ���7VVV~��ߵ��tww���?t��d'�Sd�����1���B�!w���?���`0XVVv��u��b���ʤE�B
ca�]�Fe����u�B
���iYV2���b�m{�ޥ���������ccc/^������O~"+���!�d�&fNWb;S�mR�Y�:Jyl�N&��d2��LNN�9sF]��ug���h��D�%���`8��FI̥۠�%y�:��Խ
�L����D�r��r*�iG��2�L6�M&��|>d��\.������}>_cc#���(	��؎.G�D�L�Rg;,
;�5J{3d��B�Lh���RK�S�D�N{I�ufM�3��A:uB,�uґ5F����/�㩴;Tg�
`��粡ق6�6����2P68�
��
��#KPd�
HPj�K-��))���b��u]�/�f*
���`�N��₀:��
�M����1:N��tr�1��3��yVv-
endstream
endobj
429 0 obj
<< /Type /Annot
/Subtype /Link
/A 430 0 R
/Border [0 0 0]
/H /I
/Rect [ 212.6602 651.9316 228.9232 661.8522 ]
>>
endobj
430 0 obj
<< /Type /Action
>>
endobj
431 0 obj
<< /Type /Annot
/Subtype /Link
/A 432 0 R
/Border [0 0 0]
/H /I
/Rect [ 35.2500 322.4437 147.7500 434.9437 ]
>>
endobj
432 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/files/2011/11/geparametershd.jpg)
>>
endobj
433 0 obj
<< /Type /Annot
/Subtype /Link
/A 434 0 R
/Border [0 0 0]
/H /I
/Rect [ 466.2675 209.8396 482.5305 219.7602 ]
>>
endobj
434 0 obj
<< /Type /Action
>>
endobj
435 0 obj
<< /Type /Annot
/Subtype /Link
/A 436 0 R
/Border [0 0 0]
/H /I
/Rect [ 482.5305 209.8396 498.7935 219.7602 ]
>>
endobj
436 0 obj
<< /Type /Action
>>
endobj
437 0 obj
<< /Type /Annot
/Subtype /Link
/A 438 0 R
/Border [0 0 0]
/H /I
/Rect [ 35.2500 52.9320 260.2500 112.1820 ]
>>
endobj
438 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/hd/files/2011/11/abbildungenkorrelationenfinal.png)
>>
endobj
439 0 obj
<<
/Type /XObject
/Subtype /Image
/Width 300
/Height 79
/Filter /FlateDecode
/DecodeParms << /Predictor 15 /Colors 1 /Columns 300 /BitsPerComponent 8>>
/ColorSpace /DeviceGray
/BitsPerComponent 8
/Length 212>>
stream
x���1���@��Cш�`b�+�j����\��Zo3���O<��8���Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�f�a�
endstream
endobj
440 0 obj
<<
/Type /XObject
/Subtype /Image
/Width 300
/Height 79
/SMask 439 0 R
/Filter /FlateDecode
/DecodeParms << /Predictor 15 /Colors 3 /Columns 300 /BitsPerComponent 8>>
/ColorSpace /DeviceRGB
/BitsPerComponent 8
/Length 11973>>
stream
x��]�o���Y�E.���^�KR�x�)Y�h9��
#�$H�?$@��~3�H��-H�H�	�%�AI�u��E���\.w��^�=tܪ����q�3=�u����gv˶mQL�m[��6�8=��#bF��(i|I��M'���w�\
+�)j��ש6H@&A~8dT�dگ���	m@V�(���y��R p��N8�t�����\:��O������H$"�P`���e
6�d���b<���M�������B���xė�bL�	�X�555��xF���r����χ���w�d2GGG������n�[�&��P�T���R���2���6��q{{{dd�db��E�e��/����D"�x���ڶm��R��+�������
A
�Trckk��ٳ.����������455�B������J������~������A.�K&��\�w�Q�hi��
���V9	�ř%��,�	GGGsss|����4����7��t�eY[[[����l6�J]�vmiiɲ����h4Z(Μ9���ס��B�0	�,��eY2����LNN�\���y۶GFFNNN�^o:�N&����;;;{���B��L2�Wq��������nmm}��Q&�y�������r��~�?�H���p8���ɮ]%
�|>_VV���E1n��Z��H=99B�|>�-�NWVV��hc*����tzaa���/��y�^�1�
�����Ϟ=[(jjj.\���d2�L(���H�әL���Ƕm���V�м��\뛿�2������m����O��������̯�}���O`�D"X�uuu	!,�:s�lG'�SSS^�7��F��P(���!Oq�I�U�333�m_�p�2��鉉���~�������l����}}}�pX��wvvFFF�߿��xΟ?o���{�޲�2�����,����P���Ր�+-�
WM�ٔ�'*yy���+�����E+V���'�z3V���uRJ�af���hiiB�������C���jS�Z��ӳ��Y^^>::����G���m�۶+++�\�RSS�vD��x.^�(gH,;::���m{hh�t:��ze5��Y��\��^�S��:���v�OwQ_瑇l�d2�����LJ�����u��uJ̈́�BvB9���7#V,l�կ~���m���7���O%��nUUUOOOWWW{{;<
ã�G^�����2����TW�Κ�˲���s�\ww�l���p��R������I>����ϑ":e�F��R���_>���rB�|>�"��%tJ��u���H�$R��?�����?���p8���S�Ȅ��ei�I+z6H�%#���'s�y�@��u*���׿�ӟ�t�ʕ���oN4��vɠ�At4���(��������v(D������~���������KKK�\��I����rtzzzzz���777�b�������s�Ρ�&����B���
Jӹ
zK�O�n	��
+�*/�mnnڶ-/	��a����������ʆ��������D"���+������r$AI����*Ħ~�.
S�HŎ��}��G�|�ɵkג�$�
3�
j�!k���l1u�m�����---���H�Le���̏~�#�-Ow���N�3	[[[C�P.��,+������P��|���
yE�c�;��	�:6� �P���"'�p�\n��eP#[-��`��>�f�n��������իWʘT*������&/��f>[!Q`A�Eq���y(�$�q�Y`nn��?��������myr��v�i��I�E�
(4[�E���A�ж��O����TTT ]��������>��B�`����d&acc#+��?���!5��a@)��e;�TK�>����F/_���Z�s3�t!INB�YWW����Ɵ�ĩ�e�)����O������ׯ��FD��4������h>������H��

���B�b���>��
k<�X�,��m��Й3g�ܜ��W���{��0<�o<(?���}%���3����m�'''������o��T���x��5�H�lt	p:K�adIt6�C�Xɬ@�vԑ��6�
)��56R�p��?�F򩵬I�k��l�Z��hv���*�Q��:K���j��Yb/�FCh���sss###jꀢ�Q��������Q�.�� ��������S-2�]���I�IF�N�P�N�ŝ�PҭC��l4�u�bqg������R���6۸N3𗬢tD���777���a��Q
�u�C�^�:�`���1r�NZV4�k�4���@�ģsU��A2]V,t��
wj*������Q��nS/JI�$�h/:����
����etB����T*500@-���u�;�Q�K7�-@H
;�����d C�a-A�خ�4��l���
�F�9�چ~�"����S2�pT�P��ŕ�V/ը+چ1Z^^�d2gΜa�׶m���nZT tۍ�����*	��-�lGtȠ�5�����P���_h**��F��6��nS�T���T�E�
t�������\.
��Ѩ��[\\���
�V���+++���=zq��P4??_YY����b�
O�R333������p��A��]l�Cm���!u�3�]cУ0
i �lbS����B\��uݑ=tC�zi_Ԉ
dc�#_��#{H�I)��N���6���%��w60��=UUUUUU3B$ȯh4�D�Ѐ������^�AM+�
�M���H������e����Ҳ����x���ϝ;�sR��ٳ����/B��J�
�:ŋ���$���tbdq�IC��Q��fgg�nwKKK,+//_]]Uw̠�bY�Cg2[	G�lF-,tI%��\�
�V�V(���m�~��
���F"4%P@(��h������R7Uh-�G�n��� E��E=�FR,�
���.�+��UVV�����0R%vuue�Y� �nX��ev�#�l��,Ah& �~�_>
��竪�����3�4#�������������ek���A��R#�(�FM�(+R��R!p�ؔ��
�h4�����xX~ݴ�ۺ�se`{�F7<�������_YY��!Ʌ2MQ���
��k:�N�
��b$H�@Qhq�$���"��R$�<`�϶�@ @��
��i`.����(��T4ة�!�a*�aE���4䨐l6������A� &�S���5B3І(N%���KqARtv�]���U��N�Qɤ��<�f_�ؒ�HTI:-�C~vb�$
�0�䄁
�ԅ"ڕB�����<��#T�CO�m(`tb_�E��&l�ۉDbnn��\ʷ8R�PI�ńuC���ŧ+�#tH�5�:��El��|�R�
œE�zG��G) �x�H{Q|,�,º�0%:��g��FATR��M$kkk�����k��f0�(�Z rvP۵���`prrR�K�>�߿���Du��|M�+ņ�%���� F��V�Kn����;w�PElAl'''<8::ҙj.#��
�Ū��v�2�n�1U�`0�qŘXduC
��j�Z.7677��x__:*4AH'	
K_<�
�i�����Ge��׿��ۖeMLLlooC)�M>+$o�S�
;x�OZ詇,@Nh��k$�
�B��N>��s�N"�p�,��r������ĺ��Ga:p�3쨶
Khpn�1J	�T7�)�5�bY�����ɉ|:�$�H��JN�ڀ�R���k�m��px||<�ߺu�����M����
d2N�Wd��[��A����|	2��l�1�\�recccbb"�Ɉ�!1w�ݣ���*�Ì��u�X�g;T�p���N{�C:���w~~���wtt�
Ǿ��uu[W	�*FS��$�={���wzz:�ˍ��x<Ks���(bC�c[hc�Tjւ��(�]P�
�+Ѕ;����|����n��ܹs2=)-l��:ͽ�;�Q�pHTM"��u�<թ@'*333---uuu��NjlI3J�BG� �q��/
25�ϟ?��d���|>���[Y����@�↺�\E����P�	1'������]�x���prr������MiA�7=ʺÖG4�@�/�c�B�;
Yؗ��p��X��!�l�~��Y$�ǣ\@=�^���`�n�!���;��ZZZ����`P�1���v��9Z��+����_|QWW'�g�rD�B��6"du!�PxX4-ˊ�b333UUU�`pcc���,--���R!���;;;w��moo���L��[�C��h�4'd�޻�����UUU�����唓�ؒ��}����А�����M�R�HD�����%h3�9�L�tZ��Iqrr���$Oi��
�/_����׿����;ʎ]֞�%$�ģ��n�
��NWL��tmmm"��m������^����m��B�Phaa��ݻgϞ�K&�Tj��YA2:M�Eg���	������x<���b�XCC��֖z� ��K�S�!2�L4��'�ɒ_O�E�n=%���^4����B�B� ]���8w�|Y�n���VVV������~u*:NV�,�z�����C�,V�V������%{)
sss{{{���~��`�7�^�z566[t!%4'BB�B�����{�,�z��IWW��%)�N�z�J.�N������q2����u���C�ę�E���������H$2;;����܇N��'9�a�̩ӥ�iΣ��L�\.�ٳgs�����eY###��S��o��
ri��"cY���a_]�[���D"���>22��V��\J��PC١V���O������!����l#Qv�u*;u��q�����-`�n������ѝ;w�ɤ�œ�����'�t���e�w�ʷ�P���������罾
9�;Y���?�%��
چ�A�Hr�\###��ӏ?�����*2X��߸��X;�a������W����߽{wuu�A�7����Ջ\����b]C3mee�ƍ��Q/6Ҡ����quu���D}�E ��u
i�J�I�ԂƋ&/���������/�˿���%c���*B����/���ܺu�ŋH7b���ZdgԱd�C�!��vww����g�h6�#[�О`0��;�d�ى����=ʐS'���)�!�zQ��A�T�8���^\\�����+jH;��1��ϻ�n�w<tD���(�H�Ձ�f"��������6C�RM�1�[RUUշ�����ډ����u�d����΂�\�h�v ������D�$tt�f�vWW������ֽ{����t����'��L(��zE#!�}���VXv��}�fgg���ԃ��������.�H��{G777����Ѩ0.BP���*���*��;*�LV�C��j�!�v�nYV2����~��)�Bv<���tY�u��ً/F��G��H:;uJ�u4�s�gtt��F�Jә7==���੐a��\� �7���o[���_59�|0���?��������


��O
��ɀ�\ꔜ�4�ӾH��oll��w�+�����B�xIn��…GGG7o�lll<{�l�^�
�XD5Gbu�U��
-��l����~�zcc#bcg���B�0==��߯>T����N�)����G�XrQ/]~Q&�~����Un�b�T*�r������xyy���
��++Ԩ옚��x<��N�����|6��p����]��d�g6��
�e���x�BhkkK��
�vvv|>_*���P/�:ּ��u�����x�޽�����6(���R:Ƞ�	k9j�

����	���DFf2���y��!$t�R�����|j������[R<���;99ihh����B��4��^�B$-���/����w����NNN&''������`wv�#�iC᢫<4uI�
ȜL&gff2�L}}���nSS�<�a��.���6��peee0_\\�}���࠼���BG�=�D�ZB�
�� c�	#�h!�����������P�Ȁ�S'bH�B�ԅ
�זP��+�,˒_�*++�{���`f4�I��T*��ٳ���H$��W'�4w�ض�ޡ���dc>��]{����;f�X�
7۶_�x�L&�J��@��=�_�ޛ���D"���d2�\.WQQ������600���P(�{-O���I�;fb��?Y���
�t޳+"�a����;w�tww�Ş��t�zh�nF�<�!u˕᳇4�L*ip__�\�!ԭ�f�uf������_��M�9�w���YXX�B�H�b+���h6����L$��x�&�XYYYXXx��wՃ���H�]��� ��d�e�������Z%R������ͯ^��{�n__����vQn�zYÐ4.��C�c�V>�|�I(>�������{�jjjua��5��:��A�񂌗�����f�����@@]�B�����������C�W�BGGG0���ba7;����2�4�M��m�f��
����8!�B������˱X�Ν;��2��r����766�E�)�D#IW?!'+�@l/����|���񦦦;w��&�����c�jDZأ�0��5�L�����������ٸW�����/Yv����
B�~�R2*XQ(���S�K�-.UL��C��
���z�����:*�t�����=zT(�%�m{�^t.��:�N�0]���X�s��bS���‚�<�y+'��fS(n޼���OG��v{�^(G���,��uG�˒eY���555�{�:�tG
����&;�.����eH��M�եC�x��m$V�-�jkka@�eeeccc�L���UUU���P����&%^��|����%�"fq�x1w΀���CC�S��ew�������g8f1!DGGGGG�����puu���O���t��#��!FD���n�0��ӧO;;;��'#���`���vvdQ0 ���@Q���6h�b���J���jV[R����"lW�l����0�Ё�x<�/_nmm�{���Ғ.����#�~*JK�m��ubрٶ=33#_�OXQEE�\����I.���llL�g#/nmmA�]W��.�8���$8���7===��������K����fÎ{XĐyP~nj�(��%7�����C�8� \l��P�������X,v�֭�����V:���e]�z��9�A�	
Pj��؜*�d2���������J�DPX �+�p��/^<::��~uu�{�'�l�D}YK1*���YN&�y���v�!��t�z��w4�.���bP�pSe�t���(��UUU%��@ ���uÍ��v�n��������۷o

���ڠ�¾0�������%�������kkk�ɤ��SX��������Xi#�P�Q2������ۻ���n������g�B!4�#��Vg3��BG���_�|y��y4�:pAd�t�}
�L��R��
��8�~�^�����T*�����ظ��YWW�J�Ο?O#���b�q���J������F�ϟ?�w� N�?tS�N%P�977wpp�������ɤ<}�9H����54mþ�٨��՛7o˜%��C�M�:�tS԰�J���"��	A�>��*Ս���+�:��]l�CL%�f��mg2�2���ﳞ��%;iٺD��%{�>88X(��<���eYGGG����Z�.��DE+�IJ����l6;66��������ʞ<yB�0�%��D9B! �����p4��lز[
�“'O���Н��j	� �)V>츳��LJ��)�#�Ā�
,�CQ��q��[���
g�Q�`///�G�����1��QW��pQ�.\8<<|��aee���	Y��x***��5.�":'ez_�YFB��hw����$(wr���ԔeY###���˲���eУ� ���,�Z__/
}}}�!��a�1�gH:N���a�8	"�!.E�rT�.��Q�XQ4iѰ��l����|�r<���hnnV/;�z�{�E���	�eM��$����$>��X�8����(���φU-?��Cmв,�c��7��z��H$b
��1�0CP���"��S�%sM���_eR��sN(
;����� 7���իW���'&&�44�d��Ρ
�]�<(	��ϹT]yy��˗���oݺ����#l��C�A��<y���t���/��beeE=@�Z¦	Et!V4s�]#�ƕ�H�N�E.UE�ʫ��
��	a�d$������˗���i
:Q���}���!�Hm��Ru�_��y��.�����z���֭[{{{��T)Ą�E8P�l6����N��^��l[�Z�T�/;I'�5Z�U(E�Ə-_y�SC�P���5�t��|�:�4Bu�mG"�����O�˧�uьdg�Ly�䡻�N��U������JUÌ��ė�l�KbGFF�{驑��y�`���zK����er�v�@Y�l*<������( `Ypt!�tS�Qg��S�r��� ���8�ک{�E1�;w.���k�����sH���t�Baβ�tȔ$:��e555QgUC���P��Q���ϣk6�C
ӵ�L�H�!u]t
nL�D��A;k��D�R�=�y]��$���m��������t*S���pB��#������333�y�#���+pv�$ ����$t�J��ۋ���.�Gh��m�vYYم>|�Fue��ʁG���IK�?��j8ֺ	�|�.�g���v�U�G��Y����|>�E��J������ֶ�6�	B�u[�"������������Dkk+|4�5ϐ�N۶���f���n�ڶ=00�̒���С���K�.���ݼy3���aڑ��힖�TXѹᤸ�4�
1Xn��NB��2ٶ���Cy�o8��ب����ۓ�����
��&!ق�C'��<~����~��v�-�>]__�s�Nooo(�6����l|��������zkk���ZMM��Ύ|�o�e�+��
��vtt�?�[]]ݻﾻ��z��������z
�mA�M�KTk���a#�~*<͜%E����z�sB˲z{{��xKKKYYY0�Bϟ?g����
%vb�f������f�+�̲���ͽ|�R�Z���H3\OOO"��>�������fyyY�(a�YoI_J�E�T]]l�p8������KxQ~ds�!SC��"͉��y�%�9�cI�t�=�����F�3�L.�K=j�l�>s�Lww��|
���@�eUUU����I~�H�����ypp0��OMMٶ-�-b�	n8�3��_s�Q��0CO(U>�'���==5H6��.��U+��u��yucdɸ�Uv�sܹ�:)�:�XK��F��566600 R�.�z�a�Ł� �5[�Ð5��k�n��hV���m�%��D4�m��h݂S����Wg��f	ϰP���y�n�js�QH��K�-���L�nyy�<��١Gcd|�#��5���
��<~h����E��s�B3sjv�I'U@3�U|�
2 QY���s	ȃ���7dc�E���H��y�V	Z(hl��5�,D�e��6��<(�e'5�a:c�@gu�
<C!B��6��v:(%{QG`��/�ҕ9���l#N��A#5�l�9/�|AQ������� �SH��Y���a_]�L���6b[^^.//��W���P�
����Loo��盝�mkk���2�/[x
dY�h��+�4���B_$��K�[��I�A��;͈*[C�teG��j���@2�a�p���R�Ě}4��6�v�9:G�$>�C>����=z�����d��ő�H�R���:E�B/��8��bq8�
4��F�����P�@�#��#;�4C�l��Y��^
�`v��j�uɌ>��F]���rCɅ6��jd�ba�E"O7D��ae :������<99���,K�+����+W��.�.]�),𗚇���@]�ѡ�N*�¨�0�v(�0�vD!fɈ�d��<�X�]�5��N%S�t�"�O�
Ȱ�q����#f4EY�:ՈӲ,u�8��0`�W2&i*���d#��#H!beB��$�q����ASSS,��������LJ�R�33%��S�yZ���X����(4c����݋�㍍�����@`ww>E%�8<<��*�z���T�#���~����3nf�GGG^�W��-��#�+mZ��Q�
÷����������=��OJ�D�����#������̖�厏��_����x<J�}}}��X�	Tb����H$<O6�mjjjnnF@)�ʛ�:�2����S�bJT�Gk<Z������O|��钽Ju�c,�����|�L&�[.���R0��z.������2fAS��G���t/"�m{ffF�Dݜ��Q�Z��hee%�{k � 1�<�m�%���Ƌ���9��#v@��uuu�6B�����x\tI+
����K�S��f�s�
�m������?-�jnn^ZZz뭷�g��!�͛7S�Tkk���z$�a$��w����VKK���q"��v�|g\�I	�?�f����mmmo���z�:�ҠKD4l>ʃ̀���HD����?T�W�,kiiimm-�������677_�t	���ѣ��۶}>����{�WSS��MMM%��t:���)�����V~�b�/^����
���Ǖ�B�p��퍍�������D"��|���ٳg���B�p8���>00��ى�vX� ��1�#����y��Y>�O$~���K�3��}���������ccc���l�ܾ};noog2�o���RhL&�y�������I�R~��|�srrR�t�\�"9@'#�e=z�hmm���kvvvpp���I���e.�@����p8,?i���,�<Ϣ#������D"��z����JI��v�\���>������r
�d 5L�����b1y7�|>�4�`0d�)���H���B!��9!D(��=�����'�ܐ7�{��L&������a����@ �H$\.�rS
v]]]8��ߗ8�兩\���N��a�˥�	�<��Ͳ���Q���܀�^������͇���\V��shh(��tuu��7B9r�����������n��:���xZ[[��t0lllDO~C�]]]���gΜ����������@ P(zzz��U��R�[A��T��cFUYɖ)C�a3�yj�2
�
���Y�.e��j��Oqf��ԁoP�l3N-��y�m���x@���*i'��3ǒnC�R�u�Rx�\��Z�&�.p
0:
R��#���b+++}}}��������KJ3�v�
�~%V%��i���4օ��J��r������e}���gӢC@�iH(�9'd\I���$�)C�����g�����\�T*���4<<���3��������+p�o6�ffJ��E��j��fq�As�(Ɲ���7VVV~��ߵ��tww���?t��d'�Sd�����1���B�!w���?���`0XVVv��u��b���ʤE�B
ca�]�Fe����u�B
���iYV2���b�m{�ޥ���������ccc/^������O~"+���!�d�&fNWb;S�mR�Y�:Jyl�N&��d2��LNN�9sF]��ug���h��D�%���`8��FI̥۠�%y�:��Խ
�L����D�r��r*�iG��2�L6�M&��|>d��\.������}>_cc#���(	��؎.G�D�L�Rg;,
;�5J{3d��B�Lh���RK�S�D�N{I�ufM�3��A:uB,�uґ5F����/�㩴;Tg�
`��粡ق6�6����2P68�
��
��#KPd�
HPj�K-��))���b��u]�/�f*
���`�N��₀:��
�M����1:N��tr�1��3��yVv-
endstream
endobj
441 0 obj
<<
/Type /XObject
/Subtype /Image
/Width 300
/Height 79
/Filter /FlateDecode
/DecodeParms << /Predictor 15 /Colors 1 /Columns 300 /BitsPerComponent 8>>
/ColorSpace /DeviceGray
/BitsPerComponent 8
/Length 212>>
stream
x���1���@��Cш�`b�+�j����\��Zo3���O<��8���Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�Y�f�a�
endstream
endobj
442 0 obj
<<
/Type /XObject
/Subtype /Image
/Width 300
/Height 79
/SMask 441 0 R
/Filter /FlateDecode
/DecodeParms << /Predictor 15 /Colors 3 /Columns 300 /BitsPerComponent 8>>
/ColorSpace /DeviceRGB
/BitsPerComponent 8
/Length 11973>>
stream
x��]�o���Y�E.���^�KR�x�)Y�h9��
#�$H�?$@��~3�H��-H�H�	�%�AI�u��E���\.w��^�=tܪ����q�3=�u����gv˶mQL�m[��6�8=��#bF��(i|I��M'���w�\
+�)j��ש6H@&A~8dT�dگ���	m@V�(���y��R p��N8�t�����\:��O������H$"�P`���e
6�d���b<���M�������B���xė�bL�	�X�555��xF���r����χ���w�d2GGG������n�[�&��P�T���R���2���6��q{{{dd�db��E�e��/����D"�x���ڶm��R��+�������
A
�Trckk��ٳ.����������455�B������J������~������A.�K&��\�w�Q�hi��
���V9	�ř%��,�	GGGsss|����4����7��t�eY[[[����l6�J]�vmiiɲ����h4Z(Μ9���ס��B�0	�,��eY2����LNN�\���y۶GFFNNN�^o:�N&����;;;{���B��L2�Wq��������nmm}��Q&�y�������r��~�?�H���p8���ɮ]%
�|>_VV���E1n��Z��H=99B�|>�-�NWVV��hc*����tzaa���/��y�^�1�
�����Ϟ=[(jjj.\���d2�L(���H�әL���Ƕm���V�м��\뛿�2������m����O��������̯�}���O`�D"X�uuu	!,�:s�lG'�SSS^�7��F��P(���!Oq�I�U�333�m_�p�2��鉉���~�������l����}}}�pX��wvvFFF�߿��xΟ?o���{�޲�2�����,����P���Ր�+-�
WM�ٔ�'*yy���+�����E+V���'�z3V���uRJ�af���hiiB�������C���jS�Z��ӳ��Y^^>::����G���m�۶+++�\�RSS�vD��x.^�(gH,;::���m{hh�t:��ze5��Y��\��^�S��:���v�OwQ_瑇l�d2�����LJ�����u��uJ̈́�BvB9���7#V,l�կ~���m���7���O%��nUUUOOOWWW{{;<
ã�G^�����2����TW�Κ�˲���s�\ww�l���p��R������I>����ϑ":e�F��R���_>���rB�|>�"��%tJ��u���H�$R��?�����?���p8���S�Ȅ��ei�I+z6H�%#���'s�y�@��u*���׿�ӟ�t�ʕ���oN4��vɠ�At4���(��������v(D������~���������KKK�\��I����rtzzzzz���777�b�������s�Ρ�&����B���
Jӹ
zK�O�n	��
+�*/�mnnڶ-/	��a����������ʆ��������D"���+������r$AI����*Ħ~�.
S�HŎ��}��G�|�ɵkג�$�
3�
j�!k���l1u�m�����---���H�Le���̏~�#�-Ow���N�3	[[[C�P.��,+������P��|���
yE�c�;��	�:6� �P���"'�p�\n��eP#[-��`��>�f�n��������իWʘT*������&/��f>[!Q`A�Eq���y(�$�q�Y`nn��?��������myr��v�i��I�E�
(4[�E���A�ж��O����TTT ]��������>��B�`����d&acc#+��?���!5��a@)��e;�TK�>����F/_���Z�s3�t!INB�YWW����Ɵ�ĩ�e�)����O������ׯ��FD��4������h>������H��

���B�b���>��
k<�X�,��m��Й3g�ܜ��W���{��0<�o<(?���}%���3����m�'''������o��T���x��5�H�lt	p:K�adIt6�C�Xɬ@�vԑ��6�
)��56R�p��?�F򩵬I�k��l�Z��hv���*�Q��:K���j��Yb/�FCh���sss###jꀢ�Q��������Q�.�� ��������S-2�]���I�IF�N�P�N�ŝ�PҭC��l4�u�bqg������R���6۸N3𗬢tD���777���a��Q
�u�C�^�:�`���1r�NZV4�k�4���@�ģsU��A2]V,t��
wj*������Q��nS/JI�$�h/:����
����etB����T*500@-���u�;�Q�K7�-@H
;�����d C�a-A�خ�4��l���
�F�9�چ~�"����S2�pT�P��ŕ�V/ը+چ1Z^^�d2gΜa�׶m���nZT tۍ�����*	��-�lGtȠ�5�����P���_h**��F��6��nS�T���T�E�
t�������\.
��Ѩ��[\\���
�V���+++���=zq��P4??_YY����b�
O�R333������p��A��]l�Cm���!u�3�]cУ0
i �lbS����B\��uݑ=tC�zi_Ԉ
dc�#_��#{H�I)��N���6���%��w60��=UUUUUU3B$ȯh4�D�Ѐ������^�AM+�
�M���H������e����Ҳ����x���ϝ;�sR��ٳ����/B��J�
�:ŋ���$���tbdq�IC��Q��fgg�nwKKK,+//_]]Uw̠�bY�Cg2[	G�lF-,tI%��\�
�V�V(���m�~��
���F"4%P@(��h������R7Uh-�G�n��� E��E=�FR,�
���.�+��UVV�����0R%vuue�Y� �nX��ev�#�l��,Ah& �~�_>
��竪�����3�4#�������������ek���A��R#�(�FM�(+R��R!p�ؔ��
�h4�����xX~ݴ�ۺ�se`{�F7<�������_YY��!Ʌ2MQ���
��k:�N�
��b$H�@Qhq�$���"��R$�<`�϶�@ @��
��i`.����(��T4ة�!�a*�aE���4䨐l6������A� &�S���5B3І(N%���KqARtv�]���U��N�Qɤ��<�f_�ؒ�HTI:-�C~vb�$
�0�䄁
�ԅ"ڕB�����<��#T�CO�m(`tb_�E��&l�ۉDbnn��\ʷ8R�PI�ńuC���ŧ+�#tH�5�:��El��|�R�
œE�zG��G) �x�H{Q|,�,º�0%:��g��FATR��M$kkk�����k��f0�(�Z rvP۵���`prrR�K�>�߿���Du��|M�+ņ�%���� F��V�Kn����;w�PElAl'''<8::ҙj.#��
�Ū��v�2�n�1U�`0�qŘXduC
��j�Z.7677��x__:*4AH'	
K_<�
�i�����Ge��׿��ۖeMLLlooC)�M>+$o�S�
;x�OZ詇,@Nh��k$�
�B��N>��s�N"�p�,��r������ĺ��Ga:p�3쨶
Khpn�1J	�T7�)�5�bY�����ɉ|:�$�H��JN�ڀ�R���k�m��px||<�ߺu�����M����
d2N�Wd��[��A����|	2��l�1�\�recccbb"�Ɉ�!1w�ݣ���*�Ì��u�X�g;T�p���N{�C:���w~~���wtt�
Ǿ��uu[W	�*FS��$�={���wzz:�ˍ��x<Ks���(bC�c[hc�Tjւ��(�]P�
�+Ѕ;����|����n��ܹs2=)-l��:ͽ�;�Q�pHTM"��u�<թ@'*333---uuu��NjlI3J�BG� �q��/
25�ϟ?��d���|>���[Y����@�↺�\E����P�	1'������]�x���prr������MiA�7=ʺÖG4�@�/�c�B�;
Yؗ��p��X��!�l�~��Y$�ǣ\@=�^���`�n�!���;��ZZZ����`P�1���v��9Z��+����_|QWW'�g�rD�B��6"du!�PxX4-ˊ�b333UUU�`pcc���,--���R!���;;;w��moo���L��[�C��h�4'd�޻�����UUU�����唓�ؒ��}����А�����M�R�HD�����%h3�9�L�tZ��Iqrr���$Oi��
�/_����׿����;ʎ]֞�%$�ģ��n�
��NWL��tmmm"��m������^����m��B�Phaa��ݻgϞ�K&�Tj��YA2:M�Eg���	������x<���b�XCC��֖z� ��K�S�!2�L4��'�ɒ_O�E�n=%���^4����B�B� ]���8w�|Y�n���VVV������~u*:NV�,�z�����C�,V�V������%{)
sss{{{���~��`�7�^�z566[t!%4'BB�B�����{�,�z��IWW��%)�N�z�J.�N������q2����u���C�ę�E���������H$2;;����܇N��'9�a�̩ӥ�iΣ��L�\.�ٳgs�����eY###��S��o��
ri��"cY���a_]�[���D"���>22��V��\J��PC١V���O������!����l#Qv�u*;u��q�����-`�n������ѝ;w�ɤ�œ�����'�t���e�w�ʷ�P���������罾
9�;Y���?�%��
چ�A�Hr�\###��ӏ?�����*2X��߸��X;�a������W����߽{wuu�A�7����Ջ\����b]C3mee�ƍ��Q/6Ҡ����quu���D}�E ��u
i�J�I�ԂƋ&/���������/�˿���%c���*B����/���ܺu�ŋH7b���ZdgԱd�C�!��vww����g�h6�#[�О`0��;�d�ى����=ʐS'���)�!�zQ��A�T�8���^\\�����+jH;��1��ϻ�n�w<tD���(�H�Ձ�f"��������6C�RM�1�[RUUշ�����ډ����u�d����΂�\�h�v ������D�$tt�f�vWW������ֽ{����t����'��L(��zE#!�}���VXv��}�fgg���ԃ��������.�H��{G777����Ѩ0.BP���*���*��;*�LV�C��j�!�v�nYV2����~��)�Bv<���tY�u��ً/F��G��H:;uJ�u4�s�gtt��F�Jә7==���੐a��\� �7���o[���_59�|0���?��������


��O
��ɀ�\ꔜ�4�ӾH��oll��w�+�����B�xIn��…GGG7o�lll<{�l�^�
�XD5Gbu�U��
-��l����~�zcc#bcg���B�0==��߯>T����N�)����G�XrQ/]~Q&�~����Un�b�T*�r������xyy���
��++Ԩ옚��x<��N�����|6��p����]��d�g6��
�e���x�BhkkK��
�vvv|>_*���P/�:ּ��u�����x�޽�����6(���R:Ƞ�	k9j�

����	���DFf2���y��!$t�R�����|j������[R<���;99ihh����B��4��^�B$-���/����w����NNN&''������`wv�#�iC᢫<4uI�
ȜL&gff2�L}}���nSS�<�a��.���6��peee0_\\�}���࠼���BG�=�D�ZB�
�� c�	#�h!�����������P�Ȁ�S'bH�B�ԅ
�זP��+�,˒_�*++�{���`f4�I��T*��ٳ���H$��W'�4w�ض�ޡ���dc>��]{����;f�X�
7۶_�x�L&�J��@��=�_�ޛ���D"���d2�\.WQQ������600���P(�{-O���I�;fb��?Y���
�t޳+"�a����;w�tww�Ş��t�zh�nF�<�!u˕᳇4�L*ip__�\�!ԭ�f�uf������_��M�9�w���YXX�B�H�b+���h6����L$��x�&�XYYYXXx��wՃ���H�]��� ��d�e�������Z%R������ͯ^��{�n__����vQn�zYÐ4.��C�c�V>�|�I(>�������{�jjjua��5��:��A�񂌗�����f�����@@]�B�����������C�W�BGGG0���ba7;����2�4�M��m�f��
����8!�B������˱X�Ν;��2��r����766�E�)�D#IW?!'+�@l/����|���񦦦;w��&�����c�jDZأ�0��5�L�����������ٸW�����/Yv����
B�~�R2*XQ(���S�K�-.UL��C��
���z�����:*�t�����=zT(�%�m{�^t.��:�N�0]���X�s��bS���‚�<�y+'��fS(n޼���OG��v{�^(G���,��uG�˒eY���555�{�:�tG
����&;�.����eH��M�եC�x��m$V�-�jkka@�eeeccc�L���UUU���P����&%^��|����%�"fq�x1w΀���CC�S��ew�������g8f1!DGGGGG�����puu���O���t��#��!FD���n�0��ӧO;;;��'#���`���vvdQ0 ���@Q���6h�b���J���jV[R����"lW�l����0�Ё�x<�/_nmm�{���Ғ.����#�~*JK�m��ubрٶ=33#_�OXQEE�\����I.���llL�g#/nmmA�]W��.�8���$8���7===��������K����fÎ{XĐyP~nj�(��%7�����C�8� \l��P�������X,v�֭�����V:���e]�z��9�A�	
Pj��؜*�d2���������J�DPX �+�p��/^<::��~uu�{�'�l�D}YK1*���YN&�y���v�!��t�z��w4�.���bP�pSe�t���(��UUU%��@ ���uÍ��v�n��������۷o

���ڠ�¾0�������%�������kkk�ɤ��SX��������Xi#�P�Q2������ۻ���n������g�B!4�#��Vg3��BG���_�|y��y4�:pAd�t�}
�L��R��
��8�~�^�����T*�����ظ��YWW�J�Ο?O#���b�q���J������F�ϟ?�w� N�?tS�N%P�977wpp�������ɤ<}�9H����54mþ�٨��՛7o˜%��C�M�:�tS԰�J���"��	A�>��*Ս���+�:��]l�CL%�f��mg2�2���ﳞ��%;iٺD��%{�>88X(��<���eYGGG����Z�.��DE+�IJ����l6;66��������ʞ<yB�0�%��D9B! �����p4��lز[
�“'O���Н��j	� �)V>츳��LJ��)�#�Ā�
,�CQ��q��[���
g�Q�`///�G�����1��QW��pQ�.\8<<|��aee���	Y��x***��5.�":'ez_�YFB��hw����$(wr���ԔeY###���˲���eУ� ���,�Z__/
}}}�!��a�1�gH:N���a�8	"�!.E�rT�.��Q�XQ4iѰ��l����|�r<���hnnV/;�z�{�E���	�eM��$����$>��X�8����(���φU-?��Cmв,�c��7��z��H$b
��1�0CP���"��S�%sM���_eR��sN(
;����� 7���իW���'&&�44�d��Ρ
�]�<(	��ϹT]yy��˗���oݺ����#l��C�A��<y���t���/��beeE=@�Z¦	Et!V4s�]#�ƕ�H�N�E.UE�ʫ��
��	a�d$������˗���i
:Q���}���!�Hm��Ru�_��y��.�����z���֭[{{{��T)Ą�E8P�l6����N��^��l[�Z�T�/;I'�5Z�U(E�Ə-_y�SC�P���5�t��|�:�4Bu�mG"�����O�˧�uьdg�Ly�䡻�N��U������JUÌ��ė�l�KbGFF�{驑��y�`���zK����er�v�@Y�l*<������( `Ypt!�tS�Qg��S�r��� ���8�ک{�E1�;w.���k�����sH���t�Baβ�tȔ$:��e555QgUC���P��Q���ϣk6�C
ӵ�L�H�!u]t
nL�D��A;k��D�R�=�y]��$���m��������t*S���pB��#������333�y�#���+pv�$ ����$t�J��ۋ���.�Gh��m�vYYم>|�Fue��ʁG���IK�?��j8ֺ	�|�.�g���v�U�G��Y����|>�E��J������ֶ�6�	B�u[�"������������Dkk+|4�5ϐ�N۶���f���n�ڶ=00�̒���С���K�.���ݼy3���aڑ��힖�TXѹᤸ�4�
1Xn��NB��2ٶ���Cy�o8��ب����ۓ�����
��&!ق�C'��<~����~��v�-�>]__�s�Nooo(�6����l|��������zkk���ZMM��Ύ|�o�e�+��
��vtt�?�[]]ݻﾻ��z��������z
�mA�M�KTk���a#�~*<͜%E����z�sB˲z{{��xKKKYYY0�Bϟ?g����
%vb�f������f�+�̲���ͽ|�R�Z���H3\OOO"��>�������fyyY�(a�YoI_J�E�T]]l�p8������KxQ~ds�!SC��"͉��y�%�9�cI�t�=�����F�3�L.�K=j�l�>s�Lww��|
���@�eUUU����I~�H�����ypp0��OMMٶ-�-b�	n8�3��_s�Q��0CO(U>�'���==5H6��.��U+��u��yucdɸ�Uv�sܹ�:)�:�XK��F��566600 R�.�z�a�Ł� �5[�Ð5��k�n��hV���m�%��D4�m��h݂S����Wg��f	ϰP���y�n�js�QH��K�-���L�nyy�<��١Gcd|�#��5���
��<~h����E��s�B3sjv�I'U@3�U|�
2 QY���s	ȃ���7dc�E���H��y�V	Z(hl��5�,D�e��6��<(�e'5�a:c�@gu�
<C!B��6��v:(%{QG`��/�ҕ9���l#N��A#5�l�9/�|AQ������� �SH��Y���a_]�L���6b[^^.//��W���P�
����Loo��盝�mkk���2�/[x
dY�h��+�4���B_$��K�[��I�A��;͈*[C�teG��j���@2�a�p���R�Ě}4��6�v�9:G�$>�C>����=z�����d��ő�H�R���:E�B/��8��bq8�
4��F�����P�@�#��#;�4C�l��Y��^
�`v��j�uɌ>��F]���rCɅ6��jd�ba�E"O7D��ae :������<99���,K�+����+W��.�.]�),𗚇���@]�ѡ�N*�¨�0�v(�0�vD!fɈ�d��<�X�]�5��N%S�t�"�O�
Ȱ�q����#f4EY�:ՈӲ,u�8��0`�W2&i*���d#��#H!beB��$�q����ASSS,��������LJ�R�33%��S�yZ���X����(4c����݋�㍍�����@`ww>E%�8<<��*�z���T�#���~����3nf�GGG^�W��-��#�+mZ��Q�
÷����������=��OJ�D�����#������̖�厏��_����x<J�}}}��X�	Tb����H$<O6�mjjjnnF@)�ʛ�:�2����S�bJT�Gk<Z������O|��钽Ju�c,�����|�L&�[.���R0��z.������2fAS��G���t/"�m{ffF�Dݜ��Q�Z��hee%�{k � 1�<�m�%���Ƌ���9��#v@��uuu�6B�����x\tI+
����K�S��f�s�
�m������?-�jnn^ZZz뭷�g��!�͛7S�Tkk���z$�a$��w����VKK���q"��v�|g\�I	�?�f����mmmo���z�:�ҠKD4l>ʃ̀���HD����?T�W�,kiiimm-�������677_�t	���ѣ��۶}>����{�WSS��MMM%��t:���)�����V~�b�/^����
���Ǖ�B�p��퍍�������D"��|���ٳg���B�p8���>00��ى�vX� ��1�#����y��Y>�O$~���K�3��}���������ccc���l�ܾ};noog2�o���RhL&�y�������I�R~��|�srrR�t�\�"9@'#�e=z�hmm���kvvvpp���I���e.�@����p8,?i���,�<Ϣ#������D"��z����JI��v�\���>������r
�d 5L�����b1y7�|>�4�`0d�)���H���B!��9!D(��=�����'�ܐ7�{��L&������a����@ �H$\.�rS
v]]]8��ߗ8�兩\���N��a�˥�	�<��Ͳ���Q���܀�^������͇���\V��shh(��tuu��7B9r�����������n��:���xZ[[��t0lllDO~C�]]]���gΜ����������@ P(zzz��U��R�[A��T��cFUYɖ)C�a3�yj�2
�
���Y�.e��j��Oqf��ԁoP�l3N-��y�m���x@���*i'��3ǒnC�R�u�Rx�\��Z�&�.p
0:
R��#���b+++}}}��������KJ3�v�
�~%V%��i���4օ��J��r������e}���gӢC@�iH(�9'd\I���$�)C�����g�����\�T*���4<<���3��������+p�o6�ffJ��E��j��fq�As�(Ɲ���7VVV~��ߵ��tww���?t��d'�Sd�����1���B�!w���?���`0XVVv��u��b���ʤE�B
ca�]�Fe����u�B
���iYV2���b�m{�ޥ���������ccc/^������O~"+���!�d�&fNWb;S�mR�Y�:Jyl�N&��d2��LNN�9sF]��ug���h��D�%���`8��FI̥۠�%y�:��Խ
�L����D�r��r*�iG��2�L6�M&��|>d��\.������}>_cc#���(	��؎.G�D�L�Rg;,
;�5J{3d��B�Lh���RK�S�D�N{I�ufM�3��A:uB,�uґ5F����/�㩴;Tg�
`��粡ق6�6����2P68�
��
��#KPd�
HPj�K-��))���b��u]�/�f*
���`�N��₀:��
�M����1:N��tr�1��3��yVv-
endstream
endobj
443 0 obj
<< /Type /Page
/Parent 3 0 R
/Annots [ 445 0 R 447 0 R 449 0 R 451 0 R 453 0 R 455 0 R 457 0 R 459 0 R 461 0 R 463 0 R 465 0 R 467 0 R 469 0 R 471 0 R 473 0 R 475 0 R 477 0 R 479 0 R 481 0 R 483 0 R 485 0 R 487 0 R 489 0 R 491 0 R 493 0 R 495 0 R 497 0 R 499 0 R 501 0 R 503 0 R 505 0 R 507 0 R 509 0 R 511 0 R 513 0 R 515 0 R 517 0 R 519 0 R 521 0 R 523 0 R 525 0 R 527 0 R 529 0 R 531 0 R 533 0 R 535 0 R 537 0 R 539 0 R 541 0 R 543 0 R 545 0 R 547 0 R 549 0 R 551 0 R 553 0 R 555 0 R 557 0 R 559 0 R 561 0 R 563 0 R 565 0 R 567 0 R 569 0 R 571 0 R 573 0 R 575 0 R 577 0 R 579 0 R 581 0 R 583 0 R 585 0 R 587 0 R 589 0 R 591 0 R 593 0 R 595 0 R 597 0 R 599 0 R 601 0 R 603 0 R 605 0 R 607 0 R 609 0 R 611 0 R ]
/Contents 444 0 R
>>
endobj
444 0 obj
<<
/Length 32569 >>
stream

q
15.000 17.214 577.500 759.786 re W n
0.965 0.965 0.965 rg
26.250 687.232 555.000 89.768 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 687.232 m 581.250 687.232 l 581.250 687.982 l 26.250 687.982 l  f
q
35.250 698.482 537.000 78.518 re W n
0.271 0.267 0.267 rg
BT 35.250 767.476 Td /F4 9.8 Tf  [(Fig. 2: A strong relation can be seen between gastric emptying of solids measured by 13 C sodium octanoate )] TJ ET
BT 35.250 755.571 Td /F4 9.8 Tf  [(breath test)] TJ ET
BT 35.250 736.201 Td /F1 9.8 Tf  [(A strong relation can be seen between gastric emptying of solids measured by 13 C sodium octanoate breath test, )] TJ ET
BT 35.250 722.465 Td /F1 9.8 Tf  [(presented as individual t lag \(a\) and t 50 \(b\) in minutes and the cognitive sum score of the UHDRS \(t 50 � p 0.018; r � .692 )] TJ ET
BT 35.250 708.729 Td /F1 9.8 Tf  [(and t lag � p 0.019; r � .688\), as well as for PDR max \(c\) and total functional capacity \(TFC; p 0.014, r .712\).)] TJ ET
Q
BT 26.250 670.208 Td /F1 9.8 Tf  [(The correlation analysis of GCSI and SF-LDQ with clinical symptoms showed no significant correlation with any of the clinical )] TJ ET
BT 26.250 658.303 Td /F1 9.8 Tf  [(characteristics from table 1.)] TJ ET
BT 26.250 621.701 Td /F4 12.0 Tf  [(Discussion)] TJ ET
BT 26.250 601.746 Td /F1 9.8 Tf  [(Several factors such as dysphagia, an increased motor activity, an increased metabolic rate and hypermetabolic state have )] TJ ET
BT 26.250 589.842 Td /F1 9.8 Tf  [(been discussed as contributing to weight loss even at early stages of HD. In addition, a recently published study also suggested )] TJ ET
BT 26.250 577.937 Td /F1 9.8 Tf  [(gastrointestinal tract dysfunction as a reason for weight loss in a Huntington mouse model, similar to findings for Parkinson�s )] TJ ET
BT 26.250 566.032 Td /F1 9.8 Tf  [(disease \(PD\). )] TJ ET
0.267 0.267 0.267 rg
BT 88.016 566.032 Td /F1 9.8 Tf  [([14])] TJ ET
BT 104.279 566.032 Td /F1 9.8 Tf  [([15])] TJ ET
BT 120.542 566.032 Td /F1 9.8 Tf  [([21])] TJ ET
0.271 0.267 0.267 rg
BT 136.805 566.032 Td /F1 9.8 Tf  [( Several studies describe a delay in gastric emptying for 88% or even for up to 100% of PD patients. )] TJ ET
0.267 0.267 0.267 rg
BT 26.250 554.127 Td /F1 9.8 Tf  [([16])] TJ ET
BT 42.513 554.127 Td /F1 9.8 Tf  [([17])] TJ ET
BT 58.776 554.127 Td /F1 9.8 Tf  [([18])] TJ ET
BT 75.039 554.127 Td /F1 9.8 Tf  [([19])] TJ ET
BT 91.302 554.127 Td /F1 9.8 Tf  [([20])] TJ ET
BT 107.565 554.127 Td /F1 9.8 Tf  [([21])] TJ ET
0.271 0.267 0.267 rg
BT 123.828 554.127 Td /F1 9.8 Tf  [( Contrary to this, in our pilot study on HD patients did not provide any evidence of impaired gastric )] TJ ET
BT 26.250 542.223 Td /F1 9.8 Tf  [(emptying by using a solid meal and the )] TJ ET
BT 197.499 546.111 Td /F1 8.7 Tf  [(13)] TJ ET
BT 207.136 542.223 Td /F1 9.8 Tf  [( C-sodium octanoate breath test. There were no significant differences compared to )] TJ ET
BT 26.250 530.318 Td /F1 9.8 Tf  [(controls and also compared to standard values given in literature all parameters were within normal range. In addition, we had )] TJ ET
BT 26.250 518.413 Td /F1 9.8 Tf  [(no clinical evidence of gastroparesis or dyspepsia symptoms by using the �Gastroparesis Cardinal Symptom Index� and �Short-)] TJ ET
BT 26.250 506.508 Td /F1 9.8 Tf  [(Form Leeds Dyspepsia Questionnaire� in our cohort. Thus, our data contrast with data for PD, but also with data for HD mice.)] TJ ET
BT 26.250 487.104 Td /F1 9.8 Tf  [(As a possible explanation, gastric emptying may only contribute to weight loss more severe stages of HD. R6/2 HD mice usually )] TJ ET
BT 26.250 475.199 Td /F1 9.8 Tf  [(show a very rapid course of the disease. A recent published study investigating the GI tract in a R6/2 mice model carrying a )] TJ ET
BT 26.250 463.294 Td /F1 9.8 Tf  [(mean of 204 CAG-repeats describes several GI abnormalities, including an increased water content in R6/2 compared to feces )] TJ ET
BT 26.250 451.389 Td /F1 9.8 Tf  [(in wild type mice from 8 weeks of age. The fecal output as a percentage of food intake however, was only significantly increased )] TJ ET
BT 26.250 439.485 Td /F1 9.8 Tf  [(at 12 weeks, but not at 8 weeks. )] TJ ET
0.267 0.267 0.267 rg
BT 168.249 439.485 Td /F1 9.8 Tf  [([14])] TJ ET
0.271 0.267 0.267 rg
BT 184.512 439.485 Td /F1 9.8 Tf  [( This indicates that the occurrence of malabsorption of nutrients plays an important role in )] TJ ET
BT 26.250 427.580 Td /F1 9.8 Tf  [(weight loss in HD mice only in the end stage. The study did not investigate early stages of the disease prior 8 weeks in the mice )] TJ ET
BT 26.250 415.675 Td /F1 9.8 Tf  [(model.)] TJ ET
BT 26.250 396.270 Td /F1 9.8 Tf  [(An earlier study from our group describes a high prevalence of gastritis or esophagitis as an accidental finding during PEG-)] TJ ET
BT 26.250 384.366 Td /F1 9.8 Tf  [(placement, as a possible indication of gastrointestinal tract dysfunction in HD patients at advanced stages of the disease. )] TJ ET
0.267 0.267 0.267 rg
BT 550.303 384.366 Td /F1 9.8 Tf  [([40])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 372.461 Td /F1 9.8 Tf  [(The findings in this study were also correlated with the duration and severity of the disease, also suggesting that gastrointestinal )] TJ ET
BT 26.250 360.556 Td /F1 9.8 Tf  [(tract dysfunction might occur later in the course of the disease. We presumed that influences from the disease itself as well as )] TJ ET
BT 26.250 348.651 Td /F1 9.8 Tf  [(secondary mechanisms like medication and general disability may contribute. )] TJ ET
0.267 0.267 0.267 rg
BT 362.206 348.651 Td /F1 9.8 Tf  [([40])] TJ ET
0.271 0.267 0.267 rg
BT 378.469 348.651 Td /F1 9.8 Tf  [( It was also the case in this study that the )] TJ ET
BT 26.250 336.747 Td /F1 9.8 Tf  [(focus was not on early symptomatic patients.)] TJ ET
BT 26.250 317.342 Td /F1 9.8 Tf  [(To summarize, the pilot data from our study suggest that impaired gastric emptying is not an early event in HD when compared )] TJ ET
BT 26.250 305.437 Td /F1 9.8 Tf  [(to PD. We can not exclude that gastric emptying contributes to weight loss at more advanced stages of the disease.)] TJ ET
BT 26.250 286.032 Td /F1 9.8 Tf  [(Surprisingly, we found a significant correlation for the cognitive sum score und the total functional capacity of the UHDRS and )] TJ ET
BT 26.250 274.128 Td /F1 9.8 Tf  [(breath test results, such as t )] TJ ET
BT 150.894 272.063 Td /F1 8.7 Tf  [(50)] TJ ET
BT 160.531 274.128 Td /F1 9.8 Tf  [( \(47.8% of variance\), tl )] TJ ET
BT 260.781 272.063 Td /F1 8.7 Tf  [(ag)] TJ ET
BT 270.418 274.128 Td /F1 9.8 Tf  [( \(47.4% of variance\) and PDR )] TJ ET
BT 402.638 272.063 Td /F1 8.7 Tf  [(max)] TJ ET
BT 419.009 274.128 Td /F1 9.8 Tf  [( which usually shows the most )] TJ ET
BT 26.250 262.223 Td /F1 9.8 Tf  [(precise quantification \(50.6% of variance; see figure 2\). This was not expected, since OBT results were within normal range. )] TJ ET
BT 26.250 250.318 Td /F1 9.8 Tf  [(Cognitive decline, however, is a very early event in the course of HD. )] TJ ET
0.267 0.267 0.267 rg
BT 326.452 250.318 Td /F1 9.8 Tf  [([41])] TJ ET
0.271 0.267 0.267 rg
BT 342.715 250.318 Td /F1 9.8 Tf  [( In fact the cognitive sum score from our HD )] TJ ET
BT 26.250 238.413 Td /F1 9.8 Tf  [(participants showed a broad range from 98-346 points with a mean of 195.1 points indicating a cognitive impairment in most of )] TJ ET
BT 26.250 226.509 Td /F1 9.8 Tf  [(the patients. It is well known that the performance in UHDRS cognitive tests declined during disease progression, as did the )] TJ ET
BT 26.250 214.604 Td /F1 9.8 Tf  [(functional capacity \(TFC\), which is highly dependent on cognitive tasks. )] TJ ET
0.267 0.267 0.267 rg
BT 337.295 214.604 Td /F1 9.8 Tf  [([42])] TJ ET
BT 353.558 214.604 Td /F1 9.8 Tf  [([43])] TJ ET
0.271 0.267 0.267 rg
BT 369.820 214.604 Td /F1 9.8 Tf  [( A decrement in mitochondrial function is )] TJ ET
BT 26.250 202.699 Td /F1 9.8 Tf  [(discussed as contributing to age-dependent functional deficits in neurons and myocytes in normal aging and other neurological )] TJ ET
BT 26.250 190.794 Td /F1 9.8 Tf  [(disorders, such as Alzheimer�s disease, accompanied with a cognitive decline. )] TJ ET
0.267 0.267 0.267 rg
BT 366.545 190.794 Td /F1 9.8 Tf  [([44])] TJ ET
BT 382.808 190.794 Td /F1 9.8 Tf  [([45])] TJ ET
BT 399.070 190.794 Td /F1 9.8 Tf  [([46])] TJ ET
0.271 0.267 0.267 rg
BT 415.333 190.794 Td /F1 9.8 Tf  [( Mitochondrial dysfunction is well )] TJ ET
BT 26.250 178.890 Td /F1 9.8 Tf  [(known in HD and seems to be a relevant and early feature in the pathology. )] TJ ET
0.267 0.267 0.267 rg
BT 354.669 178.890 Td /F1 9.8 Tf  [([47])] TJ ET
BT 370.932 178.890 Td /F1 9.8 Tf  [([48])] TJ ET
BT 387.195 178.890 Td /F1 9.8 Tf  [([49])] TJ ET
0.271 0.267 0.267 rg
BT 403.458 178.890 Td /F1 9.8 Tf  [( Mutant htt \(mtHtt\) tends to aggregate in )] TJ ET
BT 26.250 166.985 Td /F1 9.8 Tf  [(cytoplasm and nucleus of neurons as well as non-neuronal tissues including the liver. )] TJ ET
0.267 0.267 0.267 rg
BT 396.370 166.985 Td /F1 9.8 Tf  [([50])] TJ ET
BT 412.633 166.985 Td /F1 9.8 Tf  [([51])] TJ ET
BT 428.896 166.985 Td /F1 9.8 Tf  [([52])] TJ ET
BT 445.159 166.985 Td /F1 9.8 Tf  [([53])] TJ ET
BT 461.422 166.985 Td /F1 9.8 Tf  [([54])] TJ ET
BT 477.685 166.985 Td /F1 9.8 Tf  [([55])] TJ ET
0.271 0.267 0.267 rg
BT 493.948 166.985 Td /F1 9.8 Tf  [( Within the )] TJ ET
BT 26.250 155.080 Td /F1 9.8 Tf  [(mitochondria, octanoic acid undergoes b-oxidation. Octanic acid generates acetyl coenzyme A which enters the Krebs cycle )] TJ ET
BT 26.250 143.175 Td /F1 9.8 Tf  [(and is oxidized to CO )] TJ ET
BT 121.624 141.111 Td /F1 8.7 Tf  [(2)] TJ ET
BT 126.443 143.175 Td /F1 9.8 Tf  [( . Therefore breath tests based on octanoate, usually used to assess gastric emptying, should also )] TJ ET
BT 26.250 131.271 Td /F1 9.8 Tf  [(reflect mitochondrial function. )] TJ ET
0.267 0.267 0.267 rg
BT 155.759 131.271 Td /F1 9.8 Tf  [([56])] TJ ET
0.271 0.267 0.267 rg
BT 172.022 131.271 Td /F1 9.8 Tf  [( Thus, one can speculate that a correlation of OBT results with results of cognitive tasks might )] TJ ET
BT 26.250 119.366 Td /F1 9.8 Tf  [(reflect a parallel decline in cognitive and mitochondrial function.)] TJ ET
BT 26.250 99.961 Td /F1 9.8 Tf  [(To our knowledge this is the first study dealing with gastrointestinal track dysfunction in HD in vivo. A limitation of our study is )] TJ ET
BT 26.250 88.056 Td /F1 9.8 Tf  [(the relative small number of participants. To exclude drug effects we only included patients without any medication and without )] TJ ET
BT 26.250 76.152 Td /F1 9.8 Tf  [(serious comorbidities. On the other hand, due to the fact that this is a very rare group of patients it is a strength of our study that )] TJ ET
BT 26.250 64.247 Td /F1 9.8 Tf  [(we can exclude medication effects.)] TJ ET
Q
q
15.000 17.214 577.500 759.786 re W n
0.965 0.965 0.965 rg
26.250 687.232 555.000 89.768 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 687.232 m 581.250 687.232 l 581.250 687.982 l 26.250 687.982 l  f
q
35.250 698.482 537.000 78.518 re W n
0.271 0.267 0.267 rg
BT 35.250 767.476 Td /F4 9.8 Tf  [(Fig. 2: A strong relation can be seen between gastric emptying of solids measured by 13 C sodium octanoate )] TJ ET
BT 35.250 755.571 Td /F4 9.8 Tf  [(breath test)] TJ ET
BT 35.250 736.201 Td /F1 9.8 Tf  [(A strong relation can be seen between gastric emptying of solids measured by 13 C sodium octanoate breath test, )] TJ ET
BT 35.250 722.465 Td /F1 9.8 Tf  [(presented as individual t lag \(a\) and t 50 \(b\) in minutes and the cognitive sum score of the UHDRS \(t 50 � p 0.018; r � .692 )] TJ ET
BT 35.250 708.729 Td /F1 9.8 Tf  [(and t lag � p 0.019; r � .688\), as well as for PDR max \(c\) and total functional capacity \(TFC; p 0.014, r .712\).)] TJ ET
Q
BT 26.250 670.208 Td /F1 9.8 Tf  [(The correlation analysis of GCSI and SF-LDQ with clinical symptoms showed no significant correlation with any of the clinical )] TJ ET
BT 26.250 658.303 Td /F1 9.8 Tf  [(characteristics from table 1.)] TJ ET
BT 26.250 621.701 Td /F4 12.0 Tf  [(Discussion)] TJ ET
BT 26.250 601.746 Td /F1 9.8 Tf  [(Several factors such as dysphagia, an increased motor activity, an increased metabolic rate and hypermetabolic state have )] TJ ET
BT 26.250 589.842 Td /F1 9.8 Tf  [(been discussed as contributing to weight loss even at early stages of HD. In addition, a recently published study also suggested )] TJ ET
BT 26.250 577.937 Td /F1 9.8 Tf  [(gastrointestinal tract dysfunction as a reason for weight loss in a Huntington mouse model, similar to findings for Parkinson�s )] TJ ET
BT 26.250 566.032 Td /F1 9.8 Tf  [(disease \(PD\). )] TJ ET
0.267 0.267 0.267 rg
BT 88.016 566.032 Td /F1 9.8 Tf  [([14])] TJ ET
BT 104.279 566.032 Td /F1 9.8 Tf  [([15])] TJ ET
BT 120.542 566.032 Td /F1 9.8 Tf  [([21])] TJ ET
0.271 0.267 0.267 rg
BT 136.805 566.032 Td /F1 9.8 Tf  [( Several studies describe a delay in gastric emptying for 88% or even for up to 100% of PD patients. )] TJ ET
0.267 0.267 0.267 rg
BT 26.250 554.127 Td /F1 9.8 Tf  [([16])] TJ ET
BT 42.513 554.127 Td /F1 9.8 Tf  [([17])] TJ ET
BT 58.776 554.127 Td /F1 9.8 Tf  [([18])] TJ ET
BT 75.039 554.127 Td /F1 9.8 Tf  [([19])] TJ ET
BT 91.302 554.127 Td /F1 9.8 Tf  [([20])] TJ ET
BT 107.565 554.127 Td /F1 9.8 Tf  [([21])] TJ ET
0.271 0.267 0.267 rg
BT 123.828 554.127 Td /F1 9.8 Tf  [( Contrary to this, in our pilot study on HD patients did not provide any evidence of impaired gastric )] TJ ET
BT 26.250 542.223 Td /F1 9.8 Tf  [(emptying by using a solid meal and the )] TJ ET
BT 197.499 546.111 Td /F1 8.7 Tf  [(13)] TJ ET
BT 207.136 542.223 Td /F1 9.8 Tf  [( C-sodium octanoate breath test. There were no significant differences compared to )] TJ ET
BT 26.250 530.318 Td /F1 9.8 Tf  [(controls and also compared to standard values given in literature all parameters were within normal range. In addition, we had )] TJ ET
BT 26.250 518.413 Td /F1 9.8 Tf  [(no clinical evidence of gastroparesis or dyspepsia symptoms by using the �Gastroparesis Cardinal Symptom Index� and �Short-)] TJ ET
BT 26.250 506.508 Td /F1 9.8 Tf  [(Form Leeds Dyspepsia Questionnaire� in our cohort. Thus, our data contrast with data for PD, but also with data for HD mice.)] TJ ET
BT 26.250 487.104 Td /F1 9.8 Tf  [(As a possible explanation, gastric emptying may only contribute to weight loss more severe stages of HD. R6/2 HD mice usually )] TJ ET
BT 26.250 475.199 Td /F1 9.8 Tf  [(show a very rapid course of the disease. A recent published study investigating the GI tract in a R6/2 mice model carrying a )] TJ ET
BT 26.250 463.294 Td /F1 9.8 Tf  [(mean of 204 CAG-repeats describes several GI abnormalities, including an increased water content in R6/2 compared to feces )] TJ ET
BT 26.250 451.389 Td /F1 9.8 Tf  [(in wild type mice from 8 weeks of age. The fecal output as a percentage of food intake however, was only significantly increased )] TJ ET
BT 26.250 439.485 Td /F1 9.8 Tf  [(at 12 weeks, but not at 8 weeks. )] TJ ET
0.267 0.267 0.267 rg
BT 168.249 439.485 Td /F1 9.8 Tf  [([14])] TJ ET
0.271 0.267 0.267 rg
BT 184.512 439.485 Td /F1 9.8 Tf  [( This indicates that the occurrence of malabsorption of nutrients plays an important role in )] TJ ET
BT 26.250 427.580 Td /F1 9.8 Tf  [(weight loss in HD mice only in the end stage. The study did not investigate early stages of the disease prior 8 weeks in the mice )] TJ ET
BT 26.250 415.675 Td /F1 9.8 Tf  [(model.)] TJ ET
BT 26.250 396.270 Td /F1 9.8 Tf  [(An earlier study from our group describes a high prevalence of gastritis or esophagitis as an accidental finding during PEG-)] TJ ET
BT 26.250 384.366 Td /F1 9.8 Tf  [(placement, as a possible indication of gastrointestinal tract dysfunction in HD patients at advanced stages of the disease. )] TJ ET
0.267 0.267 0.267 rg
BT 550.303 384.366 Td /F1 9.8 Tf  [([40])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 372.461 Td /F1 9.8 Tf  [(The findings in this study were also correlated with the duration and severity of the disease, also suggesting that gastrointestinal )] TJ ET
BT 26.250 360.556 Td /F1 9.8 Tf  [(tract dysfunction might occur later in the course of the disease. We presumed that influences from the disease itself as well as )] TJ ET
BT 26.250 348.651 Td /F1 9.8 Tf  [(secondary mechanisms like medication and general disability may contribute. )] TJ ET
0.267 0.267 0.267 rg
BT 362.206 348.651 Td /F1 9.8 Tf  [([40])] TJ ET
0.271 0.267 0.267 rg
BT 378.469 348.651 Td /F1 9.8 Tf  [( It was also the case in this study that the )] TJ ET
BT 26.250 336.747 Td /F1 9.8 Tf  [(focus was not on early symptomatic patients.)] TJ ET
BT 26.250 317.342 Td /F1 9.8 Tf  [(To summarize, the pilot data from our study suggest that impaired gastric emptying is not an early event in HD when compared )] TJ ET
BT 26.250 305.437 Td /F1 9.8 Tf  [(to PD. We can not exclude that gastric emptying contributes to weight loss at more advanced stages of the disease.)] TJ ET
BT 26.250 286.032 Td /F1 9.8 Tf  [(Surprisingly, we found a significant correlation for the cognitive sum score und the total functional capacity of the UHDRS and )] TJ ET
BT 26.250 274.128 Td /F1 9.8 Tf  [(breath test results, such as t )] TJ ET
BT 150.894 272.063 Td /F1 8.7 Tf  [(50)] TJ ET
BT 160.531 274.128 Td /F1 9.8 Tf  [( \(47.8% of variance\), tl )] TJ ET
BT 260.781 272.063 Td /F1 8.7 Tf  [(ag)] TJ ET
BT 270.418 274.128 Td /F1 9.8 Tf  [( \(47.4% of variance\) and PDR )] TJ ET
BT 402.638 272.063 Td /F1 8.7 Tf  [(max)] TJ ET
BT 419.009 274.128 Td /F1 9.8 Tf  [( which usually shows the most )] TJ ET
BT 26.250 262.223 Td /F1 9.8 Tf  [(precise quantification \(50.6% of variance; see figure 2\). This was not expected, since OBT results were within normal range. )] TJ ET
BT 26.250 250.318 Td /F1 9.8 Tf  [(Cognitive decline, however, is a very early event in the course of HD. )] TJ ET
0.267 0.267 0.267 rg
BT 326.452 250.318 Td /F1 9.8 Tf  [([41])] TJ ET
0.271 0.267 0.267 rg
BT 342.715 250.318 Td /F1 9.8 Tf  [( In fact the cognitive sum score from our HD )] TJ ET
BT 26.250 238.413 Td /F1 9.8 Tf  [(participants showed a broad range from 98-346 points with a mean of 195.1 points indicating a cognitive impairment in most of )] TJ ET
BT 26.250 226.509 Td /F1 9.8 Tf  [(the patients. It is well known that the performance in UHDRS cognitive tests declined during disease progression, as did the )] TJ ET
BT 26.250 214.604 Td /F1 9.8 Tf  [(functional capacity \(TFC\), which is highly dependent on cognitive tasks. )] TJ ET
0.267 0.267 0.267 rg
BT 337.295 214.604 Td /F1 9.8 Tf  [([42])] TJ ET
BT 353.558 214.604 Td /F1 9.8 Tf  [([43])] TJ ET
0.271 0.267 0.267 rg
BT 369.820 214.604 Td /F1 9.8 Tf  [( A decrement in mitochondrial function is )] TJ ET
BT 26.250 202.699 Td /F1 9.8 Tf  [(discussed as contributing to age-dependent functional deficits in neurons and myocytes in normal aging and other neurological )] TJ ET
BT 26.250 190.794 Td /F1 9.8 Tf  [(disorders, such as Alzheimer�s disease, accompanied with a cognitive decline. )] TJ ET
0.267 0.267 0.267 rg
BT 366.545 190.794 Td /F1 9.8 Tf  [([44])] TJ ET
BT 382.808 190.794 Td /F1 9.8 Tf  [([45])] TJ ET
BT 399.070 190.794 Td /F1 9.8 Tf  [([46])] TJ ET
0.271 0.267 0.267 rg
BT 415.333 190.794 Td /F1 9.8 Tf  [( Mitochondrial dysfunction is well )] TJ ET
BT 26.250 178.890 Td /F1 9.8 Tf  [(known in HD and seems to be a relevant and early feature in the pathology. )] TJ ET
0.267 0.267 0.267 rg
BT 354.669 178.890 Td /F1 9.8 Tf  [([47])] TJ ET
BT 370.932 178.890 Td /F1 9.8 Tf  [([48])] TJ ET
BT 387.195 178.890 Td /F1 9.8 Tf  [([49])] TJ ET
0.271 0.267 0.267 rg
BT 403.458 178.890 Td /F1 9.8 Tf  [( Mutant htt \(mtHtt\) tends to aggregate in )] TJ ET
BT 26.250 166.985 Td /F1 9.8 Tf  [(cytoplasm and nucleus of neurons as well as non-neuronal tissues including the liver. )] TJ ET
0.267 0.267 0.267 rg
BT 396.370 166.985 Td /F1 9.8 Tf  [([50])] TJ ET
BT 412.633 166.985 Td /F1 9.8 Tf  [([51])] TJ ET
BT 428.896 166.985 Td /F1 9.8 Tf  [([52])] TJ ET
BT 445.159 166.985 Td /F1 9.8 Tf  [([53])] TJ ET
BT 461.422 166.985 Td /F1 9.8 Tf  [([54])] TJ ET
BT 477.685 166.985 Td /F1 9.8 Tf  [([55])] TJ ET
0.271 0.267 0.267 rg
BT 493.948 166.985 Td /F1 9.8 Tf  [( Within the )] TJ ET
BT 26.250 155.080 Td /F1 9.8 Tf  [(mitochondria, octanoic acid undergoes b-oxidation. Octanic acid generates acetyl coenzyme A which enters the Krebs cycle )] TJ ET
BT 26.250 143.175 Td /F1 9.8 Tf  [(and is oxidized to CO )] TJ ET
BT 121.624 141.111 Td /F1 8.7 Tf  [(2)] TJ ET
BT 126.443 143.175 Td /F1 9.8 Tf  [( . Therefore breath tests based on octanoate, usually used to assess gastric emptying, should also )] TJ ET
BT 26.250 131.271 Td /F1 9.8 Tf  [(reflect mitochondrial function. )] TJ ET
0.267 0.267 0.267 rg
BT 155.759 131.271 Td /F1 9.8 Tf  [([56])] TJ ET
0.271 0.267 0.267 rg
BT 172.022 131.271 Td /F1 9.8 Tf  [( Thus, one can speculate that a correlation of OBT results with results of cognitive tasks might )] TJ ET
BT 26.250 119.366 Td /F1 9.8 Tf  [(reflect a parallel decline in cognitive and mitochondrial function.)] TJ ET
BT 26.250 99.961 Td /F1 9.8 Tf  [(To our knowledge this is the first study dealing with gastrointestinal track dysfunction in HD in vivo. A limitation of our study is )] TJ ET
BT 26.250 88.056 Td /F1 9.8 Tf  [(the relative small number of participants. To exclude drug effects we only included patients without any medication and without )] TJ ET
BT 26.250 76.152 Td /F1 9.8 Tf  [(serious comorbidities. On the other hand, due to the fact that this is a very rare group of patients it is a strength of our study that )] TJ ET
BT 26.250 64.247 Td /F1 9.8 Tf  [(we can exclude medication effects.)] TJ ET
Q
q
15.000 17.214 577.500 759.786 re W n
0.965 0.965 0.965 rg
26.250 687.232 555.000 89.768 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 687.232 m 581.250 687.232 l 581.250 687.982 l 26.250 687.982 l  f
q
35.250 698.482 537.000 78.518 re W n
0.271 0.267 0.267 rg
BT 35.250 767.476 Td /F4 9.8 Tf  [(Fig. 2: A strong relation can be seen between gastric emptying of solids measured by 13 C sodium octanoate )] TJ ET
BT 35.250 755.571 Td /F4 9.8 Tf  [(breath test)] TJ ET
BT 35.250 736.201 Td /F1 9.8 Tf  [(A strong relation can be seen between gastric emptying of solids measured by 13 C sodium octanoate breath test, )] TJ ET
BT 35.250 722.465 Td /F1 9.8 Tf  [(presented as individual t lag \(a\) and t 50 \(b\) in minutes and the cognitive sum score of the UHDRS \(t 50 � p 0.018; r � .692 )] TJ ET
BT 35.250 708.729 Td /F1 9.8 Tf  [(and t lag � p 0.019; r � .688\), as well as for PDR max \(c\) and total functional capacity \(TFC; p 0.014, r .712\).)] TJ ET
Q
BT 26.250 670.208 Td /F1 9.8 Tf  [(The correlation analysis of GCSI and SF-LDQ with clinical symptoms showed no significant correlation with any of the clinical )] TJ ET
BT 26.250 658.303 Td /F1 9.8 Tf  [(characteristics from table 1.)] TJ ET
BT 26.250 621.701 Td /F4 12.0 Tf  [(Discussion)] TJ ET
BT 26.250 601.746 Td /F1 9.8 Tf  [(Several factors such as dysphagia, an increased motor activity, an increased metabolic rate and hypermetabolic state have )] TJ ET
BT 26.250 589.842 Td /F1 9.8 Tf  [(been discussed as contributing to weight loss even at early stages of HD. In addition, a recently published study also suggested )] TJ ET
BT 26.250 577.937 Td /F1 9.8 Tf  [(gastrointestinal tract dysfunction as a reason for weight loss in a Huntington mouse model, similar to findings for Parkinson�s )] TJ ET
BT 26.250 566.032 Td /F1 9.8 Tf  [(disease \(PD\). )] TJ ET
0.267 0.267 0.267 rg
BT 88.016 566.032 Td /F1 9.8 Tf  [([14])] TJ ET
BT 104.279 566.032 Td /F1 9.8 Tf  [([15])] TJ ET
BT 120.542 566.032 Td /F1 9.8 Tf  [([21])] TJ ET
0.271 0.267 0.267 rg
BT 136.805 566.032 Td /F1 9.8 Tf  [( Several studies describe a delay in gastric emptying for 88% or even for up to 100% of PD patients. )] TJ ET
0.267 0.267 0.267 rg
BT 26.250 554.127 Td /F1 9.8 Tf  [([16])] TJ ET
BT 42.513 554.127 Td /F1 9.8 Tf  [([17])] TJ ET
BT 58.776 554.127 Td /F1 9.8 Tf  [([18])] TJ ET
BT 75.039 554.127 Td /F1 9.8 Tf  [([19])] TJ ET
BT 91.302 554.127 Td /F1 9.8 Tf  [([20])] TJ ET
BT 107.565 554.127 Td /F1 9.8 Tf  [([21])] TJ ET
0.271 0.267 0.267 rg
BT 123.828 554.127 Td /F1 9.8 Tf  [( Contrary to this, in our pilot study on HD patients did not provide any evidence of impaired gastric )] TJ ET
BT 26.250 542.223 Td /F1 9.8 Tf  [(emptying by using a solid meal and the )] TJ ET
BT 197.499 546.111 Td /F1 8.7 Tf  [(13)] TJ ET
BT 207.136 542.223 Td /F1 9.8 Tf  [( C-sodium octanoate breath test. There were no significant differences compared to )] TJ ET
BT 26.250 530.318 Td /F1 9.8 Tf  [(controls and also compared to standard values given in literature all parameters were within normal range. In addition, we had )] TJ ET
BT 26.250 518.413 Td /F1 9.8 Tf  [(no clinical evidence of gastroparesis or dyspepsia symptoms by using the �Gastroparesis Cardinal Symptom Index� and �Short-)] TJ ET
BT 26.250 506.508 Td /F1 9.8 Tf  [(Form Leeds Dyspepsia Questionnaire� in our cohort. Thus, our data contrast with data for PD, but also with data for HD mice.)] TJ ET
BT 26.250 487.104 Td /F1 9.8 Tf  [(As a possible explanation, gastric emptying may only contribute to weight loss more severe stages of HD. R6/2 HD mice usually )] TJ ET
BT 26.250 475.199 Td /F1 9.8 Tf  [(show a very rapid course of the disease. A recent published study investigating the GI tract in a R6/2 mice model carrying a )] TJ ET
BT 26.250 463.294 Td /F1 9.8 Tf  [(mean of 204 CAG-repeats describes several GI abnormalities, including an increased water content in R6/2 compared to feces )] TJ ET
BT 26.250 451.389 Td /F1 9.8 Tf  [(in wild type mice from 8 weeks of age. The fecal output as a percentage of food intake however, was only significantly increased )] TJ ET
BT 26.250 439.485 Td /F1 9.8 Tf  [(at 12 weeks, but not at 8 weeks. )] TJ ET
0.267 0.267 0.267 rg
BT 168.249 439.485 Td /F1 9.8 Tf  [([14])] TJ ET
0.271 0.267 0.267 rg
BT 184.512 439.485 Td /F1 9.8 Tf  [( This indicates that the occurrence of malabsorption of nutrients plays an important role in )] TJ ET
BT 26.250 427.580 Td /F1 9.8 Tf  [(weight loss in HD mice only in the end stage. The study did not investigate early stages of the disease prior 8 weeks in the mice )] TJ ET
BT 26.250 415.675 Td /F1 9.8 Tf  [(model.)] TJ ET
BT 26.250 396.270 Td /F1 9.8 Tf  [(An earlier study from our group describes a high prevalence of gastritis or esophagitis as an accidental finding during PEG-)] TJ ET
BT 26.250 384.366 Td /F1 9.8 Tf  [(placement, as a possible indication of gastrointestinal tract dysfunction in HD patients at advanced stages of the disease. )] TJ ET
0.267 0.267 0.267 rg
BT 550.303 384.366 Td /F1 9.8 Tf  [([40])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 372.461 Td /F1 9.8 Tf  [(The findings in this study were also correlated with the duration and severity of the disease, also suggesting that gastrointestinal )] TJ ET
BT 26.250 360.556 Td /F1 9.8 Tf  [(tract dysfunction might occur later in the course of the disease. We presumed that influences from the disease itself as well as )] TJ ET
BT 26.250 348.651 Td /F1 9.8 Tf  [(secondary mechanisms like medication and general disability may contribute. )] TJ ET
0.267 0.267 0.267 rg
BT 362.206 348.651 Td /F1 9.8 Tf  [([40])] TJ ET
0.271 0.267 0.267 rg
BT 378.469 348.651 Td /F1 9.8 Tf  [( It was also the case in this study that the )] TJ ET
BT 26.250 336.747 Td /F1 9.8 Tf  [(focus was not on early symptomatic patients.)] TJ ET
BT 26.250 317.342 Td /F1 9.8 Tf  [(To summarize, the pilot data from our study suggest that impaired gastric emptying is not an early event in HD when compared )] TJ ET
BT 26.250 305.437 Td /F1 9.8 Tf  [(to PD. We can not exclude that gastric emptying contributes to weight loss at more advanced stages of the disease.)] TJ ET
BT 26.250 286.032 Td /F1 9.8 Tf  [(Surprisingly, we found a significant correlation for the cognitive sum score und the total functional capacity of the UHDRS and )] TJ ET
BT 26.250 274.128 Td /F1 9.8 Tf  [(breath test results, such as t )] TJ ET
BT 150.894 272.063 Td /F1 8.7 Tf  [(50)] TJ ET
BT 160.531 274.128 Td /F1 9.8 Tf  [( \(47.8% of variance\), tl )] TJ ET
BT 260.781 272.063 Td /F1 8.7 Tf  [(ag)] TJ ET
BT 270.418 274.128 Td /F1 9.8 Tf  [( \(47.4% of variance\) and PDR )] TJ ET
BT 402.638 272.063 Td /F1 8.7 Tf  [(max)] TJ ET
BT 419.009 274.128 Td /F1 9.8 Tf  [( which usually shows the most )] TJ ET
BT 26.250 262.223 Td /F1 9.8 Tf  [(precise quantification \(50.6% of variance; see figure 2\). This was not expected, since OBT results were within normal range. )] TJ ET
BT 26.250 250.318 Td /F1 9.8 Tf  [(Cognitive decline, however, is a very early event in the course of HD. )] TJ ET
0.267 0.267 0.267 rg
BT 326.452 250.318 Td /F1 9.8 Tf  [([41])] TJ ET
0.271 0.267 0.267 rg
BT 342.715 250.318 Td /F1 9.8 Tf  [( In fact the cognitive sum score from our HD )] TJ ET
BT 26.250 238.413 Td /F1 9.8 Tf  [(participants showed a broad range from 98-346 points with a mean of 195.1 points indicating a cognitive impairment in most of )] TJ ET
BT 26.250 226.509 Td /F1 9.8 Tf  [(the patients. It is well known that the performance in UHDRS cognitive tests declined during disease progression, as did the )] TJ ET
BT 26.250 214.604 Td /F1 9.8 Tf  [(functional capacity \(TFC\), which is highly dependent on cognitive tasks. )] TJ ET
0.267 0.267 0.267 rg
BT 337.295 214.604 Td /F1 9.8 Tf  [([42])] TJ ET
BT 353.558 214.604 Td /F1 9.8 Tf  [([43])] TJ ET
0.271 0.267 0.267 rg
BT 369.820 214.604 Td /F1 9.8 Tf  [( A decrement in mitochondrial function is )] TJ ET
BT 26.250 202.699 Td /F1 9.8 Tf  [(discussed as contributing to age-dependent functional deficits in neurons and myocytes in normal aging and other neurological )] TJ ET
BT 26.250 190.794 Td /F1 9.8 Tf  [(disorders, such as Alzheimer�s disease, accompanied with a cognitive decline. )] TJ ET
0.267 0.267 0.267 rg
BT 366.545 190.794 Td /F1 9.8 Tf  [([44])] TJ ET
BT 382.808 190.794 Td /F1 9.8 Tf  [([45])] TJ ET
BT 399.070 190.794 Td /F1 9.8 Tf  [([46])] TJ ET
0.271 0.267 0.267 rg
BT 415.333 190.794 Td /F1 9.8 Tf  [( Mitochondrial dysfunction is well )] TJ ET
BT 26.250 178.890 Td /F1 9.8 Tf  [(known in HD and seems to be a relevant and early feature in the pathology. )] TJ ET
0.267 0.267 0.267 rg
BT 354.669 178.890 Td /F1 9.8 Tf  [([47])] TJ ET
BT 370.932 178.890 Td /F1 9.8 Tf  [([48])] TJ ET
BT 387.195 178.890 Td /F1 9.8 Tf  [([49])] TJ ET
0.271 0.267 0.267 rg
BT 403.458 178.890 Td /F1 9.8 Tf  [( Mutant htt \(mtHtt\) tends to aggregate in )] TJ ET
BT 26.250 166.985 Td /F1 9.8 Tf  [(cytoplasm and nucleus of neurons as well as non-neuronal tissues including the liver. )] TJ ET
0.267 0.267 0.267 rg
BT 396.370 166.985 Td /F1 9.8 Tf  [([50])] TJ ET
BT 412.633 166.985 Td /F1 9.8 Tf  [([51])] TJ ET
BT 428.896 166.985 Td /F1 9.8 Tf  [([52])] TJ ET
BT 445.159 166.985 Td /F1 9.8 Tf  [([53])] TJ ET
BT 461.422 166.985 Td /F1 9.8 Tf  [([54])] TJ ET
BT 477.685 166.985 Td /F1 9.8 Tf  [([55])] TJ ET
0.271 0.267 0.267 rg
BT 493.948 166.985 Td /F1 9.8 Tf  [( Within the )] TJ ET
BT 26.250 155.080 Td /F1 9.8 Tf  [(mitochondria, octanoic acid undergoes b-oxidation. Octanic acid generates acetyl coenzyme A which enters the Krebs cycle )] TJ ET
BT 26.250 143.175 Td /F1 9.8 Tf  [(and is oxidized to CO )] TJ ET
BT 121.624 141.111 Td /F1 8.7 Tf  [(2)] TJ ET
BT 126.443 143.175 Td /F1 9.8 Tf  [( . Therefore breath tests based on octanoate, usually used to assess gastric emptying, should also )] TJ ET
BT 26.250 131.271 Td /F1 9.8 Tf  [(reflect mitochondrial function. )] TJ ET
0.267 0.267 0.267 rg
BT 155.759 131.271 Td /F1 9.8 Tf  [([56])] TJ ET
0.271 0.267 0.267 rg
BT 172.022 131.271 Td /F1 9.8 Tf  [( Thus, one can speculate that a correlation of OBT results with results of cognitive tasks might )] TJ ET
BT 26.250 119.366 Td /F1 9.8 Tf  [(reflect a parallel decline in cognitive and mitochondrial function.)] TJ ET
BT 26.250 99.961 Td /F1 9.8 Tf  [(To our knowledge this is the first study dealing with gastrointestinal track dysfunction in HD in vivo. A limitation of our study is )] TJ ET
BT 26.250 88.056 Td /F1 9.8 Tf  [(the relative small number of participants. To exclude drug effects we only included patients without any medication and without )] TJ ET
BT 26.250 76.152 Td /F1 9.8 Tf  [(serious comorbidities. On the other hand, due to the fact that this is a very rare group of patients it is a strength of our study that )] TJ ET
BT 26.250 64.247 Td /F1 9.8 Tf  [(we can exclude medication effects.)] 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
445 0 obj
<< /Type /Annot
/Subtype /Link
/A 446 0 R
/Border [0 0 0]
/H /I
/Rect [ 88.0162 565.1303 104.2793 575.0509 ]
>>
endobj
446 0 obj
<< /Type /Action
>>
endobj
447 0 obj
<< /Type /Annot
/Subtype /Link
/A 448 0 R
/Border [0 0 0]
/H /I
/Rect [ 104.2793 565.1303 120.5423 575.0509 ]
>>
endobj
448 0 obj
<< /Type /Action
>>
endobj
449 0 obj
<< /Type /Annot
/Subtype /Link
/A 450 0 R
/Border [0 0 0]
/H /I
/Rect [ 120.5423 565.1303 136.8053 575.0509 ]
>>
endobj
450 0 obj
<< /Type /Action
>>
endobj
451 0 obj
<< /Type /Annot
/Subtype /Link
/A 452 0 R
/Border [0 0 0]
/H /I
/Rect [ 26.2500 553.2256 42.5130 563.1462 ]
>>
endobj
452 0 obj
<< /Type /Action
>>
endobj
453 0 obj
<< /Type /Annot
/Subtype /Link
/A 454 0 R
/Border [0 0 0]
/H /I
/Rect [ 42.5130 553.2256 58.7760 563.1462 ]
>>
endobj
454 0 obj
<< /Type /Action
>>
endobj
455 0 obj
<< /Type /Annot
/Subtype /Link
/A 456 0 R
/Border [0 0 0]
/H /I
/Rect [ 58.7760 553.2256 75.0390 563.1462 ]
>>
endobj
456 0 obj
<< /Type /Action
>>
endobj
457 0 obj
<< /Type /Annot
/Subtype /Link
/A 458 0 R
/Border [0 0 0]
/H /I
/Rect [ 75.0390 553.2256 91.3020 563.1462 ]
>>
endobj
458 0 obj
<< /Type /Action
>>
endobj
459 0 obj
<< /Type /Annot
/Subtype /Link
/A 460 0 R
/Border [0 0 0]
/H /I
/Rect [ 91.3020 553.2256 107.5650 563.1462 ]
>>
endobj
460 0 obj
<< /Type /Action
>>
endobj
461 0 obj
<< /Type /Annot
/Subtype /Link
/A 462 0 R
/Border [0 0 0]
/H /I
/Rect [ 107.5650 553.2256 123.8280 563.1462 ]
>>
endobj
462 0 obj
<< /Type /Action
>>
endobj
463 0 obj
<< /Type /Annot
/Subtype /Link
/A 464 0 R
/Border [0 0 0]
/H /I
/Rect [ 168.2490 438.5828 184.5120 448.5034 ]
>>
endobj
464 0 obj
<< /Type /Action
>>
endobj
465 0 obj
<< /Type /Annot
/Subtype /Link
/A 466 0 R
/Border [0 0 0]
/H /I
/Rect [ 550.3027 383.4638 566.5657 393.3844 ]
>>
endobj
466 0 obj
<< /Type /Action
>>
endobj
467 0 obj
<< /Type /Annot
/Subtype /Link
/A 468 0 R
/Border [0 0 0]
/H /I
/Rect [ 362.2058 347.7496 378.4688 357.6702 ]
>>
endobj
468 0 obj
<< /Type /Action
>>
endobj
469 0 obj
<< /Type /Annot
/Subtype /Link
/A 470 0 R
/Border [0 0 0]
/H /I
/Rect [ 326.4525 249.4163 342.7155 259.3369 ]
>>
endobj
470 0 obj
<< /Type /Action
>>
endobj
471 0 obj
<< /Type /Annot
/Subtype /Link
/A 472 0 R
/Border [0 0 0]
/H /I
/Rect [ 337.2945 213.7021 353.5575 223.6227 ]
>>
endobj
472 0 obj
<< /Type /Action
>>
endobj
473 0 obj
<< /Type /Annot
/Subtype /Link
/A 474 0 R
/Border [0 0 0]
/H /I
/Rect [ 353.5575 213.7021 369.8205 223.6227 ]
>>
endobj
474 0 obj
<< /Type /Action
>>
endobj
475 0 obj
<< /Type /Annot
/Subtype /Link
/A 476 0 R
/Border [0 0 0]
/H /I
/Rect [ 366.5445 189.8926 382.8075 199.8132 ]
>>
endobj
476 0 obj
<< /Type /Action
>>
endobj
477 0 obj
<< /Type /Annot
/Subtype /Link
/A 478 0 R
/Border [0 0 0]
/H /I
/Rect [ 382.8075 189.8926 399.0705 199.8132 ]
>>
endobj
478 0 obj
<< /Type /Action
>>
endobj
479 0 obj
<< /Type /Annot
/Subtype /Link
/A 480 0 R
/Border [0 0 0]
/H /I
/Rect [ 399.0705 189.8926 415.3335 199.8132 ]
>>
endobj
480 0 obj
<< /Type /Action
>>
endobj
481 0 obj
<< /Type /Annot
/Subtype /Link
/A 482 0 R
/Border [0 0 0]
/H /I
/Rect [ 354.6690 177.9878 370.9320 187.9084 ]
>>
endobj
482 0 obj
<< /Type /Action
>>
endobj
483 0 obj
<< /Type /Annot
/Subtype /Link
/A 484 0 R
/Border [0 0 0]
/H /I
/Rect [ 370.9320 177.9878 387.1950 187.9084 ]
>>
endobj
484 0 obj
<< /Type /Action
>>
endobj
485 0 obj
<< /Type /Annot
/Subtype /Link
/A 486 0 R
/Border [0 0 0]
/H /I
/Rect [ 387.1950 177.9878 403.4580 187.9084 ]
>>
endobj
486 0 obj
<< /Type /Action
>>
endobj
487 0 obj
<< /Type /Annot
/Subtype /Link
/A 488 0 R
/Border [0 0 0]
/H /I
/Rect [ 396.3698 166.0831 412.6327 176.0037 ]
>>
endobj
488 0 obj
<< /Type /Action
>>
endobj
489 0 obj
<< /Type /Annot
/Subtype /Link
/A 490 0 R
/Border [0 0 0]
/H /I
/Rect [ 412.6327 166.0831 428.8957 176.0037 ]
>>
endobj
490 0 obj
<< /Type /Action
>>
endobj
491 0 obj
<< /Type /Annot
/Subtype /Link
/A 492 0 R
/Border [0 0 0]
/H /I
/Rect [ 428.8957 166.0831 445.1587 176.0037 ]
>>
endobj
492 0 obj
<< /Type /Action
>>
endobj
493 0 obj
<< /Type /Annot
/Subtype /Link
/A 494 0 R
/Border [0 0 0]
/H /I
/Rect [ 445.1587 166.0831 461.4217 176.0037 ]
>>
endobj
494 0 obj
<< /Type /Action
>>
endobj
495 0 obj
<< /Type /Annot
/Subtype /Link
/A 496 0 R
/Border [0 0 0]
/H /I
/Rect [ 461.4217 166.0831 477.6847 176.0037 ]
>>
endobj
496 0 obj
<< /Type /Action
>>
endobj
497 0 obj
<< /Type /Annot
/Subtype /Link
/A 498 0 R
/Border [0 0 0]
/H /I
/Rect [ 477.6847 166.0831 493.9477 176.0037 ]
>>
endobj
498 0 obj
<< /Type /Action
>>
endobj
499 0 obj
<< /Type /Annot
/Subtype /Link
/A 500 0 R
/Border [0 0 0]
/H /I
/Rect [ 155.7593 130.3688 172.0223 140.2894 ]
>>
endobj
500 0 obj
<< /Type /Action
>>
endobj
501 0 obj
<< /Type /Annot
/Subtype /Link
/A 502 0 R
/Border [0 0 0]
/H /I
/Rect [ 88.0162 565.1303 104.2793 575.0509 ]
>>
endobj
502 0 obj
<< /Type /Action
>>
endobj
503 0 obj
<< /Type /Annot
/Subtype /Link
/A 504 0 R
/Border [0 0 0]
/H /I
/Rect [ 104.2793 565.1303 120.5423 575.0509 ]
>>
endobj
504 0 obj
<< /Type /Action
>>
endobj
505 0 obj
<< /Type /Annot
/Subtype /Link
/A 506 0 R
/Border [0 0 0]
/H /I
/Rect [ 120.5423 565.1303 136.8053 575.0509 ]
>>
endobj
506 0 obj
<< /Type /Action
>>
endobj
507 0 obj
<< /Type /Annot
/Subtype /Link
/A 508 0 R
/Border [0 0 0]
/H /I
/Rect [ 26.2500 553.2256 42.5130 563.1462 ]
>>
endobj
508 0 obj
<< /Type /Action
>>
endobj
509 0 obj
<< /Type /Annot
/Subtype /Link
/A 510 0 R
/Border [0 0 0]
/H /I
/Rect [ 42.5130 553.2256 58.7760 563.1462 ]
>>
endobj
510 0 obj
<< /Type /Action
>>
endobj
511 0 obj
<< /Type /Annot
/Subtype /Link
/A 512 0 R
/Border [0 0 0]
/H /I
/Rect [ 58.7760 553.2256 75.0390 563.1462 ]
>>
endobj
512 0 obj
<< /Type /Action
>>
endobj
513 0 obj
<< /Type /Annot
/Subtype /Link
/A 514 0 R
/Border [0 0 0]
/H /I
/Rect [ 75.0390 553.2256 91.3020 563.1462 ]
>>
endobj
514 0 obj
<< /Type /Action
>>
endobj
515 0 obj
<< /Type /Annot
/Subtype /Link
/A 516 0 R
/Border [0 0 0]
/H /I
/Rect [ 91.3020 553.2256 107.5650 563.1462 ]
>>
endobj
516 0 obj
<< /Type /Action
>>
endobj
517 0 obj
<< /Type /Annot
/Subtype /Link
/A 518 0 R
/Border [0 0 0]
/H /I
/Rect [ 107.5650 553.2256 123.8280 563.1462 ]
>>
endobj
518 0 obj
<< /Type /Action
>>
endobj
519 0 obj
<< /Type /Annot
/Subtype /Link
/A 520 0 R
/Border [0 0 0]
/H /I
/Rect [ 168.2490 438.5828 184.5120 448.5034 ]
>>
endobj
520 0 obj
<< /Type /Action
>>
endobj
521 0 obj
<< /Type /Annot
/Subtype /Link
/A 522 0 R
/Border [0 0 0]
/H /I
/Rect [ 550.3027 383.4638 566.5657 393.3844 ]
>>
endobj
522 0 obj
<< /Type /Action
>>
endobj
523 0 obj
<< /Type /Annot
/Subtype /Link
/A 524 0 R
/Border [0 0 0]
/H /I
/Rect [ 362.2058 347.7496 378.4688 357.6702 ]
>>
endobj
524 0 obj
<< /Type /Action
>>
endobj
525 0 obj
<< /Type /Annot
/Subtype /Link
/A 526 0 R
/Border [0 0 0]
/H /I
/Rect [ 326.4525 249.4163 342.7155 259.3369 ]
>>
endobj
526 0 obj
<< /Type /Action
>>
endobj
527 0 obj
<< /Type /Annot
/Subtype /Link
/A 528 0 R
/Border [0 0 0]
/H /I
/Rect [ 337.2945 213.7021 353.5575 223.6227 ]
>>
endobj
528 0 obj
<< /Type /Action
>>
endobj
529 0 obj
<< /Type /Annot
/Subtype /Link
/A 530 0 R
/Border [0 0 0]
/H /I
/Rect [ 353.5575 213.7021 369.8205 223.6227 ]
>>
endobj
530 0 obj
<< /Type /Action
>>
endobj
531 0 obj
<< /Type /Annot
/Subtype /Link
/A 532 0 R
/Border [0 0 0]
/H /I
/Rect [ 366.5445 189.8926 382.8075 199.8132 ]
>>
endobj
532 0 obj
<< /Type /Action
>>
endobj
533 0 obj
<< /Type /Annot
/Subtype /Link
/A 534 0 R
/Border [0 0 0]
/H /I
/Rect [ 382.8075 189.8926 399.0705 199.8132 ]
>>
endobj
534 0 obj
<< /Type /Action
>>
endobj
535 0 obj
<< /Type /Annot
/Subtype /Link
/A 536 0 R
/Border [0 0 0]
/H /I
/Rect [ 399.0705 189.8926 415.3335 199.8132 ]
>>
endobj
536 0 obj
<< /Type /Action
>>
endobj
537 0 obj
<< /Type /Annot
/Subtype /Link
/A 538 0 R
/Border [0 0 0]
/H /I
/Rect [ 354.6690 177.9878 370.9320 187.9084 ]
>>
endobj
538 0 obj
<< /Type /Action
>>
endobj
539 0 obj
<< /Type /Annot
/Subtype /Link
/A 540 0 R
/Border [0 0 0]
/H /I
/Rect [ 370.9320 177.9878 387.1950 187.9084 ]
>>
endobj
540 0 obj
<< /Type /Action
>>
endobj
541 0 obj
<< /Type /Annot
/Subtype /Link
/A 542 0 R
/Border [0 0 0]
/H /I
/Rect [ 387.1950 177.9878 403.4580 187.9084 ]
>>
endobj
542 0 obj
<< /Type /Action
>>
endobj
543 0 obj
<< /Type /Annot
/Subtype /Link
/A 544 0 R
/Border [0 0 0]
/H /I
/Rect [ 396.3698 166.0831 412.6327 176.0037 ]
>>
endobj
544 0 obj
<< /Type /Action
>>
endobj
545 0 obj
<< /Type /Annot
/Subtype /Link
/A 546 0 R
/Border [0 0 0]
/H /I
/Rect [ 412.6327 166.0831 428.8957 176.0037 ]
>>
endobj
546 0 obj
<< /Type /Action
>>
endobj
547 0 obj
<< /Type /Annot
/Subtype /Link
/A 548 0 R
/Border [0 0 0]
/H /I
/Rect [ 428.8957 166.0831 445.1587 176.0037 ]
>>
endobj
548 0 obj
<< /Type /Action
>>
endobj
549 0 obj
<< /Type /Annot
/Subtype /Link
/A 550 0 R
/Border [0 0 0]
/H /I
/Rect [ 445.1587 166.0831 461.4217 176.0037 ]
>>
endobj
550 0 obj
<< /Type /Action
>>
endobj
551 0 obj
<< /Type /Annot
/Subtype /Link
/A 552 0 R
/Border [0 0 0]
/H /I
/Rect [ 461.4217 166.0831 477.6847 176.0037 ]
>>
endobj
552 0 obj
<< /Type /Action
>>
endobj
553 0 obj
<< /Type /Annot
/Subtype /Link
/A 554 0 R
/Border [0 0 0]
/H /I
/Rect [ 477.6847 166.0831 493.9477 176.0037 ]
>>
endobj
554 0 obj
<< /Type /Action
>>
endobj
555 0 obj
<< /Type /Annot
/Subtype /Link
/A 556 0 R
/Border [0 0 0]
/H /I
/Rect [ 155.7593 130.3688 172.0223 140.2894 ]
>>
endobj
556 0 obj
<< /Type /Action
>>
endobj
557 0 obj
<< /Type /Annot
/Subtype /Link
/A 558 0 R
/Border [0 0 0]
/H /I
/Rect [ 88.0162 565.1303 104.2793 575.0509 ]
>>
endobj
558 0 obj
<< /Type /Action
>>
endobj
559 0 obj
<< /Type /Annot
/Subtype /Link
/A 560 0 R
/Border [0 0 0]
/H /I
/Rect [ 104.2793 565.1303 120.5423 575.0509 ]
>>
endobj
560 0 obj
<< /Type /Action
>>
endobj
561 0 obj
<< /Type /Annot
/Subtype /Link
/A 562 0 R
/Border [0 0 0]
/H /I
/Rect [ 120.5423 565.1303 136.8053 575.0509 ]
>>
endobj
562 0 obj
<< /Type /Action
>>
endobj
563 0 obj
<< /Type /Annot
/Subtype /Link
/A 564 0 R
/Border [0 0 0]
/H /I
/Rect [ 26.2500 553.2256 42.5130 563.1462 ]
>>
endobj
564 0 obj
<< /Type /Action
>>
endobj
565 0 obj
<< /Type /Annot
/Subtype /Link
/A 566 0 R
/Border [0 0 0]
/H /I
/Rect [ 42.5130 553.2256 58.7760 563.1462 ]
>>
endobj
566 0 obj
<< /Type /Action
>>
endobj
567 0 obj
<< /Type /Annot
/Subtype /Link
/A 568 0 R
/Border [0 0 0]
/H /I
/Rect [ 58.7760 553.2256 75.0390 563.1462 ]
>>
endobj
568 0 obj
<< /Type /Action
>>
endobj
569 0 obj
<< /Type /Annot
/Subtype /Link
/A 570 0 R
/Border [0 0 0]
/H /I
/Rect [ 75.0390 553.2256 91.3020 563.1462 ]
>>
endobj
570 0 obj
<< /Type /Action
>>
endobj
571 0 obj
<< /Type /Annot
/Subtype /Link
/A 572 0 R
/Border [0 0 0]
/H /I
/Rect [ 91.3020 553.2256 107.5650 563.1462 ]
>>
endobj
572 0 obj
<< /Type /Action
>>
endobj
573 0 obj
<< /Type /Annot
/Subtype /Link
/A 574 0 R
/Border [0 0 0]
/H /I
/Rect [ 107.5650 553.2256 123.8280 563.1462 ]
>>
endobj
574 0 obj
<< /Type /Action
>>
endobj
575 0 obj
<< /Type /Annot
/Subtype /Link
/A 576 0 R
/Border [0 0 0]
/H /I
/Rect [ 168.2490 438.5828 184.5120 448.5034 ]
>>
endobj
576 0 obj
<< /Type /Action
>>
endobj
577 0 obj
<< /Type /Annot
/Subtype /Link
/A 578 0 R
/Border [0 0 0]
/H /I
/Rect [ 550.3027 383.4638 566.5657 393.3844 ]
>>
endobj
578 0 obj
<< /Type /Action
>>
endobj
579 0 obj
<< /Type /Annot
/Subtype /Link
/A 580 0 R
/Border [0 0 0]
/H /I
/Rect [ 362.2058 347.7496 378.4688 357.6702 ]
>>
endobj
580 0 obj
<< /Type /Action
>>
endobj
581 0 obj
<< /Type /Annot
/Subtype /Link
/A 582 0 R
/Border [0 0 0]
/H /I
/Rect [ 326.4525 249.4163 342.7155 259.3369 ]
>>
endobj
582 0 obj
<< /Type /Action
>>
endobj
583 0 obj
<< /Type /Annot
/Subtype /Link
/A 584 0 R
/Border [0 0 0]
/H /I
/Rect [ 337.2945 213.7021 353.5575 223.6227 ]
>>
endobj
584 0 obj
<< /Type /Action
>>
endobj
585 0 obj
<< /Type /Annot
/Subtype /Link
/A 586 0 R
/Border [0 0 0]
/H /I
/Rect [ 353.5575 213.7021 369.8205 223.6227 ]
>>
endobj
586 0 obj
<< /Type /Action
>>
endobj
587 0 obj
<< /Type /Annot
/Subtype /Link
/A 588 0 R
/Border [0 0 0]
/H /I
/Rect [ 366.5445 189.8926 382.8075 199.8132 ]
>>
endobj
588 0 obj
<< /Type /Action
>>
endobj
589 0 obj
<< /Type /Annot
/Subtype /Link
/A 590 0 R
/Border [0 0 0]
/H /I
/Rect [ 382.8075 189.8926 399.0705 199.8132 ]
>>
endobj
590 0 obj
<< /Type /Action
>>
endobj
591 0 obj
<< /Type /Annot
/Subtype /Link
/A 592 0 R
/Border [0 0 0]
/H /I
/Rect [ 399.0705 189.8926 415.3335 199.8132 ]
>>
endobj
592 0 obj
<< /Type /Action
>>
endobj
593 0 obj
<< /Type /Annot
/Subtype /Link
/A 594 0 R
/Border [0 0 0]
/H /I
/Rect [ 354.6690 177.9878 370.9320 187.9084 ]
>>
endobj
594 0 obj
<< /Type /Action
>>
endobj
595 0 obj
<< /Type /Annot
/Subtype /Link
/A 596 0 R
/Border [0 0 0]
/H /I
/Rect [ 370.9320 177.9878 387.1950 187.9084 ]
>>
endobj
596 0 obj
<< /Type /Action
>>
endobj
597 0 obj
<< /Type /Annot
/Subtype /Link
/A 598 0 R
/Border [0 0 0]
/H /I
/Rect [ 387.1950 177.9878 403.4580 187.9084 ]
>>
endobj
598 0 obj
<< /Type /Action
>>
endobj
599 0 obj
<< /Type /Annot
/Subtype /Link
/A 600 0 R
/Border [0 0 0]
/H /I
/Rect [ 396.3698 166.0831 412.6327 176.0037 ]
>>
endobj
600 0 obj
<< /Type /Action
>>
endobj
601 0 obj
<< /Type /Annot
/Subtype /Link
/A 602 0 R
/Border [0 0 0]
/H /I
/Rect [ 412.6327 166.0831 428.8957 176.0037 ]
>>
endobj
602 0 obj
<< /Type /Action
>>
endobj
603 0 obj
<< /Type /Annot
/Subtype /Link
/A 604 0 R
/Border [0 0 0]
/H /I
/Rect [ 428.8957 166.0831 445.1587 176.0037 ]
>>
endobj
604 0 obj
<< /Type /Action
>>
endobj
605 0 obj
<< /Type /Annot
/Subtype /Link
/A 606 0 R
/Border [0 0 0]
/H /I
/Rect [ 445.1587 166.0831 461.4217 176.0037 ]
>>
endobj
606 0 obj
<< /Type /Action
>>
endobj
607 0 obj
<< /Type /Annot
/Subtype /Link
/A 608 0 R
/Border [0 0 0]
/H /I
/Rect [ 461.4217 166.0831 477.6847 176.0037 ]
>>
endobj
608 0 obj
<< /Type /Action
>>
endobj
609 0 obj
<< /Type /Annot
/Subtype /Link
/A 610 0 R
/Border [0 0 0]
/H /I
/Rect [ 477.6847 166.0831 493.9477 176.0037 ]
>>
endobj
610 0 obj
<< /Type /Action
>>
endobj
611 0 obj
<< /Type /Annot
/Subtype /Link
/A 612 0 R
/Border [0 0 0]
/H /I
/Rect [ 155.7593 130.3688 172.0223 140.2894 ]
>>
endobj
612 0 obj
<< /Type /Action
>>
endobj
613 0 obj
<< /Type /Page
/Parent 3 0 R
/Contents 614 0 R
>>
endobj
614 0 obj
<<
/Length 17230 >>
stream

0.271 0.267 0.267 rg
q
15.000 37.916 577.500 739.084 re W n
0.271 0.267 0.267 rg
BT 26.250 750.278 Td /F4 12.0 Tf  [(Competing interests)] TJ ET
BT 26.250 730.324 Td /F1 9.8 Tf  [(The authors declare that they have no competing interests.)] TJ ET
BT 26.250 693.722 Td /F4 12.0 Tf  [(Ethics)] TJ ET
BT 26.250 673.767 Td /F1 9.8 Tf  [(The local ethics committee of the university approved this study.)] TJ ET
BT 26.250 637.165 Td /F4 12.0 Tf  [(Acknowledgements)] TJ ET
BT 26.250 617.211 Td /F1 9.8 Tf  [(We are grateful to all patients for participation.)] TJ ET
BT 26.250 588.108 Td /F4 12.0 Tf  [(References)] TJ ET
BT 26.250 560.654 Td /F1 9.8 Tf  [(1.)] TJ ET
BT 38.132 560.654 Td /F1 9.8 Tf  [(Djousse L, Knowlton B, Cupples LA, Marder K, Shoulson I, Myers RH. Weight loss in early stage of Huntington's disease. )] TJ ET
BT 26.250 548.749 Td /F1 9.8 Tf  [(Neurology 2002;59:1325-1330.)] TJ ET
BT 26.250 529.344 Td /F1 9.8 Tf  [(2.)] TJ ET
BT 38.132 529.344 Td /F1 9.8 Tf  [(Sanberg PR, Fibiger HC, Mark RF. Body weight and dietary factors in Huntington's disease patients compared with matched )] TJ ET
BT 26.250 517.440 Td /F1 9.8 Tf  [(controls. Med J Aust 1981;1:407-409.)] TJ ET
BT 26.250 498.035 Td /F1 9.8 Tf  [(3.)] TJ ET
BT 38.132 498.035 Td /F1 9.8 Tf  [(Trejo A, Tarrats RM, Alonso ME, Boll MC, Ochoa A, Velasquez L. Assessment of the nutrition status of patients with )] TJ ET
BT 26.250 486.130 Td /F1 9.8 Tf  [(Huntington's disease. Nutrition 2004;20:192-196.)] TJ ET
BT 26.250 466.725 Td /F1 9.8 Tf  [(4.)] TJ ET
BT 38.132 466.725 Td /F1 9.8 Tf  [(Goodman AO, Murgatroyd PR, Medina-Gomez G, et al. The metabolic profile of early Huntington's disease--a combined )] TJ ET
BT 26.250 454.821 Td /F1 9.8 Tf  [(human and transgenic mouse study. Exp Neurol 2008;210:691-698.)] TJ ET
BT 26.250 435.416 Td /F1 9.8 Tf  [(5.)] TJ ET
BT 38.132 435.416 Td /F1 9.8 Tf  [(Mochel F, Charles P, Seguin F, et al. Early energy deficit in Huntington disease: identification of a plasma biomarker )] TJ ET
BT 26.250 423.511 Td /F1 9.8 Tf  [(traceable during disease progression. PLoS One 2007;2:e647.)] TJ ET
BT 26.250 404.106 Td /F1 9.8 Tf  [(6.)] TJ ET
BT 38.132 404.106 Td /F1 9.8 Tf  [(Hamilton JM, Wolfson T, Peavy GM, Jacobson MW, Corey-Bloom J. Rate and correlates of weight change in Huntington's )] TJ ET
BT 26.250 392.202 Td /F1 9.8 Tf  [(disease. J Neurol Neurosurg Psychiatry 2004;75:209-212.)] TJ ET
BT 26.250 372.797 Td /F1 9.8 Tf  [(7.)] TJ ET
BT 38.132 372.797 Td /F1 9.8 Tf  [(Nance MA, Sanders G. Characteristics of individuals with Huntington disease in long-term care. Mov Disord 1996;11:542-548.)] TJ ET
BT 26.250 353.392 Td /F1 9.8 Tf  [(8.)] TJ ET
BT 38.132 353.392 Td /F1 9.8 Tf  [(Gaba AM, Zhang K, Marder K, Moskowitz CB, Werner P, Boozer CN. Energy balance in early-stage Huntington disease. Am )] TJ ET
BT 26.250 341.487 Td /F1 9.8 Tf  [(J Clin Nutr 2005;81:1335-1341.)] TJ ET
BT 26.250 322.083 Td /F1 9.8 Tf  [(9.)] TJ ET
BT 38.132 322.083 Td /F1 9.8 Tf  [(Mahant N, McCusker EA, Byth K, Graham S. Huntington's disease: clinical correlates of disability and progression. )] TJ ET
BT 26.250 310.178 Td /F1 9.8 Tf  [(Neurology 2003;61:1085-1092.)] TJ ET
BT 26.250 290.773 Td /F1 9.8 Tf  [(10.)] TJ ET
BT 43.553 290.773 Td /F1 9.8 Tf  [(Pratley RE, Salbe AD, Ravussin E, Caviness JN. Higher sedentary energy expenditure in patients with Huntington's )] TJ ET
BT 26.250 278.868 Td /F1 9.8 Tf  [(disease. Ann Neurol 2000;47:64-70.)] TJ ET
BT 26.250 259.464 Td /F1 9.8 Tf  [(11.)] TJ ET
BT 43.553 259.464 Td /F1 9.8 Tf  [(van der Burg JM, Bacos K, Wood NI, et al. Increased metabolism in the R6/2 mouse model of Huntington's disease. )] TJ ET
BT 26.250 247.559 Td /F1 9.8 Tf  [(Neurobiol Dis 2008;29:41-51.)] TJ ET
BT 26.250 228.154 Td /F1 9.8 Tf  [(12.)] TJ ET
BT 43.553 228.154 Td /F1 9.8 Tf  [(Weydt P, Pineda VV, Torrence AE, et al. Thermoregulatory and metabolic defects in Huntington's disease transgenic mice )] TJ ET
BT 26.250 216.249 Td /F1 9.8 Tf  [(implicate PGC-1alpha in Huntington's disease neurodegeneration. Cell Metab 2006;4:349-362.)] TJ ET
BT 26.250 196.845 Td /F1 9.8 Tf  [(13.)] TJ ET
BT 43.553 196.845 Td /F1 9.8 Tf  [(Aziz NA, van der Burg JM, Landwehrmeyer GB, Brundin P, Stijnen T, Roos RA. Weight loss in Huntington disease )] TJ ET
BT 26.250 184.940 Td /F1 9.8 Tf  [(increases with higher CAG repeat number. Neurology 2008;71:1506-1513.)] TJ ET
BT 26.250 165.535 Td /F1 9.8 Tf  [(14.)] TJ ET
BT 43.553 165.535 Td /F1 9.8 Tf  [(van der Burg JM, Winqvist A, Aziz NA, et al. Gastrointestinal dysfunction contributes to weight loss in Huntington's disease )] TJ ET
BT 26.250 153.630 Td /F1 9.8 Tf  [(mice. Neurobiol Dis;44:1-8.)] TJ ET
BT 26.250 134.226 Td /F1 9.8 Tf  [(15.)] TJ ET
BT 43.553 134.226 Td /F1 9.8 Tf  [(Pfeiffer RF. Gastrointestinal dysfunction in Parkinson's disease. Parkinsonism Relat Disord;17:10-15.)] TJ ET
BT 26.250 114.821 Td /F1 9.8 Tf  [(16.)] TJ ET
BT 43.553 114.821 Td /F1 9.8 Tf  [(Goetze O, Nikodem AB, Wiezcorek J, et al. Predictors of gastric emptying in Parkinson's disease. Neurogastroenterol Motil )] TJ ET
BT 26.250 102.916 Td /F1 9.8 Tf  [(2006;18:369-375.)] TJ ET
BT 26.250 83.511 Td /F1 9.8 Tf  [(17.)] TJ ET
BT 43.553 83.511 Td /F1 9.8 Tf  [(Goetze O, Wieczorek J, Mueller T, Przuntek H, Schmidt WE, Woitalla D. Impaired gastric emptying of a solid test meal in )] TJ ET
BT 26.250 71.607 Td /F1 9.8 Tf  [(patients with Parkinson's disease using 13C-sodium octanoate breath test. Neurosci Lett 2005;375:170-173.)] TJ ET
BT 26.250 52.202 Td /F1 9.8 Tf  [(18.)] TJ ET
BT 43.553 52.202 Td /F1 9.8 Tf  [(Muller T, Erdmann C, Bremen D, et al. Impact of gastric emptying on levodopa pharmacokinetics in Parkinson disease )] TJ ET
Q
q
15.000 37.916 577.500 739.084 re W n
0.271 0.267 0.267 rg
BT 26.250 750.278 Td /F4 12.0 Tf  [(Competing interests)] TJ ET
BT 26.250 730.324 Td /F1 9.8 Tf  [(The authors declare that they have no competing interests.)] TJ ET
BT 26.250 693.722 Td /F4 12.0 Tf  [(Ethics)] TJ ET
BT 26.250 673.767 Td /F1 9.8 Tf  [(The local ethics committee of the university approved this study.)] TJ ET
BT 26.250 637.165 Td /F4 12.0 Tf  [(Acknowledgements)] TJ ET
BT 26.250 617.211 Td /F1 9.8 Tf  [(We are grateful to all patients for participation.)] TJ ET
BT 26.250 588.108 Td /F4 12.0 Tf  [(References)] TJ ET
BT 26.250 560.654 Td /F1 9.8 Tf  [(1.)] TJ ET
BT 38.132 560.654 Td /F1 9.8 Tf  [(Djousse L, Knowlton B, Cupples LA, Marder K, Shoulson I, Myers RH. Weight loss in early stage of Huntington's disease. )] TJ ET
BT 26.250 548.749 Td /F1 9.8 Tf  [(Neurology 2002;59:1325-1330.)] TJ ET
BT 26.250 529.344 Td /F1 9.8 Tf  [(2.)] TJ ET
BT 38.132 529.344 Td /F1 9.8 Tf  [(Sanberg PR, Fibiger HC, Mark RF. Body weight and dietary factors in Huntington's disease patients compared with matched )] TJ ET
BT 26.250 517.440 Td /F1 9.8 Tf  [(controls. Med J Aust 1981;1:407-409.)] TJ ET
BT 26.250 498.035 Td /F1 9.8 Tf  [(3.)] TJ ET
BT 38.132 498.035 Td /F1 9.8 Tf  [(Trejo A, Tarrats RM, Alonso ME, Boll MC, Ochoa A, Velasquez L. Assessment of the nutrition status of patients with )] TJ ET
BT 26.250 486.130 Td /F1 9.8 Tf  [(Huntington's disease. Nutrition 2004;20:192-196.)] TJ ET
BT 26.250 466.725 Td /F1 9.8 Tf  [(4.)] TJ ET
BT 38.132 466.725 Td /F1 9.8 Tf  [(Goodman AO, Murgatroyd PR, Medina-Gomez G, et al. The metabolic profile of early Huntington's disease--a combined )] TJ ET
BT 26.250 454.821 Td /F1 9.8 Tf  [(human and transgenic mouse study. Exp Neurol 2008;210:691-698.)] TJ ET
BT 26.250 435.416 Td /F1 9.8 Tf  [(5.)] TJ ET
BT 38.132 435.416 Td /F1 9.8 Tf  [(Mochel F, Charles P, Seguin F, et al. Early energy deficit in Huntington disease: identification of a plasma biomarker )] TJ ET
BT 26.250 423.511 Td /F1 9.8 Tf  [(traceable during disease progression. PLoS One 2007;2:e647.)] TJ ET
BT 26.250 404.106 Td /F1 9.8 Tf  [(6.)] TJ ET
BT 38.132 404.106 Td /F1 9.8 Tf  [(Hamilton JM, Wolfson T, Peavy GM, Jacobson MW, Corey-Bloom J. Rate and correlates of weight change in Huntington's )] TJ ET
BT 26.250 392.202 Td /F1 9.8 Tf  [(disease. J Neurol Neurosurg Psychiatry 2004;75:209-212.)] TJ ET
BT 26.250 372.797 Td /F1 9.8 Tf  [(7.)] TJ ET
BT 38.132 372.797 Td /F1 9.8 Tf  [(Nance MA, Sanders G. Characteristics of individuals with Huntington disease in long-term care. Mov Disord 1996;11:542-548.)] TJ ET
BT 26.250 353.392 Td /F1 9.8 Tf  [(8.)] TJ ET
BT 38.132 353.392 Td /F1 9.8 Tf  [(Gaba AM, Zhang K, Marder K, Moskowitz CB, Werner P, Boozer CN. Energy balance in early-stage Huntington disease. Am )] TJ ET
BT 26.250 341.487 Td /F1 9.8 Tf  [(J Clin Nutr 2005;81:1335-1341.)] TJ ET
BT 26.250 322.083 Td /F1 9.8 Tf  [(9.)] TJ ET
BT 38.132 322.083 Td /F1 9.8 Tf  [(Mahant N, McCusker EA, Byth K, Graham S. Huntington's disease: clinical correlates of disability and progression. )] TJ ET
BT 26.250 310.178 Td /F1 9.8 Tf  [(Neurology 2003;61:1085-1092.)] TJ ET
BT 26.250 290.773 Td /F1 9.8 Tf  [(10.)] TJ ET
BT 43.553 290.773 Td /F1 9.8 Tf  [(Pratley RE, Salbe AD, Ravussin E, Caviness JN. Higher sedentary energy expenditure in patients with Huntington's )] TJ ET
BT 26.250 278.868 Td /F1 9.8 Tf  [(disease. Ann Neurol 2000;47:64-70.)] TJ ET
BT 26.250 259.464 Td /F1 9.8 Tf  [(11.)] TJ ET
BT 43.553 259.464 Td /F1 9.8 Tf  [(van der Burg JM, Bacos K, Wood NI, et al. Increased metabolism in the R6/2 mouse model of Huntington's disease. )] TJ ET
BT 26.250 247.559 Td /F1 9.8 Tf  [(Neurobiol Dis 2008;29:41-51.)] TJ ET
BT 26.250 228.154 Td /F1 9.8 Tf  [(12.)] TJ ET
BT 43.553 228.154 Td /F1 9.8 Tf  [(Weydt P, Pineda VV, Torrence AE, et al. Thermoregulatory and metabolic defects in Huntington's disease transgenic mice )] TJ ET
BT 26.250 216.249 Td /F1 9.8 Tf  [(implicate PGC-1alpha in Huntington's disease neurodegeneration. Cell Metab 2006;4:349-362.)] TJ ET
BT 26.250 196.845 Td /F1 9.8 Tf  [(13.)] TJ ET
BT 43.553 196.845 Td /F1 9.8 Tf  [(Aziz NA, van der Burg JM, Landwehrmeyer GB, Brundin P, Stijnen T, Roos RA. Weight loss in Huntington disease )] TJ ET
BT 26.250 184.940 Td /F1 9.8 Tf  [(increases with higher CAG repeat number. Neurology 2008;71:1506-1513.)] TJ ET
BT 26.250 165.535 Td /F1 9.8 Tf  [(14.)] TJ ET
BT 43.553 165.535 Td /F1 9.8 Tf  [(van der Burg JM, Winqvist A, Aziz NA, et al. Gastrointestinal dysfunction contributes to weight loss in Huntington's disease )] TJ ET
BT 26.250 153.630 Td /F1 9.8 Tf  [(mice. Neurobiol Dis;44:1-8.)] TJ ET
BT 26.250 134.226 Td /F1 9.8 Tf  [(15.)] TJ ET
BT 43.553 134.226 Td /F1 9.8 Tf  [(Pfeiffer RF. Gastrointestinal dysfunction in Parkinson's disease. Parkinsonism Relat Disord;17:10-15.)] TJ ET
BT 26.250 114.821 Td /F1 9.8 Tf  [(16.)] TJ ET
BT 43.553 114.821 Td /F1 9.8 Tf  [(Goetze O, Nikodem AB, Wiezcorek J, et al. Predictors of gastric emptying in Parkinson's disease. Neurogastroenterol Motil )] TJ ET
BT 26.250 102.916 Td /F1 9.8 Tf  [(2006;18:369-375.)] TJ ET
BT 26.250 83.511 Td /F1 9.8 Tf  [(17.)] TJ ET
BT 43.553 83.511 Td /F1 9.8 Tf  [(Goetze O, Wieczorek J, Mueller T, Przuntek H, Schmidt WE, Woitalla D. Impaired gastric emptying of a solid test meal in )] TJ ET
BT 26.250 71.607 Td /F1 9.8 Tf  [(patients with Parkinson's disease using 13C-sodium octanoate breath test. Neurosci Lett 2005;375:170-173.)] TJ ET
BT 26.250 52.202 Td /F1 9.8 Tf  [(18.)] TJ ET
BT 43.553 52.202 Td /F1 9.8 Tf  [(Muller T, Erdmann C, Bremen D, et al. Impact of gastric emptying on levodopa pharmacokinetics in Parkinson disease )] TJ ET
Q
q
15.000 37.916 577.500 739.084 re W n
0.271 0.267 0.267 rg
BT 26.250 750.278 Td /F4 12.0 Tf  [(Competing interests)] TJ ET
BT 26.250 730.324 Td /F1 9.8 Tf  [(The authors declare that they have no competing interests.)] TJ ET
BT 26.250 693.722 Td /F4 12.0 Tf  [(Ethics)] TJ ET
BT 26.250 673.767 Td /F1 9.8 Tf  [(The local ethics committee of the university approved this study.)] TJ ET
BT 26.250 637.165 Td /F4 12.0 Tf  [(Acknowledgements)] TJ ET
BT 26.250 617.211 Td /F1 9.8 Tf  [(We are grateful to all patients for participation.)] TJ ET
BT 26.250 588.108 Td /F4 12.0 Tf  [(References)] TJ ET
BT 26.250 560.654 Td /F1 9.8 Tf  [(1.)] TJ ET
BT 38.132 560.654 Td /F1 9.8 Tf  [(Djousse L, Knowlton B, Cupples LA, Marder K, Shoulson I, Myers RH. Weight loss in early stage of Huntington's disease. )] TJ ET
BT 26.250 548.749 Td /F1 9.8 Tf  [(Neurology 2002;59:1325-1330.)] TJ ET
BT 26.250 529.344 Td /F1 9.8 Tf  [(2.)] TJ ET
BT 38.132 529.344 Td /F1 9.8 Tf  [(Sanberg PR, Fibiger HC, Mark RF. Body weight and dietary factors in Huntington's disease patients compared with matched )] TJ ET
BT 26.250 517.440 Td /F1 9.8 Tf  [(controls. Med J Aust 1981;1:407-409.)] TJ ET
BT 26.250 498.035 Td /F1 9.8 Tf  [(3.)] TJ ET
BT 38.132 498.035 Td /F1 9.8 Tf  [(Trejo A, Tarrats RM, Alonso ME, Boll MC, Ochoa A, Velasquez L. Assessment of the nutrition status of patients with )] TJ ET
BT 26.250 486.130 Td /F1 9.8 Tf  [(Huntington's disease. Nutrition 2004;20:192-196.)] TJ ET
BT 26.250 466.725 Td /F1 9.8 Tf  [(4.)] TJ ET
BT 38.132 466.725 Td /F1 9.8 Tf  [(Goodman AO, Murgatroyd PR, Medina-Gomez G, et al. The metabolic profile of early Huntington's disease--a combined )] TJ ET
BT 26.250 454.821 Td /F1 9.8 Tf  [(human and transgenic mouse study. Exp Neurol 2008;210:691-698.)] TJ ET
BT 26.250 435.416 Td /F1 9.8 Tf  [(5.)] TJ ET
BT 38.132 435.416 Td /F1 9.8 Tf  [(Mochel F, Charles P, Seguin F, et al. Early energy deficit in Huntington disease: identification of a plasma biomarker )] TJ ET
BT 26.250 423.511 Td /F1 9.8 Tf  [(traceable during disease progression. PLoS One 2007;2:e647.)] TJ ET
BT 26.250 404.106 Td /F1 9.8 Tf  [(6.)] TJ ET
BT 38.132 404.106 Td /F1 9.8 Tf  [(Hamilton JM, Wolfson T, Peavy GM, Jacobson MW, Corey-Bloom J. Rate and correlates of weight change in Huntington's )] TJ ET
BT 26.250 392.202 Td /F1 9.8 Tf  [(disease. J Neurol Neurosurg Psychiatry 2004;75:209-212.)] TJ ET
BT 26.250 372.797 Td /F1 9.8 Tf  [(7.)] TJ ET
BT 38.132 372.797 Td /F1 9.8 Tf  [(Nance MA, Sanders G. Characteristics of individuals with Huntington disease in long-term care. Mov Disord 1996;11:542-548.)] TJ ET
BT 26.250 353.392 Td /F1 9.8 Tf  [(8.)] TJ ET
BT 38.132 353.392 Td /F1 9.8 Tf  [(Gaba AM, Zhang K, Marder K, Moskowitz CB, Werner P, Boozer CN. Energy balance in early-stage Huntington disease. Am )] TJ ET
BT 26.250 341.487 Td /F1 9.8 Tf  [(J Clin Nutr 2005;81:1335-1341.)] TJ ET
BT 26.250 322.083 Td /F1 9.8 Tf  [(9.)] TJ ET
BT 38.132 322.083 Td /F1 9.8 Tf  [(Mahant N, McCusker EA, Byth K, Graham S. Huntington's disease: clinical correlates of disability and progression. )] TJ ET
BT 26.250 310.178 Td /F1 9.8 Tf  [(Neurology 2003;61:1085-1092.)] TJ ET
BT 26.250 290.773 Td /F1 9.8 Tf  [(10.)] TJ ET
BT 43.553 290.773 Td /F1 9.8 Tf  [(Pratley RE, Salbe AD, Ravussin E, Caviness JN. Higher sedentary energy expenditure in patients with Huntington's )] TJ ET
BT 26.250 278.868 Td /F1 9.8 Tf  [(disease. Ann Neurol 2000;47:64-70.)] TJ ET
BT 26.250 259.464 Td /F1 9.8 Tf  [(11.)] TJ ET
BT 43.553 259.464 Td /F1 9.8 Tf  [(van der Burg JM, Bacos K, Wood NI, et al. Increased metabolism in the R6/2 mouse model of Huntington's disease. )] TJ ET
BT 26.250 247.559 Td /F1 9.8 Tf  [(Neurobiol Dis 2008;29:41-51.)] TJ ET
BT 26.250 228.154 Td /F1 9.8 Tf  [(12.)] TJ ET
BT 43.553 228.154 Td /F1 9.8 Tf  [(Weydt P, Pineda VV, Torrence AE, et al. Thermoregulatory and metabolic defects in Huntington's disease transgenic mice )] TJ ET
BT 26.250 216.249 Td /F1 9.8 Tf  [(implicate PGC-1alpha in Huntington's disease neurodegeneration. Cell Metab 2006;4:349-362.)] TJ ET
BT 26.250 196.845 Td /F1 9.8 Tf  [(13.)] TJ ET
BT 43.553 196.845 Td /F1 9.8 Tf  [(Aziz NA, van der Burg JM, Landwehrmeyer GB, Brundin P, Stijnen T, Roos RA. Weight loss in Huntington disease )] TJ ET
BT 26.250 184.940 Td /F1 9.8 Tf  [(increases with higher CAG repeat number. Neurology 2008;71:1506-1513.)] TJ ET
BT 26.250 165.535 Td /F1 9.8 Tf  [(14.)] TJ ET
BT 43.553 165.535 Td /F1 9.8 Tf  [(van der Burg JM, Winqvist A, Aziz NA, et al. Gastrointestinal dysfunction contributes to weight loss in Huntington's disease )] TJ ET
BT 26.250 153.630 Td /F1 9.8 Tf  [(mice. Neurobiol Dis;44:1-8.)] TJ ET
BT 26.250 134.226 Td /F1 9.8 Tf  [(15.)] TJ ET
BT 43.553 134.226 Td /F1 9.8 Tf  [(Pfeiffer RF. Gastrointestinal dysfunction in Parkinson's disease. Parkinsonism Relat Disord;17:10-15.)] TJ ET
BT 26.250 114.821 Td /F1 9.8 Tf  [(16.)] TJ ET
BT 43.553 114.821 Td /F1 9.8 Tf  [(Goetze O, Nikodem AB, Wiezcorek J, et al. Predictors of gastric emptying in Parkinson's disease. Neurogastroenterol Motil )] TJ ET
BT 26.250 102.916 Td /F1 9.8 Tf  [(2006;18:369-375.)] TJ ET
BT 26.250 83.511 Td /F1 9.8 Tf  [(17.)] TJ ET
BT 43.553 83.511 Td /F1 9.8 Tf  [(Goetze O, Wieczorek J, Mueller T, Przuntek H, Schmidt WE, Woitalla D. Impaired gastric emptying of a solid test meal in )] TJ ET
BT 26.250 71.607 Td /F1 9.8 Tf  [(patients with Parkinson's disease using 13C-sodium octanoate breath test. Neurosci Lett 2005;375:170-173.)] TJ ET
BT 26.250 52.202 Td /F1 9.8 Tf  [(18.)] TJ ET
BT 43.553 52.202 Td /F1 9.8 Tf  [(Muller T, Erdmann C, Bremen D, et al. Impact of gastric emptying on levodopa pharmacokinetics in Parkinson disease )] 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
615 0 obj
<< /Type /Page
/Parent 3 0 R
/Contents 616 0 R
>>
endobj
616 0 obj
<<
/Length 21328 >>
stream

0.271 0.267 0.267 rg
q
15.000 37.477 577.500 739.523 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(patients. Clin Neuropharmacol 2006;29:61-67.)] TJ ET
BT 26.250 748.071 Td /F1 9.8 Tf  [(19.)] TJ ET
BT 43.553 748.071 Td /F1 9.8 Tf  [(Woitalla D, Goetze O. Treatment approaches of gastrointestinal dysfunction in Parkinson's disease, therapeutical options )] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(and future perspectives. J Neurol Sci.)] TJ ET
BT 26.250 716.762 Td /F1 9.8 Tf  [(20.)] TJ ET
BT 43.553 716.762 Td /F1 9.8 Tf  [(Djaldetti R, Baron J, Ziv I, Melamed E. Gastric emptying in Parkinson's disease: patients with and without response )] TJ ET
BT 26.250 704.857 Td /F1 9.8 Tf  [(fluctuations. Neurology 1996;46:1051-1054.)] TJ ET
BT 26.250 685.452 Td /F1 9.8 Tf  [(21.)] TJ ET
BT 43.553 685.452 Td /F1 9.8 Tf  [(Pfeiffer RF. Gastrointestinal dysfunction in Parkinson's disease. Lancet Neurol 2003;2:107-116.)] TJ ET
BT 26.250 666.048 Td /F1 9.8 Tf  [(22.)] TJ ET
BT 43.553 666.048 Td /F1 9.8 Tf  [(Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic )] TJ ET
BT 26.250 654.143 Td /F1 9.8 Tf  [(Parkinson's disease. Neurobiol Aging 2003;24:197-211.)] TJ ET
BT 26.250 634.738 Td /F1 9.8 Tf  [(23.)] TJ ET
BT 43.553 634.738 Td /F1 9.8 Tf  [(Andrich J, Schmitz T, Saft C, et al. Autonomic nervous system function in Huntington's disease. J Neurol Neurosurg )] TJ ET
BT 26.250 622.833 Td /F1 9.8 Tf  [(Psychiatry 2002;72:726-731.)] TJ ET
BT 26.250 603.429 Td /F1 9.8 Tf  [(24.)] TJ ET
BT 43.553 603.429 Td /F1 9.8 Tf  [(Keller J, Franke A, Storr M, Wiedbrauck F, Schirra J. [Clinically relevant breath tests in gastroenterological diagnostics--)] TJ ET
BT 26.250 591.524 Td /F1 9.8 Tf  [(recommendations of the German Society for Neurogastroenterology and Motility as well as the German Society for Digestive )] TJ ET
BT 26.250 579.619 Td /F1 9.8 Tf  [(and Metabolic Diseases]. Z Gastroenterol 2005;43:1071-1090.)] TJ ET
BT 26.250 560.214 Td /F1 9.8 Tf  [(25.)] TJ ET
BT 43.553 560.214 Td /F1 9.8 Tf  [(Shoulson I. Huntington disease: functional capacities in patients treated with neuroleptic and antidepressant drugs. )] TJ ET
BT 26.250 548.310 Td /F1 9.8 Tf  [(Neurology 1981;31:1333-1335.)] TJ ET
BT 26.250 528.905 Td /F1 9.8 Tf  [(26.)] TJ ET
BT 43.553 528.905 Td /F1 9.8 Tf  [(Huntington Study Group. Unified Huntington's Disease Rating Scale: reliability and consistency. Mov Disord 1996;11:136-)] TJ ET
BT 26.250 517.000 Td /F1 9.8 Tf  [(142.)] TJ ET
BT 26.250 497.595 Td /F1 9.8 Tf  [(27.)] TJ ET
BT 43.553 497.595 Td /F1 9.8 Tf  [(Andrich J, Saft C, Ostholt N, Muller T. Assessment of simple movements and progression of Huntington's disease. J Neurol )] TJ ET
BT 26.250 485.691 Td /F1 9.8 Tf  [(Neurosurg Psychiatry 2007;78:405-407.)] TJ ET
BT 26.250 466.286 Td /F1 9.8 Tf  [(28.)] TJ ET
BT 43.553 466.286 Td /F1 9.8 Tf  [(Andrich J, Saft C, Ostholt N, Muller T. Complex movement behaviour and progression of Huntington's disease. Neurosci )] TJ ET
BT 26.250 454.381 Td /F1 9.8 Tf  [(Lett 2007;416:272-274.)] TJ ET
BT 26.250 434.976 Td /F1 9.8 Tf  [(29.)] TJ ET
BT 43.553 434.976 Td /F1 9.8 Tf  [(Saft C, Andrich J, Meisel NM, Przuntek H, Muller T. Assessment of simple movements reflects impairment in Huntington's )] TJ ET
BT 26.250 423.072 Td /F1 9.8 Tf  [(disease. Mov Disord 2006;21:1208-1212.)] TJ ET
BT 26.250 403.667 Td /F1 9.8 Tf  [(30.)] TJ ET
BT 43.553 403.667 Td /F1 9.8 Tf  [(Saft C, Andrich J, Meisel NM, Przuntek H, Muller T. Assessment of complex movements reflects dysfunction in Huntington's )] TJ ET
BT 26.250 391.762 Td /F1 9.8 Tf  [(disease. J Neurol 2003;250:1469-1474.)] TJ ET
BT 26.250 372.357 Td /F1 9.8 Tf  [(31.)] TJ ET
BT 43.553 372.357 Td /F1 9.8 Tf  [(Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56-62.)] TJ ET
BT 26.250 352.953 Td /F1 9.8 Tf  [(32.)] TJ ET
BT 43.553 352.953 Td /F1 9.8 Tf  [(Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry )] TJ ET
BT 26.250 341.048 Td /F1 9.8 Tf  [(1961;4:561-571.)] TJ ET
BT 26.250 321.643 Td /F1 9.8 Tf  [(33.)] TJ ET
BT 43.553 321.643 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 26.250 309.738 Td /F1 9.8 Tf  [(pathology in Huntington's disease. Ann Neurol 1997;41:689-692.)] TJ ET
BT 26.250 290.334 Td /F1 9.8 Tf  [(34.)] TJ ET
BT 43.553 290.334 Td /F1 9.8 Tf  [(Muller T, Woitalla D, Goetze O, Erdmann C. Entacapone improves absorption of a coadministered salt in patients with )] TJ ET
BT 26.250 278.429 Td /F1 9.8 Tf  [(Parkinson's disease. Mov Disord 2008;23:1458-1461.)] TJ ET
BT 26.250 259.024 Td /F1 9.8 Tf  [(35.)] TJ ET
BT 43.553 259.024 Td /F1 9.8 Tf  [(Ravussin E, Pahud P, Thelin-Doerner A, Arnaud MJ, Jequier E. Substrate utilization during prolonged exercise after )] TJ ET
BT 26.250 247.119 Td /F1 9.8 Tf  [(ingestion of 13C-glucose in obese and control subjects. Int J Obes 1980;4:235-242.)] TJ ET
BT 26.250 227.715 Td /F1 9.8 Tf  [(36.)] TJ ET
BT 43.553 227.715 Td /F1 9.8 Tf  [(Haycock GB, Schwartz GJ, Wisotsky DH. Geometric method for measuring body surface area: a height-weight formula )] TJ ET
BT 26.250 215.810 Td /F1 9.8 Tf  [(validated in infants, children, and adults. J Pediatr 1978;93:62-66.)] TJ ET
BT 26.250 196.405 Td /F1 9.8 Tf  [(37.)] TJ ET
BT 43.553 196.405 Td /F1 9.8 Tf  [(Ghoos YF, Maes BD, Geypens BJ, et al. Measurement of gastric emptying rate of solids by means of a carbon-labeled )] TJ ET
BT 26.250 184.500 Td /F1 9.8 Tf  [(octanoic acid breath test. Gastroenterology 1993;104:1640-1647.)] TJ ET
BT 26.250 165.096 Td /F1 9.8 Tf  [(38.)] TJ ET
BT 43.553 165.096 Td /F1 9.8 Tf  [(Revicki DA, Rentz AM, Dubois D, et al. Development and validation of a patient-assessed gastroparesis symptom severity )] TJ ET
BT 26.250 153.191 Td /F1 9.8 Tf  [(measure: the Gastroparesis Cardinal Symptom Index. Aliment Pharmacol Ther 2003;18:141-150.)] TJ ET
BT 26.250 133.786 Td /F1 9.8 Tf  [(39.)] TJ ET
BT 43.553 133.786 Td /F1 9.8 Tf  [(Fraser A, Delaney BC, Ford AC, Qume M, Moayyedi P. The Short-Form Leeds Dyspepsia Questionnaire validation study. )] TJ ET
BT 26.250 121.881 Td /F1 9.8 Tf  [(Aliment Pharmacol Ther 2007;25:477-486.)] TJ ET
BT 26.250 102.477 Td /F1 9.8 Tf  [(40.)] TJ ET
BT 43.553 102.477 Td /F1 9.8 Tf  [(Andrich JE, Wobben M, Klotz P, Goetze O, Saft C. Upper gastrointestinal findings in Huntington's disease: patients suffer )] TJ ET
BT 26.250 90.572 Td /F1 9.8 Tf  [(but do not complain. J Neural Transm 2009;116:1607-1611.)] TJ ET
BT 26.250 71.167 Td /F1 9.8 Tf  [(41.)] TJ ET
BT 43.553 71.167 Td /F1 9.8 Tf  [(Stout JC, Paulsen JS, Queller S, et al. Neurocognitive signs in prodromal Huntington disease. Neuropsychology;25:1-14.)] TJ ET
BT 26.250 51.762 Td /F1 9.8 Tf  [(42.)] TJ ET
BT 43.553 51.762 Td /F1 9.8 Tf  [(Beglinger LJ, Duff K, Allison J, et al. Cognitive change in patients with Huntington disease on the Repeatable Battery for the )] TJ ET
Q
q
15.000 37.477 577.500 739.523 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(patients. Clin Neuropharmacol 2006;29:61-67.)] TJ ET
BT 26.250 748.071 Td /F1 9.8 Tf  [(19.)] TJ ET
BT 43.553 748.071 Td /F1 9.8 Tf  [(Woitalla D, Goetze O. Treatment approaches of gastrointestinal dysfunction in Parkinson's disease, therapeutical options )] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(and future perspectives. J Neurol Sci.)] TJ ET
BT 26.250 716.762 Td /F1 9.8 Tf  [(20.)] TJ ET
BT 43.553 716.762 Td /F1 9.8 Tf  [(Djaldetti R, Baron J, Ziv I, Melamed E. Gastric emptying in Parkinson's disease: patients with and without response )] TJ ET
BT 26.250 704.857 Td /F1 9.8 Tf  [(fluctuations. Neurology 1996;46:1051-1054.)] TJ ET
BT 26.250 685.452 Td /F1 9.8 Tf  [(21.)] TJ ET
BT 43.553 685.452 Td /F1 9.8 Tf  [(Pfeiffer RF. Gastrointestinal dysfunction in Parkinson's disease. Lancet Neurol 2003;2:107-116.)] TJ ET
BT 26.250 666.048 Td /F1 9.8 Tf  [(22.)] TJ ET
BT 43.553 666.048 Td /F1 9.8 Tf  [(Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic )] TJ ET
BT 26.250 654.143 Td /F1 9.8 Tf  [(Parkinson's disease. Neurobiol Aging 2003;24:197-211.)] TJ ET
BT 26.250 634.738 Td /F1 9.8 Tf  [(23.)] TJ ET
BT 43.553 634.738 Td /F1 9.8 Tf  [(Andrich J, Schmitz T, Saft C, et al. Autonomic nervous system function in Huntington's disease. J Neurol Neurosurg )] TJ ET
BT 26.250 622.833 Td /F1 9.8 Tf  [(Psychiatry 2002;72:726-731.)] TJ ET
BT 26.250 603.429 Td /F1 9.8 Tf  [(24.)] TJ ET
BT 43.553 603.429 Td /F1 9.8 Tf  [(Keller J, Franke A, Storr M, Wiedbrauck F, Schirra J. [Clinically relevant breath tests in gastroenterological diagnostics--)] TJ ET
BT 26.250 591.524 Td /F1 9.8 Tf  [(recommendations of the German Society for Neurogastroenterology and Motility as well as the German Society for Digestive )] TJ ET
BT 26.250 579.619 Td /F1 9.8 Tf  [(and Metabolic Diseases]. Z Gastroenterol 2005;43:1071-1090.)] TJ ET
BT 26.250 560.214 Td /F1 9.8 Tf  [(25.)] TJ ET
BT 43.553 560.214 Td /F1 9.8 Tf  [(Shoulson I. Huntington disease: functional capacities in patients treated with neuroleptic and antidepressant drugs. )] TJ ET
BT 26.250 548.310 Td /F1 9.8 Tf  [(Neurology 1981;31:1333-1335.)] TJ ET
BT 26.250 528.905 Td /F1 9.8 Tf  [(26.)] TJ ET
BT 43.553 528.905 Td /F1 9.8 Tf  [(Huntington Study Group. Unified Huntington's Disease Rating Scale: reliability and consistency. Mov Disord 1996;11:136-)] TJ ET
BT 26.250 517.000 Td /F1 9.8 Tf  [(142.)] TJ ET
BT 26.250 497.595 Td /F1 9.8 Tf  [(27.)] TJ ET
BT 43.553 497.595 Td /F1 9.8 Tf  [(Andrich J, Saft C, Ostholt N, Muller T. Assessment of simple movements and progression of Huntington's disease. J Neurol )] TJ ET
BT 26.250 485.691 Td /F1 9.8 Tf  [(Neurosurg Psychiatry 2007;78:405-407.)] TJ ET
BT 26.250 466.286 Td /F1 9.8 Tf  [(28.)] TJ ET
BT 43.553 466.286 Td /F1 9.8 Tf  [(Andrich J, Saft C, Ostholt N, Muller T. Complex movement behaviour and progression of Huntington's disease. Neurosci )] TJ ET
BT 26.250 454.381 Td /F1 9.8 Tf  [(Lett 2007;416:272-274.)] TJ ET
BT 26.250 434.976 Td /F1 9.8 Tf  [(29.)] TJ ET
BT 43.553 434.976 Td /F1 9.8 Tf  [(Saft C, Andrich J, Meisel NM, Przuntek H, Muller T. Assessment of simple movements reflects impairment in Huntington's )] TJ ET
BT 26.250 423.072 Td /F1 9.8 Tf  [(disease. Mov Disord 2006;21:1208-1212.)] TJ ET
BT 26.250 403.667 Td /F1 9.8 Tf  [(30.)] TJ ET
BT 43.553 403.667 Td /F1 9.8 Tf  [(Saft C, Andrich J, Meisel NM, Przuntek H, Muller T. Assessment of complex movements reflects dysfunction in Huntington's )] TJ ET
BT 26.250 391.762 Td /F1 9.8 Tf  [(disease. J Neurol 2003;250:1469-1474.)] TJ ET
BT 26.250 372.357 Td /F1 9.8 Tf  [(31.)] TJ ET
BT 43.553 372.357 Td /F1 9.8 Tf  [(Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56-62.)] TJ ET
BT 26.250 352.953 Td /F1 9.8 Tf  [(32.)] TJ ET
BT 43.553 352.953 Td /F1 9.8 Tf  [(Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry )] TJ ET
BT 26.250 341.048 Td /F1 9.8 Tf  [(1961;4:561-571.)] TJ ET
BT 26.250 321.643 Td /F1 9.8 Tf  [(33.)] TJ ET
BT 43.553 321.643 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 26.250 309.738 Td /F1 9.8 Tf  [(pathology in Huntington's disease. Ann Neurol 1997;41:689-692.)] TJ ET
BT 26.250 290.334 Td /F1 9.8 Tf  [(34.)] TJ ET
BT 43.553 290.334 Td /F1 9.8 Tf  [(Muller T, Woitalla D, Goetze O, Erdmann C. Entacapone improves absorption of a coadministered salt in patients with )] TJ ET
BT 26.250 278.429 Td /F1 9.8 Tf  [(Parkinson's disease. Mov Disord 2008;23:1458-1461.)] TJ ET
BT 26.250 259.024 Td /F1 9.8 Tf  [(35.)] TJ ET
BT 43.553 259.024 Td /F1 9.8 Tf  [(Ravussin E, Pahud P, Thelin-Doerner A, Arnaud MJ, Jequier E. Substrate utilization during prolonged exercise after )] TJ ET
BT 26.250 247.119 Td /F1 9.8 Tf  [(ingestion of 13C-glucose in obese and control subjects. Int J Obes 1980;4:235-242.)] TJ ET
BT 26.250 227.715 Td /F1 9.8 Tf  [(36.)] TJ ET
BT 43.553 227.715 Td /F1 9.8 Tf  [(Haycock GB, Schwartz GJ, Wisotsky DH. Geometric method for measuring body surface area: a height-weight formula )] TJ ET
BT 26.250 215.810 Td /F1 9.8 Tf  [(validated in infants, children, and adults. J Pediatr 1978;93:62-66.)] TJ ET
BT 26.250 196.405 Td /F1 9.8 Tf  [(37.)] TJ ET
BT 43.553 196.405 Td /F1 9.8 Tf  [(Ghoos YF, Maes BD, Geypens BJ, et al. Measurement of gastric emptying rate of solids by means of a carbon-labeled )] TJ ET
BT 26.250 184.500 Td /F1 9.8 Tf  [(octanoic acid breath test. Gastroenterology 1993;104:1640-1647.)] TJ ET
BT 26.250 165.096 Td /F1 9.8 Tf  [(38.)] TJ ET
BT 43.553 165.096 Td /F1 9.8 Tf  [(Revicki DA, Rentz AM, Dubois D, et al. Development and validation of a patient-assessed gastroparesis symptom severity )] TJ ET
BT 26.250 153.191 Td /F1 9.8 Tf  [(measure: the Gastroparesis Cardinal Symptom Index. Aliment Pharmacol Ther 2003;18:141-150.)] TJ ET
BT 26.250 133.786 Td /F1 9.8 Tf  [(39.)] TJ ET
BT 43.553 133.786 Td /F1 9.8 Tf  [(Fraser A, Delaney BC, Ford AC, Qume M, Moayyedi P. The Short-Form Leeds Dyspepsia Questionnaire validation study. )] TJ ET
BT 26.250 121.881 Td /F1 9.8 Tf  [(Aliment Pharmacol Ther 2007;25:477-486.)] TJ ET
BT 26.250 102.477 Td /F1 9.8 Tf  [(40.)] TJ ET
BT 43.553 102.477 Td /F1 9.8 Tf  [(Andrich JE, Wobben M, Klotz P, Goetze O, Saft C. Upper gastrointestinal findings in Huntington's disease: patients suffer )] TJ ET
BT 26.250 90.572 Td /F1 9.8 Tf  [(but do not complain. J Neural Transm 2009;116:1607-1611.)] TJ ET
BT 26.250 71.167 Td /F1 9.8 Tf  [(41.)] TJ ET
BT 43.553 71.167 Td /F1 9.8 Tf  [(Stout JC, Paulsen JS, Queller S, et al. Neurocognitive signs in prodromal Huntington disease. Neuropsychology;25:1-14.)] TJ ET
BT 26.250 51.762 Td /F1 9.8 Tf  [(42.)] TJ ET
BT 43.553 51.762 Td /F1 9.8 Tf  [(Beglinger LJ, Duff K, Allison J, et al. Cognitive change in patients with Huntington disease on the Repeatable Battery for the )] TJ ET
Q
q
15.000 37.477 577.500 739.523 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(patients. Clin Neuropharmacol 2006;29:61-67.)] TJ ET
BT 26.250 748.071 Td /F1 9.8 Tf  [(19.)] TJ ET
BT 43.553 748.071 Td /F1 9.8 Tf  [(Woitalla D, Goetze O. Treatment approaches of gastrointestinal dysfunction in Parkinson's disease, therapeutical options )] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(and future perspectives. J Neurol Sci.)] TJ ET
BT 26.250 716.762 Td /F1 9.8 Tf  [(20.)] TJ ET
BT 43.553 716.762 Td /F1 9.8 Tf  [(Djaldetti R, Baron J, Ziv I, Melamed E. Gastric emptying in Parkinson's disease: patients with and without response )] TJ ET
BT 26.250 704.857 Td /F1 9.8 Tf  [(fluctuations. Neurology 1996;46:1051-1054.)] TJ ET
BT 26.250 685.452 Td /F1 9.8 Tf  [(21.)] TJ ET
BT 43.553 685.452 Td /F1 9.8 Tf  [(Pfeiffer RF. Gastrointestinal dysfunction in Parkinson's disease. Lancet Neurol 2003;2:107-116.)] TJ ET
BT 26.250 666.048 Td /F1 9.8 Tf  [(22.)] TJ ET
BT 43.553 666.048 Td /F1 9.8 Tf  [(Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic )] TJ ET
BT 26.250 654.143 Td /F1 9.8 Tf  [(Parkinson's disease. Neurobiol Aging 2003;24:197-211.)] TJ ET
BT 26.250 634.738 Td /F1 9.8 Tf  [(23.)] TJ ET
BT 43.553 634.738 Td /F1 9.8 Tf  [(Andrich J, Schmitz T, Saft C, et al. Autonomic nervous system function in Huntington's disease. J Neurol Neurosurg )] TJ ET
BT 26.250 622.833 Td /F1 9.8 Tf  [(Psychiatry 2002;72:726-731.)] TJ ET
BT 26.250 603.429 Td /F1 9.8 Tf  [(24.)] TJ ET
BT 43.553 603.429 Td /F1 9.8 Tf  [(Keller J, Franke A, Storr M, Wiedbrauck F, Schirra J. [Clinically relevant breath tests in gastroenterological diagnostics--)] TJ ET
BT 26.250 591.524 Td /F1 9.8 Tf  [(recommendations of the German Society for Neurogastroenterology and Motility as well as the German Society for Digestive )] TJ ET
BT 26.250 579.619 Td /F1 9.8 Tf  [(and Metabolic Diseases]. Z Gastroenterol 2005;43:1071-1090.)] TJ ET
BT 26.250 560.214 Td /F1 9.8 Tf  [(25.)] TJ ET
BT 43.553 560.214 Td /F1 9.8 Tf  [(Shoulson I. Huntington disease: functional capacities in patients treated with neuroleptic and antidepressant drugs. )] TJ ET
BT 26.250 548.310 Td /F1 9.8 Tf  [(Neurology 1981;31:1333-1335.)] TJ ET
BT 26.250 528.905 Td /F1 9.8 Tf  [(26.)] TJ ET
BT 43.553 528.905 Td /F1 9.8 Tf  [(Huntington Study Group. Unified Huntington's Disease Rating Scale: reliability and consistency. Mov Disord 1996;11:136-)] TJ ET
BT 26.250 517.000 Td /F1 9.8 Tf  [(142.)] TJ ET
BT 26.250 497.595 Td /F1 9.8 Tf  [(27.)] TJ ET
BT 43.553 497.595 Td /F1 9.8 Tf  [(Andrich J, Saft C, Ostholt N, Muller T. Assessment of simple movements and progression of Huntington's disease. J Neurol )] TJ ET
BT 26.250 485.691 Td /F1 9.8 Tf  [(Neurosurg Psychiatry 2007;78:405-407.)] TJ ET
BT 26.250 466.286 Td /F1 9.8 Tf  [(28.)] TJ ET
BT 43.553 466.286 Td /F1 9.8 Tf  [(Andrich J, Saft C, Ostholt N, Muller T. Complex movement behaviour and progression of Huntington's disease. Neurosci )] TJ ET
BT 26.250 454.381 Td /F1 9.8 Tf  [(Lett 2007;416:272-274.)] TJ ET
BT 26.250 434.976 Td /F1 9.8 Tf  [(29.)] TJ ET
BT 43.553 434.976 Td /F1 9.8 Tf  [(Saft C, Andrich J, Meisel NM, Przuntek H, Muller T. Assessment of simple movements reflects impairment in Huntington's )] TJ ET
BT 26.250 423.072 Td /F1 9.8 Tf  [(disease. Mov Disord 2006;21:1208-1212.)] TJ ET
BT 26.250 403.667 Td /F1 9.8 Tf  [(30.)] TJ ET
BT 43.553 403.667 Td /F1 9.8 Tf  [(Saft C, Andrich J, Meisel NM, Przuntek H, Muller T. Assessment of complex movements reflects dysfunction in Huntington's )] TJ ET
BT 26.250 391.762 Td /F1 9.8 Tf  [(disease. J Neurol 2003;250:1469-1474.)] TJ ET
BT 26.250 372.357 Td /F1 9.8 Tf  [(31.)] TJ ET
BT 43.553 372.357 Td /F1 9.8 Tf  [(Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56-62.)] TJ ET
BT 26.250 352.953 Td /F1 9.8 Tf  [(32.)] TJ ET
BT 43.553 352.953 Td /F1 9.8 Tf  [(Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry )] TJ ET
BT 26.250 341.048 Td /F1 9.8 Tf  [(1961;4:561-571.)] TJ ET
BT 26.250 321.643 Td /F1 9.8 Tf  [(33.)] TJ ET
BT 43.553 321.643 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 26.250 309.738 Td /F1 9.8 Tf  [(pathology in Huntington's disease. Ann Neurol 1997;41:689-692.)] TJ ET
BT 26.250 290.334 Td /F1 9.8 Tf  [(34.)] TJ ET
BT 43.553 290.334 Td /F1 9.8 Tf  [(Muller T, Woitalla D, Goetze O, Erdmann C. Entacapone improves absorption of a coadministered salt in patients with )] TJ ET
BT 26.250 278.429 Td /F1 9.8 Tf  [(Parkinson's disease. Mov Disord 2008;23:1458-1461.)] TJ ET
BT 26.250 259.024 Td /F1 9.8 Tf  [(35.)] TJ ET
BT 43.553 259.024 Td /F1 9.8 Tf  [(Ravussin E, Pahud P, Thelin-Doerner A, Arnaud MJ, Jequier E. Substrate utilization during prolonged exercise after )] TJ ET
BT 26.250 247.119 Td /F1 9.8 Tf  [(ingestion of 13C-glucose in obese and control subjects. Int J Obes 1980;4:235-242.)] TJ ET
BT 26.250 227.715 Td /F1 9.8 Tf  [(36.)] TJ ET
BT 43.553 227.715 Td /F1 9.8 Tf  [(Haycock GB, Schwartz GJ, Wisotsky DH. Geometric method for measuring body surface area: a height-weight formula )] TJ ET
BT 26.250 215.810 Td /F1 9.8 Tf  [(validated in infants, children, and adults. J Pediatr 1978;93:62-66.)] TJ ET
BT 26.250 196.405 Td /F1 9.8 Tf  [(37.)] TJ ET
BT 43.553 196.405 Td /F1 9.8 Tf  [(Ghoos YF, Maes BD, Geypens BJ, et al. Measurement of gastric emptying rate of solids by means of a carbon-labeled )] TJ ET
BT 26.250 184.500 Td /F1 9.8 Tf  [(octanoic acid breath test. Gastroenterology 1993;104:1640-1647.)] TJ ET
BT 26.250 165.096 Td /F1 9.8 Tf  [(38.)] TJ ET
BT 43.553 165.096 Td /F1 9.8 Tf  [(Revicki DA, Rentz AM, Dubois D, et al. Development and validation of a patient-assessed gastroparesis symptom severity )] TJ ET
BT 26.250 153.191 Td /F1 9.8 Tf  [(measure: the Gastroparesis Cardinal Symptom Index. Aliment Pharmacol Ther 2003;18:141-150.)] TJ ET
BT 26.250 133.786 Td /F1 9.8 Tf  [(39.)] TJ ET
BT 43.553 133.786 Td /F1 9.8 Tf  [(Fraser A, Delaney BC, Ford AC, Qume M, Moayyedi P. The Short-Form Leeds Dyspepsia Questionnaire validation study. )] TJ ET
BT 26.250 121.881 Td /F1 9.8 Tf  [(Aliment Pharmacol Ther 2007;25:477-486.)] TJ ET
BT 26.250 102.477 Td /F1 9.8 Tf  [(40.)] TJ ET
BT 43.553 102.477 Td /F1 9.8 Tf  [(Andrich JE, Wobben M, Klotz P, Goetze O, Saft C. Upper gastrointestinal findings in Huntington's disease: patients suffer )] TJ ET
BT 26.250 90.572 Td /F1 9.8 Tf  [(but do not complain. J Neural Transm 2009;116:1607-1611.)] TJ ET
BT 26.250 71.167 Td /F1 9.8 Tf  [(41.)] TJ ET
BT 43.553 71.167 Td /F1 9.8 Tf  [(Stout JC, Paulsen JS, Queller S, et al. Neurocognitive signs in prodromal Huntington disease. Neuropsychology;25:1-14.)] TJ ET
BT 26.250 51.762 Td /F1 9.8 Tf  [(42.)] TJ ET
BT 43.553 51.762 Td /F1 9.8 Tf  [(Beglinger LJ, Duff K, Allison J, et al. Cognitive change in patients with Huntington disease on the Repeatable Battery for the )] 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
617 0 obj
<< /Type /Page
/Parent 3 0 R
/Contents 618 0 R
>>
endobj
618 0 obj
<<
/Length 12286 >>
stream

0.271 0.267 0.267 rg
q
15.000 347.476 577.500 429.524 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(Assessment of Neuropsychological Status. J Clin Exp Neuropsychol 2010;32:573-578.)] TJ ET
BT 26.250 748.071 Td /F1 9.8 Tf  [(43.)] TJ ET
BT 43.553 748.071 Td /F1 9.8 Tf  [(Beglinger LJ, O'Rourke JJ, Wang C, Langbehn DR, Duff K, Paulsen JS. Earliest functional declines in Huntington disease. )] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(Psychiatry Res;178:414-418.)] TJ ET
BT 26.250 716.762 Td /F1 9.8 Tf  [(44.)] TJ ET
BT 43.553 716.762 Td /F1 9.8 Tf  [(Bishop NA, Lu T, Yankner BA. Neural mechanisms of ageing and cognitive decline. Nature 2010;464:529-535.)] TJ ET
BT 26.250 697.357 Td /F1 9.8 Tf  [(45.)] TJ ET
BT 43.553 697.357 Td /F1 9.8 Tf  [(Glade MJ. Oxidative stress and cognitive longevity. Nutrition 2010;26:595-603.)] TJ ET
BT 26.250 677.952 Td /F1 9.8 Tf  [(46.)] TJ ET
BT 43.553 677.952 Td /F1 9.8 Tf  [(Sultana R, Butterfield DA. Oxidatively modified, mitochondria-relevant brain proteins in subjects with Alzheimer disease and )] TJ ET
BT 26.250 666.048 Td /F1 9.8 Tf  [(mild cognitive impairment. J Bioenerg Biomembr 2009;41:441-446.)] TJ ET
BT 26.250 646.643 Td /F1 9.8 Tf  [(47.)] TJ ET
BT 43.553 646.643 Td /F1 9.8 Tf  [(Bossy-Wetzel E, Petrilli A, Knott AB. Mutant huntingtin and mitochondrial dysfunction. Trends Neurosci 2008;31:609-616.)] TJ ET
BT 26.250 627.238 Td /F1 9.8 Tf  [(48.)] TJ ET
BT 43.553 627.238 Td /F1 9.8 Tf  [(Saft C, Zange J, Andrich J, et al. Mitochondrial impairment in patients and asymptomatic mutation carriers of Huntington's )] TJ ET
BT 26.250 615.333 Td /F1 9.8 Tf  [(disease. Mov Disord 2005;20:674-679.)] TJ ET
BT 26.250 595.929 Td /F1 9.8 Tf  [(49.)] TJ ET
BT 43.553 595.929 Td /F1 9.8 Tf  [(Taherzadeh-Fard E, Saft C, Akkad DA, et al. PGC-1alpha downstream transcription factors NRF-1 and TFAM are genetic )] TJ ET
BT 26.250 584.024 Td /F1 9.8 Tf  [(modifiers of Huntington disease. Mol Neurodegener;6:32.)] TJ ET
BT 26.250 564.619 Td /F1 9.8 Tf  [(50.)] TJ ET
BT 43.553 564.619 Td /F1 9.8 Tf  [(Sassone J, Colciago C, Cislaghi G, Silani V, Ciammola A. Huntington's disease: the current state of research with )] TJ ET
BT 26.250 552.714 Td /F1 9.8 Tf  [(peripheral tissues. Exp Neurol 2009;219:385-397.)] TJ ET
BT 26.250 533.310 Td /F1 9.8 Tf  [(51.)] TJ ET
BT 43.553 533.310 Td /F1 9.8 Tf  [(Browne SE. Mitochondria and Huntington's disease pathogenesis: insight from genetic and chemical models. Ann N Y Acad )] TJ ET
BT 26.250 521.405 Td /F1 9.8 Tf  [(Sci 2008;1147:358-382.)] TJ ET
BT 26.250 502.000 Td /F1 9.8 Tf  [(52.)] TJ ET
BT 43.553 502.000 Td /F1 9.8 Tf  [(Davies SW, Turmaine M, Cozens BA, et al. Formation of neuronal intranuclear inclusions underlies the neurological )] TJ ET
BT 26.250 490.095 Td /F1 9.8 Tf  [(dysfunction in mice transgenic for the HD mutation. Cell 1997;90:537-548.)] TJ ET
BT 26.250 470.691 Td /F1 9.8 Tf  [(53.)] TJ ET
BT 43.553 470.691 Td /F1 9.8 Tf  [(Sathasivam K, Hobbs C, Turmaine M, et al. Formation of polyglutamine inclusions in non-CNS tissue. Hum Mol Genet )] TJ ET
BT 26.250 458.786 Td /F1 9.8 Tf  [(1999;8:813-822.)] TJ ET
BT 26.250 439.381 Td /F1 9.8 Tf  [(54.)] TJ ET
BT 43.553 439.381 Td /F1 9.8 Tf  [(Scherzinger E, Lurz R, Turmaine M, et al. Huntingtin-encoded polyglutamine expansions form amyloid-like protein )] TJ ET
BT 26.250 427.476 Td /F1 9.8 Tf  [(aggregates in vitro and in vivo. Cell 1997;90:549-558.)] TJ ET
BT 26.250 408.072 Td /F1 9.8 Tf  [(55.)] TJ ET
BT 43.553 408.072 Td /F1 9.8 Tf  [(Squitieri F, Cannella M, Sgarbi G, et al. Severe ultrastructural mitochondrial changes in lymphoblasts homozygous for )] TJ ET
BT 26.250 396.167 Td /F1 9.8 Tf  [(Huntington disease mutation. Mech Ageing Dev 2006;127:217-220.)] TJ ET
BT 26.250 376.762 Td /F1 9.8 Tf  [(56.)] TJ ET
BT 43.553 376.762 Td /F1 9.8 Tf  [(Grattagliano I, Lauterburg BH, Palasciano G, Portincasa P. 13C-breath tests for clinical investigation of liver mitochondrial )] TJ ET
BT 26.250 364.857 Td /F1 9.8 Tf  [(function. Eur J Clin Invest;40:843-850.)] TJ ET
Q
q
15.000 347.476 577.500 429.524 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(Assessment of Neuropsychological Status. J Clin Exp Neuropsychol 2010;32:573-578.)] TJ ET
BT 26.250 748.071 Td /F1 9.8 Tf  [(43.)] TJ ET
BT 43.553 748.071 Td /F1 9.8 Tf  [(Beglinger LJ, O'Rourke JJ, Wang C, Langbehn DR, Duff K, Paulsen JS. Earliest functional declines in Huntington disease. )] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(Psychiatry Res;178:414-418.)] TJ ET
BT 26.250 716.762 Td /F1 9.8 Tf  [(44.)] TJ ET
BT 43.553 716.762 Td /F1 9.8 Tf  [(Bishop NA, Lu T, Yankner BA. Neural mechanisms of ageing and cognitive decline. Nature 2010;464:529-535.)] TJ ET
BT 26.250 697.357 Td /F1 9.8 Tf  [(45.)] TJ ET
BT 43.553 697.357 Td /F1 9.8 Tf  [(Glade MJ. Oxidative stress and cognitive longevity. Nutrition 2010;26:595-603.)] TJ ET
BT 26.250 677.952 Td /F1 9.8 Tf  [(46.)] TJ ET
BT 43.553 677.952 Td /F1 9.8 Tf  [(Sultana R, Butterfield DA. Oxidatively modified, mitochondria-relevant brain proteins in subjects with Alzheimer disease and )] TJ ET
BT 26.250 666.048 Td /F1 9.8 Tf  [(mild cognitive impairment. J Bioenerg Biomembr 2009;41:441-446.)] TJ ET
BT 26.250 646.643 Td /F1 9.8 Tf  [(47.)] TJ ET
BT 43.553 646.643 Td /F1 9.8 Tf  [(Bossy-Wetzel E, Petrilli A, Knott AB. Mutant huntingtin and mitochondrial dysfunction. Trends Neurosci 2008;31:609-616.)] TJ ET
BT 26.250 627.238 Td /F1 9.8 Tf  [(48.)] TJ ET
BT 43.553 627.238 Td /F1 9.8 Tf  [(Saft C, Zange J, Andrich J, et al. Mitochondrial impairment in patients and asymptomatic mutation carriers of Huntington's )] TJ ET
BT 26.250 615.333 Td /F1 9.8 Tf  [(disease. Mov Disord 2005;20:674-679.)] TJ ET
BT 26.250 595.929 Td /F1 9.8 Tf  [(49.)] TJ ET
BT 43.553 595.929 Td /F1 9.8 Tf  [(Taherzadeh-Fard E, Saft C, Akkad DA, et al. PGC-1alpha downstream transcription factors NRF-1 and TFAM are genetic )] TJ ET
BT 26.250 584.024 Td /F1 9.8 Tf  [(modifiers of Huntington disease. Mol Neurodegener;6:32.)] TJ ET
BT 26.250 564.619 Td /F1 9.8 Tf  [(50.)] TJ ET
BT 43.553 564.619 Td /F1 9.8 Tf  [(Sassone J, Colciago C, Cislaghi G, Silani V, Ciammola A. Huntington's disease: the current state of research with )] TJ ET
BT 26.250 552.714 Td /F1 9.8 Tf  [(peripheral tissues. Exp Neurol 2009;219:385-397.)] TJ ET
BT 26.250 533.310 Td /F1 9.8 Tf  [(51.)] TJ ET
BT 43.553 533.310 Td /F1 9.8 Tf  [(Browne SE. Mitochondria and Huntington's disease pathogenesis: insight from genetic and chemical models. Ann N Y Acad )] TJ ET
BT 26.250 521.405 Td /F1 9.8 Tf  [(Sci 2008;1147:358-382.)] TJ ET
BT 26.250 502.000 Td /F1 9.8 Tf  [(52.)] TJ ET
BT 43.553 502.000 Td /F1 9.8 Tf  [(Davies SW, Turmaine M, Cozens BA, et al. Formation of neuronal intranuclear inclusions underlies the neurological )] TJ ET
BT 26.250 490.095 Td /F1 9.8 Tf  [(dysfunction in mice transgenic for the HD mutation. Cell 1997;90:537-548.)] TJ ET
BT 26.250 470.691 Td /F1 9.8 Tf  [(53.)] TJ ET
BT 43.553 470.691 Td /F1 9.8 Tf  [(Sathasivam K, Hobbs C, Turmaine M, et al. Formation of polyglutamine inclusions in non-CNS tissue. Hum Mol Genet )] TJ ET
BT 26.250 458.786 Td /F1 9.8 Tf  [(1999;8:813-822.)] TJ ET
BT 26.250 439.381 Td /F1 9.8 Tf  [(54.)] TJ ET
BT 43.553 439.381 Td /F1 9.8 Tf  [(Scherzinger E, Lurz R, Turmaine M, et al. Huntingtin-encoded polyglutamine expansions form amyloid-like protein )] TJ ET
BT 26.250 427.476 Td /F1 9.8 Tf  [(aggregates in vitro and in vivo. Cell 1997;90:549-558.)] TJ ET
BT 26.250 408.072 Td /F1 9.8 Tf  [(55.)] TJ ET
BT 43.553 408.072 Td /F1 9.8 Tf  [(Squitieri F, Cannella M, Sgarbi G, et al. Severe ultrastructural mitochondrial changes in lymphoblasts homozygous for )] TJ ET
BT 26.250 396.167 Td /F1 9.8 Tf  [(Huntington disease mutation. Mech Ageing Dev 2006;127:217-220.)] TJ ET
BT 26.250 376.762 Td /F1 9.8 Tf  [(56.)] TJ ET
BT 43.553 376.762 Td /F1 9.8 Tf  [(Grattagliano I, Lauterburg BH, Palasciano G, Portincasa P. 13C-breath tests for clinical investigation of liver mitochondrial )] TJ ET
BT 26.250 364.857 Td /F1 9.8 Tf  [(function. Eur J Clin Invest;40:843-850.)] TJ ET
Q
q
15.000 347.476 577.500 429.524 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(Assessment of Neuropsychological Status. J Clin Exp Neuropsychol 2010;32:573-578.)] TJ ET
BT 26.250 748.071 Td /F1 9.8 Tf  [(43.)] TJ ET
BT 43.553 748.071 Td /F1 9.8 Tf  [(Beglinger LJ, O'Rourke JJ, Wang C, Langbehn DR, Duff K, Paulsen JS. Earliest functional declines in Huntington disease. )] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(Psychiatry Res;178:414-418.)] TJ ET
BT 26.250 716.762 Td /F1 9.8 Tf  [(44.)] TJ ET
BT 43.553 716.762 Td /F1 9.8 Tf  [(Bishop NA, Lu T, Yankner BA. Neural mechanisms of ageing and cognitive decline. Nature 2010;464:529-535.)] TJ ET
BT 26.250 697.357 Td /F1 9.8 Tf  [(45.)] TJ ET
BT 43.553 697.357 Td /F1 9.8 Tf  [(Glade MJ. Oxidative stress and cognitive longevity. Nutrition 2010;26:595-603.)] TJ ET
BT 26.250 677.952 Td /F1 9.8 Tf  [(46.)] TJ ET
BT 43.553 677.952 Td /F1 9.8 Tf  [(Sultana R, Butterfield DA. Oxidatively modified, mitochondria-relevant brain proteins in subjects with Alzheimer disease and )] TJ ET
BT 26.250 666.048 Td /F1 9.8 Tf  [(mild cognitive impairment. J Bioenerg Biomembr 2009;41:441-446.)] TJ ET
BT 26.250 646.643 Td /F1 9.8 Tf  [(47.)] TJ ET
BT 43.553 646.643 Td /F1 9.8 Tf  [(Bossy-Wetzel E, Petrilli A, Knott AB. Mutant huntingtin and mitochondrial dysfunction. Trends Neurosci 2008;31:609-616.)] TJ ET
BT 26.250 627.238 Td /F1 9.8 Tf  [(48.)] TJ ET
BT 43.553 627.238 Td /F1 9.8 Tf  [(Saft C, Zange J, Andrich J, et al. Mitochondrial impairment in patients and asymptomatic mutation carriers of Huntington's )] TJ ET
BT 26.250 615.333 Td /F1 9.8 Tf  [(disease. Mov Disord 2005;20:674-679.)] TJ ET
BT 26.250 595.929 Td /F1 9.8 Tf  [(49.)] TJ ET
BT 43.553 595.929 Td /F1 9.8 Tf  [(Taherzadeh-Fard E, Saft C, Akkad DA, et al. PGC-1alpha downstream transcription factors NRF-1 and TFAM are genetic )] TJ ET
BT 26.250 584.024 Td /F1 9.8 Tf  [(modifiers of Huntington disease. Mol Neurodegener;6:32.)] TJ ET
BT 26.250 564.619 Td /F1 9.8 Tf  [(50.)] TJ ET
BT 43.553 564.619 Td /F1 9.8 Tf  [(Sassone J, Colciago C, Cislaghi G, Silani V, Ciammola A. Huntington's disease: the current state of research with )] TJ ET
BT 26.250 552.714 Td /F1 9.8 Tf  [(peripheral tissues. Exp Neurol 2009;219:385-397.)] TJ ET
BT 26.250 533.310 Td /F1 9.8 Tf  [(51.)] TJ ET
BT 43.553 533.310 Td /F1 9.8 Tf  [(Browne SE. Mitochondria and Huntington's disease pathogenesis: insight from genetic and chemical models. Ann N Y Acad )] TJ ET
BT 26.250 521.405 Td /F1 9.8 Tf  [(Sci 2008;1147:358-382.)] TJ ET
BT 26.250 502.000 Td /F1 9.8 Tf  [(52.)] TJ ET
BT 43.553 502.000 Td /F1 9.8 Tf  [(Davies SW, Turmaine M, Cozens BA, et al. Formation of neuronal intranuclear inclusions underlies the neurological )] TJ ET
BT 26.250 490.095 Td /F1 9.8 Tf  [(dysfunction in mice transgenic for the HD mutation. Cell 1997;90:537-548.)] TJ ET
BT 26.250 470.691 Td /F1 9.8 Tf  [(53.)] TJ ET
BT 43.553 470.691 Td /F1 9.8 Tf  [(Sathasivam K, Hobbs C, Turmaine M, et al. Formation of polyglutamine inclusions in non-CNS tissue. Hum Mol Genet )] TJ ET
BT 26.250 458.786 Td /F1 9.8 Tf  [(1999;8:813-822.)] TJ ET
BT 26.250 439.381 Td /F1 9.8 Tf  [(54.)] TJ ET
BT 43.553 439.381 Td /F1 9.8 Tf  [(Scherzinger E, Lurz R, Turmaine M, et al. Huntingtin-encoded polyglutamine expansions form amyloid-like protein )] TJ ET
BT 26.250 427.476 Td /F1 9.8 Tf  [(aggregates in vitro and in vivo. Cell 1997;90:549-558.)] TJ ET
BT 26.250 408.072 Td /F1 9.8 Tf  [(55.)] TJ ET
BT 43.553 408.072 Td /F1 9.8 Tf  [(Squitieri F, Cannella M, Sgarbi G, et al. Severe ultrastructural mitochondrial changes in lymphoblasts homozygous for )] TJ ET
BT 26.250 396.167 Td /F1 9.8 Tf  [(Huntington disease mutation. Mech Ageing Dev 2006;127:217-220.)] TJ ET
BT 26.250 376.762 Td /F1 9.8 Tf  [(56.)] TJ ET
BT 43.553 376.762 Td /F1 9.8 Tf  [(Grattagliano I, Lauterburg BH, Palasciano G, Portincasa P. 13C-breath tests for clinical investigation of liver mitochondrial )] TJ ET
BT 26.250 364.857 Td /F1 9.8 Tf  [(function. Eur J Clin Invest;40:843-850.)] 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
xref
0 619
0000000000 65535 f 
0000000008 00000 n 
0000000073 00000 n 
0000000119 00000 n 
0000000509 00000 n 
0000000546 00000 n 
0000000775 00000 n 
0000001479 00000 n 
0000028603 00000 n 
0000028710 00000 n 
0000028818 00000 n 
0000028929 00000 n 
0000029042 00000 n 
0000029430 00000 n 
0000033911 00000 n 
0000034038 00000 n 
0000034196 00000 n 
0000034322 00000 n 
0000034480 00000 n 
0000034608 00000 n 
0000034718 00000 n 
0000034844 00000 n 
0000034943 00000 n 
0000035070 00000 n 
0000035171 00000 n 
0000035299 00000 n 
0000035397 00000 n 
0000035525 00000 n 
0000035623 00000 n 
0000035751 00000 n 
0000035850 00000 n 
0000035978 00000 n 
0000036078 00000 n 
0000036206 00000 n 
0000036306 00000 n 
0000036434 00000 n 
0000036470 00000 n 
0000036596 00000 n 
0000036632 00000 n 
0000036758 00000 n 
0000036794 00000 n 
0000036920 00000 n 
0000036956 00000 n 
0000037082 00000 n 
0000037118 00000 n 
0000037244 00000 n 
0000037280 00000 n 
0000037407 00000 n 
0000037443 00000 n 
0000037571 00000 n 
0000037607 00000 n 
0000037735 00000 n 
0000037771 00000 n 
0000037899 00000 n 
0000037935 00000 n 
0000038063 00000 n 
0000038099 00000 n 
0000038227 00000 n 
0000038263 00000 n 
0000038391 00000 n 
0000038427 00000 n 
0000038555 00000 n 
0000038591 00000 n 
0000038719 00000 n 
0000038755 00000 n 
0000038883 00000 n 
0000038919 00000 n 
0000039045 00000 n 
0000039081 00000 n 
0000039207 00000 n 
0000039243 00000 n 
0000039370 00000 n 
0000039528 00000 n 
0000039654 00000 n 
0000039812 00000 n 
0000039940 00000 n 
0000040050 00000 n 
0000040176 00000 n 
0000040275 00000 n 
0000040402 00000 n 
0000040503 00000 n 
0000040631 00000 n 
0000040729 00000 n 
0000040857 00000 n 
0000040955 00000 n 
0000041083 00000 n 
0000041182 00000 n 
0000041310 00000 n 
0000041410 00000 n 
0000041538 00000 n 
0000041638 00000 n 
0000041766 00000 n 
0000041802 00000 n 
0000041928 00000 n 
0000041964 00000 n 
0000042090 00000 n 
0000042126 00000 n 
0000042252 00000 n 
0000042288 00000 n 
0000042414 00000 n 
0000042450 00000 n 
0000042578 00000 n 
0000042615 00000 n 
0000042744 00000 n 
0000042781 00000 n 
0000042911 00000 n 
0000042948 00000 n 
0000043078 00000 n 
0000043115 00000 n 
0000043245 00000 n 
0000043282 00000 n 
0000043412 00000 n 
0000043449 00000 n 
0000043579 00000 n 
0000043616 00000 n 
0000043746 00000 n 
0000043783 00000 n 
0000043913 00000 n 
0000043950 00000 n 
0000044080 00000 n 
0000044117 00000 n 
0000044247 00000 n 
0000044284 00000 n 
0000044412 00000 n 
0000044449 00000 n 
0000044577 00000 n 
0000044614 00000 n 
0000044743 00000 n 
0000044902 00000 n 
0000045030 00000 n 
0000045189 00000 n 
0000045319 00000 n 
0000045430 00000 n 
0000045558 00000 n 
0000045658 00000 n 
0000045787 00000 n 
0000045889 00000 n 
0000046019 00000 n 
0000046118 00000 n 
0000046248 00000 n 
0000046347 00000 n 
0000046477 00000 n 
0000046577 00000 n 
0000046707 00000 n 
0000046808 00000 n 
0000046938 00000 n 
0000047039 00000 n 
0000047169 00000 n 
0000047206 00000 n 
0000047334 00000 n 
0000047371 00000 n 
0000047499 00000 n 
0000047536 00000 n 
0000047664 00000 n 
0000047701 00000 n 
0000047829 00000 n 
0000047866 00000 n 
0000047994 00000 n 
0000048031 00000 n 
0000048160 00000 n 
0000048197 00000 n 
0000048327 00000 n 
0000048364 00000 n 
0000048494 00000 n 
0000048531 00000 n 
0000048661 00000 n 
0000048698 00000 n 
0000048828 00000 n 
0000048865 00000 n 
0000048995 00000 n 
0000049032 00000 n 
0000049162 00000 n 
0000049199 00000 n 
0000049329 00000 n 
0000049366 00000 n 
0000049496 00000 n 
0000049533 00000 n 
0000049663 00000 n 
0000049700 00000 n 
0000049828 00000 n 
0000049865 00000 n 
0000049993 00000 n 
0000050030 00000 n 
0000050757 00000 n 
0000104636 00000 n 
0000104766 00000 n 
0000104803 00000 n 
0000104933 00000 n 
0000104970 00000 n 
0000105100 00000 n 
0000105137 00000 n 
0000105267 00000 n 
0000105304 00000 n 
0000105434 00000 n 
0000105471 00000 n 
0000105601 00000 n 
0000105638 00000 n 
0000105768 00000 n 
0000105805 00000 n 
0000105935 00000 n 
0000105972 00000 n 
0000106102 00000 n 
0000106139 00000 n 
0000106269 00000 n 
0000106306 00000 n 
0000106436 00000 n 
0000106473 00000 n 
0000106603 00000 n 
0000106640 00000 n 
0000106770 00000 n 
0000106807 00000 n 
0000106937 00000 n 
0000106974 00000 n 
0000107104 00000 n 
0000107141 00000 n 
0000107271 00000 n 
0000107308 00000 n 
0000107438 00000 n 
0000107475 00000 n 
0000107605 00000 n 
0000107642 00000 n 
0000107772 00000 n 
0000107809 00000 n 
0000107939 00000 n 
0000107976 00000 n 
0000108106 00000 n 
0000108143 00000 n 
0000108273 00000 n 
0000108310 00000 n 
0000108440 00000 n 
0000108477 00000 n 
0000108607 00000 n 
0000108644 00000 n 
0000108774 00000 n 
0000108811 00000 n 
0000108941 00000 n 
0000108978 00000 n 
0000109108 00000 n 
0000109145 00000 n 
0000109275 00000 n 
0000109312 00000 n 
0000109442 00000 n 
0000109479 00000 n 
0000109609 00000 n 
0000109646 00000 n 
0000109776 00000 n 
0000109813 00000 n 
0000109943 00000 n 
0000109980 00000 n 
0000110110 00000 n 
0000110147 00000 n 
0000110277 00000 n 
0000110314 00000 n 
0000110444 00000 n 
0000110481 00000 n 
0000110611 00000 n 
0000110648 00000 n 
0000110778 00000 n 
0000110815 00000 n 
0000110945 00000 n 
0000110982 00000 n 
0000111112 00000 n 
0000111149 00000 n 
0000111279 00000 n 
0000111316 00000 n 
0000111446 00000 n 
0000111483 00000 n 
0000111613 00000 n 
0000111650 00000 n 
0000111780 00000 n 
0000111817 00000 n 
0000111947 00000 n 
0000111984 00000 n 
0000112114 00000 n 
0000112151 00000 n 
0000112281 00000 n 
0000112318 00000 n 
0000112448 00000 n 
0000112485 00000 n 
0000112615 00000 n 
0000112652 00000 n 
0000112782 00000 n 
0000112819 00000 n 
0000112949 00000 n 
0000112986 00000 n 
0000113116 00000 n 
0000113153 00000 n 
0000113283 00000 n 
0000113320 00000 n 
0000113450 00000 n 
0000113487 00000 n 
0000113617 00000 n 
0000113654 00000 n 
0000113784 00000 n 
0000113821 00000 n 
0000113951 00000 n 
0000113988 00000 n 
0000114118 00000 n 
0000114155 00000 n 
0000114285 00000 n 
0000114322 00000 n 
0000114452 00000 n 
0000114489 00000 n 
0000114619 00000 n 
0000114656 00000 n 
0000114786 00000 n 
0000114823 00000 n 
0000114953 00000 n 
0000114990 00000 n 
0000115120 00000 n 
0000115157 00000 n 
0000115287 00000 n 
0000115324 00000 n 
0000115454 00000 n 
0000115491 00000 n 
0000115621 00000 n 
0000115658 00000 n 
0000115788 00000 n 
0000115825 00000 n 
0000115955 00000 n 
0000115992 00000 n 
0000116122 00000 n 
0000116159 00000 n 
0000116289 00000 n 
0000116326 00000 n 
0000116456 00000 n 
0000116493 00000 n 
0000116623 00000 n 
0000116660 00000 n 
0000116790 00000 n 
0000116827 00000 n 
0000116957 00000 n 
0000116994 00000 n 
0000117124 00000 n 
0000117161 00000 n 
0000117291 00000 n 
0000117328 00000 n 
0000117458 00000 n 
0000117495 00000 n 
0000117625 00000 n 
0000117662 00000 n 
0000117792 00000 n 
0000117829 00000 n 
0000117959 00000 n 
0000117996 00000 n 
0000118126 00000 n 
0000118163 00000 n 
0000118458 00000 n 
0000159707 00000 n 
0000159837 00000 n 
0000159874 00000 n 
0000160004 00000 n 
0000160041 00000 n 
0000160171 00000 n 
0000160208 00000 n 
0000160338 00000 n 
0000160375 00000 n 
0000160505 00000 n 
0000160542 00000 n 
0000160672 00000 n 
0000160709 00000 n 
0000160839 00000 n 
0000160876 00000 n 
0000161006 00000 n 
0000161043 00000 n 
0000161173 00000 n 
0000161210 00000 n 
0000161340 00000 n 
0000161377 00000 n 
0000161507 00000 n 
0000161544 00000 n 
0000161674 00000 n 
0000161711 00000 n 
0000161841 00000 n 
0000161878 00000 n 
0000162008 00000 n 
0000162045 00000 n 
0000162175 00000 n 
0000162212 00000 n 
0000162342 00000 n 
0000162379 00000 n 
0000162509 00000 n 
0000162546 00000 n 
0000162676 00000 n 
0000162713 00000 n 
0000162843 00000 n 
0000162880 00000 n 
0000163010 00000 n 
0000163047 00000 n 
0000163177 00000 n 
0000163214 00000 n 
0000163344 00000 n 
0000163381 00000 n 
0000163511 00000 n 
0000163548 00000 n 
0000163678 00000 n 
0000163715 00000 n 
0000163845 00000 n 
0000163882 00000 n 
0000164012 00000 n 
0000164049 00000 n 
0000164179 00000 n 
0000164216 00000 n 
0000164415 00000 n 
0000198910 00000 n 
0000199040 00000 n 
0000199077 00000 n 
0000199206 00000 n 
0000199319 00000 n 
0000205510 00000 n 
0000205640 00000 n 
0000205677 00000 n 
0000205807 00000 n 
0000205844 00000 n 
0000205972 00000 n 
0000206100 00000 n 
0000206557 00000 n 
0000218791 00000 n 
0000218921 00000 n 
0000218958 00000 n 
0000219087 00000 n 
0000219200 00000 n 
0000219330 00000 n 
0000219367 00000 n 
0000219497 00000 n 
0000219534 00000 n 
0000219662 00000 n 
0000219790 00000 n 
0000220247 00000 n 
0000232481 00000 n 
0000232611 00000 n 
0000232648 00000 n 
0000232777 00000 n 
0000232890 00000 n 
0000233020 00000 n 
0000233057 00000 n 
0000233187 00000 n 
0000233224 00000 n 
0000233352 00000 n 
0000233480 00000 n 
0000233937 00000 n 
0000246171 00000 n 
0000246628 00000 n 
0000258862 00000 n 
0000259613 00000 n 
0000292237 00000 n 
0000292366 00000 n 
0000292403 00000 n 
0000292533 00000 n 
0000292570 00000 n 
0000292700 00000 n 
0000292737 00000 n 
0000292865 00000 n 
0000292902 00000 n 
0000293030 00000 n 
0000293067 00000 n 
0000293195 00000 n 
0000293232 00000 n 
0000293360 00000 n 
0000293397 00000 n 
0000293526 00000 n 
0000293563 00000 n 
0000293693 00000 n 
0000293730 00000 n 
0000293860 00000 n 
0000293897 00000 n 
0000294027 00000 n 
0000294064 00000 n 
0000294194 00000 n 
0000294231 00000 n 
0000294361 00000 n 
0000294398 00000 n 
0000294528 00000 n 
0000294565 00000 n 
0000294695 00000 n 
0000294732 00000 n 
0000294862 00000 n 
0000294899 00000 n 
0000295029 00000 n 
0000295066 00000 n 
0000295196 00000 n 
0000295233 00000 n 
0000295363 00000 n 
0000295400 00000 n 
0000295530 00000 n 
0000295567 00000 n 
0000295697 00000 n 
0000295734 00000 n 
0000295864 00000 n 
0000295901 00000 n 
0000296031 00000 n 
0000296068 00000 n 
0000296198 00000 n 
0000296235 00000 n 
0000296365 00000 n 
0000296402 00000 n 
0000296532 00000 n 
0000296569 00000 n 
0000296699 00000 n 
0000296736 00000 n 
0000296866 00000 n 
0000296903 00000 n 
0000297032 00000 n 
0000297069 00000 n 
0000297199 00000 n 
0000297236 00000 n 
0000297366 00000 n 
0000297403 00000 n 
0000297531 00000 n 
0000297568 00000 n 
0000297696 00000 n 
0000297733 00000 n 
0000297861 00000 n 
0000297898 00000 n 
0000298026 00000 n 
0000298063 00000 n 
0000298192 00000 n 
0000298229 00000 n 
0000298359 00000 n 
0000298396 00000 n 
0000298526 00000 n 
0000298563 00000 n 
0000298693 00000 n 
0000298730 00000 n 
0000298860 00000 n 
0000298897 00000 n 
0000299027 00000 n 
0000299064 00000 n 
0000299194 00000 n 
0000299231 00000 n 
0000299361 00000 n 
0000299398 00000 n 
0000299528 00000 n 
0000299565 00000 n 
0000299695 00000 n 
0000299732 00000 n 
0000299862 00000 n 
0000299899 00000 n 
0000300029 00000 n 
0000300066 00000 n 
0000300196 00000 n 
0000300233 00000 n 
0000300363 00000 n 
0000300400 00000 n 
0000300530 00000 n 
0000300567 00000 n 
0000300697 00000 n 
0000300734 00000 n 
0000300864 00000 n 
0000300901 00000 n 
0000301031 00000 n 
0000301068 00000 n 
0000301198 00000 n 
0000301235 00000 n 
0000301365 00000 n 
0000301402 00000 n 
0000301532 00000 n 
0000301569 00000 n 
0000301698 00000 n 
0000301735 00000 n 
0000301865 00000 n 
0000301902 00000 n 
0000302032 00000 n 
0000302069 00000 n 
0000302197 00000 n 
0000302234 00000 n 
0000302362 00000 n 
0000302399 00000 n 
0000302527 00000 n 
0000302564 00000 n 
0000302692 00000 n 
0000302729 00000 n 
0000302858 00000 n 
0000302895 00000 n 
0000303025 00000 n 
0000303062 00000 n 
0000303192 00000 n 
0000303229 00000 n 
0000303359 00000 n 
0000303396 00000 n 
0000303526 00000 n 
0000303563 00000 n 
0000303693 00000 n 
0000303730 00000 n 
0000303860 00000 n 
0000303897 00000 n 
0000304027 00000 n 
0000304064 00000 n 
0000304194 00000 n 
0000304231 00000 n 
0000304361 00000 n 
0000304398 00000 n 
0000304528 00000 n 
0000304565 00000 n 
0000304695 00000 n 
0000304732 00000 n 
0000304862 00000 n 
0000304899 00000 n 
0000305029 00000 n 
0000305066 00000 n 
0000305196 00000 n 
0000305233 00000 n 
0000305363 00000 n 
0000305400 00000 n 
0000305530 00000 n 
0000305567 00000 n 
0000305697 00000 n 
0000305734 00000 n 
0000305864 00000 n 
0000305901 00000 n 
0000306031 00000 n 
0000306068 00000 n 
0000306198 00000 n 
0000306235 00000 n 
0000306302 00000 n 
0000323587 00000 n 
0000323654 00000 n 
0000345037 00000 n 
0000345104 00000 n 
trailer
<<
/Size 619
/Root 1 0 R
/Info 5 0 R
>>
startxref
357445
%%EOF