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BT 274.446 663.247 Td /F1 9.8 Tf  [(Kevin Biglan)] TJ ET
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BT 328.636 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 212.670 651.342 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 218.091 651.342 Td /F1 9.8 Tf  [(G. Bernhard Landwehrmeyer)] TJ ET
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BT 131.375 639.438 Td /F1 9.8 Tf  [(John H. Warner)] TJ ET
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BT 26.250 603.723 Td /F1 9.8 Tf  [(Symptoms and Functional Impact in Prodromal and Early Huntington Disease. PLOS Currents Huntington Disease. 2011 Jun )] TJ ET
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BT 26.250 542.762 Td /F1 9.8 Tf  [(The Functional Rating Scale Taskforce for pre-Huntington Disease \(FuRST-pHD\) is a multinational, multidisciplinary initiative )] TJ ET
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BT 26.250 518.952 Td /F1 9.8 Tf  [(functional ability in prodromal and early Huntington disease \(HD\) gene expansion carriers. The process involves input from )] TJ ET
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BT 26.250 495.143 Td /F1 9.8 Tf  [(fields, as well as knowledge gained from the analysis of data from ongoing large-scale studies in HD using existing clinical )] TJ ET
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BT 26.250 447.524 Td /F1 9.8 Tf  [(questions aimed to assess functional impact of motor manifestations in prHD and early HD individuals.)] TJ ET
BT 26.250 410.921 Td /F4 12.0 Tf  [(Funding Statement)] TJ ET
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BT 26.250 379.062 Td /F1 9.8 Tf  [(Neurological Disorders and Stroke \(NS40068\) and CHDI Foundation, Inc.)] TJ ET
BT 26.250 349.960 Td /F4 12.0 Tf  [(Introduction)] TJ ET
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BT 238.088 282.387 Td /F1 9.8 Tf  [( Such a measurement tool is essential to better understand the earliest )] TJ ET
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BT 26.250 215.363 Td /F1 9.8 Tf  [(have been established to review existing data and develop interview questions within the specific domain under study. Once )] TJ ET
BT 26.250 203.458 Td /F1 9.8 Tf  [(these interview questions are developed, they are distributed to trained raters for beta testing in prHD and early HD individuals. )] TJ ET
BT 26.250 191.553 Td /F1 9.8 Tf  [(This is an iterative process, in which changes or deletions \(as appropriate\) are made based on empirical evidence obtained )] TJ ET
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BT 26.250 167.744 Td /F1 9.8 Tf  [(winnowed to select optimal items for scale inclusion. We report here the development and assessment of the first iteration of )] TJ ET
BT 26.250 155.839 Td /F1 9.8 Tf  [(interview questions aimed to assess functional impact of motor manifestations in prHD and early HD individuals.)] TJ ET
BT 26.250 119.237 Td /F4 12.0 Tf  [(Methods)] TJ ET
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BT 79.721 675.088 Td /F3 9.8 Tf  [(Clinical Assessment)] TJ ET
BT 26.250 663.247 Td /F1 9.8 Tf  [(Anthony L Vaccarino)] TJ ET
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BT 121.634 663.247 Td /F1 9.8 Tf  [(Terrence Sills)] TJ ET
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BT 186.647 663.247 Td /F1 9.8 Tf  [(Karen E. Anderson)] TJ ET
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BT 274.446 663.247 Td /F1 9.8 Tf  [(Kevin Biglan)] TJ ET
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BT 334.057 663.247 Td /F1 9.8 Tf  [(Beth Borowsky)] TJ ET
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BT 404.501 663.247 Td /F1 9.8 Tf  [(Joseph Giuliano)] TJ ET
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BT 479.830 663.247 Td /F1 9.8 Tf  [(Mark Guttman)] TJ ET
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BT 547.017 663.247 Td /F1 9.8 Tf  [(Aileen )] TJ ET
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BT 47.924 651.342 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 53.345 651.342 Td /F1 9.8 Tf  [(Christopher Kennard)] TJ ET
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BT 148.720 651.342 Td /F1 9.8 Tf  [(Peter Kupchak)] TJ ET
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BT 212.670 651.342 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 218.091 651.342 Td /F1 9.8 Tf  [(G. Bernhard Landwehrmeyer)] TJ ET
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BT 343.808 651.342 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 349.228 651.342 Td /F1 9.8 Tf  [(Andrew Michell)] TJ ET
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BT 420.745 651.342 Td /F1 9.8 Tf  [(Jane S. Paulsen)] TJ ET
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BT 491.744 651.342 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 497.165 651.342 Td /F1 9.8 Tf  [(Ralf Reilmann)] TJ ET
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BT 558.385 651.342 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 26.250 639.438 Td /F1 9.8 Tf  [(Daniel P. van Kammen)] TJ ET
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BT 125.954 639.438 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 131.375 639.438 Td /F1 9.8 Tf  [(John H. Warner)] TJ ET
0.271 0.267 0.267 rg
BT 199.644 639.438 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 205.065 639.438 Td /F1 9.8 Tf  [(Ken Evans)] TJ ET
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BT 26.250 615.628 Td /F1 9.8 Tf  [(Landwehrmeyer GB, Michell A, Paulsen JS, Reilmann R, van Kammen DP, Warner JH, Evans K. Assessment of Motor )] TJ ET
BT 26.250 603.723 Td /F1 9.8 Tf  [(Symptoms and Functional Impact in Prodromal and Early Huntington Disease. PLOS Currents Huntington Disease. 2011 Jun )] TJ ET
BT 26.250 591.819 Td /F1 9.8 Tf  [(14 . Edition 1. doi: 10.1371/currents.RRN1244.)] TJ ET
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BT 26.250 562.716 Td /F4 12.0 Tf  [(Abstract)] TJ ET
BT 26.250 542.762 Td /F1 9.8 Tf  [(The Functional Rating Scale Taskforce for pre-Huntington Disease \(FuRST-pHD\) is a multinational, multidisciplinary initiative )] TJ ET
BT 26.250 530.857 Td /F1 9.8 Tf  [(with the goal of developing a data-driven, comprehensive, psychometrically sound, rating scale for assessing symptoms and )] TJ ET
BT 26.250 518.952 Td /F1 9.8 Tf  [(functional ability in prodromal and early Huntington disease \(HD\) gene expansion carriers. The process involves input from )] TJ ET
BT 26.250 507.048 Td /F1 9.8 Tf  [(numerous sources to identify relevant symptom domains, including HD individuals, caregivers, and experts from a variety of )] TJ ET
BT 26.250 495.143 Td /F1 9.8 Tf  [(fields, as well as knowledge gained from the analysis of data from ongoing large-scale studies in HD using existing clinical )] TJ ET
BT 26.250 483.238 Td /F1 9.8 Tf  [(scales. This is an iterative process in which an ongoing series of field tests in prodromal \(prHD\) and early HD individuals )] TJ ET
BT 26.250 471.333 Td /F1 9.8 Tf  [(provides the team with data on which to make decisions regarding which questions should undergo further development or )] TJ ET
BT 26.250 459.429 Td /F1 9.8 Tf  [(testing and which should be excluded. We report here the development and assessment of the first iteration of interview )] TJ ET
BT 26.250 447.524 Td /F1 9.8 Tf  [(questions aimed to assess functional impact of motor manifestations in prHD and early HD individuals.)] TJ ET
BT 26.250 410.921 Td /F4 12.0 Tf  [(Funding Statement)] TJ ET
BT 26.250 390.967 Td /F1 9.8 Tf  [(FuRST-pHD is funded by CHDI. PREDICT-HD is supported by the National Institutes for Health, National Institute of )] TJ ET
BT 26.250 379.062 Td /F1 9.8 Tf  [(Neurological Disorders and Stroke \(NS40068\) and CHDI Foundation, Inc.)] TJ ET
BT 26.250 349.960 Td /F4 12.0 Tf  [(Introduction)] TJ ET
BT 26.250 330.006 Td /F1 9.8 Tf  [(Earliest clinical manifestations of Huntington disease \(HD\) are poorly characterized, and there is a need for clinical scales )] TJ ET
BT 26.250 318.101 Td /F1 9.8 Tf  [(specifically designed to measure early changes in HD gene expansion carriers. The Functional Rating Scale Taskforce for pre-)] TJ ET
BT 26.250 306.196 Td /F1 9.8 Tf  [(Huntington Disease \(FuRST-pHD\) is a multinational, multidisciplinary collaboration to develop a valid functional rating scale to )] TJ ET
BT 26.250 294.291 Td /F1 9.8 Tf  [(assess changes in symptom severity in HD gene expansion carriers who do not yet meet criteria for a formal clinical diagnosis )] TJ ET
BT 26.250 282.387 Td /F1 9.8 Tf  [(\(prodromal HD or prHD\) or are early manifest. )] TJ ET
0.267 0.267 0.267 rg
BT 227.246 282.387 Td /F1 9.8 Tf  [([1])] TJ ET
0.271 0.267 0.267 rg
BT 238.088 282.387 Td /F1 9.8 Tf  [( Such a measurement tool is essential to better understand the earliest )] TJ ET
BT 26.250 270.482 Td /F1 9.8 Tf  [(manifestations of HD and to evaluate novel therapies early in the course of disease.)] TJ ET
BT 26.250 251.077 Td /F1 9.8 Tf  [(FuRST-pHD has established an inclusive process using input from numerous sources, including prHD and early HD individuals, )] TJ ET
BT 26.250 239.172 Td /F1 9.8 Tf  [(caregivers, and experts from a variety of fields, as well as from ongoing large-scale HD studies using existing clinical scales. )] TJ ET
0.267 0.267 0.267 rg
BT 563.768 239.172 Td /F1 9.8 Tf  [([1])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 227.268 Td /F1 9.8 Tf  [(As part of the process, an inclusive series of �Working Groups� of individuals with clinical and/or scale development expertise )] TJ ET
BT 26.250 215.363 Td /F1 9.8 Tf  [(have been established to review existing data and develop interview questions within the specific domain under study. Once )] TJ ET
BT 26.250 203.458 Td /F1 9.8 Tf  [(these interview questions are developed, they are distributed to trained raters for beta testing in prHD and early HD individuals. )] TJ ET
BT 26.250 191.553 Td /F1 9.8 Tf  [(This is an iterative process, in which changes or deletions \(as appropriate\) are made based on empirical evidence obtained )] TJ ET
BT 26.250 179.649 Td /F1 9.8 Tf  [(during field testing; the modified questions are then tested during subsequent iterations so that the list can ultimately be )] TJ ET
BT 26.250 167.744 Td /F1 9.8 Tf  [(winnowed to select optimal items for scale inclusion. We report here the development and assessment of the first iteration of )] TJ ET
BT 26.250 155.839 Td /F1 9.8 Tf  [(interview questions aimed to assess functional impact of motor manifestations in prHD and early HD individuals.)] TJ ET
BT 26.250 119.237 Td /F4 12.0 Tf  [(Methods)] TJ ET
BT 26.250 99.282 Td /F1 9.8 Tf  [(A two-day Motor Symptoms Working Group meeting was held in Toronto, Canada, January 19-20, 2009. The working group )] TJ ET
BT 26.250 87.378 Td /F1 9.8 Tf  [(charge was to review available evidence and develop interview questions to assess functional impact of motor signs and )] TJ ET
BT 26.250 75.473 Td /F1 9.8 Tf  [(symptoms.)] TJ ET
BT 26.250 56.068 Td /F4 9.8 Tf  [(Evidence Reviewed)] TJ ET
BT 26.250 36.663 Td /F1 9.8 Tf  [(UHDRS Motor Subscale)] TJ ET
BT 131.355 36.663 Td /F1 9.8 Tf  [(. The Unified Huntington�s Disease Rating Scale \(UHDRS\) Motor Subscale was developed for the )] TJ ET
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0.267 0.267 0.267 rg
BT 15.000 718.042 Td /F2 21.0 Tf  [(Assessment of Motor Symptoms and Functional Impact in )] TJ ET
BT 15.000 693.094 Td /F2 21.0 Tf  [(Prodromal and Early Huntington Disease)] TJ ET
Q
0.271 0.267 0.267 rg
BT 15.000 675.088 Td /F3 9.8 Tf  [(June 14, 2011)] TJ ET
BT 74.846 675.088 Td /F3 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
BT 79.721 675.088 Td /F3 9.8 Tf  [(Clinical Assessment)] TJ ET
BT 26.250 663.247 Td /F1 9.8 Tf  [(Anthony L Vaccarino)] TJ ET
0.271 0.267 0.267 rg
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BT 26.250 755.571 Td /F1 9.8 Tf  [(developing interview questions, the Working Group reviewed retrospective data from two multicentre, longitudinal studies in )] TJ ET
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BT 240.233 743.667 Td /F1 9.8 Tf  [( As expected there were differences in the severity of UHDRS motor signs in )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(prHD and HD. In prHD, overall severity of UHDRS motor signs were low, and participants had scores of 2 or above on very few )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(items. However, there were indications that some items scored higher than others, including saccades, ocular pursuit, and )] TJ ET
BT 26.250 707.952 Td /F1 9.8 Tf  [(finger tapping. In HD, motor items that assessed ocular pursuit, saccade initiation, finger tapping, tandem walking, and to a )] TJ ET
BT 26.250 696.048 Td /F1 9.8 Tf  [(lesser extent saccade velocity, dysarthia, tongue protrusion, pronation/supination, Luria, bradykinesia, chorea, gait, and balance )] TJ ET
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BT 26.250 664.738 Td /F1 9.8 Tf  [(Although these data clearly indicate that some motor signs assessed by the UHDRS are present even at early stages of HD, the )] TJ ET
BT 26.250 652.833 Td /F1 9.8 Tf  [(degree that these motor signs are clinically meaningful has not been determined. Current data would benefit from evidence )] TJ ET
BT 26.250 640.929 Td /F1 9.8 Tf  [(indicating that UHDRS assessments of motor signs are associated with symptoms that can be perceived by the patient \(and )] TJ ET
BT 26.250 629.024 Td /F1 9.8 Tf  [(therefore also the clinician\) and interfere with their day-to-day functioning. To this end, it was agreed that some of the interview )] TJ ET
BT 26.250 617.119 Td /F1 9.8 Tf  [(questions would be developed to assess the potential functional impact of these motor signs.)] TJ ET
BT 26.250 597.714 Td /F1 9.8 Tf  [(Patient and Companion Input)] TJ ET
BT 152.532 597.714 Td /F1 9.8 Tf  [(. The FDA views input from participants, caregivers, and family members as an essential element )] TJ ET
BT 26.250 585.810 Td /F1 9.8 Tf  [(in developing valid clinical assessment tools. )] TJ ET
0.267 0.267 0.267 rg
BT 221.864 585.810 Td /F1 9.8 Tf  [([3])] TJ ET
0.271 0.267 0.267 rg
BT 232.706 585.810 Td /F1 9.8 Tf  [( To ensure that the scale reflects concepts that are important from the )] TJ ET
BT 26.250 573.905 Td /F1 9.8 Tf  [(participant�s perspective, patient/companion focus groups were held to identify early symptoms experienced by HD gene )] TJ ET
BT 26.250 562.000 Td /F1 9.8 Tf  [(carriers and to determine the functional impact of these symptoms. The focus groups were held in a number of countries using )] TJ ET
BT 26.250 550.095 Td /F1 9.8 Tf  [(the local languages \(France, Netherlands, United Kingdom, United States, Portugal, and Spain\) with all participants \(prHD, early )] TJ ET
BT 26.250 538.191 Td /F1 9.8 Tf  [(HD and companions\) being asked a series of open-ended questions related to symptom occurrence in prHD. All focus group )] TJ ET
BT 26.250 526.286 Td /F1 9.8 Tf  [(sites had IRB/EC approval, and all participants provided informed consent. These data were used to maximise symptom )] TJ ET
BT 26.250 514.381 Td /F1 9.8 Tf  [(assessment and were considered in development of the interview questions. The following motor-related symptoms/problems )] TJ ET
BT 26.250 502.476 Td /F1 9.8 Tf  [(were reported by the focus groups:)] TJ ET
BT 26.250 483.072 Td /F5 9.8 Tf  [(Head twitch; Losing balance; Hand writing; Gait; Fine motor; Choking; Hand-eye coordination; Twitching; Fidgety; Dropping )] TJ ET
BT 26.250 471.167 Td /F5 9.8 Tf  [(things; Restless feet; Chorea; Tics; Clumsiness; Falling; Movements during sleep; Tremors; Eye tracking; Walking difficulty as a )] TJ ET
BT 26.250 459.262 Td /F5 9.8 Tf  [(couple; Rigidity of muscle; Tension in face; Instability; Uncontrolled movements.)] TJ ET
BT 26.250 439.857 Td /F1 9.8 Tf  [(Expert Opinion and Experience of Participants)] TJ ET
BT 225.677 439.857 Td /F1 9.8 Tf  [(. In addition to reviewing existing data, working group participant experiences and )] TJ ET
BT 26.250 427.953 Td /F1 9.8 Tf  [(opinion were also discussed, both within HD and in other movement-related disorders, including Parkinson�s disease.)] TJ ET
BT 26.250 408.548 Td /F4 9.8 Tf  [(Development of Interview Questions)] TJ ET
BT 26.250 389.143 Td /F1 9.8 Tf  [(After review of existing data, relevant motor symptom domains were identified, and interview questions were developed to probe )] TJ ET
BT 26.250 377.238 Td /F1 9.8 Tf  [(the experience of those symptoms \(and determine their severity\) in the prHD and early HD population. The FuRST-pHD has )] TJ ET
BT 26.250 365.334 Td /F1 9.8 Tf  [(adopted a semi-structured clinician-administered interview similar to that used for the )] TJ ET
0.267 0.267 0.267 rg
BT 394.712 365.334 Td /F1 9.8 Tf  [(GRID-HAMD)] TJ ET
0.271 0.267 0.267 rg
BT 451.038 365.334 Td /F1 9.8 Tf  [(. The GRID format directs the )] TJ ET
BT 26.250 353.429 Td /F1 9.8 Tf  [(rater to score symptom frequency and intensity separately, while giving them clear scoring anchors, a semi-structured interview )] TJ ET
BT 26.250 341.524 Td /F1 9.8 Tf  [(guide, and overall definitions. This method has been employed successfully and is user-friendly, with acceptable agreement )] TJ ET
BT 26.250 329.619 Td /F1 9.8 Tf  [(among independent raters. )] TJ ET
0.267 0.267 0.267 rg
BT 145.483 329.619 Td /F1 9.8 Tf  [([4])] TJ ET
0.271 0.267 0.267 rg
BT 156.325 329.619 Td /F1 9.8 Tf  [( The working group developed interview questions, including structured interview guides, scoring )] TJ ET
BT 26.250 317.715 Td /F1 9.8 Tf  [(conventions, scoring anchors, and symptom definitions. Following the meeting, draft interview questions were circulated for )] TJ ET
BT 26.250 305.810 Td /F1 9.8 Tf  [(comment on a shared internet site \(Sharepoint\).)] TJ ET
BT 26.250 286.405 Td /F1 9.8 Tf  [(Based on a review of the evidence, 11 interview questions were developed for field testing \(Table 1\).)] TJ ET
BT 26.250 267.000 Td /F4 9.8 Tf  [(Table 1.)] TJ ET
BT 62.559 267.000 Td /F1 9.8 Tf  [( Interview Questions Developed by Working Group)] TJ ET
1.000 1.000 1.000 rg
26.250 76.388 555.000 180.731 re f
0.267 0.267 0.267 rg
26.625 255.995 96.680 0.750 re f
26.625 232.482 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 246.140 Td /F4 9.8 Tf  [(Interview )] TJ ET
BT 31.875 238.508 Td /F4 9.8 Tf  [(Question)] TJ ET
0.267 0.267 0.267 rg
122.555 255.995 255.456 0.750 re f
122.555 232.482 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 127.805 246.140 Td /F4 9.8 Tf  [(Description/definition)] TJ ET
0.267 0.267 0.267 rg
377.261 255.995 203.614 0.750 re f
377.261 232.482 0.750 24.263 re f
580.125 232.482 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 382.511 246.140 Td /F4 9.8 Tf  [(Sources of evidence reviewed and )] TJ ET
BT 382.511 238.508 Td /F4 9.8 Tf  [(considered)] TJ ET
0.267 0.267 0.267 rg
26.625 232.482 96.680 0.750 re f
26.625 201.338 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 31.875 222.627 Td /F4 9.8 Tf  [(Reading)] TJ ET
0.267 0.267 0.267 rg
122.555 232.482 255.456 0.750 re f
122.555 201.338 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 127.805 222.627 Td /F1 9.8 Tf  [(Assesses experiences of problems reading in a general )] TJ ET
BT 127.805 214.996 Td /F1 9.8 Tf  [(fashion, and not limited to any particular domain \(e.g., )] TJ ET
BT 127.805 207.365 Td /F1 9.8 Tf  [(motor difficulties, cognitive difficulties\).)] TJ ET
0.267 0.267 0.267 rg
377.261 232.482 203.614 0.750 re f
377.261 201.338 0.750 31.894 re f
580.125 201.338 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 382.511 222.627 Td /F1 9.8 Tf  [(Clinical experience \(This item was )] TJ ET
BT 382.511 214.996 Td /F1 9.8 Tf  [(developed to assess general problems with )] TJ ET
BT 382.511 207.365 Td /F1 9.8 Tf  [(reading\))] TJ ET
0.267 0.267 0.267 rg
26.625 201.338 96.680 0.750 re f
26.625 177.826 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 191.483 Td /F4 9.8 Tf  [(Tracking while )] TJ ET
BT 31.875 183.852 Td /F4 9.8 Tf  [(reading)] TJ ET
0.267 0.267 0.267 rg
122.555 201.338 255.456 0.750 re f
122.555 177.826 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 127.805 191.483 Td /F1 9.8 Tf  [(Assesses ability to track \(moving from word to word, )] TJ ET
BT 127.805 183.852 Td /F1 9.8 Tf  [(line to line or maintaining eyes on page\) during reading.)] TJ ET
0.267 0.267 0.267 rg
377.261 201.338 203.614 0.750 re f
377.261 177.826 0.750 24.263 re f
580.125 177.826 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 382.511 191.483 Td /F1 9.8 Tf  [(UHDRS \(Ocular Pursuit, Saccades\); Focus )] TJ ET
BT 382.511 183.852 Td /F1 9.8 Tf  [(groups; Clinical Experience)] TJ ET
0.267 0.267 0.267 rg
26.625 177.826 96.680 0.750 re f
26.625 139.051 0.750 39.525 re f
0.271 0.267 0.267 rg
BT 31.875 167.971 Td /F4 9.8 Tf  [(Tracking moving )] TJ ET
BT 31.875 160.340 Td /F4 9.8 Tf  [(objects with eyes)] TJ ET
0.267 0.267 0.267 rg
122.555 177.826 255.456 0.750 re f
122.555 139.051 0.750 39.525 re f
0.271 0.267 0.267 rg
BT 127.805 167.971 Td /F1 9.8 Tf  [(Assesses ability to follow/track moving objects with )] TJ ET
BT 127.805 160.340 Td /F1 9.8 Tf  [(eyes, which include ocular pursuits allowing eyes and )] TJ ET
BT 127.805 152.708 Td /F1 9.8 Tf  [(head to follow moving objects with integrated and )] TJ ET
BT 127.805 145.077 Td /F1 9.8 Tf  [(coordinated movements.)] TJ ET
0.267 0.267 0.267 rg
377.261 177.826 203.614 0.750 re f
377.261 139.051 0.750 39.525 re f
580.125 139.051 0.750 39.525 re f
0.271 0.267 0.267 rg
BT 382.511 167.971 Td /F1 9.8 Tf  [(UHDRS \(Ocular Pursuit, Saccades\); Focus )] TJ ET
BT 382.511 160.340 Td /F1 9.8 Tf  [(groups; Clinical Experience)] TJ ET
0.267 0.267 0.267 rg
26.625 139.051 96.680 0.750 re f
26.625 107.907 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 31.875 129.196 Td /F4 9.8 Tf  [(Balance on one )] TJ ET
BT 31.875 121.565 Td /F4 9.8 Tf  [(foot)] TJ ET
0.267 0.267 0.267 rg
122.555 139.051 255.456 0.750 re f
122.555 107.907 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 127.805 129.196 Td /F1 9.8 Tf  [(Assesses ability to perform tasks that require balance )] TJ ET
BT 127.805 121.565 Td /F1 9.8 Tf  [(on one foot.)] TJ ET
0.267 0.267 0.267 rg
377.261 139.051 203.614 0.750 re f
377.261 107.907 0.750 31.894 re f
580.125 107.907 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 382.511 129.196 Td /F1 9.8 Tf  [(UHDRS \(Bradykinesia, Dystonia, Chorea, )] TJ ET
BT 382.511 121.565 Td /F1 9.8 Tf  [(Gait, Tandem Walking, Retopulsion\); Focus )] TJ ET
BT 382.511 113.933 Td /F1 9.8 Tf  [(groups; Clinical Experience)] TJ ET
0.267 0.267 0.267 rg
26.625 107.907 96.680 0.750 re f
26.625 76.763 96.680 0.750 re f
26.625 76.763 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 31.875 98.052 Td /F4 9.8 Tf  [(Balance when )] TJ ET
BT 31.875 90.421 Td /F4 9.8 Tf  [(walking)] TJ ET
0.267 0.267 0.267 rg
122.555 107.907 255.456 0.750 re f
122.555 76.763 255.456 0.750 re f
122.555 76.763 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 127.805 98.052 Td /F1 9.8 Tf  [(Assesses problems with maintaining balance when )] TJ ET
BT 127.805 90.421 Td /F1 9.8 Tf  [(walking.)] TJ ET
0.267 0.267 0.267 rg
377.261 107.907 203.614 0.750 re f
377.261 76.763 203.614 0.750 re f
377.261 76.763 0.750 31.894 re f
580.125 76.763 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 382.511 98.052 Td /F1 9.8 Tf  [(UHDRS \(Bradykinesia, Dystonia, Chorea, )] TJ ET
BT 382.511 90.421 Td /F1 9.8 Tf  [(Gait, Tandem Walking, Retopulsion\); Focus )] TJ ET
BT 382.511 82.789 Td /F1 9.8 Tf  [(groups; Clinical Experience)] TJ ET
Q
q
15.000 76.388 577.500 700.612 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(clinical assessment of motor signs of HD and is the current �gold-standard� outcome measure used in clinical trials of HD. In )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(developing interview questions, the Working Group reviewed retrospective data from two multicentre, longitudinal studies in )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(prHD \( PREDICT-HD \) and HD \( REGISTRY \). )] TJ ET
0.267 0.267 0.267 rg
BT 229.391 743.667 Td /F1 9.8 Tf  [([2])] TJ ET
0.271 0.267 0.267 rg
BT 240.233 743.667 Td /F1 9.8 Tf  [( As expected there were differences in the severity of UHDRS motor signs in )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(prHD and HD. In prHD, overall severity of UHDRS motor signs were low, and participants had scores of 2 or above on very few )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(items. However, there were indications that some items scored higher than others, including saccades, ocular pursuit, and )] TJ ET
BT 26.250 707.952 Td /F1 9.8 Tf  [(finger tapping. In HD, motor items that assessed ocular pursuit, saccade initiation, finger tapping, tandem walking, and to a )] TJ ET
BT 26.250 696.048 Td /F1 9.8 Tf  [(lesser extent saccade velocity, dysarthia, tongue protrusion, pronation/supination, Luria, bradykinesia, chorea, gait, and balance )] TJ ET
BT 26.250 684.143 Td /F1 9.8 Tf  [(on the retropulsion test were found to discriminate individual differences across a broad range of motor severity. )] TJ ET
0.267 0.267 0.267 rg
BT 510.708 684.143 Td /F1 9.8 Tf  [([2])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 664.738 Td /F1 9.8 Tf  [(Although these data clearly indicate that some motor signs assessed by the UHDRS are present even at early stages of HD, the )] TJ ET
BT 26.250 652.833 Td /F1 9.8 Tf  [(degree that these motor signs are clinically meaningful has not been determined. Current data would benefit from evidence )] TJ ET
BT 26.250 640.929 Td /F1 9.8 Tf  [(indicating that UHDRS assessments of motor signs are associated with symptoms that can be perceived by the patient \(and )] TJ ET
BT 26.250 629.024 Td /F1 9.8 Tf  [(therefore also the clinician\) and interfere with their day-to-day functioning. To this end, it was agreed that some of the interview )] TJ ET
BT 26.250 617.119 Td /F1 9.8 Tf  [(questions would be developed to assess the potential functional impact of these motor signs.)] TJ ET
BT 26.250 597.714 Td /F1 9.8 Tf  [(Patient and Companion Input)] TJ ET
BT 152.532 597.714 Td /F1 9.8 Tf  [(. The FDA views input from participants, caregivers, and family members as an essential element )] TJ ET
BT 26.250 585.810 Td /F1 9.8 Tf  [(in developing valid clinical assessment tools. )] TJ ET
0.267 0.267 0.267 rg
BT 221.864 585.810 Td /F1 9.8 Tf  [([3])] TJ ET
0.271 0.267 0.267 rg
BT 232.706 585.810 Td /F1 9.8 Tf  [( To ensure that the scale reflects concepts that are important from the )] TJ ET
BT 26.250 573.905 Td /F1 9.8 Tf  [(participant�s perspective, patient/companion focus groups were held to identify early symptoms experienced by HD gene )] TJ ET
BT 26.250 562.000 Td /F1 9.8 Tf  [(carriers and to determine the functional impact of these symptoms. The focus groups were held in a number of countries using )] TJ ET
BT 26.250 550.095 Td /F1 9.8 Tf  [(the local languages \(France, Netherlands, United Kingdom, United States, Portugal, and Spain\) with all participants \(prHD, early )] TJ ET
BT 26.250 538.191 Td /F1 9.8 Tf  [(HD and companions\) being asked a series of open-ended questions related to symptom occurrence in prHD. All focus group )] TJ ET
BT 26.250 526.286 Td /F1 9.8 Tf  [(sites had IRB/EC approval, and all participants provided informed consent. These data were used to maximise symptom )] TJ ET
BT 26.250 514.381 Td /F1 9.8 Tf  [(assessment and were considered in development of the interview questions. The following motor-related symptoms/problems )] TJ ET
BT 26.250 502.476 Td /F1 9.8 Tf  [(were reported by the focus groups:)] TJ ET
BT 26.250 483.072 Td /F5 9.8 Tf  [(Head twitch; Losing balance; Hand writing; Gait; Fine motor; Choking; Hand-eye coordination; Twitching; Fidgety; Dropping )] TJ ET
BT 26.250 471.167 Td /F5 9.8 Tf  [(things; Restless feet; Chorea; Tics; Clumsiness; Falling; Movements during sleep; Tremors; Eye tracking; Walking difficulty as a )] TJ ET
BT 26.250 459.262 Td /F5 9.8 Tf  [(couple; Rigidity of muscle; Tension in face; Instability; Uncontrolled movements.)] TJ ET
BT 26.250 439.857 Td /F1 9.8 Tf  [(Expert Opinion and Experience of Participants)] TJ ET
BT 225.677 439.857 Td /F1 9.8 Tf  [(. In addition to reviewing existing data, working group participant experiences and )] TJ ET
BT 26.250 427.953 Td /F1 9.8 Tf  [(opinion were also discussed, both within HD and in other movement-related disorders, including Parkinson�s disease.)] TJ ET
BT 26.250 408.548 Td /F4 9.8 Tf  [(Development of Interview Questions)] TJ ET
BT 26.250 389.143 Td /F1 9.8 Tf  [(After review of existing data, relevant motor symptom domains were identified, and interview questions were developed to probe )] TJ ET
BT 26.250 377.238 Td /F1 9.8 Tf  [(the experience of those symptoms \(and determine their severity\) in the prHD and early HD population. The FuRST-pHD has )] TJ ET
BT 26.250 365.334 Td /F1 9.8 Tf  [(adopted a semi-structured clinician-administered interview similar to that used for the )] TJ ET
0.267 0.267 0.267 rg
BT 394.712 365.334 Td /F1 9.8 Tf  [(GRID-HAMD)] TJ ET
0.271 0.267 0.267 rg
BT 451.038 365.334 Td /F1 9.8 Tf  [(. The GRID format directs the )] TJ ET
BT 26.250 353.429 Td /F1 9.8 Tf  [(rater to score symptom frequency and intensity separately, while giving them clear scoring anchors, a semi-structured interview )] TJ ET
BT 26.250 341.524 Td /F1 9.8 Tf  [(guide, and overall definitions. This method has been employed successfully and is user-friendly, with acceptable agreement )] TJ ET
BT 26.250 329.619 Td /F1 9.8 Tf  [(among independent raters. )] TJ ET
0.267 0.267 0.267 rg
BT 145.483 329.619 Td /F1 9.8 Tf  [([4])] TJ ET
0.271 0.267 0.267 rg
BT 156.325 329.619 Td /F1 9.8 Tf  [( The working group developed interview questions, including structured interview guides, scoring )] TJ ET
BT 26.250 317.715 Td /F1 9.8 Tf  [(conventions, scoring anchors, and symptom definitions. Following the meeting, draft interview questions were circulated for )] TJ ET
BT 26.250 305.810 Td /F1 9.8 Tf  [(comment on a shared internet site \(Sharepoint\).)] TJ ET
BT 26.250 286.405 Td /F1 9.8 Tf  [(Based on a review of the evidence, 11 interview questions were developed for field testing \(Table 1\).)] TJ ET
BT 26.250 267.000 Td /F4 9.8 Tf  [(Table 1.)] TJ ET
BT 62.559 267.000 Td /F1 9.8 Tf  [( Interview Questions Developed by Working Group)] TJ ET
1.000 1.000 1.000 rg
26.250 76.388 555.000 180.731 re f
0.267 0.267 0.267 rg
26.625 255.995 96.680 0.750 re f
26.625 232.482 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 246.140 Td /F4 9.8 Tf  [(Interview )] TJ ET
BT 31.875 238.508 Td /F4 9.8 Tf  [(Question)] TJ ET
0.267 0.267 0.267 rg
122.555 255.995 255.456 0.750 re f
122.555 232.482 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 127.805 246.140 Td /F4 9.8 Tf  [(Description/definition)] TJ ET
0.267 0.267 0.267 rg
377.261 255.995 203.614 0.750 re f
377.261 232.482 0.750 24.263 re f
580.125 232.482 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 382.511 246.140 Td /F4 9.8 Tf  [(Sources of evidence reviewed and )] TJ ET
BT 382.511 238.508 Td /F4 9.8 Tf  [(considered)] TJ ET
0.267 0.267 0.267 rg
26.625 232.482 96.680 0.750 re f
26.625 201.338 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 31.875 222.627 Td /F4 9.8 Tf  [(Reading)] TJ ET
0.267 0.267 0.267 rg
122.555 232.482 255.456 0.750 re f
122.555 201.338 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 127.805 222.627 Td /F1 9.8 Tf  [(Assesses experiences of problems reading in a general )] TJ ET
BT 127.805 214.996 Td /F1 9.8 Tf  [(fashion, and not limited to any particular domain \(e.g., )] TJ ET
BT 127.805 207.365 Td /F1 9.8 Tf  [(motor difficulties, cognitive difficulties\).)] TJ ET
0.267 0.267 0.267 rg
377.261 232.482 203.614 0.750 re f
377.261 201.338 0.750 31.894 re f
580.125 201.338 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 382.511 222.627 Td /F1 9.8 Tf  [(Clinical experience \(This item was )] TJ ET
BT 382.511 214.996 Td /F1 9.8 Tf  [(developed to assess general problems with )] TJ ET
BT 382.511 207.365 Td /F1 9.8 Tf  [(reading\))] TJ ET
0.267 0.267 0.267 rg
26.625 201.338 96.680 0.750 re f
26.625 177.826 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 191.483 Td /F4 9.8 Tf  [(Tracking while )] TJ ET
BT 31.875 183.852 Td /F4 9.8 Tf  [(reading)] TJ ET
0.267 0.267 0.267 rg
122.555 201.338 255.456 0.750 re f
122.555 177.826 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 127.805 191.483 Td /F1 9.8 Tf  [(Assesses ability to track \(moving from word to word, )] TJ ET
BT 127.805 183.852 Td /F1 9.8 Tf  [(line to line or maintaining eyes on page\) during reading.)] TJ ET
0.267 0.267 0.267 rg
377.261 201.338 203.614 0.750 re f
377.261 177.826 0.750 24.263 re f
580.125 177.826 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 382.511 191.483 Td /F1 9.8 Tf  [(UHDRS \(Ocular Pursuit, Saccades\); Focus )] TJ ET
BT 382.511 183.852 Td /F1 9.8 Tf  [(groups; Clinical Experience)] TJ ET
0.267 0.267 0.267 rg
26.625 177.826 96.680 0.750 re f
26.625 139.051 0.750 39.525 re f
0.271 0.267 0.267 rg
BT 31.875 167.971 Td /F4 9.8 Tf  [(Tracking moving )] TJ ET
BT 31.875 160.340 Td /F4 9.8 Tf  [(objects with eyes)] TJ ET
0.267 0.267 0.267 rg
122.555 177.826 255.456 0.750 re f
122.555 139.051 0.750 39.525 re f
0.271 0.267 0.267 rg
BT 127.805 167.971 Td /F1 9.8 Tf  [(Assesses ability to follow/track moving objects with )] TJ ET
BT 127.805 160.340 Td /F1 9.8 Tf  [(eyes, which include ocular pursuits allowing eyes and )] TJ ET
BT 127.805 152.708 Td /F1 9.8 Tf  [(head to follow moving objects with integrated and )] TJ ET
BT 127.805 145.077 Td /F1 9.8 Tf  [(coordinated movements.)] TJ ET
0.267 0.267 0.267 rg
377.261 177.826 203.614 0.750 re f
377.261 139.051 0.750 39.525 re f
580.125 139.051 0.750 39.525 re f
0.271 0.267 0.267 rg
BT 382.511 167.971 Td /F1 9.8 Tf  [(UHDRS \(Ocular Pursuit, Saccades\); Focus )] TJ ET
BT 382.511 160.340 Td /F1 9.8 Tf  [(groups; Clinical Experience)] TJ ET
0.267 0.267 0.267 rg
26.625 139.051 96.680 0.750 re f
26.625 107.907 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 31.875 129.196 Td /F4 9.8 Tf  [(Balance on one )] TJ ET
BT 31.875 121.565 Td /F4 9.8 Tf  [(foot)] TJ ET
0.267 0.267 0.267 rg
122.555 139.051 255.456 0.750 re f
122.555 107.907 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 127.805 129.196 Td /F1 9.8 Tf  [(Assesses ability to perform tasks that require balance )] TJ ET
BT 127.805 121.565 Td /F1 9.8 Tf  [(on one foot.)] TJ ET
0.267 0.267 0.267 rg
377.261 139.051 203.614 0.750 re f
377.261 107.907 0.750 31.894 re f
580.125 107.907 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 382.511 129.196 Td /F1 9.8 Tf  [(UHDRS \(Bradykinesia, Dystonia, Chorea, )] TJ ET
BT 382.511 121.565 Td /F1 9.8 Tf  [(Gait, Tandem Walking, Retopulsion\); Focus )] TJ ET
BT 382.511 113.933 Td /F1 9.8 Tf  [(groups; Clinical Experience)] TJ ET
0.267 0.267 0.267 rg
26.625 107.907 96.680 0.750 re f
26.625 76.763 96.680 0.750 re f
26.625 76.763 0.750 31.894 re f
0.271 0.267 0.267 rg
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BT 31.875 90.421 Td /F4 9.8 Tf  [(walking)] TJ ET
0.267 0.267 0.267 rg
122.555 107.907 255.456 0.750 re f
122.555 76.763 255.456 0.750 re f
122.555 76.763 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 127.805 98.052 Td /F1 9.8 Tf  [(Assesses problems with maintaining balance when )] TJ ET
BT 127.805 90.421 Td /F1 9.8 Tf  [(walking.)] TJ ET
0.267 0.267 0.267 rg
377.261 107.907 203.614 0.750 re f
377.261 76.763 203.614 0.750 re f
377.261 76.763 0.750 31.894 re f
580.125 76.763 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 382.511 98.052 Td /F1 9.8 Tf  [(UHDRS \(Bradykinesia, Dystonia, Chorea, )] TJ ET
BT 382.511 90.421 Td /F1 9.8 Tf  [(Gait, Tandem Walking, Retopulsion\); Focus )] TJ ET
BT 382.511 82.789 Td /F1 9.8 Tf  [(groups; Clinical Experience)] TJ ET
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q
15.000 76.388 577.500 700.612 re W n
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BT 26.250 767.476 Td /F1 9.8 Tf  [(clinical assessment of motor signs of HD and is the current �gold-standard� outcome measure used in clinical trials of HD. In )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(developing interview questions, the Working Group reviewed retrospective data from two multicentre, longitudinal studies in )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(prHD \( PREDICT-HD \) and HD \( REGISTRY \). )] TJ ET
0.267 0.267 0.267 rg
BT 229.391 743.667 Td /F1 9.8 Tf  [([2])] TJ ET
0.271 0.267 0.267 rg
BT 240.233 743.667 Td /F1 9.8 Tf  [( As expected there were differences in the severity of UHDRS motor signs in )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(prHD and HD. In prHD, overall severity of UHDRS motor signs were low, and participants had scores of 2 or above on very few )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(items. However, there were indications that some items scored higher than others, including saccades, ocular pursuit, and )] TJ ET
BT 26.250 707.952 Td /F1 9.8 Tf  [(finger tapping. In HD, motor items that assessed ocular pursuit, saccade initiation, finger tapping, tandem walking, and to a )] TJ ET
BT 26.250 696.048 Td /F1 9.8 Tf  [(lesser extent saccade velocity, dysarthia, tongue protrusion, pronation/supination, Luria, bradykinesia, chorea, gait, and balance )] TJ ET
BT 26.250 684.143 Td /F1 9.8 Tf  [(on the retropulsion test were found to discriminate individual differences across a broad range of motor severity. )] TJ ET
0.267 0.267 0.267 rg
BT 510.708 684.143 Td /F1 9.8 Tf  [([2])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 664.738 Td /F1 9.8 Tf  [(Although these data clearly indicate that some motor signs assessed by the UHDRS are present even at early stages of HD, the )] TJ ET
BT 26.250 652.833 Td /F1 9.8 Tf  [(degree that these motor signs are clinically meaningful has not been determined. Current data would benefit from evidence )] TJ ET
BT 26.250 640.929 Td /F1 9.8 Tf  [(indicating that UHDRS assessments of motor signs are associated with symptoms that can be perceived by the patient \(and )] TJ ET
BT 26.250 629.024 Td /F1 9.8 Tf  [(therefore also the clinician\) and interfere with their day-to-day functioning. To this end, it was agreed that some of the interview )] TJ ET
BT 26.250 617.119 Td /F1 9.8 Tf  [(questions would be developed to assess the potential functional impact of these motor signs.)] TJ ET
BT 26.250 597.714 Td /F1 9.8 Tf  [(Patient and Companion Input)] TJ ET
BT 152.532 597.714 Td /F1 9.8 Tf  [(. The FDA views input from participants, caregivers, and family members as an essential element )] TJ ET
BT 26.250 585.810 Td /F1 9.8 Tf  [(in developing valid clinical assessment tools. )] TJ ET
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BT 221.864 585.810 Td /F1 9.8 Tf  [([3])] TJ ET
0.271 0.267 0.267 rg
BT 232.706 585.810 Td /F1 9.8 Tf  [( To ensure that the scale reflects concepts that are important from the )] TJ ET
BT 26.250 573.905 Td /F1 9.8 Tf  [(participant�s perspective, patient/companion focus groups were held to identify early symptoms experienced by HD gene )] TJ ET
BT 26.250 562.000 Td /F1 9.8 Tf  [(carriers and to determine the functional impact of these symptoms. The focus groups were held in a number of countries using )] TJ ET
BT 26.250 550.095 Td /F1 9.8 Tf  [(the local languages \(France, Netherlands, United Kingdom, United States, Portugal, and Spain\) with all participants \(prHD, early )] TJ ET
BT 26.250 538.191 Td /F1 9.8 Tf  [(HD and companions\) being asked a series of open-ended questions related to symptom occurrence in prHD. All focus group )] TJ ET
BT 26.250 526.286 Td /F1 9.8 Tf  [(sites had IRB/EC approval, and all participants provided informed consent. These data were used to maximise symptom )] TJ ET
BT 26.250 514.381 Td /F1 9.8 Tf  [(assessment and were considered in development of the interview questions. The following motor-related symptoms/problems )] TJ ET
BT 26.250 502.476 Td /F1 9.8 Tf  [(were reported by the focus groups:)] TJ ET
BT 26.250 483.072 Td /F5 9.8 Tf  [(Head twitch; Losing balance; Hand writing; Gait; Fine motor; Choking; Hand-eye coordination; Twitching; Fidgety; Dropping )] TJ ET
BT 26.250 471.167 Td /F5 9.8 Tf  [(things; Restless feet; Chorea; Tics; Clumsiness; Falling; Movements during sleep; Tremors; Eye tracking; Walking difficulty as a )] TJ ET
BT 26.250 459.262 Td /F5 9.8 Tf  [(couple; Rigidity of muscle; Tension in face; Instability; Uncontrolled movements.)] TJ ET
BT 26.250 439.857 Td /F1 9.8 Tf  [(Expert Opinion and Experience of Participants)] TJ ET
BT 225.677 439.857 Td /F1 9.8 Tf  [(. In addition to reviewing existing data, working group participant experiences and )] TJ ET
BT 26.250 427.953 Td /F1 9.8 Tf  [(opinion were also discussed, both within HD and in other movement-related disorders, including Parkinson�s disease.)] TJ ET
BT 26.250 408.548 Td /F4 9.8 Tf  [(Development of Interview Questions)] TJ ET
BT 26.250 389.143 Td /F1 9.8 Tf  [(After review of existing data, relevant motor symptom domains were identified, and interview questions were developed to probe )] TJ ET
BT 26.250 377.238 Td /F1 9.8 Tf  [(the experience of those symptoms \(and determine their severity\) in the prHD and early HD population. The FuRST-pHD has )] TJ ET
BT 26.250 365.334 Td /F1 9.8 Tf  [(adopted a semi-structured clinician-administered interview similar to that used for the )] TJ ET
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BT 394.712 365.334 Td /F1 9.8 Tf  [(GRID-HAMD)] TJ ET
0.271 0.267 0.267 rg
BT 451.038 365.334 Td /F1 9.8 Tf  [(. The GRID format directs the )] TJ ET
BT 26.250 353.429 Td /F1 9.8 Tf  [(rater to score symptom frequency and intensity separately, while giving them clear scoring anchors, a semi-structured interview )] TJ ET
BT 26.250 341.524 Td /F1 9.8 Tf  [(guide, and overall definitions. This method has been employed successfully and is user-friendly, with acceptable agreement )] TJ ET
BT 26.250 329.619 Td /F1 9.8 Tf  [(among independent raters. )] TJ ET
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BT 145.483 329.619 Td /F1 9.8 Tf  [([4])] TJ ET
0.271 0.267 0.267 rg
BT 156.325 329.619 Td /F1 9.8 Tf  [( The working group developed interview questions, including structured interview guides, scoring )] TJ ET
BT 26.250 317.715 Td /F1 9.8 Tf  [(conventions, scoring anchors, and symptom definitions. Following the meeting, draft interview questions were circulated for )] TJ ET
BT 26.250 305.810 Td /F1 9.8 Tf  [(comment on a shared internet site \(Sharepoint\).)] TJ ET
BT 26.250 286.405 Td /F1 9.8 Tf  [(Based on a review of the evidence, 11 interview questions were developed for field testing \(Table 1\).)] TJ ET
BT 26.250 267.000 Td /F4 9.8 Tf  [(Table 1.)] TJ ET
BT 62.559 267.000 Td /F1 9.8 Tf  [( Interview Questions Developed by Working Group)] TJ ET
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26.625 255.995 96.680 0.750 re f
26.625 232.482 0.750 24.263 re f
0.271 0.267 0.267 rg
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BT 31.875 238.508 Td /F4 9.8 Tf  [(Question)] TJ ET
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122.555 255.995 255.456 0.750 re f
122.555 232.482 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 127.805 246.140 Td /F4 9.8 Tf  [(Description/definition)] TJ ET
0.267 0.267 0.267 rg
377.261 255.995 203.614 0.750 re f
377.261 232.482 0.750 24.263 re f
580.125 232.482 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 382.511 246.140 Td /F4 9.8 Tf  [(Sources of evidence reviewed and )] TJ ET
BT 382.511 238.508 Td /F4 9.8 Tf  [(considered)] TJ ET
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26.625 232.482 96.680 0.750 re f
26.625 201.338 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 31.875 222.627 Td /F4 9.8 Tf  [(Reading)] TJ ET
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122.555 232.482 255.456 0.750 re f
122.555 201.338 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 127.805 222.627 Td /F1 9.8 Tf  [(Assesses experiences of problems reading in a general )] TJ ET
BT 127.805 214.996 Td /F1 9.8 Tf  [(fashion, and not limited to any particular domain \(e.g., )] TJ ET
BT 127.805 207.365 Td /F1 9.8 Tf  [(motor difficulties, cognitive difficulties\).)] TJ ET
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377.261 232.482 203.614 0.750 re f
377.261 201.338 0.750 31.894 re f
580.125 201.338 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 382.511 222.627 Td /F1 9.8 Tf  [(Clinical experience \(This item was )] TJ ET
BT 382.511 214.996 Td /F1 9.8 Tf  [(developed to assess general problems with )] TJ ET
BT 382.511 207.365 Td /F1 9.8 Tf  [(reading\))] TJ ET
0.267 0.267 0.267 rg
26.625 201.338 96.680 0.750 re f
26.625 177.826 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 191.483 Td /F4 9.8 Tf  [(Tracking while )] TJ ET
BT 31.875 183.852 Td /F4 9.8 Tf  [(reading)] TJ ET
0.267 0.267 0.267 rg
122.555 201.338 255.456 0.750 re f
122.555 177.826 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 127.805 191.483 Td /F1 9.8 Tf  [(Assesses ability to track \(moving from word to word, )] TJ ET
BT 127.805 183.852 Td /F1 9.8 Tf  [(line to line or maintaining eyes on page\) during reading.)] TJ ET
0.267 0.267 0.267 rg
377.261 201.338 203.614 0.750 re f
377.261 177.826 0.750 24.263 re f
580.125 177.826 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 382.511 191.483 Td /F1 9.8 Tf  [(UHDRS \(Ocular Pursuit, Saccades\); Focus )] TJ ET
BT 382.511 183.852 Td /F1 9.8 Tf  [(groups; Clinical Experience)] TJ ET
0.267 0.267 0.267 rg
26.625 177.826 96.680 0.750 re f
26.625 139.051 0.750 39.525 re f
0.271 0.267 0.267 rg
BT 31.875 167.971 Td /F4 9.8 Tf  [(Tracking moving )] TJ ET
BT 31.875 160.340 Td /F4 9.8 Tf  [(objects with eyes)] TJ ET
0.267 0.267 0.267 rg
122.555 177.826 255.456 0.750 re f
122.555 139.051 0.750 39.525 re f
0.271 0.267 0.267 rg
BT 127.805 167.971 Td /F1 9.8 Tf  [(Assesses ability to follow/track moving objects with )] TJ ET
BT 127.805 160.340 Td /F1 9.8 Tf  [(eyes, which include ocular pursuits allowing eyes and )] TJ ET
BT 127.805 152.708 Td /F1 9.8 Tf  [(head to follow moving objects with integrated and )] TJ ET
BT 127.805 145.077 Td /F1 9.8 Tf  [(coordinated movements.)] TJ ET
0.267 0.267 0.267 rg
377.261 177.826 203.614 0.750 re f
377.261 139.051 0.750 39.525 re f
580.125 139.051 0.750 39.525 re f
0.271 0.267 0.267 rg
BT 382.511 167.971 Td /F1 9.8 Tf  [(UHDRS \(Ocular Pursuit, Saccades\); Focus )] TJ ET
BT 382.511 160.340 Td /F1 9.8 Tf  [(groups; Clinical Experience)] TJ ET
0.267 0.267 0.267 rg
26.625 139.051 96.680 0.750 re f
26.625 107.907 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 31.875 129.196 Td /F4 9.8 Tf  [(Balance on one )] TJ ET
BT 31.875 121.565 Td /F4 9.8 Tf  [(foot)] TJ ET
0.267 0.267 0.267 rg
122.555 139.051 255.456 0.750 re f
122.555 107.907 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 127.805 129.196 Td /F1 9.8 Tf  [(Assesses ability to perform tasks that require balance )] TJ ET
BT 127.805 121.565 Td /F1 9.8 Tf  [(on one foot.)] TJ ET
0.267 0.267 0.267 rg
377.261 139.051 203.614 0.750 re f
377.261 107.907 0.750 31.894 re f
580.125 107.907 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 382.511 129.196 Td /F1 9.8 Tf  [(UHDRS \(Bradykinesia, Dystonia, Chorea, )] TJ ET
BT 382.511 121.565 Td /F1 9.8 Tf  [(Gait, Tandem Walking, Retopulsion\); Focus )] TJ ET
BT 382.511 113.933 Td /F1 9.8 Tf  [(groups; Clinical Experience)] TJ ET
0.267 0.267 0.267 rg
26.625 107.907 96.680 0.750 re f
26.625 76.763 96.680 0.750 re f
26.625 76.763 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 31.875 98.052 Td /F4 9.8 Tf  [(Balance when )] TJ ET
BT 31.875 90.421 Td /F4 9.8 Tf  [(walking)] TJ ET
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122.555 107.907 255.456 0.750 re f
122.555 76.763 255.456 0.750 re f
122.555 76.763 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 127.805 98.052 Td /F1 9.8 Tf  [(Assesses problems with maintaining balance when )] TJ ET
BT 127.805 90.421 Td /F1 9.8 Tf  [(walking.)] TJ ET
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377.261 107.907 203.614 0.750 re f
377.261 76.763 203.614 0.750 re f
377.261 76.763 0.750 31.894 re f
580.125 76.763 0.750 31.894 re f
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BT 382.511 98.052 Td /F1 9.8 Tf  [(UHDRS \(Bradykinesia, Dystonia, Chorea, )] TJ ET
BT 382.511 90.421 Td /F1 9.8 Tf  [(Gait, Tandem Walking, Retopulsion\); Focus )] TJ ET
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BT 127.805 735.514 Td /F1 9.8 Tf  [(Assesses fine motor ability requiring significant dexterity )] TJ ET
BT 127.805 727.883 Td /F1 9.8 Tf  [(of the hands and fingers.)] TJ ET
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377.261 714.225 203.614 0.750 re f
377.261 683.081 0.750 31.894 re f
580.125 683.081 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 382.511 704.370 Td /F1 9.8 Tf  [(UHDRS \(Bradykinesia, Dystonia, Chorea, )] TJ ET
BT 382.511 696.739 Td /F1 9.8 Tf  [(Finger Tapping, Pronate/Supinate, Luria, )] TJ ET
BT 382.511 689.108 Td /F1 9.8 Tf  [(Rigidity\); Focus groups; Clinical Experience)] TJ ET
0.267 0.267 0.267 rg
26.625 683.081 96.680 0.750 re f
26.625 651.938 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 31.875 673.226 Td /F4 9.8 Tf  [(Writing)] TJ ET
0.267 0.267 0.267 rg
122.555 683.081 255.456 0.750 re f
122.555 651.938 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 127.805 673.226 Td /F1 9.8 Tf  [(Assesses normal adult writing ability, including legibility.)] TJ ET
0.267 0.267 0.267 rg
377.261 683.081 203.614 0.750 re f
377.261 651.938 0.750 31.894 re f
580.125 651.938 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 382.511 673.226 Td /F1 9.8 Tf  [(UHDRS \(Bradykinesia, Dystonia, Chorea, )] TJ ET
BT 382.511 665.595 Td /F1 9.8 Tf  [(Finger Tapping, Pronate/Supinate, Luria, )] TJ ET
BT 382.511 657.964 Td /F1 9.8 Tf  [(Rigidity\); Focus groups; Clinical Experience)] TJ ET
0.267 0.267 0.267 rg
26.625 651.938 96.680 0.750 re f
26.625 613.163 0.750 39.525 re f
0.271 0.267 0.267 rg
BT 31.875 642.082 Td /F4 9.8 Tf  [(Clumsiness)] TJ ET
0.267 0.267 0.267 rg
122.555 651.938 255.456 0.750 re f
122.555 613.163 0.750 39.525 re f
0.271 0.267 0.267 rg
BT 127.805 642.082 Td /F1 9.8 Tf  [(Assesses clumsiness, including any avoidance of tasks )] TJ ET
BT 127.805 634.451 Td /F1 9.8 Tf  [(due to clumsiness or changes in behavior to )] TJ ET
BT 127.805 626.820 Td /F1 9.8 Tf  [(compensate.)] TJ ET
0.267 0.267 0.267 rg
377.261 651.938 203.614 0.750 re f
377.261 613.163 0.750 39.525 re f
580.125 613.163 0.750 39.525 re f
0.271 0.267 0.267 rg
BT 382.511 642.082 Td /F1 9.8 Tf  [(UHDRS \(Bradykinesia, Dystonia, Chorea, )] TJ ET
BT 382.511 634.451 Td /F1 9.8 Tf  [(Finger Tapping, Pronate/Supinate, Luria, )] TJ ET
BT 382.511 626.820 Td /F1 9.8 Tf  [(Ocular Pursuit, Rigidity\); Focus groups; )] TJ ET
BT 382.511 619.189 Td /F1 9.8 Tf  [(Clinical Experience)] TJ ET
0.267 0.267 0.267 rg
26.625 613.163 96.680 0.750 re f
26.625 582.019 96.680 0.750 re f
26.625 582.019 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 31.875 603.308 Td /F4 9.8 Tf  [(Functional impact)] TJ ET
0.267 0.267 0.267 rg
122.555 613.163 255.456 0.750 re f
122.555 582.019 255.456 0.750 re f
122.555 582.019 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 127.805 603.308 Td /F1 9.8 Tf  [(Assess the functional impact of motor deficits \(if any )] TJ ET
BT 127.805 595.676 Td /F1 9.8 Tf  [(reported\) on daily activities. Question gathers additional )] TJ ET
BT 127.805 588.045 Td /F1 9.8 Tf  [(patient-reported descriptive data.)] TJ ET
0.267 0.267 0.267 rg
377.261 613.163 203.614 0.750 re f
377.261 582.019 203.614 0.750 re f
377.261 582.019 0.750 31.894 re f
580.125 582.019 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 382.511 603.308 Td /F1 9.8 Tf  [(Clinical Experience)] TJ ET
BT 26.250 534.620 Td /F4 9.8 Tf  [(Field Testing of Interview Questions)] TJ ET
BT 26.250 515.215 Td /F1 9.8 Tf  [(Field testing of interview questions in prHD \(UHDRS Diagnostic Confidence Level < 4\) and early HD \(within 5 years from onset )] TJ ET
BT 26.250 503.310 Td /F1 9.8 Tf  [(of clinical motor signs\) was conducted within the PREDICT-HD program and at independently contracted sites. All data )] TJ ET
BT 26.250 491.406 Td /F1 9.8 Tf  [(collection sites had IRB/EC approval, and all participants provided informed consent. Prior to conducting the clinical interview, )] TJ ET
BT 26.250 479.501 Td /F1 9.8 Tf  [(all raters were trained \(via webinar or in person\) to ensure that all trainees had an adequate conceptual understanding for )] TJ ET
BT 26.250 467.596 Td /F1 9.8 Tf  [(administering and scoring each of the items. A minimum sample size of 100 was targeted.)] TJ ET
BT 26.250 448.191 Td /F4 9.8 Tf  [(Data Analysis)] TJ ET
BT 26.250 428.787 Td /F1 9.8 Tf  [(The distribution of the composite score for each individual item was compiled, and summary statistics associated with each item )] TJ ET
BT 26.250 416.882 Td /F1 9.8 Tf  [(score were computed. Distributions of item scores for HD and prHD subgroups were statistically compared using the non-)] TJ ET
BT 26.250 404.977 Td /F1 9.8 Tf  [(parametric Mann-Whitney U test.)] TJ ET
BT 26.250 385.572 Td /F1 9.8 Tf  [(Non-parametric item response analyses were performed to determine the relationship between scores on the individual )] TJ ET
BT 26.250 373.668 Td /F1 9.8 Tf  [(interview questions and total score. Item Response Theory has been demonstrated to be useful in evaluating the performance )] TJ ET
BT 26.250 361.763 Td /F1 9.8 Tf  [(of individual items \(symptoms\) on rating scales, by assessing the relationship between a score assigned to an item and the )] TJ ET
BT 26.250 349.858 Td /F1 9.8 Tf  [(overall severity of the disease. )] TJ ET
0.267 0.267 0.267 rg
BT 160.098 349.858 Td /F1 9.8 Tf  [([2] [5])] TJ ET
0.271 0.267 0.267 rg
BT 184.493 349.858 Td /F1 9.8 Tf  [(IRT software \( TESTGRAF\) was used to generate Option Characteristic Curves \(OCCs\) )] TJ ET
BT 26.250 337.953 Td /F1 9.8 Tf  [(that display the probability of a particular option score \(i.e., a score of 0, 1, 2, 3, 4\) on each Interview Question as a function of )] TJ ET
BT 26.250 326.049 Td /F1 9.8 Tf  [(overall level of severity. In the present analyses, total motor item score was used as a measure of severity. To illustrate this, )] TJ ET
BT 26.250 314.144 Td /F1 9.8 Tf  [(Figure 1 depicts a hypothetically ��ideal�� item from an item response perspective, which is characterized by a clear identification )] TJ ET
BT 26.250 302.239 Td /F1 9.8 Tf  [(of the range of severity scores over which an option is most likely to be endorsed, rapid changes in the curves that correspond )] TJ ET
BT 26.250 290.334 Td /F1 9.8 Tf  [(to changes in severity, and an orderly relationship between the weight assigned to the option and the region of severity over )] TJ ET
BT 26.250 278.430 Td /F1 9.8 Tf  [(which an item is likely to be endorsed. As such, OCCs provide a graphical representation of how informative a particular item \(or )] TJ ET
BT 26.250 266.525 Td /F1 9.8 Tf  [(symptom\) is as a measure of illness. Frequency distribution of option scoring within each interview question were also )] TJ ET
BT 26.250 254.620 Td /F1 9.8 Tf  [(generated.)] TJ ET
0.965 0.965 0.965 rg
26.250 48.989 555.000 195.750 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 244.739 m 581.250 244.739 l 581.250 243.989 l 26.250 243.989 l  f
q
225.000 0 0 180.000 35.250 54.989 cm /I3 Do
Q 
q
35.250 48.989 537.000 0.000 re W n
Q
Q
q
15.000 48.989 577.500 728.011 re W n
1.000 1.000 1.000 rg
26.250 581.644 555.000 195.356 re f
0.267 0.267 0.267 rg
26.625 776.625 96.680 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 /F4 9.8 Tf  [(Shifting gaze)] TJ ET
0.267 0.267 0.267 rg
122.555 776.625 255.456 0.750 re f
122.555 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 127.805 766.770 Td /F1 9.8 Tf  [(Assesses ability to shift gaze from one object to another.)] TJ ET
0.267 0.267 0.267 rg
377.261 776.625 203.614 0.750 re f
377.261 745.369 0.750 32.006 re f
580.125 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 382.511 766.770 Td /F1 9.8 Tf  [(UHDRS \(Ocular Pursuit, Saccades\); )] TJ ET
BT 382.511 759.139 Td /F1 9.8 Tf  [(Clinical Experience)] TJ ET
0.267 0.267 0.267 rg
26.625 745.369 96.680 0.750 re f
26.625 714.225 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 31.875 735.514 Td /F4 9.8 Tf  [(Fine motor ability)] TJ ET
0.267 0.267 0.267 rg
122.555 745.369 255.456 0.750 re f
122.555 714.225 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 127.805 735.514 Td /F1 9.8 Tf  [(Assesses fine motor ability requiring significant dexterity )] TJ ET
BT 127.805 727.883 Td /F1 9.8 Tf  [(of the hands and fingers.)] TJ ET
0.267 0.267 0.267 rg
377.261 745.369 203.614 0.750 re f
377.261 714.225 0.750 31.894 re f
580.125 714.225 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 382.511 735.514 Td /F1 9.8 Tf  [(UHDRS \(Bradykinesia, Dystonia, Chorea, )] TJ ET
BT 382.511 727.883 Td /F1 9.8 Tf  [(Finger Tapping, Pronate/Supinate, Luria, )] TJ ET
BT 382.511 720.251 Td /F1 9.8 Tf  [(Rigidity\); Focus groups; Clinical Experience)] TJ ET
0.267 0.267 0.267 rg
26.625 714.225 96.680 0.750 re f
26.625 683.081 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 31.875 704.370 Td /F4 9.8 Tf  [(Complex motor )] TJ ET
BT 31.875 696.739 Td /F4 9.8 Tf  [(behavior)] TJ ET
0.267 0.267 0.267 rg
122.555 714.225 255.456 0.750 re f
122.555 683.081 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 127.805 704.370 Td /F1 9.8 Tf  [(Assesses the performance of complex motor behavior.)] TJ ET
0.267 0.267 0.267 rg
377.261 714.225 203.614 0.750 re f
377.261 683.081 0.750 31.894 re f
580.125 683.081 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 382.511 704.370 Td /F1 9.8 Tf  [(UHDRS \(Bradykinesia, Dystonia, Chorea, )] TJ ET
BT 382.511 696.739 Td /F1 9.8 Tf  [(Finger Tapping, Pronate/Supinate, Luria, )] TJ ET
BT 382.511 689.108 Td /F1 9.8 Tf  [(Rigidity\); Focus groups; Clinical Experience)] TJ ET
0.267 0.267 0.267 rg
26.625 683.081 96.680 0.750 re f
26.625 651.938 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 31.875 673.226 Td /F4 9.8 Tf  [(Writing)] TJ ET
0.267 0.267 0.267 rg
122.555 683.081 255.456 0.750 re f
122.555 651.938 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 127.805 673.226 Td /F1 9.8 Tf  [(Assesses normal adult writing ability, including legibility.)] TJ ET
0.267 0.267 0.267 rg
377.261 683.081 203.614 0.750 re f
377.261 651.938 0.750 31.894 re f
580.125 651.938 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 382.511 673.226 Td /F1 9.8 Tf  [(UHDRS \(Bradykinesia, Dystonia, Chorea, )] TJ ET
BT 382.511 665.595 Td /F1 9.8 Tf  [(Finger Tapping, Pronate/Supinate, Luria, )] TJ ET
BT 382.511 657.964 Td /F1 9.8 Tf  [(Rigidity\); Focus groups; Clinical Experience)] TJ ET
0.267 0.267 0.267 rg
26.625 651.938 96.680 0.750 re f
26.625 613.163 0.750 39.525 re f
0.271 0.267 0.267 rg
BT 31.875 642.082 Td /F4 9.8 Tf  [(Clumsiness)] TJ ET
0.267 0.267 0.267 rg
122.555 651.938 255.456 0.750 re f
122.555 613.163 0.750 39.525 re f
0.271 0.267 0.267 rg
BT 127.805 642.082 Td /F1 9.8 Tf  [(Assesses clumsiness, including any avoidance of tasks )] TJ ET
BT 127.805 634.451 Td /F1 9.8 Tf  [(due to clumsiness or changes in behavior to )] TJ ET
BT 127.805 626.820 Td /F1 9.8 Tf  [(compensate.)] TJ ET
0.267 0.267 0.267 rg
377.261 651.938 203.614 0.750 re f
377.261 613.163 0.750 39.525 re f
580.125 613.163 0.750 39.525 re f
0.271 0.267 0.267 rg
BT 382.511 642.082 Td /F1 9.8 Tf  [(UHDRS \(Bradykinesia, Dystonia, Chorea, )] TJ ET
BT 382.511 634.451 Td /F1 9.8 Tf  [(Finger Tapping, Pronate/Supinate, Luria, )] TJ ET
BT 382.511 626.820 Td /F1 9.8 Tf  [(Ocular Pursuit, Rigidity\); Focus groups; )] TJ ET
BT 382.511 619.189 Td /F1 9.8 Tf  [(Clinical Experience)] TJ ET
0.267 0.267 0.267 rg
26.625 613.163 96.680 0.750 re f
26.625 582.019 96.680 0.750 re f
26.625 582.019 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 31.875 603.308 Td /F4 9.8 Tf  [(Functional impact)] TJ ET
0.267 0.267 0.267 rg
122.555 613.163 255.456 0.750 re f
122.555 582.019 255.456 0.750 re f
122.555 582.019 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 127.805 603.308 Td /F1 9.8 Tf  [(Assess the functional impact of motor deficits \(if any )] TJ ET
BT 127.805 595.676 Td /F1 9.8 Tf  [(reported\) on daily activities. Question gathers additional )] TJ ET
BT 127.805 588.045 Td /F1 9.8 Tf  [(patient-reported descriptive data.)] TJ ET
0.267 0.267 0.267 rg
377.261 613.163 203.614 0.750 re f
377.261 582.019 203.614 0.750 re f
377.261 582.019 0.750 31.894 re f
580.125 582.019 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 382.511 603.308 Td /F1 9.8 Tf  [(Clinical Experience)] TJ ET
BT 26.250 534.620 Td /F4 9.8 Tf  [(Field Testing of Interview Questions)] TJ ET
BT 26.250 515.215 Td /F1 9.8 Tf  [(Field testing of interview questions in prHD \(UHDRS Diagnostic Confidence Level < 4\) and early HD \(within 5 years from onset )] TJ ET
BT 26.250 503.310 Td /F1 9.8 Tf  [(of clinical motor signs\) was conducted within the PREDICT-HD program and at independently contracted sites. All data )] TJ ET
BT 26.250 491.406 Td /F1 9.8 Tf  [(collection sites had IRB/EC approval, and all participants provided informed consent. Prior to conducting the clinical interview, )] TJ ET
BT 26.250 479.501 Td /F1 9.8 Tf  [(all raters were trained \(via webinar or in person\) to ensure that all trainees had an adequate conceptual understanding for )] TJ ET
BT 26.250 467.596 Td /F1 9.8 Tf  [(administering and scoring each of the items. A minimum sample size of 100 was targeted.)] TJ ET
BT 26.250 448.191 Td /F4 9.8 Tf  [(Data Analysis)] TJ ET
BT 26.250 428.787 Td /F1 9.8 Tf  [(The distribution of the composite score for each individual item was compiled, and summary statistics associated with each item )] TJ ET
BT 26.250 416.882 Td /F1 9.8 Tf  [(score were computed. Distributions of item scores for HD and prHD subgroups were statistically compared using the non-)] TJ ET
BT 26.250 404.977 Td /F1 9.8 Tf  [(parametric Mann-Whitney U test.)] TJ ET
BT 26.250 385.572 Td /F1 9.8 Tf  [(Non-parametric item response analyses were performed to determine the relationship between scores on the individual )] TJ ET
BT 26.250 373.668 Td /F1 9.8 Tf  [(interview questions and total score. Item Response Theory has been demonstrated to be useful in evaluating the performance )] TJ ET
BT 26.250 361.763 Td /F1 9.8 Tf  [(of individual items \(symptoms\) on rating scales, by assessing the relationship between a score assigned to an item and the )] TJ ET
BT 26.250 349.858 Td /F1 9.8 Tf  [(overall severity of the disease. )] TJ ET
0.267 0.267 0.267 rg
BT 160.098 349.858 Td /F1 9.8 Tf  [([2] [5])] TJ ET
0.271 0.267 0.267 rg
BT 184.493 349.858 Td /F1 9.8 Tf  [(IRT software \( TESTGRAF\) was used to generate Option Characteristic Curves \(OCCs\) )] TJ ET
BT 26.250 337.953 Td /F1 9.8 Tf  [(that display the probability of a particular option score \(i.e., a score of 0, 1, 2, 3, 4\) on each Interview Question as a function of )] TJ ET
BT 26.250 326.049 Td /F1 9.8 Tf  [(overall level of severity. In the present analyses, total motor item score was used as a measure of severity. To illustrate this, )] TJ ET
BT 26.250 314.144 Td /F1 9.8 Tf  [(Figure 1 depicts a hypothetically ��ideal�� item from an item response perspective, which is characterized by a clear identification )] TJ ET
BT 26.250 302.239 Td /F1 9.8 Tf  [(of the range of severity scores over which an option is most likely to be endorsed, rapid changes in the curves that correspond )] TJ ET
BT 26.250 290.334 Td /F1 9.8 Tf  [(to changes in severity, and an orderly relationship between the weight assigned to the option and the region of severity over )] TJ ET
BT 26.250 278.430 Td /F1 9.8 Tf  [(which an item is likely to be endorsed. As such, OCCs provide a graphical representation of how informative a particular item \(or )] TJ ET
BT 26.250 266.525 Td /F1 9.8 Tf  [(symptom\) is as a measure of illness. Frequency distribution of option scoring within each interview question were also )] TJ ET
BT 26.250 254.620 Td /F1 9.8 Tf  [(generated.)] TJ ET
0.965 0.965 0.965 rg
26.250 48.989 555.000 195.750 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 244.739 m 581.250 244.739 l 581.250 243.989 l 26.250 243.989 l  f
q
225.000 0 0 180.000 35.250 54.989 cm /I3 Do
Q 
q
35.250 48.989 537.000 0.000 re W n
Q
Q
q
15.000 48.989 577.500 728.011 re W n
1.000 1.000 1.000 rg
26.250 581.644 555.000 195.356 re f
0.267 0.267 0.267 rg
26.625 776.625 96.680 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 /F4 9.8 Tf  [(Shifting gaze)] TJ ET
0.267 0.267 0.267 rg
122.555 776.625 255.456 0.750 re f
122.555 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 127.805 766.770 Td /F1 9.8 Tf  [(Assesses ability to shift gaze from one object to another.)] TJ ET
0.267 0.267 0.267 rg
377.261 776.625 203.614 0.750 re f
377.261 745.369 0.750 32.006 re f
580.125 745.369 0.750 32.006 re f
0.271 0.267 0.267 rg
BT 382.511 766.770 Td /F1 9.8 Tf  [(UHDRS \(Ocular Pursuit, Saccades\); )] TJ ET
BT 382.511 759.139 Td /F1 9.8 Tf  [(Clinical Experience)] TJ ET
0.267 0.267 0.267 rg
26.625 745.369 96.680 0.750 re f
26.625 714.225 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 31.875 735.514 Td /F4 9.8 Tf  [(Fine motor ability)] TJ ET
0.267 0.267 0.267 rg
122.555 745.369 255.456 0.750 re f
122.555 714.225 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 127.805 735.514 Td /F1 9.8 Tf  [(Assesses fine motor ability requiring significant dexterity )] TJ ET
BT 127.805 727.883 Td /F1 9.8 Tf  [(of the hands and fingers.)] TJ ET
0.267 0.267 0.267 rg
377.261 745.369 203.614 0.750 re f
377.261 714.225 0.750 31.894 re f
580.125 714.225 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 382.511 735.514 Td /F1 9.8 Tf  [(UHDRS \(Bradykinesia, Dystonia, Chorea, )] TJ ET
BT 382.511 727.883 Td /F1 9.8 Tf  [(Finger Tapping, Pronate/Supinate, Luria, )] TJ ET
BT 382.511 720.251 Td /F1 9.8 Tf  [(Rigidity\); Focus groups; Clinical Experience)] TJ ET
0.267 0.267 0.267 rg
26.625 714.225 96.680 0.750 re f
26.625 683.081 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 31.875 704.370 Td /F4 9.8 Tf  [(Complex motor )] TJ ET
BT 31.875 696.739 Td /F4 9.8 Tf  [(behavior)] TJ ET
0.267 0.267 0.267 rg
122.555 714.225 255.456 0.750 re f
122.555 683.081 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 127.805 704.370 Td /F1 9.8 Tf  [(Assesses the performance of complex motor behavior.)] TJ ET
0.267 0.267 0.267 rg
377.261 714.225 203.614 0.750 re f
377.261 683.081 0.750 31.894 re f
580.125 683.081 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 382.511 704.370 Td /F1 9.8 Tf  [(UHDRS \(Bradykinesia, Dystonia, Chorea, )] TJ ET
BT 382.511 696.739 Td /F1 9.8 Tf  [(Finger Tapping, Pronate/Supinate, Luria, )] TJ ET
BT 382.511 689.108 Td /F1 9.8 Tf  [(Rigidity\); Focus groups; Clinical Experience)] TJ ET
0.267 0.267 0.267 rg
26.625 683.081 96.680 0.750 re f
26.625 651.938 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 31.875 673.226 Td /F4 9.8 Tf  [(Writing)] TJ ET
0.267 0.267 0.267 rg
122.555 683.081 255.456 0.750 re f
122.555 651.938 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 127.805 673.226 Td /F1 9.8 Tf  [(Assesses normal adult writing ability, including legibility.)] TJ ET
0.267 0.267 0.267 rg
377.261 683.081 203.614 0.750 re f
377.261 651.938 0.750 31.894 re f
580.125 651.938 0.750 31.894 re f
0.271 0.267 0.267 rg
BT 382.511 673.226 Td /F1 9.8 Tf  [(UHDRS \(Bradykinesia, Dystonia, Chorea, )] TJ ET
BT 382.511 665.595 Td /F1 9.8 Tf  [(Finger Tapping, Pronate/Supinate, Luria, )] TJ ET
BT 382.511 657.964 Td /F1 9.8 Tf  [(Rigidity\); Focus groups; Clinical Experience)] TJ ET
0.267 0.267 0.267 rg
26.625 651.938 96.680 0.750 re f
26.625 613.163 0.750 39.525 re f
0.271 0.267 0.267 rg
BT 31.875 642.082 Td /F4 9.8 Tf  [(Clumsiness)] TJ ET
0.267 0.267 0.267 rg
122.555 651.938 255.456 0.750 re f
122.555 613.163 0.750 39.525 re f
0.271 0.267 0.267 rg
BT 127.805 642.082 Td /F1 9.8 Tf  [(Assesses clumsiness, including any avoidance of tasks )] TJ ET
BT 127.805 634.451 Td /F1 9.8 Tf  [(due to clumsiness or changes in behavior to )] TJ ET
BT 127.805 626.820 Td /F1 9.8 Tf  [(compensate.)] TJ ET
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15.000 32.954 577.500 744.046 re W n
0.965 0.965 0.965 rg
26.250 735.941 555.000 41.059 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 735.941 m 581.250 735.941 l 581.250 736.691 l 26.250 736.691 l  f
q
35.250 747.191 537.000 29.809 re W n
0.271 0.267 0.267 rg
BT 35.250 767.476 Td /F4 9.8 Tf  [(Fig. 1: OCC for a hypothetically ��ideal�� item. The OCC shows the probability \(y-axis\) of endorsing a particular )] TJ ET
BT 35.250 755.571 Td /F4 9.8 Tf  [(option for the item at different levels of the trait \(x-axis\).)] TJ ET
Q
BT 26.250 718.917 Td /F1 9.8 Tf  [(Interview questions which were found to produce scoring and discrimination across ranges of overall severity were putatively )] TJ ET
BT 26.250 707.012 Td /F1 9.8 Tf  [(selected for further testing. Scores for prHD and HD subjects were computed and compared statistically using the Mann-)] TJ ET
BT 26.250 695.107 Td /F1 9.8 Tf  [(Whitney U test. The measure of internal consistency of the subscale was estimated using Cronbach�s alpha, and item-total )] TJ ET
BT 26.250 683.202 Td /F1 9.8 Tf  [(correlations between subscale scores and scores of individual questions not included in the subscale were computed.)] TJ ET
BT 26.250 646.600 Td /F4 12.0 Tf  [(Results)] TJ ET
BT 26.250 626.646 Td /F1 9.8 Tf  [(A total of 131 CRFs were completed. The participant demographic characteristics are shown in Table 2.)] TJ ET
BT 26.250 607.241 Td /F4 9.8 Tf  [(Table 2.)] TJ ET
BT 62.559 607.241 Td /F1 9.8 Tf  [( Demographic Characteristics)] TJ ET
1.000 1.000 1.000 rg
26.250 532.335 555.000 65.025 re f
0.267 0.267 0.267 rg
26.625 596.235 145.220 0.750 re f
26.625 580.354 0.750 16.631 re f
171.095 596.235 149.553 0.750 re f
171.095 580.354 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 176.345 586.380 Td /F4 9.8 Tf  [(All Subjects)] TJ ET
0.267 0.267 0.267 rg
319.898 596.235 130.864 0.750 re f
319.898 580.354 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 325.148 586.380 Td /F4 9.8 Tf  [(prHD)] TJ ET
0.267 0.267 0.267 rg
450.011 596.235 130.864 0.750 re f
450.011 580.354 0.750 16.631 re f
580.125 580.354 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 455.261 586.380 Td /F4 9.8 Tf  [(HD)] TJ ET
0.267 0.267 0.267 rg
26.625 580.354 145.220 0.750 re f
26.625 564.472 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 570.499 Td /F4 9.8 Tf  [(Sample size)] TJ ET
0.267 0.267 0.267 rg
171.095 580.354 149.553 0.750 re f
171.095 564.472 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 176.345 570.499 Td /F1 9.8 Tf  [(N=131)] TJ ET
0.267 0.267 0.267 rg
319.898 580.354 130.864 0.750 re f
319.898 564.472 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 325.148 570.499 Td /F1 9.8 Tf  [(N=73 \(56%\))] TJ ET
0.267 0.267 0.267 rg
450.011 580.354 130.864 0.750 re f
450.011 564.472 0.750 16.631 re f
580.125 564.472 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 455.261 570.499 Td /F1 9.8 Tf  [(N=58 \(44%\))] TJ ET
0.267 0.267 0.267 rg
26.625 564.472 145.220 0.750 re f
26.625 548.591 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 554.618 Td /F4 9.8 Tf  [(Male gender)] TJ ET
0.267 0.267 0.267 rg
171.095 564.472 149.553 0.750 re f
171.095 548.591 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 176.345 554.618 Td /F1 9.8 Tf  [(N=56 \(43%\))] TJ ET
0.267 0.267 0.267 rg
319.898 564.472 130.864 0.750 re f
319.898 548.591 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 325.148 554.618 Td /F1 9.8 Tf  [(N=26 \(36%\))] TJ ET
0.267 0.267 0.267 rg
450.011 564.472 130.864 0.750 re f
450.011 548.591 0.750 16.631 re f
580.125 548.591 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 455.261 554.618 Td /F1 9.8 Tf  [(N=30 \(52%\))] TJ ET
0.267 0.267 0.267 rg
26.625 548.591 145.220 0.750 re f
26.625 532.710 145.220 0.750 re f
26.625 532.710 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 538.736 Td /F4 9.8 Tf  [(Age)] TJ ET
0.267 0.267 0.267 rg
171.095 548.591 149.553 0.750 re f
171.095 532.710 149.553 0.750 re f
171.095 532.710 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 176.345 538.736 Td /F1 9.8 Tf  [(48.0 \(18-73\))] TJ ET
0.267 0.267 0.267 rg
319.898 548.591 130.864 0.750 re f
319.898 532.710 130.864 0.750 re f
319.898 532.710 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 325.148 538.736 Td /F1 9.8 Tf  [(45.0 \(18-71\))] TJ ET
0.267 0.267 0.267 rg
450.011 548.591 130.864 0.750 re f
450.011 532.710 130.864 0.750 re f
450.011 532.710 0.750 16.631 re f
580.125 532.710 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 455.261 538.736 Td /F1 9.8 Tf  [(51.9 \(23-73\))] TJ ET
BT 26.250 485.311 Td /F1 9.8 Tf  [(A follow-up Motor Working Group meeting was held \(via webinar\) to review data and make recommendations in moving )] TJ ET
BT 26.250 473.406 Td /F1 9.8 Tf  [(forward, including item deletion and modification/refinement. The )] TJ ET
0.267 0.267 0.267 rg
BT 308.035 473.406 Td /F1 9.8 Tf  [(FDA PRO Guidance)] TJ ET
0.271 0.267 0.267 rg
BT 395.814 473.406 Td /F1 9.8 Tf  [( was used to guide the decision making )] TJ ET
BT 26.250 461.502 Td /F1 9.8 Tf  [(process. )] TJ ET
0.267 0.267 0.267 rg
BT 65.806 461.502 Td /F1 9.8 Tf  [([3])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 442.097 Td /F1 9.8 Tf  [(OCCs and scoring frequency distributions were generated for each of the interview questions. Of the 11 tested, 7 interview )] TJ ET
BT 26.250 430.192 Td /F1 9.8 Tf  [(questions were found to produce scoring and discrimination across ranges of overall severity:)] TJ ET
BT 26.250 410.787 Td /F1 9.8 Tf  [(? Balance on one foot)] TJ ET
BT 26.250 391.383 Td /F1 9.8 Tf  [(? Balance when walking)] TJ ET
BT 26.250 371.978 Td /F1 9.8 Tf  [(? Fine motor ability)] TJ ET
BT 26.250 352.573 Td /F1 9.8 Tf  [(? Complex motor behavior)] TJ ET
BT 26.250 333.168 Td /F1 9.8 Tf  [(? Writing)] TJ ET
BT 26.250 313.764 Td /F1 9.8 Tf  [(? Clumsiness)] TJ ET
BT 26.250 294.359 Td /F1 9.8 Tf  [(? Functional impact)] TJ ET
BT 26.250 274.954 Td /F1 9.8 Tf  [(The internal consistency of these seven items was very high, as were the corrected item-total correlations \(Table 3, shaded )] TJ ET
BT 26.250 263.049 Td /F1 9.8 Tf  [(rows\). Cronbach�s alpha was 0.93 with respect to the entire study population, 0.89 with respect to the prHD subgroup, and 0.93 )] TJ ET
BT 26.250 251.145 Td /F1 9.8 Tf  [(with respect to the HD subgroup. All corrected item-total correlations were 0.69 or higher with respect to the HD subgroup; the )] TJ ET
BT 26.250 239.240 Td /F1 9.8 Tf  [(only items displaying a low item-total correlation with respect to the prHD subgroup were the �Fine motor ability� item and the )] TJ ET
BT 26.250 227.335 Td /F1 9.8 Tf  [(remainder \(Table 3\).)] TJ ET
0.965 0.965 0.965 rg
26.250 32.954 555.000 184.500 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 217.454 m 581.250 217.454 l 581.250 216.704 l 26.250 216.704 l  f
q
225.000 0 0 168.750 35.250 38.954 cm /I4 Do
Q 
q
35.250 32.954 537.000 0.000 re W n
Q
Q
q
15.000 32.954 577.500 744.046 re W n
0.965 0.965 0.965 rg
26.250 735.941 555.000 41.059 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 735.941 m 581.250 735.941 l 581.250 736.691 l 26.250 736.691 l  f
q
35.250 747.191 537.000 29.809 re W n
0.271 0.267 0.267 rg
BT 35.250 767.476 Td /F4 9.8 Tf  [(Fig. 1: OCC for a hypothetically ��ideal�� item. The OCC shows the probability \(y-axis\) of endorsing a particular )] TJ ET
BT 35.250 755.571 Td /F4 9.8 Tf  [(option for the item at different levels of the trait \(x-axis\).)] TJ ET
Q
BT 26.250 718.917 Td /F1 9.8 Tf  [(Interview questions which were found to produce scoring and discrimination across ranges of overall severity were putatively )] TJ ET
BT 26.250 707.012 Td /F1 9.8 Tf  [(selected for further testing. Scores for prHD and HD subjects were computed and compared statistically using the Mann-)] TJ ET
BT 26.250 695.107 Td /F1 9.8 Tf  [(Whitney U test. The measure of internal consistency of the subscale was estimated using Cronbach�s alpha, and item-total )] TJ ET
BT 26.250 683.202 Td /F1 9.8 Tf  [(correlations between subscale scores and scores of individual questions not included in the subscale were computed.)] TJ ET
BT 26.250 646.600 Td /F4 12.0 Tf  [(Results)] TJ ET
BT 26.250 626.646 Td /F1 9.8 Tf  [(A total of 131 CRFs were completed. The participant demographic characteristics are shown in Table 2.)] TJ ET
BT 26.250 607.241 Td /F4 9.8 Tf  [(Table 2.)] TJ ET
BT 62.559 607.241 Td /F1 9.8 Tf  [( Demographic Characteristics)] TJ ET
1.000 1.000 1.000 rg
26.250 532.335 555.000 65.025 re f
0.267 0.267 0.267 rg
26.625 596.235 145.220 0.750 re f
26.625 580.354 0.750 16.631 re f
171.095 596.235 149.553 0.750 re f
171.095 580.354 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 176.345 586.380 Td /F4 9.8 Tf  [(All Subjects)] TJ ET
0.267 0.267 0.267 rg
319.898 596.235 130.864 0.750 re f
319.898 580.354 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 325.148 586.380 Td /F4 9.8 Tf  [(prHD)] TJ ET
0.267 0.267 0.267 rg
450.011 596.235 130.864 0.750 re f
450.011 580.354 0.750 16.631 re f
580.125 580.354 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 455.261 586.380 Td /F4 9.8 Tf  [(HD)] TJ ET
0.267 0.267 0.267 rg
26.625 580.354 145.220 0.750 re f
26.625 564.472 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 570.499 Td /F4 9.8 Tf  [(Sample size)] TJ ET
0.267 0.267 0.267 rg
171.095 580.354 149.553 0.750 re f
171.095 564.472 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 176.345 570.499 Td /F1 9.8 Tf  [(N=131)] TJ ET
0.267 0.267 0.267 rg
319.898 580.354 130.864 0.750 re f
319.898 564.472 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 325.148 570.499 Td /F1 9.8 Tf  [(N=73 \(56%\))] TJ ET
0.267 0.267 0.267 rg
450.011 580.354 130.864 0.750 re f
450.011 564.472 0.750 16.631 re f
580.125 564.472 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 455.261 570.499 Td /F1 9.8 Tf  [(N=58 \(44%\))] TJ ET
0.267 0.267 0.267 rg
26.625 564.472 145.220 0.750 re f
26.625 548.591 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 554.618 Td /F4 9.8 Tf  [(Male gender)] TJ ET
0.267 0.267 0.267 rg
171.095 564.472 149.553 0.750 re f
171.095 548.591 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 176.345 554.618 Td /F1 9.8 Tf  [(N=56 \(43%\))] TJ ET
0.267 0.267 0.267 rg
319.898 564.472 130.864 0.750 re f
319.898 548.591 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 325.148 554.618 Td /F1 9.8 Tf  [(N=26 \(36%\))] TJ ET
0.267 0.267 0.267 rg
450.011 564.472 130.864 0.750 re f
450.011 548.591 0.750 16.631 re f
580.125 548.591 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 455.261 554.618 Td /F1 9.8 Tf  [(N=30 \(52%\))] TJ ET
0.267 0.267 0.267 rg
26.625 548.591 145.220 0.750 re f
26.625 532.710 145.220 0.750 re f
26.625 532.710 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 538.736 Td /F4 9.8 Tf  [(Age)] TJ ET
0.267 0.267 0.267 rg
171.095 548.591 149.553 0.750 re f
171.095 532.710 149.553 0.750 re f
171.095 532.710 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 176.345 538.736 Td /F1 9.8 Tf  [(48.0 \(18-73\))] TJ ET
0.267 0.267 0.267 rg
319.898 548.591 130.864 0.750 re f
319.898 532.710 130.864 0.750 re f
319.898 532.710 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 325.148 538.736 Td /F1 9.8 Tf  [(45.0 \(18-71\))] TJ ET
0.267 0.267 0.267 rg
450.011 548.591 130.864 0.750 re f
450.011 532.710 130.864 0.750 re f
450.011 532.710 0.750 16.631 re f
580.125 532.710 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 455.261 538.736 Td /F1 9.8 Tf  [(51.9 \(23-73\))] TJ ET
BT 26.250 485.311 Td /F1 9.8 Tf  [(A follow-up Motor Working Group meeting was held \(via webinar\) to review data and make recommendations in moving )] TJ ET
BT 26.250 473.406 Td /F1 9.8 Tf  [(forward, including item deletion and modification/refinement. The )] TJ ET
0.267 0.267 0.267 rg
BT 308.035 473.406 Td /F1 9.8 Tf  [(FDA PRO Guidance)] TJ ET
0.271 0.267 0.267 rg
BT 395.814 473.406 Td /F1 9.8 Tf  [( was used to guide the decision making )] TJ ET
BT 26.250 461.502 Td /F1 9.8 Tf  [(process. )] TJ ET
0.267 0.267 0.267 rg
BT 65.806 461.502 Td /F1 9.8 Tf  [([3])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 442.097 Td /F1 9.8 Tf  [(OCCs and scoring frequency distributions were generated for each of the interview questions. Of the 11 tested, 7 interview )] TJ ET
BT 26.250 430.192 Td /F1 9.8 Tf  [(questions were found to produce scoring and discrimination across ranges of overall severity:)] TJ ET
BT 26.250 410.787 Td /F1 9.8 Tf  [(? Balance on one foot)] TJ ET
BT 26.250 391.383 Td /F1 9.8 Tf  [(? Balance when walking)] TJ ET
BT 26.250 371.978 Td /F1 9.8 Tf  [(? Fine motor ability)] TJ ET
BT 26.250 352.573 Td /F1 9.8 Tf  [(? Complex motor behavior)] TJ ET
BT 26.250 333.168 Td /F1 9.8 Tf  [(? Writing)] TJ ET
BT 26.250 313.764 Td /F1 9.8 Tf  [(? Clumsiness)] TJ ET
BT 26.250 294.359 Td /F1 9.8 Tf  [(? Functional impact)] TJ ET
BT 26.250 274.954 Td /F1 9.8 Tf  [(The internal consistency of these seven items was very high, as were the corrected item-total correlations \(Table 3, shaded )] TJ ET
BT 26.250 263.049 Td /F1 9.8 Tf  [(rows\). Cronbach�s alpha was 0.93 with respect to the entire study population, 0.89 with respect to the prHD subgroup, and 0.93 )] TJ ET
BT 26.250 251.145 Td /F1 9.8 Tf  [(with respect to the HD subgroup. All corrected item-total correlations were 0.69 or higher with respect to the HD subgroup; the )] TJ ET
BT 26.250 239.240 Td /F1 9.8 Tf  [(only items displaying a low item-total correlation with respect to the prHD subgroup were the �Fine motor ability� item and the )] TJ ET
BT 26.250 227.335 Td /F1 9.8 Tf  [(remainder \(Table 3\).)] TJ ET
0.965 0.965 0.965 rg
26.250 32.954 555.000 184.500 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 217.454 m 581.250 217.454 l 581.250 216.704 l 26.250 216.704 l  f
q
225.000 0 0 168.750 35.250 38.954 cm /I4 Do
Q 
q
35.250 32.954 537.000 0.000 re W n
Q
Q
q
15.000 32.954 577.500 744.046 re W n
0.965 0.965 0.965 rg
26.250 735.941 555.000 41.059 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 735.941 m 581.250 735.941 l 581.250 736.691 l 26.250 736.691 l  f
q
35.250 747.191 537.000 29.809 re W n
0.271 0.267 0.267 rg
BT 35.250 767.476 Td /F4 9.8 Tf  [(Fig. 1: OCC for a hypothetically ��ideal�� item. The OCC shows the probability \(y-axis\) of endorsing a particular )] TJ ET
BT 35.250 755.571 Td /F4 9.8 Tf  [(option for the item at different levels of the trait \(x-axis\).)] TJ ET
Q
BT 26.250 718.917 Td /F1 9.8 Tf  [(Interview questions which were found to produce scoring and discrimination across ranges of overall severity were putatively )] TJ ET
BT 26.250 707.012 Td /F1 9.8 Tf  [(selected for further testing. Scores for prHD and HD subjects were computed and compared statistically using the Mann-)] TJ ET
BT 26.250 695.107 Td /F1 9.8 Tf  [(Whitney U test. The measure of internal consistency of the subscale was estimated using Cronbach�s alpha, and item-total )] TJ ET
BT 26.250 683.202 Td /F1 9.8 Tf  [(correlations between subscale scores and scores of individual questions not included in the subscale were computed.)] TJ ET
BT 26.250 646.600 Td /F4 12.0 Tf  [(Results)] TJ ET
BT 26.250 626.646 Td /F1 9.8 Tf  [(A total of 131 CRFs were completed. The participant demographic characteristics are shown in Table 2.)] TJ ET
BT 26.250 607.241 Td /F4 9.8 Tf  [(Table 2.)] TJ ET
BT 62.559 607.241 Td /F1 9.8 Tf  [( Demographic Characteristics)] TJ ET
1.000 1.000 1.000 rg
26.250 532.335 555.000 65.025 re f
0.267 0.267 0.267 rg
26.625 596.235 145.220 0.750 re f
26.625 580.354 0.750 16.631 re f
171.095 596.235 149.553 0.750 re f
171.095 580.354 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 176.345 586.380 Td /F4 9.8 Tf  [(All Subjects)] TJ ET
0.267 0.267 0.267 rg
319.898 596.235 130.864 0.750 re f
319.898 580.354 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 325.148 586.380 Td /F4 9.8 Tf  [(prHD)] TJ ET
0.267 0.267 0.267 rg
450.011 596.235 130.864 0.750 re f
450.011 580.354 0.750 16.631 re f
580.125 580.354 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 455.261 586.380 Td /F4 9.8 Tf  [(HD)] TJ ET
0.267 0.267 0.267 rg
26.625 580.354 145.220 0.750 re f
26.625 564.472 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 570.499 Td /F4 9.8 Tf  [(Sample size)] TJ ET
0.267 0.267 0.267 rg
171.095 580.354 149.553 0.750 re f
171.095 564.472 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 176.345 570.499 Td /F1 9.8 Tf  [(N=131)] TJ ET
0.267 0.267 0.267 rg
319.898 580.354 130.864 0.750 re f
319.898 564.472 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 325.148 570.499 Td /F1 9.8 Tf  [(N=73 \(56%\))] TJ ET
0.267 0.267 0.267 rg
450.011 580.354 130.864 0.750 re f
450.011 564.472 0.750 16.631 re f
580.125 564.472 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 455.261 570.499 Td /F1 9.8 Tf  [(N=58 \(44%\))] TJ ET
0.267 0.267 0.267 rg
26.625 564.472 145.220 0.750 re f
26.625 548.591 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 554.618 Td /F4 9.8 Tf  [(Male gender)] TJ ET
0.267 0.267 0.267 rg
171.095 564.472 149.553 0.750 re f
171.095 548.591 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 176.345 554.618 Td /F1 9.8 Tf  [(N=56 \(43%\))] TJ ET
0.267 0.267 0.267 rg
319.898 564.472 130.864 0.750 re f
319.898 548.591 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 325.148 554.618 Td /F1 9.8 Tf  [(N=26 \(36%\))] TJ ET
0.267 0.267 0.267 rg
450.011 564.472 130.864 0.750 re f
450.011 548.591 0.750 16.631 re f
580.125 548.591 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 455.261 554.618 Td /F1 9.8 Tf  [(N=30 \(52%\))] TJ ET
0.267 0.267 0.267 rg
26.625 548.591 145.220 0.750 re f
26.625 532.710 145.220 0.750 re f
26.625 532.710 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 538.736 Td /F4 9.8 Tf  [(Age)] TJ ET
0.267 0.267 0.267 rg
171.095 548.591 149.553 0.750 re f
171.095 532.710 149.553 0.750 re f
171.095 532.710 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 176.345 538.736 Td /F1 9.8 Tf  [(48.0 \(18-73\))] TJ ET
0.267 0.267 0.267 rg
319.898 548.591 130.864 0.750 re f
319.898 532.710 130.864 0.750 re f
319.898 532.710 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 325.148 538.736 Td /F1 9.8 Tf  [(45.0 \(18-71\))] TJ ET
0.267 0.267 0.267 rg
450.011 548.591 130.864 0.750 re f
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0.271 0.267 0.267 rg
BT 76.112 647.488 Td /F1 9.8 Tf  [( For example, in assessing ability to perform tasks that require balance on one foot, scoring was driven primarily by )] TJ ET
BT 26.250 635.583 Td /F1 9.8 Tf  [(early HD participants \(Figure 2, Table 4\). In prHD, the option with the highest probably of being scored for symptom intensity )] TJ ET
BT 26.250 623.679 Td /F1 9.8 Tf  [(increased from �0� to �1� \(mild: sense of unsteadiness/imbalance on one foot that others may not notice, but no impact on )] TJ ET
BT 26.250 611.774 Td /F1 9.8 Tf  [(function of daily activities\) suggesting that although these changes are noticeable to the participant, the functional impact may )] TJ ET
BT 26.250 599.869 Td /F1 9.8 Tf  [(be minimal. By contrast, in early HD participants scores of �3� \(severe: needs support to maintain balance\) and �4� \(very severe: )] TJ ET
BT 26.250 587.964 Td /F1 9.8 Tf  [(cannot stand on one foot, must sit down to do things\) were sometimes endorsed. The poor discrimination between symptom )] TJ ET
BT 26.250 576.060 Td /F1 9.8 Tf  [(intensity scores of �3� and �4� indicates that modifications to the wording of these options would be needed to allow for better )] TJ ET
BT 26.250 564.155 Td /F1 9.8 Tf  [(discrimination.)] TJ ET
BT 26.250 544.750 Td /F4 9.8 Tf  [(Table 3. )] TJ ET
BT 65.269 544.750 Td /F1 9.8 Tf  [( Correlations between Interview Questions Scores)] TJ ET
1.000 1.000 1.000 rg
26.250 335.163 555.000 199.706 re f
0.267 0.267 0.267 rg
26.625 533.744 155.836 0.750 re f
26.625 510.232 0.750 24.262 re f
0.271 0.267 0.267 rg
BT 31.875 523.889 Td /F1 9.8 Tf  [(Item)] TJ ET
0.267 0.267 0.267 rg
181.711 533.744 133.555 0.750 re f
181.711 510.232 0.750 24.262 re f
0.271 0.267 0.267 rg
BT 186.961 523.889 Td /F1 9.8 Tf  [(Item-total correlation )] TJ ET
BT 186.961 516.258 Td /F1 9.8 Tf  [(\(all subjects\))] TJ ET
0.267 0.267 0.267 rg
314.515 533.744 133.555 0.750 re f
314.515 510.232 0.750 24.262 re f
0.271 0.267 0.267 rg
BT 319.765 523.889 Td /F1 9.8 Tf  [(Item-total correlation )] TJ ET
BT 319.765 516.258 Td /F1 9.8 Tf  [(\(prHD subjects\))] TJ ET
0.267 0.267 0.267 rg
447.320 533.744 133.555 0.750 re f
447.320 510.232 0.750 24.262 re f
580.125 510.232 0.750 24.262 re f
0.271 0.267 0.267 rg
BT 452.570 523.889 Td /F1 9.8 Tf  [(Item-total correlation )] TJ ET
BT 452.570 516.258 Td /F1 9.8 Tf  [(\(HD subjects\))] TJ ET
0.267 0.267 0.267 rg
26.625 510.232 155.836 0.750 re f
26.625 494.350 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 500.377 Td /F1 9.8 Tf  [(Reading)] TJ ET
0.267 0.267 0.267 rg
181.711 510.232 133.555 0.750 re f
181.711 494.350 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 500.377 Td /F1 9.8 Tf  [(0.389)] TJ ET
0.267 0.267 0.267 rg
314.515 510.232 133.555 0.750 re f
314.515 494.350 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 500.377 Td /F1 9.8 Tf  [(0.340)] TJ ET
0.267 0.267 0.267 rg
447.320 510.232 133.555 0.750 re f
447.320 494.350 0.750 16.631 re f
580.125 494.350 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 500.377 Td /F1 9.8 Tf  [(0.360)] TJ ET
0.267 0.267 0.267 rg
26.625 494.350 155.836 0.750 re f
26.625 478.469 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 484.495 Td /F1 9.8 Tf  [(Tracking while reading)] TJ ET
0.267 0.267 0.267 rg
181.711 494.350 133.555 0.750 re f
181.711 478.469 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 484.495 Td /F1 9.8 Tf  [(0.489)] TJ ET
0.267 0.267 0.267 rg
314.515 494.350 133.555 0.750 re f
314.515 478.469 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 484.495 Td /F1 9.8 Tf  [(0.202)] TJ ET
0.267 0.267 0.267 rg
447.320 494.350 133.555 0.750 re f
447.320 478.469 0.750 16.631 re f
580.125 478.469 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 484.495 Td /F1 9.8 Tf  [(0.639)] TJ ET
0.267 0.267 0.267 rg
26.625 478.469 155.836 0.750 re f
26.625 462.588 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 468.614 Td /F1 9.8 Tf  [(Tracking objects with eyes)] TJ ET
0.267 0.267 0.267 rg
181.711 478.469 133.555 0.750 re f
181.711 462.588 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 468.614 Td /F1 9.8 Tf  [(0.169)] TJ ET
0.267 0.267 0.267 rg
314.515 478.469 133.555 0.750 re f
314.515 462.588 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 468.614 Td /F1 9.8 Tf  [(0.373)] TJ ET
0.267 0.267 0.267 rg
447.320 478.469 133.555 0.750 re f
447.320 462.588 0.750 16.631 re f
580.125 462.588 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 468.614 Td /F1 9.8 Tf  [(0.190)] TJ ET
0.812 0.886 0.953 rg
27.000 447.082 155.086 15.881 re f
0.267 0.267 0.267 rg
26.625 462.588 155.836 0.750 re f
26.625 446.707 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 452.733 Td /F1 9.8 Tf  [(Balance on one foot)] TJ ET
0.812 0.886 0.953 rg
182.086 447.082 132.805 15.881 re f
0.267 0.267 0.267 rg
181.711 462.588 133.555 0.750 re f
181.711 446.707 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 452.733 Td /F1 9.8 Tf  [(0.758)] TJ ET
0.812 0.886 0.953 rg
314.890 447.082 132.805 15.881 re f
0.267 0.267 0.267 rg
314.515 462.588 133.555 0.750 re f
314.515 446.707 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 452.733 Td /F1 9.8 Tf  [(0.785)] TJ ET
0.812 0.886 0.953 rg
447.695 447.082 132.805 15.881 re f
0.267 0.267 0.267 rg
447.320 462.588 133.555 0.750 re f
447.320 446.707 0.750 16.631 re f
580.125 446.707 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 452.733 Td /F1 9.8 Tf  [(0.690)] TJ ET
0.812 0.886 0.953 rg
27.000 431.200 155.086 15.881 re f
0.267 0.267 0.267 rg
26.625 446.707 155.836 0.750 re f
26.625 430.825 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 436.852 Td /F1 9.8 Tf  [(Balance when walking)] TJ ET
0.812 0.886 0.953 rg
182.086 431.200 132.805 15.881 re f
0.267 0.267 0.267 rg
181.711 446.707 133.555 0.750 re f
181.711 430.825 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 436.852 Td /F1 9.8 Tf  [(0.858)] TJ ET
0.812 0.886 0.953 rg
314.890 431.200 132.805 15.881 re f
0.267 0.267 0.267 rg
314.515 446.707 133.555 0.750 re f
314.515 430.825 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 436.852 Td /F1 9.8 Tf  [(0.817)] TJ ET
0.812 0.886 0.953 rg
447.695 431.200 132.805 15.881 re f
0.267 0.267 0.267 rg
447.320 446.707 133.555 0.750 re f
447.320 430.825 0.750 16.631 re f
580.125 430.825 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 436.852 Td /F1 9.8 Tf  [(0.857)] TJ ET
0.267 0.267 0.267 rg
26.625 430.825 155.836 0.750 re f
26.625 414.944 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 420.970 Td /F1 9.8 Tf  [(Shifting gaze)] TJ ET
0.267 0.267 0.267 rg
181.711 430.825 133.555 0.750 re f
181.711 414.944 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 420.970 Td /F1 9.8 Tf  [(0.289)] TJ ET
0.267 0.267 0.267 rg
314.515 430.825 133.555 0.750 re f
314.515 414.944 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 420.970 Td /F1 9.8 Tf  [(0.333)] TJ ET
0.267 0.267 0.267 rg
447.320 430.825 133.555 0.750 re f
447.320 414.944 0.750 16.631 re f
580.125 414.944 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 420.970 Td /F1 9.8 Tf  [(0.349)] TJ ET
0.812 0.886 0.953 rg
27.000 399.438 155.086 15.881 re f
0.267 0.267 0.267 rg
26.625 414.944 155.836 0.750 re f
26.625 399.063 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 405.089 Td /F1 9.8 Tf  [(Fine motor ability)] TJ ET
0.812 0.886 0.953 rg
182.086 399.438 132.805 15.881 re f
0.267 0.267 0.267 rg
181.711 414.944 133.555 0.750 re f
181.711 399.063 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 405.089 Td /F1 9.8 Tf  [(0.718)] TJ ET
0.812 0.886 0.953 rg
314.890 399.438 132.805 15.881 re f
0.267 0.267 0.267 rg
314.515 414.944 133.555 0.750 re f
314.515 399.063 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 405.089 Td /F1 9.8 Tf  [(0.257)] TJ ET
0.812 0.886 0.953 rg
447.695 399.438 132.805 15.881 re f
0.267 0.267 0.267 rg
447.320 414.944 133.555 0.750 re f
447.320 399.063 0.750 16.631 re f
580.125 399.063 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 405.089 Td /F1 9.8 Tf  [(0.774)] TJ ET
0.812 0.886 0.953 rg
27.000 383.557 155.086 15.881 re f
0.267 0.267 0.267 rg
26.625 399.063 155.836 0.750 re f
26.625 383.182 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 389.208 Td /F1 9.8 Tf  [(Complex motor behavior)] TJ ET
0.812 0.886 0.953 rg
182.086 383.557 132.805 15.881 re f
0.267 0.267 0.267 rg
181.711 399.063 133.555 0.750 re f
181.711 383.182 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 389.208 Td /F1 9.8 Tf  [(0.722)] TJ ET
0.812 0.886 0.953 rg
314.890 383.557 132.805 15.881 re f
0.267 0.267 0.267 rg
314.515 399.063 133.555 0.750 re f
314.515 383.182 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 389.208 Td /F1 9.8 Tf  [(0.532)] TJ ET
0.812 0.886 0.953 rg
447.695 383.557 132.805 15.881 re f
0.267 0.267 0.267 rg
447.320 399.063 133.555 0.750 re f
447.320 383.182 0.750 16.631 re f
580.125 383.182 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 389.208 Td /F1 9.8 Tf  [(0.733)] TJ ET
0.812 0.886 0.953 rg
27.000 367.675 155.086 15.881 re f
0.267 0.267 0.267 rg
26.625 383.182 155.836 0.750 re f
26.625 367.300 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 373.327 Td /F1 9.8 Tf  [(Writing)] TJ ET
0.812 0.886 0.953 rg
182.086 367.675 132.805 15.881 re f
0.267 0.267 0.267 rg
181.711 383.182 133.555 0.750 re f
181.711 367.300 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 373.327 Td /F1 9.8 Tf  [(0.820)] TJ ET
0.812 0.886 0.953 rg
314.890 367.675 132.805 15.881 re f
0.267 0.267 0.267 rg
314.515 383.182 133.555 0.750 re f
314.515 367.300 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 373.327 Td /F1 9.8 Tf  [(0.805)] TJ ET
0.812 0.886 0.953 rg
447.695 367.675 132.805 15.881 re f
0.267 0.267 0.267 rg
447.320 383.182 133.555 0.750 re f
447.320 367.300 0.750 16.631 re f
580.125 367.300 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 373.327 Td /F1 9.8 Tf  [(0.776)] TJ ET
0.812 0.886 0.953 rg
27.000 351.794 155.086 15.881 re f
0.267 0.267 0.267 rg
26.625 367.300 155.836 0.750 re f
26.625 351.419 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 357.445 Td /F1 9.8 Tf  [(Clumsiness)] TJ ET
0.812 0.886 0.953 rg
182.086 351.794 132.805 15.881 re f
0.267 0.267 0.267 rg
181.711 367.300 133.555 0.750 re f
181.711 351.419 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 357.445 Td /F1 9.8 Tf  [(0.795)] TJ ET
0.812 0.886 0.953 rg
314.890 351.794 132.805 15.881 re f
0.267 0.267 0.267 rg
314.515 367.300 133.555 0.750 re f
314.515 351.419 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 357.445 Td /F1 9.8 Tf  [(0.744)] TJ ET
0.812 0.886 0.953 rg
447.695 351.794 132.805 15.881 re f
0.267 0.267 0.267 rg
447.320 367.300 133.555 0.750 re f
447.320 351.419 0.750 16.631 re f
580.125 351.419 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 357.445 Td /F1 9.8 Tf  [(0.774)] TJ ET
0.812 0.886 0.953 rg
27.000 335.913 155.086 15.881 re f
0.267 0.267 0.267 rg
26.625 351.419 155.836 0.750 re f
26.625 335.538 155.836 0.750 re f
26.625 335.538 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 341.564 Td /F1 9.8 Tf  [(Functional impact)] TJ ET
0.812 0.886 0.953 rg
182.086 335.913 132.805 15.881 re f
0.267 0.267 0.267 rg
181.711 351.419 133.555 0.750 re f
181.711 335.538 133.555 0.750 re f
181.711 335.538 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 341.564 Td /F1 9.8 Tf  [(0.858)] TJ ET
0.812 0.886 0.953 rg
314.890 335.913 132.805 15.881 re f
0.267 0.267 0.267 rg
314.515 351.419 133.555 0.750 re f
314.515 335.538 133.555 0.750 re f
314.515 335.538 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 341.564 Td /F1 9.8 Tf  [(0.902)] TJ ET
0.812 0.886 0.953 rg
447.695 335.913 132.805 15.881 re f
0.267 0.267 0.267 rg
447.320 351.419 133.555 0.750 re f
447.320 335.538 133.555 0.750 re f
447.320 335.538 0.750 16.631 re f
580.125 335.538 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 341.564 Td /F1 9.8 Tf  [(0.828)] TJ ET
BT 26.250 288.139 Td /F4 9.8 Tf  [(Table 4. )] TJ ET
BT 65.269 288.139 Td /F1 9.8 Tf  [(Summary of Mean Composite Scores)] TJ ET
1.000 1.000 1.000 rg
26.250 93.683 555.000 192.075 re f
0.267 0.267 0.267 rg
26.625 284.633 179.129 0.750 re f
26.625 268.752 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 274.778 Td /F4 9.8 Tf  [(Item)] TJ ET
0.267 0.267 0.267 rg
205.004 284.633 141.176 0.750 re f
205.004 268.752 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 274.778 Td /F4 9.8 Tf  [(Overall mean score)] TJ ET
0.267 0.267 0.267 rg
345.430 284.633 122.744 0.750 re f
345.430 268.752 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 274.778 Td /F4 9.8 Tf  [(prHD mean score)] TJ ET
0.267 0.267 0.267 rg
467.424 284.633 113.451 0.750 re f
467.424 268.752 0.750 16.631 re f
580.125 268.752 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 274.778 Td /F4 9.8 Tf  [(HD mean score)] TJ ET
0.267 0.267 0.267 rg
26.625 268.752 179.129 0.750 re f
26.625 252.871 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 258.897 Td /F1 9.8 Tf  [(Reading)] TJ ET
0.267 0.267 0.267 rg
205.004 268.752 141.176 0.750 re f
205.004 252.871 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 258.897 Td /F1 9.8 Tf  [(0.33)] TJ ET
0.267 0.267 0.267 rg
345.430 268.752 122.744 0.750 re f
345.430 252.871 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 258.897 Td /F1 9.8 Tf  [(0.21)] TJ ET
0.267 0.267 0.267 rg
467.424 268.752 113.451 0.750 re f
467.424 252.871 0.750 16.631 re f
580.125 252.871 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 258.897 Td /F1 9.8 Tf  [(0.48)] TJ ET
0.267 0.267 0.267 rg
26.625 252.871 179.129 0.750 re f
26.625 236.989 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 243.016 Td /F1 9.8 Tf  [(Tracking while reading)] TJ ET
0.267 0.267 0.267 rg
205.004 252.871 141.176 0.750 re f
205.004 236.989 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 243.016 Td /F1 9.8 Tf  [(0.29)] TJ ET
0.267 0.267 0.267 rg
345.430 252.871 122.744 0.750 re f
345.430 236.989 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 243.016 Td /F1 9.8 Tf  [(0.22)] TJ ET
0.267 0.267 0.267 rg
467.424 252.871 113.451 0.750 re f
467.424 236.989 0.750 16.631 re f
580.125 236.989 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 243.016 Td /F1 9.8 Tf  [(0.37)] TJ ET
0.267 0.267 0.267 rg
26.625 236.989 179.129 0.750 re f
26.625 221.108 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 227.134 Td /F1 9.8 Tf  [(Tracking objects with eyes)] TJ ET
0.267 0.267 0.267 rg
205.004 236.989 141.176 0.750 re f
205.004 221.108 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 227.134 Td /F1 9.8 Tf  [(0.08)] TJ ET
0.267 0.267 0.267 rg
345.430 236.989 122.744 0.750 re f
345.430 221.108 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 227.134 Td /F1 9.8 Tf  [(0.11)] TJ ET
0.267 0.267 0.267 rg
467.424 236.989 113.451 0.750 re f
467.424 221.108 0.750 16.631 re f
580.125 221.108 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 227.134 Td /F1 9.8 Tf  [(0.03)] TJ ET
0.812 0.886 0.953 rg
27.000 205.602 178.379 15.881 re f
0.267 0.267 0.267 rg
26.625 221.108 179.129 0.750 re f
26.625 205.227 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 211.253 Td /F1 9.8 Tf  [(Balance on one foot)] TJ ET
0.812 0.886 0.953 rg
205.379 205.602 140.426 15.881 re f
0.267 0.267 0.267 rg
205.004 221.108 141.176 0.750 re f
205.004 205.227 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 211.253 Td /F1 9.8 Tf  [(0.98)] TJ ET
0.812 0.886 0.953 rg
345.805 205.602 121.994 15.881 re f
0.267 0.267 0.267 rg
345.430 221.108 122.744 0.750 re f
345.430 205.227 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 211.253 Td /F1 9.8 Tf  [(0.51)] TJ ET
0.812 0.886 0.953 rg
467.799 205.602 112.701 15.881 re f
0.267 0.267 0.267 rg
467.424 221.108 113.451 0.750 re f
467.424 205.227 0.750 16.631 re f
580.125 205.227 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 211.253 Td /F1 9.8 Tf  [(1.56)] TJ ET
0.812 0.886 0.953 rg
27.000 189.721 178.379 15.881 re f
0.267 0.267 0.267 rg
26.625 205.227 179.129 0.750 re f
26.625 189.346 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 195.372 Td /F1 9.8 Tf  [(Balance when walking)] TJ ET
0.812 0.886 0.953 rg
205.379 189.721 140.426 15.881 re f
0.267 0.267 0.267 rg
205.004 205.227 141.176 0.750 re f
205.004 189.346 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 195.372 Td /F1 9.8 Tf  [(0.76)] TJ ET
0.812 0.886 0.953 rg
345.805 189.721 121.994 15.881 re f
0.267 0.267 0.267 rg
345.430 205.227 122.744 0.750 re f
345.430 189.346 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 195.372 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.812 0.886 0.953 rg
467.799 189.721 112.701 15.881 re f
0.267 0.267 0.267 rg
467.424 205.227 113.451 0.750 re f
467.424 189.346 0.750 16.631 re f
580.125 189.346 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 195.372 Td /F1 9.8 Tf  [(1.17)] TJ ET
0.267 0.267 0.267 rg
26.625 189.346 179.129 0.750 re f
26.625 173.464 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 179.491 Td /F1 9.8 Tf  [(Shifting gaze)] TJ ET
0.267 0.267 0.267 rg
205.004 189.346 141.176 0.750 re f
205.004 173.464 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 179.491 Td /F1 9.8 Tf  [(0.12)] TJ ET
0.267 0.267 0.267 rg
345.430 189.346 122.744 0.750 re f
345.430 173.464 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 179.491 Td /F1 9.8 Tf  [(0.12)] TJ ET
0.267 0.267 0.267 rg
467.424 189.346 113.451 0.750 re f
467.424 173.464 0.750 16.631 re f
580.125 173.464 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 179.491 Td /F1 9.8 Tf  [(0.12)] TJ ET
0.812 0.886 0.953 rg
27.000 157.958 178.379 15.881 re f
0.267 0.267 0.267 rg
26.625 173.464 179.129 0.750 re f
26.625 157.583 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 163.609 Td /F1 9.8 Tf  [(Fine motor ability)] TJ ET
0.812 0.886 0.953 rg
205.379 157.958 140.426 15.881 re f
0.267 0.267 0.267 rg
205.004 173.464 141.176 0.750 re f
205.004 157.583 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 163.609 Td /F1 9.8 Tf  [(0.66)] TJ ET
0.812 0.886 0.953 rg
345.805 157.958 121.994 15.881 re f
0.267 0.267 0.267 rg
345.430 173.464 122.744 0.750 re f
345.430 157.583 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 163.609 Td /F1 9.8 Tf  [(0.16)] TJ ET
0.812 0.886 0.953 rg
467.799 157.958 112.701 15.881 re f
0.267 0.267 0.267 rg
467.424 173.464 113.451 0.750 re f
467.424 157.583 0.750 16.631 re f
580.125 157.583 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 163.609 Td /F1 9.8 Tf  [(1.28)] TJ ET
0.812 0.886 0.953 rg
27.000 142.077 178.379 15.881 re f
0.267 0.267 0.267 rg
26.625 157.583 179.129 0.750 re f
26.625 141.702 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 147.728 Td /F1 9.8 Tf  [(Complex motor behavior)] TJ ET
0.812 0.886 0.953 rg
205.379 142.077 140.426 15.881 re f
0.267 0.267 0.267 rg
205.004 157.583 141.176 0.750 re f
205.004 141.702 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 147.728 Td /F1 9.8 Tf  [(0.50)] TJ ET
0.812 0.886 0.953 rg
345.805 142.077 121.994 15.881 re f
0.267 0.267 0.267 rg
345.430 157.583 122.744 0.750 re f
345.430 141.702 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 147.728 Td /F1 9.8 Tf  [(0.18)] TJ ET
0.812 0.886 0.953 rg
467.799 142.077 112.701 15.881 re f
0.267 0.267 0.267 rg
467.424 157.583 113.451 0.750 re f
467.424 141.702 0.750 16.631 re f
580.125 141.702 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 147.728 Td /F1 9.8 Tf  [(0.90)] TJ ET
0.812 0.886 0.953 rg
27.000 126.196 178.379 15.881 re f
0.267 0.267 0.267 rg
26.625 141.702 179.129 0.750 re f
26.625 125.821 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 131.847 Td /F1 9.8 Tf  [(Writing)] TJ ET
0.812 0.886 0.953 rg
205.379 126.196 140.426 15.881 re f
0.267 0.267 0.267 rg
205.004 141.702 141.176 0.750 re f
205.004 125.821 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 131.847 Td /F1 9.8 Tf  [(0.96)] TJ ET
0.812 0.886 0.953 rg
345.805 126.196 121.994 15.881 re f
0.267 0.267 0.267 rg
345.430 141.702 122.744 0.750 re f
345.430 125.821 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 131.847 Td /F1 9.8 Tf  [(0.49)] TJ ET
0.812 0.886 0.953 rg
467.799 126.196 112.701 15.881 re f
0.267 0.267 0.267 rg
467.424 141.702 113.451 0.750 re f
467.424 125.821 0.750 16.631 re f
580.125 125.821 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 131.847 Td /F1 9.8 Tf  [(1.55)] TJ ET
0.812 0.886 0.953 rg
27.000 110.314 178.379 15.881 re f
0.267 0.267 0.267 rg
26.625 125.821 179.129 0.750 re f
26.625 109.939 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 115.966 Td /F1 9.8 Tf  [(Clumsiness)] TJ ET
0.812 0.886 0.953 rg
205.379 110.314 140.426 15.881 re f
0.267 0.267 0.267 rg
205.004 125.821 141.176 0.750 re f
205.004 109.939 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 115.966 Td /F1 9.8 Tf  [(0.88)] TJ ET
0.812 0.886 0.953 rg
345.805 110.314 121.994 15.881 re f
0.267 0.267 0.267 rg
345.430 125.821 122.744 0.750 re f
345.430 109.939 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 115.966 Td /F1 9.8 Tf  [(0.55)] TJ ET
0.812 0.886 0.953 rg
467.799 110.314 112.701 15.881 re f
0.267 0.267 0.267 rg
467.424 125.821 113.451 0.750 re f
467.424 109.939 0.750 16.631 re f
580.125 109.939 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 115.966 Td /F1 9.8 Tf  [(1.29)] TJ ET
0.812 0.886 0.953 rg
27.000 94.433 178.379 15.881 re f
0.267 0.267 0.267 rg
26.625 109.939 179.129 0.750 re f
26.625 94.058 179.129 0.750 re f
26.625 94.058 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 100.084 Td /F1 9.8 Tf  [(Functional impact)] TJ ET
0.812 0.886 0.953 rg
205.379 94.433 140.426 15.881 re f
0.267 0.267 0.267 rg
205.004 109.939 141.176 0.750 re f
205.004 94.058 141.176 0.750 re f
205.004 94.058 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 100.084 Td /F1 9.8 Tf  [(0.80)] TJ ET
0.812 0.886 0.953 rg
345.805 94.433 121.994 15.881 re f
0.267 0.267 0.267 rg
345.430 109.939 122.744 0.750 re f
345.430 94.058 122.744 0.750 re f
345.430 94.058 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 100.084 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.812 0.886 0.953 rg
467.799 94.433 112.701 15.881 re f
0.267 0.267 0.267 rg
467.424 109.939 113.451 0.750 re f
467.424 94.058 113.451 0.750 re f
467.424 94.058 0.750 16.631 re f
580.125 94.058 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 100.084 Td /F1 9.8 Tf  [(1.24)] TJ ET
BT 26.250 46.659 Td /F1 9.8 Tf  [(It was agreed that these 7 interview questions would be modified accordingly for testing in subsequent iterations; examination of )] TJ ET
Q
q
15.000 32.374 577.500 744.626 re W n
0.965 0.965 0.965 rg
26.250 724.036 555.000 52.964 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 724.036 m 581.250 724.036 l 581.250 724.786 l 26.250 724.786 l  f
q
35.250 735.286 537.000 41.714 re W n
0.271 0.267 0.267 rg
BT 35.250 767.476 Td /F4 9.8 Tf  [(Fig. 2: OCCs and Frequency distribution for interview question assessing ability to perform tasks that require )] TJ ET
BT 35.250 755.571 Td /F4 9.8 Tf  [(balance on one foot for all participants, HD and prHD. Data is presented separately for symptom intensity \(left row\), )] TJ ET
BT 35.250 743.667 Td /F4 9.8 Tf  [(frequency \(middle row\), and composite \(right row\) scores.)] TJ ET
Q
BT 26.250 707.012 Td /F1 9.8 Tf  [(The mean total composite score with respect to the above 7 items was 2.55 in prHD subjects and 8.98 in HD subjects; the )] TJ ET
BT 26.250 695.107 Td /F1 9.8 Tf  [(difference in mean scores was statistically significant \( )] TJ ET
BT 262.493 695.107 Td /F5 9.8 Tf  [(p)] TJ ET
BT 267.913 695.107 Td /F1 9.8 Tf  [( < 0.001, Mann-Whitney U test\). In addition, significant differences were )] TJ ET
BT 26.250 683.202 Td /F1 9.8 Tf  [(noted in scoring between prHD and HD for each of the individual items, with greater intensity and frequency of symptoms noted )] TJ ET
BT 26.250 671.298 Td /F1 9.8 Tf  [(in early HD participants \( )] TJ ET
BT 135.694 671.298 Td /F5 9.8 Tf  [(p)] TJ ET
BT 141.115 671.298 Td /F1 9.8 Tf  [( < 0.001 with respect to each item, Mann-Whitney U test\) \(Table 4\). This is not surprising given that )] TJ ET
BT 26.250 659.393 Td /F1 9.8 Tf  [(the classification of prHD is defined as the absence of sufficient motor signs to meet conventional diagnostic criteria for manifest )] TJ ET
BT 26.250 647.488 Td /F1 9.8 Tf  [(disease. )] TJ ET
0.267 0.267 0.267 rg
BT 65.269 647.488 Td /F1 9.8 Tf  [([6])] TJ ET
0.271 0.267 0.267 rg
BT 76.112 647.488 Td /F1 9.8 Tf  [( For example, in assessing ability to perform tasks that require balance on one foot, scoring was driven primarily by )] TJ ET
BT 26.250 635.583 Td /F1 9.8 Tf  [(early HD participants \(Figure 2, Table 4\). In prHD, the option with the highest probably of being scored for symptom intensity )] TJ ET
BT 26.250 623.679 Td /F1 9.8 Tf  [(increased from �0� to �1� \(mild: sense of unsteadiness/imbalance on one foot that others may not notice, but no impact on )] TJ ET
BT 26.250 611.774 Td /F1 9.8 Tf  [(function of daily activities\) suggesting that although these changes are noticeable to the participant, the functional impact may )] TJ ET
BT 26.250 599.869 Td /F1 9.8 Tf  [(be minimal. By contrast, in early HD participants scores of �3� \(severe: needs support to maintain balance\) and �4� \(very severe: )] TJ ET
BT 26.250 587.964 Td /F1 9.8 Tf  [(cannot stand on one foot, must sit down to do things\) were sometimes endorsed. The poor discrimination between symptom )] TJ ET
BT 26.250 576.060 Td /F1 9.8 Tf  [(intensity scores of �3� and �4� indicates that modifications to the wording of these options would be needed to allow for better )] TJ ET
BT 26.250 564.155 Td /F1 9.8 Tf  [(discrimination.)] TJ ET
BT 26.250 544.750 Td /F4 9.8 Tf  [(Table 3. )] TJ ET
BT 65.269 544.750 Td /F1 9.8 Tf  [( Correlations between Interview Questions Scores)] TJ ET
1.000 1.000 1.000 rg
26.250 335.163 555.000 199.706 re f
0.267 0.267 0.267 rg
26.625 533.744 155.836 0.750 re f
26.625 510.232 0.750 24.262 re f
0.271 0.267 0.267 rg
BT 31.875 523.889 Td /F1 9.8 Tf  [(Item)] TJ ET
0.267 0.267 0.267 rg
181.711 533.744 133.555 0.750 re f
181.711 510.232 0.750 24.262 re f
0.271 0.267 0.267 rg
BT 186.961 523.889 Td /F1 9.8 Tf  [(Item-total correlation )] TJ ET
BT 186.961 516.258 Td /F1 9.8 Tf  [(\(all subjects\))] TJ ET
0.267 0.267 0.267 rg
314.515 533.744 133.555 0.750 re f
314.515 510.232 0.750 24.262 re f
0.271 0.267 0.267 rg
BT 319.765 523.889 Td /F1 9.8 Tf  [(Item-total correlation )] TJ ET
BT 319.765 516.258 Td /F1 9.8 Tf  [(\(prHD subjects\))] TJ ET
0.267 0.267 0.267 rg
447.320 533.744 133.555 0.750 re f
447.320 510.232 0.750 24.262 re f
580.125 510.232 0.750 24.262 re f
0.271 0.267 0.267 rg
BT 452.570 523.889 Td /F1 9.8 Tf  [(Item-total correlation )] TJ ET
BT 452.570 516.258 Td /F1 9.8 Tf  [(\(HD subjects\))] TJ ET
0.267 0.267 0.267 rg
26.625 510.232 155.836 0.750 re f
26.625 494.350 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 500.377 Td /F1 9.8 Tf  [(Reading)] TJ ET
0.267 0.267 0.267 rg
181.711 510.232 133.555 0.750 re f
181.711 494.350 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 500.377 Td /F1 9.8 Tf  [(0.389)] TJ ET
0.267 0.267 0.267 rg
314.515 510.232 133.555 0.750 re f
314.515 494.350 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 500.377 Td /F1 9.8 Tf  [(0.340)] TJ ET
0.267 0.267 0.267 rg
447.320 510.232 133.555 0.750 re f
447.320 494.350 0.750 16.631 re f
580.125 494.350 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 500.377 Td /F1 9.8 Tf  [(0.360)] TJ ET
0.267 0.267 0.267 rg
26.625 494.350 155.836 0.750 re f
26.625 478.469 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 484.495 Td /F1 9.8 Tf  [(Tracking while reading)] TJ ET
0.267 0.267 0.267 rg
181.711 494.350 133.555 0.750 re f
181.711 478.469 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 484.495 Td /F1 9.8 Tf  [(0.489)] TJ ET
0.267 0.267 0.267 rg
314.515 494.350 133.555 0.750 re f
314.515 478.469 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 484.495 Td /F1 9.8 Tf  [(0.202)] TJ ET
0.267 0.267 0.267 rg
447.320 494.350 133.555 0.750 re f
447.320 478.469 0.750 16.631 re f
580.125 478.469 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 484.495 Td /F1 9.8 Tf  [(0.639)] TJ ET
0.267 0.267 0.267 rg
26.625 478.469 155.836 0.750 re f
26.625 462.588 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 468.614 Td /F1 9.8 Tf  [(Tracking objects with eyes)] TJ ET
0.267 0.267 0.267 rg
181.711 478.469 133.555 0.750 re f
181.711 462.588 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 468.614 Td /F1 9.8 Tf  [(0.169)] TJ ET
0.267 0.267 0.267 rg
314.515 478.469 133.555 0.750 re f
314.515 462.588 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 468.614 Td /F1 9.8 Tf  [(0.373)] TJ ET
0.267 0.267 0.267 rg
447.320 478.469 133.555 0.750 re f
447.320 462.588 0.750 16.631 re f
580.125 462.588 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 468.614 Td /F1 9.8 Tf  [(0.190)] TJ ET
0.812 0.886 0.953 rg
27.000 447.082 155.086 15.881 re f
0.267 0.267 0.267 rg
26.625 462.588 155.836 0.750 re f
26.625 446.707 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 452.733 Td /F1 9.8 Tf  [(Balance on one foot)] TJ ET
0.812 0.886 0.953 rg
182.086 447.082 132.805 15.881 re f
0.267 0.267 0.267 rg
181.711 462.588 133.555 0.750 re f
181.711 446.707 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 452.733 Td /F1 9.8 Tf  [(0.758)] TJ ET
0.812 0.886 0.953 rg
314.890 447.082 132.805 15.881 re f
0.267 0.267 0.267 rg
314.515 462.588 133.555 0.750 re f
314.515 446.707 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 452.733 Td /F1 9.8 Tf  [(0.785)] TJ ET
0.812 0.886 0.953 rg
447.695 447.082 132.805 15.881 re f
0.267 0.267 0.267 rg
447.320 462.588 133.555 0.750 re f
447.320 446.707 0.750 16.631 re f
580.125 446.707 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 452.733 Td /F1 9.8 Tf  [(0.690)] TJ ET
0.812 0.886 0.953 rg
27.000 431.200 155.086 15.881 re f
0.267 0.267 0.267 rg
26.625 446.707 155.836 0.750 re f
26.625 430.825 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 436.852 Td /F1 9.8 Tf  [(Balance when walking)] TJ ET
0.812 0.886 0.953 rg
182.086 431.200 132.805 15.881 re f
0.267 0.267 0.267 rg
181.711 446.707 133.555 0.750 re f
181.711 430.825 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 436.852 Td /F1 9.8 Tf  [(0.858)] TJ ET
0.812 0.886 0.953 rg
314.890 431.200 132.805 15.881 re f
0.267 0.267 0.267 rg
314.515 446.707 133.555 0.750 re f
314.515 430.825 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 436.852 Td /F1 9.8 Tf  [(0.817)] TJ ET
0.812 0.886 0.953 rg
447.695 431.200 132.805 15.881 re f
0.267 0.267 0.267 rg
447.320 446.707 133.555 0.750 re f
447.320 430.825 0.750 16.631 re f
580.125 430.825 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 436.852 Td /F1 9.8 Tf  [(0.857)] TJ ET
0.267 0.267 0.267 rg
26.625 430.825 155.836 0.750 re f
26.625 414.944 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 420.970 Td /F1 9.8 Tf  [(Shifting gaze)] TJ ET
0.267 0.267 0.267 rg
181.711 430.825 133.555 0.750 re f
181.711 414.944 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 420.970 Td /F1 9.8 Tf  [(0.289)] TJ ET
0.267 0.267 0.267 rg
314.515 430.825 133.555 0.750 re f
314.515 414.944 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 420.970 Td /F1 9.8 Tf  [(0.333)] TJ ET
0.267 0.267 0.267 rg
447.320 430.825 133.555 0.750 re f
447.320 414.944 0.750 16.631 re f
580.125 414.944 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 420.970 Td /F1 9.8 Tf  [(0.349)] TJ ET
0.812 0.886 0.953 rg
27.000 399.438 155.086 15.881 re f
0.267 0.267 0.267 rg
26.625 414.944 155.836 0.750 re f
26.625 399.063 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 405.089 Td /F1 9.8 Tf  [(Fine motor ability)] TJ ET
0.812 0.886 0.953 rg
182.086 399.438 132.805 15.881 re f
0.267 0.267 0.267 rg
181.711 414.944 133.555 0.750 re f
181.711 399.063 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 405.089 Td /F1 9.8 Tf  [(0.718)] TJ ET
0.812 0.886 0.953 rg
314.890 399.438 132.805 15.881 re f
0.267 0.267 0.267 rg
314.515 414.944 133.555 0.750 re f
314.515 399.063 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 405.089 Td /F1 9.8 Tf  [(0.257)] TJ ET
0.812 0.886 0.953 rg
447.695 399.438 132.805 15.881 re f
0.267 0.267 0.267 rg
447.320 414.944 133.555 0.750 re f
447.320 399.063 0.750 16.631 re f
580.125 399.063 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 405.089 Td /F1 9.8 Tf  [(0.774)] TJ ET
0.812 0.886 0.953 rg
27.000 383.557 155.086 15.881 re f
0.267 0.267 0.267 rg
26.625 399.063 155.836 0.750 re f
26.625 383.182 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 389.208 Td /F1 9.8 Tf  [(Complex motor behavior)] TJ ET
0.812 0.886 0.953 rg
182.086 383.557 132.805 15.881 re f
0.267 0.267 0.267 rg
181.711 399.063 133.555 0.750 re f
181.711 383.182 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 389.208 Td /F1 9.8 Tf  [(0.722)] TJ ET
0.812 0.886 0.953 rg
314.890 383.557 132.805 15.881 re f
0.267 0.267 0.267 rg
314.515 399.063 133.555 0.750 re f
314.515 383.182 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 389.208 Td /F1 9.8 Tf  [(0.532)] TJ ET
0.812 0.886 0.953 rg
447.695 383.557 132.805 15.881 re f
0.267 0.267 0.267 rg
447.320 399.063 133.555 0.750 re f
447.320 383.182 0.750 16.631 re f
580.125 383.182 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 389.208 Td /F1 9.8 Tf  [(0.733)] TJ ET
0.812 0.886 0.953 rg
27.000 367.675 155.086 15.881 re f
0.267 0.267 0.267 rg
26.625 383.182 155.836 0.750 re f
26.625 367.300 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 373.327 Td /F1 9.8 Tf  [(Writing)] TJ ET
0.812 0.886 0.953 rg
182.086 367.675 132.805 15.881 re f
0.267 0.267 0.267 rg
181.711 383.182 133.555 0.750 re f
181.711 367.300 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 373.327 Td /F1 9.8 Tf  [(0.820)] TJ ET
0.812 0.886 0.953 rg
314.890 367.675 132.805 15.881 re f
0.267 0.267 0.267 rg
314.515 383.182 133.555 0.750 re f
314.515 367.300 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 373.327 Td /F1 9.8 Tf  [(0.805)] TJ ET
0.812 0.886 0.953 rg
447.695 367.675 132.805 15.881 re f
0.267 0.267 0.267 rg
447.320 383.182 133.555 0.750 re f
447.320 367.300 0.750 16.631 re f
580.125 367.300 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 373.327 Td /F1 9.8 Tf  [(0.776)] TJ ET
0.812 0.886 0.953 rg
27.000 351.794 155.086 15.881 re f
0.267 0.267 0.267 rg
26.625 367.300 155.836 0.750 re f
26.625 351.419 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 357.445 Td /F1 9.8 Tf  [(Clumsiness)] TJ ET
0.812 0.886 0.953 rg
182.086 351.794 132.805 15.881 re f
0.267 0.267 0.267 rg
181.711 367.300 133.555 0.750 re f
181.711 351.419 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 357.445 Td /F1 9.8 Tf  [(0.795)] TJ ET
0.812 0.886 0.953 rg
314.890 351.794 132.805 15.881 re f
0.267 0.267 0.267 rg
314.515 367.300 133.555 0.750 re f
314.515 351.419 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 357.445 Td /F1 9.8 Tf  [(0.744)] TJ ET
0.812 0.886 0.953 rg
447.695 351.794 132.805 15.881 re f
0.267 0.267 0.267 rg
447.320 367.300 133.555 0.750 re f
447.320 351.419 0.750 16.631 re f
580.125 351.419 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 357.445 Td /F1 9.8 Tf  [(0.774)] TJ ET
0.812 0.886 0.953 rg
27.000 335.913 155.086 15.881 re f
0.267 0.267 0.267 rg
26.625 351.419 155.836 0.750 re f
26.625 335.538 155.836 0.750 re f
26.625 335.538 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 341.564 Td /F1 9.8 Tf  [(Functional impact)] TJ ET
0.812 0.886 0.953 rg
182.086 335.913 132.805 15.881 re f
0.267 0.267 0.267 rg
181.711 351.419 133.555 0.750 re f
181.711 335.538 133.555 0.750 re f
181.711 335.538 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 341.564 Td /F1 9.8 Tf  [(0.858)] TJ ET
0.812 0.886 0.953 rg
314.890 335.913 132.805 15.881 re f
0.267 0.267 0.267 rg
314.515 351.419 133.555 0.750 re f
314.515 335.538 133.555 0.750 re f
314.515 335.538 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 341.564 Td /F1 9.8 Tf  [(0.902)] TJ ET
0.812 0.886 0.953 rg
447.695 335.913 132.805 15.881 re f
0.267 0.267 0.267 rg
447.320 351.419 133.555 0.750 re f
447.320 335.538 133.555 0.750 re f
447.320 335.538 0.750 16.631 re f
580.125 335.538 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 341.564 Td /F1 9.8 Tf  [(0.828)] TJ ET
BT 26.250 288.139 Td /F4 9.8 Tf  [(Table 4. )] TJ ET
BT 65.269 288.139 Td /F1 9.8 Tf  [(Summary of Mean Composite Scores)] TJ ET
1.000 1.000 1.000 rg
26.250 93.683 555.000 192.075 re f
0.267 0.267 0.267 rg
26.625 284.633 179.129 0.750 re f
26.625 268.752 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 274.778 Td /F4 9.8 Tf  [(Item)] TJ ET
0.267 0.267 0.267 rg
205.004 284.633 141.176 0.750 re f
205.004 268.752 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 274.778 Td /F4 9.8 Tf  [(Overall mean score)] TJ ET
0.267 0.267 0.267 rg
345.430 284.633 122.744 0.750 re f
345.430 268.752 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 274.778 Td /F4 9.8 Tf  [(prHD mean score)] TJ ET
0.267 0.267 0.267 rg
467.424 284.633 113.451 0.750 re f
467.424 268.752 0.750 16.631 re f
580.125 268.752 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 274.778 Td /F4 9.8 Tf  [(HD mean score)] TJ ET
0.267 0.267 0.267 rg
26.625 268.752 179.129 0.750 re f
26.625 252.871 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 258.897 Td /F1 9.8 Tf  [(Reading)] TJ ET
0.267 0.267 0.267 rg
205.004 268.752 141.176 0.750 re f
205.004 252.871 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 258.897 Td /F1 9.8 Tf  [(0.33)] TJ ET
0.267 0.267 0.267 rg
345.430 268.752 122.744 0.750 re f
345.430 252.871 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 258.897 Td /F1 9.8 Tf  [(0.21)] TJ ET
0.267 0.267 0.267 rg
467.424 268.752 113.451 0.750 re f
467.424 252.871 0.750 16.631 re f
580.125 252.871 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 258.897 Td /F1 9.8 Tf  [(0.48)] TJ ET
0.267 0.267 0.267 rg
26.625 252.871 179.129 0.750 re f
26.625 236.989 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 243.016 Td /F1 9.8 Tf  [(Tracking while reading)] TJ ET
0.267 0.267 0.267 rg
205.004 252.871 141.176 0.750 re f
205.004 236.989 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 243.016 Td /F1 9.8 Tf  [(0.29)] TJ ET
0.267 0.267 0.267 rg
345.430 252.871 122.744 0.750 re f
345.430 236.989 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 243.016 Td /F1 9.8 Tf  [(0.22)] TJ ET
0.267 0.267 0.267 rg
467.424 252.871 113.451 0.750 re f
467.424 236.989 0.750 16.631 re f
580.125 236.989 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 243.016 Td /F1 9.8 Tf  [(0.37)] TJ ET
0.267 0.267 0.267 rg
26.625 236.989 179.129 0.750 re f
26.625 221.108 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 227.134 Td /F1 9.8 Tf  [(Tracking objects with eyes)] TJ ET
0.267 0.267 0.267 rg
205.004 236.989 141.176 0.750 re f
205.004 221.108 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 227.134 Td /F1 9.8 Tf  [(0.08)] TJ ET
0.267 0.267 0.267 rg
345.430 236.989 122.744 0.750 re f
345.430 221.108 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 227.134 Td /F1 9.8 Tf  [(0.11)] TJ ET
0.267 0.267 0.267 rg
467.424 236.989 113.451 0.750 re f
467.424 221.108 0.750 16.631 re f
580.125 221.108 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 227.134 Td /F1 9.8 Tf  [(0.03)] TJ ET
0.812 0.886 0.953 rg
27.000 205.602 178.379 15.881 re f
0.267 0.267 0.267 rg
26.625 221.108 179.129 0.750 re f
26.625 205.227 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 211.253 Td /F1 9.8 Tf  [(Balance on one foot)] TJ ET
0.812 0.886 0.953 rg
205.379 205.602 140.426 15.881 re f
0.267 0.267 0.267 rg
205.004 221.108 141.176 0.750 re f
205.004 205.227 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 211.253 Td /F1 9.8 Tf  [(0.98)] TJ ET
0.812 0.886 0.953 rg
345.805 205.602 121.994 15.881 re f
0.267 0.267 0.267 rg
345.430 221.108 122.744 0.750 re f
345.430 205.227 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 211.253 Td /F1 9.8 Tf  [(0.51)] TJ ET
0.812 0.886 0.953 rg
467.799 205.602 112.701 15.881 re f
0.267 0.267 0.267 rg
467.424 221.108 113.451 0.750 re f
467.424 205.227 0.750 16.631 re f
580.125 205.227 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 211.253 Td /F1 9.8 Tf  [(1.56)] TJ ET
0.812 0.886 0.953 rg
27.000 189.721 178.379 15.881 re f
0.267 0.267 0.267 rg
26.625 205.227 179.129 0.750 re f
26.625 189.346 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 195.372 Td /F1 9.8 Tf  [(Balance when walking)] TJ ET
0.812 0.886 0.953 rg
205.379 189.721 140.426 15.881 re f
0.267 0.267 0.267 rg
205.004 205.227 141.176 0.750 re f
205.004 189.346 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 195.372 Td /F1 9.8 Tf  [(0.76)] TJ ET
0.812 0.886 0.953 rg
345.805 189.721 121.994 15.881 re f
0.267 0.267 0.267 rg
345.430 205.227 122.744 0.750 re f
345.430 189.346 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 195.372 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.812 0.886 0.953 rg
467.799 189.721 112.701 15.881 re f
0.267 0.267 0.267 rg
467.424 205.227 113.451 0.750 re f
467.424 189.346 0.750 16.631 re f
580.125 189.346 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 195.372 Td /F1 9.8 Tf  [(1.17)] TJ ET
0.267 0.267 0.267 rg
26.625 189.346 179.129 0.750 re f
26.625 173.464 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 179.491 Td /F1 9.8 Tf  [(Shifting gaze)] TJ ET
0.267 0.267 0.267 rg
205.004 189.346 141.176 0.750 re f
205.004 173.464 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 179.491 Td /F1 9.8 Tf  [(0.12)] TJ ET
0.267 0.267 0.267 rg
345.430 189.346 122.744 0.750 re f
345.430 173.464 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 179.491 Td /F1 9.8 Tf  [(0.12)] TJ ET
0.267 0.267 0.267 rg
467.424 189.346 113.451 0.750 re f
467.424 173.464 0.750 16.631 re f
580.125 173.464 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 179.491 Td /F1 9.8 Tf  [(0.12)] TJ ET
0.812 0.886 0.953 rg
27.000 157.958 178.379 15.881 re f
0.267 0.267 0.267 rg
26.625 173.464 179.129 0.750 re f
26.625 157.583 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 163.609 Td /F1 9.8 Tf  [(Fine motor ability)] TJ ET
0.812 0.886 0.953 rg
205.379 157.958 140.426 15.881 re f
0.267 0.267 0.267 rg
205.004 173.464 141.176 0.750 re f
205.004 157.583 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 163.609 Td /F1 9.8 Tf  [(0.66)] TJ ET
0.812 0.886 0.953 rg
345.805 157.958 121.994 15.881 re f
0.267 0.267 0.267 rg
345.430 173.464 122.744 0.750 re f
345.430 157.583 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 163.609 Td /F1 9.8 Tf  [(0.16)] TJ ET
0.812 0.886 0.953 rg
467.799 157.958 112.701 15.881 re f
0.267 0.267 0.267 rg
467.424 173.464 113.451 0.750 re f
467.424 157.583 0.750 16.631 re f
580.125 157.583 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 163.609 Td /F1 9.8 Tf  [(1.28)] TJ ET
0.812 0.886 0.953 rg
27.000 142.077 178.379 15.881 re f
0.267 0.267 0.267 rg
26.625 157.583 179.129 0.750 re f
26.625 141.702 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 147.728 Td /F1 9.8 Tf  [(Complex motor behavior)] TJ ET
0.812 0.886 0.953 rg
205.379 142.077 140.426 15.881 re f
0.267 0.267 0.267 rg
205.004 157.583 141.176 0.750 re f
205.004 141.702 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 147.728 Td /F1 9.8 Tf  [(0.50)] TJ ET
0.812 0.886 0.953 rg
345.805 142.077 121.994 15.881 re f
0.267 0.267 0.267 rg
345.430 157.583 122.744 0.750 re f
345.430 141.702 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 147.728 Td /F1 9.8 Tf  [(0.18)] TJ ET
0.812 0.886 0.953 rg
467.799 142.077 112.701 15.881 re f
0.267 0.267 0.267 rg
467.424 157.583 113.451 0.750 re f
467.424 141.702 0.750 16.631 re f
580.125 141.702 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 147.728 Td /F1 9.8 Tf  [(0.90)] TJ ET
0.812 0.886 0.953 rg
27.000 126.196 178.379 15.881 re f
0.267 0.267 0.267 rg
26.625 141.702 179.129 0.750 re f
26.625 125.821 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 131.847 Td /F1 9.8 Tf  [(Writing)] TJ ET
0.812 0.886 0.953 rg
205.379 126.196 140.426 15.881 re f
0.267 0.267 0.267 rg
205.004 141.702 141.176 0.750 re f
205.004 125.821 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 131.847 Td /F1 9.8 Tf  [(0.96)] TJ ET
0.812 0.886 0.953 rg
345.805 126.196 121.994 15.881 re f
0.267 0.267 0.267 rg
345.430 141.702 122.744 0.750 re f
345.430 125.821 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 131.847 Td /F1 9.8 Tf  [(0.49)] TJ ET
0.812 0.886 0.953 rg
467.799 126.196 112.701 15.881 re f
0.267 0.267 0.267 rg
467.424 141.702 113.451 0.750 re f
467.424 125.821 0.750 16.631 re f
580.125 125.821 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 131.847 Td /F1 9.8 Tf  [(1.55)] TJ ET
0.812 0.886 0.953 rg
27.000 110.314 178.379 15.881 re f
0.267 0.267 0.267 rg
26.625 125.821 179.129 0.750 re f
26.625 109.939 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 115.966 Td /F1 9.8 Tf  [(Clumsiness)] TJ ET
0.812 0.886 0.953 rg
205.379 110.314 140.426 15.881 re f
0.267 0.267 0.267 rg
205.004 125.821 141.176 0.750 re f
205.004 109.939 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 115.966 Td /F1 9.8 Tf  [(0.88)] TJ ET
0.812 0.886 0.953 rg
345.805 110.314 121.994 15.881 re f
0.267 0.267 0.267 rg
345.430 125.821 122.744 0.750 re f
345.430 109.939 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 115.966 Td /F1 9.8 Tf  [(0.55)] TJ ET
0.812 0.886 0.953 rg
467.799 110.314 112.701 15.881 re f
0.267 0.267 0.267 rg
467.424 125.821 113.451 0.750 re f
467.424 109.939 0.750 16.631 re f
580.125 109.939 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 115.966 Td /F1 9.8 Tf  [(1.29)] TJ ET
0.812 0.886 0.953 rg
27.000 94.433 178.379 15.881 re f
0.267 0.267 0.267 rg
26.625 109.939 179.129 0.750 re f
26.625 94.058 179.129 0.750 re f
26.625 94.058 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 100.084 Td /F1 9.8 Tf  [(Functional impact)] TJ ET
0.812 0.886 0.953 rg
205.379 94.433 140.426 15.881 re f
0.267 0.267 0.267 rg
205.004 109.939 141.176 0.750 re f
205.004 94.058 141.176 0.750 re f
205.004 94.058 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 100.084 Td /F1 9.8 Tf  [(0.80)] TJ ET
0.812 0.886 0.953 rg
345.805 94.433 121.994 15.881 re f
0.267 0.267 0.267 rg
345.430 109.939 122.744 0.750 re f
345.430 94.058 122.744 0.750 re f
345.430 94.058 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 100.084 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.812 0.886 0.953 rg
467.799 94.433 112.701 15.881 re f
0.267 0.267 0.267 rg
467.424 109.939 113.451 0.750 re f
467.424 94.058 113.451 0.750 re f
467.424 94.058 0.750 16.631 re f
580.125 94.058 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 100.084 Td /F1 9.8 Tf  [(1.24)] TJ ET
BT 26.250 46.659 Td /F1 9.8 Tf  [(It was agreed that these 7 interview questions would be modified accordingly for testing in subsequent iterations; examination of )] TJ ET
Q
q
15.000 32.374 577.500 744.626 re W n
0.965 0.965 0.965 rg
26.250 724.036 555.000 52.964 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 724.036 m 581.250 724.036 l 581.250 724.786 l 26.250 724.786 l  f
q
35.250 735.286 537.000 41.714 re W n
0.271 0.267 0.267 rg
BT 35.250 767.476 Td /F4 9.8 Tf  [(Fig. 2: OCCs and Frequency distribution for interview question assessing ability to perform tasks that require )] TJ ET
BT 35.250 755.571 Td /F4 9.8 Tf  [(balance on one foot for all participants, HD and prHD. Data is presented separately for symptom intensity \(left row\), )] TJ ET
BT 35.250 743.667 Td /F4 9.8 Tf  [(frequency \(middle row\), and composite \(right row\) scores.)] TJ ET
Q
BT 26.250 707.012 Td /F1 9.8 Tf  [(The mean total composite score with respect to the above 7 items was 2.55 in prHD subjects and 8.98 in HD subjects; the )] TJ ET
BT 26.250 695.107 Td /F1 9.8 Tf  [(difference in mean scores was statistically significant \( )] TJ ET
BT 262.493 695.107 Td /F5 9.8 Tf  [(p)] TJ ET
BT 267.913 695.107 Td /F1 9.8 Tf  [( < 0.001, Mann-Whitney U test\). In addition, significant differences were )] TJ ET
BT 26.250 683.202 Td /F1 9.8 Tf  [(noted in scoring between prHD and HD for each of the individual items, with greater intensity and frequency of symptoms noted )] TJ ET
BT 26.250 671.298 Td /F1 9.8 Tf  [(in early HD participants \( )] TJ ET
BT 135.694 671.298 Td /F5 9.8 Tf  [(p)] TJ ET
BT 141.115 671.298 Td /F1 9.8 Tf  [( < 0.001 with respect to each item, Mann-Whitney U test\) \(Table 4\). This is not surprising given that )] TJ ET
BT 26.250 659.393 Td /F1 9.8 Tf  [(the classification of prHD is defined as the absence of sufficient motor signs to meet conventional diagnostic criteria for manifest )] TJ ET
BT 26.250 647.488 Td /F1 9.8 Tf  [(disease. )] TJ ET
0.267 0.267 0.267 rg
BT 65.269 647.488 Td /F1 9.8 Tf  [([6])] TJ ET
0.271 0.267 0.267 rg
BT 76.112 647.488 Td /F1 9.8 Tf  [( For example, in assessing ability to perform tasks that require balance on one foot, scoring was driven primarily by )] TJ ET
BT 26.250 635.583 Td /F1 9.8 Tf  [(early HD participants \(Figure 2, Table 4\). In prHD, the option with the highest probably of being scored for symptom intensity )] TJ ET
BT 26.250 623.679 Td /F1 9.8 Tf  [(increased from �0� to �1� \(mild: sense of unsteadiness/imbalance on one foot that others may not notice, but no impact on )] TJ ET
BT 26.250 611.774 Td /F1 9.8 Tf  [(function of daily activities\) suggesting that although these changes are noticeable to the participant, the functional impact may )] TJ ET
BT 26.250 599.869 Td /F1 9.8 Tf  [(be minimal. By contrast, in early HD participants scores of �3� \(severe: needs support to maintain balance\) and �4� \(very severe: )] TJ ET
BT 26.250 587.964 Td /F1 9.8 Tf  [(cannot stand on one foot, must sit down to do things\) were sometimes endorsed. The poor discrimination between symptom )] TJ ET
BT 26.250 576.060 Td /F1 9.8 Tf  [(intensity scores of �3� and �4� indicates that modifications to the wording of these options would be needed to allow for better )] TJ ET
BT 26.250 564.155 Td /F1 9.8 Tf  [(discrimination.)] TJ ET
BT 26.250 544.750 Td /F4 9.8 Tf  [(Table 3. )] TJ ET
BT 65.269 544.750 Td /F1 9.8 Tf  [( Correlations between Interview Questions Scores)] TJ ET
1.000 1.000 1.000 rg
26.250 335.163 555.000 199.706 re f
0.267 0.267 0.267 rg
26.625 533.744 155.836 0.750 re f
26.625 510.232 0.750 24.262 re f
0.271 0.267 0.267 rg
BT 31.875 523.889 Td /F1 9.8 Tf  [(Item)] TJ ET
0.267 0.267 0.267 rg
181.711 533.744 133.555 0.750 re f
181.711 510.232 0.750 24.262 re f
0.271 0.267 0.267 rg
BT 186.961 523.889 Td /F1 9.8 Tf  [(Item-total correlation )] TJ ET
BT 186.961 516.258 Td /F1 9.8 Tf  [(\(all subjects\))] TJ ET
0.267 0.267 0.267 rg
314.515 533.744 133.555 0.750 re f
314.515 510.232 0.750 24.262 re f
0.271 0.267 0.267 rg
BT 319.765 523.889 Td /F1 9.8 Tf  [(Item-total correlation )] TJ ET
BT 319.765 516.258 Td /F1 9.8 Tf  [(\(prHD subjects\))] TJ ET
0.267 0.267 0.267 rg
447.320 533.744 133.555 0.750 re f
447.320 510.232 0.750 24.262 re f
580.125 510.232 0.750 24.262 re f
0.271 0.267 0.267 rg
BT 452.570 523.889 Td /F1 9.8 Tf  [(Item-total correlation )] TJ ET
BT 452.570 516.258 Td /F1 9.8 Tf  [(\(HD subjects\))] TJ ET
0.267 0.267 0.267 rg
26.625 510.232 155.836 0.750 re f
26.625 494.350 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 500.377 Td /F1 9.8 Tf  [(Reading)] TJ ET
0.267 0.267 0.267 rg
181.711 510.232 133.555 0.750 re f
181.711 494.350 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 500.377 Td /F1 9.8 Tf  [(0.389)] TJ ET
0.267 0.267 0.267 rg
314.515 510.232 133.555 0.750 re f
314.515 494.350 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 500.377 Td /F1 9.8 Tf  [(0.340)] TJ ET
0.267 0.267 0.267 rg
447.320 510.232 133.555 0.750 re f
447.320 494.350 0.750 16.631 re f
580.125 494.350 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 500.377 Td /F1 9.8 Tf  [(0.360)] TJ ET
0.267 0.267 0.267 rg
26.625 494.350 155.836 0.750 re f
26.625 478.469 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 484.495 Td /F1 9.8 Tf  [(Tracking while reading)] TJ ET
0.267 0.267 0.267 rg
181.711 494.350 133.555 0.750 re f
181.711 478.469 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 484.495 Td /F1 9.8 Tf  [(0.489)] TJ ET
0.267 0.267 0.267 rg
314.515 494.350 133.555 0.750 re f
314.515 478.469 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 484.495 Td /F1 9.8 Tf  [(0.202)] TJ ET
0.267 0.267 0.267 rg
447.320 494.350 133.555 0.750 re f
447.320 478.469 0.750 16.631 re f
580.125 478.469 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 484.495 Td /F1 9.8 Tf  [(0.639)] TJ ET
0.267 0.267 0.267 rg
26.625 478.469 155.836 0.750 re f
26.625 462.588 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 468.614 Td /F1 9.8 Tf  [(Tracking objects with eyes)] TJ ET
0.267 0.267 0.267 rg
181.711 478.469 133.555 0.750 re f
181.711 462.588 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 468.614 Td /F1 9.8 Tf  [(0.169)] TJ ET
0.267 0.267 0.267 rg
314.515 478.469 133.555 0.750 re f
314.515 462.588 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 468.614 Td /F1 9.8 Tf  [(0.373)] TJ ET
0.267 0.267 0.267 rg
447.320 478.469 133.555 0.750 re f
447.320 462.588 0.750 16.631 re f
580.125 462.588 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 468.614 Td /F1 9.8 Tf  [(0.190)] TJ ET
0.812 0.886 0.953 rg
27.000 447.082 155.086 15.881 re f
0.267 0.267 0.267 rg
26.625 462.588 155.836 0.750 re f
26.625 446.707 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 452.733 Td /F1 9.8 Tf  [(Balance on one foot)] TJ ET
0.812 0.886 0.953 rg
182.086 447.082 132.805 15.881 re f
0.267 0.267 0.267 rg
181.711 462.588 133.555 0.750 re f
181.711 446.707 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 452.733 Td /F1 9.8 Tf  [(0.758)] TJ ET
0.812 0.886 0.953 rg
314.890 447.082 132.805 15.881 re f
0.267 0.267 0.267 rg
314.515 462.588 133.555 0.750 re f
314.515 446.707 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 452.733 Td /F1 9.8 Tf  [(0.785)] TJ ET
0.812 0.886 0.953 rg
447.695 447.082 132.805 15.881 re f
0.267 0.267 0.267 rg
447.320 462.588 133.555 0.750 re f
447.320 446.707 0.750 16.631 re f
580.125 446.707 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 452.733 Td /F1 9.8 Tf  [(0.690)] TJ ET
0.812 0.886 0.953 rg
27.000 431.200 155.086 15.881 re f
0.267 0.267 0.267 rg
26.625 446.707 155.836 0.750 re f
26.625 430.825 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 436.852 Td /F1 9.8 Tf  [(Balance when walking)] TJ ET
0.812 0.886 0.953 rg
182.086 431.200 132.805 15.881 re f
0.267 0.267 0.267 rg
181.711 446.707 133.555 0.750 re f
181.711 430.825 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 436.852 Td /F1 9.8 Tf  [(0.858)] TJ ET
0.812 0.886 0.953 rg
314.890 431.200 132.805 15.881 re f
0.267 0.267 0.267 rg
314.515 446.707 133.555 0.750 re f
314.515 430.825 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 436.852 Td /F1 9.8 Tf  [(0.817)] TJ ET
0.812 0.886 0.953 rg
447.695 431.200 132.805 15.881 re f
0.267 0.267 0.267 rg
447.320 446.707 133.555 0.750 re f
447.320 430.825 0.750 16.631 re f
580.125 430.825 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 436.852 Td /F1 9.8 Tf  [(0.857)] TJ ET
0.267 0.267 0.267 rg
26.625 430.825 155.836 0.750 re f
26.625 414.944 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 420.970 Td /F1 9.8 Tf  [(Shifting gaze)] TJ ET
0.267 0.267 0.267 rg
181.711 430.825 133.555 0.750 re f
181.711 414.944 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 420.970 Td /F1 9.8 Tf  [(0.289)] TJ ET
0.267 0.267 0.267 rg
314.515 430.825 133.555 0.750 re f
314.515 414.944 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 420.970 Td /F1 9.8 Tf  [(0.333)] TJ ET
0.267 0.267 0.267 rg
447.320 430.825 133.555 0.750 re f
447.320 414.944 0.750 16.631 re f
580.125 414.944 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 420.970 Td /F1 9.8 Tf  [(0.349)] TJ ET
0.812 0.886 0.953 rg
27.000 399.438 155.086 15.881 re f
0.267 0.267 0.267 rg
26.625 414.944 155.836 0.750 re f
26.625 399.063 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 405.089 Td /F1 9.8 Tf  [(Fine motor ability)] TJ ET
0.812 0.886 0.953 rg
182.086 399.438 132.805 15.881 re f
0.267 0.267 0.267 rg
181.711 414.944 133.555 0.750 re f
181.711 399.063 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 405.089 Td /F1 9.8 Tf  [(0.718)] TJ ET
0.812 0.886 0.953 rg
314.890 399.438 132.805 15.881 re f
0.267 0.267 0.267 rg
314.515 414.944 133.555 0.750 re f
314.515 399.063 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 405.089 Td /F1 9.8 Tf  [(0.257)] TJ ET
0.812 0.886 0.953 rg
447.695 399.438 132.805 15.881 re f
0.267 0.267 0.267 rg
447.320 414.944 133.555 0.750 re f
447.320 399.063 0.750 16.631 re f
580.125 399.063 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 405.089 Td /F1 9.8 Tf  [(0.774)] TJ ET
0.812 0.886 0.953 rg
27.000 383.557 155.086 15.881 re f
0.267 0.267 0.267 rg
26.625 399.063 155.836 0.750 re f
26.625 383.182 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 389.208 Td /F1 9.8 Tf  [(Complex motor behavior)] TJ ET
0.812 0.886 0.953 rg
182.086 383.557 132.805 15.881 re f
0.267 0.267 0.267 rg
181.711 399.063 133.555 0.750 re f
181.711 383.182 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 389.208 Td /F1 9.8 Tf  [(0.722)] TJ ET
0.812 0.886 0.953 rg
314.890 383.557 132.805 15.881 re f
0.267 0.267 0.267 rg
314.515 399.063 133.555 0.750 re f
314.515 383.182 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 389.208 Td /F1 9.8 Tf  [(0.532)] TJ ET
0.812 0.886 0.953 rg
447.695 383.557 132.805 15.881 re f
0.267 0.267 0.267 rg
447.320 399.063 133.555 0.750 re f
447.320 383.182 0.750 16.631 re f
580.125 383.182 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 389.208 Td /F1 9.8 Tf  [(0.733)] TJ ET
0.812 0.886 0.953 rg
27.000 367.675 155.086 15.881 re f
0.267 0.267 0.267 rg
26.625 383.182 155.836 0.750 re f
26.625 367.300 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 373.327 Td /F1 9.8 Tf  [(Writing)] TJ ET
0.812 0.886 0.953 rg
182.086 367.675 132.805 15.881 re f
0.267 0.267 0.267 rg
181.711 383.182 133.555 0.750 re f
181.711 367.300 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 373.327 Td /F1 9.8 Tf  [(0.820)] TJ ET
0.812 0.886 0.953 rg
314.890 367.675 132.805 15.881 re f
0.267 0.267 0.267 rg
314.515 383.182 133.555 0.750 re f
314.515 367.300 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 373.327 Td /F1 9.8 Tf  [(0.805)] TJ ET
0.812 0.886 0.953 rg
447.695 367.675 132.805 15.881 re f
0.267 0.267 0.267 rg
447.320 383.182 133.555 0.750 re f
447.320 367.300 0.750 16.631 re f
580.125 367.300 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 373.327 Td /F1 9.8 Tf  [(0.776)] TJ ET
0.812 0.886 0.953 rg
27.000 351.794 155.086 15.881 re f
0.267 0.267 0.267 rg
26.625 367.300 155.836 0.750 re f
26.625 351.419 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 357.445 Td /F1 9.8 Tf  [(Clumsiness)] TJ ET
0.812 0.886 0.953 rg
182.086 351.794 132.805 15.881 re f
0.267 0.267 0.267 rg
181.711 367.300 133.555 0.750 re f
181.711 351.419 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 357.445 Td /F1 9.8 Tf  [(0.795)] TJ ET
0.812 0.886 0.953 rg
314.890 351.794 132.805 15.881 re f
0.267 0.267 0.267 rg
314.515 367.300 133.555 0.750 re f
314.515 351.419 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 357.445 Td /F1 9.8 Tf  [(0.744)] TJ ET
0.812 0.886 0.953 rg
447.695 351.794 132.805 15.881 re f
0.267 0.267 0.267 rg
447.320 367.300 133.555 0.750 re f
447.320 351.419 0.750 16.631 re f
580.125 351.419 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 357.445 Td /F1 9.8 Tf  [(0.774)] TJ ET
0.812 0.886 0.953 rg
27.000 335.913 155.086 15.881 re f
0.267 0.267 0.267 rg
26.625 351.419 155.836 0.750 re f
26.625 335.538 155.836 0.750 re f
26.625 335.538 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 341.564 Td /F1 9.8 Tf  [(Functional impact)] TJ ET
0.812 0.886 0.953 rg
182.086 335.913 132.805 15.881 re f
0.267 0.267 0.267 rg
181.711 351.419 133.555 0.750 re f
181.711 335.538 133.555 0.750 re f
181.711 335.538 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 186.961 341.564 Td /F1 9.8 Tf  [(0.858)] TJ ET
0.812 0.886 0.953 rg
314.890 335.913 132.805 15.881 re f
0.267 0.267 0.267 rg
314.515 351.419 133.555 0.750 re f
314.515 335.538 133.555 0.750 re f
314.515 335.538 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.765 341.564 Td /F1 9.8 Tf  [(0.902)] TJ ET
0.812 0.886 0.953 rg
447.695 335.913 132.805 15.881 re f
0.267 0.267 0.267 rg
447.320 351.419 133.555 0.750 re f
447.320 335.538 133.555 0.750 re f
447.320 335.538 0.750 16.631 re f
580.125 335.538 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 452.570 341.564 Td /F1 9.8 Tf  [(0.828)] TJ ET
BT 26.250 288.139 Td /F4 9.8 Tf  [(Table 4. )] TJ ET
BT 65.269 288.139 Td /F1 9.8 Tf  [(Summary of Mean Composite Scores)] TJ ET
1.000 1.000 1.000 rg
26.250 93.683 555.000 192.075 re f
0.267 0.267 0.267 rg
26.625 284.633 179.129 0.750 re f
26.625 268.752 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 274.778 Td /F4 9.8 Tf  [(Item)] TJ ET
0.267 0.267 0.267 rg
205.004 284.633 141.176 0.750 re f
205.004 268.752 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 274.778 Td /F4 9.8 Tf  [(Overall mean score)] TJ ET
0.267 0.267 0.267 rg
345.430 284.633 122.744 0.750 re f
345.430 268.752 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 274.778 Td /F4 9.8 Tf  [(prHD mean score)] TJ ET
0.267 0.267 0.267 rg
467.424 284.633 113.451 0.750 re f
467.424 268.752 0.750 16.631 re f
580.125 268.752 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 274.778 Td /F4 9.8 Tf  [(HD mean score)] TJ ET
0.267 0.267 0.267 rg
26.625 268.752 179.129 0.750 re f
26.625 252.871 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 258.897 Td /F1 9.8 Tf  [(Reading)] TJ ET
0.267 0.267 0.267 rg
205.004 268.752 141.176 0.750 re f
205.004 252.871 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 258.897 Td /F1 9.8 Tf  [(0.33)] TJ ET
0.267 0.267 0.267 rg
345.430 268.752 122.744 0.750 re f
345.430 252.871 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 258.897 Td /F1 9.8 Tf  [(0.21)] TJ ET
0.267 0.267 0.267 rg
467.424 268.752 113.451 0.750 re f
467.424 252.871 0.750 16.631 re f
580.125 252.871 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 258.897 Td /F1 9.8 Tf  [(0.48)] TJ ET
0.267 0.267 0.267 rg
26.625 252.871 179.129 0.750 re f
26.625 236.989 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 243.016 Td /F1 9.8 Tf  [(Tracking while reading)] TJ ET
0.267 0.267 0.267 rg
205.004 252.871 141.176 0.750 re f
205.004 236.989 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 243.016 Td /F1 9.8 Tf  [(0.29)] TJ ET
0.267 0.267 0.267 rg
345.430 252.871 122.744 0.750 re f
345.430 236.989 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 243.016 Td /F1 9.8 Tf  [(0.22)] TJ ET
0.267 0.267 0.267 rg
467.424 252.871 113.451 0.750 re f
467.424 236.989 0.750 16.631 re f
580.125 236.989 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 243.016 Td /F1 9.8 Tf  [(0.37)] TJ ET
0.267 0.267 0.267 rg
26.625 236.989 179.129 0.750 re f
26.625 221.108 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 227.134 Td /F1 9.8 Tf  [(Tracking objects with eyes)] TJ ET
0.267 0.267 0.267 rg
205.004 236.989 141.176 0.750 re f
205.004 221.108 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 227.134 Td /F1 9.8 Tf  [(0.08)] TJ ET
0.267 0.267 0.267 rg
345.430 236.989 122.744 0.750 re f
345.430 221.108 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 227.134 Td /F1 9.8 Tf  [(0.11)] TJ ET
0.267 0.267 0.267 rg
467.424 236.989 113.451 0.750 re f
467.424 221.108 0.750 16.631 re f
580.125 221.108 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 227.134 Td /F1 9.8 Tf  [(0.03)] TJ ET
0.812 0.886 0.953 rg
27.000 205.602 178.379 15.881 re f
0.267 0.267 0.267 rg
26.625 221.108 179.129 0.750 re f
26.625 205.227 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 211.253 Td /F1 9.8 Tf  [(Balance on one foot)] TJ ET
0.812 0.886 0.953 rg
205.379 205.602 140.426 15.881 re f
0.267 0.267 0.267 rg
205.004 221.108 141.176 0.750 re f
205.004 205.227 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 211.253 Td /F1 9.8 Tf  [(0.98)] TJ ET
0.812 0.886 0.953 rg
345.805 205.602 121.994 15.881 re f
0.267 0.267 0.267 rg
345.430 221.108 122.744 0.750 re f
345.430 205.227 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 211.253 Td /F1 9.8 Tf  [(0.51)] TJ ET
0.812 0.886 0.953 rg
467.799 205.602 112.701 15.881 re f
0.267 0.267 0.267 rg
467.424 221.108 113.451 0.750 re f
467.424 205.227 0.750 16.631 re f
580.125 205.227 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 211.253 Td /F1 9.8 Tf  [(1.56)] TJ ET
0.812 0.886 0.953 rg
27.000 189.721 178.379 15.881 re f
0.267 0.267 0.267 rg
26.625 205.227 179.129 0.750 re f
26.625 189.346 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 195.372 Td /F1 9.8 Tf  [(Balance when walking)] TJ ET
0.812 0.886 0.953 rg
205.379 189.721 140.426 15.881 re f
0.267 0.267 0.267 rg
205.004 205.227 141.176 0.750 re f
205.004 189.346 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 195.372 Td /F1 9.8 Tf  [(0.76)] TJ ET
0.812 0.886 0.953 rg
345.805 189.721 121.994 15.881 re f
0.267 0.267 0.267 rg
345.430 205.227 122.744 0.750 re f
345.430 189.346 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 195.372 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.812 0.886 0.953 rg
467.799 189.721 112.701 15.881 re f
0.267 0.267 0.267 rg
467.424 205.227 113.451 0.750 re f
467.424 189.346 0.750 16.631 re f
580.125 189.346 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 195.372 Td /F1 9.8 Tf  [(1.17)] TJ ET
0.267 0.267 0.267 rg
26.625 189.346 179.129 0.750 re f
26.625 173.464 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 179.491 Td /F1 9.8 Tf  [(Shifting gaze)] TJ ET
0.267 0.267 0.267 rg
205.004 189.346 141.176 0.750 re f
205.004 173.464 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 179.491 Td /F1 9.8 Tf  [(0.12)] TJ ET
0.267 0.267 0.267 rg
345.430 189.346 122.744 0.750 re f
345.430 173.464 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 179.491 Td /F1 9.8 Tf  [(0.12)] TJ ET
0.267 0.267 0.267 rg
467.424 189.346 113.451 0.750 re f
467.424 173.464 0.750 16.631 re f
580.125 173.464 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 179.491 Td /F1 9.8 Tf  [(0.12)] TJ ET
0.812 0.886 0.953 rg
27.000 157.958 178.379 15.881 re f
0.267 0.267 0.267 rg
26.625 173.464 179.129 0.750 re f
26.625 157.583 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 163.609 Td /F1 9.8 Tf  [(Fine motor ability)] TJ ET
0.812 0.886 0.953 rg
205.379 157.958 140.426 15.881 re f
0.267 0.267 0.267 rg
205.004 173.464 141.176 0.750 re f
205.004 157.583 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 163.609 Td /F1 9.8 Tf  [(0.66)] TJ ET
0.812 0.886 0.953 rg
345.805 157.958 121.994 15.881 re f
0.267 0.267 0.267 rg
345.430 173.464 122.744 0.750 re f
345.430 157.583 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 163.609 Td /F1 9.8 Tf  [(0.16)] TJ ET
0.812 0.886 0.953 rg
467.799 157.958 112.701 15.881 re f
0.267 0.267 0.267 rg
467.424 173.464 113.451 0.750 re f
467.424 157.583 0.750 16.631 re f
580.125 157.583 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 163.609 Td /F1 9.8 Tf  [(1.28)] TJ ET
0.812 0.886 0.953 rg
27.000 142.077 178.379 15.881 re f
0.267 0.267 0.267 rg
26.625 157.583 179.129 0.750 re f
26.625 141.702 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 147.728 Td /F1 9.8 Tf  [(Complex motor behavior)] TJ ET
0.812 0.886 0.953 rg
205.379 142.077 140.426 15.881 re f
0.267 0.267 0.267 rg
205.004 157.583 141.176 0.750 re f
205.004 141.702 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 147.728 Td /F1 9.8 Tf  [(0.50)] TJ ET
0.812 0.886 0.953 rg
345.805 142.077 121.994 15.881 re f
0.267 0.267 0.267 rg
345.430 157.583 122.744 0.750 re f
345.430 141.702 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 147.728 Td /F1 9.8 Tf  [(0.18)] TJ ET
0.812 0.886 0.953 rg
467.799 142.077 112.701 15.881 re f
0.267 0.267 0.267 rg
467.424 157.583 113.451 0.750 re f
467.424 141.702 0.750 16.631 re f
580.125 141.702 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 147.728 Td /F1 9.8 Tf  [(0.90)] TJ ET
0.812 0.886 0.953 rg
27.000 126.196 178.379 15.881 re f
0.267 0.267 0.267 rg
26.625 141.702 179.129 0.750 re f
26.625 125.821 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 131.847 Td /F1 9.8 Tf  [(Writing)] TJ ET
0.812 0.886 0.953 rg
205.379 126.196 140.426 15.881 re f
0.267 0.267 0.267 rg
205.004 141.702 141.176 0.750 re f
205.004 125.821 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 131.847 Td /F1 9.8 Tf  [(0.96)] TJ ET
0.812 0.886 0.953 rg
345.805 126.196 121.994 15.881 re f
0.267 0.267 0.267 rg
345.430 141.702 122.744 0.750 re f
345.430 125.821 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 131.847 Td /F1 9.8 Tf  [(0.49)] TJ ET
0.812 0.886 0.953 rg
467.799 126.196 112.701 15.881 re f
0.267 0.267 0.267 rg
467.424 141.702 113.451 0.750 re f
467.424 125.821 0.750 16.631 re f
580.125 125.821 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 131.847 Td /F1 9.8 Tf  [(1.55)] TJ ET
0.812 0.886 0.953 rg
27.000 110.314 178.379 15.881 re f
0.267 0.267 0.267 rg
26.625 125.821 179.129 0.750 re f
26.625 109.939 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 115.966 Td /F1 9.8 Tf  [(Clumsiness)] TJ ET
0.812 0.886 0.953 rg
205.379 110.314 140.426 15.881 re f
0.267 0.267 0.267 rg
205.004 125.821 141.176 0.750 re f
205.004 109.939 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 115.966 Td /F1 9.8 Tf  [(0.88)] TJ ET
0.812 0.886 0.953 rg
345.805 110.314 121.994 15.881 re f
0.267 0.267 0.267 rg
345.430 125.821 122.744 0.750 re f
345.430 109.939 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 115.966 Td /F1 9.8 Tf  [(0.55)] TJ ET
0.812 0.886 0.953 rg
467.799 110.314 112.701 15.881 re f
0.267 0.267 0.267 rg
467.424 125.821 113.451 0.750 re f
467.424 109.939 0.750 16.631 re f
580.125 109.939 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 115.966 Td /F1 9.8 Tf  [(1.29)] TJ ET
0.812 0.886 0.953 rg
27.000 94.433 178.379 15.881 re f
0.267 0.267 0.267 rg
26.625 109.939 179.129 0.750 re f
26.625 94.058 179.129 0.750 re f
26.625 94.058 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 100.084 Td /F1 9.8 Tf  [(Functional impact)] TJ ET
0.812 0.886 0.953 rg
205.379 94.433 140.426 15.881 re f
0.267 0.267 0.267 rg
205.004 109.939 141.176 0.750 re f
205.004 94.058 141.176 0.750 re f
205.004 94.058 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.254 100.084 Td /F1 9.8 Tf  [(0.80)] TJ ET
0.812 0.886 0.953 rg
345.805 94.433 121.994 15.881 re f
0.267 0.267 0.267 rg
345.430 109.939 122.744 0.750 re f
345.430 94.058 122.744 0.750 re f
345.430 94.058 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 350.680 100.084 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.812 0.886 0.953 rg
467.799 94.433 112.701 15.881 re f
0.267 0.267 0.267 rg
467.424 109.939 113.451 0.750 re f
467.424 94.058 113.451 0.750 re f
467.424 94.058 0.750 16.631 re f
580.125 94.058 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 472.674 100.084 Td /F1 9.8 Tf  [(1.24)] TJ ET
BT 26.250 46.659 Td /F1 9.8 Tf  [(It was agreed that these 7 interview questions would be modified accordingly for testing in subsequent iterations; examination of )] TJ ET
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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

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BT 26.250 767.476 Td /F1 9.8 Tf  [(the OCCs provided data on which modifications should be made to improve item performance, including changes in wording )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(and scoring options.)] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(The remaining 4 questions were very rarely endorsed \(see Table 4, non-shaded items\), and a score of zero had the highest )] TJ ET
BT 26.250 724.262 Td /F1 9.8 Tf  [(probability of being scored across most of the range of severity \(Figure 3, as example\):)] TJ ET
BT 26.250 704.857 Td /F1 9.8 Tf  [(? Reading)] TJ ET
BT 26.250 685.452 Td /F1 9.8 Tf  [(? Tracking while reading)] TJ ET
BT 26.250 666.048 Td /F1 9.8 Tf  [(? Tracking moving objects with eyes)] TJ ET
BT 26.250 646.643 Td /F1 9.8 Tf  [(? Shifting gaze)] TJ ET
BT 26.250 627.238 Td /F1 9.8 Tf  [(The low frequency of response \(Table 4\) and generally poor discriminative properties \(Figure 3\) limit the usefulness of these )] TJ ET
BT 26.250 615.333 Td /F1 9.8 Tf  [(interview questions for assessing motor manifestations in prHD and early HD. In general, the correlations between each of )] TJ ET
BT 26.250 603.429 Td /F1 9.8 Tf  [(these 4 individual item composite scores and the total score from the 7 highly-endorsed items were low; �Tracking while )] TJ ET
BT 26.250 591.524 Td /F1 9.8 Tf  [(reading� correlated highly with the motor subscale score in the subset of HD subjects \(Table 3\), but was nonetheless rarely )] TJ ET
BT 26.250 579.619 Td /F1 9.8 Tf  [(endorsed \(Table 4\).)] TJ ET
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BT 35.250 375.714 Td /F4 9.8 Tf  [(Fig. 3: OCCs and frequency distribution of a representative rarely endorsed interview question \(assessing ability to )] TJ ET
BT 35.250 363.810 Td /F4 9.8 Tf  [(track while reading\) for all participants, HD and prHD. Data is presented separately for symptom intensity \(left row\), )] TJ ET
BT 35.250 351.905 Td /F4 9.8 Tf  [(frequency \(middle row\), and composite \(right row\) scores.)] TJ ET
Q
BT 26.250 315.250 Td /F1 9.8 Tf  [(It was agreed that these 4 interview questions should be removed from subsequent iterations on the basis of Relevance )] TJ ET
BT 26.250 303.345 Td /F1 9.8 Tf  [(\(Reported as not relevant by a large segment of the population of interest\) and Response Range \(A high percentage of patients )] TJ ET
BT 26.250 291.441 Td /F1 9.8 Tf  [(respond at the floor\) as outlined in Table 1 of the )] TJ ET
0.267 0.267 0.267 rg
BT 238.702 291.441 Td /F1 9.8 Tf  [(FDA PRO Guidance)] TJ ET
0.271 0.267 0.267 rg
BT 326.482 291.441 Td /F1 9.8 Tf  [(. )] TJ ET
0.267 0.267 0.267 rg
BT 331.903 291.441 Td /F1 9.8 Tf  [([3])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 254.838 Td /F4 12.0 Tf  [(Discussion)] TJ ET
BT 26.250 234.884 Td /F1 9.8 Tf  [(As part of FuRST-pHD, interview questions are being developed to assess symptoms and functional ability in prodromal and )] TJ ET
BT 26.250 222.979 Td /F1 9.8 Tf  [(early HD gene expansion carriers. We report here the development and beta testing of first iteration interview questions )] TJ ET
BT 26.250 211.074 Td /F1 9.8 Tf  [(designed to assess motor-related changes and functional impact.)] TJ ET
BT 26.250 191.670 Td /F1 9.8 Tf  [(These data suggest that although UHDRS motor signs may indeed be present \(see Table 1\), the functional impact of some of )] TJ ET
BT 26.250 179.765 Td /F1 9.8 Tf  [(these motor signs may be minimal in prHD and early HD. For example, ocular pursuit dysfunction is associated with difficulty in )] TJ ET
BT 26.250 167.860 Td /F1 9.8 Tf  [(visually tracking or following objects, as well as problems with reading, including loss of place and repetition \()] TJ ET
0.267 0.267 0.267 rg
BT 495.508 167.860 Td /F1 9.8 Tf  [(COVD, 2009)] TJ ET
0.271 0.267 0.267 rg
BT 550.780 167.860 Td /F1 9.8 Tf  [(\). In )] TJ ET
BT 26.250 155.955 Td /F1 9.8 Tf  [(the present study, however, very few participants reported related problems \(i.e., tracking while reading, tracking moving )] TJ ET
BT 26.250 144.051 Td /F1 9.8 Tf  [(objects, and shifting gaze, see Figure 3, Table 4\) despite the presence of significant deficits in ocular pursuit and saccades in )] TJ ET
BT 26.250 132.146 Td /F1 9.8 Tf  [(prodromal and early stages of HD. )] TJ ET
0.267 0.267 0.267 rg
BT 177.434 132.146 Td /F1 9.8 Tf  [([2] [7] [8])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 112.741 Td /F1 9.8 Tf  [(On the other hand, although the presence of some UHDRS motor signs may have minimal impact in the populations tested \(i.e., )] TJ ET
BT 26.250 100.836 Td /F1 9.8 Tf  [(ocular pursuit and saccades\), other motor signs may indeed be associated with symptoms that can be perceived and may )] TJ ET
BT 26.250 88.932 Td /F1 9.8 Tf  [(interfere with day-to-day functioning. For example, problems in the ability to perform tasks that require balance on one foot \(see )] TJ ET
BT 26.250 77.027 Td /F1 9.8 Tf  [(Figure 2, Table 4\) may reflect the presence of motor signs assessed in the UHDRS such as Bradykinesia, Dystonia, Chorea, )] TJ ET
BT 26.250 65.122 Td /F1 9.8 Tf  [(Gait, Tandem Walking, and/or Retopulsion. Indeed, as the severity of these UHDRS motor signs increase from prHD to HD so )] TJ ET
BT 26.250 53.217 Td /F1 9.8 Tf  [(did the severity of symptoms that assessed the potential functional impact of these signs. It is also important to note that many )] TJ ET
BT 26.250 41.313 Td /F1 9.8 Tf  [(symptoms reported as problems in prHD by focus groups, including losing balance, hand writing, gait, fine motor, hand-eye )] TJ ET
Q
q
15.000 27.027 577.500 749.973 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(the OCCs provided data on which modifications should be made to improve item performance, including changes in wording )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(and scoring options.)] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(The remaining 4 questions were very rarely endorsed \(see Table 4, non-shaded items\), and a score of zero had the highest )] TJ ET
BT 26.250 724.262 Td /F1 9.8 Tf  [(probability of being scored across most of the range of severity \(Figure 3, as example\):)] TJ ET
BT 26.250 704.857 Td /F1 9.8 Tf  [(? Reading)] TJ ET
BT 26.250 685.452 Td /F1 9.8 Tf  [(? Tracking while reading)] TJ ET
BT 26.250 666.048 Td /F1 9.8 Tf  [(? Tracking moving objects with eyes)] TJ ET
BT 26.250 646.643 Td /F1 9.8 Tf  [(? Shifting gaze)] TJ ET
BT 26.250 627.238 Td /F1 9.8 Tf  [(The low frequency of response \(Table 4\) and generally poor discriminative properties \(Figure 3\) limit the usefulness of these )] TJ ET
BT 26.250 615.333 Td /F1 9.8 Tf  [(interview questions for assessing motor manifestations in prHD and early HD. In general, the correlations between each of )] TJ ET
BT 26.250 603.429 Td /F1 9.8 Tf  [(these 4 individual item composite scores and the total score from the 7 highly-endorsed items were low; �Tracking while )] TJ ET
BT 26.250 591.524 Td /F1 9.8 Tf  [(reading� correlated highly with the motor subscale score in the subset of HD subjects \(Table 3\), but was nonetheless rarely )] TJ ET
BT 26.250 579.619 Td /F1 9.8 Tf  [(endorsed \(Table 4\).)] TJ ET
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26.250 332.274 555.000 237.464 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
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0.271 0.267 0.267 rg
BT 35.250 375.714 Td /F4 9.8 Tf  [(Fig. 3: OCCs and frequency distribution of a representative rarely endorsed interview question \(assessing ability to )] TJ ET
BT 35.250 363.810 Td /F4 9.8 Tf  [(track while reading\) for all participants, HD and prHD. Data is presented separately for symptom intensity \(left row\), )] TJ ET
BT 35.250 351.905 Td /F4 9.8 Tf  [(frequency \(middle row\), and composite \(right row\) scores.)] TJ ET
Q
BT 26.250 315.250 Td /F1 9.8 Tf  [(It was agreed that these 4 interview questions should be removed from subsequent iterations on the basis of Relevance )] TJ ET
BT 26.250 303.345 Td /F1 9.8 Tf  [(\(Reported as not relevant by a large segment of the population of interest\) and Response Range \(A high percentage of patients )] TJ ET
BT 26.250 291.441 Td /F1 9.8 Tf  [(respond at the floor\) as outlined in Table 1 of the )] TJ ET
0.267 0.267 0.267 rg
BT 238.702 291.441 Td /F1 9.8 Tf  [(FDA PRO Guidance)] TJ ET
0.271 0.267 0.267 rg
BT 326.482 291.441 Td /F1 9.8 Tf  [(. )] TJ ET
0.267 0.267 0.267 rg
BT 331.903 291.441 Td /F1 9.8 Tf  [([3])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 254.838 Td /F4 12.0 Tf  [(Discussion)] TJ ET
BT 26.250 234.884 Td /F1 9.8 Tf  [(As part of FuRST-pHD, interview questions are being developed to assess symptoms and functional ability in prodromal and )] TJ ET
BT 26.250 222.979 Td /F1 9.8 Tf  [(early HD gene expansion carriers. We report here the development and beta testing of first iteration interview questions )] TJ ET
BT 26.250 211.074 Td /F1 9.8 Tf  [(designed to assess motor-related changes and functional impact.)] TJ ET
BT 26.250 191.670 Td /F1 9.8 Tf  [(These data suggest that although UHDRS motor signs may indeed be present \(see Table 1\), the functional impact of some of )] TJ ET
BT 26.250 179.765 Td /F1 9.8 Tf  [(these motor signs may be minimal in prHD and early HD. For example, ocular pursuit dysfunction is associated with difficulty in )] TJ ET
BT 26.250 167.860 Td /F1 9.8 Tf  [(visually tracking or following objects, as well as problems with reading, including loss of place and repetition \()] TJ ET
0.267 0.267 0.267 rg
BT 495.508 167.860 Td /F1 9.8 Tf  [(COVD, 2009)] TJ ET
0.271 0.267 0.267 rg
BT 550.780 167.860 Td /F1 9.8 Tf  [(\). In )] TJ ET
BT 26.250 155.955 Td /F1 9.8 Tf  [(the present study, however, very few participants reported related problems \(i.e., tracking while reading, tracking moving )] TJ ET
BT 26.250 144.051 Td /F1 9.8 Tf  [(objects, and shifting gaze, see Figure 3, Table 4\) despite the presence of significant deficits in ocular pursuit and saccades in )] TJ ET
BT 26.250 132.146 Td /F1 9.8 Tf  [(prodromal and early stages of HD. )] TJ ET
0.267 0.267 0.267 rg
BT 177.434 132.146 Td /F1 9.8 Tf  [([2] [7] [8])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 112.741 Td /F1 9.8 Tf  [(On the other hand, although the presence of some UHDRS motor signs may have minimal impact in the populations tested \(i.e., )] TJ ET
BT 26.250 100.836 Td /F1 9.8 Tf  [(ocular pursuit and saccades\), other motor signs may indeed be associated with symptoms that can be perceived and may )] TJ ET
BT 26.250 88.932 Td /F1 9.8 Tf  [(interfere with day-to-day functioning. For example, problems in the ability to perform tasks that require balance on one foot \(see )] TJ ET
BT 26.250 77.027 Td /F1 9.8 Tf  [(Figure 2, Table 4\) may reflect the presence of motor signs assessed in the UHDRS such as Bradykinesia, Dystonia, Chorea, )] TJ ET
BT 26.250 65.122 Td /F1 9.8 Tf  [(Gait, Tandem Walking, and/or Retopulsion. Indeed, as the severity of these UHDRS motor signs increase from prHD to HD so )] TJ ET
BT 26.250 53.217 Td /F1 9.8 Tf  [(did the severity of symptoms that assessed the potential functional impact of these signs. It is also important to note that many )] TJ ET
BT 26.250 41.313 Td /F1 9.8 Tf  [(symptoms reported as problems in prHD by focus groups, including losing balance, hand writing, gait, fine motor, hand-eye )] TJ ET
Q
q
15.000 27.027 577.500 749.973 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(the OCCs provided data on which modifications should be made to improve item performance, including changes in wording )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(and scoring options.)] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(The remaining 4 questions were very rarely endorsed \(see Table 4, non-shaded items\), and a score of zero had the highest )] TJ ET
BT 26.250 724.262 Td /F1 9.8 Tf  [(probability of being scored across most of the range of severity \(Figure 3, as example\):)] TJ ET
BT 26.250 704.857 Td /F1 9.8 Tf  [(? Reading)] TJ ET
BT 26.250 685.452 Td /F1 9.8 Tf  [(? Tracking while reading)] TJ ET
BT 26.250 666.048 Td /F1 9.8 Tf  [(? Tracking moving objects with eyes)] TJ ET
BT 26.250 646.643 Td /F1 9.8 Tf  [(? Shifting gaze)] TJ ET
BT 26.250 627.238 Td /F1 9.8 Tf  [(The low frequency of response \(Table 4\) and generally poor discriminative properties \(Figure 3\) limit the usefulness of these )] TJ ET
BT 26.250 615.333 Td /F1 9.8 Tf  [(interview questions for assessing motor manifestations in prHD and early HD. In general, the correlations between each of )] TJ ET
BT 26.250 603.429 Td /F1 9.8 Tf  [(these 4 individual item composite scores and the total score from the 7 highly-endorsed items were low; �Tracking while )] TJ ET
BT 26.250 591.524 Td /F1 9.8 Tf  [(reading� correlated highly with the motor subscale score in the subset of HD subjects \(Table 3\), but was nonetheless rarely )] TJ ET
BT 26.250 579.619 Td /F1 9.8 Tf  [(endorsed \(Table 4\).)] TJ ET
0.965 0.965 0.965 rg
26.250 332.274 555.000 237.464 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 569.738 m 581.250 569.738 l 581.250 568.988 l 26.250 568.988 l  f
26.250 332.274 m 581.250 332.274 l 581.250 333.024 l 26.250 333.024 l  f
q
225.000 0 0 168.750 35.250 391.238 cm /I5 Do
Q 
q
35.250 343.524 537.000 41.714 re W n
0.271 0.267 0.267 rg
BT 35.250 375.714 Td /F4 9.8 Tf  [(Fig. 3: OCCs and frequency distribution of a representative rarely endorsed interview question \(assessing ability to )] TJ ET
BT 35.250 363.810 Td /F4 9.8 Tf  [(track while reading\) for all participants, HD and prHD. Data is presented separately for symptom intensity \(left row\), )] TJ ET
BT 35.250 351.905 Td /F4 9.8 Tf  [(frequency \(middle row\), and composite \(right row\) scores.)] TJ ET
Q
BT 26.250 315.250 Td /F1 9.8 Tf  [(It was agreed that these 4 interview questions should be removed from subsequent iterations on the basis of Relevance )] TJ ET
BT 26.250 303.345 Td /F1 9.8 Tf  [(\(Reported as not relevant by a large segment of the population of interest\) and Response Range \(A high percentage of patients )] TJ ET
BT 26.250 291.441 Td /F1 9.8 Tf  [(respond at the floor\) as outlined in Table 1 of the )] TJ ET
0.267 0.267 0.267 rg
BT 238.702 291.441 Td /F1 9.8 Tf  [(FDA PRO Guidance)] TJ ET
0.271 0.267 0.267 rg
BT 326.482 291.441 Td /F1 9.8 Tf  [(. )] TJ ET
0.267 0.267 0.267 rg
BT 331.903 291.441 Td /F1 9.8 Tf  [([3])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 254.838 Td /F4 12.0 Tf  [(Discussion)] TJ ET
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BT 26.250 144.051 Td /F1 9.8 Tf  [(objects, and shifting gaze, see Figure 3, Table 4\) despite the presence of significant deficits in ocular pursuit and saccades in )] TJ ET
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BT 26.250 755.571 Td /F1 9.8 Tf  [(problematic in the present study \(see Table 1\).)] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(Based on the results, seven interview questions have been selected for further testing, have been modified accordingly by the )] TJ ET
BT 26.250 724.262 Td /F1 9.8 Tf  [(working group, and are currently undergoing a second iteration of field testing. The results of the second iteration will be )] TJ ET
BT 26.250 712.357 Td /F1 9.8 Tf  [(reported once completed.)] TJ ET
BT 26.250 675.755 Td /F4 12.0 Tf  [(Competing Interests)] TJ ET
BT 26.250 655.800 Td /F1 9.8 Tf  [(The authors have declared that no competing interests exist.)] TJ ET
BT 26.250 619.198 Td /F4 12.0 Tf  [(FuRST-pHD Core Team)] TJ ET
BT 26.250 599.244 Td /F1 9.8 Tf  [(K Anderson, B Borowsky, K Evans, J Giuliano, M. Guttman. A Ho, JS Paulsen, T Sills, A Vaccarino, D van Kammen)] TJ ET
BT 26.250 562.641 Td /F4 12.0 Tf  [(Motor Symptoms Working Group)] TJ ET
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BT 26.250 417.669 Td /F1 9.8 Tf  [(William Ondo, MD\); OCBN Contracted: Birmingham and Solihull Mental Health, Birmingham, UK \(Hugh Rickards, MD, Jenny )] TJ ET
BT 26.250 405.764 Td /F1 9.8 Tf  [(Crooks, BA, Jan Wright, BA\); Center for Movement Disorders, Markham, Ontario, Canada \(Mark Guttman, MD, Irita Karmalkar, )] TJ ET
BT 26.250 393.859 Td /F1 9.8 Tf  [(BA, Alanna Sheinberg, BA, and Adam Singer, BA\); University of Melbourne, AU \(David Ames, MD, Edmond Chiu, MD, Phyllis )] TJ ET
BT 26.250 381.954 Td /F1 9.8 Tf  [(Chua, MD, Olga Yastrubetskaya, PhD, Joy Preston, Anita Goh, D.Psych, and Angela Komiti, BS, MA\); University of Iowa, Iowa )] TJ ET
BT 26.250 370.050 Td /F1 9.8 Tf  [(City, IA, USA \(Leigh Beglinger, PhD, Thomas Wassink, MD, Patricia Ryan, MSW, MA, Stephen Cross, BA, Mycah Kimble, BA, )] TJ ET
BT 26.250 358.145 Td /F1 9.8 Tf  [(Stacie Vik, BA\); Huntington Disease Drug Works, Seattle, WA, USA \(LaVonne Goodman, MD\); North York General Hospital, )] TJ ET
BT 26.250 346.240 Td /F1 9.8 Tf  [(Toronto. Ontario, Canada \(Clare Gibbons, MS, Jeanne Kennedy, BScNEd, RN, and Wendy Meschino, MD\))] TJ ET
BT 26.250 309.638 Td /F4 12.0 Tf  [(Focus Groups)] TJ ET
BT 26.250 289.683 Td /F1 9.8 Tf  [(Portugal \(J Ferreira, T Mestre\), Spain \(A Mart�nez Descals\), France \(A Durr, C Jauffret\), The Netherlands \(R Bos, R Roos, M-N )] TJ ET
BT 26.250 277.779 Td /F1 9.8 Tf  [(Witjes-An�\), UK \(R Fullam, O Handley, J Naji\); HD Drug Works, Seattle, USA \(L Goodman\))] TJ ET
BT 26.250 241.176 Td /F4 12.0 Tf  [(Corresponding Author)] TJ ET
BT 26.250 221.222 Td /F1 9.8 Tf  [(Anthony L Vaccarino, )] TJ ET
0.267 0.267 0.267 rg
BT 121.634 221.222 Td /F1 9.8 Tf  [(avaccarino@ocbn.ca)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 184.619 Td /F4 12.0 Tf  [(Acknowledgements)] TJ ET
BT 26.250 164.665 Td /F1 9.8 Tf  [(CHDI Foundation, Inc. � a not-for-profit research organisation whose mission is to rapidly and collaboratively discover and )] TJ ET
BT 26.250 152.760 Td /F1 9.8 Tf  [(develop therapies that slow the progression of Huntington�s disease � initiated and sponsored the development of the FuRST-)] TJ ET
BT 26.250 140.856 Td /F1 9.8 Tf  [(pHD. We thank Jamie Levey for her help coordinating the European focus groups, LaVonne Goodman for her help coordinating )] TJ ET
BT 26.250 128.951 Td /F1 9.8 Tf  [(the USA focus groups, and Stacie M Vik and Barbara McQuaid for administrative assistance.)] TJ ET
BT 26.250 99.848 Td /F4 12.0 Tf  [(References)] TJ ET
BT 26.250 72.394 Td /F1 9.8 Tf  [(1.)] TJ ET
BT 38.132 72.394 Td /F1 9.8 Tf  [(Evans K, K Anderson, B Borowsky, J Giuliano, M Guttman, A Ho, J Paulsen, T Sills, A Vaccarino, D van Kammen, And the )] TJ ET
BT 26.250 60.489 Td /F1 9.8 Tf  [(FuRST-pHD, PREDICT-HD investigators and coordinators. The Functional Rating Scale Taskforce for pre-Huntington Disease: )] TJ ET
BT 26.250 48.585 Td /F1 9.8 Tf  [(Results So Far, J Neurol Neurosurg Psychiatry 2010;81:A25)] TJ ET
Q
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BT 26.250 767.476 Td /F1 9.8 Tf  [(coordination, dropping things, clumsiness, falling, walking difficulty, and instability were also assessed and reported as )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(problematic in the present study \(see Table 1\).)] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(Based on the results, seven interview questions have been selected for further testing, have been modified accordingly by the )] TJ ET
BT 26.250 724.262 Td /F1 9.8 Tf  [(working group, and are currently undergoing a second iteration of field testing. The results of the second iteration will be )] TJ ET
BT 26.250 712.357 Td /F1 9.8 Tf  [(reported once completed.)] TJ ET
BT 26.250 675.755 Td /F4 12.0 Tf  [(Competing Interests)] TJ ET
BT 26.250 655.800 Td /F1 9.8 Tf  [(The authors have declared that no competing interests exist.)] TJ ET
BT 26.250 619.198 Td /F4 12.0 Tf  [(FuRST-pHD Core Team)] TJ ET
BT 26.250 599.244 Td /F1 9.8 Tf  [(K Anderson, B Borowsky, K Evans, J Giuliano, M. Guttman. A Ho, JS Paulsen, T Sills, A Vaccarino, D van Kammen)] TJ ET
BT 26.250 562.641 Td /F4 12.0 Tf  [(Motor Symptoms Working Group)] TJ ET
BT 26.250 542.687 Td /F1 9.8 Tf  [(FuRST-pHD Core Team, K Biglan, C Kennard, B Landwehrmeyer, A Michell, R Reilmann, J Warner)] TJ ET
BT 26.250 506.084 Td /F4 12.0 Tf  [(Statistics)] TJ ET
BT 26.250 486.130 Td /F1 9.8 Tf  [(S Gilbert-Evans, P Kupchak, T Sills, A Vaccarino)] TJ ET
BT 26.250 449.528 Td /F4 12.0 Tf  [(Contributing Field Testing Sites and Coordinators)] TJ ET
BT 26.250 429.573 Td /F1 9.8 Tf  [(PREDICT-HD: Baylor College of Medicine, Houston, Texas, USA \(Joseph Jankovic, MD, Christine Hunter, RN, CCRC, and )] TJ ET
BT 26.250 417.669 Td /F1 9.8 Tf  [(William Ondo, MD\); OCBN Contracted: Birmingham and Solihull Mental Health, Birmingham, UK \(Hugh Rickards, MD, Jenny )] TJ ET
BT 26.250 405.764 Td /F1 9.8 Tf  [(Crooks, BA, Jan Wright, BA\); Center for Movement Disorders, Markham, Ontario, Canada \(Mark Guttman, MD, Irita Karmalkar, )] TJ ET
BT 26.250 393.859 Td /F1 9.8 Tf  [(BA, Alanna Sheinberg, BA, and Adam Singer, BA\); University of Melbourne, AU \(David Ames, MD, Edmond Chiu, MD, Phyllis )] TJ ET
BT 26.250 381.954 Td /F1 9.8 Tf  [(Chua, MD, Olga Yastrubetskaya, PhD, Joy Preston, Anita Goh, D.Psych, and Angela Komiti, BS, MA\); University of Iowa, Iowa )] TJ ET
BT 26.250 370.050 Td /F1 9.8 Tf  [(City, IA, USA \(Leigh Beglinger, PhD, Thomas Wassink, MD, Patricia Ryan, MSW, MA, Stephen Cross, BA, Mycah Kimble, BA, )] TJ ET
BT 26.250 358.145 Td /F1 9.8 Tf  [(Stacie Vik, BA\); Huntington Disease Drug Works, Seattle, WA, USA \(LaVonne Goodman, MD\); North York General Hospital, )] TJ ET
BT 26.250 346.240 Td /F1 9.8 Tf  [(Toronto. Ontario, Canada \(Clare Gibbons, MS, Jeanne Kennedy, BScNEd, RN, and Wendy Meschino, MD\))] TJ ET
BT 26.250 309.638 Td /F4 12.0 Tf  [(Focus Groups)] TJ ET
BT 26.250 289.683 Td /F1 9.8 Tf  [(Portugal \(J Ferreira, T Mestre\), Spain \(A Mart�nez Descals\), France \(A Durr, C Jauffret\), The Netherlands \(R Bos, R Roos, M-N )] TJ ET
BT 26.250 277.779 Td /F1 9.8 Tf  [(Witjes-An�\), UK \(R Fullam, O Handley, J Naji\); HD Drug Works, Seattle, USA \(L Goodman\))] TJ ET
BT 26.250 241.176 Td /F4 12.0 Tf  [(Corresponding Author)] TJ ET
BT 26.250 221.222 Td /F1 9.8 Tf  [(Anthony L Vaccarino, )] TJ ET
0.267 0.267 0.267 rg
BT 121.634 221.222 Td /F1 9.8 Tf  [(avaccarino@ocbn.ca)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 184.619 Td /F4 12.0 Tf  [(Acknowledgements)] TJ ET
BT 26.250 164.665 Td /F1 9.8 Tf  [(CHDI Foundation, Inc. � a not-for-profit research organisation whose mission is to rapidly and collaboratively discover and )] TJ ET
BT 26.250 152.760 Td /F1 9.8 Tf  [(develop therapies that slow the progression of Huntington�s disease � initiated and sponsored the development of the FuRST-)] TJ ET
BT 26.250 140.856 Td /F1 9.8 Tf  [(pHD. We thank Jamie Levey for her help coordinating the European focus groups, LaVonne Goodman for her help coordinating )] TJ ET
BT 26.250 128.951 Td /F1 9.8 Tf  [(the USA focus groups, and Stacie M Vik and Barbara McQuaid for administrative assistance.)] TJ ET
BT 26.250 99.848 Td /F4 12.0 Tf  [(References)] TJ ET
BT 26.250 72.394 Td /F1 9.8 Tf  [(1.)] TJ ET
BT 38.132 72.394 Td /F1 9.8 Tf  [(Evans K, K Anderson, B Borowsky, J Giuliano, M Guttman, A Ho, J Paulsen, T Sills, A Vaccarino, D van Kammen, And the )] TJ ET
BT 26.250 60.489 Td /F1 9.8 Tf  [(FuRST-pHD, PREDICT-HD investigators and coordinators. The Functional Rating Scale Taskforce for pre-Huntington Disease: )] TJ ET
BT 26.250 48.585 Td /F1 9.8 Tf  [(Results So Far, J Neurol Neurosurg Psychiatry 2010;81:A25)] TJ ET
Q
q
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0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(coordination, dropping things, clumsiness, falling, walking difficulty, and instability were also assessed and reported as )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(problematic in the present study \(see Table 1\).)] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(Based on the results, seven interview questions have been selected for further testing, have been modified accordingly by the )] TJ ET
BT 26.250 724.262 Td /F1 9.8 Tf  [(working group, and are currently undergoing a second iteration of field testing. The results of the second iteration will be )] TJ ET
BT 26.250 712.357 Td /F1 9.8 Tf  [(reported once completed.)] TJ ET
BT 26.250 675.755 Td /F4 12.0 Tf  [(Competing Interests)] TJ ET
BT 26.250 655.800 Td /F1 9.8 Tf  [(The authors have declared that no competing interests exist.)] TJ ET
BT 26.250 619.198 Td /F4 12.0 Tf  [(FuRST-pHD Core Team)] TJ ET
BT 26.250 599.244 Td /F1 9.8 Tf  [(K Anderson, B Borowsky, K Evans, J Giuliano, M. Guttman. A Ho, JS Paulsen, T Sills, A Vaccarino, D van Kammen)] TJ ET
BT 26.250 562.641 Td /F4 12.0 Tf  [(Motor Symptoms Working Group)] TJ ET
BT 26.250 542.687 Td /F1 9.8 Tf  [(FuRST-pHD Core Team, K Biglan, C Kennard, B Landwehrmeyer, A Michell, R Reilmann, J Warner)] TJ ET
BT 26.250 506.084 Td /F4 12.0 Tf  [(Statistics)] TJ ET
BT 26.250 486.130 Td /F1 9.8 Tf  [(S Gilbert-Evans, P Kupchak, T Sills, A Vaccarino)] TJ ET
BT 26.250 449.528 Td /F4 12.0 Tf  [(Contributing Field Testing Sites and Coordinators)] TJ ET
BT 26.250 429.573 Td /F1 9.8 Tf  [(PREDICT-HD: Baylor College of Medicine, Houston, Texas, USA \(Joseph Jankovic, MD, Christine Hunter, RN, CCRC, and )] TJ ET
BT 26.250 417.669 Td /F1 9.8 Tf  [(William Ondo, MD\); OCBN Contracted: Birmingham and Solihull Mental Health, Birmingham, UK \(Hugh Rickards, MD, Jenny )] TJ ET
BT 26.250 405.764 Td /F1 9.8 Tf  [(Crooks, BA, Jan Wright, BA\); Center for Movement Disorders, Markham, Ontario, Canada \(Mark Guttman, MD, Irita Karmalkar, )] TJ ET
BT 26.250 393.859 Td /F1 9.8 Tf  [(BA, Alanna Sheinberg, BA, and Adam Singer, BA\); University of Melbourne, AU \(David Ames, MD, Edmond Chiu, MD, Phyllis )] TJ ET
BT 26.250 381.954 Td /F1 9.8 Tf  [(Chua, MD, Olga Yastrubetskaya, PhD, Joy Preston, Anita Goh, D.Psych, and Angela Komiti, BS, MA\); University of Iowa, Iowa )] TJ ET
BT 26.250 370.050 Td /F1 9.8 Tf  [(City, IA, USA \(Leigh Beglinger, PhD, Thomas Wassink, MD, Patricia Ryan, MSW, MA, Stephen Cross, BA, Mycah Kimble, BA, )] TJ ET
BT 26.250 358.145 Td /F1 9.8 Tf  [(Stacie Vik, BA\); Huntington Disease Drug Works, Seattle, WA, USA \(LaVonne Goodman, MD\); North York General Hospital, )] TJ ET
BT 26.250 346.240 Td /F1 9.8 Tf  [(Toronto. Ontario, Canada \(Clare Gibbons, MS, Jeanne Kennedy, BScNEd, RN, and Wendy Meschino, MD\))] TJ ET
BT 26.250 309.638 Td /F4 12.0 Tf  [(Focus Groups)] TJ ET
BT 26.250 289.683 Td /F1 9.8 Tf  [(Portugal \(J Ferreira, T Mestre\), Spain \(A Mart�nez Descals\), France \(A Durr, C Jauffret\), The Netherlands \(R Bos, R Roos, M-N )] TJ ET
BT 26.250 277.779 Td /F1 9.8 Tf  [(Witjes-An�\), UK \(R Fullam, O Handley, J Naji\); HD Drug Works, Seattle, USA \(L Goodman\))] TJ ET
BT 26.250 241.176 Td /F4 12.0 Tf  [(Corresponding Author)] TJ ET
BT 26.250 221.222 Td /F1 9.8 Tf  [(Anthony L Vaccarino, )] TJ ET
0.267 0.267 0.267 rg
BT 121.634 221.222 Td /F1 9.8 Tf  [(avaccarino@ocbn.ca)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 184.619 Td /F4 12.0 Tf  [(Acknowledgements)] TJ ET
BT 26.250 164.665 Td /F1 9.8 Tf  [(CHDI Foundation, Inc. � a not-for-profit research organisation whose mission is to rapidly and collaboratively discover and )] TJ ET
BT 26.250 152.760 Td /F1 9.8 Tf  [(develop therapies that slow the progression of Huntington�s disease � initiated and sponsored the development of the FuRST-)] TJ ET
BT 26.250 140.856 Td /F1 9.8 Tf  [(pHD. We thank Jamie Levey for her help coordinating the European focus groups, LaVonne Goodman for her help coordinating )] TJ ET
BT 26.250 128.951 Td /F1 9.8 Tf  [(the USA focus groups, and Stacie M Vik and Barbara McQuaid for administrative assistance.)] TJ ET
BT 26.250 99.848 Td /F4 12.0 Tf  [(References)] TJ ET
BT 26.250 72.394 Td /F1 9.8 Tf  [(1.)] TJ ET
BT 38.132 72.394 Td /F1 9.8 Tf  [(Evans K, K Anderson, B Borowsky, J Giuliano, M Guttman, A Ho, J Paulsen, T Sills, A Vaccarino, D van Kammen, And the )] TJ ET
BT 26.250 60.489 Td /F1 9.8 Tf  [(FuRST-pHD, PREDICT-HD investigators and coordinators. The Functional Rating Scale Taskforce for pre-Huntington Disease: )] TJ ET
BT 26.250 48.585 Td /F1 9.8 Tf  [(Results So Far, J Neurol Neurosurg Psychiatry 2010;81:A25)] TJ ET
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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

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BT 26.250 759.976 Td /F1 9.8 Tf  [(2.)] TJ ET
BT 38.132 759.976 Td /F1 9.8 Tf  [(Vaccarino, A.L., K. Anderson, B. Borowsky, K. Duff, J. Giuliano, M. Guttman, A.K. Ho, M. Orth, J.S. Paulsen, T.L. Sills, D.P. )] TJ ET
BT 26.250 748.071 Td /F1 9.8 Tf  [(van Kammen, K.R. Evans, PREDICT-HD and REGISTRY Investigators and Coordinators, An Item Response Analysis of the )] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(Motor and Behavioral Subscales of the Unified Huntington's Disease Rating Scale in Huntington Disease Gene Expansion )] TJ ET
BT 26.250 724.262 Td /F1 9.8 Tf  [(Carriers, Movement Disorders, 2011; 26:877-884.)] TJ ET
BT 26.250 704.857 Td /F1 9.8 Tf  [(3.)] TJ ET
BT 38.132 704.857 Td /F1 9.8 Tf  [(Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research, Center for Devices and )] TJ ET
BT 26.250 692.952 Td /F1 9.8 Tf  [(Radiological Health Guidance for Industry, Patient-Reported Outcome Measures: Use in Medical Product Development to )] TJ ET
BT 26.250 681.048 Td /F1 9.8 Tf  [(Support Labeling Claims. U.S. Dept of Health and Human Services Food and Drug Administration, December, 2009.)] TJ ET
BT 26.250 661.643 Td /F1 9.8 Tf  [(4.)] TJ ET
BT 38.132 661.643 Td /F1 9.8 Tf  [(Williams JBW, Kobak KA, Bech P, et al. The GRID-HAMD: standardization of the Hamilton Depression Rating Scale. Int Clin )] TJ ET
BT 26.250 649.738 Td /F1 9.8 Tf  [(Psychopharm 2008;23:120-129.)] TJ ET
BT 26.250 630.333 Td /F1 9.8 Tf  [(5.)] TJ ET
BT 38.132 630.333 Td /F1 9.8 Tf  [(Ramsay JO. Kernel Smoothing Approaches to Nonparametric Item Characteristic Curve Estimation. Psychometrika. 1991; )] TJ ET
BT 26.250 618.429 Td /F1 9.8 Tf  [(56:611-630.)] TJ ET
BT 26.250 599.024 Td /F1 9.8 Tf  [(6.)] TJ ET
BT 38.132 599.024 Td /F1 9.8 Tf  [(Paulsen JS. Early Detection of Huntington's Disease. Future Neurol. 2010; 5\(1\):85-104.)] TJ ET
BT 26.250 579.619 Td /F1 9.8 Tf  [(7.)] TJ ET
BT 38.132 579.619 Td /F1 9.8 Tf  [(Blekher TM, Yee RD, Kirkwood SC, et al. Oculomotor control in asymptomatic and recently diagnosed individuals with the )] TJ ET
BT 26.250 567.714 Td /F1 9.8 Tf  [(genetic marker for Huntington�s disease. Vision Res. 2004;44:2729 �273)] TJ ET
BT 26.250 548.310 Td /F1 9.8 Tf  [(8.)] TJ ET
BT 38.132 548.310 Td /F1 9.8 Tf  [(Blekher T, Johnson SA, Marshall BS, White K, Hui MS, Weaver M, Gray J, Yee R, Stout JC, Beristain X, Wojcieszek J, )] TJ ET
BT 26.250 536.405 Td /F1 9.8 Tf  [(Foroud T \(2006\) Saccades in presymptomatic and early stages of Huntington disease. Neurology; 67:394�39)] TJ ET
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BT 26.250 759.976 Td /F1 9.8 Tf  [(2.)] TJ ET
BT 38.132 759.976 Td /F1 9.8 Tf  [(Vaccarino, A.L., K. Anderson, B. Borowsky, K. Duff, J. Giuliano, M. Guttman, A.K. Ho, M. Orth, J.S. Paulsen, T.L. Sills, D.P. )] TJ ET
BT 26.250 748.071 Td /F1 9.8 Tf  [(van Kammen, K.R. Evans, PREDICT-HD and REGISTRY Investigators and Coordinators, An Item Response Analysis of the )] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(Motor and Behavioral Subscales of the Unified Huntington's Disease Rating Scale in Huntington Disease Gene Expansion )] TJ ET
BT 26.250 724.262 Td /F1 9.8 Tf  [(Carriers, Movement Disorders, 2011; 26:877-884.)] TJ ET
BT 26.250 704.857 Td /F1 9.8 Tf  [(3.)] TJ ET
BT 38.132 704.857 Td /F1 9.8 Tf  [(Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research, Center for Devices and )] TJ ET
BT 26.250 692.952 Td /F1 9.8 Tf  [(Radiological Health Guidance for Industry, Patient-Reported Outcome Measures: Use in Medical Product Development to )] TJ ET
BT 26.250 681.048 Td /F1 9.8 Tf  [(Support Labeling Claims. U.S. Dept of Health and Human Services Food and Drug Administration, December, 2009.)] TJ ET
BT 26.250 661.643 Td /F1 9.8 Tf  [(4.)] TJ ET
BT 38.132 661.643 Td /F1 9.8 Tf  [(Williams JBW, Kobak KA, Bech P, et al. The GRID-HAMD: standardization of the Hamilton Depression Rating Scale. Int Clin )] TJ ET
BT 26.250 649.738 Td /F1 9.8 Tf  [(Psychopharm 2008;23:120-129.)] TJ ET
BT 26.250 630.333 Td /F1 9.8 Tf  [(5.)] TJ ET
BT 38.132 630.333 Td /F1 9.8 Tf  [(Ramsay JO. Kernel Smoothing Approaches to Nonparametric Item Characteristic Curve Estimation. Psychometrika. 1991; )] TJ ET
BT 26.250 618.429 Td /F1 9.8 Tf  [(56:611-630.)] TJ ET
BT 26.250 599.024 Td /F1 9.8 Tf  [(6.)] TJ ET
BT 38.132 599.024 Td /F1 9.8 Tf  [(Paulsen JS. Early Detection of Huntington's Disease. Future Neurol. 2010; 5\(1\):85-104.)] TJ ET
BT 26.250 579.619 Td /F1 9.8 Tf  [(7.)] TJ ET
BT 38.132 579.619 Td /F1 9.8 Tf  [(Blekher TM, Yee RD, Kirkwood SC, et al. Oculomotor control in asymptomatic and recently diagnosed individuals with the )] TJ ET
BT 26.250 567.714 Td /F1 9.8 Tf  [(genetic marker for Huntington�s disease. Vision Res. 2004;44:2729 �273)] TJ ET
BT 26.250 548.310 Td /F1 9.8 Tf  [(8.)] TJ ET
BT 38.132 548.310 Td /F1 9.8 Tf  [(Blekher T, Johnson SA, Marshall BS, White K, Hui MS, Weaver M, Gray J, Yee R, Stout JC, Beristain X, Wojcieszek J, )] TJ ET
BT 26.250 536.405 Td /F1 9.8 Tf  [(Foroud T \(2006\) Saccades in presymptomatic and early stages of Huntington disease. Neurology; 67:394�39)] TJ ET
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BT 26.250 759.976 Td /F1 9.8 Tf  [(2.)] TJ ET
BT 38.132 759.976 Td /F1 9.8 Tf  [(Vaccarino, A.L., K. Anderson, B. Borowsky, K. Duff, J. Giuliano, M. Guttman, A.K. Ho, M. Orth, J.S. Paulsen, T.L. Sills, D.P. )] TJ ET
BT 26.250 748.071 Td /F1 9.8 Tf  [(van Kammen, K.R. Evans, PREDICT-HD and REGISTRY Investigators and Coordinators, An Item Response Analysis of the )] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(Motor and Behavioral Subscales of the Unified Huntington's Disease Rating Scale in Huntington Disease Gene Expansion )] TJ ET
BT 26.250 724.262 Td /F1 9.8 Tf  [(Carriers, Movement Disorders, 2011; 26:877-884.)] TJ ET
BT 26.250 704.857 Td /F1 9.8 Tf  [(3.)] TJ ET
BT 38.132 704.857 Td /F1 9.8 Tf  [(Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research, Center for Devices and )] TJ ET
BT 26.250 692.952 Td /F1 9.8 Tf  [(Radiological Health Guidance for Industry, Patient-Reported Outcome Measures: Use in Medical Product Development to )] TJ ET
BT 26.250 681.048 Td /F1 9.8 Tf  [(Support Labeling Claims. U.S. Dept of Health and Human Services Food and Drug Administration, December, 2009.)] TJ ET
BT 26.250 661.643 Td /F1 9.8 Tf  [(4.)] TJ ET
BT 38.132 661.643 Td /F1 9.8 Tf  [(Williams JBW, Kobak KA, Bech P, et al. The GRID-HAMD: standardization of the Hamilton Depression Rating Scale. Int Clin )] TJ ET
BT 26.250 649.738 Td /F1 9.8 Tf  [(Psychopharm 2008;23:120-129.)] TJ ET
BT 26.250 630.333 Td /F1 9.8 Tf  [(5.)] TJ ET
BT 38.132 630.333 Td /F1 9.8 Tf  [(Ramsay JO. Kernel Smoothing Approaches to Nonparametric Item Characteristic Curve Estimation. Psychometrika. 1991; )] TJ ET
BT 26.250 618.429 Td /F1 9.8 Tf  [(56:611-630.)] TJ ET
BT 26.250 599.024 Td /F1 9.8 Tf  [(6.)] TJ ET
BT 38.132 599.024 Td /F1 9.8 Tf  [(Paulsen JS. Early Detection of Huntington's Disease. Future Neurol. 2010; 5\(1\):85-104.)] TJ ET
BT 26.250 579.619 Td /F1 9.8 Tf  [(7.)] TJ ET
BT 38.132 579.619 Td /F1 9.8 Tf  [(Blekher TM, Yee RD, Kirkwood SC, et al. Oculomotor control in asymptomatic and recently diagnosed individuals with the )] TJ ET
BT 26.250 567.714 Td /F1 9.8 Tf  [(genetic marker for Huntington�s disease. Vision Res. 2004;44:2729 �273)] TJ ET
BT 26.250 548.310 Td /F1 9.8 Tf  [(8.)] TJ ET
BT 38.132 548.310 Td /F1 9.8 Tf  [(Blekher T, Johnson SA, Marshall BS, White K, Hui MS, Weaver M, Gray J, Yee R, Stout JC, Beristain X, Wojcieszek J, )] TJ ET
BT 26.250 536.405 Td /F1 9.8 Tf  [(Foroud T \(2006\) Saccades in presymptomatic and early stages of Huntington disease. Neurology; 67:394�39)] TJ ET
Q
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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

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