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BT 479.254 638.299 Td /F1 9.8 Tf  [(Jean Endicott)] TJ ET
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BT 195.841 626.394 Td /F1 9.8 Tf  [(Aileen K Ho)] TJ ET
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BT 136.786 614.490 Td /F1 9.8 Tf  [(Kevin D Wu)] TJ ET
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BT 26.250 537.768 Td /F4 12.0 Tf  [(Abstract)] TJ ET
BT 26.250 517.814 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 26.250 494.004 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 26.250 354.114 Td /F1 9.8 Tf  [(Neurological Disorders and Stroke \(NS40068\) and CHDI Foundation, Inc.)] TJ ET
BT 26.250 325.012 Td /F4 12.0 Tf  [(Introduction)] TJ ET
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BT 240.799 257.439 Td /F1 9.8 Tf  [(Such a measurement tool is essential to better understand the earliest )] TJ ET
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BT 26.250 226.129 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
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BT 26.250 178.510 Td /F1 9.8 Tf  [(these interview questions are developed, they are distributed to trained raters for beta testing in gene expansion carriers. This is )] TJ ET
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BT 26.250 142.796 Td /F1 9.8 Tf  [(optimal items for scale inclusion.)] TJ ET
BT 26.250 123.391 Td /F1 9.8 Tf  [(�Anger and Irritability� and �Obsessions and Compulsions� were identified as potential early symptoms exhibited by gene )] TJ ET
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BT 479.254 638.299 Td /F1 9.8 Tf  [(Jean Endicott)] TJ ET
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BT 67.434 626.394 Td /F1 9.8 Tf  [(Mark Groves)] TJ ET
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BT 128.654 626.394 Td /F1 9.8 Tf  [(Mark Guttman)] TJ ET
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BT 195.841 626.394 Td /F1 9.8 Tf  [(Aileen K Ho)] TJ ET
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BT 252.742 626.394 Td /F1 9.8 Tf  [(Peter Kupchak)] TJ ET
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BT 316.693 626.394 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 322.114 626.394 Td /F1 9.8 Tf  [(Jane S. Paulsen)] TJ ET
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BT 393.113 626.394 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 398.534 626.394 Td /F1 9.8 Tf  [(Matthew S. Stanford)] TJ ET
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BT 486.869 626.394 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 65.260 614.490 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 70.681 614.490 Td /F1 9.8 Tf  [(David Watson)] TJ ET
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BT 136.786 614.490 Td /F1 9.8 Tf  [(Kevin D Wu)] TJ ET
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BT 188.256 614.490 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 26.250 602.585 Td /F1 9.8 Tf  [(Vaccarino AL, Sills T, Anderson KE, Borowsky B, Coccaro E, Craufurd D, Endicott J, Giuliano J, Groves M, Guttman M, Ho AK, )] TJ ET
BT 26.250 590.680 Td /F1 9.8 Tf  [(Kupchak P, Paulsen JS, Stanford MS, van Kammen DP, Watson D, Wu KD, Evans K. Assessing Behavioural Manifestations )] TJ ET
BT 26.250 578.775 Td /F1 9.8 Tf  [(Prior to Clinical Diagnosis of Huntington Disease: �Anger and Irritability� and �Obsessions and Compulsions�. PLOS Currents )] TJ ET
BT 26.250 566.871 Td /F1 9.8 Tf  [(Huntington Disease. 2011 Jun 10 . Edition 1. doi: 10.1371/currents.RRN1241.)] TJ ET
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BT 26.250 537.768 Td /F4 12.0 Tf  [(Abstract)] TJ ET
BT 26.250 517.814 Td /F1 9.8 Tf  [(The Functional Rating Scale Taskforce for pre-Huntington Disease \(FuRST-pHD\) is a multinational, multidisciplinary initiative )] TJ ET
BT 26.250 505.909 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 26.250 494.004 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 26.250 482.100 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 26.250 470.195 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 26.250 458.290 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 26.250 446.385 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 26.250 434.481 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 26.250 422.576 Td /F1 9.8 Tf  [(questions aimed to assess �Anger and Irritability� and �Obsessions and Compulsions� in prHD individuals.)] TJ ET
BT 26.250 385.973 Td /F4 12.0 Tf  [(Funding Statement)] TJ ET
BT 26.250 366.019 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 26.250 354.114 Td /F1 9.8 Tf  [(Neurological Disorders and Stroke \(NS40068\) and CHDI Foundation, Inc.)] TJ ET
BT 26.250 325.012 Td /F4 12.0 Tf  [(Introduction)] TJ ET
BT 26.250 305.058 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 26.250 293.153 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 26.250 281.248 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 26.250 269.343 Td /F1 9.8 Tf  [(assess severity of manifestations in HD gene expansion carriers who do not yet meet criteria for a formal clinical diagnosis )] TJ ET
BT 26.250 257.439 Td /F1 9.8 Tf  [(\(prodromal HD or prHD\) or are early manifest. )] TJ ET
0.267 0.267 0.267 rg
BT 227.246 257.439 Td /F1 9.8 Tf  [([1] )] TJ ET
0.271 0.267 0.267 rg
BT 240.799 257.439 Td /F1 9.8 Tf  [(Such a measurement tool is essential to better understand the earliest )] TJ ET
BT 26.250 245.534 Td /F1 9.8 Tf  [(manifestations of HD and to evaluate novel therapies early in the course of disease.)] TJ ET
BT 26.250 226.129 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 26.250 214.224 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 563.768 214.224 Td /F1 9.8 Tf  [([1])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 202.320 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 26.250 190.415 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 26.250 178.510 Td /F1 9.8 Tf  [(these interview questions are developed, they are distributed to trained raters for beta testing in gene expansion carriers. This is )] TJ ET
BT 26.250 166.605 Td /F1 9.8 Tf  [(an iterative process, in which changes or deletions \(as appropriate\) are made based on empirical evidence obtained during field )] TJ ET
BT 26.250 154.701 Td /F1 9.8 Tf  [(testing; the modified questions are then tested during subsequent iterations so that the list can ultimately be winnowed to select )] TJ ET
BT 26.250 142.796 Td /F1 9.8 Tf  [(optimal items for scale inclusion.)] TJ ET
BT 26.250 123.391 Td /F1 9.8 Tf  [(�Anger and Irritability� and �Obsessions and Compulsions� were identified as potential early symptoms exhibited by gene )] TJ ET
BT 26.250 111.486 Td /F1 9.8 Tf  [(carriers for which proven measures are unavailable for this population. We report here the development and assessment of the )] TJ ET
BT 26.250 99.582 Td /F1 9.8 Tf  [(first iteration of interview questions aimed to assess �Anger and Irritability� and �Obsessions and Compulsions� in prHD.)] TJ ET
BT 26.250 62.979 Td /F4 12.0 Tf  [(Methods)] TJ ET
BT 26.250 43.025 Td /F1 9.8 Tf  [(Two-day Working Group meetings of individuals with a broad range of relevant expertise were held in Toronto, Canada to )] TJ ET
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BT 269.025 638.299 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 344.890 638.299 Td /F1 9.8 Tf  [(Emil Coccaro)] TJ ET
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BT 402.853 638.299 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 473.833 638.299 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 479.254 638.299 Td /F1 9.8 Tf  [(Jean Endicott)] TJ ET
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BT 538.330 638.299 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 26.250 626.394 Td /F1 9.8 Tf  [(Giuliano)] TJ ET
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BT 398.534 626.394 Td /F1 9.8 Tf  [(Matthew S. Stanford)] TJ ET
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202.393 507.739 0.750 24.263 re f
580.125 507.739 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 207.643 521.396 Td /F1 9.8 Tf  [(Assesses both irritability \(proneness to annoyance\) as well as anger \(strong )] TJ ET
BT 207.643 513.765 Td /F1 9.8 Tf  [(displeasure with self or others, accompanied by signs of autonomic arousal\).)] TJ ET
0.267 0.267 0.267 rg
26.625 507.739 176.518 0.750 re f
26.625 484.226 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 497.884 Td /F4 9.8 Tf  [(Ease of Anger � provocation)] TJ ET
0.267 0.267 0.267 rg
202.393 507.739 378.482 0.750 re f
202.393 484.226 0.750 24.263 re f
580.125 484.226 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 207.643 497.884 Td /F1 9.8 Tf  [(Assesses the ease with which individual becomes annoyed or angered when they )] TJ ET
BT 207.643 490.252 Td /F1 9.8 Tf  [(are confronted or provoked by others.)] TJ ET
0.267 0.267 0.267 rg
26.625 484.226 176.518 0.750 re f
26.625 460.714 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 474.371 Td /F4 9.8 Tf  [(Ease of anger � stressor)] TJ ET
0.267 0.267 0.267 rg
202.393 484.226 378.482 0.750 re f
202.393 460.714 0.750 24.263 re f
580.125 460.714 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 207.643 474.371 Td /F1 9.8 Tf  [(Assesses the ease with which individual becomes annoyed or angered when under )] TJ ET
BT 207.643 466.740 Td /F1 9.8 Tf  [(conditions of stress or confronted with day-to-day hassles.)] TJ ET
0.267 0.267 0.267 rg
26.625 460.714 176.518 0.750 re f
26.625 437.201 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 450.859 Td /F4 9.8 Tf  [(Ease of calming down)] TJ ET
0.267 0.267 0.267 rg
202.393 460.714 378.482 0.750 re f
202.393 437.201 0.750 24.263 re f
580.125 437.201 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 207.643 450.859 Td /F1 9.8 Tf  [(Assesses the ease with which individual can calm down after they have become )] TJ ET
BT 207.643 443.227 Td /F1 9.8 Tf  [(angered or annoyed.)] TJ ET
0.267 0.267 0.267 rg
26.625 437.201 176.518 0.750 re f
26.625 413.689 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 427.346 Td /F4 9.8 Tf  [(Calm down time)] TJ ET
0.267 0.267 0.267 rg
202.393 437.201 378.482 0.750 re f
202.393 413.689 0.750 24.263 re f
580.125 413.689 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 207.643 427.346 Td /F1 9.8 Tf  [(Assesses the amount of time it takes individual to calm down once annoyed or )] TJ ET
BT 207.643 419.715 Td /F1 9.8 Tf  [(angered.)] TJ ET
0.267 0.267 0.267 rg
26.625 413.689 176.518 0.750 re f
26.625 397.807 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 403.834 Td /F4 9.8 Tf  [(Aggression � People)] TJ ET
0.267 0.267 0.267 rg
202.393 413.689 378.482 0.750 re f
202.393 397.807 0.750 16.631 re f
580.125 397.807 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 207.643 403.834 Td /F1 9.8 Tf  [(Assesses the individual�s aggressive behaviors toward other people.)] TJ ET
0.267 0.267 0.267 rg
26.625 397.807 176.518 0.750 re f
26.625 381.926 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 387.952 Td /F4 9.8 Tf  [(Aggression � Animals/Objects)] TJ ET
0.267 0.267 0.267 rg
202.393 397.807 378.482 0.750 re f
202.393 381.926 0.750 16.631 re f
580.125 381.926 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 207.643 387.952 Td /F1 9.8 Tf  [(Assesses the individual�s aggressive behaviors toward animals or objects.)] TJ ET
0.267 0.267 0.267 rg
26.625 381.926 176.518 0.750 re f
26.625 366.045 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 372.071 Td /F4 9.8 Tf  [(Repetitive Thoughts)] TJ ET
0.267 0.267 0.267 rg
202.393 381.926 378.482 0.750 re f
202.393 366.045 0.750 16.631 re f
580.125 366.045 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 207.643 372.071 Td /F1 9.8 Tf  [(Assesses the experience of repetitive thoughts.)] TJ ET
0.267 0.267 0.267 rg
26.625 366.045 176.518 0.750 re f
26.625 350.164 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 356.190 Td /F4 9.8 Tf  [(Compromise)] TJ ET
0.267 0.267 0.267 rg
202.393 366.045 378.482 0.750 re f
202.393 350.164 0.750 16.631 re f
580.125 350.164 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 207.643 356.190 Td /F1 9.8 Tf  [(Assesses ability to compromise.)] TJ ET
0.267 0.267 0.267 rg
26.625 350.164 176.518 0.750 re f
26.625 334.282 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 340.309 Td /F4 9.8 Tf  [(Perseveration � Tasks)] TJ ET
0.267 0.267 0.267 rg
202.393 350.164 378.482 0.750 re f
202.393 334.282 0.750 16.631 re f
580.125 334.282 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 207.643 340.309 Td /F1 9.8 Tf  [(Assesses fixation on tasks and the difficulty in shifting away from those tasks.)] TJ ET
0.267 0.267 0.267 rg
26.625 334.282 176.518 0.750 re f
26.625 310.770 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 324.427 Td /F4 9.8 Tf  [(Perseveration � Topics of )] TJ ET
BT 31.875 316.796 Td /F4 9.8 Tf  [(conversation)] TJ ET
0.267 0.267 0.267 rg
202.393 334.282 378.482 0.750 re f
202.393 310.770 0.750 24.263 re f
580.125 310.770 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 207.643 324.427 Td /F1 9.8 Tf  [(Assesses fixation on specific topics of conversation and the difficulty in shifting away )] TJ ET
BT 207.643 316.796 Td /F1 9.8 Tf  [(from those conversations.)] TJ ET
0.267 0.267 0.267 rg
26.625 310.770 176.518 0.750 re f
26.625 287.257 176.518 0.750 re f
26.625 287.257 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 300.915 Td /F4 9.8 Tf  [(Mental inflexibility/Rigidity)] TJ ET
0.267 0.267 0.267 rg
202.393 310.770 378.482 0.750 re f
202.393 287.257 378.482 0.750 re f
202.393 287.257 0.750 24.263 re f
580.125 287.257 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 207.643 300.915 Td /F1 9.8 Tf  [(Assesses mental rigidity and inflexibility; defined as insisting on having own way, or )] TJ ET
BT 207.643 293.284 Td /F1 9.8 Tf  [(have increasing difficulty adapting to new or changing circumstances.)] TJ ET
BT 26.250 239.859 Td /F4 9.8 Tf  [(Field Testing of Interview Questions)] TJ ET
BT 26.250 220.454 Td /F1 9.8 Tf  [(Field testing of interview questions in prHD \(UHDRS Diagnostic Confidence Level < 4\) and early HD \(within 5 years from onset )] TJ ET
BT 26.250 208.549 Td /F1 9.8 Tf  [(of clinical motor signs\) was conducted within the PREDICT-HD program and at independently contracted sites. All data )] TJ ET
BT 26.250 196.644 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 26.250 184.740 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 26.250 172.835 Td /F1 9.8 Tf  [(administering and scoring each of the items. A minimum sample size of 100 was targeted.)] TJ ET
BT 26.250 153.430 Td /F4 9.8 Tf  [(Data Analysis)] TJ ET
BT 26.250 134.025 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 26.250 122.121 Td /F1 9.8 Tf  [(score were computed. Distributions of item scores for prHD and HD subgroups were statistically compared using the non-)] TJ ET
BT 26.250 110.216 Td /F1 9.8 Tf  [(parametric Mann-Whitney U test.)] TJ ET
BT 26.250 90.811 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 78.906 Td /F1 9.8 Tf  [(interview questions and total score. Item Response Theory \(IRT\) has been demonstrated to be useful in evaluating the )] TJ ET
BT 26.250 67.002 Td /F1 9.8 Tf  [(performance of individual items \(symptoms\) on rating scales, by assessing the relationship between a score assigned to an item )] TJ ET
BT 26.250 55.097 Td /F1 9.8 Tf  [(and the overall severity of the disease. )] TJ ET
0.267 0.267 0.267 rg
BT 195.334 55.097 Td /F1 9.8 Tf  [([4] [5])] TJ ET
0.271 0.267 0.267 rg
BT 219.729 55.097 Td /F1 9.8 Tf  [( IRT software \()] TJ ET
0.267 0.267 0.267 rg
BT 283.660 55.097 Td /F1 9.8 Tf  [(TESTGRAF)] TJ ET
0.271 0.267 0.267 rg
BT 335.666 55.097 Td /F1 9.8 Tf  [(\) was used to generate Option Characteristic Curves )] TJ ET
BT 26.250 43.192 Td /F1 9.8 Tf  [(\(OCCs\) 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 )] TJ ET
Q
q
15.000 28.906 577.500 748.094 re W n
0.965 0.965 0.965 rg
26.250 685.400 555.000 91.600 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 685.400 m 581.250 685.400 l 581.250 686.150 l 26.250 686.150 l  f
q
35.250 696.650 537.000 80.350 re W n
0.271 0.267 0.267 rg
BT 35.250 767.476 Td /F4 9.8 Tf  [(Fig. 2: Development of interview questions to assess anger and irritability.)] TJ ET
BT 35.250 748.106 Td /F1 9.8 Tf  [(Based on patient, caregiver, expert, and literature input, symptom domains are identified that are thought to be important to )] TJ ET
BT 35.250 734.370 Td /F1 9.8 Tf  [(prHD. The Working Groups identify the constituent symptoms based on the words used by patients and caregivers, )] TJ ET
BT 35.250 720.634 Td /F1 9.8 Tf  [(conventional definitions and their clinical and scientific opinion. Interview questions are then developed for each of these )] TJ ET
BT 35.250 706.897 Td /F1 9.8 Tf  [(narrowly defined symptoms.)] TJ ET
Q
BT 26.250 668.376 Td /F1 9.8 Tf  [(The FuRST-pHD has adopted a semi-structured clinician-administered interview similar to that used for the )] TJ ET
0.267 0.267 0.267 rg
BT 488.985 668.376 Td /F1 9.8 Tf  [(GRID-HAMD )] TJ ET
0.271 0.267 0.267 rg
BT 548.021 668.376 Td /F1 9.8 Tf  [(. The )] TJ ET
BT 26.250 656.472 Td /F1 9.8 Tf  [(GRID format directs the rater to score symptom frequency and intensity separately, while giving them clear scoring anchors, a )] TJ ET
BT 26.250 644.567 Td /F1 9.8 Tf  [(semi-structured interview guide, and overall definitions. This method has been employed successfully and is user-friendly, with )] TJ ET
BT 26.250 632.662 Td /F1 9.8 Tf  [(acceptable agreement among independent raters. )] TJ ET
0.267 0.267 0.267 rg
BT 244.660 632.662 Td /F1 9.8 Tf  [([3])] TJ ET
0.271 0.267 0.267 rg
BT 255.502 632.662 Td /F1 9.8 Tf  [( The working group developed interview questions, including structured )] TJ ET
BT 26.250 620.757 Td /F1 9.8 Tf  [(interview guides, scoring conventions, scoring anchors, and symptom definitions. Following the meeting, draft interview )] TJ ET
BT 26.250 608.853 Td /F1 9.8 Tf  [(questions were circulated for comment on a shared internet site \(Sharepoint\).)] TJ ET
BT 26.250 589.448 Td /F1 9.8 Tf  [(Based on a review of the evidence, 7 interview questions assessing �Anger and Irritability� and 5 interview questions assessing )] TJ ET
BT 26.250 577.543 Td /F1 9.8 Tf  [(�Obsessions and Compulsions� were developed for field testing \(Table 1\).)] TJ ET
BT 26.250 558.138 Td /F4 9.8 Tf  [(Table 1)] TJ ET
BT 59.849 558.138 Td /F1 9.8 Tf  [( . Interview Questions)] TJ ET
1.000 1.000 1.000 rg
26.250 286.882 555.000 261.375 re f
0.267 0.267 0.267 rg
26.625 547.132 176.518 0.750 re f
26.625 531.251 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 537.277 Td /F4 9.8 Tf  [(Interview Question)] TJ ET
0.267 0.267 0.267 rg
202.393 547.132 378.482 0.750 re f
202.393 531.251 0.750 16.631 re f
580.125 531.251 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 207.643 537.277 Td /F4 9.8 Tf  [(Description/definition)] TJ ET
0.267 0.267 0.267 rg
26.625 531.251 176.518 0.750 re f
26.625 507.739 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 521.396 Td /F4 9.8 Tf  [(Anger/irritability)] TJ ET
0.267 0.267 0.267 rg
202.393 531.251 378.482 0.750 re f
202.393 507.739 0.750 24.263 re f
580.125 507.739 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 207.643 521.396 Td /F1 9.8 Tf  [(Assesses both irritability \(proneness to annoyance\) as well as anger \(strong )] TJ ET
BT 207.643 513.765 Td /F1 9.8 Tf  [(displeasure with self or others, accompanied by signs of autonomic arousal\).)] TJ ET
0.267 0.267 0.267 rg
26.625 507.739 176.518 0.750 re f
26.625 484.226 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 497.884 Td /F4 9.8 Tf  [(Ease of Anger � provocation)] TJ ET
0.267 0.267 0.267 rg
202.393 507.739 378.482 0.750 re f
202.393 484.226 0.750 24.263 re f
580.125 484.226 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 207.643 497.884 Td /F1 9.8 Tf  [(Assesses the ease with which individual becomes annoyed or angered when they )] TJ ET
BT 207.643 490.252 Td /F1 9.8 Tf  [(are confronted or provoked by others.)] TJ ET
0.267 0.267 0.267 rg
26.625 484.226 176.518 0.750 re f
26.625 460.714 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 474.371 Td /F4 9.8 Tf  [(Ease of anger � stressor)] TJ ET
0.267 0.267 0.267 rg
202.393 484.226 378.482 0.750 re f
202.393 460.714 0.750 24.263 re f
580.125 460.714 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 207.643 474.371 Td /F1 9.8 Tf  [(Assesses the ease with which individual becomes annoyed or angered when under )] TJ ET
BT 207.643 466.740 Td /F1 9.8 Tf  [(conditions of stress or confronted with day-to-day hassles.)] TJ ET
0.267 0.267 0.267 rg
26.625 460.714 176.518 0.750 re f
26.625 437.201 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 450.859 Td /F4 9.8 Tf  [(Ease of calming down)] TJ ET
0.267 0.267 0.267 rg
202.393 460.714 378.482 0.750 re f
202.393 437.201 0.750 24.263 re f
580.125 437.201 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 207.643 450.859 Td /F1 9.8 Tf  [(Assesses the ease with which individual can calm down after they have become )] TJ ET
BT 207.643 443.227 Td /F1 9.8 Tf  [(angered or annoyed.)] TJ ET
0.267 0.267 0.267 rg
26.625 437.201 176.518 0.750 re f
26.625 413.689 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 427.346 Td /F4 9.8 Tf  [(Calm down time)] TJ ET
0.267 0.267 0.267 rg
202.393 437.201 378.482 0.750 re f
202.393 413.689 0.750 24.263 re f
580.125 413.689 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 207.643 427.346 Td /F1 9.8 Tf  [(Assesses the amount of time it takes individual to calm down once annoyed or )] TJ ET
BT 207.643 419.715 Td /F1 9.8 Tf  [(angered.)] TJ ET
0.267 0.267 0.267 rg
26.625 413.689 176.518 0.750 re f
26.625 397.807 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 403.834 Td /F4 9.8 Tf  [(Aggression � People)] TJ ET
0.267 0.267 0.267 rg
202.393 413.689 378.482 0.750 re f
202.393 397.807 0.750 16.631 re f
580.125 397.807 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 207.643 403.834 Td /F1 9.8 Tf  [(Assesses the individual�s aggressive behaviors toward other people.)] TJ ET
0.267 0.267 0.267 rg
26.625 397.807 176.518 0.750 re f
26.625 381.926 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 387.952 Td /F4 9.8 Tf  [(Aggression � Animals/Objects)] TJ ET
0.267 0.267 0.267 rg
202.393 397.807 378.482 0.750 re f
202.393 381.926 0.750 16.631 re f
580.125 381.926 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 207.643 387.952 Td /F1 9.8 Tf  [(Assesses the individual�s aggressive behaviors toward animals or objects.)] TJ ET
0.267 0.267 0.267 rg
26.625 381.926 176.518 0.750 re f
26.625 366.045 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 372.071 Td /F4 9.8 Tf  [(Repetitive Thoughts)] TJ ET
0.267 0.267 0.267 rg
202.393 381.926 378.482 0.750 re f
202.393 366.045 0.750 16.631 re f
580.125 366.045 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 207.643 372.071 Td /F1 9.8 Tf  [(Assesses the experience of repetitive thoughts.)] TJ ET
0.267 0.267 0.267 rg
26.625 366.045 176.518 0.750 re f
26.625 350.164 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 356.190 Td /F4 9.8 Tf  [(Compromise)] TJ ET
0.267 0.267 0.267 rg
202.393 366.045 378.482 0.750 re f
202.393 350.164 0.750 16.631 re f
580.125 350.164 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 207.643 356.190 Td /F1 9.8 Tf  [(Assesses ability to compromise.)] TJ ET
0.267 0.267 0.267 rg
26.625 350.164 176.518 0.750 re f
26.625 334.282 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 340.309 Td /F4 9.8 Tf  [(Perseveration � Tasks)] TJ ET
0.267 0.267 0.267 rg
202.393 350.164 378.482 0.750 re f
202.393 334.282 0.750 16.631 re f
580.125 334.282 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 207.643 340.309 Td /F1 9.8 Tf  [(Assesses fixation on tasks and the difficulty in shifting away from those tasks.)] TJ ET
0.267 0.267 0.267 rg
26.625 334.282 176.518 0.750 re f
26.625 310.770 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 324.427 Td /F4 9.8 Tf  [(Perseveration � Topics of )] TJ ET
BT 31.875 316.796 Td /F4 9.8 Tf  [(conversation)] TJ ET
0.267 0.267 0.267 rg
202.393 334.282 378.482 0.750 re f
202.393 310.770 0.750 24.263 re f
580.125 310.770 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 207.643 324.427 Td /F1 9.8 Tf  [(Assesses fixation on specific topics of conversation and the difficulty in shifting away )] TJ ET
BT 207.643 316.796 Td /F1 9.8 Tf  [(from those conversations.)] TJ ET
0.267 0.267 0.267 rg
26.625 310.770 176.518 0.750 re f
26.625 287.257 176.518 0.750 re f
26.625 287.257 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 300.915 Td /F4 9.8 Tf  [(Mental inflexibility/Rigidity)] TJ ET
0.267 0.267 0.267 rg
202.393 310.770 378.482 0.750 re f
202.393 287.257 378.482 0.750 re f
202.393 287.257 0.750 24.263 re f
580.125 287.257 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 207.643 300.915 Td /F1 9.8 Tf  [(Assesses mental rigidity and inflexibility; defined as insisting on having own way, or )] TJ ET
BT 207.643 293.284 Td /F1 9.8 Tf  [(have increasing difficulty adapting to new or changing circumstances.)] TJ ET
BT 26.250 239.859 Td /F4 9.8 Tf  [(Field Testing of Interview Questions)] TJ ET
BT 26.250 220.454 Td /F1 9.8 Tf  [(Field testing of interview questions in prHD \(UHDRS Diagnostic Confidence Level < 4\) and early HD \(within 5 years from onset )] TJ ET
BT 26.250 208.549 Td /F1 9.8 Tf  [(of clinical motor signs\) was conducted within the PREDICT-HD program and at independently contracted sites. All data )] TJ ET
BT 26.250 196.644 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 26.250 184.740 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 26.250 172.835 Td /F1 9.8 Tf  [(administering and scoring each of the items. A minimum sample size of 100 was targeted.)] TJ ET
BT 26.250 153.430 Td /F4 9.8 Tf  [(Data Analysis)] TJ ET
BT 26.250 134.025 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 26.250 122.121 Td /F1 9.8 Tf  [(score were computed. Distributions of item scores for prHD and HD subgroups were statistically compared using the non-)] TJ ET
BT 26.250 110.216 Td /F1 9.8 Tf  [(parametric Mann-Whitney U test.)] TJ ET
BT 26.250 90.811 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 78.906 Td /F1 9.8 Tf  [(interview questions and total score. Item Response Theory \(IRT\) has been demonstrated to be useful in evaluating the )] TJ ET
BT 26.250 67.002 Td /F1 9.8 Tf  [(performance of individual items \(symptoms\) on rating scales, by assessing the relationship between a score assigned to an item )] TJ ET
BT 26.250 55.097 Td /F1 9.8 Tf  [(and the overall severity of the disease. )] TJ ET
0.267 0.267 0.267 rg
BT 195.334 55.097 Td /F1 9.8 Tf  [([4] [5])] TJ ET
0.271 0.267 0.267 rg
BT 219.729 55.097 Td /F1 9.8 Tf  [( IRT software \()] TJ ET
0.267 0.267 0.267 rg
BT 283.660 55.097 Td /F1 9.8 Tf  [(TESTGRAF)] TJ ET
0.271 0.267 0.267 rg
BT 335.666 55.097 Td /F1 9.8 Tf  [(\) was used to generate Option Characteristic Curves )] TJ ET
BT 26.250 43.192 Td /F1 9.8 Tf  [(\(OCCs\) 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 )] TJ ET
Q
q
15.000 28.906 577.500 748.094 re W n
0.965 0.965 0.965 rg
26.250 685.400 555.000 91.600 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 685.400 m 581.250 685.400 l 581.250 686.150 l 26.250 686.150 l  f
q
35.250 696.650 537.000 80.350 re W n
0.271 0.267 0.267 rg
BT 35.250 767.476 Td /F4 9.8 Tf  [(Fig. 2: Development of interview questions to assess anger and irritability.)] TJ ET
BT 35.250 748.106 Td /F1 9.8 Tf  [(Based on patient, caregiver, expert, and literature input, symptom domains are identified that are thought to be important to )] TJ ET
BT 35.250 734.370 Td /F1 9.8 Tf  [(prHD. The Working Groups identify the constituent symptoms based on the words used by patients and caregivers, )] TJ ET
BT 35.250 720.634 Td /F1 9.8 Tf  [(conventional definitions and their clinical and scientific opinion. Interview questions are then developed for each of these )] TJ ET
BT 35.250 706.897 Td /F1 9.8 Tf  [(narrowly defined symptoms.)] TJ ET
Q
BT 26.250 668.376 Td /F1 9.8 Tf  [(The FuRST-pHD has adopted a semi-structured clinician-administered interview similar to that used for the )] TJ ET
0.267 0.267 0.267 rg
BT 488.985 668.376 Td /F1 9.8 Tf  [(GRID-HAMD )] TJ ET
0.271 0.267 0.267 rg
BT 548.021 668.376 Td /F1 9.8 Tf  [(. The )] TJ ET
BT 26.250 656.472 Td /F1 9.8 Tf  [(GRID format directs the rater to score symptom frequency and intensity separately, while giving them clear scoring anchors, a )] TJ ET
BT 26.250 644.567 Td /F1 9.8 Tf  [(semi-structured interview guide, and overall definitions. This method has been employed successfully and is user-friendly, with )] TJ ET
BT 26.250 632.662 Td /F1 9.8 Tf  [(acceptable agreement among independent raters. )] TJ ET
0.267 0.267 0.267 rg
BT 244.660 632.662 Td /F1 9.8 Tf  [([3])] TJ ET
0.271 0.267 0.267 rg
BT 255.502 632.662 Td /F1 9.8 Tf  [( The working group developed interview questions, including structured )] TJ ET
BT 26.250 620.757 Td /F1 9.8 Tf  [(interview guides, scoring conventions, scoring anchors, and symptom definitions. Following the meeting, draft interview )] TJ ET
BT 26.250 608.853 Td /F1 9.8 Tf  [(questions were circulated for comment on a shared internet site \(Sharepoint\).)] TJ ET
BT 26.250 589.448 Td /F1 9.8 Tf  [(Based on a review of the evidence, 7 interview questions assessing �Anger and Irritability� and 5 interview questions assessing )] TJ ET
BT 26.250 577.543 Td /F1 9.8 Tf  [(�Obsessions and Compulsions� were developed for field testing \(Table 1\).)] TJ ET
BT 26.250 558.138 Td /F4 9.8 Tf  [(Table 1)] TJ ET
BT 59.849 558.138 Td /F1 9.8 Tf  [( . Interview Questions)] TJ ET
1.000 1.000 1.000 rg
26.250 286.882 555.000 261.375 re f
0.267 0.267 0.267 rg
26.625 547.132 176.518 0.750 re f
26.625 531.251 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 537.277 Td /F4 9.8 Tf  [(Interview Question)] TJ ET
0.267 0.267 0.267 rg
202.393 547.132 378.482 0.750 re f
202.393 531.251 0.750 16.631 re f
580.125 531.251 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 207.643 537.277 Td /F4 9.8 Tf  [(Description/definition)] TJ ET
0.267 0.267 0.267 rg
26.625 531.251 176.518 0.750 re f
26.625 507.739 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 521.396 Td /F4 9.8 Tf  [(Anger/irritability)] TJ ET
0.267 0.267 0.267 rg
202.393 531.251 378.482 0.750 re f
202.393 507.739 0.750 24.263 re f
580.125 507.739 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 207.643 521.396 Td /F1 9.8 Tf  [(Assesses both irritability \(proneness to annoyance\) as well as anger \(strong )] TJ ET
BT 207.643 513.765 Td /F1 9.8 Tf  [(displeasure with self or others, accompanied by signs of autonomic arousal\).)] TJ ET
0.267 0.267 0.267 rg
26.625 507.739 176.518 0.750 re f
26.625 484.226 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 497.884 Td /F4 9.8 Tf  [(Ease of Anger � provocation)] TJ ET
0.267 0.267 0.267 rg
202.393 507.739 378.482 0.750 re f
202.393 484.226 0.750 24.263 re f
580.125 484.226 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 207.643 497.884 Td /F1 9.8 Tf  [(Assesses the ease with which individual becomes annoyed or angered when they )] TJ ET
BT 207.643 490.252 Td /F1 9.8 Tf  [(are confronted or provoked by others.)] TJ ET
0.267 0.267 0.267 rg
26.625 484.226 176.518 0.750 re f
26.625 460.714 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 474.371 Td /F4 9.8 Tf  [(Ease of anger � stressor)] TJ ET
0.267 0.267 0.267 rg
202.393 484.226 378.482 0.750 re f
202.393 460.714 0.750 24.263 re f
580.125 460.714 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 207.643 474.371 Td /F1 9.8 Tf  [(Assesses the ease with which individual becomes annoyed or angered when under )] TJ ET
BT 207.643 466.740 Td /F1 9.8 Tf  [(conditions of stress or confronted with day-to-day hassles.)] TJ ET
0.267 0.267 0.267 rg
26.625 460.714 176.518 0.750 re f
26.625 437.201 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 450.859 Td /F4 9.8 Tf  [(Ease of calming down)] TJ ET
0.267 0.267 0.267 rg
202.393 460.714 378.482 0.750 re f
202.393 437.201 0.750 24.263 re f
580.125 437.201 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 207.643 450.859 Td /F1 9.8 Tf  [(Assesses the ease with which individual can calm down after they have become )] TJ ET
BT 207.643 443.227 Td /F1 9.8 Tf  [(angered or annoyed.)] TJ ET
0.267 0.267 0.267 rg
26.625 437.201 176.518 0.750 re f
26.625 413.689 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 427.346 Td /F4 9.8 Tf  [(Calm down time)] TJ ET
0.267 0.267 0.267 rg
202.393 437.201 378.482 0.750 re f
202.393 413.689 0.750 24.263 re f
580.125 413.689 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 207.643 427.346 Td /F1 9.8 Tf  [(Assesses the amount of time it takes individual to calm down once annoyed or )] TJ ET
BT 207.643 419.715 Td /F1 9.8 Tf  [(angered.)] TJ ET
0.267 0.267 0.267 rg
26.625 413.689 176.518 0.750 re f
26.625 397.807 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 403.834 Td /F4 9.8 Tf  [(Aggression � People)] TJ ET
0.267 0.267 0.267 rg
202.393 413.689 378.482 0.750 re f
202.393 397.807 0.750 16.631 re f
580.125 397.807 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 207.643 403.834 Td /F1 9.8 Tf  [(Assesses the individual�s aggressive behaviors toward other people.)] TJ ET
0.267 0.267 0.267 rg
26.625 397.807 176.518 0.750 re f
26.625 381.926 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 387.952 Td /F4 9.8 Tf  [(Aggression � Animals/Objects)] TJ ET
0.267 0.267 0.267 rg
202.393 397.807 378.482 0.750 re f
202.393 381.926 0.750 16.631 re f
580.125 381.926 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 207.643 387.952 Td /F1 9.8 Tf  [(Assesses the individual�s aggressive behaviors toward animals or objects.)] TJ ET
0.267 0.267 0.267 rg
26.625 381.926 176.518 0.750 re f
26.625 366.045 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 372.071 Td /F4 9.8 Tf  [(Repetitive Thoughts)] TJ ET
0.267 0.267 0.267 rg
202.393 381.926 378.482 0.750 re f
202.393 366.045 0.750 16.631 re f
580.125 366.045 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 207.643 372.071 Td /F1 9.8 Tf  [(Assesses the experience of repetitive thoughts.)] TJ ET
0.267 0.267 0.267 rg
26.625 366.045 176.518 0.750 re f
26.625 350.164 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 356.190 Td /F4 9.8 Tf  [(Compromise)] TJ ET
0.267 0.267 0.267 rg
202.393 366.045 378.482 0.750 re f
202.393 350.164 0.750 16.631 re f
580.125 350.164 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 207.643 356.190 Td /F1 9.8 Tf  [(Assesses ability to compromise.)] TJ ET
0.267 0.267 0.267 rg
26.625 350.164 176.518 0.750 re f
26.625 334.282 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 340.309 Td /F4 9.8 Tf  [(Perseveration � Tasks)] TJ ET
0.267 0.267 0.267 rg
202.393 350.164 378.482 0.750 re f
202.393 334.282 0.750 16.631 re f
580.125 334.282 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 207.643 340.309 Td /F1 9.8 Tf  [(Assesses fixation on tasks and the difficulty in shifting away from those tasks.)] TJ ET
0.267 0.267 0.267 rg
26.625 334.282 176.518 0.750 re f
26.625 310.770 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 324.427 Td /F4 9.8 Tf  [(Perseveration � Topics of )] TJ ET
BT 31.875 316.796 Td /F4 9.8 Tf  [(conversation)] TJ ET
0.267 0.267 0.267 rg
202.393 334.282 378.482 0.750 re f
202.393 310.770 0.750 24.263 re f
580.125 310.770 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 207.643 324.427 Td /F1 9.8 Tf  [(Assesses fixation on specific topics of conversation and the difficulty in shifting away )] TJ ET
BT 207.643 316.796 Td /F1 9.8 Tf  [(from those conversations.)] TJ ET
0.267 0.267 0.267 rg
26.625 310.770 176.518 0.750 re f
26.625 287.257 176.518 0.750 re f
26.625 287.257 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 300.915 Td /F4 9.8 Tf  [(Mental inflexibility/Rigidity)] TJ ET
0.267 0.267 0.267 rg
202.393 310.770 378.482 0.750 re f
202.393 287.257 378.482 0.750 re f
202.393 287.257 0.750 24.263 re f
580.125 287.257 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 207.643 300.915 Td /F1 9.8 Tf  [(Assesses mental rigidity and inflexibility; defined as insisting on having own way, or )] TJ ET
BT 207.643 293.284 Td /F1 9.8 Tf  [(have increasing difficulty adapting to new or changing circumstances.)] TJ ET
BT 26.250 239.859 Td /F4 9.8 Tf  [(Field Testing of Interview Questions)] TJ ET
BT 26.250 220.454 Td /F1 9.8 Tf  [(Field testing of interview questions in prHD \(UHDRS Diagnostic Confidence Level < 4\) and early HD \(within 5 years from onset )] TJ ET
BT 26.250 208.549 Td /F1 9.8 Tf  [(of clinical motor signs\) was conducted within the PREDICT-HD program and at independently contracted sites. All data )] TJ ET
BT 26.250 196.644 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 26.250 184.740 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 26.250 172.835 Td /F1 9.8 Tf  [(administering and scoring each of the items. A minimum sample size of 100 was targeted.)] TJ ET
BT 26.250 153.430 Td /F4 9.8 Tf  [(Data Analysis)] TJ ET
BT 26.250 134.025 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 26.250 122.121 Td /F1 9.8 Tf  [(score were computed. Distributions of item scores for prHD and HD subgroups were statistically compared using the non-)] TJ ET
BT 26.250 110.216 Td /F1 9.8 Tf  [(parametric Mann-Whitney U test.)] TJ ET
BT 26.250 90.811 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 78.906 Td /F1 9.8 Tf  [(interview questions and total score. Item Response Theory \(IRT\) has been demonstrated to be useful in evaluating the )] TJ ET
BT 26.250 67.002 Td /F1 9.8 Tf  [(performance of individual items \(symptoms\) on rating scales, by assessing the relationship between a score assigned to an item )] TJ ET
BT 26.250 55.097 Td /F1 9.8 Tf  [(and the overall severity of the disease. )] TJ ET
0.267 0.267 0.267 rg
BT 195.334 55.097 Td /F1 9.8 Tf  [([4] [5])] TJ ET
0.271 0.267 0.267 rg
BT 219.729 55.097 Td /F1 9.8 Tf  [( IRT software \()] TJ ET
0.267 0.267 0.267 rg
BT 283.660 55.097 Td /F1 9.8 Tf  [(TESTGRAF)] TJ ET
0.271 0.267 0.267 rg
BT 335.666 55.097 Td /F1 9.8 Tf  [(\) was used to generate Option Characteristic Curves )] TJ ET
BT 26.250 43.192 Td /F1 9.8 Tf  [(\(OCCs\) 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 )] TJ ET
Q
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BT 291.710 19.825 Td /F1 11.0 Tf  [(3)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Huntington Disease)] TJ ET

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0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(function of overall level of severity. In the present analyses, total score of all interview questions was used as a measure of )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(severity. To illustrate this, Figure 3 depicts a hypothetically ��ideal�� item from an item response perspective, which is )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(characterized by a clear identification of the range of severity scores over which an option is most likely to be endorsed, rapid )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(changes in the curves that correspond to changes in severity, and an orderly relationship between the weight assigned to the )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(option and the region of severity over which an item is likely to be endorsed. As such, OCCs provide a graphical representation )] TJ ET
BT 26.250 707.952 Td /F1 9.8 Tf  [(of how informative a particular item \(or symptom\) is as a measure of illness. Frequency distribution of option scoring within each )] TJ ET
BT 26.250 696.048 Td /F1 9.8 Tf  [(interview question were also generated.)] TJ ET
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0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
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q
35.250 451.276 537.000 39.141 re W n
0.271 0.267 0.267 rg
BT 35.250 480.893 Td /F4 9.8 Tf  [(Fig. 3: OCC for a hypothetically ��ideal�� item.)] TJ ET
BT 35.250 461.523 Td /F1 9.8 Tf  [(The OCC shows the probability \( y -axis\) of endorsing a particular option for the item at different levels of the trait \( x -axis\).)] TJ ET
Q
BT 26.250 423.002 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 26.250 411.097 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 26.250 399.192 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 26.250 387.288 Td /F1 9.8 Tf  [(correlations between subscale scores and scores of individual questions not included in the subscale were computed.)] TJ ET
BT 26.250 350.685 Td /F4 12.0 Tf  [(Results)] TJ ET
BT 26.250 330.731 Td /F1 9.8 Tf  [(A total of 225 CRFs were completed. The participant demographic characteristics are shown in Table 2.)] TJ ET
BT 26.250 311.326 Td /F4 9.8 Tf  [(Table 2. Demographic Characteristics)] TJ ET
1.000 1.000 1.000 rg
26.250 236.420 555.000 65.025 re f
0.267 0.267 0.267 rg
26.625 300.320 146.706 0.750 re f
26.625 284.439 0.750 16.631 re f
172.581 300.320 135.259 0.750 re f
172.581 284.439 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 177.831 290.465 Td /F4 9.8 Tf  [(Total)] TJ ET
0.267 0.267 0.267 rg
307.090 300.320 142.270 0.750 re f
307.090 284.439 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 312.340 290.465 Td /F4 9.8 Tf  [(prHD)] TJ ET
0.267 0.267 0.267 rg
448.610 300.320 132.265 0.750 re f
448.610 284.439 0.750 16.631 re f
580.125 284.439 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 453.860 290.465 Td /F4 9.8 Tf  [(HD)] TJ ET
0.267 0.267 0.267 rg
26.625 284.439 146.706 0.750 re f
26.625 268.558 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 274.584 Td /F4 9.8 Tf  [(Sample size)] TJ ET
0.267 0.267 0.267 rg
172.581 284.439 135.259 0.750 re f
172.581 268.558 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 177.831 274.584 Td /F1 9.8 Tf  [(N=225)] TJ ET
0.267 0.267 0.267 rg
307.090 284.439 142.270 0.750 re f
307.090 268.558 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 312.340 274.584 Td /F1 9.8 Tf  [(N=190 \(84%\))] TJ ET
0.267 0.267 0.267 rg
448.610 284.439 132.265 0.750 re f
448.610 268.558 0.750 16.631 re f
580.125 268.558 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 453.860 274.584 Td /F1 9.8 Tf  [(N=35 \(16%\))] TJ ET
0.267 0.267 0.267 rg
26.625 268.558 146.706 0.750 re f
26.625 252.676 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 258.703 Td /F4 9.8 Tf  [(Male gender)] TJ ET
0.267 0.267 0.267 rg
172.581 268.558 135.259 0.750 re f
172.581 252.676 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 177.831 258.703 Td /F1 9.8 Tf  [(N=98 \(44%\))] TJ ET
0.267 0.267 0.267 rg
307.090 268.558 142.270 0.750 re f
307.090 252.676 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 312.340 258.703 Td /F1 9.8 Tf  [(N=80 \(42%\))] TJ ET
0.267 0.267 0.267 rg
448.610 268.558 132.265 0.750 re f
448.610 252.676 0.750 16.631 re f
580.125 252.676 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 453.860 258.703 Td /F1 9.8 Tf  [(N=18 \(51%\))] TJ ET
0.267 0.267 0.267 rg
26.625 252.676 146.706 0.750 re f
26.625 236.795 146.706 0.750 re f
26.625 236.795 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 242.821 Td /F4 9.8 Tf  [(Age)] TJ ET
0.267 0.267 0.267 rg
172.581 252.676 135.259 0.750 re f
172.581 236.795 135.259 0.750 re f
172.581 236.795 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 177.831 242.821 Td /F1 9.8 Tf  [(44.4 \(18-81\))] TJ ET
0.267 0.267 0.267 rg
307.090 252.676 142.270 0.750 re f
307.090 236.795 142.270 0.750 re f
307.090 236.795 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 312.340 242.821 Td /F1 9.8 Tf  [(42.2 \(18-77\))] TJ ET
0.267 0.267 0.267 rg
448.610 252.676 132.265 0.750 re f
448.610 236.795 132.265 0.750 re f
448.610 236.795 0.750 16.631 re f
580.125 236.795 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 453.860 242.821 Td /F1 9.8 Tf  [(49.9 \(25-81\))] TJ ET
BT 26.250 189.396 Td /F1 9.8 Tf  [(A follow-up meeting \(via webinar\) was held with the working group to review data and make recommendations in moving )] TJ ET
BT 26.250 177.492 Td /F1 9.8 Tf  [(forward, including item deletion and modification/refinement. The FDA PRO Guidance was used to guide the decision making )] TJ ET
BT 26.250 165.587 Td /F1 9.8 Tf  [(process. )] TJ ET
0.267 0.267 0.267 rg
BT 65.806 165.587 Td /F1 9.8 Tf  [([2])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 146.182 Td /F1 9.8 Tf  [(OCCs and scoring frequency distributions were generated for each of the interview questions. Of the 12 tested, 6 interview )] TJ ET
BT 26.250 134.277 Td /F1 9.8 Tf  [(questions were found to produce scoring and discrimination across ranges of overall severity:)] TJ ET
0.271 0.267 0.267 RG
40.337 117.840 m 
40.337 118.287 40.154 118.731 39.838 119.047 c
39.522 119.363 39.078 119.546 38.631 119.546 c
38.185 119.546 37.741 119.363 37.425 119.047 c
37.109 118.731 36.925 118.287 36.925 117.840 c
36.925 117.394 37.109 116.950 37.425 116.634 c
37.741 116.318 38.185 116.134 38.631 116.134 c
39.078 116.134 39.522 116.318 39.838 116.634 c
40.154 116.950 40.337 117.394 40.337 117.840 c f
BT 45.750 114.873 Td /F1 9.8 Tf  [(Anger/irritability)] TJ ET
40.337 102.185 m 
40.337 102.632 40.154 103.076 39.838 103.392 c
39.522 103.708 39.078 103.892 38.631 103.892 c
38.185 103.892 37.741 103.708 37.425 103.392 c
37.109 103.076 36.925 102.632 36.925 102.185 c
36.925 101.739 37.109 101.295 37.425 100.979 c
37.741 100.663 38.185 100.479 38.631 100.479 c
39.078 100.479 39.522 100.663 39.838 100.979 c
40.154 101.295 40.337 101.739 40.337 102.185 c f
BT 45.750 99.218 Td /F1 9.8 Tf  [(Ease of Anger � provocation by other people)] TJ ET
40.337 86.531 m 
40.337 86.977 40.154 87.421 39.838 87.737 c
39.522 88.053 39.078 88.237 38.631 88.237 c
38.185 88.237 37.741 88.053 37.425 87.737 c
37.109 87.421 36.925 86.977 36.925 86.531 c
36.925 86.084 37.109 85.640 37.425 85.324 c
37.741 85.008 38.185 84.824 38.631 84.824 c
39.078 84.824 39.522 85.008 39.838 85.324 c
40.154 85.640 40.337 86.084 40.337 86.531 c f
BT 45.750 83.563 Td /F1 9.8 Tf  [(Ease of Anger � stressor)] TJ ET
40.337 70.876 m 
40.337 71.323 40.154 71.767 39.838 72.083 c
39.522 72.398 39.078 72.582 38.631 72.582 c
38.185 72.582 37.741 72.398 37.425 72.083 c
37.109 71.767 36.925 71.323 36.925 70.876 c
36.925 70.429 37.109 69.985 37.425 69.669 c
37.741 69.354 38.185 69.170 38.631 69.170 c
39.078 69.170 39.522 69.354 39.838 69.669 c
40.154 69.985 40.337 70.429 40.337 70.876 c f
BT 45.750 67.908 Td /F1 9.8 Tf  [(Ease of calming down)] TJ ET
40.337 55.221 m 
40.337 55.668 40.154 56.112 39.838 56.428 c
39.522 56.744 39.078 56.927 38.631 56.927 c
38.185 56.927 37.741 56.744 37.425 56.428 c
37.109 56.112 36.925 55.668 36.925 55.221 c
36.925 54.775 37.109 54.331 37.425 54.015 c
37.741 53.699 38.185 53.515 38.631 53.515 c
39.078 53.515 39.522 53.699 39.838 54.015 c
40.154 54.331 40.337 54.775 40.337 55.221 c f
BT 45.750 52.254 Td /F1 9.8 Tf  [(Calm down time)] TJ ET
Q
q
15.000 46.123 577.500 730.877 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(function of overall level of severity. In the present analyses, total score of all interview questions was used as a measure of )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(severity. To illustrate this, Figure 3 depicts a hypothetically ��ideal�� item from an item response perspective, which is )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(characterized by a clear identification of the range of severity scores over which an option is most likely to be endorsed, rapid )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(changes in the curves that correspond to changes in severity, and an orderly relationship between the weight assigned to the )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(option and the region of severity over which an item is likely to be endorsed. As such, OCCs provide a graphical representation )] TJ ET
BT 26.250 707.952 Td /F1 9.8 Tf  [(of how informative a particular item \(or symptom\) is as a measure of illness. Frequency distribution of option scoring within each )] TJ ET
BT 26.250 696.048 Td /F1 9.8 Tf  [(interview question were also generated.)] TJ ET
0.965 0.965 0.965 rg
26.250 440.026 555.000 246.141 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 686.167 m 581.250 686.167 l 581.250 685.417 l 26.250 685.417 l  f
26.250 440.026 m 581.250 440.026 l 581.250 440.776 l 26.250 440.776 l  f
q
225.000 0 0 180.000 35.250 496.417 cm /I5 Do
Q 
q
35.250 451.276 537.000 39.141 re W n
0.271 0.267 0.267 rg
BT 35.250 480.893 Td /F4 9.8 Tf  [(Fig. 3: OCC for a hypothetically ��ideal�� item.)] TJ ET
BT 35.250 461.523 Td /F1 9.8 Tf  [(The OCC shows the probability \( y -axis\) of endorsing a particular option for the item at different levels of the trait \( x -axis\).)] TJ ET
Q
BT 26.250 423.002 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 26.250 411.097 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 26.250 399.192 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 26.250 387.288 Td /F1 9.8 Tf  [(correlations between subscale scores and scores of individual questions not included in the subscale were computed.)] TJ ET
BT 26.250 350.685 Td /F4 12.0 Tf  [(Results)] TJ ET
BT 26.250 330.731 Td /F1 9.8 Tf  [(A total of 225 CRFs were completed. The participant demographic characteristics are shown in Table 2.)] TJ ET
BT 26.250 311.326 Td /F4 9.8 Tf  [(Table 2. Demographic Characteristics)] TJ ET
1.000 1.000 1.000 rg
26.250 236.420 555.000 65.025 re f
0.267 0.267 0.267 rg
26.625 300.320 146.706 0.750 re f
26.625 284.439 0.750 16.631 re f
172.581 300.320 135.259 0.750 re f
172.581 284.439 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 177.831 290.465 Td /F4 9.8 Tf  [(Total)] TJ ET
0.267 0.267 0.267 rg
307.090 300.320 142.270 0.750 re f
307.090 284.439 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 312.340 290.465 Td /F4 9.8 Tf  [(prHD)] TJ ET
0.267 0.267 0.267 rg
448.610 300.320 132.265 0.750 re f
448.610 284.439 0.750 16.631 re f
580.125 284.439 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 453.860 290.465 Td /F4 9.8 Tf  [(HD)] TJ ET
0.267 0.267 0.267 rg
26.625 284.439 146.706 0.750 re f
26.625 268.558 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 274.584 Td /F4 9.8 Tf  [(Sample size)] TJ ET
0.267 0.267 0.267 rg
172.581 284.439 135.259 0.750 re f
172.581 268.558 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 177.831 274.584 Td /F1 9.8 Tf  [(N=225)] TJ ET
0.267 0.267 0.267 rg
307.090 284.439 142.270 0.750 re f
307.090 268.558 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 312.340 274.584 Td /F1 9.8 Tf  [(N=190 \(84%\))] TJ ET
0.267 0.267 0.267 rg
448.610 284.439 132.265 0.750 re f
448.610 268.558 0.750 16.631 re f
580.125 268.558 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 453.860 274.584 Td /F1 9.8 Tf  [(N=35 \(16%\))] TJ ET
0.267 0.267 0.267 rg
26.625 268.558 146.706 0.750 re f
26.625 252.676 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 258.703 Td /F4 9.8 Tf  [(Male gender)] TJ ET
0.267 0.267 0.267 rg
172.581 268.558 135.259 0.750 re f
172.581 252.676 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 177.831 258.703 Td /F1 9.8 Tf  [(N=98 \(44%\))] TJ ET
0.267 0.267 0.267 rg
307.090 268.558 142.270 0.750 re f
307.090 252.676 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 312.340 258.703 Td /F1 9.8 Tf  [(N=80 \(42%\))] TJ ET
0.267 0.267 0.267 rg
448.610 268.558 132.265 0.750 re f
448.610 252.676 0.750 16.631 re f
580.125 252.676 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 453.860 258.703 Td /F1 9.8 Tf  [(N=18 \(51%\))] TJ ET
0.267 0.267 0.267 rg
26.625 252.676 146.706 0.750 re f
26.625 236.795 146.706 0.750 re f
26.625 236.795 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 242.821 Td /F4 9.8 Tf  [(Age)] TJ ET
0.267 0.267 0.267 rg
172.581 252.676 135.259 0.750 re f
172.581 236.795 135.259 0.750 re f
172.581 236.795 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 177.831 242.821 Td /F1 9.8 Tf  [(44.4 \(18-81\))] TJ ET
0.267 0.267 0.267 rg
307.090 252.676 142.270 0.750 re f
307.090 236.795 142.270 0.750 re f
307.090 236.795 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 312.340 242.821 Td /F1 9.8 Tf  [(42.2 \(18-77\))] TJ ET
0.267 0.267 0.267 rg
448.610 252.676 132.265 0.750 re f
448.610 236.795 132.265 0.750 re f
448.610 236.795 0.750 16.631 re f
580.125 236.795 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 453.860 242.821 Td /F1 9.8 Tf  [(49.9 \(25-81\))] TJ ET
BT 26.250 189.396 Td /F1 9.8 Tf  [(A follow-up meeting \(via webinar\) was held with the working group to review data and make recommendations in moving )] TJ ET
BT 26.250 177.492 Td /F1 9.8 Tf  [(forward, including item deletion and modification/refinement. The FDA PRO Guidance was used to guide the decision making )] TJ ET
BT 26.250 165.587 Td /F1 9.8 Tf  [(process. )] TJ ET
0.267 0.267 0.267 rg
BT 65.806 165.587 Td /F1 9.8 Tf  [([2])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 146.182 Td /F1 9.8 Tf  [(OCCs and scoring frequency distributions were generated for each of the interview questions. Of the 12 tested, 6 interview )] TJ ET
BT 26.250 134.277 Td /F1 9.8 Tf  [(questions were found to produce scoring and discrimination across ranges of overall severity:)] TJ ET
0.271 0.267 0.267 RG
40.337 117.840 m 
40.337 118.287 40.154 118.731 39.838 119.047 c
39.522 119.363 39.078 119.546 38.631 119.546 c
38.185 119.546 37.741 119.363 37.425 119.047 c
37.109 118.731 36.925 118.287 36.925 117.840 c
36.925 117.394 37.109 116.950 37.425 116.634 c
37.741 116.318 38.185 116.134 38.631 116.134 c
39.078 116.134 39.522 116.318 39.838 116.634 c
40.154 116.950 40.337 117.394 40.337 117.840 c f
BT 45.750 114.873 Td /F1 9.8 Tf  [(Anger/irritability)] TJ ET
40.337 102.185 m 
40.337 102.632 40.154 103.076 39.838 103.392 c
39.522 103.708 39.078 103.892 38.631 103.892 c
38.185 103.892 37.741 103.708 37.425 103.392 c
37.109 103.076 36.925 102.632 36.925 102.185 c
36.925 101.739 37.109 101.295 37.425 100.979 c
37.741 100.663 38.185 100.479 38.631 100.479 c
39.078 100.479 39.522 100.663 39.838 100.979 c
40.154 101.295 40.337 101.739 40.337 102.185 c f
BT 45.750 99.218 Td /F1 9.8 Tf  [(Ease of Anger � provocation by other people)] TJ ET
40.337 86.531 m 
40.337 86.977 40.154 87.421 39.838 87.737 c
39.522 88.053 39.078 88.237 38.631 88.237 c
38.185 88.237 37.741 88.053 37.425 87.737 c
37.109 87.421 36.925 86.977 36.925 86.531 c
36.925 86.084 37.109 85.640 37.425 85.324 c
37.741 85.008 38.185 84.824 38.631 84.824 c
39.078 84.824 39.522 85.008 39.838 85.324 c
40.154 85.640 40.337 86.084 40.337 86.531 c f
BT 45.750 83.563 Td /F1 9.8 Tf  [(Ease of Anger � stressor)] TJ ET
40.337 70.876 m 
40.337 71.323 40.154 71.767 39.838 72.083 c
39.522 72.398 39.078 72.582 38.631 72.582 c
38.185 72.582 37.741 72.398 37.425 72.083 c
37.109 71.767 36.925 71.323 36.925 70.876 c
36.925 70.429 37.109 69.985 37.425 69.669 c
37.741 69.354 38.185 69.170 38.631 69.170 c
39.078 69.170 39.522 69.354 39.838 69.669 c
40.154 69.985 40.337 70.429 40.337 70.876 c f
BT 45.750 67.908 Td /F1 9.8 Tf  [(Ease of calming down)] TJ ET
40.337 55.221 m 
40.337 55.668 40.154 56.112 39.838 56.428 c
39.522 56.744 39.078 56.927 38.631 56.927 c
38.185 56.927 37.741 56.744 37.425 56.428 c
37.109 56.112 36.925 55.668 36.925 55.221 c
36.925 54.775 37.109 54.331 37.425 54.015 c
37.741 53.699 38.185 53.515 38.631 53.515 c
39.078 53.515 39.522 53.699 39.838 54.015 c
40.154 54.331 40.337 54.775 40.337 55.221 c f
BT 45.750 52.254 Td /F1 9.8 Tf  [(Calm down time)] TJ ET
Q
q
15.000 46.123 577.500 730.877 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(function of overall level of severity. In the present analyses, total score of all interview questions was used as a measure of )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(severity. To illustrate this, Figure 3 depicts a hypothetically ��ideal�� item from an item response perspective, which is )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(characterized by a clear identification of the range of severity scores over which an option is most likely to be endorsed, rapid )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(changes in the curves that correspond to changes in severity, and an orderly relationship between the weight assigned to the )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(option and the region of severity over which an item is likely to be endorsed. As such, OCCs provide a graphical representation )] TJ ET
BT 26.250 707.952 Td /F1 9.8 Tf  [(of how informative a particular item \(or symptom\) is as a measure of illness. Frequency distribution of option scoring within each )] TJ ET
BT 26.250 696.048 Td /F1 9.8 Tf  [(interview question were also generated.)] TJ ET
0.965 0.965 0.965 rg
26.250 440.026 555.000 246.141 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 686.167 m 581.250 686.167 l 581.250 685.417 l 26.250 685.417 l  f
26.250 440.026 m 581.250 440.026 l 581.250 440.776 l 26.250 440.776 l  f
q
225.000 0 0 180.000 35.250 496.417 cm /I5 Do
Q 
q
35.250 451.276 537.000 39.141 re W n
0.271 0.267 0.267 rg
BT 35.250 480.893 Td /F4 9.8 Tf  [(Fig. 3: OCC for a hypothetically ��ideal�� item.)] TJ ET
BT 35.250 461.523 Td /F1 9.8 Tf  [(The OCC shows the probability \( y -axis\) of endorsing a particular option for the item at different levels of the trait \( x -axis\).)] TJ ET
Q
BT 26.250 423.002 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 26.250 411.097 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 26.250 399.192 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 26.250 387.288 Td /F1 9.8 Tf  [(correlations between subscale scores and scores of individual questions not included in the subscale were computed.)] TJ ET
BT 26.250 350.685 Td /F4 12.0 Tf  [(Results)] TJ ET
BT 26.250 330.731 Td /F1 9.8 Tf  [(A total of 225 CRFs were completed. The participant demographic characteristics are shown in Table 2.)] TJ ET
BT 26.250 311.326 Td /F4 9.8 Tf  [(Table 2. Demographic Characteristics)] TJ ET
1.000 1.000 1.000 rg
26.250 236.420 555.000 65.025 re f
0.267 0.267 0.267 rg
26.625 300.320 146.706 0.750 re f
26.625 284.439 0.750 16.631 re f
172.581 300.320 135.259 0.750 re f
172.581 284.439 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 177.831 290.465 Td /F4 9.8 Tf  [(Total)] TJ ET
0.267 0.267 0.267 rg
307.090 300.320 142.270 0.750 re f
307.090 284.439 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 312.340 290.465 Td /F4 9.8 Tf  [(prHD)] TJ ET
0.267 0.267 0.267 rg
448.610 300.320 132.265 0.750 re f
448.610 284.439 0.750 16.631 re f
580.125 284.439 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 453.860 290.465 Td /F4 9.8 Tf  [(HD)] TJ ET
0.267 0.267 0.267 rg
26.625 284.439 146.706 0.750 re f
26.625 268.558 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 274.584 Td /F4 9.8 Tf  [(Sample size)] TJ ET
0.267 0.267 0.267 rg
172.581 284.439 135.259 0.750 re f
172.581 268.558 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 177.831 274.584 Td /F1 9.8 Tf  [(N=225)] TJ ET
0.267 0.267 0.267 rg
307.090 284.439 142.270 0.750 re f
307.090 268.558 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 312.340 274.584 Td /F1 9.8 Tf  [(N=190 \(84%\))] TJ ET
0.267 0.267 0.267 rg
448.610 284.439 132.265 0.750 re f
448.610 268.558 0.750 16.631 re f
580.125 268.558 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 453.860 274.584 Td /F1 9.8 Tf  [(N=35 \(16%\))] TJ ET
0.267 0.267 0.267 rg
26.625 268.558 146.706 0.750 re f
26.625 252.676 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 258.703 Td /F4 9.8 Tf  [(Male gender)] TJ ET
0.267 0.267 0.267 rg
172.581 268.558 135.259 0.750 re f
172.581 252.676 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 177.831 258.703 Td /F1 9.8 Tf  [(N=98 \(44%\))] TJ ET
0.267 0.267 0.267 rg
307.090 268.558 142.270 0.750 re f
307.090 252.676 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 312.340 258.703 Td /F1 9.8 Tf  [(N=80 \(42%\))] TJ ET
0.267 0.267 0.267 rg
448.610 268.558 132.265 0.750 re f
448.610 252.676 0.750 16.631 re f
580.125 252.676 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 453.860 258.703 Td /F1 9.8 Tf  [(N=18 \(51%\))] TJ ET
0.267 0.267 0.267 rg
26.625 252.676 146.706 0.750 re f
26.625 236.795 146.706 0.750 re f
26.625 236.795 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 242.821 Td /F4 9.8 Tf  [(Age)] TJ ET
0.267 0.267 0.267 rg
172.581 252.676 135.259 0.750 re f
172.581 236.795 135.259 0.750 re f
172.581 236.795 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 177.831 242.821 Td /F1 9.8 Tf  [(44.4 \(18-81\))] TJ ET
0.267 0.267 0.267 rg
307.090 252.676 142.270 0.750 re f
307.090 236.795 142.270 0.750 re f
307.090 236.795 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 312.340 242.821 Td /F1 9.8 Tf  [(42.2 \(18-77\))] TJ ET
0.267 0.267 0.267 rg
448.610 252.676 132.265 0.750 re f
448.610 236.795 132.265 0.750 re f
448.610 236.795 0.750 16.631 re f
580.125 236.795 0.750 16.631 re f
0.271 0.267 0.267 rg
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40.154 769.553 40.337 769.997 40.337 770.444 c f
BT 45.750 767.476 Td /F1 9.8 Tf  [(Compromise)] TJ ET
BT 26.250 744.321 Td /F1 9.8 Tf  [(The internal consistency of these six items was high, as were the corrected item-total correlations \(Table 3, shaded rows\). )] TJ ET
BT 26.250 732.417 Td /F1 9.8 Tf  [(Cronbach�s alpha was 0.86 with respect to the entire study population, 0.85 with respect to the prHD subgroup, and 0.92 with )] TJ ET
BT 26.250 720.512 Td /F1 9.8 Tf  [(respect to the HD subgroup. All corrected item-total correlations were 0.52 or higher with respect to the prHD subgroup and )] TJ ET
BT 26.250 708.607 Td /F1 9.8 Tf  [(0.67 or higher with respect to the HD subgroup \(Table 3\).)] TJ ET
BT 26.250 689.202 Td /F1 9.8 Tf  [(The mean total composite score with respect to the above 6 questions was 3.69 in prHD subjects and 3.70 in HD subjects; the )] TJ ET
BT 26.250 677.298 Td /F1 9.8 Tf  [(difference in mean scores was not statistically significant \(p = 0.81, Mann-Whitney U test\). No significant differences were noted )] TJ ET
BT 26.250 665.393 Td /F1 9.8 Tf  [(in scoring between prHD and HD for any of the 6 individual interview questions, with respect to either intensity or frequency of )] TJ ET
BT 26.250 653.488 Td /F1 9.8 Tf  [(symptoms.)] TJ ET
BT 26.250 634.083 Td /F4 9.8 Tf  [(Table 3. )] TJ ET
BT 65.269 634.083 Td /F1 9.8 Tf  [( Correlations Between Interview Questions Scores)] TJ ET
1.000 1.000 1.000 rg
26.250 408.615 555.000 215.588 re f
0.267 0.267 0.267 rg
26.625 623.077 179.617 0.750 re f
26.625 599.565 0.750 24.262 re f
0.271 0.267 0.267 rg
BT 31.875 613.223 Td /F1 9.8 Tf  [(Interview Question)] TJ ET
0.267 0.267 0.267 rg
205.492 623.077 125.628 0.750 re f
205.492 599.565 0.750 24.262 re f
0.271 0.267 0.267 rg
BT 210.742 613.223 Td /F1 9.8 Tf  [(Item-total correlation )] TJ ET
BT 210.742 605.591 Td /F1 9.8 Tf  [(\(all subjects\))] TJ ET
0.267 0.267 0.267 rg
330.370 623.077 125.628 0.750 re f
330.370 599.565 0.750 24.262 re f
0.271 0.267 0.267 rg
BT 335.620 613.223 Td /F1 9.8 Tf  [(Item-total correlation )] TJ ET
BT 335.620 605.591 Td /F1 9.8 Tf  [(\(prHD subjects\))] TJ ET
0.267 0.267 0.267 rg
455.247 623.077 125.628 0.750 re f
455.247 599.565 0.750 24.262 re f
580.125 599.565 0.750 24.262 re f
0.271 0.267 0.267 rg
BT 460.497 613.223 Td /F1 9.8 Tf  [(Item-total correlation )] TJ ET
BT 460.497 605.591 Td /F1 9.8 Tf  [(\(HD subjects\))] TJ ET
0.812 0.886 0.953 rg
27.000 584.059 178.867 15.881 re f
0.267 0.267 0.267 rg
26.625 599.565 179.617 0.750 re f
26.625 583.684 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 589.710 Td /F1 9.8 Tf  [(Anger/Irritability)] TJ ET
0.812 0.886 0.953 rg
205.867 584.059 124.878 15.881 re f
0.267 0.267 0.267 rg
205.492 599.565 125.628 0.750 re f
205.492 583.684 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 589.710 Td /F1 9.8 Tf  [(0.71)] TJ ET
0.812 0.886 0.953 rg
330.745 584.059 124.878 15.881 re f
0.267 0.267 0.267 rg
330.370 599.565 125.628 0.750 re f
330.370 583.684 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 589.710 Td /F1 9.8 Tf  [(0.70)] TJ ET
0.812 0.886 0.953 rg
455.622 584.059 124.878 15.881 re f
0.267 0.267 0.267 rg
455.247 599.565 125.628 0.750 re f
455.247 583.684 0.750 16.631 re f
580.125 583.684 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 589.710 Td /F1 9.8 Tf  [(0.79)] TJ ET
0.812 0.886 0.953 rg
27.000 568.178 178.867 15.881 re f
0.267 0.267 0.267 rg
26.625 583.684 179.617 0.750 re f
26.625 567.803 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 573.829 Td /F1 9.8 Tf  [(Ease of anger � provocation)] TJ ET
0.812 0.886 0.953 rg
205.867 568.178 124.878 15.881 re f
0.267 0.267 0.267 rg
205.492 583.684 125.628 0.750 re f
205.492 567.803 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 573.829 Td /F1 9.8 Tf  [(0.63)] TJ ET
0.812 0.886 0.953 rg
330.745 568.178 124.878 15.881 re f
0.267 0.267 0.267 rg
330.370 583.684 125.628 0.750 re f
330.370 567.803 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 573.829 Td /F1 9.8 Tf  [(0.60)] TJ ET
0.812 0.886 0.953 rg
455.622 568.178 124.878 15.881 re f
0.267 0.267 0.267 rg
455.247 583.684 125.628 0.750 re f
455.247 567.803 0.750 16.631 re f
580.125 567.803 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 573.829 Td /F1 9.8 Tf  [(0.78)] TJ ET
0.812 0.886 0.953 rg
27.000 552.296 178.867 15.881 re f
0.267 0.267 0.267 rg
26.625 567.803 179.617 0.750 re f
26.625 551.921 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 557.947 Td /F1 9.8 Tf  [(Ease of anger � stressor)] TJ ET
0.812 0.886 0.953 rg
205.867 552.296 124.878 15.881 re f
0.267 0.267 0.267 rg
205.492 567.803 125.628 0.750 re f
205.492 551.921 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 557.947 Td /F1 9.8 Tf  [(0.70)] TJ ET
0.812 0.886 0.953 rg
330.745 552.296 124.878 15.881 re f
0.267 0.267 0.267 rg
330.370 567.803 125.628 0.750 re f
330.370 551.921 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 557.947 Td /F1 9.8 Tf  [(0.68)] TJ ET
0.812 0.886 0.953 rg
455.622 552.296 124.878 15.881 re f
0.267 0.267 0.267 rg
455.247 567.803 125.628 0.750 re f
455.247 551.921 0.750 16.631 re f
580.125 551.921 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 557.947 Td /F1 9.8 Tf  [(0.75)] TJ ET
0.812 0.886 0.953 rg
27.000 536.415 178.867 15.881 re f
0.267 0.267 0.267 rg
26.625 551.921 179.617 0.750 re f
26.625 536.040 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 542.066 Td /F1 9.8 Tf  [(Ease of calming down)] TJ ET
0.812 0.886 0.953 rg
205.867 536.415 124.878 15.881 re f
0.267 0.267 0.267 rg
205.492 551.921 125.628 0.750 re f
205.492 536.040 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 542.066 Td /F1 9.8 Tf  [(0.69)] TJ ET
0.812 0.886 0.953 rg
330.745 536.415 124.878 15.881 re f
0.267 0.267 0.267 rg
330.370 551.921 125.628 0.750 re f
330.370 536.040 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 542.066 Td /F1 9.8 Tf  [(0.64)] TJ ET
0.812 0.886 0.953 rg
455.622 536.415 124.878 15.881 re f
0.267 0.267 0.267 rg
455.247 551.921 125.628 0.750 re f
455.247 536.040 0.750 16.631 re f
580.125 536.040 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 542.066 Td /F1 9.8 Tf  [(0.92)] TJ ET
0.812 0.886 0.953 rg
27.000 520.534 178.867 15.881 re f
0.267 0.267 0.267 rg
26.625 536.040 179.617 0.750 re f
26.625 520.159 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 526.185 Td /F1 9.8 Tf  [(Calm down time)] TJ ET
0.812 0.886 0.953 rg
205.867 520.534 124.878 15.881 re f
0.267 0.267 0.267 rg
205.492 536.040 125.628 0.750 re f
205.492 520.159 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 526.185 Td /F1 9.8 Tf  [(0.69)] TJ ET
0.812 0.886 0.953 rg
330.745 520.534 124.878 15.881 re f
0.267 0.267 0.267 rg
330.370 536.040 125.628 0.750 re f
330.370 520.159 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 526.185 Td /F1 9.8 Tf  [(0.68)] TJ ET
0.812 0.886 0.953 rg
455.622 520.534 124.878 15.881 re f
0.267 0.267 0.267 rg
455.247 536.040 125.628 0.750 re f
455.247 520.159 0.750 16.631 re f
580.125 520.159 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 526.185 Td /F1 9.8 Tf  [(0.78)] TJ ET
0.267 0.267 0.267 rg
26.625 520.159 179.617 0.750 re f
26.625 504.278 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 510.304 Td /F1 9.8 Tf  [(Aggression � people)] TJ ET
0.267 0.267 0.267 rg
205.492 520.159 125.628 0.750 re f
205.492 504.278 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 510.304 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
330.370 520.159 125.628 0.750 re f
330.370 504.278 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 510.304 Td /F1 9.8 Tf  [(0.39)] TJ ET
0.267 0.267 0.267 rg
455.247 520.159 125.628 0.750 re f
455.247 504.278 0.750 16.631 re f
580.125 504.278 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 510.304 Td /F1 9.8 Tf  [(0.62)] TJ ET
0.267 0.267 0.267 rg
26.625 504.278 179.617 0.750 re f
26.625 488.396 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 494.423 Td /F1 9.8 Tf  [(Aggression � animals/objects)] TJ ET
0.267 0.267 0.267 rg
205.492 504.278 125.628 0.750 re f
205.492 488.396 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 494.423 Td /F1 9.8 Tf  [(0.36)] TJ ET
0.267 0.267 0.267 rg
330.370 504.278 125.628 0.750 re f
330.370 488.396 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 494.423 Td /F1 9.8 Tf  [(0.38)] TJ ET
0.267 0.267 0.267 rg
455.247 504.278 125.628 0.750 re f
455.247 488.396 0.750 16.631 re f
580.125 488.396 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 494.423 Td /F1 9.8 Tf  [(0.29)] TJ ET
0.267 0.267 0.267 rg
26.625 488.396 179.617 0.750 re f
26.625 472.515 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 478.541 Td /F1 9.8 Tf  [(Repetitive thoughts)] TJ ET
0.267 0.267 0.267 rg
205.492 488.396 125.628 0.750 re f
205.492 472.515 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 478.541 Td /F1 9.8 Tf  [(0.29)] TJ ET
0.267 0.267 0.267 rg
330.370 488.396 125.628 0.750 re f
330.370 472.515 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 478.541 Td /F1 9.8 Tf  [(0.34)] TJ ET
0.267 0.267 0.267 rg
455.247 488.396 125.628 0.750 re f
455.247 472.515 0.750 16.631 re f
580.125 472.515 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 478.541 Td /F1 9.8 Tf  [(0.14)] TJ ET
0.812 0.886 0.953 rg
27.000 457.009 178.867 15.881 re f
0.267 0.267 0.267 rg
26.625 472.515 179.617 0.750 re f
26.625 456.634 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 462.660 Td /F1 9.8 Tf  [(Compromise)] TJ ET
0.812 0.886 0.953 rg
205.867 457.009 124.878 15.881 re f
0.267 0.267 0.267 rg
205.492 472.515 125.628 0.750 re f
205.492 456.634 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 462.660 Td /F1 9.8 Tf  [(0.54)] TJ ET
0.812 0.886 0.953 rg
330.745 457.009 124.878 15.881 re f
0.267 0.267 0.267 rg
330.370 472.515 125.628 0.750 re f
330.370 456.634 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 462.660 Td /F1 9.8 Tf  [(0.52)] TJ ET
0.812 0.886 0.953 rg
455.622 457.009 124.878 15.881 re f
0.267 0.267 0.267 rg
455.247 472.515 125.628 0.750 re f
455.247 456.634 0.750 16.631 re f
580.125 456.634 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 462.660 Td /F1 9.8 Tf  [(0.67)] TJ ET
0.267 0.267 0.267 rg
26.625 456.634 179.617 0.750 re f
26.625 440.752 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 446.779 Td /F1 9.8 Tf  [(Perseveration � tasks)] TJ ET
0.267 0.267 0.267 rg
205.492 456.634 125.628 0.750 re f
205.492 440.752 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 446.779 Td /F1 9.8 Tf  [(0.23)] TJ ET
0.267 0.267 0.267 rg
330.370 456.634 125.628 0.750 re f
330.370 440.752 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 446.779 Td /F1 9.8 Tf  [(0.22)] TJ ET
0.267 0.267 0.267 rg
455.247 456.634 125.628 0.750 re f
455.247 440.752 0.750 16.631 re f
580.125 440.752 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 446.779 Td /F1 9.8 Tf  [(0.28)] TJ ET
0.267 0.267 0.267 rg
26.625 440.752 179.617 0.750 re f
26.625 424.871 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 430.897 Td /F1 9.8 Tf  [(Perseveration � conversation)] TJ ET
0.267 0.267 0.267 rg
205.492 440.752 125.628 0.750 re f
205.492 424.871 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 430.897 Td /F1 9.8 Tf  [(0.16)] TJ ET
0.267 0.267 0.267 rg
330.370 440.752 125.628 0.750 re f
330.370 424.871 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 430.897 Td /F1 9.8 Tf  [(0.14)] TJ ET
0.267 0.267 0.267 rg
455.247 440.752 125.628 0.750 re f
455.247 424.871 0.750 16.631 re f
580.125 424.871 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 430.897 Td /F1 9.8 Tf  [(0.24)] TJ ET
0.267 0.267 0.267 rg
26.625 424.871 179.617 0.750 re f
26.625 408.990 179.617 0.750 re f
26.625 408.990 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 415.016 Td /F1 9.8 Tf  [(Mental inflexibility/rigidity)] TJ ET
0.267 0.267 0.267 rg
205.492 424.871 125.628 0.750 re f
205.492 408.990 125.628 0.750 re f
205.492 408.990 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 415.016 Td /F1 9.8 Tf  [(0.16)] TJ ET
0.267 0.267 0.267 rg
330.370 424.871 125.628 0.750 re f
330.370 408.990 125.628 0.750 re f
330.370 408.990 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 415.016 Td /F1 9.8 Tf  [(0.16)] TJ ET
0.267 0.267 0.267 rg
455.247 424.871 125.628 0.750 re f
455.247 408.990 125.628 0.750 re f
455.247 408.990 0.750 16.631 re f
580.125 408.990 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 415.016 Td /F1 9.8 Tf  [(0.16)] TJ ET
BT 26.250 361.591 Td /F1 9.8 Tf  [(It was agreed that these 6 interview questions would be modified accordingly for testing in subsequent iterations; examination of )] TJ ET
BT 26.250 349.686 Td /F1 9.8 Tf  [(the OCCs provided data on which decisions could be made as to where modifications should be made to improve item )] TJ ET
BT 26.250 337.782 Td /F1 9.8 Tf  [(performance, including changes in wording and scoring options. For example, Figure 4 shows the OCCs for the Anger/Irritability )] TJ ET
BT 26.250 325.877 Td /F1 9.8 Tf  [(question. The options with the highest probably of being scored for symptom intensity increased from �0� to �1� \(mild: somewhat )] TJ ET
BT 26.250 313.972 Td /F1 9.8 Tf  [(irritable, with minor autonomic arousal\) to �2� \(moderate: very irritable, definite autonomic arousal, but no overt aggression )] TJ ET
BT 26.250 302.067 Td /F1 9.8 Tf  [(expressed\); however, scores of �3� \(severe: definite expression of anger, transient loss of control\) and �4� \(very severe: definite )] TJ ET
BT 26.250 290.163 Td /F1 9.8 Tf  [(loss of control, throwing objects, injury to persons, animals, objects, or self\) were rarely endorsed, suggesting that aggressive or )] TJ ET
BT 26.250 278.258 Td /F1 9.8 Tf  [(violent outbursts are not typically characteristic symptoms in this population. Indeed, interview questions aimed to directly )] TJ ET
BT 26.250 266.353 Td /F1 9.8 Tf  [(assess aggression \(see Table 1\) were hardly endorsed. Also of note was that the distribution of options scoring was similar in )] TJ ET
BT 26.250 254.448 Td /F1 9.8 Tf  [(prHD and HD participants \(Figure 4, as example\), suggesting that these behavioral symptoms do not worsen in early HD or )] TJ ET
BT 26.250 242.544 Td /F1 9.8 Tf  [(track with the development of early motor manifestations.)] TJ ET
0.267 0.267 0.267 rg
BT 272.808 242.544 Td /F1 9.8 Tf  [([6])] TJ ET
0.271 0.267 0.267 rg
BT 283.650 242.544 Td /F1 9.8 Tf  [(Finally, with respect to the frequency of symptoms, most symptoms )] TJ ET
BT 26.250 230.639 Td /F1 9.8 Tf  [(\(when present\) were described as occurring occasionally \(i.e., score of 1, see Figure 4\), suggesting that the measurement of )] TJ ET
BT 26.250 218.734 Td /F1 9.8 Tf  [(severity of anger/irritability may sufficiently be captured by symptom intensity alone.)] TJ ET
0.965 0.965 0.965 rg
26.250 24.353 555.000 184.500 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 208.853 m 581.250 208.853 l 581.250 208.103 l 26.250 208.103 l  f
q
225.000 0 0 168.750 35.250 30.353 cm /I6 Do
Q 
q
35.250 24.353 537.000 0.000 re W n
Q
Q
q
15.000 24.353 577.500 752.647 re W n
0.271 0.267 0.267 rg
0.271 0.267 0.267 RG
40.337 770.444 m 
40.337 770.890 40.154 771.334 39.838 771.650 c
39.522 771.966 39.078 772.150 38.631 772.150 c
38.185 772.150 37.741 771.966 37.425 771.650 c
37.109 771.334 36.925 770.890 36.925 770.444 c
36.925 769.997 37.109 769.553 37.425 769.237 c
37.741 768.921 38.185 768.738 38.631 768.738 c
39.078 768.738 39.522 768.921 39.838 769.237 c
40.154 769.553 40.337 769.997 40.337 770.444 c f
BT 45.750 767.476 Td /F1 9.8 Tf  [(Compromise)] TJ ET
BT 26.250 744.321 Td /F1 9.8 Tf  [(The internal consistency of these six items was high, as were the corrected item-total correlations \(Table 3, shaded rows\). )] TJ ET
BT 26.250 732.417 Td /F1 9.8 Tf  [(Cronbach�s alpha was 0.86 with respect to the entire study population, 0.85 with respect to the prHD subgroup, and 0.92 with )] TJ ET
BT 26.250 720.512 Td /F1 9.8 Tf  [(respect to the HD subgroup. All corrected item-total correlations were 0.52 or higher with respect to the prHD subgroup and )] TJ ET
BT 26.250 708.607 Td /F1 9.8 Tf  [(0.67 or higher with respect to the HD subgroup \(Table 3\).)] TJ ET
BT 26.250 689.202 Td /F1 9.8 Tf  [(The mean total composite score with respect to the above 6 questions was 3.69 in prHD subjects and 3.70 in HD subjects; the )] TJ ET
BT 26.250 677.298 Td /F1 9.8 Tf  [(difference in mean scores was not statistically significant \(p = 0.81, Mann-Whitney U test\). No significant differences were noted )] TJ ET
BT 26.250 665.393 Td /F1 9.8 Tf  [(in scoring between prHD and HD for any of the 6 individual interview questions, with respect to either intensity or frequency of )] TJ ET
BT 26.250 653.488 Td /F1 9.8 Tf  [(symptoms.)] TJ ET
BT 26.250 634.083 Td /F4 9.8 Tf  [(Table 3. )] TJ ET
BT 65.269 634.083 Td /F1 9.8 Tf  [( Correlations Between Interview Questions Scores)] TJ ET
1.000 1.000 1.000 rg
26.250 408.615 555.000 215.588 re f
0.267 0.267 0.267 rg
26.625 623.077 179.617 0.750 re f
26.625 599.565 0.750 24.262 re f
0.271 0.267 0.267 rg
BT 31.875 613.223 Td /F1 9.8 Tf  [(Interview Question)] TJ ET
0.267 0.267 0.267 rg
205.492 623.077 125.628 0.750 re f
205.492 599.565 0.750 24.262 re f
0.271 0.267 0.267 rg
BT 210.742 613.223 Td /F1 9.8 Tf  [(Item-total correlation )] TJ ET
BT 210.742 605.591 Td /F1 9.8 Tf  [(\(all subjects\))] TJ ET
0.267 0.267 0.267 rg
330.370 623.077 125.628 0.750 re f
330.370 599.565 0.750 24.262 re f
0.271 0.267 0.267 rg
BT 335.620 613.223 Td /F1 9.8 Tf  [(Item-total correlation )] TJ ET
BT 335.620 605.591 Td /F1 9.8 Tf  [(\(prHD subjects\))] TJ ET
0.267 0.267 0.267 rg
455.247 623.077 125.628 0.750 re f
455.247 599.565 0.750 24.262 re f
580.125 599.565 0.750 24.262 re f
0.271 0.267 0.267 rg
BT 460.497 613.223 Td /F1 9.8 Tf  [(Item-total correlation )] TJ ET
BT 460.497 605.591 Td /F1 9.8 Tf  [(\(HD subjects\))] TJ ET
0.812 0.886 0.953 rg
27.000 584.059 178.867 15.881 re f
0.267 0.267 0.267 rg
26.625 599.565 179.617 0.750 re f
26.625 583.684 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 589.710 Td /F1 9.8 Tf  [(Anger/Irritability)] TJ ET
0.812 0.886 0.953 rg
205.867 584.059 124.878 15.881 re f
0.267 0.267 0.267 rg
205.492 599.565 125.628 0.750 re f
205.492 583.684 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 589.710 Td /F1 9.8 Tf  [(0.71)] TJ ET
0.812 0.886 0.953 rg
330.745 584.059 124.878 15.881 re f
0.267 0.267 0.267 rg
330.370 599.565 125.628 0.750 re f
330.370 583.684 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 589.710 Td /F1 9.8 Tf  [(0.70)] TJ ET
0.812 0.886 0.953 rg
455.622 584.059 124.878 15.881 re f
0.267 0.267 0.267 rg
455.247 599.565 125.628 0.750 re f
455.247 583.684 0.750 16.631 re f
580.125 583.684 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 589.710 Td /F1 9.8 Tf  [(0.79)] TJ ET
0.812 0.886 0.953 rg
27.000 568.178 178.867 15.881 re f
0.267 0.267 0.267 rg
26.625 583.684 179.617 0.750 re f
26.625 567.803 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 573.829 Td /F1 9.8 Tf  [(Ease of anger � provocation)] TJ ET
0.812 0.886 0.953 rg
205.867 568.178 124.878 15.881 re f
0.267 0.267 0.267 rg
205.492 583.684 125.628 0.750 re f
205.492 567.803 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 573.829 Td /F1 9.8 Tf  [(0.63)] TJ ET
0.812 0.886 0.953 rg
330.745 568.178 124.878 15.881 re f
0.267 0.267 0.267 rg
330.370 583.684 125.628 0.750 re f
330.370 567.803 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 573.829 Td /F1 9.8 Tf  [(0.60)] TJ ET
0.812 0.886 0.953 rg
455.622 568.178 124.878 15.881 re f
0.267 0.267 0.267 rg
455.247 583.684 125.628 0.750 re f
455.247 567.803 0.750 16.631 re f
580.125 567.803 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 573.829 Td /F1 9.8 Tf  [(0.78)] TJ ET
0.812 0.886 0.953 rg
27.000 552.296 178.867 15.881 re f
0.267 0.267 0.267 rg
26.625 567.803 179.617 0.750 re f
26.625 551.921 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 557.947 Td /F1 9.8 Tf  [(Ease of anger � stressor)] TJ ET
0.812 0.886 0.953 rg
205.867 552.296 124.878 15.881 re f
0.267 0.267 0.267 rg
205.492 567.803 125.628 0.750 re f
205.492 551.921 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 557.947 Td /F1 9.8 Tf  [(0.70)] TJ ET
0.812 0.886 0.953 rg
330.745 552.296 124.878 15.881 re f
0.267 0.267 0.267 rg
330.370 567.803 125.628 0.750 re f
330.370 551.921 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 557.947 Td /F1 9.8 Tf  [(0.68)] TJ ET
0.812 0.886 0.953 rg
455.622 552.296 124.878 15.881 re f
0.267 0.267 0.267 rg
455.247 567.803 125.628 0.750 re f
455.247 551.921 0.750 16.631 re f
580.125 551.921 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 557.947 Td /F1 9.8 Tf  [(0.75)] TJ ET
0.812 0.886 0.953 rg
27.000 536.415 178.867 15.881 re f
0.267 0.267 0.267 rg
26.625 551.921 179.617 0.750 re f
26.625 536.040 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 542.066 Td /F1 9.8 Tf  [(Ease of calming down)] TJ ET
0.812 0.886 0.953 rg
205.867 536.415 124.878 15.881 re f
0.267 0.267 0.267 rg
205.492 551.921 125.628 0.750 re f
205.492 536.040 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 542.066 Td /F1 9.8 Tf  [(0.69)] TJ ET
0.812 0.886 0.953 rg
330.745 536.415 124.878 15.881 re f
0.267 0.267 0.267 rg
330.370 551.921 125.628 0.750 re f
330.370 536.040 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 542.066 Td /F1 9.8 Tf  [(0.64)] TJ ET
0.812 0.886 0.953 rg
455.622 536.415 124.878 15.881 re f
0.267 0.267 0.267 rg
455.247 551.921 125.628 0.750 re f
455.247 536.040 0.750 16.631 re f
580.125 536.040 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 542.066 Td /F1 9.8 Tf  [(0.92)] TJ ET
0.812 0.886 0.953 rg
27.000 520.534 178.867 15.881 re f
0.267 0.267 0.267 rg
26.625 536.040 179.617 0.750 re f
26.625 520.159 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 526.185 Td /F1 9.8 Tf  [(Calm down time)] TJ ET
0.812 0.886 0.953 rg
205.867 520.534 124.878 15.881 re f
0.267 0.267 0.267 rg
205.492 536.040 125.628 0.750 re f
205.492 520.159 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 526.185 Td /F1 9.8 Tf  [(0.69)] TJ ET
0.812 0.886 0.953 rg
330.745 520.534 124.878 15.881 re f
0.267 0.267 0.267 rg
330.370 536.040 125.628 0.750 re f
330.370 520.159 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 526.185 Td /F1 9.8 Tf  [(0.68)] TJ ET
0.812 0.886 0.953 rg
455.622 520.534 124.878 15.881 re f
0.267 0.267 0.267 rg
455.247 536.040 125.628 0.750 re f
455.247 520.159 0.750 16.631 re f
580.125 520.159 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 526.185 Td /F1 9.8 Tf  [(0.78)] TJ ET
0.267 0.267 0.267 rg
26.625 520.159 179.617 0.750 re f
26.625 504.278 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 510.304 Td /F1 9.8 Tf  [(Aggression � people)] TJ ET
0.267 0.267 0.267 rg
205.492 520.159 125.628 0.750 re f
205.492 504.278 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 510.304 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
330.370 520.159 125.628 0.750 re f
330.370 504.278 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 510.304 Td /F1 9.8 Tf  [(0.39)] TJ ET
0.267 0.267 0.267 rg
455.247 520.159 125.628 0.750 re f
455.247 504.278 0.750 16.631 re f
580.125 504.278 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 510.304 Td /F1 9.8 Tf  [(0.62)] TJ ET
0.267 0.267 0.267 rg
26.625 504.278 179.617 0.750 re f
26.625 488.396 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 494.423 Td /F1 9.8 Tf  [(Aggression � animals/objects)] TJ ET
0.267 0.267 0.267 rg
205.492 504.278 125.628 0.750 re f
205.492 488.396 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 494.423 Td /F1 9.8 Tf  [(0.36)] TJ ET
0.267 0.267 0.267 rg
330.370 504.278 125.628 0.750 re f
330.370 488.396 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 494.423 Td /F1 9.8 Tf  [(0.38)] TJ ET
0.267 0.267 0.267 rg
455.247 504.278 125.628 0.750 re f
455.247 488.396 0.750 16.631 re f
580.125 488.396 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 494.423 Td /F1 9.8 Tf  [(0.29)] TJ ET
0.267 0.267 0.267 rg
26.625 488.396 179.617 0.750 re f
26.625 472.515 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 478.541 Td /F1 9.8 Tf  [(Repetitive thoughts)] TJ ET
0.267 0.267 0.267 rg
205.492 488.396 125.628 0.750 re f
205.492 472.515 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 478.541 Td /F1 9.8 Tf  [(0.29)] TJ ET
0.267 0.267 0.267 rg
330.370 488.396 125.628 0.750 re f
330.370 472.515 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 478.541 Td /F1 9.8 Tf  [(0.34)] TJ ET
0.267 0.267 0.267 rg
455.247 488.396 125.628 0.750 re f
455.247 472.515 0.750 16.631 re f
580.125 472.515 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 478.541 Td /F1 9.8 Tf  [(0.14)] TJ ET
0.812 0.886 0.953 rg
27.000 457.009 178.867 15.881 re f
0.267 0.267 0.267 rg
26.625 472.515 179.617 0.750 re f
26.625 456.634 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 462.660 Td /F1 9.8 Tf  [(Compromise)] TJ ET
0.812 0.886 0.953 rg
205.867 457.009 124.878 15.881 re f
0.267 0.267 0.267 rg
205.492 472.515 125.628 0.750 re f
205.492 456.634 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 462.660 Td /F1 9.8 Tf  [(0.54)] TJ ET
0.812 0.886 0.953 rg
330.745 457.009 124.878 15.881 re f
0.267 0.267 0.267 rg
330.370 472.515 125.628 0.750 re f
330.370 456.634 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 462.660 Td /F1 9.8 Tf  [(0.52)] TJ ET
0.812 0.886 0.953 rg
455.622 457.009 124.878 15.881 re f
0.267 0.267 0.267 rg
455.247 472.515 125.628 0.750 re f
455.247 456.634 0.750 16.631 re f
580.125 456.634 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 462.660 Td /F1 9.8 Tf  [(0.67)] TJ ET
0.267 0.267 0.267 rg
26.625 456.634 179.617 0.750 re f
26.625 440.752 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 446.779 Td /F1 9.8 Tf  [(Perseveration � tasks)] TJ ET
0.267 0.267 0.267 rg
205.492 456.634 125.628 0.750 re f
205.492 440.752 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 446.779 Td /F1 9.8 Tf  [(0.23)] TJ ET
0.267 0.267 0.267 rg
330.370 456.634 125.628 0.750 re f
330.370 440.752 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 446.779 Td /F1 9.8 Tf  [(0.22)] TJ ET
0.267 0.267 0.267 rg
455.247 456.634 125.628 0.750 re f
455.247 440.752 0.750 16.631 re f
580.125 440.752 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 446.779 Td /F1 9.8 Tf  [(0.28)] TJ ET
0.267 0.267 0.267 rg
26.625 440.752 179.617 0.750 re f
26.625 424.871 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 430.897 Td /F1 9.8 Tf  [(Perseveration � conversation)] TJ ET
0.267 0.267 0.267 rg
205.492 440.752 125.628 0.750 re f
205.492 424.871 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 430.897 Td /F1 9.8 Tf  [(0.16)] TJ ET
0.267 0.267 0.267 rg
330.370 440.752 125.628 0.750 re f
330.370 424.871 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 430.897 Td /F1 9.8 Tf  [(0.14)] TJ ET
0.267 0.267 0.267 rg
455.247 440.752 125.628 0.750 re f
455.247 424.871 0.750 16.631 re f
580.125 424.871 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 430.897 Td /F1 9.8 Tf  [(0.24)] TJ ET
0.267 0.267 0.267 rg
26.625 424.871 179.617 0.750 re f
26.625 408.990 179.617 0.750 re f
26.625 408.990 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 415.016 Td /F1 9.8 Tf  [(Mental inflexibility/rigidity)] TJ ET
0.267 0.267 0.267 rg
205.492 424.871 125.628 0.750 re f
205.492 408.990 125.628 0.750 re f
205.492 408.990 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 415.016 Td /F1 9.8 Tf  [(0.16)] TJ ET
0.267 0.267 0.267 rg
330.370 424.871 125.628 0.750 re f
330.370 408.990 125.628 0.750 re f
330.370 408.990 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 415.016 Td /F1 9.8 Tf  [(0.16)] TJ ET
0.267 0.267 0.267 rg
455.247 424.871 125.628 0.750 re f
455.247 408.990 125.628 0.750 re f
455.247 408.990 0.750 16.631 re f
580.125 408.990 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 415.016 Td /F1 9.8 Tf  [(0.16)] TJ ET
BT 26.250 361.591 Td /F1 9.8 Tf  [(It was agreed that these 6 interview questions would be modified accordingly for testing in subsequent iterations; examination of )] TJ ET
BT 26.250 349.686 Td /F1 9.8 Tf  [(the OCCs provided data on which decisions could be made as to where modifications should be made to improve item )] TJ ET
BT 26.250 337.782 Td /F1 9.8 Tf  [(performance, including changes in wording and scoring options. For example, Figure 4 shows the OCCs for the Anger/Irritability )] TJ ET
BT 26.250 325.877 Td /F1 9.8 Tf  [(question. The options with the highest probably of being scored for symptom intensity increased from �0� to �1� \(mild: somewhat )] TJ ET
BT 26.250 313.972 Td /F1 9.8 Tf  [(irritable, with minor autonomic arousal\) to �2� \(moderate: very irritable, definite autonomic arousal, but no overt aggression )] TJ ET
BT 26.250 302.067 Td /F1 9.8 Tf  [(expressed\); however, scores of �3� \(severe: definite expression of anger, transient loss of control\) and �4� \(very severe: definite )] TJ ET
BT 26.250 290.163 Td /F1 9.8 Tf  [(loss of control, throwing objects, injury to persons, animals, objects, or self\) were rarely endorsed, suggesting that aggressive or )] TJ ET
BT 26.250 278.258 Td /F1 9.8 Tf  [(violent outbursts are not typically characteristic symptoms in this population. Indeed, interview questions aimed to directly )] TJ ET
BT 26.250 266.353 Td /F1 9.8 Tf  [(assess aggression \(see Table 1\) were hardly endorsed. Also of note was that the distribution of options scoring was similar in )] TJ ET
BT 26.250 254.448 Td /F1 9.8 Tf  [(prHD and HD participants \(Figure 4, as example\), suggesting that these behavioral symptoms do not worsen in early HD or )] TJ ET
BT 26.250 242.544 Td /F1 9.8 Tf  [(track with the development of early motor manifestations.)] TJ ET
0.267 0.267 0.267 rg
BT 272.808 242.544 Td /F1 9.8 Tf  [([6])] TJ ET
0.271 0.267 0.267 rg
BT 283.650 242.544 Td /F1 9.8 Tf  [(Finally, with respect to the frequency of symptoms, most symptoms )] TJ ET
BT 26.250 230.639 Td /F1 9.8 Tf  [(\(when present\) were described as occurring occasionally \(i.e., score of 1, see Figure 4\), suggesting that the measurement of )] TJ ET
BT 26.250 218.734 Td /F1 9.8 Tf  [(severity of anger/irritability may sufficiently be captured by symptom intensity alone.)] TJ ET
0.965 0.965 0.965 rg
26.250 24.353 555.000 184.500 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 208.853 m 581.250 208.853 l 581.250 208.103 l 26.250 208.103 l  f
q
225.000 0 0 168.750 35.250 30.353 cm /I6 Do
Q 
q
35.250 24.353 537.000 0.000 re W n
Q
Q
q
15.000 24.353 577.500 752.647 re W n
0.271 0.267 0.267 rg
0.271 0.267 0.267 RG
40.337 770.444 m 
40.337 770.890 40.154 771.334 39.838 771.650 c
39.522 771.966 39.078 772.150 38.631 772.150 c
38.185 772.150 37.741 771.966 37.425 771.650 c
37.109 771.334 36.925 770.890 36.925 770.444 c
36.925 769.997 37.109 769.553 37.425 769.237 c
37.741 768.921 38.185 768.738 38.631 768.738 c
39.078 768.738 39.522 768.921 39.838 769.237 c
40.154 769.553 40.337 769.997 40.337 770.444 c f
BT 45.750 767.476 Td /F1 9.8 Tf  [(Compromise)] TJ ET
BT 26.250 744.321 Td /F1 9.8 Tf  [(The internal consistency of these six items was high, as were the corrected item-total correlations \(Table 3, shaded rows\). )] TJ ET
BT 26.250 732.417 Td /F1 9.8 Tf  [(Cronbach�s alpha was 0.86 with respect to the entire study population, 0.85 with respect to the prHD subgroup, and 0.92 with )] TJ ET
BT 26.250 720.512 Td /F1 9.8 Tf  [(respect to the HD subgroup. All corrected item-total correlations were 0.52 or higher with respect to the prHD subgroup and )] TJ ET
BT 26.250 708.607 Td /F1 9.8 Tf  [(0.67 or higher with respect to the HD subgroup \(Table 3\).)] TJ ET
BT 26.250 689.202 Td /F1 9.8 Tf  [(The mean total composite score with respect to the above 6 questions was 3.69 in prHD subjects and 3.70 in HD subjects; the )] TJ ET
BT 26.250 677.298 Td /F1 9.8 Tf  [(difference in mean scores was not statistically significant \(p = 0.81, Mann-Whitney U test\). No significant differences were noted )] TJ ET
BT 26.250 665.393 Td /F1 9.8 Tf  [(in scoring between prHD and HD for any of the 6 individual interview questions, with respect to either intensity or frequency of )] TJ ET
BT 26.250 653.488 Td /F1 9.8 Tf  [(symptoms.)] TJ ET
BT 26.250 634.083 Td /F4 9.8 Tf  [(Table 3. )] TJ ET
BT 65.269 634.083 Td /F1 9.8 Tf  [( Correlations Between Interview Questions Scores)] TJ ET
1.000 1.000 1.000 rg
26.250 408.615 555.000 215.588 re f
0.267 0.267 0.267 rg
26.625 623.077 179.617 0.750 re f
26.625 599.565 0.750 24.262 re f
0.271 0.267 0.267 rg
BT 31.875 613.223 Td /F1 9.8 Tf  [(Interview Question)] TJ ET
0.267 0.267 0.267 rg
205.492 623.077 125.628 0.750 re f
205.492 599.565 0.750 24.262 re f
0.271 0.267 0.267 rg
BT 210.742 613.223 Td /F1 9.8 Tf  [(Item-total correlation )] TJ ET
BT 210.742 605.591 Td /F1 9.8 Tf  [(\(all subjects\))] TJ ET
0.267 0.267 0.267 rg
330.370 623.077 125.628 0.750 re f
330.370 599.565 0.750 24.262 re f
0.271 0.267 0.267 rg
BT 335.620 613.223 Td /F1 9.8 Tf  [(Item-total correlation )] TJ ET
BT 335.620 605.591 Td /F1 9.8 Tf  [(\(prHD subjects\))] TJ ET
0.267 0.267 0.267 rg
455.247 623.077 125.628 0.750 re f
455.247 599.565 0.750 24.262 re f
580.125 599.565 0.750 24.262 re f
0.271 0.267 0.267 rg
BT 460.497 613.223 Td /F1 9.8 Tf  [(Item-total correlation )] TJ ET
BT 460.497 605.591 Td /F1 9.8 Tf  [(\(HD subjects\))] TJ ET
0.812 0.886 0.953 rg
27.000 584.059 178.867 15.881 re f
0.267 0.267 0.267 rg
26.625 599.565 179.617 0.750 re f
26.625 583.684 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 589.710 Td /F1 9.8 Tf  [(Anger/Irritability)] TJ ET
0.812 0.886 0.953 rg
205.867 584.059 124.878 15.881 re f
0.267 0.267 0.267 rg
205.492 599.565 125.628 0.750 re f
205.492 583.684 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 589.710 Td /F1 9.8 Tf  [(0.71)] TJ ET
0.812 0.886 0.953 rg
330.745 584.059 124.878 15.881 re f
0.267 0.267 0.267 rg
330.370 599.565 125.628 0.750 re f
330.370 583.684 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 589.710 Td /F1 9.8 Tf  [(0.70)] TJ ET
0.812 0.886 0.953 rg
455.622 584.059 124.878 15.881 re f
0.267 0.267 0.267 rg
455.247 599.565 125.628 0.750 re f
455.247 583.684 0.750 16.631 re f
580.125 583.684 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 589.710 Td /F1 9.8 Tf  [(0.79)] TJ ET
0.812 0.886 0.953 rg
27.000 568.178 178.867 15.881 re f
0.267 0.267 0.267 rg
26.625 583.684 179.617 0.750 re f
26.625 567.803 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 573.829 Td /F1 9.8 Tf  [(Ease of anger � provocation)] TJ ET
0.812 0.886 0.953 rg
205.867 568.178 124.878 15.881 re f
0.267 0.267 0.267 rg
205.492 583.684 125.628 0.750 re f
205.492 567.803 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 573.829 Td /F1 9.8 Tf  [(0.63)] TJ ET
0.812 0.886 0.953 rg
330.745 568.178 124.878 15.881 re f
0.267 0.267 0.267 rg
330.370 583.684 125.628 0.750 re f
330.370 567.803 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 573.829 Td /F1 9.8 Tf  [(0.60)] TJ ET
0.812 0.886 0.953 rg
455.622 568.178 124.878 15.881 re f
0.267 0.267 0.267 rg
455.247 583.684 125.628 0.750 re f
455.247 567.803 0.750 16.631 re f
580.125 567.803 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 573.829 Td /F1 9.8 Tf  [(0.78)] TJ ET
0.812 0.886 0.953 rg
27.000 552.296 178.867 15.881 re f
0.267 0.267 0.267 rg
26.625 567.803 179.617 0.750 re f
26.625 551.921 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 557.947 Td /F1 9.8 Tf  [(Ease of anger � stressor)] TJ ET
0.812 0.886 0.953 rg
205.867 552.296 124.878 15.881 re f
0.267 0.267 0.267 rg
205.492 567.803 125.628 0.750 re f
205.492 551.921 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 557.947 Td /F1 9.8 Tf  [(0.70)] TJ ET
0.812 0.886 0.953 rg
330.745 552.296 124.878 15.881 re f
0.267 0.267 0.267 rg
330.370 567.803 125.628 0.750 re f
330.370 551.921 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 557.947 Td /F1 9.8 Tf  [(0.68)] TJ ET
0.812 0.886 0.953 rg
455.622 552.296 124.878 15.881 re f
0.267 0.267 0.267 rg
455.247 567.803 125.628 0.750 re f
455.247 551.921 0.750 16.631 re f
580.125 551.921 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 557.947 Td /F1 9.8 Tf  [(0.75)] TJ ET
0.812 0.886 0.953 rg
27.000 536.415 178.867 15.881 re f
0.267 0.267 0.267 rg
26.625 551.921 179.617 0.750 re f
26.625 536.040 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 542.066 Td /F1 9.8 Tf  [(Ease of calming down)] TJ ET
0.812 0.886 0.953 rg
205.867 536.415 124.878 15.881 re f
0.267 0.267 0.267 rg
205.492 551.921 125.628 0.750 re f
205.492 536.040 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 542.066 Td /F1 9.8 Tf  [(0.69)] TJ ET
0.812 0.886 0.953 rg
330.745 536.415 124.878 15.881 re f
0.267 0.267 0.267 rg
330.370 551.921 125.628 0.750 re f
330.370 536.040 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 542.066 Td /F1 9.8 Tf  [(0.64)] TJ ET
0.812 0.886 0.953 rg
455.622 536.415 124.878 15.881 re f
0.267 0.267 0.267 rg
455.247 551.921 125.628 0.750 re f
455.247 536.040 0.750 16.631 re f
580.125 536.040 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 542.066 Td /F1 9.8 Tf  [(0.92)] TJ ET
0.812 0.886 0.953 rg
27.000 520.534 178.867 15.881 re f
0.267 0.267 0.267 rg
26.625 536.040 179.617 0.750 re f
26.625 520.159 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 526.185 Td /F1 9.8 Tf  [(Calm down time)] TJ ET
0.812 0.886 0.953 rg
205.867 520.534 124.878 15.881 re f
0.267 0.267 0.267 rg
205.492 536.040 125.628 0.750 re f
205.492 520.159 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 526.185 Td /F1 9.8 Tf  [(0.69)] TJ ET
0.812 0.886 0.953 rg
330.745 520.534 124.878 15.881 re f
0.267 0.267 0.267 rg
330.370 536.040 125.628 0.750 re f
330.370 520.159 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 526.185 Td /F1 9.8 Tf  [(0.68)] TJ ET
0.812 0.886 0.953 rg
455.622 520.534 124.878 15.881 re f
0.267 0.267 0.267 rg
455.247 536.040 125.628 0.750 re f
455.247 520.159 0.750 16.631 re f
580.125 520.159 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 526.185 Td /F1 9.8 Tf  [(0.78)] TJ ET
0.267 0.267 0.267 rg
26.625 520.159 179.617 0.750 re f
26.625 504.278 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 510.304 Td /F1 9.8 Tf  [(Aggression � people)] TJ ET
0.267 0.267 0.267 rg
205.492 520.159 125.628 0.750 re f
205.492 504.278 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 510.304 Td /F1 9.8 Tf  [(0.44)] TJ ET
0.267 0.267 0.267 rg
330.370 520.159 125.628 0.750 re f
330.370 504.278 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 510.304 Td /F1 9.8 Tf  [(0.39)] TJ ET
0.267 0.267 0.267 rg
455.247 520.159 125.628 0.750 re f
455.247 504.278 0.750 16.631 re f
580.125 504.278 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 510.304 Td /F1 9.8 Tf  [(0.62)] TJ ET
0.267 0.267 0.267 rg
26.625 504.278 179.617 0.750 re f
26.625 488.396 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 494.423 Td /F1 9.8 Tf  [(Aggression � animals/objects)] TJ ET
0.267 0.267 0.267 rg
205.492 504.278 125.628 0.750 re f
205.492 488.396 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 494.423 Td /F1 9.8 Tf  [(0.36)] TJ ET
0.267 0.267 0.267 rg
330.370 504.278 125.628 0.750 re f
330.370 488.396 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 494.423 Td /F1 9.8 Tf  [(0.38)] TJ ET
0.267 0.267 0.267 rg
455.247 504.278 125.628 0.750 re f
455.247 488.396 0.750 16.631 re f
580.125 488.396 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 494.423 Td /F1 9.8 Tf  [(0.29)] TJ ET
0.267 0.267 0.267 rg
26.625 488.396 179.617 0.750 re f
26.625 472.515 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 478.541 Td /F1 9.8 Tf  [(Repetitive thoughts)] TJ ET
0.267 0.267 0.267 rg
205.492 488.396 125.628 0.750 re f
205.492 472.515 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 478.541 Td /F1 9.8 Tf  [(0.29)] TJ ET
0.267 0.267 0.267 rg
330.370 488.396 125.628 0.750 re f
330.370 472.515 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 478.541 Td /F1 9.8 Tf  [(0.34)] TJ ET
0.267 0.267 0.267 rg
455.247 488.396 125.628 0.750 re f
455.247 472.515 0.750 16.631 re f
580.125 472.515 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 478.541 Td /F1 9.8 Tf  [(0.14)] TJ ET
0.812 0.886 0.953 rg
27.000 457.009 178.867 15.881 re f
0.267 0.267 0.267 rg
26.625 472.515 179.617 0.750 re f
26.625 456.634 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 462.660 Td /F1 9.8 Tf  [(Compromise)] TJ ET
0.812 0.886 0.953 rg
205.867 457.009 124.878 15.881 re f
0.267 0.267 0.267 rg
205.492 472.515 125.628 0.750 re f
205.492 456.634 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 462.660 Td /F1 9.8 Tf  [(0.54)] TJ ET
0.812 0.886 0.953 rg
330.745 457.009 124.878 15.881 re f
0.267 0.267 0.267 rg
330.370 472.515 125.628 0.750 re f
330.370 456.634 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 462.660 Td /F1 9.8 Tf  [(0.52)] TJ ET
0.812 0.886 0.953 rg
455.622 457.009 124.878 15.881 re f
0.267 0.267 0.267 rg
455.247 472.515 125.628 0.750 re f
455.247 456.634 0.750 16.631 re f
580.125 456.634 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 462.660 Td /F1 9.8 Tf  [(0.67)] TJ ET
0.267 0.267 0.267 rg
26.625 456.634 179.617 0.750 re f
26.625 440.752 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 446.779 Td /F1 9.8 Tf  [(Perseveration � tasks)] TJ ET
0.267 0.267 0.267 rg
205.492 456.634 125.628 0.750 re f
205.492 440.752 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 446.779 Td /F1 9.8 Tf  [(0.23)] TJ ET
0.267 0.267 0.267 rg
330.370 456.634 125.628 0.750 re f
330.370 440.752 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 446.779 Td /F1 9.8 Tf  [(0.22)] TJ ET
0.267 0.267 0.267 rg
455.247 456.634 125.628 0.750 re f
455.247 440.752 0.750 16.631 re f
580.125 440.752 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 446.779 Td /F1 9.8 Tf  [(0.28)] TJ ET
0.267 0.267 0.267 rg
26.625 440.752 179.617 0.750 re f
26.625 424.871 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 430.897 Td /F1 9.8 Tf  [(Perseveration � conversation)] TJ ET
0.267 0.267 0.267 rg
205.492 440.752 125.628 0.750 re f
205.492 424.871 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 430.897 Td /F1 9.8 Tf  [(0.16)] TJ ET
0.267 0.267 0.267 rg
330.370 440.752 125.628 0.750 re f
330.370 424.871 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 430.897 Td /F1 9.8 Tf  [(0.14)] TJ ET
0.267 0.267 0.267 rg
455.247 440.752 125.628 0.750 re f
455.247 424.871 0.750 16.631 re f
580.125 424.871 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 430.897 Td /F1 9.8 Tf  [(0.24)] TJ ET
0.267 0.267 0.267 rg
26.625 424.871 179.617 0.750 re f
26.625 408.990 179.617 0.750 re f
26.625 408.990 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 415.016 Td /F1 9.8 Tf  [(Mental inflexibility/rigidity)] TJ ET
0.267 0.267 0.267 rg
205.492 424.871 125.628 0.750 re f
205.492 408.990 125.628 0.750 re f
205.492 408.990 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 210.742 415.016 Td /F1 9.8 Tf  [(0.16)] TJ ET
0.267 0.267 0.267 rg
330.370 424.871 125.628 0.750 re f
330.370 408.990 125.628 0.750 re f
330.370 408.990 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.620 415.016 Td /F1 9.8 Tf  [(0.16)] TJ ET
0.267 0.267 0.267 rg
455.247 424.871 125.628 0.750 re f
455.247 408.990 125.628 0.750 re f
455.247 408.990 0.750 16.631 re f
580.125 408.990 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 460.497 415.016 Td /F1 9.8 Tf  [(0.16)] TJ ET
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BT 26.250 349.686 Td /F1 9.8 Tf  [(the OCCs provided data on which decisions could be made as to where modifications should be made to improve item )] TJ ET
BT 26.250 337.782 Td /F1 9.8 Tf  [(performance, including changes in wording and scoring options. For example, Figure 4 shows the OCCs for the Anger/Irritability )] TJ ET
BT 26.250 325.877 Td /F1 9.8 Tf  [(question. The options with the highest probably of being scored for symptom intensity increased from �0� to �1� \(mild: somewhat )] TJ ET
BT 26.250 313.972 Td /F1 9.8 Tf  [(irritable, with minor autonomic arousal\) to �2� \(moderate: very irritable, definite autonomic arousal, but no overt aggression )] TJ ET
BT 26.250 302.067 Td /F1 9.8 Tf  [(expressed\); however, scores of �3� \(severe: definite expression of anger, transient loss of control\) and �4� \(very severe: definite )] TJ ET
BT 26.250 290.163 Td /F1 9.8 Tf  [(loss of control, throwing objects, injury to persons, animals, objects, or self\) were rarely endorsed, suggesting that aggressive or )] TJ ET
BT 26.250 278.258 Td /F1 9.8 Tf  [(violent outbursts are not typically characteristic symptoms in this population. Indeed, interview questions aimed to directly )] TJ ET
BT 26.250 266.353 Td /F1 9.8 Tf  [(assess aggression \(see Table 1\) were hardly endorsed. Also of note was that the distribution of options scoring was similar in )] TJ ET
BT 26.250 254.448 Td /F1 9.8 Tf  [(prHD and HD participants \(Figure 4, as example\), suggesting that these behavioral symptoms do not worsen in early HD or )] TJ ET
BT 26.250 242.544 Td /F1 9.8 Tf  [(track with the development of early motor manifestations.)] TJ ET
0.267 0.267 0.267 rg
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0.271 0.267 0.267 rg
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0.267 0.267 0.267 RG
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39.522 670.861 39.078 671.045 38.631 671.045 c
38.185 671.045 37.741 670.861 37.425 670.545 c
37.109 670.229 36.925 669.785 36.925 669.338 c
36.925 668.892 37.109 668.448 37.425 668.132 c
37.741 667.816 38.185 667.632 38.631 667.632 c
39.078 667.632 39.522 667.816 39.838 668.132 c
40.154 668.448 40.337 668.892 40.337 669.338 c f
BT 45.750 666.371 Td /F1 9.8 Tf  [(Aggression � People)] TJ ET
40.337 653.684 m 
40.337 654.130 40.154 654.574 39.838 654.890 c
39.522 655.206 39.078 655.390 38.631 655.390 c
38.185 655.390 37.741 655.206 37.425 654.890 c
37.109 654.574 36.925 654.130 36.925 653.684 c
36.925 653.237 37.109 652.793 37.425 652.477 c
37.741 652.161 38.185 651.977 38.631 651.977 c
39.078 651.977 39.522 652.161 39.838 652.477 c
40.154 652.793 40.337 653.237 40.337 653.684 c f
BT 45.750 650.716 Td /F1 9.8 Tf  [(Aggression � Animals/Objects)] TJ ET
40.337 638.029 m 
40.337 638.476 40.154 638.920 39.838 639.236 c
39.522 639.551 39.078 639.735 38.631 639.735 c
38.185 639.735 37.741 639.551 37.425 639.236 c
37.109 638.920 36.925 638.476 36.925 638.029 c
36.925 637.582 37.109 637.138 37.425 636.822 c
37.741 636.507 38.185 636.323 38.631 636.323 c
39.078 636.323 39.522 636.507 39.838 636.822 c
40.154 637.138 40.337 637.582 40.337 638.029 c f
BT 45.750 635.061 Td /F1 9.8 Tf  [(Repetitive Thoughts)] TJ ET
40.337 622.374 m 
40.337 622.821 40.154 623.265 39.838 623.581 c
39.522 623.897 39.078 624.080 38.631 624.080 c
38.185 624.080 37.741 623.897 37.425 623.581 c
37.109 623.265 36.925 622.821 36.925 622.374 c
36.925 621.928 37.109 621.484 37.425 621.168 c
37.741 620.852 38.185 620.668 38.631 620.668 c
39.078 620.668 39.522 620.852 39.838 621.168 c
40.154 621.484 40.337 621.928 40.337 622.374 c f
BT 45.750 619.407 Td /F1 9.8 Tf  [(Perseveration � Tasks)] TJ ET
40.337 606.719 m 
40.337 607.166 40.154 607.610 39.838 607.926 c
39.522 608.242 39.078 608.426 38.631 608.426 c
38.185 608.426 37.741 608.242 37.425 607.926 c
37.109 607.610 36.925 607.166 36.925 606.719 c
36.925 606.273 37.109 605.829 37.425 605.513 c
37.741 605.197 38.185 605.013 38.631 605.013 c
39.078 605.013 39.522 605.197 39.838 605.513 c
40.154 605.829 40.337 606.273 40.337 606.719 c f
BT 45.750 603.752 Td /F1 9.8 Tf  [(Perseveration � Topics of Conversation)] TJ ET
40.337 591.065 m 
40.337 591.511 40.154 591.955 39.838 592.271 c
39.522 592.587 39.078 592.771 38.631 592.771 c
38.185 592.771 37.741 592.587 37.425 592.271 c
37.109 591.955 36.925 591.511 36.925 591.065 c
36.925 590.618 37.109 590.174 37.425 589.858 c
37.741 589.542 38.185 589.358 38.631 589.358 c
39.078 589.358 39.522 589.542 39.838 589.858 c
40.154 590.174 40.337 590.618 40.337 591.065 c f
BT 45.750 588.097 Td /F1 9.8 Tf  [(Mental inflexibility/Rigidity)] TJ ET
BT 26.250 564.942 Td /F1 9.8 Tf  [(The mean composite scores for these six questions were lower than those for the six highly-endorsed interview questions, with )] TJ ET
BT 26.250 553.038 Td /F1 9.8 Tf  [(respect to the overall study population and the subgroup of prHD subjects \(p < 0.05\). The low frequency of response and poor )] TJ ET
BT 26.250 541.133 Td /F1 9.8 Tf  [(discriminative properties limit the usefulness of these interview questions for assessment in prHD and early HD, including the )] TJ ET
BT 26.250 529.228 Td /F1 9.8 Tf  [(measures of obsessive-compulsive behaviors. The only questions which discriminated between prHD and early HD subjects )] TJ ET
BT 26.250 517.323 Td /F1 9.8 Tf  [(was �Perseveration � topics of conversation,� with significantly higher scores in HD subjects with respect to both frequency \(p < )] TJ ET
BT 26.250 505.419 Td /F1 9.8 Tf  [(0.05\) and intensity \(p < 0.05\) of symptoms; however, this question was nonetheless very rarely endorsed in the subject )] TJ ET
BT 26.250 493.514 Td /F1 9.8 Tf  [(population. For the other five items, there were no statistically significant differences in either the severity or frequency of )] TJ ET
BT 26.250 481.609 Td /F1 9.8 Tf  [(symptoms between prHD and HD subjects \(Figure 5, as example\). In general, the correlations between each of these 6 )] TJ ET
BT 26.250 469.704 Td /F1 9.8 Tf  [(individual composite scores and the total composite score from the 6 highly-endorsed interview questions were low \(Table 3\); )] TJ ET
BT 26.250 457.800 Td /F1 9.8 Tf  [(the item-total correlation was high for �Aggression towards people� in the subset of prHD subjects, but this item was )] TJ ET
BT 26.250 445.895 Td /F1 9.8 Tf  [(nonetheless rarely endorsed in the subject population.)] TJ ET
0.965 0.965 0.965 rg
26.250 189.218 555.000 246.796 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 436.014 m 581.250 436.014 l 581.250 435.264 l 26.250 435.264 l  f
26.250 189.218 m 581.250 189.218 l 581.250 189.968 l 26.250 189.968 l  f
q
225.000 0 0 168.750 35.250 257.514 cm /I7 Do
Q 
q
35.250 200.468 537.000 51.046 re W n
0.271 0.267 0.267 rg
BT 35.250 241.990 Td /F4 9.8 Tf  [(Fig. 5: OCCs \(All participants\) and frequency distribution \(HD and prHD\) of representative rarely-endorsed )] TJ ET
BT 35.250 230.085 Td /F4 9.8 Tf  [(interview question \(perseveration-tasks\).)] TJ ET
BT 35.250 210.715 Td /F1 9.8 Tf  [(Data presented separately for symptom intensity \(left row\), frequency \(middle row\), and composite \(right row\) scores.)] TJ ET
Q
BT 26.250 172.194 Td /F1 9.8 Tf  [(It was agreed that that these 6 questions should be removed from subsequent iterations on the basis of Relevance \(Reported )] TJ ET
BT 26.250 160.290 Td /F1 9.8 Tf  [(as not relevant by a large segment of the population of interest\) and Response Range \(A high percentage of patients respond at )] TJ ET
BT 26.250 148.385 Td /F1 9.8 Tf  [(the floor\) as outlined in Table 1 of the FDA PRO Guidance.)] TJ ET
0.267 0.267 0.267 rg
BT 280.413 148.385 Td /F1 9.8 Tf  [([2])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 111.782 Td /F4 12.0 Tf  [(Discussion)] TJ ET
BT 26.250 91.828 Td /F1 9.8 Tf  [(FuRST-pHD has used an inclusive, iterative process to generate interview questions to assess symptoms in prodromal and )] TJ ET
BT 26.250 79.923 Td /F1 9.8 Tf  [(early HD gene expansion carriers. While testing is still ongoing, it is clear that many CAG expanded individuals exhibit a range )] TJ ET
BT 26.250 68.019 Td /F1 9.8 Tf  [(of behavioral manifestations prior to clinical diagnosis, but some symptoms are likely to be better candidates for inclusion in a )] TJ ET
BT 26.250 56.114 Td /F1 9.8 Tf  [(final instrument than others. We report here the development and beta testing of first iteration interview questions designed to )] TJ ET
BT 26.250 44.209 Td /F1 9.8 Tf  [(assess anger/irritability and obsessions/compulsions. Six questions have been selected for further testing, have been modified )] TJ ET
Q
q
15.000 29.923 577.500 747.077 re W n
0.965 0.965 0.965 rg
26.250 714.704 555.000 62.296 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 714.704 m 581.250 714.704 l 581.250 715.454 l 26.250 715.454 l  f
q
35.250 725.954 537.000 51.046 re W n
0.271 0.267 0.267 rg
BT 35.250 767.476 Td /F4 9.8 Tf  [(Fig. 4: OCCs \(All participants\) and Frequency distribution \(HD and prHD\) for interview question assessing �anger )] TJ ET
BT 35.250 755.571 Td /F4 9.8 Tf  [(and irritability.�)] TJ ET
BT 35.250 736.201 Td /F1 9.8 Tf  [(Data are presented separately for symptom intensity \(left row\), frequency \(middle row\), and composite \(right row\) scores.)] TJ ET
Q
BT 26.250 697.680 Td /F1 9.8 Tf  [(The remaining 6 questions were very rarely endorsed and a score of zero had the highest probability of being scored across the )] TJ ET
BT 26.250 685.776 Td /F1 9.8 Tf  [(full range of severity \(Figure 5, as example\):)] TJ ET
0.271 0.267 0.267 RG
40.337 669.338 m 
40.337 669.785 40.154 670.229 39.838 670.545 c
39.522 670.861 39.078 671.045 38.631 671.045 c
38.185 671.045 37.741 670.861 37.425 670.545 c
37.109 670.229 36.925 669.785 36.925 669.338 c
36.925 668.892 37.109 668.448 37.425 668.132 c
37.741 667.816 38.185 667.632 38.631 667.632 c
39.078 667.632 39.522 667.816 39.838 668.132 c
40.154 668.448 40.337 668.892 40.337 669.338 c f
BT 45.750 666.371 Td /F1 9.8 Tf  [(Aggression � People)] TJ ET
40.337 653.684 m 
40.337 654.130 40.154 654.574 39.838 654.890 c
39.522 655.206 39.078 655.390 38.631 655.390 c
38.185 655.390 37.741 655.206 37.425 654.890 c
37.109 654.574 36.925 654.130 36.925 653.684 c
36.925 653.237 37.109 652.793 37.425 652.477 c
37.741 652.161 38.185 651.977 38.631 651.977 c
39.078 651.977 39.522 652.161 39.838 652.477 c
40.154 652.793 40.337 653.237 40.337 653.684 c f
BT 45.750 650.716 Td /F1 9.8 Tf  [(Aggression � Animals/Objects)] TJ ET
40.337 638.029 m 
40.337 638.476 40.154 638.920 39.838 639.236 c
39.522 639.551 39.078 639.735 38.631 639.735 c
38.185 639.735 37.741 639.551 37.425 639.236 c
37.109 638.920 36.925 638.476 36.925 638.029 c
36.925 637.582 37.109 637.138 37.425 636.822 c
37.741 636.507 38.185 636.323 38.631 636.323 c
39.078 636.323 39.522 636.507 39.838 636.822 c
40.154 637.138 40.337 637.582 40.337 638.029 c f
BT 45.750 635.061 Td /F1 9.8 Tf  [(Repetitive Thoughts)] TJ ET
40.337 622.374 m 
40.337 622.821 40.154 623.265 39.838 623.581 c
39.522 623.897 39.078 624.080 38.631 624.080 c
38.185 624.080 37.741 623.897 37.425 623.581 c
37.109 623.265 36.925 622.821 36.925 622.374 c
36.925 621.928 37.109 621.484 37.425 621.168 c
37.741 620.852 38.185 620.668 38.631 620.668 c
39.078 620.668 39.522 620.852 39.838 621.168 c
40.154 621.484 40.337 621.928 40.337 622.374 c f
BT 45.750 619.407 Td /F1 9.8 Tf  [(Perseveration � Tasks)] TJ ET
40.337 606.719 m 
40.337 607.166 40.154 607.610 39.838 607.926 c
39.522 608.242 39.078 608.426 38.631 608.426 c
38.185 608.426 37.741 608.242 37.425 607.926 c
37.109 607.610 36.925 607.166 36.925 606.719 c
36.925 606.273 37.109 605.829 37.425 605.513 c
37.741 605.197 38.185 605.013 38.631 605.013 c
39.078 605.013 39.522 605.197 39.838 605.513 c
40.154 605.829 40.337 606.273 40.337 606.719 c f
BT 45.750 603.752 Td /F1 9.8 Tf  [(Perseveration � Topics of Conversation)] TJ ET
40.337 591.065 m 
40.337 591.511 40.154 591.955 39.838 592.271 c
39.522 592.587 39.078 592.771 38.631 592.771 c
38.185 592.771 37.741 592.587 37.425 592.271 c
37.109 591.955 36.925 591.511 36.925 591.065 c
36.925 590.618 37.109 590.174 37.425 589.858 c
37.741 589.542 38.185 589.358 38.631 589.358 c
39.078 589.358 39.522 589.542 39.838 589.858 c
40.154 590.174 40.337 590.618 40.337 591.065 c f
BT 45.750 588.097 Td /F1 9.8 Tf  [(Mental inflexibility/Rigidity)] TJ ET
BT 26.250 564.942 Td /F1 9.8 Tf  [(The mean composite scores for these six questions were lower than those for the six highly-endorsed interview questions, with )] TJ ET
BT 26.250 553.038 Td /F1 9.8 Tf  [(respect to the overall study population and the subgroup of prHD subjects \(p < 0.05\). The low frequency of response and poor )] TJ ET
BT 26.250 541.133 Td /F1 9.8 Tf  [(discriminative properties limit the usefulness of these interview questions for assessment in prHD and early HD, including the )] TJ ET
BT 26.250 529.228 Td /F1 9.8 Tf  [(measures of obsessive-compulsive behaviors. The only questions which discriminated between prHD and early HD subjects )] TJ ET
BT 26.250 517.323 Td /F1 9.8 Tf  [(was �Perseveration � topics of conversation,� with significantly higher scores in HD subjects with respect to both frequency \(p < )] TJ ET
BT 26.250 505.419 Td /F1 9.8 Tf  [(0.05\) and intensity \(p < 0.05\) of symptoms; however, this question was nonetheless very rarely endorsed in the subject )] TJ ET
BT 26.250 493.514 Td /F1 9.8 Tf  [(population. For the other five items, there were no statistically significant differences in either the severity or frequency of )] TJ ET
BT 26.250 481.609 Td /F1 9.8 Tf  [(symptoms between prHD and HD subjects \(Figure 5, as example\). In general, the correlations between each of these 6 )] TJ ET
BT 26.250 469.704 Td /F1 9.8 Tf  [(individual composite scores and the total composite score from the 6 highly-endorsed interview questions were low \(Table 3\); )] TJ ET
BT 26.250 457.800 Td /F1 9.8 Tf  [(the item-total correlation was high for �Aggression towards people� in the subset of prHD subjects, but this item was )] TJ ET
BT 26.250 445.895 Td /F1 9.8 Tf  [(nonetheless rarely endorsed in the subject population.)] TJ ET
0.965 0.965 0.965 rg
26.250 189.218 555.000 246.796 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 436.014 m 581.250 436.014 l 581.250 435.264 l 26.250 435.264 l  f
26.250 189.218 m 581.250 189.218 l 581.250 189.968 l 26.250 189.968 l  f
q
225.000 0 0 168.750 35.250 257.514 cm /I7 Do
Q 
q
35.250 200.468 537.000 51.046 re W n
0.271 0.267 0.267 rg
BT 35.250 241.990 Td /F4 9.8 Tf  [(Fig. 5: OCCs \(All participants\) and frequency distribution \(HD and prHD\) of representative rarely-endorsed )] TJ ET
BT 35.250 230.085 Td /F4 9.8 Tf  [(interview question \(perseveration-tasks\).)] TJ ET
BT 35.250 210.715 Td /F1 9.8 Tf  [(Data presented separately for symptom intensity \(left row\), frequency \(middle row\), and composite \(right row\) scores.)] TJ ET
Q
BT 26.250 172.194 Td /F1 9.8 Tf  [(It was agreed that that these 6 questions should be removed from subsequent iterations on the basis of Relevance \(Reported )] TJ ET
BT 26.250 160.290 Td /F1 9.8 Tf  [(as not relevant by a large segment of the population of interest\) and Response Range \(A high percentage of patients respond at )] TJ ET
BT 26.250 148.385 Td /F1 9.8 Tf  [(the floor\) as outlined in Table 1 of the FDA PRO Guidance.)] TJ ET
0.267 0.267 0.267 rg
BT 280.413 148.385 Td /F1 9.8 Tf  [([2])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 111.782 Td /F4 12.0 Tf  [(Discussion)] TJ ET
BT 26.250 91.828 Td /F1 9.8 Tf  [(FuRST-pHD has used an inclusive, iterative process to generate interview questions to assess symptoms in prodromal and )] TJ ET
BT 26.250 79.923 Td /F1 9.8 Tf  [(early HD gene expansion carriers. While testing is still ongoing, it is clear that many CAG expanded individuals exhibit a range )] TJ ET
BT 26.250 68.019 Td /F1 9.8 Tf  [(of behavioral manifestations prior to clinical diagnosis, but some symptoms are likely to be better candidates for inclusion in a )] TJ ET
BT 26.250 56.114 Td /F1 9.8 Tf  [(final instrument than others. We report here the development and beta testing of first iteration interview questions designed to )] TJ ET
BT 26.250 44.209 Td /F1 9.8 Tf  [(assess anger/irritability and obsessions/compulsions. Six questions have been selected for further testing, have been modified )] TJ ET
Q
q
15.000 29.923 577.500 747.077 re W n
0.965 0.965 0.965 rg
26.250 714.704 555.000 62.296 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 714.704 m 581.250 714.704 l 581.250 715.454 l 26.250 715.454 l  f
q
35.250 725.954 537.000 51.046 re W n
0.271 0.267 0.267 rg
BT 35.250 767.476 Td /F4 9.8 Tf  [(Fig. 4: OCCs \(All participants\) and Frequency distribution \(HD and prHD\) for interview question assessing �anger )] TJ ET
BT 35.250 755.571 Td /F4 9.8 Tf  [(and irritability.�)] TJ ET
BT 35.250 736.201 Td /F1 9.8 Tf  [(Data are presented separately for symptom intensity \(left row\), frequency \(middle row\), and composite \(right row\) scores.)] TJ ET
Q
BT 26.250 697.680 Td /F1 9.8 Tf  [(The remaining 6 questions were very rarely endorsed and a score of zero had the highest probability of being scored across the )] TJ ET
BT 26.250 685.776 Td /F1 9.8 Tf  [(full range of severity \(Figure 5, as example\):)] TJ ET
0.271 0.267 0.267 RG
40.337 669.338 m 
40.337 669.785 40.154 670.229 39.838 670.545 c
39.522 670.861 39.078 671.045 38.631 671.045 c
38.185 671.045 37.741 670.861 37.425 670.545 c
37.109 670.229 36.925 669.785 36.925 669.338 c
36.925 668.892 37.109 668.448 37.425 668.132 c
37.741 667.816 38.185 667.632 38.631 667.632 c
39.078 667.632 39.522 667.816 39.838 668.132 c
40.154 668.448 40.337 668.892 40.337 669.338 c f
BT 45.750 666.371 Td /F1 9.8 Tf  [(Aggression � People)] TJ ET
40.337 653.684 m 
40.337 654.130 40.154 654.574 39.838 654.890 c
39.522 655.206 39.078 655.390 38.631 655.390 c
38.185 655.390 37.741 655.206 37.425 654.890 c
37.109 654.574 36.925 654.130 36.925 653.684 c
36.925 653.237 37.109 652.793 37.425 652.477 c
37.741 652.161 38.185 651.977 38.631 651.977 c
39.078 651.977 39.522 652.161 39.838 652.477 c
40.154 652.793 40.337 653.237 40.337 653.684 c f
BT 45.750 650.716 Td /F1 9.8 Tf  [(Aggression � Animals/Objects)] TJ ET
40.337 638.029 m 
40.337 638.476 40.154 638.920 39.838 639.236 c
39.522 639.551 39.078 639.735 38.631 639.735 c
38.185 639.735 37.741 639.551 37.425 639.236 c
37.109 638.920 36.925 638.476 36.925 638.029 c
36.925 637.582 37.109 637.138 37.425 636.822 c
37.741 636.507 38.185 636.323 38.631 636.323 c
39.078 636.323 39.522 636.507 39.838 636.822 c
40.154 637.138 40.337 637.582 40.337 638.029 c f
BT 45.750 635.061 Td /F1 9.8 Tf  [(Repetitive Thoughts)] TJ ET
40.337 622.374 m 
40.337 622.821 40.154 623.265 39.838 623.581 c
39.522 623.897 39.078 624.080 38.631 624.080 c
38.185 624.080 37.741 623.897 37.425 623.581 c
37.109 623.265 36.925 622.821 36.925 622.374 c
36.925 621.928 37.109 621.484 37.425 621.168 c
37.741 620.852 38.185 620.668 38.631 620.668 c
39.078 620.668 39.522 620.852 39.838 621.168 c
40.154 621.484 40.337 621.928 40.337 622.374 c f
BT 45.750 619.407 Td /F1 9.8 Tf  [(Perseveration � Tasks)] TJ ET
40.337 606.719 m 
40.337 607.166 40.154 607.610 39.838 607.926 c
39.522 608.242 39.078 608.426 38.631 608.426 c
38.185 608.426 37.741 608.242 37.425 607.926 c
37.109 607.610 36.925 607.166 36.925 606.719 c
36.925 606.273 37.109 605.829 37.425 605.513 c
37.741 605.197 38.185 605.013 38.631 605.013 c
39.078 605.013 39.522 605.197 39.838 605.513 c
40.154 605.829 40.337 606.273 40.337 606.719 c f
BT 45.750 603.752 Td /F1 9.8 Tf  [(Perseveration � Topics of Conversation)] TJ ET
40.337 591.065 m 
40.337 591.511 40.154 591.955 39.838 592.271 c
39.522 592.587 39.078 592.771 38.631 592.771 c
38.185 592.771 37.741 592.587 37.425 592.271 c
37.109 591.955 36.925 591.511 36.925 591.065 c
36.925 590.618 37.109 590.174 37.425 589.858 c
37.741 589.542 38.185 589.358 38.631 589.358 c
39.078 589.358 39.522 589.542 39.838 589.858 c
40.154 590.174 40.337 590.618 40.337 591.065 c f
BT 45.750 588.097 Td /F1 9.8 Tf  [(Mental inflexibility/Rigidity)] TJ ET
BT 26.250 564.942 Td /F1 9.8 Tf  [(The mean composite scores for these six questions were lower than those for the six highly-endorsed interview questions, with )] TJ ET
BT 26.250 553.038 Td /F1 9.8 Tf  [(respect to the overall study population and the subgroup of prHD subjects \(p < 0.05\). The low frequency of response and poor )] TJ ET
BT 26.250 541.133 Td /F1 9.8 Tf  [(discriminative properties limit the usefulness of these interview questions for assessment in prHD and early HD, including the )] TJ ET
BT 26.250 529.228 Td /F1 9.8 Tf  [(measures of obsessive-compulsive behaviors. The only questions which discriminated between prHD and early HD subjects )] TJ ET
BT 26.250 517.323 Td /F1 9.8 Tf  [(was �Perseveration � topics of conversation,� with significantly higher scores in HD subjects with respect to both frequency \(p < )] TJ ET
BT 26.250 505.419 Td /F1 9.8 Tf  [(0.05\) and intensity \(p < 0.05\) of symptoms; however, this question was nonetheless very rarely endorsed in the subject )] TJ ET
BT 26.250 493.514 Td /F1 9.8 Tf  [(population. For the other five items, there were no statistically significant differences in either the severity or frequency of )] TJ ET
BT 26.250 481.609 Td /F1 9.8 Tf  [(symptoms between prHD and HD subjects \(Figure 5, as example\). In general, the correlations between each of these 6 )] TJ ET
BT 26.250 469.704 Td /F1 9.8 Tf  [(individual composite scores and the total composite score from the 6 highly-endorsed interview questions were low \(Table 3\); )] TJ ET
BT 26.250 457.800 Td /F1 9.8 Tf  [(the item-total correlation was high for �Aggression towards people� in the subset of prHD subjects, but this item was )] TJ ET
BT 26.250 445.895 Td /F1 9.8 Tf  [(nonetheless rarely endorsed in the subject population.)] TJ ET
0.965 0.965 0.965 rg
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BT 26.250 309.088 Td /F1 9.8 Tf  [(PsyD\); University of California San Francisco, California, USA \(Michael D. Geschwind, MD, PhD and Jon Gooblar, BA\); )] TJ ET
BT 26.250 297.183 Td /F1 9.8 Tf  [(University of Rochester, Rochester, New York, USA \(Amy Chesire, LCSW-R, MSG and Frederick Marshall, MD\); )] TJ ET
BT 26.250 285.279 Td /F1 9.8 Tf  [(Neurosciences Unit, Graylands, Selby-Lemnos & Special Care Health Services, Perth, Australia \(Peter Panegyres, MB, BS, )] TJ ET
BT 26.250 273.374 Td /F1 9.8 Tf  [(PhD, Elizabeth Vuletich, BSC, Steve Andrew\); Washington University, St. Louis, Missouri, USA \(Joel Perlmutter, MD and )] TJ ET
BT 26.250 261.469 Td /F1 9.8 Tf  [(Stacey Barton, MSW, LCSW\); Columbia University Medical Center, New York, New York, USA \(Pietro Mazzoni, MD, PhD and )] TJ ET
BT 26.250 249.564 Td /F1 9.8 Tf  [(Paula Wasserman, MA\); Colorado Neurological Institute, Englewood, Colorado, USA \(Diane Erickson, RN and Rajeev Kumar, )] TJ ET
BT 26.250 237.660 Td /F1 9.8 Tf  [(MD\); University of California Davis, Sacramento, California, USA \(Vicki Wheelock, MD, Terry Tempkin, RNC, MSN\); Baylor )] TJ ET
BT 26.250 225.755 Td /F1 9.8 Tf  [(College of Medicine, Houston, Texas, USA \(Joseph Jankovic, MD, Christine Hunter, RN, CCRC, and William Ondo, MD\); )] TJ ET
BT 26.250 213.850 Td /F1 9.8 Tf  [(Cleveland Clinic Foundation, Cleveland, Ohio, USA \(Anwar Ahmed, PhD, Christine Reece, BS, Alexandra Bea, BA, Alex Bura, )] TJ ET
BT 26.250 201.945 Td /F1 9.8 Tf  [(BA and Emily Newman, BA\). OCBN Contracted: Birmingham and Solihull Mental Health, Birmingham, UK \(Hugh Rickards, MD, )] TJ ET
BT 26.250 190.041 Td /F1 9.8 Tf  [(Jenny Crooks, BA, Jan Wright, BA\); Center for Movement Disorders, Markham, Ontario, Canada \(Mark Guttman, MD, Irita )] TJ ET
BT 26.250 178.136 Td /F1 9.8 Tf  [(Karmalkar, BA, and Alanna Sheinberg, BA, and Adam Singer, BA\); University of Melbourne, AU \(David Ames, MD, Edmond )] TJ ET
BT 26.250 166.231 Td /F1 9.8 Tf  [(Chiu, MD, Phyllis Chua, MD, Olga Yastrubetskaya, PhD, Joy Preston, Anita Goh, D.Psych, and Angela Komiti, BS, MA\); )] TJ ET
BT 26.250 154.326 Td /F1 9.8 Tf  [(University of Iowa, Iowa City, IA, USA \(Leigh Beglinger, PhD., Kevin Duff, PhD, Tom Wassink, MD, Patricia Ryan, MSW, MA, )] TJ ET
BT 26.250 142.422 Td /F1 9.8 Tf  [(Stephen Cross, BA, Mycah Kimble, BA, Stacie Vik, BA\); Huntington Disease Drug Works, Seattle, WA, USA \(LaVonne )] TJ ET
BT 26.250 130.517 Td /F1 9.8 Tf  [(Goodman, MD\); North York General Hospital, Toronto. Ontario, Canada \(Clare Gibbons, MS, Jeanne Kennedy, BScNEd, RN, )] TJ ET
BT 26.250 118.612 Td /F1 9.8 Tf  [(and Wendy Meschino, MD\).)] TJ ET
BT 26.250 82.010 Td /F4 12.0 Tf  [(Focus Groups)] TJ ET
BT 26.250 62.055 Td /F1 9.8 Tf  [(Portugal \(J Ferreira, T Mestre\), Spain \(A Mart�nez Descals\), France \(A Durr, C Jauffret\), The Netherlands \(R Bos, R Roos, M-N )] TJ ET
BT 26.250 50.151 Td /F1 9.8 Tf  [(Witjes-An�\), and England \(R Fullam, O Handley, J Naji\); HD Drug Works, Seattle, USA \(L Goodman\).)] TJ ET
Q
q
0.000 0.000 0.000 rg
BT 291.710 19.825 Td /F1 11.0 Tf  [(7)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Huntington Disease)] TJ ET

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>>
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/Length 11395 >>
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0.271 0.267 0.267 rg
q
15.000 324.235 577.500 452.765 re W n
0.271 0.267 0.267 rg
BT 26.250 750.278 Td /F4 12.0 Tf  [(Corresponding Author)] TJ ET
BT 26.250 730.324 Td /F1 9.8 Tf  [(Anthony L Vaccarino, avaccarino@ocbn.ca)] TJ ET
BT 26.250 693.722 Td /F4 12.0 Tf  [(Acknowledgements)] TJ ET
BT 26.250 673.767 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 26.250 661.863 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 26.250 649.958 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 26.250 638.053 Td /F1 9.8 Tf  [(the USA focus groups, and Stacie Vik and Barbara McQuaid for administrative assistance.)] TJ ET
BT 26.250 608.951 Td /F4 12.0 Tf  [(References)] TJ ET
BT 26.250 581.496 Td /F1 9.8 Tf  [(1.)] TJ ET
BT 38.132 581.496 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 26.250 569.592 Td /F1 9.8 Tf  [(FuRST-pHD, PREDICT-HD Investigators and Coordinators. The Functional Rating Scale Taskforce for pre-Huntington Disease: )] TJ ET
BT 26.250 557.687 Td /F1 9.8 Tf  [(Results So Far, J Neurol Neurosurg Psychiatry 2010; 81:A25)] TJ ET
BT 26.250 538.282 Td /F1 9.8 Tf  [(2.)] TJ ET
BT 38.132 538.282 Td /F1 9.8 Tf  [(Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research, Center for Devices and )] TJ ET
BT 26.250 526.377 Td /F1 9.8 Tf  [(Radiological Health Guidance for Industry, Patient-Reported Outcome Measures: Use in Medical Product Development to )] TJ ET
BT 26.250 514.473 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 26.250 495.068 Td /F1 9.8 Tf  [(3.)] TJ ET
BT 38.132 495.068 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 26.250 483.163 Td /F1 9.8 Tf  [(Psychopharm 2008;23:120-129)] TJ ET
BT 26.250 463.758 Td /F1 9.8 Tf  [(4.)] TJ ET
BT 38.132 463.758 Td /F1 9.8 Tf  [(Ramsay JO. Kernel Smoothing Approaches to Nonparametric Item Characteristic Curve Estimation. Psychometrika. 1991; )] TJ ET
BT 26.250 451.854 Td /F1 9.8 Tf  [(56:611-630)] TJ ET
BT 26.250 432.449 Td /F1 9.8 Tf  [(5.)] TJ ET
BT 38.132 432.449 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 26.250 420.544 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 26.250 408.639 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 26.250 396.735 Td /F1 9.8 Tf  [(Carriers, Movement Disorders, in press.)] TJ ET
BT 26.250 377.330 Td /F1 9.8 Tf  [(6.)] TJ ET
BT 38.132 377.330 Td /F1 9.8 Tf  [(Orth, Michael; Handley, Olivia J; Schwenke, Carsten; Dunnett, Stephen B.; Craufurd, David; Ho, Aileen K; Wild, Edward; )] TJ ET
BT 26.250 365.425 Td /F1 9.8 Tf  [(Tabrizi, Sarah J; Landwehrmeyer, G. Bernhard; the European Huntington's Disease Network, the investigators of. Observing )] TJ ET
BT 26.250 353.520 Td /F1 9.8 Tf  [(Huntington�s Disease: the European Huntington�s Disease Network�s REGISTRY [Internet]. Version 19. PLoS Currents: )] TJ ET
BT 26.250 341.616 Td /F1 9.8 Tf  [(Huntington Disease. 2010 Sep 28 [revised 2011 Apr 13]:PMC2947793.)] TJ ET
Q
q
15.000 324.235 577.500 452.765 re W n
0.271 0.267 0.267 rg
BT 26.250 750.278 Td /F4 12.0 Tf  [(Corresponding Author)] TJ ET
BT 26.250 730.324 Td /F1 9.8 Tf  [(Anthony L Vaccarino, avaccarino@ocbn.ca)] TJ ET
BT 26.250 693.722 Td /F4 12.0 Tf  [(Acknowledgements)] TJ ET
BT 26.250 673.767 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 26.250 661.863 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 26.250 649.958 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 26.250 638.053 Td /F1 9.8 Tf  [(the USA focus groups, and Stacie Vik and Barbara McQuaid for administrative assistance.)] TJ ET
BT 26.250 608.951 Td /F4 12.0 Tf  [(References)] TJ ET
BT 26.250 581.496 Td /F1 9.8 Tf  [(1.)] TJ ET
BT 38.132 581.496 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 26.250 569.592 Td /F1 9.8 Tf  [(FuRST-pHD, PREDICT-HD Investigators and Coordinators. The Functional Rating Scale Taskforce for pre-Huntington Disease: )] TJ ET
BT 26.250 557.687 Td /F1 9.8 Tf  [(Results So Far, J Neurol Neurosurg Psychiatry 2010; 81:A25)] TJ ET
BT 26.250 538.282 Td /F1 9.8 Tf  [(2.)] TJ ET
BT 38.132 538.282 Td /F1 9.8 Tf  [(Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research, Center for Devices and )] TJ ET
BT 26.250 526.377 Td /F1 9.8 Tf  [(Radiological Health Guidance for Industry, Patient-Reported Outcome Measures: Use in Medical Product Development to )] TJ ET
BT 26.250 514.473 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 26.250 495.068 Td /F1 9.8 Tf  [(3.)] TJ ET
BT 38.132 495.068 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 26.250 483.163 Td /F1 9.8 Tf  [(Psychopharm 2008;23:120-129)] TJ ET
BT 26.250 463.758 Td /F1 9.8 Tf  [(4.)] TJ ET
BT 38.132 463.758 Td /F1 9.8 Tf  [(Ramsay JO. Kernel Smoothing Approaches to Nonparametric Item Characteristic Curve Estimation. Psychometrika. 1991; )] TJ ET
BT 26.250 451.854 Td /F1 9.8 Tf  [(56:611-630)] TJ ET
BT 26.250 432.449 Td /F1 9.8 Tf  [(5.)] TJ ET
BT 38.132 432.449 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 26.250 420.544 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 26.250 408.639 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 26.250 396.735 Td /F1 9.8 Tf  [(Carriers, Movement Disorders, in press.)] TJ ET
BT 26.250 377.330 Td /F1 9.8 Tf  [(6.)] TJ ET
BT 38.132 377.330 Td /F1 9.8 Tf  [(Orth, Michael; Handley, Olivia J; Schwenke, Carsten; Dunnett, Stephen B.; Craufurd, David; Ho, Aileen K; Wild, Edward; )] TJ ET
BT 26.250 365.425 Td /F1 9.8 Tf  [(Tabrizi, Sarah J; Landwehrmeyer, G. Bernhard; the European Huntington's Disease Network, the investigators of. Observing )] TJ ET
BT 26.250 353.520 Td /F1 9.8 Tf  [(Huntington�s Disease: the European Huntington�s Disease Network�s REGISTRY [Internet]. Version 19. PLoS Currents: )] TJ ET
BT 26.250 341.616 Td /F1 9.8 Tf  [(Huntington Disease. 2010 Sep 28 [revised 2011 Apr 13]:PMC2947793.)] TJ ET
Q
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BT 26.250 750.278 Td /F4 12.0 Tf  [(Corresponding Author)] TJ ET
BT 26.250 730.324 Td /F1 9.8 Tf  [(Anthony L Vaccarino, avaccarino@ocbn.ca)] TJ ET
BT 26.250 693.722 Td /F4 12.0 Tf  [(Acknowledgements)] TJ ET
BT 26.250 673.767 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 26.250 661.863 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 26.250 649.958 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 26.250 638.053 Td /F1 9.8 Tf  [(the USA focus groups, and Stacie Vik and Barbara McQuaid for administrative assistance.)] TJ ET
BT 26.250 608.951 Td /F4 12.0 Tf  [(References)] TJ ET
BT 26.250 581.496 Td /F1 9.8 Tf  [(1.)] TJ ET
BT 38.132 581.496 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 26.250 569.592 Td /F1 9.8 Tf  [(FuRST-pHD, PREDICT-HD Investigators and Coordinators. The Functional Rating Scale Taskforce for pre-Huntington Disease: )] TJ ET
BT 26.250 557.687 Td /F1 9.8 Tf  [(Results So Far, J Neurol Neurosurg Psychiatry 2010; 81:A25)] TJ ET
BT 26.250 538.282 Td /F1 9.8 Tf  [(2.)] TJ ET
BT 38.132 538.282 Td /F1 9.8 Tf  [(Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research, Center for Devices and )] TJ ET
BT 26.250 526.377 Td /F1 9.8 Tf  [(Radiological Health Guidance for Industry, Patient-Reported Outcome Measures: Use in Medical Product Development to )] TJ ET
BT 26.250 514.473 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 26.250 495.068 Td /F1 9.8 Tf  [(3.)] TJ ET
BT 38.132 495.068 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 26.250 483.163 Td /F1 9.8 Tf  [(Psychopharm 2008;23:120-129)] TJ ET
BT 26.250 463.758 Td /F1 9.8 Tf  [(4.)] TJ ET
BT 38.132 463.758 Td /F1 9.8 Tf  [(Ramsay JO. Kernel Smoothing Approaches to Nonparametric Item Characteristic Curve Estimation. Psychometrika. 1991; )] TJ ET
BT 26.250 451.854 Td /F1 9.8 Tf  [(56:611-630)] TJ ET
BT 26.250 432.449 Td /F1 9.8 Tf  [(5.)] TJ ET
BT 38.132 432.449 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 26.250 420.544 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 26.250 408.639 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 26.250 396.735 Td /F1 9.8 Tf  [(Carriers, Movement Disorders, in press.)] TJ ET
BT 26.250 377.330 Td /F1 9.8 Tf  [(6.)] TJ ET
BT 38.132 377.330 Td /F1 9.8 Tf  [(Orth, Michael; Handley, Olivia J; Schwenke, Carsten; Dunnett, Stephen B.; Craufurd, David; Ho, Aileen K; Wild, Edward; )] TJ ET
BT 26.250 365.425 Td /F1 9.8 Tf  [(Tabrizi, Sarah J; Landwehrmeyer, G. Bernhard; the European Huntington's Disease Network, the investigators of. Observing )] TJ ET
BT 26.250 353.520 Td /F1 9.8 Tf  [(Huntington�s Disease: the European Huntington�s Disease Network�s REGISTRY [Internet]. Version 19. PLoS Currents: )] TJ ET
BT 26.250 341.616 Td /F1 9.8 Tf  [(Huntington Disease. 2010 Sep 28 [revised 2011 Apr 13]:PMC2947793.)] TJ ET
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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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trailer
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/Size 285
/Root 1 0 R
/Info 5 0 R
>>
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