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Keywords: attention-deficit/hyperactivity disorder, lisdexamfetamine, methylphenidate, mathematical modeling, in silico clinical trial Author: José Ramón Gutiérrez-Casares and Guillem Jorba Creator: LaTeX with hyperref package + hypdvips Producer: dvips + MiKTeX GPL Ghostscript 9.0 CreationDate: Thu Oct 28 12:01:57 2021 CEST ModDate: Thu Oct 28 14:29:48 2021 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 21 Encrypted: no Page size: 595.26 x 779.52 pts Page rot: 0 File size: 4537022 bytes Optimized: no PDF version: 1.6 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- UOONVV+HelveticaNeueLTStd-Bd Type 1C Custom yes yes no 51 0 PLVBQO+HelveticaNeueLTStd-Lt Type 1C Custom yes yes no 56 0 PUGCYQ+HelveticaNeueLTStd-BdIt Type 1C WinAnsi yes yes no 69 0 ADVJXT+HelveticaNeueLTStd-LtIt Type 1C Custom yes yes no 71 0 OSAPCR+HelveticaNeueLTStd-MdIt Type 1C WinAnsi yes yes no 77 0 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UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseOutlines Language: en Outlines: Item: Title: Methods to Develop an in silico Clinical Trial: Computational Head-to-Head Comparison of Lisdexamfetamine and Methylphenidate Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Children: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Children: Item: Title: Systems Biology and MID3 Guidelines Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Item: Title: Proof-of-Concept: ADHD Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4eb7f003 Item: Title: Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@eafc191 Children: Item: Title: Population Definition—Virtual Patients Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612fc6eb Children: Item: Title: Sample Size Calculation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1060b431 Item: Title: Patient Distribution Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612679d6 Item: Title: Intervention Definition Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@11758f2a Children: Item: Title: Dosage Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@e720b71 Item: Title: Molecular Target Profile Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1b26f7b2 Item: Title: Pharmacokinetics Information Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@491cc5c9 Item: Title: Modeling Methodology Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@74ad1f1f Children: Item: Title: Virtual Population Modeling Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6a1aab78 Item: Title: Systems Biology Maps and Models Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@462d5aee Item: Title: Physiologically Based Pharmacokinetic Models Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@69b0fd6f Item: Title: Quantitative Systems Pharmacology Models—Quantitative Mechanism of Action Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@757942a1 Item: Title: Efficacy Outcomes and Measures Definition and Optimization Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4a87761d Children: Item: Title: Molecular Measures Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@66d1af89 Item: Title: Efficacy Outcome Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@8646db9 Item: Title: Data Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@37374a5e Item: Title: Ethics Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4671e53b Item: Title: Computational Availability Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@2db7a79b Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6950e31 Children: Item: Title: Demographic Characteristics Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@b7dd107 Item: Title: Local Sensitivity Analysis of Systems Biology-Based Models Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@42eca56e Item: Title: Physiologically Based Pharmacokinetic Models Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@52f759d7 Item: Title: Efficacy Outcomes and Measures Definition and Optimization Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7cbd213e Item: Title: Quantitative Systems Pharmacology Models in the Virtual Populations Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@192d3247 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3ecd23d9 Children: Item: Title: Related Work Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@569cfc36 Item: Title: Strengths and Limitations Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@43bd930a Item: Title: Conclusion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@33723e30 Item: Title: Data Availability Statement Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@64f6106c Item: Title: Author Contributions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@553a3d88 Item: Title: Funding Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a30d1e6 Item: Title: Acknowledgments Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5891e32e Item: Title: Supplementary Material Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@cb0ed20 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@8e24743 Info: Title: Methods to Develop an in silico Clinical Trial: Computational Head-to-Head Comparison of Lisdexamfetamine and Methylphenidate Author: José Ramón Gutiérrez-Casares and Guillem Jorba Subject: Regulatory agencies encourage computer modeling and simulation to reduce the time and cost of clinical trials. Keywords: attention-deficit/hyperactivity disorder, lisdexamfetamine, methylphenidate, mathematical modeling, in silico clinical trial Creator: LaTeX with hyperref package + hypdvips Producer: dvips + MiKTeX GPL Ghostscript 9.0 CreationDate: Thu Oct 28 12:31:57 CEST 2021 ModDate: Thu Oct 28 14:59:48 CEST 2021 ID: 0x5e387a14a726abb86fb223af3f14c820, 0xb418fe55d5f71a4c81b5a980e2f21ab7 Filters: FilterPipeline: FlateDecode FilterPipeline: DCTDecode Images: Image: NisoImageMetadata: FormatName: image/png ImageWidth: 279 ImageHeight: 279 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/jpg CompressionScheme: JPEG ImageWidth: 2008 ImageHeight: 1945 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Interpolate: true Image: NisoImageMetadata: FormatName: image/jpg CompressionScheme: JPEG ImageWidth: 2008 ImageHeight: 1253 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Interpolate: true Image: 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Destination: External Annotation: Subtype: Link Rect: 482, 404, 493, 415 Destination: External Annotation: Subtype: Link Rect: 428, 392, 439, 404 Destination: External Annotation: Subtype: Link Rect: 416, 337, 427, 349 Destination: External Annotation: Subtype: Link Rect: 430, 337, 441, 349 Destination: External Annotation: Subtype: Link Rect: 445, 337, 456, 349 Destination: External Annotation: Subtype: Link Rect: 459, 337, 470, 349 Destination: External Annotation: Subtype: Link Rect: 473, 337, 484, 349 Destination: External Annotation: Subtype: Link Rect: 488, 337, 499, 349 Destination: External Annotation: Subtype: Link Rect: 340, 76, 382, 86 Destination: External Annotation: Subtype: Link Rect: 441, 76, 481, 86 Destination: External Annotation: Subtype: Link Rect: 43, 29, 111, 37 Annotation: Subtype: Link Rect: 114, 29, 174, 37 Annotation: Subtype: Link Rect: 414, 29, 551, 38 Page: Label: 10 Sequence: 10 Annotations: Annotation: Subtype: Link Rect: 522, 650, 532, 659 Destination: External Annotation: Subtype: Link Rect: 522, 638, 532, 648 Destination: External Annotation: Subtype: Link Rect: 522, 617, 532, 626 Destination: External Annotation: Subtype: Link Rect: 522, 596, 532, 605 Destination: External Annotation: Subtype: Link Rect: 522, 575, 532, 584 Destination: External Annotation: Subtype: Link Rect: 522, 553, 532, 563 Destination: External Annotation: Subtype: Link Rect: 522, 532, 532, 542 Destination: External Annotation: Subtype: Link Rect: 522, 499, 532, 509 Destination: External Annotation: Subtype: Link Rect: 522, 478, 532, 488 Destination: External Annotation: Subtype: Link Rect: 522, 457, 532, 466 Destination: External Annotation: Subtype: Link Rect: 522, 436, 532, 445 Destination: External Annotation: Subtype: Link Rect: 522, 414, 532, 424 Destination: External Annotation: Subtype: Link Rect: 522, 403, 532, 412 Destination: External Annotation: Subtype: Link Rect: 522, 372, 532, 382 Destination: External Annotation: Subtype: Link Rect: 522, 341, 532, 351 Destination: External Annotation: Subtype: Link Rect: 155, 276, 185, 285 Destination: External Annotation: Subtype: Link Rect: 150, 265, 180, 273 Destination: External Annotation: Subtype: Link Rect: 54, 99, 159, 110 Destination: External Annotation: Subtype: Link Rect: 459, 203, 494, 213 Destination: External Annotation: Subtype: Link Rect: 43, 29, 111, 37 Annotation: Subtype: Link Rect: 114, 29, 174, 37 Annotation: Subtype: Link Rect: 414, 29, 551, 38 Page: Label: 11 Sequence: 11 Annotations: Annotation: Subtype: Link Rect: 164, 103, 269, 113 Destination: External Annotation: Subtype: Link Rect: 43, 68, 148, 79 Destination: External Annotation: Subtype: Link Rect: 43, 29, 111, 37 Annotation: Subtype: Link Rect: 114, 29, 174, 37 Annotation: Subtype: Link Rect: 414, 29, 551, 38 Page: Label: 12 Sequence: 12 Annotations: Annotation: Subtype: Link Rect: 255, 67, 285, 75 Destination: External Annotation: Subtype: Link Rect: 343, 695, 377, 705 Destination: External Annotation: Subtype: Link Rect: 407, 422, 438, 430 Destination: External Annotation: Subtype: Link Rect: 475, 90, 486, 101 Destination: External Annotation: Subtype: Link Rect: 307, 67, 323, 78 Destination: External Annotation: Subtype: Link Rect: 325, 67, 341, 78 Destination: External Annotation: Subtype: Link Rect: 43, 29, 111, 37 Annotation: Subtype: Link Rect: 114, 29, 174, 37 Annotation: Subtype: Link Rect: 414, 29, 551, 38 Page: Label: 13 Sequence: 13 Annotations: Annotation: Subtype: Link Rect: 325, 386, 335, 395 Destination: External Annotation: Subtype: Link Rect: 209, 376, 218, 386 Destination: External Annotation: Subtype: Link Rect: 109, 367, 118, 376 Destination: External Annotation: Subtype: Link Rect: 67, 358, 77, 367 Destination: External Annotation: Subtype: Link Rect: 230, 329, 246, 340 Destination: External Annotation: Subtype: Link Rect: 249, 329, 264, 340 Destination: External Annotation: Subtype: Link Rect: 78, 306, 93, 317 Destination: External Annotation: Subtype: Link Rect: 96, 306, 112, 317 Destination: External Annotation: Subtype: Link Rect: 66, 226, 82, 237 Destination: External Annotation: Subtype: Link Rect: 70, 158, 85, 170 Destination: External Annotation: Subtype: Link Rect: 200, 113, 216, 124 Destination: External Annotation: Subtype: Link Rect: 221, 113, 236, 124 Destination: External Annotation: Subtype: Link Rect: 245, 78, 261, 90 Destination: External Annotation: Subtype: Link Rect: 364, 226, 380, 237 Destination: External Annotation: Subtype: Link Rect: 345, 146, 361, 157 Destination: External Annotation: Subtype: Link Rect: 356, 113, 372, 124 Destination: External Annotation: Subtype: Link Rect: 530, 101, 546, 113 Destination: External Annotation: Subtype: Link Rect: 530, 67, 546, 78 Destination: External Annotation: Subtype: Link Rect: 43, 29, 111, 37 Annotation: Subtype: Link Rect: 114, 29, 174, 37 Annotation: Subtype: Link Rect: 414, 29, 551, 38 Page: Label: 14 Sequence: 14 Annotations: Annotation: Subtype: Link Rect: 180, 434, 195, 446 Destination: External Annotation: Subtype: Link Rect: 93, 365, 109, 377 Destination: External Annotation: Subtype: Link Rect: 108, 170, 119, 181 Destination: External Annotation: Subtype: Link Rect: 209, 124, 225, 135 Destination: External Annotation: Subtype: Link Rect: 228, 124, 244, 135 Destination: External Annotation: Subtype: Link Rect: 484, 525, 500, 536 Destination: External Annotation: Subtype: Link Rect: 503, 525, 519, 536 Destination: External Annotation: Subtype: Link Rect: 385, 330, 400, 342 Destination: External Annotation: Subtype: Link Rect: 406, 330, 422, 342 Destination: External Annotation: Subtype: Link Rect: 403, 319, 418, 330 Destination: External Annotation: Subtype: Link Rect: 425, 319, 440, 330 Destination: External Annotation: Subtype: Link Rect: 416, 307, 432, 319 Destination: External Annotation: Subtype: Link Rect: 435, 307, 450, 319 Destination: External Annotation: Subtype: Link Rect: 537, 158, 548, 170 Destination: External Annotation: Subtype: Link Rect: 43, 29, 111, 37 Annotation: Subtype: Link Rect: 114, 29, 174, 37 Annotation: Subtype: Link Rect: 414, 29, 551, 38 Page: Label: 15 Sequence: 15 Annotations: Annotation: Subtype: Link Rect: 43, 29, 111, 37 Annotation: Subtype: Link Rect: 114, 29, 174, 37 Annotation: Subtype: Link Rect: 414, 29, 551, 38 Page: Label: 16 Sequence: 16 Annotations: Annotation: Subtype: Link Rect: 47, 426, 58, 438 Destination: External Annotation: Subtype: Link Rect: 274, 381, 285, 392 Destination: External Annotation: Subtype: Link Rect: 122, 289, 152, 297 Destination: External Annotation: Subtype: Link Rect: 43, 218, 148, 229 Destination: External Annotation: Subtype: Link Rect: 370, 184, 475, 194 Destination: External Annotation: Subtype: Link Rect: 304, 126, 409, 137 Destination: External Annotation: Subtype: Link Rect: 43, 29, 111, 37 Annotation: Subtype: Link Rect: 114, 29, 174, 37 Annotation: Subtype: Link Rect: 414, 29, 551, 38 Page: Label: 17 Sequence: 17 Annotations: Annotation: Subtype: Link Rect: 96, 442, 194, 453 Destination: External Annotation: Subtype: Link Rect: 304, 578, 392, 587 Annotation: Subtype: Link Rect: 552, 336, 303, 361 Annotation: Subtype: Link Rect: 180, 265, 248, 274 Annotation: Subtype: Link Rect: 164, 238, 246, 245 Annotation: Subtype: Link Rect: 112, 209, 232, 217 Annotation: Subtype: Link Rect: 161, 180, 240, 189 Annotation: Subtype: Link Rect: 122, 151, 225, 160 Annotation: Subtype: Link Rect: 85, 115, 150, 122 Annotation: Subtype: Link Rect: 112, 68, 229, 75 Annotation: Subtype: Link Rect: 371, 274, 419, 283 Annotation: Subtype: Link Rect: 365, 247, 426, 255 Annotation: Subtype: Link Rect: 341, 209, 441, 217 Annotation: Subtype: Link Rect: 353, 161, 413, 170 Annotation: Subtype: Link Rect: 552, 112, 320, 133 Annotation: Subtype: Link Rect: 510, 94, 551, 104 Annotation: Subtype: Link Rect: 321, 85, 544, 94 Annotation: Subtype: Link Rect: 321, 75, 490, 85 Annotation: Subtype: Link Rect: 43, 28, 111, 36 Annotation: Subtype: Link Rect: 114, 28, 174, 36 Annotation: Subtype: Link Rect: 414, 28, 551, 37 Page: Label: 18 Sequence: 18 Annotations: Annotation: Subtype: Link Rect: 88, 678, 150, 687 Annotation: Subtype: Link Rect: 104, 650, 160, 659 Annotation: Subtype: Link Rect: 112, 612, 195, 621 Annotation: Subtype: Link Rect: 108, 574, 166, 583 Annotation: Subtype: Link Rect: 107, 536, 222, 545 Annotation: Subtype: Link Rect: 85, 500, 197, 507 Annotation: Subtype: Link Rect: 211, 479, 284, 488 Annotation: Subtype: Link Rect: 112, 451, 186, 460 Annotation: Subtype: Link Rect: 152, 424, 237, 431 Annotation: Subtype: Link Rect: 115, 394, 204, 403 Annotation: Subtype: Link Rect: 81, 328, 148, 337 Annotation: Subtype: Link Rect: 151, 282, 214, 290 Annotation: Subtype: Link Rect: 108, 206, 197, 214 Annotation: Subtype: Link Rect: 204, 187, 282, 195 Annotation: Subtype: Link Rect: 112, 139, 212, 148 Annotation: Subtype: Link Rect: 122, 91, 207, 100 Annotation: Subtype: Link Rect: 365, 689, 460, 696 Annotation: Subtype: Link Rect: 442, 651, 538, 659 Annotation: Subtype: Link Rect: 384, 612, 551, 621 Annotation: Subtype: Link Rect: 321, 604, 351, 612 Annotation: Subtype: Link Rect: 365, 566, 437, 573 Annotation: Subtype: Link Rect: 552, 516, 320, 537 Annotation: Subtype: Link Rect: 405, 489, 469, 498 Annotation: Subtype: Link Rect: 378, 462, 473, 470 Annotation: Subtype: Link Rect: 434, 434, 527, 441 Annotation: Subtype: Link Rect: 350, 405, 425, 413 Annotation: Subtype: Link Rect: 493, 347, 551, 356 Annotation: Subtype: Link Rect: 552, 291, 320, 309 Annotation: Subtype: Link Rect: 372, 263, 484, 271 Annotation: Subtype: Link Rect: 345, 205, 415, 214 Annotation: Subtype: Link Rect: 430, 176, 495, 186 Annotation: Subtype: Link Rect: 462, 148, 528, 157 Annotation: Subtype: Link Rect: 426, 120, 487, 129 Annotation: Subtype: Link Rect: 393, 91, 475, 101 Annotation: Subtype: Link Rect: 43, 29, 111, 37 Annotation: Subtype: Link Rect: 114, 29, 174, 37 Annotation: Subtype: Link Rect: 414, 29, 551, 38 Page: Label: 19 Sequence: 19 Annotations: Annotation: Subtype: Link Rect: 85, 697, 191, 706 Annotation: Subtype: Link Rect: 85, 650, 172, 659 Annotation: Subtype: Link Rect: 154, 612, 234, 621 Annotation: Subtype: Link Rect: 115, 585, 203, 592 Annotation: Subtype: Link Rect: 104, 546, 197, 555 Annotation: Subtype: Link Rect: 108, 509, 193, 517 Annotation: Subtype: Link Rect: 85, 481, 180, 488 Annotation: Subtype: Link Rect: 85, 442, 160, 450 Annotation: Subtype: Link Rect: 161, 413, 229, 422 Annotation: Subtype: Link Rect: 221, 385, 291, 394 Annotation: Subtype: Link Rect: 61, 377, 103, 384 Annotation: Subtype: Link Rect: 140, 329, 225, 337 Annotation: Subtype: Link Rect: 189, 300, 291, 309 Annotation: Subtype: Link Rect: 61, 290, 281, 299 Annotation: Subtype: Link Rect: 61, 281, 171, 290 Annotation: Subtype: Link Rect: 155, 262, 291, 271 Annotation: Subtype: Link Rect: 61, 252, 111, 261 Annotation: Subtype: Link Rect: 122, 233, 291, 243 Annotation: Subtype: Link Rect: 61, 225, 140, 233 Annotation: Subtype: Link Rect: 107, 167, 291, 176 Annotation: Subtype: Link Rect: 88, 121, 173, 129 Annotation: Subtype: Link Rect: 368, 697, 464, 706 Annotation: Subtype: Link Rect: 340, 659, 522, 668 Annotation: Subtype: Link Rect: 435, 623, 531, 630 Annotation: Subtype: Link Rect: 484, 593, 546, 602 Annotation: Subtype: Link Rect: 552, 565, 320, 584 Annotation: Subtype: Link Rect: 368, 538, 480, 545 Annotation: Subtype: Link Rect: 393, 460, 489, 469 Annotation: Subtype: Link Rect: 345, 423, 409, 432 Annotation: Subtype: Link Rect: 471, 404, 541, 413 Annotation: Subtype: Link Rect: 368, 328, 464, 337 Annotation: Subtype: Link Rect: 552, 272, 320, 290 Annotation: Subtype: Link Rect: 333, 243, 481, 252 Annotation: Subtype: Link Rect: 552, 186, 320, 205 Annotation: Subtype: Link Rect: 372, 148, 467, 157 Annotation: Subtype: Link Rect: 368, 102, 453, 110 Annotation: Subtype: Link Rect: 43, 29, 111, 37 Annotation: Subtype: Link Rect: 114, 29, 174, 37 Annotation: Subtype: Link Rect: 414, 29, 551, 38 Page: Label: 20 Sequence: 20 Annotations: Annotation: Subtype: Link Rect: 81, 697, 176, 706 Annotation: Subtype: Link Rect: 129, 650, 230, 659 Annotation: Subtype: Link Rect: 215, 612, 291, 621 Annotation: Subtype: Link Rect: 61, 604, 136, 612 Annotation: Subtype: Link Rect: 292, 554, 60, 574 Annotation: Subtype: Link Rect: 81, 517, 161, 526 Annotation: Subtype: Link Rect: 112, 470, 212, 479 Annotation: Subtype: Link Rect: 292, 421, 60, 442 Annotation: Subtype: Link Rect: 88, 394, 198, 403 Annotation: Subtype: Link Rect: 239, 366, 286, 375 Annotation: Subtype: Link Rect: 180, 337, 291, 347 Annotation: Subtype: Link Rect: 85, 262, 180, 271 Annotation: Subtype: Link Rect: 182, 235, 267, 242 Annotation: Subtype: Link Rect: 147, 197, 231, 204 Annotation: Subtype: Link Rect: 136, 167, 206, 176 Annotation: Subtype: Link Rect: 85, 140, 170, 148 Annotation: Subtype: Link Rect: 187, 112, 272, 119 Annotation: Subtype: Link Rect: 187, 74, 272, 81 Annotation: Subtype: Link Rect: 341, 670, 426, 678 Annotation: Subtype: Link Rect: 348, 632, 448, 640 Annotation: Subtype: Link Rect: 421, 603, 480, 611 Annotation: Subtype: Link Rect: 375, 557, 461, 564 Annotation: Subtype: Link Rect: 368, 528, 428, 536 Annotation: Subtype: Link Rect: 465, 500, 550, 507 Annotation: Subtype: Link Rect: 447, 462, 532, 469 Annotation: Subtype: Link Rect: 468, 423, 527, 432 Annotation: Subtype: Link Rect: 345, 377, 430, 384 Annotation: Subtype: Link Rect: 368, 339, 437, 347 Annotation: Subtype: Link Rect: 552, 291, 320, 309 Annotation: Subtype: Link Rect: 552, 253, 320, 272 Annotation: Subtype: Link Rect: 345, 216, 441, 223 Annotation: Subtype: Link Rect: 367, 178, 459, 186 Annotation: Subtype: Link Rect: 390, 140, 445, 148 Annotation: Subtype: Link Rect: 475, 112, 543, 119 Annotation: Subtype: Link Rect: 455, 74, 518, 81 Annotation: Subtype: Link Rect: 43, 29, 111, 37 Annotation: Subtype: Link Rect: 114, 29, 174, 37 Annotation: Subtype: Link Rect: 414, 29, 551, 38 Page: Label: 21 Sequence: 21 Annotations: Annotation: Subtype: Link Rect: 115, 670, 193, 678 Annotation: Subtype: Link Rect: 108, 632, 177, 640 Annotation: Subtype: Link Rect: 85, 583, 168, 592 Annotation: Subtype: Link Rect: 97, 547, 186, 554 Annotation: Subtype: Link Rect: 292, 497, 60, 518 Annotation: Subtype: Link Rect: 108, 460, 180, 469 Annotation: Subtype: Link Rect: 85, 432, 163, 441 Annotation: Subtype: Link Rect: 176, 415, 262, 422 Annotation: Subtype: Link Rect: 85, 375, 188, 384 Annotation: Subtype: Link Rect: 108, 347, 194, 356 Annotation: Subtype: Link Rect: 401, 699, 501, 706 Annotation: Subtype: Link Rect: 345, 659, 445, 668 Annotation: Subtype: Link Rect: 478, 640, 536, 649 Annotation: Subtype: Link Rect: 345, 612, 431, 621 Annotation: Subtype: Link Rect: 372, 583, 461, 593 Annotation: Subtype: Link Rect: 341, 386, 367, 393 Annotation: Subtype: Link Rect: 367, 386, 399, 393 Annotation: Subtype: Link Rect: 399, 386, 435, 394 Annotation: Subtype: Link Rect: 435, 386, 458, 393 Annotation: Subtype: Link Rect: 458, 385, 486, 394 Annotation: Subtype: Link Rect: 43, 29, 111, 37 Annotation: Subtype: Link Rect: 114, 29, 174, 37 Annotation: Subtype: Link Rect: 414, 29, 551, 38 Checksum: efe64f16 Type: CRC32 Checksum: 47d589574ba4f56fbfb41db8f9c86fdb Type: MD5 Checksum: 8af50db5c239ad8d1ad4c2ac37e9ca4b860a08a8 Type: SHA-1