d912fe0ba55dc20f98ab41d7001346b0 pmc_9917981.pdf ca581f0e20e1670f5800d5db6d86e99881442496 pmc_9917981.pdf 192ccb5afe73dce298e6e2b0ea7197e8c5a9472df3e34bdaaf022b2584b862cc pmc_9917981.pdf Title: An Exploratory Analysis on the 2D:4D Digit Ratio and Its Relationship with Social Responsiveness in Adults with Prader–Willi Syndrome Subject: Prader–Willi syndrome (PWS) is a genetic disorder produced by a lack of expression of paternally derived genes in the 15q11–13 region. Research has generally focused on its genetic and behavioral expression, but only a few studies have examined epigenetic influences. Prenatal testosterone or the maternal testosterone-to-estradiol ratio (MaTtEr) has been suggested to play an important role in the development of the ‘social brain’ during pregnancy. Some studies propose the 2D:4D digit ratio of the hand as an indirect MaTtEr measure. The relationship between social performance and MaTtEr has been studied in other neurodevelopmental conditions such as Autism Spectrum Disorder (ASD), but to our best knowledge, it has never been studied in PWS. Therefore, our study aims to clarify the possible existence of a relationship between social performance—as measured using the Social Responsiveness Scale (SRS)—and MaTtEr levels using the 2D:4D ratio. We found that, as a group, PWS individuals have shorter index and ring fingers than the control group, but no significant difference in the 2D:4D ratios. The 2D:4D ratio showed a correlation only with Restricted Interests and Repetitive Behavior Subscale, where a positive correlation only for male individuals with PWS was found. Considering only PWS with previous GH treatment during childhood/adolescence (PWS-GH), index and ring fingers did not show differences in length with the control group, but the 2D:4D ratio was significantly higher in the right or dominant hand compared to controls. Keywords: Prader–Willi syndrome; epigenetic; testosterone; estradiol; prenatal; D2:D4; social responsiveness; social functioning; functionality; function Author: Sara Gámez, Jesus Cobo, Meritxell Fernández-Lafitte, Ramón Coronas, Isabel Parra, Joan Carles Oliva, Aida Àlvarez, Susanna Esteba-Castillo, Olga Giménez-Palop, Raquel Corripio, Diego J. Palao and Assumpta Caixàs Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Feb 1 10:52:29 2023 CET ModDate: Wed Feb 1 10:59:37 2023 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 18 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 3172102 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- WQJREQ+VnURWPalladioL Type 1 Custom yes yes no 10 0 IVDMNY+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 UUQQDU+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 DQNUIF+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 LIOWFH+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 XPUSBJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 46 0 BSDWLC+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 49 0 EILUJF+CMSY10 Type 1 Builtin yes yes no 77 0 OHDMLJ+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 93 0 OHDMLL+PalatinoLinotype TrueType WinAnsi yes yes no 96 0 OHDMLN+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 99 0 OHDMLJ+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 113 0 OHDMLL+PalatinoLinotype TrueType WinAnsi yes yes no 116 0 OHDMLN+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 119 0 OHDMLJ+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 134 0 OHDMLL+PalatinoLinotype TrueType WinAnsi yes yes no 137 0 OHDMLN+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 140 0 OHDMLJ+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 152 0 OHDMLL+PalatinoLinotype TrueType WinAnsi yes yes no 155 0 OHDMLN+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 158 0 OHDMLJ+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 189 0 OHDMLL+PalatinoLinotype TrueType WinAnsi yes yes no 192 0 OHDMLN+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 195 0 OHDMLJ+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 209 0 OHDMLL+PalatinoLinotype TrueType WinAnsi yes yes no 212 0 OHDMLN+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 215 0 NJWNDJ+VnURWPalladioL-Italic Type 1 Custom yes yes no 231 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-05-20 02:29:27 CEST RepresentationInformation: pmc_9917981.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-03-30 02:15:23 CEST Size: 3172102 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 472 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Design and Sample Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Procedure Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Assessment Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Children: Item: Title: Sociodemographic, Hormonal, and Anthropometric Variables in Both Groups Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Bivariate Correlation of Severity VAS, Estimated Intelligence Quotient (IQ), Behavior (SDQ), Functionality (SPS), and Social Responsiveness (SRS) in the PWS Sample Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Sex Interactions in Both Samples Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Relationship and SRS Sex Interactions of 2D:4D Digits on the Right Hand in the PWS Sample Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Relationship and SRS Sex Interactions of 2D:4D Digit on the Left Hand in the PWS Sample Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Relationship and SRS Sex Interactions of 2D:4D Digit on the Dominant Hand in the PWS Sample Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Relationship between 2D or 4D Finger Lengths, 2D:4D Digit Ratios, and GH Administration during the Childhood and Adolescent Period Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Relationship of GH Administration during the Childhood and Adolescent Period with Hormonal and SRS Factors Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Limitations and Strengths Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Info: Title: An Exploratory Analysis on the 2D:4D Digit Ratio and Its Relationship with Social Responsiveness in Adults with Prader Willi Syndrome Author: Sara Gámez, Jesus Cobo, Meritxell Fernández-Lafitte, Ramón Coronas, Isabel Parra, Joan Carles Oliva, Aida Àlvarez, Susanna Esteba-Castillo, Olga Giménez-Palop, Raquel Corripio, Diego J. Palao and Assumpta Caixàs Subject: Prader Willi syndrome (PWS) is a genetic disorder produced by a lack of expression of paternally derived genes in the 15q11 13 region. Research has generally focused on its genetic and behavioral expression, but only a few studies have examined epigenetic influences. Prenatal testosterone or the maternal testosterone-to-estradiol ratio (MaTtEr) has been suggested to play an important role in the development of the ‘social brain’ during pregnancy. Some studies propose the 2D:4D digit ratio of the hand as an indirect MaTtEr measure. The relationship between social performance and MaTtEr has been studied in other neurodevelopmental conditions such as Autism Spectrum Disorder (ASD), but to our best knowledge, it has never been studied in PWS. Therefore, our study aims to clarify the possible existence of a relationship between social performance as measured using the Social Responsiveness Scale (SRS) and MaTtEr levels using the 2D:4D ratio. We found that, as a group, PWS individuals have shorter index and ring fingers than the control group, but no significant difference in the 2D:4D ratios. The 2D:4D ratio showed a correlation only with Restricted Interests and Repetitive Behavior Subscale, where a positive correlation only for male individuals with PWS was found. Considering only PWS with previous GH treatment during childhood/adolescence (PWS-GH), index and ring fingers did not show differences in length with the control group, but the 2D:4D ratio was significantly higher in the right or dominant hand compared to controls. Keywords: Prader Willi syndrome; epigenetic; testosterone; estradiol; prenatal; D2:D4; social responsiveness; social functioning; functionality; function Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Feb 01 10:52:29 CET 2023 ModDate: Wed Feb 01 10:59:37 CET 2023 ID: 0x1d75069e482a9b568651b71a145a0115, 0x1d75069e482a9b568651b71a145a0115 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: UUQQDU+URWPalladioL-Roma FontSubset: true FirstChar: 1 LastChar: 246 FontDescriptor: FontName: UUQQDU+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: NJWNDJ+VnURWPalladioL-Italic FontSubset: true FirstChar: 189 LastChar: 226 FontDescriptor: FontName: NJWNDJ+VnURWPalladioL-Italic Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: DQNUIF+URWPalladioL-Ital FontSubset: true FirstChar: 40 LastChar: 122 FontDescriptor: FontName: DQNUIF+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: WQJREQ+VnURWPalladioL FontSubset: true FirstChar: 128 LastChar: 243 FontDescriptor: FontName: WQJREQ+VnURWPalladioL Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: LIOWFH+VnURWPalladioL-Bold FontSubset: true FirstChar: 128 LastChar: 226 FontDescriptor: FontName: LIOWFH+VnURWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: EILUJF+CMSY10 FontSubset: true FirstChar: 0 LastChar: 21 FontDescriptor: FontName: EILUJF+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true Font: BaseFont: IVDMNY+URWPalladioL-Bold FontSubset: true FirstChar: 2 LastChar: 150 FontDescriptor: FontName: IVDMNY+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 82, 281, 152, 290 Annotation: Subtype: Link Rect: 34, 269, 102, 278 Annotation: Subtype: Link Rect: 34, 164, 96, 186 Annotation: Subtype: Link Rect: 126, 90, 154, 99 Annotation: Subtype: Link Rect: 34, 78, 147, 87 Annotation: Subtype: Link Rect: 34, 756, 176, 792 Annotation: Subtype: Link Rect: 515, 756, 560, 792 Annotation: Subtype: Link Rect: 192, 642, 203, 655 Annotation: Subtype: Link Rect: 321, 629, 332, 643 Annotation: Subtype: Link Rect: 444, 629, 455, 643 Annotation: Subtype: Link Rect: 542, 629, 553, 643 Annotation: Subtype: Link Rect: 118, 617, 129, 630 Annotation: Subtype: Link Rect: 248, 617, 259, 630 Annotation: Subtype: Link Rect: 130, 17, 267, 28 Annotation: Subtype: Link Rect: 424, 17, 560, 28 Annotation: Subtype: Link Rect: 34, 402, 87, 421 Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 343, 723, 350, 732 ActionDest: 225 Annotation: Subtype: Link Rect: 245, 698, 252, 707 ActionDest: 225 Annotation: Subtype: Link Rect: 488, 685, 495, 694 ActionDest: 225 Annotation: Subtype: Link Rect: 505, 660, 511, 669 ActionDest: 225 Annotation: Subtype: Link Rect: 504, 597, 511, 606 ActionDest: 225 Annotation: Subtype: Link Rect: 511, 597, 518, 606 ActionDest: 225 Annotation: Subtype: Link Rect: 323, 572, 330, 581 ActionDest: 225 Annotation: Subtype: Link Rect: 330, 572, 337, 581 ActionDest: 225 Annotation: Subtype: Link Rect: 367, 560, 374, 569 ActionDest: 225 Annotation: Subtype: Link Rect: 375, 560, 382, 569 ActionDest: 225 Annotation: Subtype: Link Rect: 241, 509, 248, 519 ActionDest: 225 Annotation: Subtype: Link Rect: 292, 497, 299, 506 ActionDest: 225 Annotation: Subtype: Link Rect: 302, 497, 313, 506 ActionDest: 225 Annotation: Subtype: Link Rect: 454, 484, 461, 493 ActionDest: 225 Annotation: Subtype: Link Rect: 461, 484, 468, 493 ActionDest: 225 Annotation: Subtype: Link Rect: 469, 484, 481, 493 ActionDest: 225 Annotation: Subtype: Link Rect: 484, 484, 496, 493 ActionDest: 225 Annotation: Subtype: Link Rect: 397, 459, 409, 468 ActionDest: 225 Annotation: Subtype: Link Rect: 399, 434, 406, 443 ActionDest: 225 Annotation: Subtype: Link Rect: 406, 434, 418, 443 ActionDest: 225 Annotation: Subtype: Link Rect: 473, 409, 485, 418 ActionDest: 225 Annotation: Subtype: Link Rect: 228, 259, 240, 267 ActionDest: 225 Annotation: Subtype: Link Rect: 243, 258, 255, 267 ActionDest: 225 Annotation: Subtype: Link Rect: 446, 246, 458, 255 ActionDest: 225 Annotation: Subtype: Link Rect: 462, 246, 473, 255 ActionDest: 225 Annotation: Subtype: Link Rect: 219, 221, 231, 230 ActionDest: 225 Annotation: Subtype: Link Rect: 231, 221, 243, 230 ActionDest: 225 Annotation: Subtype: Link Rect: 395, 221, 407, 230 ActionDest: 225 Annotation: Subtype: Link Rect: 413, 171, 425, 180 ActionDest: 228 Annotation: Subtype: Link Rect: 425, 170, 437, 180 ActionDest: 228 Annotation: Subtype: Link Rect: 375, 158, 387, 167 ActionDest: 228 Annotation: Subtype: Link Rect: 517, 108, 529, 117 ActionDest: 228 Annotation: Subtype: Link Rect: 530, 108, 542, 117 ActionDest: 228 Annotation: Subtype: Link Rect: 361, 83, 372, 92 ActionDest: 228 Annotation: Subtype: Link Rect: 389, 70, 401, 79 ActionDest: 228 Page: Sequence: 3 Annotations: Annotation: Subtype: Link Rect: 275, 723, 287, 732 ActionDest: 228 Annotation: Subtype: Link Rect: 355, 660, 367, 669 ActionDest: 228 Annotation: Subtype: Link Rect: 199, 623, 211, 631 ActionDest: 228 Annotation: Subtype: Link Rect: 375, 597, 387, 606 ActionDest: 228 Annotation: Subtype: Link Rect: 390, 597, 402, 606 ActionDest: 228 Annotation: Subtype: Link Rect: 530, 560, 542, 569 ActionDest: 228 Annotation: Subtype: Link Rect: 544, 560, 556, 569 ActionDest: 228 Annotation: Subtype: Link Rect: 224, 535, 236, 544 ActionDest: 228 Annotation: Subtype: Link Rect: 422, 497, 434, 506 ActionDest: 228 Annotation: Subtype: Link Rect: 495, 497, 506, 506 ActionDest: 228 Annotation: Subtype: Link Rect: 441, 459, 453, 468 ActionDest: 228 Page: Sequence: 4 Annotations: Annotation: Subtype: Link Rect: 531, 707, 543, 716 ActionDest: 228 Annotation: Subtype: Link Rect: 194, 670, 205, 679 ActionDest: 228 Annotation: Subtype: Link Rect: 515, 657, 527, 666 ActionDest: 228 Annotation: Subtype: Link Rect: 528, 657, 540, 666 ActionDest: 228 Annotation: Subtype: Link Rect: 410, 644, 422, 654 ActionDest: 228 Annotation: Subtype: Link Rect: 282, 431, 294, 440 ActionDest: 228 Annotation: Subtype: Link Rect: 405, 419, 417, 428 ActionDest: 228 Annotation: Subtype: Link Rect: 418, 419, 430, 428 ActionDest: 228 Annotation: Subtype: Link Rect: 277, 406, 288, 415 ActionDest: 225 Annotation: Subtype: Link Rect: 396, 381, 408, 390 ActionDest: 228 Annotation: Subtype: Link Rect: 411, 381, 423, 390 ActionDest: 228 Annotation: Subtype: Link Rect: 358, 318, 370, 327 ActionDest: 228 Annotation: Subtype: Link Rect: 416, 281, 428, 290 ActionDest: 228 Annotation: Subtype: Link Rect: 428, 280, 440, 290 ActionDest: 228 Annotation: Subtype: Link Rect: 335, 243, 347, 252 ActionDest: 228 Annotation: Subtype: Link Rect: 347, 243, 359, 252 ActionDest: 228 Annotation: Subtype: Link Rect: 222, 155, 234, 164 ActionDest: 228 Annotation: Subtype: Link Rect: 445, 117, 457, 126 ActionDest: 228 Annotation: Subtype: Link Rect: 357, 64, 364, 76 ActionDest: 81 Annotation: Subtype: Link Rect: 384, 64, 391, 76 ActionDest: 81 Page: Sequence: 5 Annotations: Annotation: Subtype: Link Rect: 494, 723, 506, 732 ActionDest: 228 Annotation: Subtype: Link Rect: 506, 723, 518, 732 ActionDest: 228 Page: Sequence: 6 Annotations: Annotation: Subtype: Link Rect: 289, 578, 296, 590 ActionDest: 163 Annotation: Subtype: Link Rect: 529, 578, 536, 590 ActionDest: 163 Annotation: Subtype: Link Rect: 250, 566, 257, 577 ActionDest: 163 Annotation: Subtype: Link Rect: 219, 553, 226, 565 ActionDest: 124 Annotation: Subtype: Link Rect: 248, 553, 255, 565 ActionDest: 124 Page: Sequence: 7 Page: Sequence: 8 Page: Sequence: 9 Annotations: Annotation: Subtype: Link Rect: 477, 339, 484, 351 ActionDest: 163 Annotation: Subtype: Link Rect: 358, 266, 365, 278 ActionDest: 172 Annotation: Subtype: Link Rect: 469, 179, 476, 190 ActionDest: 172 Page: Sequence: 10 Annotations: Annotation: Subtype: Link Rect: 549, 133, 556, 145 ActionDest: 175 Annotation: Subtype: Link Rect: 219, 96, 226, 108 ActionDest: 175 Annotation: Subtype: Link Rect: 517, 71, 524, 83 ActionDest: 175 Page: Sequence: 11 Annotations: Annotation: Subtype: Link Rect: 198, 438, 205, 449 ActionDest: 175 Annotation: Subtype: Link Rect: 225, 438, 232, 449 ActionDest: 175 Annotation: Subtype: Link Rect: 198, 364, 205, 375 ActionDest: 175 Annotation: Subtype: Link Rect: 225, 364, 232, 375 ActionDest: 175 Annotation: Subtype: Link Rect: 308, 278, 315, 289 ActionDest: 179 Annotation: Subtype: Link Rect: 216, 252, 223, 264 ActionDest: 179 Annotation: Subtype: Link Rect: 194, 215, 201, 227 ActionDest: 179 Annotation: Subtype: Link Rect: 218, 202, 225, 214 ActionDest: 179 Annotation: Subtype: Link Rect: 244, 202, 251, 214 ActionDest: 199 Page: Sequence: 12 Page: Sequence: 13 Annotations: Annotation: Subtype: Link Rect: 330, 175, 342, 184 ActionDest: 225 Annotation: Subtype: Link Rect: 345, 175, 357, 184 ActionDest: 225 Annotation: Subtype: Link Rect: 371, 125, 383, 134 ActionDest: 225 Annotation: Subtype: Link Rect: 386, 125, 398, 134 ActionDest: 225 Annotation: Subtype: Link Rect: 184, 62, 196, 71 ActionDest: 228 Annotation: Subtype: Link Rect: 199, 62, 211, 71 ActionDest: 228 Page: Sequence: 14 Annotations: Annotation: Subtype: Link Rect: 272, 708, 279, 720 ActionDest: 179 Annotation: Subtype: Link Rect: 357, 695, 364, 707 ActionDest: 179 Annotation: Subtype: Link Rect: 407, 610, 419, 619 ActionDest: 228 Annotation: Subtype: Link Rect: 544, 610, 556, 619 ActionDest: 235 Annotation: Subtype: Link Rect: 198, 560, 210, 569 ActionDest: 235 Annotation: Subtype: Link Rect: 225, 509, 237, 519 ActionDest: 235 Annotation: Subtype: Link Rect: 530, 484, 542, 493 ActionDest: 235 Annotation: Subtype: Link Rect: 544, 484, 556, 493 ActionDest: 235 Annotation: Subtype: Link Rect: 231, 459, 238, 468 ActionDest: 225 Annotation: Subtype: Link Rect: 241, 396, 253, 406 ActionDest: 235 Annotation: Subtype: Link Rect: 514, 346, 526, 355 ActionDest: 228 Annotation: Subtype: Link Rect: 453, 233, 465, 242 ActionDest: 235 Annotation: Subtype: Link Rect: 443, 208, 450, 217 ActionDest: 225 Annotation: Subtype: Link Rect: 191, 133, 203, 142 ActionDest: 235 Page: Sequence: 15 Annotations: Annotation: Subtype: Link Rect: 230, 607, 242, 616 ActionDest: 235 Annotation: Subtype: Link Rect: 243, 607, 255, 616 ActionDest: 235 Annotation: Subtype: Link Rect: 506, 607, 513, 616 ActionDest: 225 Annotation: Subtype: Link Rect: 514, 607, 526, 616 ActionDest: 235 Annotation: Subtype: Link Rect: 531, 569, 543, 578 ActionDest: 228 Annotation: Subtype: Link Rect: 544, 569, 556, 578 ActionDest: 228 Page: Sequence: 16 Annotations: Annotation: Subtype: Link Rect: 452, 632, 490, 643 Annotation: Subtype: Link Rect: 496, 632, 532, 643 Annotation: Subtype: Link Rect: 471, 620, 508, 631 Annotation: Subtype: Link Rect: 515, 620, 551, 631 Annotation: Subtype: Link Rect: 150, 586, 187, 597 Annotation: Subtype: Link Rect: 193, 586, 229, 597 Annotation: Subtype: Link Rect: 261, 563, 298, 574 Annotation: Subtype: Link Rect: 305, 563, 341, 574 Annotation: Subtype: Link Rect: 197, 540, 235, 551 Annotation: Subtype: Link Rect: 241, 540, 277, 551 Annotation: Subtype: Link Rect: 140, 517, 177, 528 Annotation: Subtype: Link Rect: 59, 494, 96, 504 Annotation: Subtype: Link Rect: 149, 471, 186, 481 Annotation: Subtype: Link Rect: 186, 448, 224, 458 Annotation: Subtype: Link Rect: 331, 424, 369, 435 Annotation: Subtype: Link Rect: 181, 390, 218, 401 Annotation: Subtype: Link Rect: 225, 390, 261, 401 Annotation: Subtype: Link Rect: 519, 367, 557, 378 Annotation: Subtype: Link Rect: 59, 356, 95, 366 Annotation: Subtype: Link Rect: 230, 332, 268, 343 Annotation: Subtype: Link Rect: 274, 332, 310, 343 Annotation: Subtype: Link Rect: 498, 309, 536, 320 Annotation: Subtype: Link Rect: 86, 276, 123, 286 Annotation: Subtype: Link Rect: 59, 241, 95, 251 Annotation: Subtype: Link Rect: 228, 217, 266, 228 Annotation: Subtype: Link Rect: 104, 195, 141, 205 Annotation: Subtype: Link Rect: 473, 171, 511, 182 Annotation: Subtype: Link Rect: 131, 149, 168, 159 Annotation: Subtype: Link Rect: 150, 126, 188, 136 Annotation: Subtype: Link Rect: 194, 126, 230, 136 Annotation: Subtype: Link Rect: 310, 102, 347, 113 Annotation: Subtype: Link Rect: 353, 102, 389, 113 Annotation: Subtype: Link Rect: 366, 79, 403, 90 Annotation: Subtype: Link Rect: 409, 79, 445, 90 Page: Sequence: 17 Annotations: Annotation: Subtype: Link Rect: 208, 722, 246, 733 Annotation: Subtype: Link Rect: 59, 688, 96, 698 Annotation: Subtype: Link Rect: 140, 653, 177, 664 Annotation: Subtype: Link Rect: 59, 630, 96, 640 Annotation: Subtype: Link Rect: 490, 618, 527, 629 Annotation: Subtype: Link Rect: 113, 596, 150, 606 Annotation: Subtype: Link Rect: 154, 573, 191, 583 Annotation: Subtype: Link Rect: 135, 538, 173, 548 Annotation: Subtype: Link Rect: 179, 538, 215, 548 Annotation: Subtype: Link Rect: 387, 503, 424, 514 Annotation: Subtype: Link Rect: 430, 503, 466, 514 Annotation: Subtype: Link Rect: 59, 458, 96, 468 Annotation: Subtype: Link Rect: 372, 422, 409, 433 Annotation: Subtype: Link Rect: 165, 400, 202, 410 Annotation: Subtype: Link Rect: 200, 377, 237, 387 Annotation: Subtype: Link Rect: 59, 354, 96, 364 Annotation: Subtype: Link Rect: 59, 331, 96, 341 Annotation: Subtype: Link Rect: 102, 331, 138, 341 Annotation: Subtype: Link Rect: 407, 307, 445, 318 Annotation: Subtype: Link Rect: 451, 307, 487, 318 Annotation: Subtype: Link Rect: 331, 261, 368, 272 Annotation: Subtype: Link Rect: 374, 261, 410, 272 Annotation: Subtype: Link Rect: 231, 238, 268, 249 Annotation: Subtype: Link Rect: 275, 238, 311, 249 Annotation: Subtype: Link Rect: 162, 205, 200, 215 Annotation: Subtype: Link Rect: 206, 205, 242, 215 Annotation: Subtype: Link Rect: 113, 170, 151, 180 Annotation: Subtype: Link Rect: 157, 170, 193, 180 Annotation: Subtype: Link Rect: 401, 146, 438, 157 Annotation: Subtype: Link Rect: 235, 123, 273, 134 Annotation: Subtype: Link Rect: 279, 123, 315, 134 Annotation: Subtype: Link Rect: 165, 101, 203, 111 Annotation: Subtype: Link Rect: 59, 67, 96, 77 Page: Sequence: 18 Annotations: Annotation: Subtype: Link Rect: 59, 711, 96, 721 Annotation: Subtype: Link Rect: 447, 687, 484, 698 Annotation: Subtype: Link Rect: 141, 665, 179, 675 Annotation: Subtype: Link Rect: 185, 665, 221, 675 Annotation: Subtype: Link Rect: 504, 641, 541, 652 Annotation: Subtype: Link Rect: 190, 618, 227, 629 Annotation: Subtype: Link Rect: 122, 584, 160, 594 Annotation: Subtype: Link Rect: 166, 584, 202, 594 Annotation: Subtype: Link Rect: 441, 560, 479, 571 Annotation: Subtype: Link Rect: 485, 560, 521, 571 Annotation: Subtype: Link Rect: 143, 538, 180, 548 Annotation: Subtype: Link Rect: 380, 514, 418, 525 Annotation: Subtype: Link Rect: 150, 480, 187, 491 Checksum: c8ac6457 Type: CRC32 Checksum: d912fe0ba55dc20f98ab41d7001346b0 Type: MD5 Checksum: ca581f0e20e1670f5800d5db6d86e99881442496 Type: SHA-1