6076a9705adcc0dcb502ded5724bf154 jouclimed_a2020v9n10p3246.pdf 65cbc192903b224a098bfda875bca50de4dad071 jouclimed_a2020v9n10p3246.pdf e96a4118aa99b026de39b968eafa4291419a2279dfedd9c42999c21a053f77a1 jouclimed_a2020v9n10p3246.pdf Title: Mindfulness-Based Program Plus Amygdala and Insula Retraining (MAIR) for the Treatment of Women with Fibromyalgia: A Pilot Randomized Controlled Trial Subject: The lack of highly effective treatments for fibromyalgia (FM) represents a great challenge for public health. The objective of this parallel, pilot randomized controlled trial (RCT) was two-fold: (1) to analyze the clinical effects of mindfulness plus amygdala and insula retraining (MAIR) compared to a structurally equivalent active control group of relaxation therapy (RT) in the treatment of FM; and (2) to evaluate its impact on immune-inflammatory markers and brain-derived neurotrophic factor (BDNF) in serum. A total of 41 FM patients were randomized into two study arms: MAIR (intervention group) and RT (active control group), both as add-ons of treatment as usual. MAIR demonstrated significantly greater reductions in functional impairment, anxiety, and depression, as well as higher improvements in mindfulness, and self-compassion at post-treatment and follow-up, with moderate to large effect sizes. Significant decreases in pain catastrophizing and psychological inflexibility and improvements in clinical severity and health-related quality of life were found at follow-up, but not at post-treatment, showing large effect sizes. The number needed to treat was three based on the criteria of 50% Fibromyalgia Impact Questionnaire (FIQ) reduction post-treatment. Compared to RT, the MAIR showed significant decreases in BDNF. No effect of MAIR was observed in immune-inflammatory biomarkers (i.e., TNF-, IL-6, IL-10, and hs-CRP). In conclusion, these results suggest that MAIR, as an adjuvant of treatment-as-usual (TAU), appears to be effective for the management of FM symptoms and for reducing BDNF levels in serum. Keywords: fibromyalgia; mindfulness; amygdala and insula retraining; mind–body techniques; multicomponent intervention; brain-derived neurotrophic factor; immune-inflammatory markers; randomized controlled trial; pilot study Author: Juan P. Sanabria-Mazo, Jesus Montero-Marin, Albert Feliu-Soler, Virginia Gasión, Mayte Navarro-Gil, Héctor Morillo-Sarto, Ariadna Colomer-Carbonell, Xavier Borràs, Mattie Tops, Juan V. Luciano and Javier García-Campayo Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.18 CreationDate: Thu Oct 22 11:34:28 2020 CEST ModDate: Thu Oct 22 11:38:53 2020 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 16 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 667804 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- ZSBPMM+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 NFJHER+Pxsy Type 1 Builtin yes yes no 15 0 HKQHZQ+VnURWPalladioL Type 1 Custom yes yes no 19 0 EYZCXA+URWPalladioL-Ital Type 1 Custom yes yes no 23 0 FERASI+URWPalladioL-Bold Type 1 Custom yes yes no 28 0 CQXCJX+URWPalladioL-Roma Type 1 Custom yes yes no 32 0 OFLXAT+Rpxr Type 1 Builtin yes yes no 36 0 ZIPEAN+EURM10 Type 1 Builtin yes yes no 40 0 KGZKFU+Pxbsy Type 1 Builtin yes yes no 44 0 XPUSBJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 52 0 BSDWLC+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 55 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 77 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 81 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 85 0 FANMEB+PalatinoLinotype TrueType WinAnsi yes yes no 105 0 FANMKB+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 108 0 FANMLC+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 111 0 FANNDA+TimesNewRoman CID TrueType Identity-H yes yes yes 114 0 VSHNAE+Rpcxr Type 1 Builtin yes yes no 130 0 NAOUCR+Rpxb Type 1 Builtin yes yes no 137 0 JNLIIF+Rpxi Type 1 Builtin yes yes no 141 0 OCBYQX+URWPalladioL-BoldItal Type 1 Custom yes yes no 145 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2020-11-18 07:09:42 CET RepresentationInformation: jouclimed_a2020v9n10p3246.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2020-11-16 12:17:26 CET Size: 667804 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 387 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Experimental Section Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Children: Item: Title: Research Design Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Study Sample Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Procedure Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Treatments Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Children: Item: Title: Relaxation Therapy (RT) Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Mindfulness + Amygdala and Insula Retraining (MAIR) Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Measures Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Children: Item: Title: Socio-Demographic Characteristics Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Primary Outcome Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Secondary Outcomes Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Biomarkers Outcomes Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Data Analyses Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Children: Item: Title: Patients Flow and Compliance Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Item: Title: Baseline Socio-Demographic and Clinical Characteristics of Patients Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Item: Title: Effects on Primary and Secondary Outcomes Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Item: Title: Effects on Biomarkers Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4eb7f003 Item: Title: Absolute Risk Reduction and Number Needed to Treat (NNT) Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@eafc191 Item: Title: Patient Preferences and Credibility of Therapies Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612fc6eb Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1060b431 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612679d6 Info: Title: Mindfulness-Based Program Plus Amygdala and Insula Retraining (MAIR) for the Treatment of Women with Fibromyalgia: A Pilot Randomized Controlled Trial Author: Juan P. Sanabria-Mazo, Jesus Montero-Marin, Albert Feliu-Soler, Virginia Gasión, Mayte Navarro-Gil, Héctor Morillo-Sarto, Ariadna Colomer-Carbonell, Xavier Borràs, Mattie Tops, Juan V. Luciano and Javier García-Campayo Subject: The lack of highly effective treatments for fibromyalgia (FM) represents a great challenge for public health. The objective of this parallel, pilot randomized controlled trial (RCT) was two-fold: (1) to analyze the clinical effects of mindfulness plus amygdala and insula retraining (MAIR) compared to a structurally equivalent active control group of relaxation therapy (RT) in the treatment of FM; and (2) to evaluate its impact on immune-inflammatory markers and brain-derived neurotrophic factor (BDNF) in serum. A total of 41 FM patients were randomized into two study arms: MAIR (intervention group) and RT (active control group), both as add-ons of treatment as usual. MAIR demonstrated significantly greater reductions in functional impairment, anxiety, and depression, as well as higher improvements in mindfulness, and self-compassion at post-treatment and follow-up, with moderate to large effect sizes. Significant decreases in pain catastrophizing and psychological inflexibility and improvements in clinical severity and health-related quality of life were found at follow-up, but not at post-treatment, showing large effect sizes. The number needed to treat was three based on the criteria of 50% Fibromyalgia Impact Questionnaire (FIQ) reduction post-treatment. Compared to RT, the MAIR showed significant decreases in BDNF. No effect of MAIR was observed in immune-inflammatory biomarkers (i.e., TNF-, IL-6, IL-10, and hs-CRP). In conclusion, these results suggest that MAIR, as an adjuvant of treatment-as-usual (TAU), appears to be effective for the management of FM symptoms and for reducing BDNF levels in serum. Keywords: fibromyalgia; mindfulness; amygdala and insula retraining; mind body techniques; multicomponent intervention; brain-derived neurotrophic factor; immune-inflammatory markers; randomized controlled trial; pilot study Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.18 CreationDate: Thu Oct 22 11:34:28 CEST 2020 ModDate: Thu Oct 22 11:38:53 CEST 2020 ID: 0x6be16ffc4f81619bb4866b30222ad749, 0x6be16ffc4f81619bb4866b30222ad749 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: CQXCJX+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 246 FontDescriptor: FontName: CQXCJX+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: VSHNAE+Rpcxr FontSubset: true FirstChar: 169 LastChar: 169 FontDescriptor: FontName: VSHNAE+Rpcxr Flags: Symbolic FontBBox: -212, -286, 1344, 973 FontFile: true Font: BaseFont: OFLXAT+Rpxr FontSubset: true FirstChar: 11 LastChar: 62 FontDescriptor: FontName: OFLXAT+Rpxr Flags: Symbolic FontBBox: -40, -283, 904, 728 FontFile: true Font: BaseFont: ZIPEAN+EURM10 FontSubset: true FirstChar: 11 LastChar: 31 FontDescriptor: FontName: ZIPEAN+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true Font: BaseFont: NAOUCR+Rpxb FontSubset: true FirstChar: 60 LastChar: 61 FontDescriptor: FontName: NAOUCR+Rpxb Flags: Symbolic FontBBox: -57, -266, 932, 729 FontFile: true Font: BaseFont: ZSBPMM+VnURWPalladioL-Bold FontSubset: true FirstChar: 160 LastChar: 226 FontDescriptor: FontName: ZSBPMM+VnURWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: KGZKFU+Pxbsy FontSubset: true FirstChar: 0 LastChar: 122 FontDescriptor: FontName: KGZKFU+Pxbsy Flags: Symbolic FontBBox: 5, -978, 1382, 913 FontFile: true Font: BaseFont: JNLIIF+Rpxi FontSubset: true FirstChar: 11 LastChar: 47 FontDescriptor: FontName: JNLIIF+Rpxi Flags: Symbolic FontBBox: -162, -280, 856, 733 FontFile: true Font: BaseFont: NFJHER+Pxsy FontSubset: true FirstChar: 0 LastChar: 122 FontDescriptor: FontName: NFJHER+Pxsy Flags: Symbolic FontBBox: -21, -994, 1292, 912 FontFile: true Font: BaseFont: OCBYQX+URWPalladioL-BoldItal FontSubset: true FirstChar: 100 LastChar: 122 FontDescriptor: FontName: OCBYQX+URWPalladioL-BoldItal Flags: Symbolic FontBBox: -170, -300, 1073, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: HKQHZQ+VnURWPalladioL FontSubset: true FirstChar: 129 LastChar: 243 FontDescriptor: FontName: HKQHZQ+VnURWPalladioL Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: EYZCXA+URWPalladioL-Ital FontSubset: true FirstChar: 3 LastChar: 122 FontDescriptor: FontName: EYZCXA+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: FERASI+URWPalladioL-Bold FontSubset: true FirstChar: 3 LastChar: 122 FontDescriptor: FontName: FERASI+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 75, 757, 217, 793 Annotation: Subtype: Link Rect: 474, 757, 519, 793 Annotation: Subtype: Link Rect: 211, 621, 222, 634 Annotation: Subtype: Link Rect: 335, 621, 347, 634 Annotation: Subtype: Link Rect: 459, 621, 470, 634 Annotation: Subtype: Link Rect: 222, 594, 233, 607 Annotation: Subtype: Link Rect: 304, 594, 315, 607 Annotation: Subtype: Link Rect: 482, 594, 493, 607 Annotation: Subtype: Link Rect: 200, 580, 211, 594 Annotation: Subtype: Link Rect: 181, 38, 251, 50 Annotation: Subtype: Link Rect: 418, 38, 519, 50 Annotation: Subtype: Link Rect: 466, 296, 518, 315 Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 239, 579, 246, 588 ActionDest: 162 Annotation: Subtype: Link Rect: 325, 566, 332, 575 ActionDest: 162 Annotation: Subtype: Link Rect: 314, 552, 321, 561 ActionDest: 162 Annotation: Subtype: Link Rect: 330, 525, 337, 534 ActionDest: 162 Annotation: Subtype: Link Rect: 115, 498, 122, 507 ActionDest: 165 Annotation: Subtype: Link Rect: 123, 498, 130, 507 ActionDest: 165 Annotation: Subtype: Link Rect: 294, 444, 301, 453 ActionDest: 165 Annotation: Subtype: Link Rect: 304, 444, 316, 453 ActionDest: 165 Annotation: Subtype: Link Rect: 496, 430, 503, 440 ActionDest: 165 Annotation: Subtype: Link Rect: 503, 430, 515, 440 ActionDest: 165 Annotation: Subtype: Link Rect: 130, 390, 142, 399 ActionDest: 165 Annotation: Subtype: Link Rect: 143, 390, 154, 399 ActionDest: 165 Annotation: Subtype: Link Rect: 219, 376, 231, 386 ActionDest: 165 Annotation: Subtype: Link Rect: 375, 349, 387, 359 ActionDest: 165 Annotation: Subtype: Link Rect: 180, 336, 192, 345 ActionDest: 165 Annotation: Subtype: Link Rect: 134, 309, 146, 318 ActionDest: 165 Annotation: Subtype: Link Rect: 146, 309, 158, 318 ActionDest: 165 Annotation: Subtype: Link Rect: 122, 255, 134, 264 ActionDest: 165 Annotation: Subtype: Link Rect: 137, 255, 149, 264 ActionDest: 165 Annotation: Subtype: Link Rect: 439, 241, 451, 250 ActionDest: 165 Annotation: Subtype: Link Rect: 143, 187, 155, 196 ActionDest: 165 Annotation: Subtype: Link Rect: 189, 160, 201, 169 ActionDest: 165 Annotation: Subtype: Link Rect: 503, 106, 515, 115 ActionDest: 165 Annotation: Subtype: Link Rect: 337, 93, 349, 102 ActionDest: 168 Annotation: Subtype: Link Rect: 420, 93, 432, 102 ActionDest: 168 Annotation: Subtype: Link Rect: 432, 93, 444, 102 ActionDest: 168 Annotation: Subtype: Link Rect: 391, 79, 403, 88 ActionDest: 168 Page: Sequence: 3 Annotations: Annotation: Subtype: Link Rect: 252, 702, 264, 711 ActionDest: 165 Annotation: Subtype: Link Rect: 178, 675, 190, 684 ActionDest: 168 Annotation: Subtype: Link Rect: 381, 661, 393, 671 ActionDest: 168 Annotation: Subtype: Link Rect: 479, 648, 491, 657 ActionDest: 165 Annotation: Subtype: Link Rect: 492, 648, 504, 657 ActionDest: 168 Annotation: Subtype: Link Rect: 504, 648, 516, 657 ActionDest: 168 Annotation: Subtype: Link Rect: 174, 607, 186, 617 ActionDest: 168 Annotation: Subtype: Link Rect: 232, 540, 244, 549 ActionDest: 165 Annotation: Subtype: Link Rect: 102, 377, 183, 388 Annotation: Subtype: Link Rect: 321, 379, 333, 388 ActionDest: 168 Annotation: Subtype: Link Rect: 334, 379, 345, 388 ActionDest: 168 Annotation: Subtype: Link Rect: 407, 366, 419, 375 ActionDest: 165 Annotation: Subtype: Link Rect: 500, 352, 512, 361 ActionDest: 168 Annotation: Subtype: Link Rect: 373, 161, 385, 170 ActionDest: 168 Annotation: Subtype: Link Rect: 442, 120, 454, 130 ActionDest: 168 Page: Sequence: 4 Annotations: Annotation: Subtype: Link Rect: 316, 612, 323, 624 ActionDest: 95 Annotation: Subtype: Link Rect: 333, 95, 344, 103 ActionDest: 168 Annotation: Subtype: Link Rect: 348, 69, 359, 78 ActionDest: 168 Page: Sequence: 5 Annotations: Annotation: Subtype: Link Rect: 125, 607, 137, 617 ActionDest: 168 Annotation: Subtype: Link Rect: 102, 514, 114, 524 ActionDest: 168 Annotation: Subtype: Link Rect: 508, 512, 515, 524 ActionDest: 121 Page: Sequence: 6 Annotations: Annotation: Subtype: Link Rect: 503, 710, 515, 719 ActionDest: 165 Annotation: Subtype: Link Rect: 171, 653, 178, 665 ActionDest: 121 Annotation: Subtype: Link Rect: 503, 452, 515, 461 ActionDest: 168 Annotation: Subtype: Link Rect: 384, 369, 396, 378 ActionDest: 168 Annotation: Subtype: Link Rect: 414, 315, 426, 324 ActionDest: 168 Annotation: Subtype: Link Rect: 96, 234, 108, 243 ActionDest: 168 Annotation: Subtype: Link Rect: 137, 180, 149, 189 ActionDest: 168 Annotation: Subtype: Link Rect: 441, 139, 453, 149 ActionDest: 168 Annotation: Subtype: Link Rect: 126, 72, 138, 81 ActionDest: 168 Page: Sequence: 7 Annotations: Annotation: Subtype: Link Rect: 315, 702, 327, 711 ActionDest: 171 Annotation: Subtype: Link Rect: 503, 333, 515, 342 ActionDest: 171 Annotation: Subtype: Link Rect: 168, 265, 180, 274 ActionDest: 171 Annotation: Subtype: Link Rect: 229, 225, 241, 234 ActionDest: 171 Annotation: Subtype: Link Rect: 304, 198, 316, 207 ActionDest: 171 Annotation: Subtype: Link Rect: 126, 184, 138, 193 ActionDest: 168 Page: Sequence: 8 Annotations: Annotation: Subtype: Link Rect: 356, 670, 363, 682 ActionDest: 95 Annotation: Subtype: Link Rect: 207, 506, 214, 518 ActionDest: 149 Annotation: Subtype: Link Rect: 163, 481, 175, 491 ActionDest: 171 Annotation: Subtype: Link Rect: 266, 465, 273, 477 ActionDest: 149 Page: Sequence: 9 Annotations: Annotation: Subtype: Link Rect: 121, 420, 128, 432 ActionDest: 152 Page: Sequence: 10 Annotations: Annotation: Subtype: Link Rect: 170, 181, 177, 192 ActionDest: 155 Page: Sequence: 11 Annotations: Annotation: Subtype: Link Rect: 356, 274, 368, 283 ActionDest: 165 Annotation: Subtype: Link Rect: 419, 273, 431, 283 ActionDest: 165 Annotation: Subtype: Link Rect: 431, 274, 443, 283 ActionDest: 165 Annotation: Subtype: Link Rect: 504, 84, 516, 93 ActionDest: 165 Page: Sequence: 12 Annotations: Annotation: Subtype: Link Rect: 106, 702, 118, 711 ActionDest: 165 Annotation: Subtype: Link Rect: 412, 675, 424, 684 ActionDest: 165 Annotation: Subtype: Link Rect: 184, 607, 196, 617 ActionDest: 171 Annotation: Subtype: Link Rect: 282, 553, 293, 562 ActionDest: 171 Annotation: Subtype: Link Rect: 389, 513, 400, 522 ActionDest: 165 Annotation: Subtype: Link Rect: 186, 499, 198, 508 ActionDest: 165 Annotation: Subtype: Link Rect: 163, 472, 175, 481 ActionDest: 171 Annotation: Subtype: Link Rect: 233, 459, 245, 468 ActionDest: 171 Annotation: Subtype: Link Rect: 304, 405, 316, 414 ActionDest: 168 Annotation: Subtype: Link Rect: 437, 378, 449, 387 ActionDest: 171 Annotation: Subtype: Link Rect: 408, 364, 420, 373 ActionDest: 171 Annotation: Subtype: Link Rect: 300, 337, 312, 346 ActionDest: 171 Annotation: Subtype: Link Rect: 312, 337, 324, 346 ActionDest: 171 Annotation: Subtype: Link Rect: 172, 324, 184, 333 ActionDest: 171 Annotation: Subtype: Link Rect: 285, 297, 297, 306 ActionDest: 168 Annotation: Subtype: Link Rect: 503, 297, 515, 306 ActionDest: 171 Annotation: Subtype: Link Rect: 142, 270, 154, 279 ActionDest: 171 Annotation: Subtype: Link Rect: 313, 202, 325, 211 ActionDest: 171 Annotation: Subtype: Link Rect: 252, 161, 264, 171 ActionDest: 171 Annotation: Subtype: Link Rect: 364, 148, 375, 157 ActionDest: 171 Annotation: Subtype: Link Rect: 178, 107, 190, 117 ActionDest: 171 Page: Sequence: 13 Annotations: Annotation: Subtype: Link Rect: 136, 193, 174, 203 Annotation: Subtype: Link Rect: 100, 155, 137, 165 Annotation: Subtype: Link Rect: 213, 129, 251, 139 Annotation: Subtype: Link Rect: 369, 102, 406, 113 Page: Sequence: 14 Annotations: Annotation: Subtype: Link Rect: 100, 715, 137, 725 Annotation: Subtype: Link Rect: 150, 676, 187, 686 Annotation: Subtype: Link Rect: 217, 637, 255, 648 Annotation: Subtype: Link Rect: 123, 599, 160, 609 Annotation: Subtype: Link Rect: 354, 559, 392, 570 Annotation: Subtype: Link Rect: 131, 496, 169, 506 Annotation: Subtype: Link Rect: 100, 457, 137, 467 Annotation: Subtype: Link Rect: 143, 457, 179, 467 Annotation: Subtype: Link Rect: 205, 418, 243, 428 Annotation: Subtype: Link Rect: 249, 418, 285, 428 Annotation: Subtype: Link Rect: 172, 366, 210, 376 Annotation: Subtype: Link Rect: 216, 366, 252, 376 Annotation: Subtype: Link Rect: 416, 314, 453, 325 Annotation: Subtype: Link Rect: 294, 276, 332, 286 Annotation: Subtype: Link Rect: 407, 249, 445, 260 Annotation: Subtype: Link Rect: 237, 198, 274, 209 Annotation: Subtype: Link Rect: 232, 172, 270, 183 Annotation: Subtype: Link Rect: 215, 133, 252, 144 Annotation: Subtype: Link Rect: 437, 94, 474, 105 Annotation: Subtype: Link Rect: 480, 94, 516, 105 Page: Sequence: 15 Annotations: Annotation: Subtype: Link Rect: 145, 702, 183, 712 Annotation: Subtype: Link Rect: 189, 702, 225, 712 Annotation: Subtype: Link Rect: 136, 663, 174, 673 Annotation: Subtype: Link Rect: 180, 663, 216, 673 Annotation: Subtype: Link Rect: 320, 637, 357, 648 Annotation: Subtype: Link Rect: 363, 637, 400, 648 Annotation: Subtype: Link Rect: 136, 612, 174, 622 Annotation: Subtype: Link Rect: 305, 572, 342, 583 Annotation: Subtype: Link Rect: 436, 546, 473, 557 Annotation: Subtype: Link Rect: 271, 521, 309, 531 Annotation: Subtype: Link Rect: 259, 469, 296, 480 Annotation: Subtype: Link Rect: 397, 430, 434, 441 Annotation: Subtype: Link Rect: 284, 404, 322, 415 Annotation: Subtype: Link Rect: 328, 404, 364, 415 Annotation: Subtype: Link Rect: 424, 366, 461, 376 Annotation: Subtype: Link Rect: 468, 366, 504, 376 Annotation: Subtype: Link Rect: 154, 328, 192, 338 Annotation: Subtype: Link Rect: 198, 328, 234, 338 Annotation: Subtype: Link Rect: 429, 301, 465, 312 Annotation: Subtype: Link Rect: 136, 263, 174, 273 Annotation: Subtype: Link Rect: 180, 263, 216, 273 Annotation: Subtype: Link Rect: 145, 199, 183, 209 Annotation: Subtype: Link Rect: 208, 94, 245, 105 Page: Sequence: 16 Annotations: Annotation: Subtype: Link Rect: 299, 714, 336, 725 Annotation: Subtype: Link Rect: 342, 714, 378, 725 Annotation: Subtype: Link Rect: 100, 676, 137, 686 Annotation: Subtype: Link Rect: 143, 676, 179, 686 Annotation: Subtype: Link Rect: 136, 651, 174, 661 Annotation: Subtype: Link Rect: 429, 624, 467, 635 Annotation: Subtype: Link Rect: 473, 624, 509, 635 Annotation: Subtype: Link Rect: 407, 598, 443, 609 Annotation: Subtype: Link Rect: 478, 546, 516, 557 Annotation: Subtype: Link Rect: 100, 534, 136, 544 Annotation: Subtype: Link Rect: 150, 483, 187, 493 Annotation: Subtype: Link Rect: 348, 443, 386, 454 Annotation: Subtype: Link Rect: 323, 404, 360, 415 Annotation: Subtype: Link Rect: 177, 379, 214, 389 Annotation: Subtype: Link Rect: 172, 328, 210, 338 Annotation: Subtype: Link Rect: 216, 328, 252, 338 Annotation: Subtype: Link Rect: 478, 301, 516, 312 Annotation: Subtype: Link Rect: 100, 289, 136, 299 Annotation: Subtype: Link Rect: 352, 262, 390, 273 Annotation: Subtype: Link Rect: 100, 224, 137, 234 Annotation: Subtype: Link Rect: 143, 224, 179, 234 Annotation: Subtype: Link Rect: 380, 185, 416, 196 Annotation: Subtype: Link Rect: 354, 146, 392, 157 Annotation: Subtype: Link Rect: 398, 146, 434, 157 Annotation: Subtype: Link Rect: 380, 120, 418, 131 Annotation: Subtype: Link Rect: 76, 78, 166, 109 Annotation: Subtype: Link Rect: 234, 73, 407, 83 Checksum: 51a19d3f Type: CRC32 Checksum: 6076a9705adcc0dcb502ded5724bf154 Type: MD5 Checksum: 65cbc192903b224a098bfda875bca50de4dad071 Type: SHA-1