139cdedc07a36dd5312952edd7bdc525 diagnostics-15-00299-v2.pdf 0ef6881f82106f1bbe4b8d0faf154e7cd92dd2d1 diagnostics-15-00299-v2.pdf 3ca25ec03df4228bd3b1be26876809ed840a516ee4024b81ebe064eb4617d901 diagnostics-15-00299-v2.pdf Title: Evaluating Pediatric NAFLD with Controlled Attenuation Parameter: A Comprehensive Narrative Review Subject: Non-alcoholic fatty liver disease (NAFLD) in the pediatric population has emerged as a significant health concern due to its alarming rise in prevalence. In children, the characteristics of the disease differ from those seen in adults. NAFLD may progress to more severe liver disease in children compared to adults with similar profiles. Liver biopsy remains the gold standard for diagnosis; its invasive nature and high cost limit its use as a first-line tool. Alternatively, magnetic resonance imaging (MRI) techniques, such as magnetic resonance imaging-estimated liver proton density fat fraction (MRI-PDFF), have shown a good correlation with the degree of histological steatosis, although their use is limited by high costs and limited accessibility. Controlled attenuation parameter (CAP), integrated with vibration-controlled transient elastography (VCTE) (FibroScan®), is a novel non-invasive, accessible, and effective method for diagnosing hepatic steatosis. In this article, we reviewed the existing literature on the diagnostic accuracy of CAP in pediatric NAFLD. The PubMed and EMBASE databases were searched. Seven relevant studies were identified, conducted in pediatric hospital populations with specific demographic characteristics. Two of these studies compared CAP with liver biopsy, one compared CAP with liver biopsy and MRI-PDFF, and the remaining four compared CAP with MRI. Overall, CAP proved to be accurate in detecting the presence or absence of fatty infiltration, positioning it as a promising tool to simplify the diagnosis of NAFLD in children. However, further studies in larger populations are needed to confirm these findings and facilitate its implementation in routine clinical practice. Keywords: NAFLD; non-alcoholic fatty liver disease; CAP; controlled attenuation parameter; elastography; liver; children; adolescents; pediatrics Author: Ingrid Arteaga, Carla Chacón, Alba Martínez-Escudé, Irene Ruiz Rojano, Galadriel Diez-Fadrique, Meritxell Carmona-Cervelló and Pere Torán-Monserrat Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Mon Feb 10 08:56:00 2025 CET ModDate: Mon Feb 10 08:58:26 2025 CET Custom Metadata: no Metadata Stream: no 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: 326793 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- BAUJNL+VnURWPalladioL Type 1 Custom yes yes yes 10 0 ADPDOS+URWPalladioL-Roma Type 1 Custom yes yes yes 16 0 ZINRXD+URWPalladioL-Bold Type 1 Custom yes yes yes 22 0 CZVXSD+URWPalladioL-Ital Type 1 Custom yes yes yes 27 0 KOSUXD+CMSY10 Type 1 Builtin yes yes yes 62 0 URYLRZ+URWPalladioL-BoldItal Type 1 Custom yes yes yes 76 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-07-09 02:10:03 CEST RepresentationInformation: diagnostics-15-00299-v2.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-07-08 09:58:23 CEST Size: 326793 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 456 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Children: Item: Title: Understanding NAFLD in Pediatric Populations Destination: subsection.1.1 Item: Title: Assessment of Steatosis in Children and Adolescents Destination: subsection.1.2 Children: Item: Title: Blood Test and Serological Markers Destination: subsubsection.1.2.1 Item: Title: Imaging Diagnosis Destination: subsubsection.1.2.2 Item: Title: Controlled Attenuation Parameter Destination: subsubsection.1.2.3 Item: Title: Materials and Methods Destination: section.2 Item: Title: Results Destination: section.3 Children: Item: Title: Assessment of CAP Diagnostic Accuracy in Contrast to Liver Biopsy Destination: subsection.3.1 Item: Title: Assessment of CAP Diagnostic Accuracy in Contrast to Imaging Tests Destination: subsection.3.2 Item: Title: Discussion Destination: section.4 Children: Item: Title: CAP Performance and Diagnostic Accuracy in Contrast to Liver Biopsy Destination: subsection.4.1 Item: Title: CAP Performance and Diagnostic Accuracy in Contrast to Magnetic Resonance Destination: subsection.4.2 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.6 Info: Title: Evaluating Pediatric NAFLD with Controlled Attenuation Parameter: A Comprehensive Narrative Review Author: Ingrid Arteaga, Carla Chacón, Alba Martínez-Escudé, Irene Ruiz Rojano, Galadriel Diez-Fadrique, Meritxell Carmona-Cervelló and Pere Torán-Monserrat Subject: Non-alcoholic fatty liver disease (NAFLD) in the pediatric population has emerged as a significant health concern due to its alarming rise in prevalence. In children, the characteristics of the disease differ from those seen in adults. NAFLD may progress to more severe liver disease in children compared to adults with similar profiles. Liver biopsy remains the gold standard for diagnosis; its invasive nature and high cost limit its use as a first-line tool. Alternatively, magnetic resonance imaging (MRI) techniques, such as magnetic resonance imaging-estimated liver proton density fat fraction (MRI-PDFF), have shown a good correlation with the degree of histological steatosis, although their use is limited by high costs and limited accessibility. Controlled attenuation parameter (CAP), integrated with vibration-controlled transient elastography (VCTE) (FibroScan®), is a novel non-invasive, accessible, and effective method for diagnosing hepatic steatosis. In this article, we reviewed the existing literature on the diagnostic accuracy of CAP in pediatric NAFLD. The PubMed and EMBASE databases were searched. Seven relevant studies were identified, conducted in pediatric hospital populations with specific demographic characteristics. Two of these studies compared CAP with liver biopsy, one compared CAP with liver biopsy and MRI-PDFF, and the remaining four compared CAP with MRI. Overall, CAP proved to be accurate in detecting the presence or absence of fatty infiltration, positioning it as a promising tool to simplify the diagnosis of NAFLD in children. However, further studies in larger populations are needed to confirm these findings and facilitate its implementation in routine clinical practice. Keywords: NAFLD; non-alcoholic fatty liver disease; CAP; controlled attenuation parameter; elastography; liver; children; adolescents; pediatrics Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Mon Feb 10 08:56:00 CET 2025 ModDate: Mon Feb 10 08:58:26 CET 2025 ID: 0xd7df378d87ed4bd0a5daee695df1db6b, 0xd7df378d87ed4bd0a5daee695df1db6b Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: ADPDOS+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 246 FontDescriptor: FontName: ADPDOS+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: ZINRXD+URWPalladioL-Bold FontSubset: true FirstChar: 2 LastChar: 243 FontDescriptor: FontName: ZINRXD+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: BAUJNL+VnURWPalladioL FontSubset: true FirstChar: 128 LastChar: 177 FontDescriptor: FontName: BAUJNL+VnURWPalladioL Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: CZVXSD+URWPalladioL-Ital FontSubset: true FirstChar: 45 LastChar: 121 FontDescriptor: FontName: CZVXSD+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: URYLRZ+URWPalladioL-BoldItal FontSubset: true FirstChar: 110 LastChar: 110 FontDescriptor: FontName: URYLRZ+URWPalladioL-BoldItal Flags: Symbolic FontBBox: -170, -300, 1073, 935 FontFile: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: KOSUXD+CMSY10 FontSubset: true FirstChar: 0 LastChar: 21 FontDescriptor: FontName: KOSUXD+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true ToUnicode: true Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 112, 177, 152, 186 Annotation: Subtype: Link Rect: 34, 165, 146, 174 Annotation: Subtype: Link Rect: 36, 75, 152, 84 Annotation: Subtype: Link Rect: 34, 63, 89, 72 Annotation: Subtype: Link Rect: 34, 773, 157, 809 Annotation: Subtype: Link Rect: 515, 773, 560, 809 Annotation: Subtype: Link Rect: 354, 664, 365, 677 Annotation: Subtype: Link Rect: 440, 650, 451, 663 Annotation: Subtype: Link Rect: 396, 27, 560, 37 Annotation: Subtype: Link Rect: 34, 344, 87, 363 Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 202, 711, 209, 720 ActionDest: 97 Annotation: Subtype: Link Rect: 461, 684, 468, 692 ActionDest: 97 Annotation: Subtype: Link Rect: 469, 683, 476, 692 ActionDest: 97 Annotation: Subtype: Link Rect: 348, 656, 355, 665 ActionDest: 97 Annotation: Subtype: Link Rect: 518, 642, 525, 651 ActionDest: 97 Annotation: Subtype: Link Rect: 275, 614, 282, 623 ActionDest: 97 Annotation: Subtype: Link Rect: 282, 614, 289, 623 ActionDest: 97 Annotation: Subtype: Link Rect: 351, 586, 358, 595 ActionDest: 97 Annotation: Subtype: Link Rect: 359, 586, 366, 595 ActionDest: 97 Annotation: Subtype: Link Rect: 549, 544, 556, 553 ActionDest: 97 Annotation: Subtype: Link Rect: 247, 516, 254, 525 ActionDest: 97 Annotation: Subtype: Link Rect: 254, 516, 261, 525 ActionDest: 97 Annotation: Subtype: Link Rect: 359, 488, 371, 497 ActionDest: 100 Annotation: Subtype: Link Rect: 275, 461, 287, 470 ActionDest: 100 Annotation: Subtype: Link Rect: 320, 405, 332, 414 ActionDest: 100 Annotation: Subtype: Link Rect: 467, 377, 479, 386 ActionDest: 100 Annotation: Subtype: Link Rect: 312, 321, 319, 330 ActionDest: 97 Annotation: Subtype: Link Rect: 319, 321, 331, 330 ActionDest: 100 Annotation: Subtype: Link Rect: 332, 321, 344, 330 ActionDest: 100 Annotation: Subtype: Link Rect: 206, 293, 213, 302 ActionDest: 97 Annotation: Subtype: Link Rect: 387, 279, 394, 289 ActionDest: 97 Annotation: Subtype: Link Rect: 395, 280, 407, 289 ActionDest: 100 Annotation: Subtype: Link Rect: 474, 210, 486, 219 ActionDest: 100 Annotation: Subtype: Link Rect: 388, 154, 400, 163 ActionDest: 100 Annotation: Subtype: Link Rect: 536, 140, 543, 149 ActionDest: 97 Annotation: Subtype: Link Rect: 544, 140, 556, 149 ActionDest: 100 Annotation: Subtype: Link Rect: 356, 85, 368, 94 ActionDest: 100 Page: Sequence: 3 Annotations: Annotation: Subtype: Link Rect: 216, 744, 228, 754 ActionDest: 100 Annotation: Subtype: Link Rect: 476, 730, 488, 740 ActionDest: 100 Annotation: Subtype: Link Rect: 488, 730, 500, 740 ActionDest: 100 Annotation: Subtype: Link Rect: 467, 717, 479, 726 ActionDest: 100 Annotation: Subtype: Link Rect: 482, 717, 494, 726 ActionDest: 100 Annotation: Subtype: Link Rect: 511, 689, 523, 698 ActionDest: 100 Annotation: Subtype: Link Rect: 536, 633, 548, 642 ActionDest: 100 Annotation: Subtype: Link Rect: 255, 591, 267, 600 ActionDest: 100 Annotation: Subtype: Link Rect: 268, 591, 280, 600 ActionDest: 100 Annotation: Subtype: Link Rect: 520, 577, 531, 586 ActionDest: 100 Annotation: Subtype: Link Rect: 458, 480, 470, 489 ActionDest: 100 Annotation: Subtype: Link Rect: 521, 424, 528, 433 ActionDest: 97 Annotation: Subtype: Link Rect: 529, 424, 541, 433 ActionDest: 100 Annotation: Subtype: Link Rect: 544, 424, 556, 433 ActionDest: 103 Annotation: Subtype: Link Rect: 273, 356, 280, 365 ActionDest: 97 Annotation: Subtype: Link Rect: 281, 356, 293, 365 ActionDest: 103 Annotation: Subtype: Link Rect: 260, 300, 272, 309 ActionDest: 100 Annotation: Subtype: Link Rect: 272, 300, 284, 309 ActionDest: 100 Annotation: Subtype: Link Rect: 507, 258, 519, 267 ActionDest: 100 Annotation: Subtype: Link Rect: 519, 258, 531, 267 ActionDest: 103 Annotation: Subtype: Link Rect: 544, 216, 556, 226 ActionDest: 103 Annotation: Subtype: Link Rect: 371, 189, 383, 198 ActionDest: 103 Annotation: Subtype: Link Rect: 257, 175, 269, 184 ActionDest: 103 Annotation: Subtype: Link Rect: 283, 147, 295, 156 ActionDest: 103 Annotation: Subtype: Link Rect: 459, 133, 471, 142 ActionDest: 103 Annotation: Subtype: Link Rect: 471, 133, 483, 142 ActionDest: 103 Annotation: Subtype: Link Rect: 282, 105, 293, 114 ActionDest: 100 Page: Sequence: 4 Annotations: Annotation: Subtype: Link Rect: 209, 717, 221, 726 ActionDest: 103 Annotation: Subtype: Link Rect: 202, 675, 209, 684 ActionDest: 97 Annotation: Subtype: Link Rect: 210, 675, 222, 684 ActionDest: 100 Annotation: Subtype: Link Rect: 225, 675, 237, 684 ActionDest: 103 Annotation: Subtype: Link Rect: 544, 661, 556, 670 ActionDest: 103 Annotation: Subtype: Link Rect: 415, 605, 422, 614 ActionDest: 97 Annotation: Subtype: Link Rect: 454, 591, 466, 600 ActionDest: 103 Annotation: Subtype: Link Rect: 350, 481, 357, 490 ActionDest: 97 Annotation: Subtype: Link Rect: 358, 481, 370, 490 ActionDest: 103 Annotation: Subtype: Link Rect: 380, 440, 387, 448 ActionDest: 97 Annotation: Subtype: Link Rect: 288, 384, 300, 393 ActionDest: 103 Annotation: Subtype: Link Rect: 303, 384, 315, 393 ActionDest: 103 Annotation: Subtype: Link Rect: 451, 273, 463, 283 ActionDest: 103 Annotation: Subtype: Link Rect: 262, 232, 274, 241 ActionDest: 103 Annotation: Subtype: Link Rect: 311, 204, 323, 213 ActionDest: 103 Annotation: Subtype: Link Rect: 531, 190, 543, 199 ActionDest: 100 Annotation: Subtype: Link Rect: 543, 190, 555, 199 ActionDest: 103 Annotation: Subtype: Link Rect: 444, 176, 451, 185 ActionDest: 97 Annotation: Subtype: Link Rect: 279, 134, 291, 143 ActionDest: 103 Annotation: Subtype: Link Rect: 244, 92, 256, 102 ActionDest: 103 Page: Sequence: 5 Annotations: Annotation: Subtype: Link Rect: 250, 744, 261, 754 ActionDest: 103 Annotation: Subtype: Link Rect: 264, 744, 276, 754 ActionDest: 103 Annotation: Subtype: Link Rect: 364, 717, 376, 726 ActionDest: 103 Annotation: Subtype: Link Rect: 379, 717, 391, 726 ActionDest: 106 Annotation: Subtype: Link Rect: 409, 593, 421, 602 ActionDest: 106 Annotation: Subtype: Link Rect: 327, 551, 339, 560 ActionDest: 106 Annotation: Subtype: Link Rect: 470, 398, 482, 407 ActionDest: 106 Annotation: Subtype: Link Rect: 212, 370, 224, 379 ActionDest: 106 Annotation: Subtype: Link Rect: 224, 370, 236, 379 ActionDest: 106 Annotation: Subtype: Link Rect: 347, 356, 359, 365 ActionDest: 106 Annotation: Subtype: Link Rect: 511, 342, 523, 351 ActionDest: 106 Annotation: Subtype: Link Rect: 346, 286, 358, 295 ActionDest: 106 Annotation: Subtype: Link Rect: 359, 286, 371, 295 ActionDest: 106 Annotation: Subtype: Link Rect: 461, 258, 473, 267 ActionDest: 106 Annotation: Subtype: Link Rect: 476, 258, 488, 267 ActionDest: 106 Annotation: Subtype: Link Rect: 343, 203, 355, 212 ActionDest: 103 Annotation: Subtype: Link Rect: 253, 175, 260, 184 ActionDest: 97 Annotation: Subtype: Link Rect: 261, 175, 273, 184 ActionDest: 100 Annotation: Subtype: Link Rect: 276, 175, 288, 184 ActionDest: 103 Page: Sequence: 6 Annotations: Annotation: Subtype: Link Rect: 516, 714, 528, 723 ActionDest: 100 Annotation: Subtype: Link Rect: 528, 714, 540, 723 ActionDest: 100 Annotation: Subtype: Link Rect: 523, 533, 535, 542 ActionDest: 106 Annotation: Subtype: Link Rect: 382, 293, 389, 305 ActionDest: 73 Annotation: Subtype: Link Rect: 356, 282, 368, 291 ActionDest: 106 Page: Sequence: 7 Annotations: Annotation: Subtype: Link Rect: 252, 717, 264, 726 ActionDest: 106 Annotation: Subtype: Link Rect: 282, 452, 294, 461 ActionDest: 106 Annotation: Subtype: Link Rect: 190, 161, 197, 170 ActionDest: 73 Page: Sequence: 8 Annotations: Annotation: Subtype: Link Rect: 60, 450, 70, 458 ActionDest: 106 Annotation: Subtype: Link Rect: 70, 426, 80, 434 ActionDest: 106 Annotation: Subtype: Link Rect: 60, 398, 70, 406 ActionDest: 106 Annotation: Subtype: Link Rect: 78, 292, 87, 299 ActionDest: 106 Annotation: Subtype: Link Rect: 61, 259, 70, 266 ActionDest: 106 Annotation: Subtype: Link Rect: 61, 218, 70, 225 ActionDest: 109 Annotation: Subtype: Link Rect: 61, 170, 70, 177 ActionDest: 109 Annotation: Subtype: Link Rect: 78, 125, 87, 132 ActionDest: 106 Page: Sequence: 9 Annotations: Annotation: Subtype: Link Rect: 230, 744, 242, 754 ActionDest: 106 Annotation: Subtype: Link Rect: 245, 745, 257, 754 ActionDest: 109 Annotation: Subtype: Link Rect: 543, 745, 555, 754 ActionDest: 106 Annotation: Subtype: Link Rect: 402, 536, 414, 545 ActionDest: 106 Annotation: Subtype: Link Rect: 285, 382, 297, 391 ActionDest: 109 Annotation: Subtype: Link Rect: 256, 271, 268, 280 ActionDest: 109 Annotation: Subtype: Link Rect: 282, 146, 294, 155 ActionDest: 106 Page: Sequence: 10 Annotations: Annotation: Subtype: Link Rect: 529, 725, 541, 734 ActionDest: 106 Annotation: Subtype: Link Rect: 544, 725, 556, 734 ActionDest: 106 Annotation: Subtype: Link Rect: 247, 697, 259, 706 ActionDest: 103 Annotation: Subtype: Link Rect: 345, 600, 357, 609 ActionDest: 109 Annotation: Subtype: Link Rect: 224, 572, 236, 581 ActionDest: 109 Annotation: Subtype: Link Rect: 321, 572, 333, 581 ActionDest: 106 Annotation: Subtype: Link Rect: 260, 502, 272, 511 ActionDest: 103 Annotation: Subtype: Link Rect: 273, 502, 285, 511 ActionDest: 109 Annotation: Subtype: Link Rect: 239, 447, 251, 456 ActionDest: 103 Annotation: Subtype: Link Rect: 529, 447, 541, 456 ActionDest: 106 Annotation: Subtype: Link Rect: 544, 447, 556, 456 ActionDest: 106 Annotation: Subtype: Link Rect: 234, 433, 246, 442 ActionDest: 106 Annotation: Subtype: Link Rect: 277, 419, 289, 428 ActionDest: 106 Annotation: Subtype: Link Rect: 381, 419, 393, 428 ActionDest: 106 Annotation: Subtype: Link Rect: 452, 266, 464, 275 ActionDest: 109 Annotation: Subtype: Link Rect: 467, 266, 479, 275 ActionDest: 109 Annotation: Subtype: Link Rect: 331, 210, 343, 219 ActionDest: 106 Annotation: Subtype: Link Rect: 346, 210, 358, 219 ActionDest: 106 Annotation: Subtype: Link Rect: 465, 210, 477, 219 ActionDest: 106 Annotation: Subtype: Link Rect: 231, 154, 243, 163 ActionDest: 106 Annotation: Subtype: Link Rect: 373, 140, 385, 149 ActionDest: 106 Page: Sequence: 11 Annotations: Annotation: Subtype: Link Rect: 229, 730, 241, 740 ActionDest: 109 Annotation: Subtype: Link Rect: 241, 730, 253, 740 ActionDest: 109 Annotation: Subtype: Link Rect: 254, 730, 266, 740 ActionDest: 109 Annotation: Subtype: Link Rect: 205, 703, 217, 712 ActionDest: 109 Annotation: Subtype: Link Rect: 220, 689, 232, 698 ActionDest: 109 Annotation: Subtype: Link Rect: 388, 675, 400, 684 ActionDest: 109 Annotation: Subtype: Link Rect: 373, 633, 385, 642 ActionDest: 106 Annotation: Subtype: Link Rect: 494, 619, 506, 628 ActionDest: 106 Annotation: Subtype: Link Rect: 510, 605, 522, 614 ActionDest: 106 Annotation: Subtype: Link Rect: 220, 577, 232, 586 ActionDest: 106 Annotation: Subtype: Link Rect: 544, 494, 556, 503 ActionDest: 109 Annotation: Subtype: Link Rect: 337, 466, 349, 475 ActionDest: 109 Annotation: Subtype: Link Rect: 468, 438, 480, 447 ActionDest: 109 Annotation: Subtype: Link Rect: 544, 424, 556, 433 ActionDest: 109 Annotation: Subtype: Link Rect: 220, 410, 232, 419 ActionDest: 106 Annotation: Subtype: Link Rect: 545, 396, 557, 405 ActionDest: 106 Annotation: Subtype: Link Rect: 450, 368, 462, 377 ActionDest: 106 Annotation: Subtype: Link Rect: 462, 313, 474, 322 ActionDest: 103 Annotation: Subtype: Link Rect: 474, 313, 486, 322 ActionDest: 106 Annotation: Subtype: Link Rect: 487, 313, 499, 322 ActionDest: 106 Annotation: Subtype: Link Rect: 499, 313, 511, 322 ActionDest: 109 Annotation: Subtype: Link Rect: 261, 271, 273, 280 ActionDest: 106 Annotation: Subtype: Link Rect: 274, 271, 286, 280 ActionDest: 106 Annotation: Subtype: Link Rect: 504, 257, 516, 266 ActionDest: 106 Annotation: Subtype: Link Rect: 193, 215, 205, 224 ActionDest: 106 Annotation: Subtype: Link Rect: 206, 215, 218, 224 ActionDest: 106 Annotation: Subtype: Link Rect: 396, 215, 408, 224 ActionDest: 106 Annotation: Subtype: Link Rect: 461, 187, 473, 196 ActionDest: 106 Annotation: Subtype: Link Rect: 316, 159, 328, 169 ActionDest: 106 Annotation: Subtype: Link Rect: 302, 146, 314, 155 ActionDest: 106 Annotation: Subtype: Link Rect: 335, 118, 347, 127 ActionDest: 106 Annotation: Subtype: Link Rect: 242, 104, 253, 113 ActionDest: 106 Page: Sequence: 12 Annotations: Annotation: Subtype: Link Rect: 456, 744, 468, 754 ActionDest: 106 Annotation: Subtype: Link Rect: 360, 717, 372, 726 ActionDest: 106 Annotation: Subtype: Link Rect: 373, 717, 385, 726 ActionDest: 106 Annotation: Subtype: Link Rect: 318, 703, 330, 712 ActionDest: 106 Annotation: Subtype: Link Rect: 439, 689, 451, 698 ActionDest: 106 Annotation: Subtype: Link Rect: 544, 620, 556, 629 ActionDest: 103 Annotation: Subtype: Link Rect: 519, 593, 531, 602 ActionDest: 103 Annotation: Subtype: Link Rect: 531, 593, 543, 602 ActionDest: 106 Annotation: Subtype: Link Rect: 544, 593, 556, 602 ActionDest: 109 Annotation: Subtype: Link Rect: 456, 537, 468, 546 ActionDest: 100 Annotation: Subtype: Link Rect: 424, 509, 436, 518 ActionDest: 103 Annotation: Subtype: Link Rect: 421, 481, 433, 490 ActionDest: 109 Annotation: Subtype: Link Rect: 414, 425, 421, 435 ActionDest: 97 Annotation: Subtype: Link Rect: 422, 425, 434, 435 ActionDest: 100 Annotation: Subtype: Link Rect: 437, 425, 449, 435 ActionDest: 103 Annotation: Subtype: Link Rect: 192, 286, 204, 295 ActionDest: 106 Page: Sequence: 13 Annotations: Annotation: Subtype: Link Rect: 422, 730, 434, 740 ActionDest: 109 Annotation: Subtype: Link Rect: 384, 675, 396, 684 ActionDest: 106 Annotation: Subtype: Link Rect: 372, 619, 384, 628 ActionDest: 109 Annotation: Subtype: Link Rect: 370, 577, 382, 586 ActionDest: 109 Annotation: Subtype: Link Rect: 457, 577, 469, 586 ActionDest: 109 Annotation: Subtype: Link Rect: 463, 536, 475, 545 ActionDest: 106 Annotation: Subtype: Link Rect: 544, 480, 556, 489 ActionDest: 106 Annotation: Subtype: Link Rect: 168, 424, 180, 433 ActionDest: 109 Annotation: Subtype: Link Rect: 181, 424, 193, 433 ActionDest: 109 Annotation: Subtype: Link Rect: 379, 313, 391, 322 ActionDest: 109 Annotation: Subtype: Link Rect: 208, 257, 220, 266 ActionDest: 109 Annotation: Subtype: Link Rect: 361, 215, 373, 224 ActionDest: 106 Annotation: Subtype: Link Rect: 373, 215, 385, 224 ActionDest: 106 Annotation: Subtype: Link Rect: 454, 201, 466, 210 ActionDest: 106 Annotation: Subtype: Link Rect: 469, 201, 481, 210 ActionDest: 109 Page: Sequence: 14 Annotations: Annotation: Subtype: Link Rect: 185, 321, 221, 331 Annotation: Subtype: Link Rect: 519, 294, 557, 305 Annotation: Subtype: Link Rect: 59, 282, 95, 293 Annotation: Subtype: Link Rect: 182, 257, 220, 267 Annotation: Subtype: Link Rect: 226, 257, 262, 267 Annotation: Subtype: Link Rect: 369, 230, 406, 242 Annotation: Subtype: Link Rect: 131, 193, 168, 203 Annotation: Subtype: Link Rect: 356, 167, 394, 178 Annotation: Subtype: Link Rect: 500, 154, 537, 165 Annotation: Subtype: Link Rect: 416, 103, 454, 114 Annotation: Subtype: Link Rect: 149, 78, 187, 88 Page: Sequence: 15 Annotations: Annotation: Subtype: Link Rect: 59, 731, 96, 742 Annotation: Subtype: Link Rect: 59, 629, 96, 639 Annotation: Subtype: Link Rect: 102, 629, 138, 639 Annotation: Subtype: Link Rect: 231, 604, 269, 614 Annotation: Subtype: Link Rect: 275, 604, 311, 614 Annotation: Subtype: Link Rect: 376, 577, 413, 588 Annotation: Subtype: Link Rect: 350, 552, 388, 563 Annotation: Subtype: Link Rect: 275, 514, 312, 524 Annotation: Subtype: Link Rect: 59, 476, 96, 486 Annotation: Subtype: Link Rect: 458, 450, 496, 461 Annotation: Subtype: Link Rect: 422, 437, 460, 448 Annotation: Subtype: Link Rect: 338, 411, 375, 422 Annotation: Subtype: Link Rect: 413, 386, 451, 397 Annotation: Subtype: Link Rect: 198, 348, 236, 358 Annotation: Subtype: Link Rect: 242, 348, 278, 358 Annotation: Subtype: Link Rect: 95, 310, 132, 320 Annotation: Subtype: Link Rect: 109, 272, 146, 282 Annotation: Subtype: Link Rect: 152, 272, 188, 282 Annotation: Subtype: Link Rect: 59, 233, 96, 244 Annotation: Subtype: Link Rect: 144, 194, 181, 205 Annotation: Subtype: Link Rect: 187, 194, 223, 205 Annotation: Subtype: Link Rect: 364, 169, 401, 180 Annotation: Subtype: Link Rect: 498, 143, 536, 154 Annotation: Subtype: Link Rect: 160, 106, 197, 116 Annotation: Subtype: Link Rect: 498, 79, 535, 90 Page: Sequence: 16 Annotations: Annotation: Subtype: Link Rect: 302, 731, 339, 742 Annotation: Subtype: Link Rect: 214, 692, 251, 703 Annotation: Subtype: Link Rect: 257, 692, 293, 703 Annotation: Subtype: Link Rect: 469, 679, 506, 690 Annotation: Subtype: Link Rect: 512, 679, 548, 690 Annotation: Subtype: Link Rect: 198, 655, 236, 665 Annotation: Subtype: Link Rect: 459, 641, 497, 652 Annotation: Subtype: Link Rect: 431, 628, 469, 639 Annotation: Subtype: Link Rect: 99, 591, 137, 601 Annotation: Subtype: Link Rect: 459, 565, 496, 576 Annotation: Subtype: Link Rect: 503, 565, 539, 576 Annotation: Subtype: Link Rect: 104, 527, 141, 537 Annotation: Subtype: Link Rect: 255, 501, 292, 512 Annotation: Subtype: Link Rect: 299, 501, 335, 512 Annotation: Subtype: Link Rect: 287, 476, 325, 486 Annotation: Subtype: Link Rect: 520, 450, 557, 461 Annotation: Subtype: Link Rect: 59, 412, 96, 422 Annotation: Subtype: Link Rect: 435, 399, 472, 410 Annotation: Subtype: Link Rect: 479, 399, 515, 410 Annotation: Subtype: Link Rect: 355, 373, 393, 384 Annotation: Subtype: Link Rect: 232, 348, 269, 358 Annotation: Subtype: Link Rect: 275, 348, 311, 358 Annotation: Subtype: Link Rect: 453, 322, 490, 333 Annotation: Subtype: Link Rect: 520, 296, 557, 307 Annotation: Subtype: Link Rect: 156, 259, 193, 269 Annotation: Subtype: Link Rect: 59, 221, 96, 231 Annotation: Subtype: Link Rect: 396, 194, 433, 205 Annotation: Subtype: Link Rect: 399, 169, 437, 180 Annotation: Subtype: Link Rect: 113, 131, 150, 141 Annotation: Subtype: Link Rect: 255, 92, 293, 103 Annotation: Subtype: Link Rect: 299, 92, 335, 103 Annotation: Subtype: Link Rect: 234, 67, 271, 78 Annotation: Subtype: Link Rect: 278, 67, 314, 78 Page: Sequence: 17 Annotations: Annotation: Subtype: Link Rect: 117, 719, 155, 729 Annotation: Subtype: Link Rect: 161, 719, 197, 729 Annotation: Subtype: Link Rect: 233, 679, 271, 690 Annotation: Subtype: Link Rect: 140, 642, 177, 652 Annotation: Subtype: Link Rect: 95, 616, 133, 627 Annotation: Subtype: Link Rect: 140, 565, 177, 576 Annotation: Subtype: Link Rect: 223, 526, 260, 537 Annotation: Subtype: Link Rect: 164, 488, 202, 499 Annotation: Subtype: Link Rect: 208, 488, 244, 499 Annotation: Subtype: Link Rect: 173, 450, 211, 461 Annotation: Subtype: Link Rect: 162, 412, 200, 422 Annotation: Subtype: Link Rect: 206, 412, 242, 422 Annotation: Subtype: Link Rect: 438, 373, 475, 384 Annotation: Subtype: Link Rect: 131, 336, 168, 346 Annotation: Subtype: Link Rect: 86, 297, 124, 307 Annotation: Subtype: Link Rect: 485, 272, 523, 282 Annotation: Subtype: Link Rect: 59, 233, 96, 244 Annotation: Subtype: Link Rect: 314, 194, 351, 205 Annotation: Subtype: Link Rect: 482, 156, 519, 167 Annotation: Subtype: Link Rect: 455, 130, 493, 141 Annotation: Subtype: Link Rect: 499, 130, 535, 141 Annotation: Subtype: Link Rect: 186, 93, 224, 103 Annotation: Subtype: Link Rect: 230, 93, 266, 103 Page: Sequence: 18 Annotations: Annotation: Subtype: Link Rect: 59, 731, 96, 742 Annotation: Subtype: Link Rect: 102, 731, 138, 742 Annotation: Subtype: Link Rect: 351, 705, 389, 716 Annotation: Subtype: Link Rect: 476, 679, 514, 690 Annotation: Subtype: Link Rect: 520, 667, 557, 678 Annotation: Subtype: Link Rect: 140, 629, 177, 639 Annotation: Subtype: Link Rect: 234, 591, 271, 601 Annotation: Subtype: Link Rect: 173, 565, 211, 576 Annotation: Subtype: Link Rect: 168, 540, 206, 550 Annotation: Subtype: Link Rect: 103, 502, 141, 512 Annotation: Subtype: Link Rect: 147, 502, 183, 512 Annotation: Subtype: Link Rect: 272, 462, 309, 473 Annotation: Subtype: Link Rect: 315, 462, 351, 473 Annotation: Subtype: Link Rect: 238, 411, 276, 422 Annotation: Subtype: Link Rect: 282, 411, 318, 422 Annotation: Subtype: Link Rect: 272, 386, 310, 397 Annotation: Subtype: Link Rect: 351, 347, 389, 358 Annotation: Subtype: Link Rect: 104, 297, 141, 307 Annotation: Subtype: Link Rect: 118, 272, 155, 282 Annotation: Subtype: Link Rect: 197, 245, 234, 256 Annotation: Subtype: Link Rect: 184, 208, 222, 218 Checksum: 1d705703 Type: CRC32 Checksum: 139cdedc07a36dd5312952edd7bdc525 Type: MD5 Checksum: 0ef6881f82106f1bbe4b8d0faf154e7cd92dd2d1 Type: SHA-1 Checksum: 3ca25ec03df4228bd3b1be26876809ed840a516ee4024b81ebe064eb4617d901 Type: SHA-256