\\n\\n
Dr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\\n\\nSeeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\\n\\nOver these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\\n\\nWe are excited about the present, and we look forward to sharing many more successes in the future.
\\n\\nThank you all for being part of the journey. 5,000 times thank you!
\\n\\nNow with 5,000 titles available Open Access, which one will you read next?
\\n\\nRead, share and download for free: https://www.intechopen.com/books
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Preparation of Space Experiments edited by international leading expert Dr. Vladimir Pletser, Director of Space Training Operations at Blue Abyss is the 5,000th Open Access book published by IntechOpen and our milestone publication!
\n\n"This book presents some of the current trends in space microgravity research. The eleven chapters introduce various facets of space research in physical sciences, human physiology and technology developed using the microgravity environment not only to improve our fundamental understanding in these domains but also to adapt this new knowledge for application on earth." says the editor. Listen what else Dr. Pletser has to say...
\n\n\n\nDr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\n\nSeeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\n\nOver these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\n\nWe are excited about the present, and we look forward to sharing many more successes in the future.
\n\nThank you all for being part of the journey. 5,000 times thank you!
\n\nNow with 5,000 titles available Open Access, which one will you read next?
\n\nRead, share and download for free: https://www.intechopen.com/books
\n\n\n\n
\n'}],latestNews:[{slug:"stanford-university-identifies-top-2-scientists-over-1-000-are-intechopen-authors-and-editors-20210122",title:"Stanford University Identifies Top 2% Scientists, Over 1,000 are IntechOpen Authors and Editors"},{slug:"intechopen-authors-included-in-the-highly-cited-researchers-list-for-2020-20210121",title:"IntechOpen Authors Included in the Highly Cited Researchers List for 2020"},{slug:"intechopen-maintains-position-as-the-world-s-largest-oa-book-publisher-20201218",title:"IntechOpen Maintains Position as the World’s Largest OA Book Publisher"},{slug:"all-intechopen-books-available-on-perlego-20201215",title:"All IntechOpen Books Available on Perlego"},{slug:"oiv-awards-recognizes-intechopen-s-editors-20201127",title:"OIV Awards Recognizes IntechOpen's Editors"},{slug:"intechopen-joins-crossref-s-initiative-for-open-abstracts-i4oa-to-boost-the-discovery-of-research-20201005",title:"IntechOpen joins Crossref's Initiative for Open Abstracts (I4OA) to Boost the Discovery of Research"},{slug:"intechopen-hits-milestone-5-000-open-access-books-published-20200908",title:"IntechOpen hits milestone: 5,000 Open Access books published!"},{slug:"intechopen-books-hosted-on-the-mathworks-book-program-20200819",title:"IntechOpen Books Hosted on the MathWorks Book Program"}]},book:{item:{type:"book",id:"4724",leadTitle:null,fullTitle:"Recent Advances in Liver Diseases and Surgery",title:"Recent Advances in Liver Diseases and Surgery",subtitle:null,reviewType:"peer-reviewed",abstract:"This book presents the most recent advances in the field of liver diseases and surgery, including the remarkable advances in Hepatitis C therapy, liver tumors, injuries, cysts, resections, transplantation, and preoperative management of patients with liver diseases. The editors are the dean and vice deans of the National Liver Institute, Menoufia University, a dedicated international center of excellence and a leading medical institution in the Middle East for the diagnosis and management of liver diseases and advanced training and research in hepatobiliary sciences. The authors are leading experts from four continents across the globe (North America, Europe, Asia, and Africa). In other words, the book team reflects an international dream team of experts in the area of liver diseases.",isbn:null,printIsbn:"978-953-51-2193-0",pdfIsbn:"978-953-51-7260-4",doi:"10.5772/59737",price:139,priceEur:155,priceUsd:179,slug:"recent-advances-in-liver-diseases-and-surgery",numberOfPages:330,isOpenForSubmission:!1,isInWos:null,hash:"00acb64dc687301436a332e905747071",bookSignature:"Hesham Abdeldayem,Ahmed El-Shaarawy, Tary Salman",publishedDate:"October 28th 2015",coverURL:"https://cdn.intechopen.com/books/images_new/4724.jpg",numberOfDownloads:13258,numberOfWosCitations:0,numberOfCrossrefCitations:2,numberOfDimensionsCitations:2,hasAltmetrics:1,numberOfTotalCitations:4,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 4th 2014",dateEndSecondStepPublish:"November 25th 2014",dateEndThirdStepPublish:"March 1st 2015",dateEndFourthStepPublish:"May 30th 2015",dateEndFifthStepPublish:"June 29th 2015",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,editors:[{id:"72383",title:"Prof.",name:"Hesham",middleName:null,surname:"Abdeldayem",slug:"hesham-abdeldayem",fullName:"Hesham Abdeldayem",profilePictureURL:"https://mts.intechopen.com/storage/users/72383/images/system/72383.png",biography:"Professor Abdeldayem graduated from Kasr Elaini School of Medicine in 1987. He received training at Cairo University Hospitals, Menoufia University, University of Pittsburgh Medical Center and King Abdul-Aziz Medical City. He Joined the National Liver Institute in 1993. He has several publications in the fields of hepato-pancreato-biliary surgery and organ transplantation. He is a Member of InTechOpen\\'s Editorial Advisory Board, and is Associate editor in another publication. He currently holds the positions of Professor of Surgery and Dean of the National Liver Institute, Menoufia University, Egypt.",institutionString:"Menoufia University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"8",totalChapterViews:"0",totalEditedBooks:"9",institution:{name:"Menoufia University",institutionURL:null,country:{name:"Egypt"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"174812",title:"Prof.",name:"Ahmed",middleName:null,surname:"Elshaarawy",slug:"ahmed-elshaarawy",fullName:"Ahmed Elshaarawy",profilePictureURL:"https://mts.intechopen.com/storage/users/174812/images/5499_n.jpg",biography:"Ahmed El-Shaarawy, Professor of Clinical Pathology and Dean of the National Liver Institute, Menoufia University, Egypt. He has graduated from the School of Medicine, Benha University in 1981, where he was appointed as a resident of Clinical Pathology, after which he moved to the National Liver Institute in 1988 as an Assistant Lecturer in Clinical Pathology. There he was promoted to a position of Lecturer, Assistant Professor and lastly, to Professor of Clinical Pathology. Prof. Elshaarawy has contributed to many research projects and publications in the field of clinical pathology, liver diseases, liver transplantation and stem cells.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorTwo:{id:"174813",title:"Prof.",name:"Tary",middleName:null,surname:"Salman",slug:"tary-salman",fullName:"Tary Salman",profilePictureURL:"https://mts.intechopen.com/storage/users/174813/images/system/174813.jpg",biography:"Tary Salman, Professor of Hepatology and Vice Dean for Community and Environmental Service, National Liver Institute, Menoufia University, Egypt. She has graduated from the School of Medicine, Alexandria University in 1985, where she was appointed as a resident of Tropical Medicine, after which she moved to the National Liver Institute in 1990 as an assistant Lecturer in Hepatology. There Prof. Salman was promoted to a position of Lecturer, Assistant Professor and lastly, to Professor of Hepatology. She contributed in many research projects and publications in the field of liver diseases and transplantation.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1021",title:"Hepatology",slug:"gastroenterology-hepatology"}],chapters:[{id:"48993",title:"Preoperative Evaluation and Management of Patients with Liver Disease",doi:"10.5772/60999",slug:"preoperative-evaluation-and-management-of-patients-with-liver-disease",totalDownloads:2086,totalCrossrefCites:1,totalDimensionsCites:1,signatures:"Hesham Abdeldayem, Ahmed El Shaarawy, Tary Salman and Essam\nSalah Hammad",downloadPdfUrl:"/chapter/pdf-download/48993",previewPdfUrl:"/chapter/pdf-preview/48993",authors:[{id:"72383",title:"Prof.",name:"Hesham",surname:"Abdeldayem",slug:"hesham-abdeldayem",fullName:"Hesham Abdeldayem"},{id:"174812",title:"Prof.",name:"Ahmed",surname:"Elshaarawy",slug:"ahmed-elshaarawy",fullName:"Ahmed Elshaarawy"},{id:"174813",title:"Prof.",name:"Tary",surname:"Salman",slug:"tary-salman",fullName:"Tary Salman"}],corrections:null},{id:"49212",title:"New Perspective in HCV Clinical and Economical Management of the Current and Future Therapies",doi:"10.5772/61187",slug:"new-perspective-in-hcv-clinical-and-economical-management-of-the-current-and-future-therapies",totalDownloads:990,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"P. Pierimarchi, G. Nicotera, G. Sferrazza, F. Andreola, A. Serafino and\nP.D. Siviero",downloadPdfUrl:"/chapter/pdf-download/49212",previewPdfUrl:"/chapter/pdf-preview/49212",authors:[{id:"81619",title:"Dr.",name:"Annalucia",surname:"Serafino",slug:"annalucia-serafino",fullName:"Annalucia Serafino"},{id:"85571",title:"Dr.",name:"Pasquale",surname:"Pierimarchi",slug:"pasquale-pierimarchi",fullName:"Pasquale Pierimarchi"},{id:"177205",title:"Dr.",name:"Giuseppe",surname:"Nicotera",slug:"giuseppe-nicotera",fullName:"Giuseppe Nicotera"},{id:"177206",title:"Dr.",name:"Gianluca",surname:"Sferrazza",slug:"gianluca-sferrazza",fullName:"Gianluca Sferrazza"},{id:"177207",title:"Dr.",name:"Federica",surname:"Andreola",slug:"federica-andreola",fullName:"Federica Andreola"},{id:"177208",title:"Dr.",name:"Paolo Daniele",surname:"Siviero",slug:"paolo-daniele-siviero",fullName:"Paolo Daniele Siviero"}],corrections:null},{id:"48972",title:"Advances in HCV Therapy",doi:"10.5772/60986",slug:"advances-in-hcv-therapy",totalDownloads:861,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Eric Hilgenfeldt and Roberto J. Firpi",downloadPdfUrl:"/chapter/pdf-download/48972",previewPdfUrl:"/chapter/pdf-preview/48972",authors:[{id:"175266",title:"Dr.",name:"Eric",surname:"Hilgenfeldt",slug:"eric-hilgenfeldt",fullName:"Eric Hilgenfeldt"}],corrections:null},{id:"48923",title:"Hepatitis C — Overview and Update in Treatment",doi:"10.5772/60949",slug:"hepatitis-c-overview-and-update-in-treatment",totalDownloads:903,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Abdullah Saeed Gozai Al-Ghamdi",downloadPdfUrl:"/chapter/pdf-download/48923",previewPdfUrl:"/chapter/pdf-preview/48923",authors:[{id:"34176",title:"Dr",name:"Abdullah",surname:"Al-Ghamdi",slug:"abdullah-al-ghamdi",fullName:"Abdullah Al-Ghamdi"}],corrections:null},{id:"48962",title:"Past, Present, and Future Perspectives on the Systemic Therapy for Advanced Hepatocellular Carcinoma (HCC) — A Comprehensive Review",doi:"10.5772/60991",slug:"past-present-and-future-perspectives-on-the-systemic-therapy-for-advanced-hepatocellular-carcinoma-h",totalDownloads:866,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Ahmed Abu-Zaid, Lynn Alkhatib, Judie Noemie Hoilat, Sana Samer\nKadan, Abdulaziz Mohammed Eshaq, Ahmed Mubarak Fothan,\nAbdulrahman Mohammed Bakather, Mohammed Abuzaid, Daniah\nSaud Aloufi, Abdulhadi A. Alamodi and Ayman Azzam",downloadPdfUrl:"/chapter/pdf-download/48962",previewPdfUrl:"/chapter/pdf-preview/48962",authors:[{id:"99947",title:"Dr.",name:"Ayman",surname:"Azzam",slug:"ayman-azzam",fullName:"Ayman Azzam"},{id:"173093",title:"Dr.",name:"Ahmed",surname:"Abu-Zaid",slug:"ahmed-abu-zaid",fullName:"Ahmed Abu-Zaid"}],corrections:null},{id:"49241",title:"LAPTM4B Targeting as Potential Therapy for Hepatocellular Carcinoma",doi:"10.5772/61345",slug:"laptm4b-targeting-as-potential-therapy-for-hepatocellular-carcinoma",totalDownloads:1025,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Rou Li Zhou, Mao Jin Li, Xuan Hui Wei, Hua Yang, Yi Shan, Ly Li and\nXin Rong Liu",downloadPdfUrl:"/chapter/pdf-download/49241",previewPdfUrl:"/chapter/pdf-preview/49241",authors:[{id:"69088",title:"Prof.",name:"Rou Li",surname:"Zhou",slug:"rou-li-zhou",fullName:"Rou Li Zhou"}],corrections:null},{id:"49104",title:"Hepatic Surgery for Colorectal Cancer Metastasis — Possibilities and Prerequisites",doi:"10.5772/60971",slug:"hepatic-surgery-for-colorectal-cancer-metastasis-possibilities-and-prerequisites",totalDownloads:1147,totalCrossrefCites:1,totalDimensionsCites:1,signatures:"Ilze Strumfa, Ervins Vasko, Andrejs Vanags, Zane Simtniece, Peteris\nTrapencieris and Janis Gardovskis",downloadPdfUrl:"/chapter/pdf-download/49104",previewPdfUrl:"/chapter/pdf-preview/49104",authors:[{id:"54021",title:"Prof.",name:"Ilze",surname:"Strumfa",slug:"ilze-strumfa",fullName:"Ilze Strumfa"},{id:"159996",title:"Dr.",name:"Zane",surname:"Simtniece",slug:"zane-simtniece",fullName:"Zane Simtniece"},{id:"160000",title:"Prof.",name:"Janis",surname:"Gardovskis",slug:"janis-gardovskis",fullName:"Janis Gardovskis"},{id:"165981",title:"Dr.",name:"Ervins",surname:"Vasko",slug:"ervins-vasko",fullName:"Ervins Vasko"},{id:"174929",title:"Dr.",name:"Andrejs",surname:"Vanags",slug:"andrejs-vanags",fullName:"Andrejs Vanags"},{id:"175847",title:"MSc.",name:"Peteris",surname:"Trapencieris",slug:"peteris-trapencieris",fullName:"Peteris Trapencieris"}],corrections:null},{id:"49022",title:"Surgical Indications, Timing, and Strategy in Non-colorectal Liver Metastases",doi:"10.5772/61079",slug:"surgical-indications-timing-and-strategy-in-non-colorectal-liver-metastases",totalDownloads:918,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Alessandro Uzzau, Serena Bertozzi, Ambrogio P Londero, Stefano\nBacchetti, Enrico Maria Pasqual and Andrea Risaliti",downloadPdfUrl:"/chapter/pdf-download/49022",previewPdfUrl:"/chapter/pdf-preview/49022",authors:[{id:"74447",title:"Dr.",name:"Ambrogio P",surname:"Londero",slug:"ambrogio-p-londero",fullName:"Ambrogio P Londero"},{id:"139756",title:"Prof.",name:"Enricomaria",surname:"Pasqual",slug:"enricomaria-pasqual",fullName:"Enricomaria Pasqual"},{id:"167094",title:"Dr.",name:"Serena",surname:"Bertozzi",slug:"serena-bertozzi",fullName:"Serena Bertozzi"},{id:"174592",title:"Prof.",name:"Alessandro",surname:"Uzzau",slug:"alessandro-uzzau",fullName:"Alessandro Uzzau"},{id:"174824",title:"Dr.",name:"Stefano",surname:"Bacchetti",slug:"stefano-bacchetti",fullName:"Stefano Bacchetti"},{id:"174825",title:"Prof.",name:"Andrea",surname:"Risaliti",slug:"andrea-risaliti",fullName:"Andrea Risaliti"}],corrections:null},{id:"49065",title:"Old versus New – Tumor Ablation versus Tumor Nanoablation with Particular Emphasis on Liver Tumors",doi:"10.5772/61008",slug:"old-versus-new-tumor-ablation-versus-tumor-nanoablation-with-particular-emphasis-on-liver-tumors",totalDownloads:869,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Zeno Sparchez, Tudor Mocan and Pompilia Radu",downloadPdfUrl:"/chapter/pdf-download/49065",previewPdfUrl:"/chapter/pdf-preview/49065",authors:[{id:"76354",title:"Prof.",name:"Zeno",surname:"Sparchez",slug:"zeno-sparchez",fullName:"Zeno Sparchez"},{id:"175715",title:"Dr.",name:"Tudor",surname:"Mocan",slug:"tudor-mocan",fullName:"Tudor Mocan"},{id:"175716",title:"Dr.",name:"Pompilia",surname:"Radu",slug:"pompilia-radu",fullName:"Pompilia Radu"}],corrections:null},{id:"49101",title:"Diagnostic and Therapeutic Challenges in Nonparasitic Liver Cysts",doi:"10.5772/61057",slug:"diagnostic-and-therapeutic-challenges-in-nonparasitic-liver-cysts",totalDownloads:1302,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Mirela Patricia Sîrbu Boeți, Mirela Boroș, Vlad Herlea, Amalia\nPetrișor and Irinel Popescu",downloadPdfUrl:"/chapter/pdf-download/49101",previewPdfUrl:"/chapter/pdf-preview/49101",authors:[{id:"76702",title:"Dr.",name:"Mirela Patricia",surname:"Sîrbu Boeți",slug:"mirela-patricia-sirbu-boeti",fullName:"Mirela Patricia Sîrbu Boeți"},{id:"76729",title:"Prof.",name:"Irinel",surname:"Popescu",slug:"irinel-popescu",fullName:"Irinel Popescu"},{id:"174773",title:"Dr.",name:"Mirela",surname:"Boros",slug:"mirela-boros",fullName:"Mirela Boros"},{id:"174775",title:"Ph.D. Student",name:"Amalia",surname:"Petrisor",slug:"amalia-petrisor",fullName:"Amalia Petrisor"},{id:"175687",title:"Dr.",name:"Vlad",surname:"Herlea",slug:"vlad-herlea",fullName:"Vlad Herlea"}],corrections:null},{id:"49329",title:"Experiences of 30 Years in Right Trisectionectomy for Huge Liver Tumor",doi:"10.5772/61175",slug:"experiences-of-30-years-in-right-trisectionectomy-for-huge-liver-tumor",totalDownloads:938,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Jing An Rui",downloadPdfUrl:"/chapter/pdf-download/49329",previewPdfUrl:"/chapter/pdf-preview/49329",authors:[{id:"76322",title:"Prof.",name:"Jing An",surname:"Rui",slug:"jing-an-rui",fullName:"Jing An Rui"}],corrections:null},{id:"49218",title:"Liver Trauma",doi:"10.5772/61333",slug:"liver-trauma",totalDownloads:1366,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Hanan Alghamdi",downloadPdfUrl:"/chapter/pdf-download/49218",previewPdfUrl:"/chapter/pdf-preview/49218",authors:[{id:"41917",title:"Dr.",name:"Hanan",surname:"Alghamdi",slug:"hanan-alghamdi",fullName:"Hanan Alghamdi"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},relatedBooks:[{type:"book",id:"5744",title:"Updates in Gallbladder Diseases",subtitle:null,isOpenForSubmission:!1,hash:"7b9d968408893bda6c194ebf3fea5ef6",slug:"updates-in-gallbladder-diseases",bookSignature:"Hesham Mohamed Abdeldayem",coverURL:"https://cdn.intechopen.com/books/images_new/5744.jpg",editedByType:"Edited by",editors:[{id:"72383",title:"Prof.",name:"Hesham",surname:"Abdeldayem",slug:"hesham-abdeldayem",fullName:"Hesham Abdeldayem"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3164",title:"Hepatic Surgery",subtitle:null,isOpenForSubmission:!1,hash:"e54bf2639e53e684ac2233e94ae53c19",slug:"hepatic-surgery",bookSignature:"Hesham Abdeldayem",coverURL:"https://cdn.intechopen.com/books/images_new/3164.jpg",editedByType:"Edited by",editors:[{id:"72383",title:"Prof.",name:"Hesham",surname:"Abdeldayem",slug:"hesham-abdeldayem",fullName:"Hesham Abdeldayem"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2060",title:"Liver Transplantation",subtitle:"Technical Issues and Complications",isOpenForSubmission:!1,hash:"f1a1413332fb74229afd9d4d68248cbc",slug:"liver-transplantation-technical-issues-and-complications",bookSignature:"Hesham Abdeldayem and Naglaa Allam",coverURL:"https://cdn.intechopen.com/books/images_new/2060.jpg",editedByType:"Edited by",editors:[{id:"72383",title:"Prof.",name:"Hesham",surname:"Abdeldayem",slug:"hesham-abdeldayem",fullName:"Hesham Abdeldayem"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"967",title:"Liver Transplantation",subtitle:"Basic Issues",isOpenForSubmission:!1,hash:"d61ca05025c7154ff4579b2d6c95d7ae",slug:"liver-transplantation-basic-issues",bookSignature:"Hesham Abdeldayem and Naglaa Allam",coverURL:"https://cdn.intechopen.com/books/images_new/967.jpg",editedByType:"Edited by",editors:[{id:"72383",title:"Prof.",name:"Hesham",surname:"Abdeldayem",slug:"hesham-abdeldayem",fullName:"Hesham Abdeldayem"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6502",title:"Topics in the Surgery of the Biliary Tree",subtitle:null,isOpenForSubmission:!1,hash:"6e1e8b08aab8583fc30db6351ae123d6",slug:"topics-in-the-surgery-of-the-biliary-tree",bookSignature:"Hesham Abdeldayem",coverURL:"https://cdn.intechopen.com/books/images_new/6502.jpg",editedByType:"Edited by",editors:[{id:"72383",title:"Prof.",name:"Hesham",surname:"Abdeldayem",slug:"hesham-abdeldayem",fullName:"Hesham Abdeldayem"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5155",title:"Frontiers in Transplantology",subtitle:null,isOpenForSubmission:!1,hash:"f358194cd9d33671b03808b346f354dc",slug:"frontiers-in-transplantology",bookSignature:"Hesham Abdeldayem, Ahmed F. El-Kased and Ahmed El-Shaarawy",coverURL:"https://cdn.intechopen.com/books/images_new/5155.jpg",editedByType:"Edited by",editors:[{id:"72383",title:"Prof.",name:"Hesham",surname:"Abdeldayem",slug:"hesham-abdeldayem",fullName:"Hesham Abdeldayem"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5394",title:"Updates in Liver Cancer",subtitle:null,isOpenForSubmission:!1,hash:"a502cea22e6d113a70f609c947235665",slug:"updates-in-liver-cancer",bookSignature:"Hesham Mohamed Abdeldayem",coverURL:"https://cdn.intechopen.com/books/images_new/5394.jpg",editedByType:"Edited by",editors:[{id:"72383",title:"Prof.",name:"Hesham",surname:"Abdeldayem",slug:"hesham-abdeldayem",fullName:"Hesham Abdeldayem"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6417",title:"The Management of Clinical Trials",subtitle:null,isOpenForSubmission:!1,hash:"5e50e22f9fc899a4c438299287c506f9",slug:"the-management-of-clinical-trials",bookSignature:"Hesham Abdeldayem",coverURL:"https://cdn.intechopen.com/books/images_new/6417.jpg",editedByType:"Edited by",editors:[{id:"72383",title:"Prof.",name:"Hesham",surname:"Abdeldayem",slug:"hesham-abdeldayem",fullName:"Hesham Abdeldayem"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1807",title:"New Advances in the Basic and Clinical Gastroenterology",subtitle:null,isOpenForSubmission:!1,hash:"a7ec52cb83e9fc2064e573afcfc87a71",slug:"new-advances-in-the-basic-and-clinical-gastroenterology",bookSignature:"Thomas Brzozowski",coverURL:"https://cdn.intechopen.com/books/images_new/1807.jpg",editedByType:"Edited by",editors:[{id:"35854",title:"Prof.",name:"Tomasz",surname:"Brzozowski",slug:"tomasz-brzozowski",fullName:"Tomasz Brzozowski"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"225",title:"Peptic Ulcer Disease",subtitle:null,isOpenForSubmission:!1,hash:"d739f4ee9bd8e8521a50ab44d67dd160",slug:"peptic-ulcer-disease",bookSignature:"Jianyuan Chai",coverURL:"https://cdn.intechopen.com/books/images_new/225.jpg",editedByType:"Edited by",editors:[{id:"28281",title:"Dr.",name:"Jianyuan",surname:"Chai",slug:"jianyuan-chai",fullName:"Jianyuan Chai"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],ofsBooks:[]},correction:{item:{id:"59773",slug:"corrigendum-to-systematic-study-of-ethylene-vinyl-acetate-eva-in-the-manufacturing-of-protector-devi",title:"Corrigendum to: Systematic Study of Ethylene-Vinyl Acetate (EVA) in the Manufacturing of Protector Devices for the Orofacial System",doi:null,correctionPDFUrl:"https://cdn.intechopen.com/pdfs/59773.pdf",downloadPdfUrl:"/chapter/pdf-download/59773",previewPdfUrl:"/chapter/pdf-preview/59773",totalDownloads:null,totalCrossrefCites:null,bibtexUrl:"/chapter/bibtex/59773",risUrl:"/chapter/ris/59773",chapter:{id:"56614",slug:"systematic-study-of-ethylene-vinyl-acetate-eva-in-the-manufacturing-of-protector-devices-for-the-oro",signatures:"Reinaldo Brito e Dias, Neide Pena Coto, Gilmar Ferreira Batalha and\nLarissa Driemeier",dateSubmitted:"January 25th 2017",dateReviewed:"May 31st 2017",datePrePublished:null,datePublished:"February 14th 2018",book:{id:"5951",title:"Biomaterials in Regenerative Medicine",subtitle:null,fullTitle:"Biomaterials in Regenerative Medicine",slug:"biomaterials-in-regenerative-medicine",publishedDate:"February 14th 2018",bookSignature:"Leszek A. Dobrzański",coverURL:"https://cdn.intechopen.com/books/images_new/5951.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"15880",title:"Prof.",name:"Leszek A.",middleName:null,surname:"Dobrzański",slug:"leszek-a.-dobrzanski",fullName:"Leszek A. Dobrzański"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"204968",title:"Dr.",name:"Neide",middleName:null,surname:"Pena Coto",fullName:"Neide Pena Coto",slug:"neide-pena-coto",email:"neidecoto@gmail.com",position:null,institution:null}]}},chapter:{id:"56614",slug:"systematic-study-of-ethylene-vinyl-acetate-eva-in-the-manufacturing-of-protector-devices-for-the-oro",signatures:"Reinaldo Brito e Dias, Neide Pena Coto, Gilmar Ferreira Batalha and\nLarissa Driemeier",dateSubmitted:"January 25th 2017",dateReviewed:"May 31st 2017",datePrePublished:null,datePublished:"February 14th 2018",book:{id:"5951",title:"Biomaterials in Regenerative Medicine",subtitle:null,fullTitle:"Biomaterials in Regenerative Medicine",slug:"biomaterials-in-regenerative-medicine",publishedDate:"February 14th 2018",bookSignature:"Leszek A. Dobrzański",coverURL:"https://cdn.intechopen.com/books/images_new/5951.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"15880",title:"Prof.",name:"Leszek A.",middleName:null,surname:"Dobrzański",slug:"leszek-a.-dobrzanski",fullName:"Leszek A. Dobrzański"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"204968",title:"Dr.",name:"Neide",middleName:null,surname:"Pena Coto",fullName:"Neide Pena Coto",slug:"neide-pena-coto",email:"neidecoto@gmail.com",position:null,institution:null}]},book:{id:"5951",title:"Biomaterials in Regenerative Medicine",subtitle:null,fullTitle:"Biomaterials in Regenerative Medicine",slug:"biomaterials-in-regenerative-medicine",publishedDate:"February 14th 2018",bookSignature:"Leszek A. Dobrzański",coverURL:"https://cdn.intechopen.com/books/images_new/5951.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"15880",title:"Prof.",name:"Leszek A.",middleName:null,surname:"Dobrzański",slug:"leszek-a.-dobrzanski",fullName:"Leszek A. Dobrzański"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"10699",leadTitle:null,title:"Foams",subtitle:null,reviewType:"peer-reviewed",abstract:"
\r\n\tFoams had always been a paramount material form for industry and science thanks to their wide application range in several industrial, civil and chemical processes. Foams also have many desirable properties, like lightness, resilience, thermal and acoustic insulation, noise absorption, adjustable airflow resistivity and porosity, resistivity to the diffusion of energy flow like heat and so on. They are also stable materials that can absorb gases or liquids and can be used as filters, bio-scaffolds for tissue engineering. Their principal characteristic is to feature a high surface area capable of storing energy or convert it from one form to another. This property could be used to enhance the performance of foams in terms of life existence, robustness and reliability. For these reasons, this book aim is to offer to readers a broad state-of-the-art situation of the current applications of foams, including thermal and acoustic issues and focusing on their new functions, usages and future trends.
",isbn:"978-1-83969-585-8",printIsbn:"978-1-83969-584-1",pdfIsbn:"978-1-83969-586-5",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,hash:"9495e848f41431e0ffb3be12b4d80544",bookSignature:"Dr. Marco Caniato",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10699.jpg",keywords:"Foaming, Vacuum, Molten Metal, Formability, Lightweight, Insulation, Vibration Reduction, Absorption, Resistance, Shock, Environmental Protection, Recycling",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 24th 2021",dateEndSecondStepPublish:"March 24th 2021",dateEndThirdStepPublish:"May 23rd 2021",dateEndFourthStepPublish:"August 11th 2021",dateEndFifthStepPublish:"October 10th 2021",remainingDaysToSecondStep:"a month",secondStepPassed:!1,currentStepOfPublishingProcess:2,editedByType:null,kuFlag:!1,biosketch:'Dr. Marco Caniato is an internationally-oriented scientist with 10 years of experience in the Italian Universities of Trieste and of Ferrara. He is the inventor of 6 registered patents among which are "Acoustic panel for noise barriers and noise barrier provided with such a panel" and “Multilayer panel for building use".',coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"312499",title:"Dr.",name:"Marco",middleName:null,surname:"Caniato",slug:"marco-caniato",fullName:"Marco Caniato",profilePictureURL:"https://mts.intechopen.com/storage/users/312499/images/system/312499.jpg",biography:"Dr. Marco Caniato is an internationally-oriented scientist with 10 years of experience in well-known Italian universities. His research is focused on the effects of materials thermal and acoustic insulation and behavior. Specifically, his interests are addressed to their influence on human beings' comfort. Dr. Caniato published more than 80 papers, including conference proceedings, journal papers, and book chapters. He is also the inventor of 6 registered patents and often he is appointed organizer in several international congresses.",institutionString:"Free University of Bozen-Bolzano",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Free University of Bozen-Bolzano",institutionURL:null,country:{name:"Italy"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"8",title:"Chemistry",slug:"chemistry"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"347258",firstName:"Marica",lastName:"Novakovic",middleName:null,title:"Dr.",imageUrl:"//cdnintech.com/web/frontend/www/assets/author.svg",email:"marica@intechopen.com",biography:null}},relatedBooks:[{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4816",title:"Face Recognition",subtitle:null,isOpenForSubmission:!1,hash:"146063b5359146b7718ea86bad47c8eb",slug:"face_recognition",bookSignature:"Kresimir Delac and Mislav Grgic",coverURL:"https://cdn.intechopen.com/books/images_new/4816.jpg",editedByType:"Edited by",editors:[{id:"528",title:"Dr.",name:"Kresimir",surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3621",title:"Silver Nanoparticles",subtitle:null,isOpenForSubmission:!1,hash:null,slug:"silver-nanoparticles",bookSignature:"David Pozo Perez",coverURL:"https://cdn.intechopen.com/books/images_new/3621.jpg",editedByType:"Edited by",editors:[{id:"6667",title:"Dr.",name:"David",surname:"Pozo",slug:"david-pozo",fullName:"David Pozo"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"48923",title:"Hepatitis C — Overview and Update in Treatment",doi:"10.5772/60949",slug:"hepatitis-c-overview-and-update-in-treatment",body:'Hepatitis C virus (HCV) infection is one of the main causes of progressive liver disease worldwide, making it a major public health issue. World Health Organization (WHO) estimates indicate that more than 185 million people around the world have been infected with HCV, of whom 350,000 die each year [1].
HCV induces chronic infection in up to 80% of infected individuals. One third of those who become chronically infected are predicted to develop cirrhosis or hepatocellular carcinoma. Despite its high prevalence, most people infected with the virus are unaware of their infection.
The purpose of this chapter is to give an overview on HCV and existing treatments and to outline recent innovations in the treatment of HCV patients. To do this, a broad search of the published literature has been undertaken. The search included epidemiology of HCV, its natural history, the risk factors involved, as well as the diagnosis and treatment of HCV, all of which have been graded on the best available evidence. The ultimate purpose is to improve HCV patient care and to promote and encourage the multidisciplinary care required in the treatment of these patients.
In most countries, surveys undertaken to establish the prevalence of HCV have focused on specific groups of individuals, for example, drug users, those indulging in high-risk sexual behavior, and blood donors who are not representative of the general population. Consequently, global estimates of HCV prevalence in the year 2008 are still not accurate [2].
Overall, the available data suggest that 130-170 million individuals are infected with HCV (approximately 2.2-3.0%) worldwide, with its highest prevalence occurring in Eastern Mediterranean and African regions [2,3].
Previously undertaken analyses on global, regional, and country levels have mostly failed to estimate the correct HCV disease burden with studies based on age distribution and active infection. Most country-level studies have been carried out on the adult population; however, when these estimates were applied to a country’s entire population, the disease burden was probably overestimated. In addition, studies focused on anti-HCV (antibody positive) testing overestimated the disease burden because they often included those subjects who have been cured, either spontaneously or after treatment [4].
Globally, genotype 1 (G1) has been found to account for 46% of all anti-HCV infections among adults, making it the most common, followed by G3 (22%), G2 (13%), G4 (13%), G6 (2%), and G5 (1%). Undefined or combination genotypes accounted for 3% of total HCV infections [4]. Genotype 1b was the most common subtype, accounting for 22% of all infections. However, significant regional, country, and local variations were found to exist. Infections in North America, Latin America, and Europe were predominately G1 (62-71%), with G1b accounting for 26%, 39%, and 50% of all cases, respectively. North Africa and the Middle East had a large G4 population (71%), which was attributable to the high prevalence of G4 in Egypt. When Egypt was excluded, genotype 4 accounted for 34% of all infections, and the genotype distribution of this region was dominated by G1 (46%). Asia was predominately G3 (39%) followed by G1 (36%), largely driven by the HCV infections in India and Pakistan. G1b accounted for 25% of all infections in this region. In Australasia, G1 dominated (53%), followed by G3 (39%). G1b was present in 16% of cases [4].
The hepatitis C virus is a hepatotropic RNA virus of the genus Hepacivirus in the Flaviviridae family, originally cloned in 1989 as the causative agent of non-A, non-B hepatitis [5,6,7]. HCV is a positive-sense, single-stranded enveloped RNA virus approximately 9600 nucleotides in length. Approximately 1012 viral particles are generated daily in chronically HCV-infected patients [5,8]. The genome is organized to include nontranslated RNA segments (NTRs) at 5 and 3 ends and a single large open reading frame (ORF) encoding a giant 327 kDa polyprotein that is processed by cellular and virally encoded proteases into three structural proteins (core, E1, E2) and seven nonstructural proteins (p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B) [9].
The HCV 5 NTR contains 341 nucleotides located upstream of the coding region and is composed of four domains (numbered I to IV) with highly structured RNA elements, including numerous stem loops and a pseudoknot. The 5 NTR also contains the internal ribosome entry site (IRES), which initiates the cap-independent translation of HCV genome into a single polyprotein by recruiting both viral proteins and cellular proteins such as eukaryotic initiation factors (eIF) 2 and 3 [5].
The core protein is the viral capsid protein with a length of 191 amino acids (p21c). It can be further cleaved to generate a smaller 179-amino-acid core protein (p19c). The core protein has numerous functionalities involving RNA binding, immune modulation, cell signaling, oncogenic potential, and autophagy [5,9,10]. E1 and E2 are the two viral envelope proteins that surround the viral particles. p7 contains two transmembrane domains and is required for viral assembly and release. NS2 is the viral autoprotease that likely contains at least four transmembrane domains and plays a key role in viral assembly, mediating the cleavage between NS2 and NS3 [5,9,11,12]. NS3 protease plays a critical role in HCV processing by cleaving downstream of NS3 at four sites (between NS3/4A, NS4A/4B, NS4B/NS5A, and NS5A/NS5B) [5,9]. NS4A is a cofactor for the NS3 protease, and NS5B is the viral RNA polymerase. The functions of NS4B and NS5A are not totally clear, but they are probably involved in viral RNA replication and pathogenesis. All of these HCV proteins are believed to form replication complexes on intracellular membranes for either viral morphogenesis or RNA replication [5,9,13-15].
Hepatitis C is a heterogeneous disease with considerable morbidity and mortality rates. More than 80% of infected individuals develop chronic infection; the remaining 10-20% develop spontaneous clearance with natural immunity. The acute infection has an incubation period of 7 weeks (range, 4-20 weeks) and is symptomatic in only 20% of patients and rarely severely icteric. Serum aminotransferase levels generally increase to more than 10 times the normal range and go back to normal once the disease symptoms resolve themselves. HCV antibodies usually develop at the time of onset of symptoms. HCV RNA appears even earlier, during the incubation period, with an increase in titer at the time of the manifestation of symptoms, and then disappears once the disease disappears. Once acute HCV infection has established itself, around 85% of patients develop chronic infection, which is generally asymptomatic. In these patients, HCV RNA remains present and in approximately 75% of patients, alanine aminotransferases (ALT), and aspartate aminotransferases (AST) remain elevated at more than 1.5 times the upper normal limit. The course of chronic hepatitis C is variable, with vague, intermittent, and nonspecific symptoms of chronic fatigue and malaise, which usually present in less than 20% of patients. Extrahepatic manifestations of HCV, including glomerulonephritis and cryoglobulinemia, can develop in a small percentage of patients. The development of progressive liver injury, fibrosis, and cirrhosis can occur in 20% to 30% of chronically infected patients over a period of 20-30 years. In patients presenting with chronic hepatitis C, fibrosis progression is extremely variable over time and can be partially predicted based on the age of the patient at infection, disease duration, liver histologic activity and stage of fibrosis, and ALT profile. However, it is often difficult to predict clinical outcomes in individual cases. In patients who have developed cirrhosis, the 5-year risk of decompensation is between 15% and 20% and that of hepatocellular carcinoma around 10%. The relationship between virus load, HCV genotype, quasi-species variability, and progression of liver disease is controversial. Acquired infection after age 40 years, being male, excessive alcohol consumption, hepatitis B virus (HBV) or HIV coinfection, steatosis, and immunosuppressed state have all been identified as cofactors associated with progression of fibrosis and development of cirrhosis. Once cirrhosis develops, symptoms are more common, and the signs of end-stage liver disease can appear, manifesting themselves as jaundice, weakness, wasting, and gastrointestinal bleeding. The incidence of developing hepatocellular carcinoma is 2-5% per year in patients with hepatitis C-related cirrhosis. Thus, this important liver disease has protean manifestations but is often insidious and can often lead to end-stage liver disease that needs liver transplantation, despite the presence of few overt symptoms and signs of illness [16-20].
The risk factors for the transmission of HCV infection vary substantially between countries and geographic regions. HCV is spread primarily by contact with blood and blood products. With the introduction in 1991 of routine blood screening for HCV antibodies and improvements in the test in mid-1992, transfusion-related hepatitis C has virtually disappeared. Illicit use of injectable drugs is currently the main source of HCV infections in most developed countries (e.g., Western Europe, US) and is becoming a major source of infection in transitional economy and developing countries, accounting for 40% or more of those infected. Of the estimated 16 million people in 148 countries who actively inject drugs, 10 million are infected with HCV [2,21,22]. In developing and transitional economy countries, the nosocomial transmission of new HCV infections is a major problem because of the reuse of contaminated or inadequately sterilized syringes and needles used in medical, paramedical, and dental procedures, with an estimated 2.3-4.7 million new infections occurring each year [2,23-25]. In patients on chronic hemodialysis, overall, the current prevalence of HCV is below 5% in most of Northern Europe, around 10% in most of Southern Europe and the US, but between 10% and 50% and up to 70% in many parts of the developing world, including many Asian, Latin American, and North African countries. It is important to emphasize that the prevalence of HCV is highly variable from unit to unit within the same country, with recent reports from some dialysis units in the US reporting a prevalence above 20% [26]. The risk of transmission of HCV from a mother to her child occurs in 4-8% of births to women with HCV infection and in 17-25% of births to women with HIV and HCV coinfection. The risk posed to the infant from breastfeeding is negligible, and nonsexual intrafamilial transmission is very rare [27,28]. The risk of heterosexual transmission is low, while recent data indicate that promiscuous male homosexual activity is related to HCV infection [29]. Folk medicine practices, including acupuncture and ritual scarification, as well as body piercing, tattooing, and commercial barbering are potential modes for transmission of HCV infection when performed without appropriate infection control measures [30,31].
The test for anti-HCV is usually performed in the presence of an elevated ALT level and a positive history of risk factors for HCV infection, or physical findings suggest the presence of chronic liver disease. WHO recommends that HCV serology testing be performed on individuals who are part of a population with high HCV seroprevalence or who have a history of HCV risk exposure and/or behavior rather than at the time of presentation with symptomatic disease. The application of this recommendation will require taking into consideration which populations meet these criteria. In some countries with a high seroprevalence of HCV or a low level of infection control, HCV testing might be recommended for the general population. Clearly, this would have significant resource implications [1]. Diagnosis of HCV infection is based on the detection of anti-HCV antibodies by enzyme immunoassay and the detection of HCV RNA by a sensitive molecular method, ideally a real-time PCR assay. These assays have no role in the assessment of disease severity or its prognosis [32,33]. Genotyping is useful in epidemiological studies, and also in clinical management, for predicting the likelihood of response and determining the optimal duration of therapy. Several commercial assays are available to determine HCV genotypes using direct sequence analysis of the 5 noncoding region, which includes Trugene 5 NC HCV genotyping kit, reverse hybridization analysis using genotype-specific oligonucleotide probes located in the 5 noncoding region, INNO-LiPa HCV II, and Versant HCV Genotyping Assay 2.0 [34,35].
Laboratory tests that are commonly obtained following the initial diagnosis of chronic hepatitis C include liver enzymes and function tests, a complete blood cell count, tests for coinfection with HBV or HIV, tests for immunoglobulin G antibody to hepatitis A virus (anti-HAV) to determine if immunity is present or if vaccination is recommended, and antinuclear antibody to exclude coexistent autoimmune hepatitis.
Elevated blood levels of liver enzymes ALT and AST occur when the membrane of the liver cells is damaged and liver enzymes leak into the blood stream, thus indicating ongoing liver injury. The degree of elevation of liver enzymes present in the blood correlates with the severity of liver cell injury. However, blood levels of liver enzymes do not correlate with the degree or severity of hepatic fibrosis. The important tests that reflect liver synthetic function are serum bilirubin, albumin, and international normalized ratio (INR). Abnormal serum albumin, bilirubin, or prothrombin time may be seen in the setting of impaired hepatic synthetic function. Some models used to evaluate liver disease severity are helpful for the assessment of liver function, for example, the model for end-stage liver disease (MELD). The MELD score was adopted by UNOS in 2002 for use in deceased donor liver allocation for adults with cirrhosis. MELD is a prospectively developed and validated chronic liver disease severity scoring system that uses a patient’s laboratory values for serum bilirubin, serum creatinine, and INR to predict a 3-month survival [36]. The MELD equation that is currently used by UNOS for prioritizing allocation of deceased donor livers for transplantation is as follows: MELD = 3.8*loge(serum bilirubin [mg/dL]) + 11.2*loge(INR) + 9.6*loge(serum creatinine [mg/dL]) + 6.4. Patients with the combination of serum creatinine ≤1 mg/dl, serum bilirubin ≤1 mg/dl, and INR ≤1 will receive the minimum score of 6 MELD points. In addition, UNOS has set an upper limit for the MELD score at 40 points. However, there is no need to go through the above time-consuming equation because several online tools are available for calculating the MELD score [37-39].
Noninvasive tests of hepatic fibrosis are used for the staging of fibrosis in patients with chronic liver disease. The tests are often used to differentiate patients with significant fibrosis (F2 to F4) from those with minimal or no fibrosis (F0 to F1). There are four commercial serum marker systems that have been validated: FibroTest/FibroSure (marketed in the United States by LabCorp), Hepascore (Quest Diagnostics), FibroSpect (Prometheus Corp), and the European Liver Fibrosis Study Group panel (not available in the United States). In addition, the aspartate aminotransferase-to-platelet ratio (APRI) has also been studied. The APRI has the advantage of being easily calculated using data available from routine laboratory tests.
All the serum tests have limitations: (a) they typically reflect the rate of matrix turnover, not deposition, and thus tend to be more elevated when there is high inflammatory activity. By contrast, extensive matrix deposition can go undetected if there is minimal inflammation. (b) None of the markers are liver specific, and concurrent sites of inflammation may contribute to serum levels. (c) Serum levels are affected by clearance rates, which may be impaired due to either sinusoidal endothelial cell dysfunction or impaired biliary excretion. (d) They are surrogates, not biomarkers [40].
Fibroscan can quantify fibrosis in the liver by means of elastography. Tissue elasticity is acquired through pulse-echo ultrasound, measuring shear wave velocity, the S-wave. The wave travels faster in less elastic and stiff livers. Results of liver elasticity are expressed in kilopascals (kPa). The scan can be performed easily; it is inexpensive and produces no side effects. The position of the patient is similar to when performing a liver biopsy, that is, on the back, with the right hand under the head. Patients only feel the probe pressure in the intercostal space without anticipated pain. It is possible to measure liver elasticity from different angles in the right as well as the left lobe. A liver stiffness measurement using Fibroscan is reproducible and independent of the operator, and explores a volume of liver parenchyma, which can be approximated to a cylinder of 1 cm in diameter and 4 cm in length. This volume is 100 times larger than the biopsy specimen volume and is thus much more representative of the entire hepatic parenchyma. Some extensive studies have demonstrated that the measurement of liver stiffness with Fibroscan is a good alternative for liver biopsy. The amount of fibrosis can be quantified very easily and reliably and is feasible in more than 95% of the patients. Obesity, ascites, and narrow intercostal spaces are physiological boundaries that can hamper the accuracy of the test. Acute hepatitis and liver congestion as in cardiac failure can cause false high scores, and they need to be ruled out before carrying out Fibroscan. Sometimes it may be virtually impossible to take measurements in such patients [41, 42]. Fibroscan value ranged from 2.4 to 75.5 kPa with a cutoff value of 7.1 kPa for F ≥ 2, 9.5 kPa for F ≥3, and 12.5 kPa for F = 4 (according to Metavir histological classification system) [41, 43]. One of the studies comparing elastography to histological examination on 327 patients concluded that liver stiffness measurements and fibrosis grades correlated well, with increasing reliability in more extensive fibrosis (F ≥ 3) or cirrhosis. It was impossible to determine a cutoff value to differentiate between F0 and F1 by Fibroscan [41,44].
Percutaneous liver biopsy is the gold standard for grading and staging of liver disease, which can help to determine the extent of progress of hepatic fibrosis and inflammation. It is important in clinical practice, where it may reflect the severity of liver disease and predict response to treatment. Liver biopsy is an invasive procedure associated with discomfort and, in rare cases, with serious complications. The accuracy of liver biopsy is limited and prone to sampling error and interpretational variability. Although this procedure continues to be recommended, current practice is changing for two main reasons: first, treatment is being shown to be more effective, and second, biochemical tests, serological tests, and elastograms can all provide a great deal of information on disease progression. Pathologists can increase the importance and utility of liver biopsy in chronic hepatitis C, providing information not only on the stage of fibrosis and necro-inflammatory activity but also on the grade of steatosis and iron accumulation, which are implicated in disease progression. Moreover, other diseases, such as steatohepatitis and hereditary hemochromatosis can be identified by liver biopsy. Nevertheless, the use of serological and radiological tests will reduce the indications for liver biopsy [45].
The ultimate goal of treatment in patients with chronic HCV is to eradicate HCV RNA, which is associated with decreases in all-cause mortality, liver-related death, need for liver transplantation, hepatocellular carcinoma rates, and liver-related complications.
Since interferon-alpha (IFN-α) was first introduced for treatment of non-A, non-B hepatitis 1990, therapy for patients with chronic HCV has improved dramatically. Sustained virological response rates (SVRs) have increased from 5% to 10% with standard interferon therapy, to over 40% when standard interferon is combined with ribavirin. The modification of interferon (pegylation) to improve its pharmacokinetics has further increased rates of SVR. Two types of pegylated interferon, pegylated interferon α2a and pegylated interferon α2b,which differ in their pharmacokinetics and chemical properties, were approved by the FDA in 2001. Treatment with combined pegylated interferon and ribavirin may result in SVR in 42% to 52% of genotype 1 infected patients, 70% to 80% of genotype 2 or 3 infected patients, and 54-68% of genotype 4 infected patients [46,47].
The landscape of treatment for HCV infection has evolved substantially since the introduction of highly effective HCV protease inhibitor therapies, namely, boceprevir and telaprevir, in 2011. Both drugs were approved as directly acting antiviral treatments for use in HCV genotype 1 infection, in combination with pegylated interferon and ribavirin. These NS3/4A protease inhibitors have been shown to substantially increase rates of SVR to 59-75% in both treatment-naive and previously treated patients, compared with dual therapy [48-52]. Although their development was a major advance, both agents are associated with significant toxicity, numerous drug-drug interactions, and low response rates in those patients with cirrhosis and nonresponders to previous treatment. In addition, boceprevir and telaprevir required the addition of pegylated interferon and ribavirin for 24 to 48 weeks, which markedly increased the overall cost of therapy, and are associated with the emergence of resistance-associated variants in the majority of patients who fail treatment [53].
In 2013 and 2014, the FDA approved new direct acting antiviral treatments, including second generation protease inhibitors, NS5A inhibitors, and NS5B RNA-dependent RNA polymerase inhibitors with HCV eradication rates of >95%.
The eradication of HCV RNA is predicted by the achievement of SVR and defined by the absence of HCV RNA by polymerase chain reaction three to 6 months after stopping treatment. An SVR is associated with a 99% chance of being HCV RNA negative during long-term follow-up and can therefore be considered an indication of a cure of the HCV infection. With the growing availability of highly effective interferon-free regimens for HCV infection, a curative all-oral treatment is becoming a possibility for the vast majority of patients. The second-generation protease inhibitors that have been approved for treatment of HCV and are available in the market are simeprevir, sofosbuvir, ledipasvir/sofosbuvir, daclatasvir, and the combination of ombitasvir-paritaprevir-ritonavir and dasabuvir. Trials are still ongoing on other new products, many of which are expected to appear in the near future.
This is the first available second-generation protease inhibitor (NS3/4A protease inhibitor) indicated for the treatment of chronic hepatitis C infection as a component of a combination antiviral treatment regimen [54]. Simeprevir is available in 150 mg capsules to be taken orally once daily with food. The elimination of simeprevir is by the liver, and no dose adjustment is required in the setting of renal impairment [55]. Simeprevir is not recommended in patients with hepatic impairment Child-Pugh Class B and C because of two- to five-fold increases in exposure. In general, simeprevir is well tolerated. Its most common adverse effects are rash (including a potentially serious photosensitivity reaction), pruritus, and nausea. The photosensitivity reaction that related to simeprevir usually occurs during the first 4 weeks of therapy but can develop at any time on treatment. Patients taking simeprevir may experience transient increases in serum bilirubin levels that peak at week 2 of treatment, but these are typically mild in severity and not associated with elevated hepatic aminotransferase levels [56,57]. The coadministration of simeprevir with substances that are moderate or strong inducers or inhibitors of cytochrome P450 3A (CYP3A) is not recommended, as this may lead to significantly lower or higher exposure of simeprevir, respectively, which may result in reduced therapeutic effect or adverse reactions. A number of compounds are contraindicated in patients receiving simeprevir, including the following:
Antibiotics (erythromycin, clarithromycin, telithromycin, rifampin, rifabutin, rifapentine)
Systemically administered antifungals (itroconazole, ketoconazole, voriconazole, posaconazole, fluconazole)
Anticonvulsants (carbamazepine, oxcarbazepine, phenobarbital, phenytoin)
Systemically administered dexamethasone
Herbal products (milk thistle, St. John’s wort)
A number of antiretroviral drugs, including cobicistat-based regimens, efavirenz, delavirdine, etravirine, nevirapine, ritonavir, and any HIV protease inhibitor, boosted or not by ritonavir.
Simeprevir is safe in patients using immunosuppressants, such as cyclosporine and tacrolimus, with no dose adjustment, and safe in those using lamivudine, emtricitabine, tenofovir, abacavir, raltegravir, maraviroc, and rilpivirine. The dose of simeprevir needs adjustment with some antiarrhythmics, warfarin, HMG Co-A reductase inhibitors, sedative/anxiolytics, and calcium channel blockers [58-64].
This is an HCV nucleotide analog NS5B polymerase inhibitor indicated for the treatment of chronic hepatitis C infection as a component of a combination antiviral treatment regimen. Sofosbuvir is available as a 400-mg tablet. The recommended dose of sofosbuvir is 400 mg taken orally once daily, with or without food, regardless of the patient’s genotype or prior hepatitis C treatment experience. No dose adjustment is needed for mild-to-moderate renal impairment or with mild, moderate, or severe hepatic impairment. Currently, no dose recommendation can be given for patients with severe renal impairment (estimated glomerular filtration rate <30 ml/min) or with end-stage renal disease due to higher exposures (up to 20-fold) of the predominant sofosbuvir metabolite. Sofosbuvir has pan-genotypic HCV activity and is effective in treatment-naive, treatment-experienced, and HIV-coinfected patients with compensated cirrhosis, and in patients with hepatocellular carcinoma meeting Milan criteria awaiting liver transplantation. Sofosbuvir has been very well tolerated in clinical trials. The most common adverse effects (≥20%) observed with sofosbuvir, when used in combination with ribavirin, have been fatigue and headaches. The most common adverse events (≥20%) observed in combination with pegylated IFN-α and ribavirin were fatigue, headaches, nausea, insomnia, and anemia. Drugs that are potent P-glycoprotein (P-gp) inducers significantly decrease sofosbuvir plasma concentrations and may lead to a reduced therapeutic effect. Thus, sofosbuvir should not be administered with other known inducers of P-gp, such as rifampin, carbamazepine, phenytoin or St. John’s wort [62,65-77].
The nucleotide polymerase inhibitor sofosbuvir (400 mg) has been combined with the NS5A inhibitor ledipasvir (90 mg) in a single tablet regimen (SOF/LDV) administered once daily. The combination of ledipasvir-sofosbuvir has primarily been studied as an all-oral (interferon-free) combination regimen in treatment-naive and treatment-experienced patients with genotype 1 chronic HCV infection. For patients with mild to moderate renal impairment, no dosage adjustment of ledipasvir/sofosbuvir is recommended. Severe renal impairment (estimated glomerular filtration rate <30 mL/min) does not substantially affect the pharmacokinetics of ledipasvir, but because levels of sofosbuvir and its metabolite accumulate in the setting of severe renal impairment, the combination should not be used in such settings pending further data. Thus, no dosage recommendation has been given for patients with severe renal impairment or end-stage renal disease requiring dialysis. Available data from clinical trials have shown that the combination of ledipasvir and sofosbuvir has been very well tolerated. The most commonly reported adverse effects are fatigue and headaches. Ledipasvir, like sofosbuvir, is a substrate of the P-gp drug transporter, so drugs that are potent intestinal P-gp inducers may decrease ledipasvir levels. Thus, the coadministration of ledipasvir-sofosbuvir is not recommended with rifampin, St. John’s wort, carbamazepine, phenytoin, phenobarbital, oxcarbazepine, or tipranavir/ritonavir. In addition, ledipasvir is an inhibitor of P-gp and may increase absorption of P-gp substrates. The coadministration of ledipasvir with tenofovir results in increased levels of tenofovir, particularly in the presence of other boosting agents. Until further data are available, ledipasvir-sofosbuvir should not be used with the combination of elvitegravir, cobicistat, emtricitabine, and tenofovir, and should only be used cautiously with regimens that contain tenofovir and a ritonavir-boosted protease inhibitor [73,78-83].
The Viekira Pak is an all-oral regimen comprised of four medications: ombitasvir, paritaprevir, ritonavir, and dasabuvir. This regimen can be used with or without ribavirin. In the Viekira Pak, ombitasvir, paritaprevir, and ritonavir (Viekirax®) are combined as a fixed-dose tablet and the dasabuvir (Exviera®) is a separate tablet. Ombitasvir, paritaprevir, and dasabuvir are direct-acting antivirals (DAAs) that directly interfere with HCV replication. Ombitasvir is an NS5A inhibitor with potent pan-genotypic picomolar antiviral activity, paritaprevir is an inhibitor of the NS3/4A serine protease, and dasabuvir is a nonnucleoside NS5B polymerase inhibitor. Ritonavir is a CYP3A inhibitor, and it boosts the blood levels of paritaprevir. Paritaprevir (150 mg), ritonavir (100 mg), and ombitasvir (25 mg) are coformulated in a single tablet taken as two tablets once daily. This tablet is combined with dasabuvir (250 mg) taken as one tablet twice daily. The regimen ombitasvir-paritaprevir-ritonavir plus dasabuvir is FDA approved for the treatment of chronic hepatitis C genotype 1, including those with compensated cirrhosis. The regimen ombitasvir-paritaprevir-ritonavir plus dasabuvir, with or without ribavirin, has primarily been studied as an all-oral (interferon-free) regimen in treatment-naive and treatment-experienced patients with genotype 1a or 1b chronic HCV infection, including those with compensated cirrhosis, HIV coinfection, and after receipt of liver transplantation. For patients with mild hepatic impairment (Child-Pugh A), no dosage adjustment is required for ombitasvir-paritaprevir-ritonavir and dasabuvir; however, this regimen is not recommended in patients with moderate hepatic impairment (Child-Pugh B) and is contraindicated with severe hepatic impairment (Child-Pugh C). For patients with mild, moderate, or severe renal insufficiency, no dosing adjustment is required for the regimen ombitasvir-paritaprevir-ritonavir and dasabuvir; this regimen, however, has not been adequately studied in patients with end-stage renal disease on dialysis. Available data from clinical trials have demonstrated excellent tolerance with the ombitasvir-paritaprevir-ritonavir and dasabuvir regimen. The most common (greater than 10%) adverse effects observed in clinical trials when used without ribavirin have been fatigue, nausea, pruritus, other skin reactions, insomnia, and asthenia. The concomitant use of ombitasvir-paritaprevir-ritonavir and dasabuvir with ethinyl estradiol-containing medications (e.g., oral contraceptives) can result in significant elevations in hepatic aminotransferase levels; accordingly, patients should discontinue any ethinyl estradiol-containing medications prior to starting ombitasvir-paritaprevir-ritonavir and dasabuvir. The use of ombitasvir-paritaprevir-ritonavir plus dasabuvir can potentially cause significant drug-drug interactions, primarily because of the potent ritonavir inhibition of CYP3A4 enzyme. There are a number of medications contraindicated to use concomitantly with ombitasvir-paritaprevir-ritonavir and dasabuvir, like carbamazepine, phenytoin, phenobarbital, gemfibrozil, rifampin, ergotamine, oral contraceptives containing ethinyl estradiol, lovastatin, simvastatin, sildenafil, orally administered midazolam, and St. John’s wort. The efficacy of ombitasvir-paritaprevir-ritonavir plus dasabuvir is not known for patients with prior virologic failure and resistance with treatment that included another NS3/4A inhibitor, NS5A inhibitor, or NS5B inhibitor [84-90].
The European Commission approved daclatasvir, a potent pan-genotypic NS5A replication complex inhibitor (in vitro), at the end of August 2014. Daclatasvir should be administered at the dose of 60 mg (one tablet) once per day. It is well tolerated overall. Dose adjustments are not needed in patients with Child B or C disease. Daclatasvir can be used in combination with other drugs for the treatment of chronic HCV infection genotypes 1, 2, 3, and 4 in adults. Daclatasvir, when used in combination with sofosbuvir, is an all-oral, interferon-free regimen that provided cure rates of more than 95% in clinical trials, including in patients with advanced liver disease, genotype 3, and those who have previously failed treatment with protease inhibitors. Across clinical studies, daclatasvir-based regimens have been generally well tolerated, with low discontinuation rates. The most common adverse effects with daclatasvir when used in combination with other drugs are fatigue, headaches, and nausea. Little information has been released on daclatasvir drug-drug interactions. Daclatasvir is a substrate of CYP34A and a substrate and inhibitor of P-gp. The daclatasvir dose should be adjusted to 30 mg daily in HIV-infected patients receiving atazanavir/ritonavir and to 90 mg daily in those receiving efavirenz. No dose adjustment is needed with tenofovir. No information on other antiretroviral drugs is available yet. No dose adjustments are required with cyclosporine or tacrolimus. Total daclatasvir AUC is decreased by 40% and 43% in patients with mild or moderate liver impairment, respectively. However, the unbound pharmacologically active fraction is unchanged; thus, dose adjustment is not needed in patients with liver impairment [77,91,92].
The direct acting antiviral treatment is usually used in combination for HCV treatment according to genotypes and stage of liver disease, and the patient is either naive or has previous experience of treatment.
The following recommendations can be used for treatment of HCV according to genotypes with a high response rate (>90%):
Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) for 12 weeks. The addition of daily weight-based ribavirin (1000 mg [<75 kg] to 1200 mg [>75 kg]) is recommended in patients with cirrhosis. The duration of treatment extended to 24 weeks in patients with contraindications to ribavirin.
Daily fixed-dose combination of paritaprevir (150 mg)/ritonavir (100 mg)/ombitasvir (25 mg) plus twice-daily dosed dasabuvir (250 mg) and daily weight-based ribavirin (1000 mg [<75 kg] to 1200 mg [>75 kg]) for 12 weeks (no cirrhosis) or 24 weeks (cirrhosis) for treatment of both naive and prior pegylated interferon and ribavirin treatment failure, in patients with HCV genotype 1a infection.
Daily fixed-dose combination of paritaprevir (150 mg)/ritonavir (100 mg)/ombitasvir (25 mg) plus twice-daily dosed dasabuvir (250 mg) for 12 weeks for treatment-naive and prior pegylated interferon and ribavirin treatment failure, in patients with HCV genotype 1b infection. The addition of daily weight-based ribavirin (1000 mg [<75 kg] to 1200 mg [>75 kg]) is recommended in patients with cirrhosis.
Daily fixed-dose combination of daclatasvir 60 mg and sofosbuvir 400 mg for 12 weeks. The addition of daily weight-based ribavirin (1000 mg [<75 kg] to 1200 mg [>75 kg]) is recommended in patients with cirrhosis. The duration of treatment extended to 24 weeks in patients with contraindications to ribavirin.
Daily sofosbuvir (400 mg) plus simeprevir (150 mg) for 12 weeks. The addition of daily weight-based ribavirin (1000 mg [<75 kg] to 1200 mg [>75 kg]) is recommended in patients with cirrhosis. The duration of treatment extended to 24 weeks in patients with contraindications to ribavirin.
Daily sofosbuvir (400 mg) and weight-based ribavirin (1000 mg [<75 kg] to 1200 mg [>75 kg]) plus weekly pegylated interferon for 12 weeks.
Daily sofosbuvir (400 mg) and weight-based ribavirin (1000 mg [<75 kg] to 1200 mg [>75 kg]) for 12 weeks; extending duration of treatment to 16-20 weeks is recommended in patients with cirrhosis and those in whom prior pegylated interferon and ribavirin treatment has failed.
Daily sofosbuvir (400 mg) and daclatasvir (60 mg) for 12 weeks in cirrhotic or treatment-experienced patients.
Retreatment with daily sofosbuvir (400 mg) and weight-based ribavirin (1000 mg [<75 kg] to 1200 mg [≥75 kg]) plus weekly pegylated interferon for 12 weeks is an alternative in patients where prior pegylated interferon and ribavirin treatment has failed.
HCV genotype 3
When pegylated interferon and ribavirin was the treatment for HCV, the same regimen was administered to all subjects, and patients were defined as easy or difficult to treat according to viral genotype. HCV genotypes 1 and 4 were considered to be difficult to treat, and HCV genotypes 2 and 3 were considered to be easy to treat. The SVR rates in the latter group were above 80% with shorter treatment [94,95]. The availability of interferon-free regimens has confirmed that HCV genotype 2 patients are easy to treat, while the paradigm for HCV genotype 3 patients has been reversed compared to “older, difficult-to-treat” HCV genotype 1 patients. In fact, today, with available direct acting antiviral drugs, patients with HCV genotype 3 are the most difficult to treat patients. In large studies on HCV genotype 3 to assess the effectiveness of 12-16 weeks treatment with sofosbuvir and ribavirin, it has been shown that 12 weeks of therapy in treatment-naive patients resulted in an SVR in 61% and 34% of noncirrhotic and cirrhotic patients, respectively. Moreover, the SVR rates in experienced noncirrhotic patients were 37% at 12 weeks and were increased to 63% in patients with 16 weeks’ course [70,67,95]. Extended treatments to 24 weeks of sofosbuvir and ribavirin were evaluated in the valence trial, resulting in an overall SVR rate of 83%. In particular, this was the result of higher SVR rates in treatment-naive (93% and 92% in patients without and with cirrhosis, respectively) and experienced patients without cirrhosis (87%), while rates were lower in experienced (61%) patients with cirrhosis [80,95,96]. The Lonestar-2 study tested treatment with pegylated interferon/sofosbuvir/ribavirin for 12 weeks in treatment-experienced HCV-2 and HCV-3 patients. The SVR in HCV genotype 3 patients was 83% with no difference in relation to baseline cirrhosis (SVR 83% vs. 83%, respectively) [69]. The second study tested a combination of daclatasvir/sofosbuvir, resulting in an SVR of 89% of 18 treatment-naive patients with HCV genotype 3 [97].
The following treatment options with similar efficacy can be used in genotype 3 naive patients and patients in whom prior pegylated interferon and ribavirin treatment has failed [91-93,97]:
Daily fixed-dose combination of daclatasvir 60 mg and sofosbuvir 400 mg for 12 weeks in patients without cirrhosis. Daily weight-based ribavirin (1000 mg [<75 kg] to 1200 mg [>75 kg]) is added to regimen to treat naive and treatment-experienced patients with cirrhosis for 24 weeks.
Daily sofosbuvir (400 mg) and weight-based ribavirin (1000 mg [<75 kg] to 1200 mg [>75 kg]) for 24 weeks.
Daily sofosbuvir (400 mg) and weight-based ribavirin (1000 mg [<75 kg] to 1200 mg [>75 kg]) plus weekly pegylated interferon for 12 weeks is an acceptable regimen for interferon-eligible, treatment-naive patients with HCV genotype 3 infection.
HCV genotype 4 [70,91,93,98-101]
Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) for 12 weeks. The addition of daily weight-based ribavirin (1000 mg [<75 kg] to 1200 mg [>75 kg]) is recommended in patients with cirrhosis. The duration of treatment extended to 24 weeks in patients with contraindications to ribavirin.
Daily fixed-dose combination of paritaprevir (150 mg)/ritonavir (100 mg)/ombitasvir (25 mg) and weight-based ribavirin (1000 mg [<75 kg] to 1200 mg [>75 kg]) for 12 weeks for treatment of both naive and prior pegylated interferon and ribavirin treatment failure, and treatment can be extended to 24 weeks in patients with cirrhosis.
Daily fixed-dose combination of daclatasvir 60 mg and sofosbuvir 400 mg for 12 weeks. The addition of daily weight-based ribavirin (1000 mg [<75 kg] to 1200 mg [>75 kg]) is recommended in patients with cirrhosis. The duration of treatment extended to 24 weeks in patients with contraindications to ribavirin.
Daily sofosbuvir (400 mg) plus simeprevir (150 mg) for 12 weeks. The addition of daily weight-based ribavirin (1000 mg [<75 kg] to 1200 mg [>75 kg]) is recommended in patients with cirrhosis. The duration of treatment extended to 24 weeks in patients with contraindications to ribavirin.
Daily sofosbuvir (400 mg) and weight-based ribavirin (1000 mg [<75 kg] to 1200 mg [>75 kg]) plus weekly pegylated interferon for 12 weeks.
A few data are available to help guide decision making for patients infected with HCV genotype 5 or 6, but currently the following are the recommendations until more data are available:
Daily sofosbuvir (400 mg) and weight-based ribavirin (1000 mg [<75 kg] to 1200 mg [>75 kg]) plus weekly pegylated interferon for 12 weeks
Daily sofosbuvir (400 mg) and weight-based ribavirin (1000 mg [<75 kg] to 1200 mg [>75 kg]) for 24 weeks
Weekly pegylated interferon plus weight-based ribavirin (1000 mg [<75 kg] to 1200 mg [>75 kg]) for 48 weeks is an alternative regimen for interferon-eligible, treatment-naive patients.
Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) for 12 weeks
Daily sofosbuvir (400 mg) and weight-based ribavirin (1000 mg [<75 kg] to 1200 mg [>75 kg]) plus weekly pegylated interferon for 12 weeks
Daily sofosbuvir (400 mg) and weight-based ribavirin (1000 mg [<75 kg] to 1200 mg [>75 kg]) for 24 weeks
Due to the very high efficacy and the excellent tolerability of IFN-free regimens, response-guided shortening or prolongation of therapy have not been studied and, indeed, may not be needed to achieve high cure chances in the individual patient. However, given the high costs of direct antiviral drugs, HCV RNA testing during treatment may be helpful for surveillance of compliance and motivation of patients. HCV RNA should be measured at baseline, week 2 (assessment of adherence), week 4, week 12 or 24 (end of treatment), and 12 or 24 weeks after the end of therapy [102].
Hepatitis C virus (HCV)-related liver disease is a major source of mortality in HIV-infected patients. Approximately one third of all patients with HIV are coinfected with HCV. Patients coinfected with HIV/HCV have shown lower rates of SVR with pegylated-interferon and weight-based ribavirin as well as more rapid progression of fibrosis than those with HCV monoinfection [103]. HIV/HCV-coinfected persons should be treated and retreated the same as persons without HIV infection, after recognizing and managing interactions with antiretroviral medications. Based on AASLD/IDSA/IAS-USA [93], the following precautions should be considered:
Antiretroviral treatment interruption in patients with HIV/HCV is not recommended to allow HCV therapy.
Fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) should not be used with cobicistat and elvitegravir, pending further data.
Sofosbuvir or ledipasvir/sofosbuvir should not be used with tipranavir because of the potential of this antiretroviral drug to induce P-gp.
Fixed-dose combination of paritaprevir (150 mg)/ritonavir (100 mg)/ombitasvir (25 mg) plus twice-daily dosed dasabuvir (250 mg) should not be used with efavirenz, rilpivirine, darunavir, or ritonavir-boosted lopinavir.
Paritaprevir/ritonavir/ombitasvir with or without dasabuvir should not be used in HIV/HCV-coinfected individuals who are not taking antiretroviral therapy.
Simeprevir should not be used with efavirenz, etravirine, nevirapine, cobicistat, or any HIV protease inhibitors.
Ribavirin should not be used with didanosine, stavudine, or zidovudine.
The management of HIV/HCV patients should take place in collaboration with an HIV practitioner. Special precautions should be taken when prescribing DAAs in patient on AIDS treatment to avoid under- or overdose in such patients as a result of drug-drug interactions. For example, ledipasvir increases tenofovir levels, concomitant use needs to be avoided in patients with CrCl below 60 mL/min. Because potentiation of this effect is expected when tenofovir is used with ritonavir-boosted HIV protease inhibitors, ledipasvir should be avoided with this combination. Paritaprevir/ritonavir/ombitasvir plus dasabuvir should be used with antiretroviral drugs with which it does not have substantial interactions like atazanavir, enfuvirtide, lamivudine, emtricitabine, tenofovir, and raltegravir (and probably dolutegravir) [93].
The dose of ritonavir used for boosting of HIV protease inhibitors may need to be adjusted (or held) when administered with paritaprevir/ritonavir/ombitasvir plus dasabuvir, and then restored when HCV treatment is completed. The HIV protease inhibitor should be administered at the same time as the fixed-dose HCV combination. Simeprevir should only be used with antiretroviral drugs, with which it does not have clinically significant interactions like raltegravir (and probably dolutegravir), rilpivirine, maraviroc, enfuvirtide, tenofovir, emtricitabine, lamivudine, and abacavir [93].
In patients with Child-Pugh B or C cirrhosis awaiting transplantation, antiviral therapy may be offered on an individual basis in experienced centers, pending the presentation of more data in this population. It is possible that patients with decompensated cirrhosis who are not on a transplant list could benefit from an interferon-free treatment regimen. However, the safety and efficacy of an interferon-free regimen in patients with decompensated cirrhosis not on a transplant waiting list is unknown, and the impact on mortality in this group is not yet established. According to AASLD/IDSA/IAS-USA [93] and EASL recommendations on treatment of hepatitis C 2015 [91], the following medications can be used with high virological response >90%:
Decompensated cirrhosis: genotypes 1 and 4
Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) and ribavirin (initial dose of 600 mg, increased as tolerated) for 12 weeks is recommended for patients with decompensated cirrhosis.
For patients with decompensated cirrhosis and anemia or ribavirin intolerance, daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) for 24 weeks is recommended.
For patients with decompensated cirrhosis in whom prior sofosbuvir-based treatment has failed, daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) and ribavirin (initial dose of 600 mg, increased as tolerated) for 24 weeks is an alternative regimen.
Daily fixed-dose combination of sofosbuvir (400 mg), ribavirin (initial dose of 600 mg, increased as tolerated), and daclatasvir 60 mg for 12 weeks before liver transplantation is recommended for patients with decompensated cirrhosis.
Decompensated cirrhosis: genotypes 2 and 3
Daily sofosbuvir (400 mg) and weight-based ribavirin (1000 mg [<75 kg] to 1200 mg [>75 kg]) (doses need to be adjusted according to the patient’s creatinine clearance rate and hemoglobin level) for up to 48 weeks is recommended for patients with HCV genotype 2 or 3 who have decompensated cirrhosis.
Patients with posttransplant recurrence of HCV infection should be considered for therapy. Significant fibrosis or portal hypertension 1 year after transplantation could predict rapid disease progression and graft loss and could indicate the need for more urgent antiviral treatment. Interferon-free DAA can cure most liver transplant recipients with recurrent hepatitis C, including a majority of those with severe post-transplant liver disease. In addition to viral suppression, treatment also improves liver function. DAA treatment is generally safe and well tolerated, certainly more so than interferon-based therapy, although anemia remains a concern for people taking ribavirin. Drug-drug interactions may be important in the posttransplant setting. No clinically significant drug-drug interactions have been found between sofosbuvir, simeprevir, or daclatasvir on the one hand, and cyclosporine and tacrolimus on the other hand.
The following options proved to be useful in post-liver transplantation patients according to genotypes, with high virological response, waiting more data in near future [91,93,104,105]:
Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) with weight-based ribavirin (1000 mg [<75 kg] to 1200 mg [>75 kg]) for 12 weeks is recommended for patients with HCV genotype 1 or 4 infection in the allograft, including compensated cirrhosis.
Patients who are ribavirin intolerant or ineligible, ledipasvir (90 mg)/sofosbuvir (400 mg) usually extended for 24 weeks in patients with HCV genotype 1 or 4 infection.
Daily sofosbuvir (400 mg) plus simeprevir (150 mg) with or without weight-based ribavirin (1000 mg [<75 kg] to 1200 mg [>75 kg]) for 12 to 24 weeks in patients with genotype 1 or 4 infection in the allograft, including compensated cirrhosis.
Daily fixed-dose combination of paritaprevir (150 mg)/ritonavir (100 mg)/ombitasvir (25 mg) plus twice-daily dosed dasabuvir (250 mg) and weight-based ribavirin (1000 mg [<75 kg] to 1200 mg [>75 mg]), in the allograft, without cirrhosis, for 24 weeks in patients with HCV genotype 1 infection.
Daily sofosbuvir (400 mg) plus daclatasvir (60 mg) with or without weight-based ribavirin (1000 mg [<75 kg] to 1200 mg [>75 kg]) for 24 weeks for patients with HCV genotypes 1, 3, 4, 5, and 6 in the allograft, including those with compensated and decompensated cirrhosis is another combination with high virological response and improvement of liver function.
Daily sofosbuvir (400 mg) and weight-based ribavirin (1000 mg [<75 kg] to 1200 mg [>75 kg]) for 24 weeks is recommended for patients with HCV genotype 2 in the allograft, including compensated cirrhosis.
Daily sofosbuvir (400 mg) and weight-based ribavirin (1000 mg [<75 kg] to 1200 mg [>75 kg]) for 24 weeks is recommended as alternative for treatment patients with HCV genotype 3 infection in the allograft, including compensated and decompensated cirrhosis.
For patients with creatinine clearance of >30 mL/min, no dosage adjustment is required when using simeprevir, sofosbuvir, daclatasvir, fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg), or fixed-dose combination of paritaprevir (150 mg)/ritonavir (100 mg)/ombitasvir (25 mg) plus twice-daily dosed dasabuvir (250 mg) to treat patients with HCV infection. Simeprevir, daclatasvir, and the combination of paritaprevir, ritonavir, ombitasvir and dasabuvir are cleared by hepatic metabolism and can be used in patients with severe renal impairment [91].
EASL Recommendations on Treatment of Hepatitis C 2015 and AASLD/IDSA/IAS-USA 2014 guidelines on HCV treatment do not recommend sofosbuvir in patients with creatinine clearance of <30 mL/min or with ESRD until more data are available [91,93].
When the efficacy of the treatment of acute HCV infection was superior to the treatment of chronic infection, there was a strong impetus to identify and treat acute HCV infection with interferon [106]. The current availability of interferon-sparing HCV treatments that have high safety and efficacy reduces the advantage of early treatment of HCV infection. Until data documenting the efficacy and safety of treatment of acute hepatitis C with direct acting antiviral drugs are available, monitoring for spontaneous clearance for minimum of 6 months before initiating treatment is required. When a decision is made to treat patients after 6 months of acute infection, then the patient can be treated as described for chronic HCV [93].
Chronic hepatitis C in the presence of the new direct-acting antiviral drugs became a curable disease, with a sustained virological response of more than 90%. The second-generation protease inhibitors that have been approved for treatment of HCV and are available in the market are simeprevir, sofosbuvir, ledipasvir/sofosbuvir, daclatasvir, and the combination of ombitasvir-paritaprevir-ritonavir and dasabuvir. The cost of these new agents prevents universal delivery of medications and prioritization of treatment should be given to patients who are in need of immediate care like those with advanced liver disease and extrahepatic complications. Trials are still ongoing with other new products, many of which are expected to appear in the market soon.
Maintaining the health of civil infrastructures such as bridges, roads, and tunnels is important to achieve a safe and reliable society [1, 2, 3]. Because a large number of concrete structures were built in the age of rapid economic growth in Japan, many of them are approaching their designed life spans. Thus, the development of a reliable health diagnosis technology is currently an urgent task. For example, many of the prestressed concrete (PC) bridges have life spans of 50 years, and they show apparent damage as they approach their designed life spans (Figure 1). Approximately 42 and 63% of all bridges will be over 50 years of age by 2021 and 2031, respectively.
\nImages of degraded bridge and parts. (i) Whole view of the bridge, (ii) degraded surface, and (iii) crack and leak of Ca components.
Normally, concrete bridges are regularly inspected by visual check and hammering tests. If damages or abnormalities are detected, more detailed nondestructive tests (NDTs) must be conducted.
\nNDT by X-ray radiography is one of the promising technologies for the detailed local inspection of a bridge. X-ray radiography provides high-resolution images of steel wires and rods inside thick concrete bridges. Its penetration capability depends on the thickness of the object and the energy of the X-ray; higher energy X-rays penetrate thicker concrete structures. However, the energy produced by X-ray sources for industrial NDTs is not sufficiently high for the inspection of bridges, because of their thick concrete structure. A low energy source does not provide clear contrast inside the concrete, and in addition, the exposure time required is very long. Some radioisotopes provide high-energy X(γ)-rays. However, they continuously emit X(γ)-rays and operator health becomes another concern. Thus, a new, safer bridge inspection technology using high-energy powerful X-ray sources is needed.
\nWe have developed X-band electron linear accelerator (linac)-based portable X-ray sources with high maximum energies of 950 keV and 3.95 MeV and have been demonstrating X-ray inspection of infrastructures using these sources [4, 5, 6, 7]. We have successfully conducted ten on-site inspections using these X-ray sources to date, and we are also working on technology development in laboratories using samples from dismantled bridges.
\nThe main focus of X-ray visualization of a bridge is damage of prestressed concrete (PC) wires and unfilled sheath pipes. Not only the rupture of wires but also the wastage of wires by corrosion reduces the residual strength of a bridge. Therefore, the quantitative evaluation of wire diameters within a resolution of 1 mm is required for X-ray imaging. The grout fill in the sheath pipes of a PC bridge is important to prevent wire corrosion from rainwater and to make the wires and the concrete operate as a composite material. Detecting unfilled sheath pipe areas by X-ray is therefore important for detecting wire damage or for calculating stress imbalances in the bridge. The results of X-ray visualization are used to evaluate the residual strength of a bridge using a reliable numerical calculation method.
\nThe goal of our research is to establish a structural health diagnosis method based on X-ray imaging of the inner structure of a bridge. In this chapter, we present the results of X-ray imaging of an actual bridge still in use and the calculated results of its residual strength through a numerical simulation. Investigation of the validity of X-ray partial-angle computed tomography (CT) or tomosynthesis image reconstruction for precise bridge inspection was also performed.
\nWe used X-band (9.3 GHz) linac-based 950 keV/3.95 MeV X-ray sources for the inspection of the actual bridge. The systems are shown in Figures 2 and 3, respectively.
\n950 keV portable X-band linac-based X-ray source and its specifications. The maximum X-ray energy is 950 keV. The system consists of three units: X-ray head, magnetron, and power units.
3.95 MeV portable X-band linac-based X-ray source and its major parameters. The system consists of four units: X-ray head, magnetron, power, and chiller units.
In the former, the electrons are accelerated up to 950 keV by radio-frequency (RF) fields. We also adopted the side-coupled standing wave-type accelerating structure. Electrons are injected into a Tungsten target that generates bremsstrahlung X-rays. The generated X-rays are collimated by a Tungsten collimator into the shape of a cone which has an opening angle of 17°. The most important is the X-ray intensity, which is 50 mSv/min at 1 m for a full magnetron RF power of 250 kW. The system consists of a 50-kg X-ray head, 50-kg magnetron box, and stationary electric power source and water chiller unit. The X-ray head and magnetron box are portable, and because they are connected to each other by a flexible waveguide, only the position and angle of the X-ray head are finely tuned. We have optimized the design with respect to X-ray intensity, compactness, and weight. The parameters of the 950 keV X-ray source are summarized in the table of Figure 2. We place an X-ray detector on the opposite site of the X-ray source between the object and source to detect the transmitted X-rays through the object. We use a flat panel detector (FPD) from PerkinElmer Corporation for the detector.
\nThe 3.95 MeV system is shown in Figure 3. This system consists of a 62-kg X-ray head with target collimator of 80 kg, magnetron box of 62 kg, electric power sources of 116 kg, and water cooling system of 30 kg. The X-ray head and magnetron box are portable, and the position and angle of the former are also finely tuned. The X-ray intensity of this system is 2 Gy/min at 1 m.
\nCalculated attenuations in concrete for the X-rays from the 950 keV/3.95 MeV sources are shown in Figure 4. The results indicate that concrete with thicknesses of up to 400 mm and 800 mm can be penetrated by the 950 keV/3.95 MeV sources, respectively.
\nCalculated results of attenuation for the X-rays in concrete from the 950 keV/3.95 MeV X-ray sources.
We comply with Japan’s Law Concerning Prevention of Radiation Hazards Due to Radioisotopes and Regulations on Prevention of Ionizing Radiation Hazards when we use the 950 keV/3.95 MeV X-ray sources in the field for on-site bridge inspection. According to the law, an electron beam source below 1 MeV is not an accelerator. Thus, we comply with this regulation. The 950 keV X-ray source is registered with the local agency of labor supervision. We usually operate the source in a radiation-controlled area, which has a radiation safety system complying with the Regulations on Prevention of Ionizing Radiation Hazards. The use of the source outside the controlled area is also allowed. In this case, we temporally set up a controlled area at the measurement site and place sufficient shielding around the source and object to suppress the air dose rate below 1.3 mSv/3 months. Moreover, we have to set a temporal facility boundary of 250 μSv/3 months. Amendment of the law that allows the use of accelerators below 4 MeV only for on-site bridge inspection was implemented in Japan in 2005. After we completed governmental registration as a radiation source, we submitted for permission of use outside the radiation-controlled area. Finally, we performed the on-site inspection under the Regulations on Prevention of Ionizing Radiation Hazards similar to the 950 keV case.
\nThree types of PC bridges (T-shaped bar type, box-shaped type, and hollow floor bar type) are investigated by the X-ray sources. Possible patterns of X-ray transmission and scanning (partial-angle CT and tomosynthesis) are depicted in Figure 5. An X-ray flat panel detector (FPD) and imaging plate (IP) are used for X-ray imaging acquisition. By using the FPD, online measurement in seconds is available so that sparse and fine-tuning of the position of the X-ray sources and detector can be accomplished. Stacking measurement in minutes is more appropriate for the IP. Imaging processing of IPs can be carried out on-site immediately. An aerial work platform and stage are used for measurement of the web and flange parts of a T-shaped bar bridge. The X-ray source can be installed inside a box for bottom floor slab inspection or on a pedestal for upper slabs of box-shaped bar types with the help of a crane. As for hollow floor bar types, the X-ray source is placed on the road or inside a hollow box. Even partial-angle CT and tomosynthesis are applicable for those types of inspections.
\nTypical techniques of X-ray transmission/scanning inspections for bridges of T-shaped bar type, box-shaped bar type, and hollow floor bar type.
Figure 6 shows typical transmission images of the inner structure of the slab of a certain T-shaped bar-type bridge obtained by the 950 keV X-ray source. We successfully observed the inner structure in detail with the linac-based X-ray system. The PC wires were clearly visualized. Cutting and thinning of PC wires are clearly apparent. Reduction of the PC wire cross sections is estimated visually, and images are used for the structural analysis to evaluate any reduction of structural strength quantitatively.
\nSeries of X-ray images of PC wires in a bottom slab of a box-shaped bar-type bridge acquired by the 950 keV X-ray source. Cutting and thinning of PC wires are observed.
PC wires, sheath, and grout in a web part of other T-shaped bar types obtained by the 950 keV X-ray source are given in Figure 7. Even grout filling and missing grout are clearly visible.
\nSurface view and X-ray transmission images of near PC wires, sheath, and grout in a web part of a T-shaped bar-type bridge acquired by the 950 keV X-ray source. Cracks and leak of Ca components are visible. Moreover, grout filling and missing grout are clearly observed in the near PC sheath.
Figure 8 shows an X-ray transmission imaged by the 3.95 MeV X-ray source from a cut sample of a hollow flow bar-type PC bridge. Several PC wires located deep in the concrete are visualized.
\nCut sample from a hollow flow bar-type bridge and X-ray transmission image acquired by the 3.95 MeV X-ray source. The total thickness of the concrete where the X-rays penetrate is ~400 mm. Several PC wires located deep in concrete are visualized.
However, the contrast between the wires and concrete was not sufficiently high. We consider that one reason is noise produced by X-rays scattered by the concrete structure. The probability of Compton scattering of an X-ray becomes higher as the energy of the X-ray becomes higher. If Compton scattering occurs between an X-ray photon and an atom of the material, the photon loses a portion of its energy and changes its direction. Because the original energies of X-rays are high, the energies of scattered X-rays are also high. Thus, many photons may have been scattered within the concrete structure and were detected at the FPD. It is an important task to reduce the image noise caused by scattering X-rays. A possible means to resolve this issue is by introducing a fine pitch metal mesh in front of the FPD to absorb only the X-rays impinging on the FPD and block scattered X-rays coming from other directions. Of course, image processing can be used to reduce noise. This aspect is discussed later.
\nWe calculated the residual strength of a block of the bridge using X-ray inspection results and the 3D nonlinear three-dimensional finite element method (FEM) software for reinforced concrete, named DuCOM-COM3 developed by Prof. Hirokazu Maekawa (Department of Civil Engineering, University of Tokyo). The model for FEM analysis is shown in Figure 9. We modeled a block of the bridge with an X-ray inspected part at its center, as shown in Figure 9(i). The X-ray inspected part is 1600 mm in the longitudinal direction. The boundary conditions were the moments when the designed load is applied, which were calculated by Newmark’s method.
\nTypical results of 3D nonlinear structural analysis of iron-reinforced concrete based on DuCOM-COM3 simulation using the cross-sectional reduction based on the measured X-ray transmission images such as those in Figure 6. Mesh model of the finite element method (FEM) and typical load pattern for structural degradation evaluation and stress contour results are shown in (i) and (ii), respectively. Curves of applied moment versus stress for the initial and degraded (measured) states are shown in (iii).
As a result of the FEM analysis, we found that the stress increased about 0.3 MPa at the lower edge of the box girder. This is because the stress resistance was decreased owing to damage of some PC wires. On the other hand, the compressive stress at the upper edge was not affected. The 3D distributions of stress after wire damage are depicted in Figure 9(ii). From the calculations, the load that generates concrete cracks is estimated as 8417 kN for the healthy condition and 8016 kN for the damaged condition. Curves of given moment versus stress for the initial and degraded states are shown in Figure 9(iii). Although the residual strength decreased by approximately 5%, the stress after damage remained within the range of the allowable stress, and the bridge was judged as operable at its current condition.
\nThree-dimensional information of the inner structure of the concrete bridge is more helpful than a simple X-ray transmission image if the structure is complicated by densely concentrated wires. In a simple radiography image, the wires are superimposed, and thus a precise evaluation of wire condition is not possible. However, in a three-dimensional image, each wire can be separated, and evaluating the diameters of the wires is easier and more precise.
\nX-ray CT has been a powerful tool used for this type of purpose in a wide variety of fields, such as medical and industrial applications. In a CT system, the X-ray source and the detector are rotated 360° around the object, and X-ray images are obtained at different angles. Slice images of the object will be reconstructed from the X-ray absorption factors calculated from the images. CT is widely used for the precise inspection of industrial products in the field of NDT; thus, we can expect it is also applicable for bridge inspections using higher energy X-rays.
\nHowever, it is usually impossible to widely rotate the source and detector around a target part of a bridge because of limited spaces around the target. We therefore consider applying partial-angle CT for bridge inspections. In partial-angle CT, the source and the detector are rotated less than 360°, and cross-sectional images are reconstructed from those partial-angle projection images. Partial-angle CT formulation is explained as follows, and its coordinate system for the spatial domain is illustrated in Figure 10(i). When the 2D X-ray attenuation constant distribution is f(x, y), the relation between the initial X-ray intensity from the X-ray source, I0, and input intensity at the detector, Ii, along the arrow in the figure is approximately given as
Coordinate system for the partial-angle CT. (i) Spatial domain, and (ii) Frequency domain.
Therefore, the Radon integral is measured by
The Fourier transform of f(x, y), F(μ, v), is given by the measured Radon transform data as
where
and the coordinate system in the frequency domain is shown in Figure 10(ii). In case of the partial-angle CT, the angle range is rather limited so that the Fourier transform data cannot be obtained in the whole frequency domain. Finally, the original X-ray attenuation distribution is calculated numerical by the filtered back projection method in the following:
Typical results for limited angles are introduced in Section 3.2.
\nAnother promising technology for obtaining three-dimensional information inside a bridge is tomosynthesis. Tomosynthesis has been used for applications such as breast imaging or dental imaging [8]. In normal tomosynthesis, the source is rotated against the detector with limited angle, and “parallax” X-ray images are obtained. The cross-sectional images of a target object are reconstructed from the parallax images. Tomosynthesis has been used in applications where full-angle CT cannot be applied. Thus, it is also a promising technology for bridge inspections.
\nAs a first step, we experimentally investigated the feasibility of partial-angle CT and tomosynthesis using mock-up samples of bridges.
\nWe have applied the partial-angle CT and tomosynthesis to cut samples from the real PC bridge and acrylic phantoms.
\nThe CT reconstructed results for PC wires in a cut sample of the flange part of a T-shaped bar bridge by scanning at 360, 180, and 90° using the 3.95 MeV X-ray source are shown in Figure 11. All PC wires in a sheath are perfectly reconstructed by 360° scanning. The circular shape is intrinsically deformed to an elliptic shape by partial-angle scanning using the CT algorithm. However, the minor axis diameter of the ellipse is almost the same as the real diameter of the PC wires.
\nCT reconstructed results of PC wires in the flange part of a T-shaped bar bridge by scanning at 360, 180 and 90° using the 3.95 MeV X-ray source. All PC wires in a sheath are perfectly reconstructed by 360° scanning.
Figure 12 is a reconstructed image of the cross section of an acrylic phantom by tomosynthesis. Although we also observed the deformation of the cross-sectional shapes from circles to ellipses in tomosynthesis, we can estimate the original diameters from the minor axes of the ellipses. We extracted a profile from the tomosynthesis image and plotted its gray values (see Figure 13). The profile included three rods with different diameters (6, 8, and 10 mm). We were able to estimate the diameter of the center rod (8 mm) within 1 mm accuracy. From the profile plotting, the estimated diameter of the rods was between 7.2 and 8.0 mm.
\nCross-sectional X-ray images of the acrylic phantom reconstructed by (i) full-angle CT and (ii) tomosynthesis. The tomosynthesis image was obtained with 25 projections taken in 3° steps.
Gray value plot of a profile in the tomosynthesis image of the acrylic phantom.
Software image processing is inevitable for this work. Fourier transform (FT) with low-pass filter, high-pass filter, and band-pass filter is a standard technique. If we apply FT with a low-pass filter, the image becomes blurred, and the boundary between an iron rod and a PC wire is difficult to recognize. As for FT with a high-pass filter, the boundary is emphasized, but the overall view is spotty. When we construct a gray value profile to evaluate the diameter of a rod or PC wire, the profile is noisy. Regarding a band-pass filter, trial and error is necessary to choose an appropriate band. Instead, the wavelet transform is effective for emphasizing local signals. Recently, the curvelet transform has become popular. It is an upgraded wavelet transform fit to emphasize curved and declined boundaries. We applied the curvelet transform to the X-ray transmission images of PC wires of the upper slab of the hollow box bar-type bridge (Figure 6). We attempted to evaluate the diameter of one of the PC wires in the somewhat blurred image of the 400 mm slab, which is close to the transmission limit of the X-rays from the 950 keV source. We can observe that spatially high-frequency noises are suppressed and the full width at half maximum (FWHM) can be used to estimate the diameter, which is 6.18 mm for the designed 7 mm wire as shown in Figure 14.
\nImage processing using the curvelet transform and evaluation of the diameter of PC wires.
We check the relationship between the states of a concrete surface and near inner PC wires. We evaluate cut samples from a decommissioned T-shaped bar-type bridge. One example is shown in Figure 15. The surface concrete is somewhat degraded and cracked (see Figure 15(i)). The cut cross-sectional view and X-ray transmission image of the near PC wires are shown in Figure 15(ii) and (iii), respectively. The PC wires look healthy in this case. Because this bridge was located near the sea, the degradation of the concrete was due to salt damage. Furthermore, a load test was performed on this bridge. It was confirmed that its mechanical strength was not degraded, and this mechanically healthy bridge was wastefully decommissioned.
\nTypical case of heavily corrupted concrete surface (i) and healthy PC wires in a cut sample from a T-shaped bar bridge. The direction of the X-ray transmission is shown in (ii). X-ray transmission images of PC wires in two sheaths are shown in (iii).
In the above case, inner PC wires were healthy even though the surface concrete was degraded and cracked. Opposite cases involving corroded PC wires in bridges with healthy surface concrete have also been found.
\nThese facts indicate that visible and hammer-sound inspections are not necessarily sufficient for checking the degradation of a bridge’s mechanical strength. X-ray inspection is needed to check the state of inner PC wires and to evaluate the mechanical strength of a bridge.
\nX-ray transmission images using the 950 keV source in the web part of the T-shaped bar-type bridge in the case of Figure 7 overlap at the designated location of the two PC sheaths and wires, as shown in Figure 16. Grout fills the upper sheath but is missing in the lower. This is the first observation of grout missing after the initial construction. This vacancy may become a puddle of rainwater which would induce corrosion of PC wires in the near future.
\nX-ray transmission images of grout filling and missing grout in the PC sheaths in the web part of a T-shaped bar bridge measured by the 950 keV X-ray source.
Our collaborator, Kanto Giken Co. (Tokai, Ibaraki, Japan), developed a new special inspection car for the X-ray sources as shown in Figure 17. It can carry the X-ray sources, detectors, computers, and inspectors and contains a diesel engine 100 V power source. Some diesel engine power sources have poor quality unstable output voltage and frequency (50 and 60 Hz in east and west Japan, respectively). The electric power source of the magnetron may be sensitive to such instability. To avoid this, we decided to acquire our own reliable diesel engine power source, which we can carry to perform on-site X-ray inspections anywhere in Japan.
\nSpecial inspection car for the 950 keV/3.95 MeV X-ray sources. (i) Front view, (ii) Back view, (iii) Control units, and (iv) On site set-up.
The most important procedure of this task are the sparse and fine-tuning of the position and angle of the X-ray sources with respect to the bridge part and the X-ray detectors (FPD and IP) as shown in Figure 18(i), (ii), and (iii). The procedure typically requires approximately 1 h. We use an aerial work platform, stage, and special inspection car for initial settings ((i)), and then by using a rotating function of the X-ray head, we adjust its angle. Finally, fine-tuning among the X-ray source, targeted area, and detector is performed. The whole tuning procedure takes approximately 1 h. This procedure consists of using and setting many devices, including the X-ray sources, detectors, mechanical positioners, and so on.
\nInitial setup (i), control of angle (ii), and fine positioning (iii) of the 950 keV X-ray source with an aerial work platform.
Usually, we start setting up all devices at 9 am. We then perform sparse and fine-tuning of the position and angle of the X-ray sources and detectors and begin taking real measurement at 11 am. We scan several parts until 3 pm. Finally, dismantling and storing the equipment occurs between 3 pm and 5 pm. Targeted bridge parts are completely different depending on the three types of bridges (T-shaped bar, box-shaped bar, or hollow floor bar). Thus, we are always improving and upgrading not only the X-ray sources but also our devices and software to better deal with many complicated situations.
\nDamage to bridges in northern and highland areas in Japan is serious because water in the concrete of a bridge freezes and expands, causing cracks in the concrete. It may snow in those areas in winter. Therefore, inspections should not be carried out during winter. It often rains from June through October in the semitropical climate areas of Japan. We have to be prepared for rain and high humidity, so we use waterproof housing for electric sources and perform very careful equipment treatments and inspections to avoid electric breakdown.
\nThe Public Works Research Institute and the University of Tokyo are developing new technical guidelines for special inspections of bridges using 950 keV/3.95 MeV X-ray sources. An overview is provided in Figure 19. First, visual and hammer-sound inspection screening should be performed based on regular inspection guidelines. Advanced hardware and software techniques such as drawn and acoustic analysis are adopted in this step. If degraded parts are found, the special X-ray transmission inspection is performed using the 950 keV or 3.95 MeV X-ray sources, depending on the thickness of the concrete containing the degraded parts. Here, the states of PC wires and rods as affected by corrosion, cuts, and reduction of cross sections are quantitatively evaluated with spatial resolution of 1 mm. Then, 3D nonlinear structural analysis is performed to evaluate the degradation of the structural strength quantitatively. Based on this evaluation, repair, reinforcement, or other decisions should be reviewed. Several inspection industries are joining our project and technical transfer is being promoted. We hope to soon apply these guidelines to all aged bridges in Japan and finally across the world.
\nGuidelines for special X-ray transmission inspection using 950 keV/3.95 MeV X-ray sources accompanied with visual and hammer-sound inspections, structural analysis, final repair, and/or reinforcement.
We have been developing a new X-ray diagnostic method for social and industrial infrastructures using linear accelerator-based X-ray sources. Our 950 keV/3.95 MeV X-ray sources have been applied to many different cases involving on-site X-ray inspection of bridges in Japan. We are currently undertaking on-site inspections of actual bridges. We have demonstrated X-ray inspection of an actual bridge still in use. Clear X-ray transmission images inside the concrete were successfully obtained in the demonstration. The information regarding PC wire conditions from X-ray images was applied to the structural analysis using the finite element method to evaluate the residual strength of a bridge. We found that the residual strength of the bridge in question had decreased by approximately 5% from its original state based on application of the designed load.
\nWe also studied three-dimensional image reconstruction methods that can be applied to bridge inspections. Because of the limitations in spaces and rotation angles involved in actual on-site inspections, full-angle CT is normally not possible to apply for bridge inspections. Thus, we investigated the effectiveness of partial-angle CT and tomosynthesis for bridge inspections. Although the cross-sectional shape of a wire or rod was deformed from its original circular shape to an ellipse-like shape, we could estimate the diameter of the rod or wire from the length of the minor axis of the ellipse. The estimated diameter of a steel rod in a tomosynthesis image was in good agreement with its real value.
\nFurther studies are required to realize the practical use of this X-ray bridge inspection method. We should continue the demonstrations involving on-site bridge inspection for different types of bridges and evaluate the effectiveness of the special X-ray transmission inspection using the 950 keV/3.95 MeV X-ray sources based on the new technical guidelines.
\nThis work was supported by the “Infrastructure Maintenance, Renovation, and Management program” of Cross-ministerial Strategic Innovation Promotion Program (SIP), Cabinet Office, Government of Japan. The authors thank for Mr. Kentaro Murata of XIT Co. for the partial CT analysis.
\nEdited by Jan Oxholm Gordeladze, ISBN 978-953-51-3020-8, Print ISBN 978-953-51-3019-2, 336 pages,
\nPublisher: IntechOpen
\nChapters published March 22, 2017 under CC BY 3.0 license
\nDOI: 10.5772/61430
\nEdited Volume
This book serves as a comprehensive survey of the impact of vitamin K2 on cellular functions and organ systems, indicating that vitamin K2 plays an important role in the differentiation/preservation of various cell phenotypes and as a stimulator and/or mediator of interorgan cross talk. Vitamin K2 binds to the transcription factor SXR/PXR, thus acting like a hormone (very much in the same manner as vitamin A and vitamin D). Therefore, vitamin K2 affects a multitude of organ systems, and it is reckoned to be one positive factor in bringing about "longevity" to the human body, e.g., supporting the functions/health of different organ systems, as well as correcting the functioning or even "curing" ailments striking several organs in our body.
\\n\\nChapter 1 Introductory Chapter: Vitamin K2 by Jan Oxholm Gordeladze
\\n\\nChapter 2 Vitamin K, SXR, and GGCX by Kotaro Azuma and Satoshi Inoue
\\n\\nChapter 3 Vitamin K2 Rich Food Products by Muhammad Yasin, Masood Sadiq Butt and Aurang Zeb
\\n\\nChapter 4 Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet by Barbara Walther and Magali Chollet
\\n\\nChapter 5 The Impact of Vitamin K2 on Energy Metabolism by Mona Møller, Serena Tonstad, Tone Bathen and Jan Oxholm Gordeladze
\\n\\nChapter 6 Vitamin K2 and Bone Health by Niels Erik Frandsen and Jan Oxholm Gordeladze
\\n\\nChapter 7 Vitamin K2 and its Impact on Tooth Epigenetics by Jan Oxholm Gordeladze, Maria A. Landin, Gaute Floer Johnsen, Håvard Jostein Haugen and Harald Osmundsen
\\n\\nChapter 8 Anti-Inflammatory Actions of Vitamin K by Stephen J. Hodges, Andrew A. Pitsillides, Lars M. Ytrebø and Robin Soper
\\n\\nChapter 9 Vitamin K2: Implications for Cardiovascular Health in the Context of Plant-Based Diets, with Applications for Prostate Health by Michael S. Donaldson
\\n\\nChapter 11 Vitamin K2 Facilitating Inter-Organ Cross-Talk by Jan O. Gordeladze, Håvard J. Haugen, Gaute Floer Johnsen and Mona Møller
\\n\\nChapter 13 Medicinal Chemistry of Vitamin K Derivatives and Metabolites by Shinya Fujii and Hiroyuki Kagechika
\\n"}]'},components:[{type:"htmlEditorComponent",content:'This book serves as a comprehensive survey of the impact of vitamin K2 on cellular functions and organ systems, indicating that vitamin K2 plays an important role in the differentiation/preservation of various cell phenotypes and as a stimulator and/or mediator of interorgan cross talk. Vitamin K2 binds to the transcription factor SXR/PXR, thus acting like a hormone (very much in the same manner as vitamin A and vitamin D). Therefore, vitamin K2 affects a multitude of organ systems, and it is reckoned to be one positive factor in bringing about "longevity" to the human body, e.g., supporting the functions/health of different organ systems, as well as correcting the functioning or even "curing" ailments striking several organs in our body.
\n\nChapter 1 Introductory Chapter: Vitamin K2 by Jan Oxholm Gordeladze
\n\nChapter 2 Vitamin K, SXR, and GGCX by Kotaro Azuma and Satoshi Inoue
\n\nChapter 3 Vitamin K2 Rich Food Products by Muhammad Yasin, Masood Sadiq Butt and Aurang Zeb
\n\nChapter 4 Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet by Barbara Walther and Magali Chollet
\n\nChapter 5 The Impact of Vitamin K2 on Energy Metabolism by Mona Møller, Serena Tonstad, Tone Bathen and Jan Oxholm Gordeladze
\n\nChapter 6 Vitamin K2 and Bone Health by Niels Erik Frandsen and Jan Oxholm Gordeladze
\n\nChapter 7 Vitamin K2 and its Impact on Tooth Epigenetics by Jan Oxholm Gordeladze, Maria A. Landin, Gaute Floer Johnsen, Håvard Jostein Haugen and Harald Osmundsen
\n\nChapter 8 Anti-Inflammatory Actions of Vitamin K by Stephen J. Hodges, Andrew A. Pitsillides, Lars M. Ytrebø and Robin Soper
\n\nChapter 9 Vitamin K2: Implications for Cardiovascular Health in the Context of Plant-Based Diets, with Applications for Prostate Health by Michael S. Donaldson
\n\nChapter 11 Vitamin K2 Facilitating Inter-Organ Cross-Talk by Jan O. Gordeladze, Håvard J. Haugen, Gaute Floer Johnsen and Mona Møller
\n\nChapter 13 Medicinal Chemistry of Vitamin K Derivatives and Metabolites by Shinya Fujii and Hiroyuki Kagechika
\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{sort:"featured,name"},profiles:[{id:"6700",title:"Dr.",name:"Abbass A.",middleName:null,surname:"Hashim",slug:"abbass-a.-hashim",fullName:"Abbass A. Hashim",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/6700/images/1864_n.jpg",biography:"Currently I am carrying out research in several areas of interest, mainly covering work on chemical and bio-sensors, semiconductor thin film device fabrication and characterisation.\nAt the moment I have very strong interest in radiation environmental pollution and bacteriology treatment. The teams of researchers are working very hard to bring novel results in this field. I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. I have served as the editor for many books, been a member of the editorial board in science journals, have published many papers and hold many patents.",institutionString:null,institution:{name:"Sheffield Hallam University",country:{name:"United Kingdom"}}},{id:"54525",title:"Prof.",name:"Abdul Latif",middleName:null,surname:"Ahmad",slug:"abdul-latif-ahmad",fullName:"Abdul Latif Ahmad",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"20567",title:"Prof.",name:"Ado",middleName:null,surname:"Jorio",slug:"ado-jorio",fullName:"Ado Jorio",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidade Federal de Minas Gerais",country:{name:"Brazil"}}},{id:"47940",title:"Dr.",name:"Alberto",middleName:null,surname:"Mantovani",slug:"alberto-mantovani",fullName:"Alberto Mantovani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"12392",title:"Mr.",name:"Alex",middleName:null,surname:"Lazinica",slug:"alex-lazinica",fullName:"Alex Lazinica",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12392/images/7282_n.png",biography:"Alex Lazinica is the founder and CEO of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his PhD studies in Robotics at the Vienna University of Technology. Here he worked as a robotic researcher with the university's Intelligent Manufacturing Systems Group as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and most importantly he co-founded and built the International Journal of Advanced Robotic Systems- world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career, since it was a pathway to founding IntechOpen - Open Access publisher focused on addressing academic researchers needs. Alex is a personification of IntechOpen key values being trusted, open and entrepreneurial. Today his focus is on defining the growth and development strategy for the company.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"19816",title:"Prof.",name:"Alexander",middleName:null,surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/19816/images/1607_n.jpg",biography:"Alexander I. Kokorin: born: 1947, Moscow; DSc., PhD; Principal Research Fellow (Research Professor) of Department of Kinetics and Catalysis, N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow.\r\nArea of research interests: physical chemistry of complex-organized molecular and nanosized systems, including polymer-metal complexes; the surface of doped oxide semiconductors. He is an expert in structural, absorptive, catalytic and photocatalytic properties, in structural organization and dynamic features of ionic liquids, in magnetic interactions between paramagnetic centers. The author or co-author of 3 books, over 200 articles and reviews in scientific journals and books. He is an actual member of the International EPR/ESR Society, European Society on Quantum Solar Energy Conversion, Moscow House of Scientists, of the Board of Moscow Physical Society.",institutionString:null,institution:{name:"Semenov Institute of Chemical Physics",country:{name:"Russia"}}},{id:"62389",title:"PhD.",name:"Ali Demir",middleName:null,surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62389/images/3413_n.jpg",biography:"Dr. Ali Demir Sezer has a Ph.D. from Pharmaceutical Biotechnology at the Faculty of Pharmacy, University of Marmara (Turkey). He is the member of many Pharmaceutical Associations and acts as a reviewer of scientific journals and European projects under different research areas such as: drug delivery systems, nanotechnology and pharmaceutical biotechnology. Dr. Sezer is the author of many scientific publications in peer-reviewed journals and poster communications. Focus of his research activity is drug delivery, physico-chemical characterization and biological evaluation of biopolymers micro and nanoparticles as modified drug delivery system, and colloidal drug carriers (liposomes, nanoparticles etc.).",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"61051",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"100762",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"St David's Medical Center",country:{name:"United States of America"}}},{id:"107416",title:"Dr.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Texas Cardiac Arrhythmia",country:{name:"United States of America"}}},{id:"64434",title:"Dr.",name:"Angkoon",middleName:null,surname:"Phinyomark",slug:"angkoon-phinyomark",fullName:"Angkoon Phinyomark",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/64434/images/2619_n.jpg",biography:"My name is Angkoon Phinyomark. I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. I had been a visiting research student at Faculty of Computer Science, University of Murcia, Murcia, Spain for three months.\n\nI have published over 40 papers during 5 years in refereed journals, books, and conference proceedings in the areas of electro-physiological signals processing and classification, notably EMG and EOG signals, fractal analysis, wavelet analysis, texture analysis, feature extraction and machine learning algorithms, and assistive and rehabilitative devices. I have several computer programming language certificates, i.e. Sun Certified Programmer for the Java 2 Platform 1.4 (SCJP), Microsoft Certified Professional Developer, Web Developer (MCPD), Microsoft Certified Technology Specialist, .NET Framework 2.0 Web (MCTS). I am a Reviewer for several refereed journals and international conferences, such as IEEE Transactions on Biomedical Engineering, IEEE Transactions on Industrial Electronics, Optic Letters, Measurement Science Review, and also a member of the International Advisory Committee for 2012 IEEE Business Engineering and Industrial Applications and 2012 IEEE Symposium on Business, Engineering and Industrial Applications.",institutionString:null,institution:{name:"Joseph Fourier University",country:{name:"France"}}},{id:"55578",title:"Dr.",name:"Antonio",middleName:null,surname:"Jurado-Navas",slug:"antonio-jurado-navas",fullName:"Antonio Jurado-Navas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/55578/images/4574_n.png",biography:"Antonio Jurado-Navas received the M.S. degree (2002) and the Ph.D. degree (2009) in Telecommunication Engineering, both from the University of Málaga (Spain). He first worked as a consultant at Vodafone-Spain. From 2004 to 2011, he was a Research Assistant with the Communications Engineering Department at the University of Málaga. In 2011, he became an Assistant Professor in the same department. From 2012 to 2015, he was with Ericsson Spain, where he was working on geo-location\ntools for third generation mobile networks. Since 2015, he is a Marie-Curie fellow at the Denmark Technical University. His current research interests include the areas of mobile communication systems and channel modeling in addition to atmospheric optical communications, adaptive optics and statistics",institutionString:null,institution:{name:"University of Malaga",country:{name:"Spain"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:5766},{group:"region",caption:"Middle and South America",value:2,count:5227},{group:"region",caption:"Africa",value:3,count:1717},{group:"region",caption:"Asia",value:4,count:10366},{group:"region",caption:"Australia and Oceania",value:5,count:897},{group:"region",caption:"Europe",value:6,count:15789}],offset:12,limit:12,total:118187},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{topicId:"23"},books:[{type:"book",id:"10656",title:"Intellectual Property",subtitle:null,isOpenForSubmission:!0,hash:"135df9b403b125a6458eba971faab3f6",slug:null,bookSignature:"Dr. Sakthivel Lakshmana Prabu and Dr. Suriyaprakash TNK",coverURL:"https://cdn.intechopen.com/books/images_new/10656.jpg",editedByType:null,editors:[{id:"91590",title:"Dr.",name:"Sakthivel",surname:"Lakshmana Prabu",slug:"sakthivel-lakshmana-prabu",fullName:"Sakthivel Lakshmana Prabu"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10658",title:"Multilingualism",subtitle:null,isOpenForSubmission:!0,hash:"a6bf171e05831c00f8687891ab1b10b5",slug:null,bookSignature:"Prof. Xiaoming Jiang",coverURL:"https://cdn.intechopen.com/books/images_new/10658.jpg",editedByType:null,editors:[{id:"189844",title:"Prof.",name:"Xiaoming",surname:"Jiang",slug:"xiaoming-jiang",fullName:"Xiaoming Jiang"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10662",title:"Pedagogy",subtitle:null,isOpenForSubmission:!0,hash:"c858e1c6fb878d3b895acbacec624576",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10662.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10913",title:"Indigenous Populations",subtitle:null,isOpenForSubmission:!0,hash:"c5e8cd4e3ec004d0479494ca190db4cb",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10913.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10914",title:"Racism",subtitle:null,isOpenForSubmission:!0,hash:"0737383fcc202641f59e4a5df02eb509",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10914.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:14},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:3},{group:"topic",caption:"Business, Management and Economics",value:7,count:1},{group:"topic",caption:"Chemistry",value:8,count:6},{group:"topic",caption:"Computer and Information Science",value:9,count:6},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:7},{group:"topic",caption:"Engineering",value:11,count:15},{group:"topic",caption:"Environmental Sciences",value:12,count:2},{group:"topic",caption:"Immunology and Microbiology",value:13,count:3},{group:"topic",caption:"Materials Science",value:14,count:5},{group:"topic",caption:"Mathematics",value:15,count:1},{group:"topic",caption:"Medicine",value:16,count:24},{group:"topic",caption:"Neuroscience",value:18,count:1},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:2},{group:"topic",caption:"Physics",value:20,count:2},{group:"topic",caption:"Psychology",value:21,count:4},{group:"topic",caption:"Social Sciences",value:23,count:2},{group:"topic",caption:"Technology",value:24,count:1},{group:"topic",caption:"Veterinary Medicine and Science",value:25,count:1}],offset:12,limit:12,total:5},popularBooks:{featuredBooks:[{type:"book",id:"9385",title:"Renewable Energy",subtitle:"Technologies and Applications",isOpenForSubmission:!1,hash:"a6b446d19166f17f313008e6c056f3d8",slug:"renewable-energy-technologies-and-applications",bookSignature:"Tolga Taner, Archana Tiwari and Taha Selim Ustun",coverURL:"https://cdn.intechopen.com/books/images_new/9385.jpg",editors:[{id:"197240",title:"Associate Prof.",name:"Tolga",middleName:null,surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner"}],equalEditorOne:{id:"186791",title:"Dr.",name:"Archana",middleName:null,surname:"Tiwari",slug:"archana-tiwari",fullName:"Archana Tiwari",profilePictureURL:"https://mts.intechopen.com/storage/users/186791/images/system/186791.jpg",biography:"Dr. Archana Tiwari is Associate Professor at Amity University, India. Her research interests include renewable sources of energy from microalgae and further utilizing the residual biomass for the generation of value-added products, bioremediation through microalgae and microbial consortium, antioxidative enzymes and stress, and nutraceuticals from microalgae. She has been working on algal biotechnology for the last two decades. She has published her research in many international journals and has authored many books and chapters with renowned publishing houses. She has also delivered talks as an invited speaker at many national and international conferences. Dr. Tiwari is the recipient of several awards including Researcher of the Year and Distinguished Scientist.",institutionString:"Amity University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Amity University",institutionURL:null,country:{name:"India"}}},equalEditorTwo:{id:"197609",title:"Prof.",name:"Taha Selim",middleName:null,surname:"Ustun",slug:"taha-selim-ustun",fullName:"Taha Selim Ustun",profilePictureURL:"https://mts.intechopen.com/storage/users/197609/images/system/197609.jpeg",biography:"Dr. Taha Selim Ustun received a Ph.D. in Electrical Engineering from Victoria University, Melbourne, Australia. He is a researcher with the Fukushima Renewable Energy Institute, AIST (FREA), where he leads the Smart Grid Cybersecurity Laboratory. Prior to that, he was a faculty member with the School of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA. His current research interests include power systems protection, communication in power networks, distributed generation, microgrids, electric vehicle integration, and cybersecurity in smart grids. He serves on the editorial boards of IEEE Access, IEEE Transactions on Industrial Informatics, Energies, Electronics, Electricity, World Electric Vehicle and Information journals. Dr. Ustun is a member of the IEEE 2004 and 2800, IEC Renewable Energy Management WG 8, and IEC TC 57 WG17. He has been invited to run specialist courses in Africa, India, and China. He has delivered talks for the Qatar Foundation, the World Energy Council, the Waterloo Global Science Initiative, and the European Union Energy Initiative (EUEI). His research has attracted funding from prestigious programs in Japan, Australia, the European Union, and North America.",institutionString:"Fukushima Renewable Energy Institute, AIST (FREA)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"National Institute of Advanced Industrial Science and Technology",institutionURL:null,country:{name:"Japan"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8985",title:"Natural Resources Management and Biological Sciences",subtitle:null,isOpenForSubmission:!1,hash:"5c2e219a6c021a40b5a20c041dea88c4",slug:"natural-resources-management-and-biological-sciences",bookSignature:"Edward R. Rhodes and Humood Naser",coverURL:"https://cdn.intechopen.com/books/images_new/8985.jpg",editors:[{id:"280886",title:"Prof.",name:"Edward R",middleName:null,surname:"Rhodes",slug:"edward-r-rhodes",fullName:"Edward R Rhodes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9027",title:"Human Blood Group Systems and Haemoglobinopathies",subtitle:null,isOpenForSubmission:!1,hash:"d00d8e40b11cfb2547d1122866531c7e",slug:"human-blood-group-systems-and-haemoglobinopathies",bookSignature:"Osaro Erhabor and Anjana Munshi",coverURL:"https://cdn.intechopen.com/books/images_new/9027.jpg",editors:[{id:"35140",title:null,name:"Osaro",middleName:null,surname:"Erhabor",slug:"osaro-erhabor",fullName:"Osaro Erhabor"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7841",title:"New Insights Into Metabolic Syndrome",subtitle:null,isOpenForSubmission:!1,hash:"ef5accfac9772b9e2c9eff884f085510",slug:"new-insights-into-metabolic-syndrome",bookSignature:"Akikazu Takada",coverURL:"https://cdn.intechopen.com/books/images_new/7841.jpg",editors:[{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8558",title:"Aerodynamics",subtitle:null,isOpenForSubmission:!1,hash:"db7263fc198dfb539073ba0260a7f1aa",slug:"aerodynamics",bookSignature:"Mofid Gorji-Bandpy and Aly-Mousaad Aly",coverURL:"https://cdn.intechopen.com/books/images_new/8558.jpg",editors:[{id:"35542",title:"Prof.",name:"Mofid",middleName:null,surname:"Gorji-Bandpy",slug:"mofid-gorji-bandpy",fullName:"Mofid Gorji-Bandpy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9668",title:"Chemistry and Biochemistry of Winemaking, Wine Stabilization and Aging",subtitle:null,isOpenForSubmission:!1,hash:"c5484276a314628acf21ec1bdc3a86b9",slug:"chemistry-and-biochemistry-of-winemaking-wine-stabilization-and-aging",bookSignature:"Fernanda Cosme, Fernando M. Nunes and Luís Filipe-Ribeiro",coverURL:"https://cdn.intechopen.com/books/images_new/9668.jpg",editors:[{id:"186819",title:"Prof.",name:"Fernanda",middleName:null,surname:"Cosme",slug:"fernanda-cosme",fullName:"Fernanda Cosme"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7847",title:"Medical Toxicology",subtitle:null,isOpenForSubmission:!1,hash:"db9b65bea093de17a0855a1b27046247",slug:"medical-toxicology",bookSignature:"Pınar Erkekoglu and Tomohisa Ogawa",coverURL:"https://cdn.intechopen.com/books/images_new/7847.jpg",editors:[{id:"109978",title:"Prof.",name:"Pınar",middleName:null,surname:"Erkekoglu",slug:"pinar-erkekoglu",fullName:"Pınar Erkekoglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8620",title:"Mining Techniques",subtitle:"Past, Present and Future",isOpenForSubmission:!1,hash:"b65658f81d14e9e57e49377869d3a575",slug:"mining-techniques-past-present-and-future",bookSignature:"Abhay Soni",coverURL:"https://cdn.intechopen.com/books/images_new/8620.jpg",editors:[{id:"271093",title:"Dr.",name:"Abhay",middleName:null,surname:"Soni",slug:"abhay-soni",fullName:"Abhay Soni"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9660",title:"Inland Waters",subtitle:"Dynamics and Ecology",isOpenForSubmission:!1,hash:"975c26819ceb11a926793bc2adc62bd6",slug:"inland-waters-dynamics-and-ecology",bookSignature:"Adam Devlin, Jiayi Pan and Mohammad Manjur Shah",coverURL:"https://cdn.intechopen.com/books/images_new/9660.jpg",editors:[{id:"280757",title:"Dr.",name:"Adam",middleName:"Thomas",surname:"Devlin",slug:"adam-devlin",fullName:"Adam Devlin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9122",title:"Cosmetic Surgery",subtitle:null,isOpenForSubmission:!1,hash:"207026ca4a4125e17038e770d00ee152",slug:"cosmetic-surgery",bookSignature:"Yueh-Bih Tang",coverURL:"https://cdn.intechopen.com/books/images_new/9122.jpg",editors:[{id:"202122",title:"Prof.",name:"Yueh-Bih",middleName:null,surname:"Tang",slug:"yueh-bih-tang",fullName:"Yueh-Bih Tang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9043",title:"Parenting",subtitle:"Studies by an Ecocultural and Transactional Perspective",isOpenForSubmission:!1,hash:"6d21066c7438e459e4c6fb13217a5c8c",slug:"parenting-studies-by-an-ecocultural-and-transactional-perspective",bookSignature:"Loredana Benedetto and Massimo Ingrassia",coverURL:"https://cdn.intechopen.com/books/images_new/9043.jpg",editors:[{id:"193200",title:"Prof.",name:"Loredana",middleName:null,surname:"Benedetto",slug:"loredana-benedetto",fullName:"Loredana Benedetto"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9731",title:"Oxidoreductase",subtitle:null,isOpenForSubmission:!1,hash:"852e6f862c85fc3adecdbaf822e64e6e",slug:"oxidoreductase",bookSignature:"Mahmoud Ahmed Mansour",coverURL:"https://cdn.intechopen.com/books/images_new/9731.jpg",editors:[{id:"224662",title:"Prof.",name:"Mahmoud Ahmed",middleName:null,surname:"Mansour",slug:"mahmoud-ahmed-mansour",fullName:"Mahmoud Ahmed Mansour"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:5227},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"9385",title:"Renewable Energy",subtitle:"Technologies and Applications",isOpenForSubmission:!1,hash:"a6b446d19166f17f313008e6c056f3d8",slug:"renewable-energy-technologies-and-applications",bookSignature:"Tolga Taner, Archana Tiwari and Taha Selim Ustun",coverURL:"https://cdn.intechopen.com/books/images_new/9385.jpg",editors:[{id:"197240",title:"Associate Prof.",name:"Tolga",middleName:null,surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner"}],equalEditorOne:{id:"186791",title:"Dr.",name:"Archana",middleName:null,surname:"Tiwari",slug:"archana-tiwari",fullName:"Archana Tiwari",profilePictureURL:"https://mts.intechopen.com/storage/users/186791/images/system/186791.jpg",biography:"Dr. Archana Tiwari is Associate Professor at Amity University, India. Her research interests include renewable sources of energy from microalgae and further utilizing the residual biomass for the generation of value-added products, bioremediation through microalgae and microbial consortium, antioxidative enzymes and stress, and nutraceuticals from microalgae. She has been working on algal biotechnology for the last two decades. She has published her research in many international journals and has authored many books and chapters with renowned publishing houses. She has also delivered talks as an invited speaker at many national and international conferences. Dr. Tiwari is the recipient of several awards including Researcher of the Year and Distinguished Scientist.",institutionString:"Amity University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Amity University",institutionURL:null,country:{name:"India"}}},equalEditorTwo:{id:"197609",title:"Prof.",name:"Taha Selim",middleName:null,surname:"Ustun",slug:"taha-selim-ustun",fullName:"Taha Selim Ustun",profilePictureURL:"https://mts.intechopen.com/storage/users/197609/images/system/197609.jpeg",biography:"Dr. Taha Selim Ustun received a Ph.D. in Electrical Engineering from Victoria University, Melbourne, Australia. He is a researcher with the Fukushima Renewable Energy Institute, AIST (FREA), where he leads the Smart Grid Cybersecurity Laboratory. Prior to that, he was a faculty member with the School of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA. His current research interests include power systems protection, communication in power networks, distributed generation, microgrids, electric vehicle integration, and cybersecurity in smart grids. He serves on the editorial boards of IEEE Access, IEEE Transactions on Industrial Informatics, Energies, Electronics, Electricity, World Electric Vehicle and Information journals. Dr. Ustun is a member of the IEEE 2004 and 2800, IEC Renewable Energy Management WG 8, and IEC TC 57 WG17. He has been invited to run specialist courses in Africa, India, and China. He has delivered talks for the Qatar Foundation, the World Energy Council, the Waterloo Global Science Initiative, and the European Union Energy Initiative (EUEI). His research has attracted funding from prestigious programs in Japan, Australia, the European Union, and North America.",institutionString:"Fukushima Renewable Energy Institute, AIST (FREA)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"National Institute of Advanced Industrial Science and Technology",institutionURL:null,country:{name:"Japan"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8985",title:"Natural Resources Management and Biological Sciences",subtitle:null,isOpenForSubmission:!1,hash:"5c2e219a6c021a40b5a20c041dea88c4",slug:"natural-resources-management-and-biological-sciences",bookSignature:"Edward R. Rhodes and Humood Naser",coverURL:"https://cdn.intechopen.com/books/images_new/8985.jpg",editors:[{id:"280886",title:"Prof.",name:"Edward R",middleName:null,surname:"Rhodes",slug:"edward-r-rhodes",fullName:"Edward R Rhodes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9027",title:"Human Blood Group Systems and Haemoglobinopathies",subtitle:null,isOpenForSubmission:!1,hash:"d00d8e40b11cfb2547d1122866531c7e",slug:"human-blood-group-systems-and-haemoglobinopathies",bookSignature:"Osaro Erhabor and Anjana Munshi",coverURL:"https://cdn.intechopen.com/books/images_new/9027.jpg",editors:[{id:"35140",title:null,name:"Osaro",middleName:null,surname:"Erhabor",slug:"osaro-erhabor",fullName:"Osaro Erhabor"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7841",title:"New Insights Into Metabolic Syndrome",subtitle:null,isOpenForSubmission:!1,hash:"ef5accfac9772b9e2c9eff884f085510",slug:"new-insights-into-metabolic-syndrome",bookSignature:"Akikazu Takada",coverURL:"https://cdn.intechopen.com/books/images_new/7841.jpg",editors:[{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8558",title:"Aerodynamics",subtitle:null,isOpenForSubmission:!1,hash:"db7263fc198dfb539073ba0260a7f1aa",slug:"aerodynamics",bookSignature:"Mofid Gorji-Bandpy and Aly-Mousaad Aly",coverURL:"https://cdn.intechopen.com/books/images_new/8558.jpg",editors:[{id:"35542",title:"Prof.",name:"Mofid",middleName:null,surname:"Gorji-Bandpy",slug:"mofid-gorji-bandpy",fullName:"Mofid Gorji-Bandpy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9668",title:"Chemistry and Biochemistry of Winemaking, Wine Stabilization and Aging",subtitle:null,isOpenForSubmission:!1,hash:"c5484276a314628acf21ec1bdc3a86b9",slug:"chemistry-and-biochemistry-of-winemaking-wine-stabilization-and-aging",bookSignature:"Fernanda Cosme, Fernando M. Nunes and Luís Filipe-Ribeiro",coverURL:"https://cdn.intechopen.com/books/images_new/9668.jpg",editors:[{id:"186819",title:"Prof.",name:"Fernanda",middleName:null,surname:"Cosme",slug:"fernanda-cosme",fullName:"Fernanda Cosme"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7847",title:"Medical Toxicology",subtitle:null,isOpenForSubmission:!1,hash:"db9b65bea093de17a0855a1b27046247",slug:"medical-toxicology",bookSignature:"Pınar Erkekoglu and Tomohisa Ogawa",coverURL:"https://cdn.intechopen.com/books/images_new/7847.jpg",editors:[{id:"109978",title:"Prof.",name:"Pınar",middleName:null,surname:"Erkekoglu",slug:"pinar-erkekoglu",fullName:"Pınar Erkekoglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8620",title:"Mining Techniques",subtitle:"Past, Present and Future",isOpenForSubmission:!1,hash:"b65658f81d14e9e57e49377869d3a575",slug:"mining-techniques-past-present-and-future",bookSignature:"Abhay Soni",coverURL:"https://cdn.intechopen.com/books/images_new/8620.jpg",editors:[{id:"271093",title:"Dr.",name:"Abhay",middleName:null,surname:"Soni",slug:"abhay-soni",fullName:"Abhay Soni"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9660",title:"Inland Waters",subtitle:"Dynamics and Ecology",isOpenForSubmission:!1,hash:"975c26819ceb11a926793bc2adc62bd6",slug:"inland-waters-dynamics-and-ecology",bookSignature:"Adam Devlin, Jiayi Pan and Mohammad Manjur Shah",coverURL:"https://cdn.intechopen.com/books/images_new/9660.jpg",editors:[{id:"280757",title:"Dr.",name:"Adam",middleName:"Thomas",surname:"Devlin",slug:"adam-devlin",fullName:"Adam Devlin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9122",title:"Cosmetic Surgery",subtitle:null,isOpenForSubmission:!1,hash:"207026ca4a4125e17038e770d00ee152",slug:"cosmetic-surgery",bookSignature:"Yueh-Bih Tang",coverURL:"https://cdn.intechopen.com/books/images_new/9122.jpg",editors:[{id:"202122",title:"Prof.",name:"Yueh-Bih",middleName:null,surname:"Tang",slug:"yueh-bih-tang",fullName:"Yueh-Bih Tang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"9550",title:"Entrepreneurship",subtitle:"Contemporary Issues",isOpenForSubmission:!1,hash:"9b4ac1ee5b743abf6f88495452b1e5e7",slug:"entrepreneurship-contemporary-issues",bookSignature:"Mladen Turuk",coverURL:"https://cdn.intechopen.com/books/images_new/9550.jpg",editedByType:"Edited by",editors:[{id:"319755",title:"Prof.",name:"Mladen",middleName:null,surname:"Turuk",slug:"mladen-turuk",fullName:"Mladen Turuk"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10065",title:"Wavelet Theory",subtitle:null,isOpenForSubmission:!1,hash:"d8868e332169597ba2182d9b004d60de",slug:"wavelet-theory",bookSignature:"Somayeh Mohammady",coverURL:"https://cdn.intechopen.com/books/images_new/10065.jpg",editedByType:"Edited by",editors:[{id:"109280",title:"Dr.",name:"Somayeh",middleName:null,surname:"Mohammady",slug:"somayeh-mohammady",fullName:"Somayeh Mohammady"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9313",title:"Clay Science and Technology",subtitle:null,isOpenForSubmission:!1,hash:"6fa7e70396ff10620e032bb6cfa6fb72",slug:"clay-science-and-technology",bookSignature:"Gustavo Morari Do Nascimento",coverURL:"https://cdn.intechopen.com/books/images_new/9313.jpg",editedByType:"Edited by",editors:[{id:"7153",title:"Prof.",name:"Gustavo",middleName:null,surname:"Morari Do Nascimento",slug:"gustavo-morari-do-nascimento",fullName:"Gustavo Morari Do Nascimento"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9888",title:"Nuclear Power Plants",subtitle:"The Processes from the Cradle to the Grave",isOpenForSubmission:!1,hash:"c2c8773e586f62155ab8221ebb72a849",slug:"nuclear-power-plants-the-processes-from-the-cradle-to-the-grave",bookSignature:"Nasser Awwad",coverURL:"https://cdn.intechopen.com/books/images_new/9888.jpg",editedByType:"Edited by",editors:[{id:"145209",title:"Prof.",name:"Nasser",middleName:"S",surname:"Awwad",slug:"nasser-awwad",fullName:"Nasser Awwad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8098",title:"Resources of Water",subtitle:null,isOpenForSubmission:!1,hash:"d251652996624d932ef7b8ed62cf7cfc",slug:"resources-of-water",bookSignature:"Prathna Thanjavur Chandrasekaran, Muhammad Salik Javaid, Aftab Sadiq",coverURL:"https://cdn.intechopen.com/books/images_new/8098.jpg",editedByType:"Edited by",editors:[{id:"167917",title:"Dr.",name:"Prathna",middleName:null,surname:"Thanjavur Chandrasekaran",slug:"prathna-thanjavur-chandrasekaran",fullName:"Prathna Thanjavur Chandrasekaran"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9644",title:"Glaciers and the Polar Environment",subtitle:null,isOpenForSubmission:!1,hash:"e8cfdc161794e3753ced54e6ff30873b",slug:"glaciers-and-the-polar-environment",bookSignature:"Masaki Kanao, Danilo Godone and Niccolò Dematteis",coverURL:"https://cdn.intechopen.com/books/images_new/9644.jpg",editedByType:"Edited by",editors:[{id:"51959",title:"Dr.",name:"Masaki",middleName:null,surname:"Kanao",slug:"masaki-kanao",fullName:"Masaki Kanao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10432",title:"Casting Processes and Modelling of Metallic Materials",subtitle:null,isOpenForSubmission:!1,hash:"2c5c9df938666bf5d1797727db203a6d",slug:"casting-processes-and-modelling-of-metallic-materials",bookSignature:"Zakaria Abdallah and Nada Aldoumani",coverURL:"https://cdn.intechopen.com/books/images_new/10432.jpg",editedByType:"Edited by",editors:[{id:"201670",title:"Dr.",name:"Zak",middleName:null,surname:"Abdallah",slug:"zak-abdallah",fullName:"Zak Abdallah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9671",title:"Macrophages",subtitle:null,isOpenForSubmission:!1,hash:"03b00fdc5f24b71d1ecdfd75076bfde6",slug:"macrophages",bookSignature:"Hridayesh Prakash",coverURL:"https://cdn.intechopen.com/books/images_new/9671.jpg",editedByType:"Edited by",editors:[{id:"287184",title:"Dr.",name:"Hridayesh",middleName:null,surname:"Prakash",slug:"hridayesh-prakash",fullName:"Hridayesh Prakash"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8415",title:"Extremophilic Microbes and Metabolites",subtitle:"Diversity, Bioprospecting and Biotechnological Applications",isOpenForSubmission:!1,hash:"93e0321bc93b89ff73730157738f8f97",slug:"extremophilic-microbes-and-metabolites-diversity-bioprospecting-and-biotechnological-applications",bookSignature:"Afef Najjari, Ameur Cherif, Haïtham Sghaier and Hadda Imene Ouzari",coverURL:"https://cdn.intechopen.com/books/images_new/8415.jpg",editedByType:"Edited by",editors:[{id:"196823",title:"Dr.",name:"Afef",middleName:null,surname:"Najjari",slug:"afef-najjari",fullName:"Afef Najjari"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9731",title:"Oxidoreductase",subtitle:null,isOpenForSubmission:!1,hash:"852e6f862c85fc3adecdbaf822e64e6e",slug:"oxidoreductase",bookSignature:"Mahmoud Ahmed Mansour",coverURL:"https://cdn.intechopen.com/books/images_new/9731.jpg",editedByType:"Edited by",editors:[{id:"224662",title:"Prof.",name:"Mahmoud Ahmed",middleName:null,surname:"Mansour",slug:"mahmoud-ahmed-mansour",fullName:"Mahmoud Ahmed Mansour"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"209",title:"Cognitive Neuroscience",slug:"cognitive-neuroscience",parent:{title:"Neuroscience",slug:"life-sciences-neuroscience"},numberOfBooks:11,numberOfAuthorsAndEditors:304,numberOfWosCitations:162,numberOfCrossrefCitations:122,numberOfDimensionsCitations:296,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"cognitive-neuroscience",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"6819",title:"Prefrontal Cortex",subtitle:null,isOpenForSubmission:!1,hash:"903b3a38d3c8196f6a865526c124a6de",slug:"prefrontal-cortex",bookSignature:"Ana Starcevic and Branislav Filipovic",coverURL:"https://cdn.intechopen.com/books/images_new/6819.jpg",editedByType:"Edited by",editors:[{id:"182584",title:"Dr.",name:"Ana",middleName:null,surname:"Starcevic",slug:"ana-starcevic",fullName:"Ana Starcevic"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6614",title:"Alzheimer's Disease",subtitle:"The 21st Century Challenge",isOpenForSubmission:!1,hash:"91df6c15517737c8fb91543f870d484d",slug:"alzheimer-s-disease-the-21st-century-challenge",bookSignature:"Jolanta Dorszewska and Wojciech Kozubski",coverURL:"https://cdn.intechopen.com/books/images_new/6614.jpg",editedByType:"Edited by",editors:[{id:"31962",title:"Dr.",name:"Jolanta",middleName:null,surname:"Dorszewska",slug:"jolanta-dorszewska",fullName:"Jolanta Dorszewska"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6167",title:"Cognitive and Computational Neuroscience",subtitle:"Principles, Algorithms and Applications",isOpenForSubmission:!1,hash:"828beb18d956dedaf19b5a87c8bfb828",slug:"cognitive-and-computational-neuroscience-principles-algorithms-and-applications",bookSignature:"Seyyed Abed Hosseini",coverURL:"https://cdn.intechopen.com/books/images_new/6167.jpg",editedByType:"Edited by",editors:[{id:"86475",title:"Dr.",name:"Seyyed Abed",middleName:null,surname:"Hosseini",slug:"seyyed-abed-hosseini",fullName:"Seyyed Abed Hosseini"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6144",title:"High-Resolution Neuroimaging",subtitle:"Basic Physical Principles and Clinical Applications",isOpenForSubmission:!1,hash:"505b513060f90e61167b5e46e8cd9fea",slug:"high-resolution-neuroimaging-basic-physical-principles-and-clinical-applications",bookSignature:"Ahmet Mesrur Halefoğlu",coverURL:"https://cdn.intechopen.com/books/images_new/6144.jpg",editedByType:"Edited by",editors:[{id:"51736",title:"Prof.",name:"Ahmet Mesrur",middleName:null,surname:"Halefoğlu",slug:"ahmet-mesrur-halefoglu",fullName:"Ahmet Mesrur Halefoğlu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5947",title:"Mechanisms of Neuroinflammation",subtitle:null,isOpenForSubmission:!1,hash:"e4ade830cd06a3aebc5eae0dae96aff2",slug:"mechanisms-of-neuroinflammation",bookSignature:"Gonzalo Emiliano Aranda Abreu",coverURL:"https://cdn.intechopen.com/books/images_new/5947.jpg",editedByType:"Edited by",editors:[{id:"72314",title:"Dr.",name:"Gonzalo Emiliano",middleName:null,surname:"Aranda Abreu",slug:"gonzalo-emiliano-aranda-abreu",fullName:"Gonzalo Emiliano Aranda Abreu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5313",title:"Update on Dementia",subtitle:null,isOpenForSubmission:!1,hash:"6b264ef130a59fe71274c3811750e6c3",slug:"update-on-dementia",bookSignature:"Davide Vito Moretti",coverURL:"https://cdn.intechopen.com/books/images_new/5313.jpg",editedByType:"Edited by",editors:[{id:"147154",title:"Dr.",name:"Davide",middleName:"Vito",surname:"Moretti",slug:"davide-moretti",fullName:"Davide Moretti"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2604",title:"Basal Ganglia",subtitle:"An Integrative View",isOpenForSubmission:!1,hash:"76d19f809182eea657ce36eb4817c5b8",slug:"basal-ganglia-an-integrative-view",bookSignature:"Fernando A. Barrios and Clemens Bauer",coverURL:"https://cdn.intechopen.com/books/images_new/2604.jpg",editedByType:"Edited by",editors:[{id:"147924",title:"Dr.",name:"Fernando A.",middleName:null,surname:"Barrios",slug:"fernando-a.-barrios",fullName:"Fernando A. Barrios"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2599",title:"The Amygdala",subtitle:"A Discrete Multitasking Manager",isOpenForSubmission:!1,hash:"429fa5522790c0837406fd1fed1280bd",slug:"the-amygdala-a-discrete-multitasking-manager",bookSignature:"Barbara Ferry",coverURL:"https://cdn.intechopen.com/books/images_new/2599.jpg",editedByType:"Edited by",editors:[{id:"139945",title:"Dr.",name:"Barbara",middleName:null,surname:"Ferry",slug:"barbara-ferry",fullName:"Barbara Ferry"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2646",title:"Visual Cortex",subtitle:"Current Status and Perspectives",isOpenForSubmission:!1,hash:"8a5632344dfe9b3f0153eeee84a6ea83",slug:"visual-cortex-current-status-and-perspectives",bookSignature:"Stephane Molotchnikoff and Jean Rouat",coverURL:"https://cdn.intechopen.com/books/images_new/2646.jpg",editedByType:"Edited by",editors:[{id:"145800",title:"Prof.",name:"Stephane",middleName:null,surname:"Molotchnikoff",slug:"stephane-molotchnikoff",fullName:"Stephane Molotchnikoff"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"673",title:"Dyslexia",subtitle:"A Comprehensive and International Approach",isOpenForSubmission:!1,hash:"9a88d127d035ab53de96a00f9ed407ba",slug:"dyslexia-a-comprehensive-and-international-approach",bookSignature:"Taeko N. Wydell and Liory Fern-Pollak",coverURL:"https://cdn.intechopen.com/books/images_new/673.jpg",editedByType:"Edited by",editors:[{id:"87489",title:"Prof.",name:"Taeko",middleName:"N.",surname:"Wydell",slug:"taeko-wydell",fullName:"Taeko Wydell"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1069",title:"Paresthesia",subtitle:null,isOpenForSubmission:!1,hash:"c0225cd8274b4384cd1c91e586645958",slug:"paresthesia",bookSignature:"Luiz E. Imbelloni and Marildo A. Gouveia",coverURL:"https://cdn.intechopen.com/books/images_new/1069.jpg",editedByType:"Edited by",editors:[{id:"80284",title:"Dr.",name:"Luiz Eduardo",middleName:null,surname:"Imbelloni",slug:"luiz-eduardo-imbelloni",fullName:"Luiz Eduardo Imbelloni"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:11,mostCitedChapters:[{id:"41589",doi:"10.5772/50323",title:"The Role of the Amygdala in Anxiety Disorders",slug:"the-role-of-the-amygdala-in-anxiety-disorders",totalDownloads:8946,totalCrossrefCites:3,totalDimensionsCites:24,book:{slug:"the-amygdala-a-discrete-multitasking-manager",title:"The Amygdala",fullTitle:"The Amygdala - A Discrete Multitasking Manager"},signatures:"Gina L. Forster, Andrew M. Novick, Jamie L. Scholl and Michael J. Watt",authors:[{id:"145620",title:"Dr.",name:"Gina",middleName:null,surname:"Forster",slug:"gina-forster",fullName:"Gina Forster"},{id:"146553",title:"BSc.",name:"Andrew",middleName:null,surname:"Novick",slug:"andrew-novick",fullName:"Andrew Novick"},{id:"146554",title:"MSc.",name:"Jamie",middleName:null,surname:"Scholl",slug:"jamie-scholl",fullName:"Jamie Scholl"},{id:"146555",title:"Dr.",name:"Michael",middleName:null,surname:"Watt",slug:"michael-watt",fullName:"Michael Watt"}]},{id:"39300",doi:"10.5772/51914",title:"Visual Field Map Organization in Human Visual Cortex",slug:"visual-field-map-organization-in-human-visual-cortex",totalDownloads:3532,totalCrossrefCites:4,totalDimensionsCites:20,book:{slug:"visual-cortex-current-status-and-perspectives",title:"Visual Cortex",fullTitle:"Visual Cortex - Current Status and Perspectives"},signatures:"Alyssa A. Brewer and Brian Barton",authors:[{id:"115304",title:"Dr.",name:"Alyssa",middleName:"A",surname:"Brewer",slug:"alyssa-brewer",fullName:"Alyssa Brewer"},{id:"149246",title:"Dr.",name:"Brian",middleName:null,surname:"Barton",slug:"brian-barton",fullName:"Brian Barton"}]},{id:"41588",doi:"10.5772/48495",title:"The Insular Cortex and the Amygdala: Shared Functions and Interactions",slug:"the-insular-cortex-and-the-amygdala-shared-functions-and-interactions",totalDownloads:4557,totalCrossrefCites:7,totalDimensionsCites:18,book:{slug:"the-amygdala-a-discrete-multitasking-manager",title:"The Amygdala",fullTitle:"The Amygdala - A Discrete Multitasking Manager"},signatures:"Rodrigo Moraga-Amaro and Jimmy Stehberg",authors:[{id:"144923",title:"Dr.",name:"Jimmy",middleName:null,surname:"Stehberg",slug:"jimmy-stehberg",fullName:"Jimmy Stehberg"},{id:"154657",title:"MSc.",name:"Rodrigo",middleName:null,surname:"Moraga-Amaro",slug:"rodrigo-moraga-amaro",fullName:"Rodrigo Moraga-Amaro"}]}],mostDownloadedChaptersLast30Days:[{id:"29764",title:"Underlying Causes of Paresthesia",slug:"underlying-causes-of-paresthesia",totalDownloads:188869,totalCrossrefCites:2,totalDimensionsCites:6,book:{slug:"paresthesia",title:"Paresthesia",fullTitle:"Paresthesia"},signatures:"Mahdi Sharif-Alhoseini, Vafa Rahimi-Movaghar and Alexander R. Vaccaro",authors:[{id:"91165",title:"Prof.",name:"Vafa",middleName:null,surname:"Rahimi-Movaghar",slug:"vafa-rahimi-movaghar",fullName:"Vafa Rahimi-Movaghar"}]},{id:"41589",title:"The Role of the Amygdala in Anxiety Disorders",slug:"the-role-of-the-amygdala-in-anxiety-disorders",totalDownloads:8949,totalCrossrefCites:3,totalDimensionsCites:24,book:{slug:"the-amygdala-a-discrete-multitasking-manager",title:"The Amygdala",fullTitle:"The Amygdala - A Discrete Multitasking Manager"},signatures:"Gina L. Forster, Andrew M. Novick, Jamie L. Scholl and Michael J. Watt",authors:[{id:"145620",title:"Dr.",name:"Gina",middleName:null,surname:"Forster",slug:"gina-forster",fullName:"Gina Forster"},{id:"146553",title:"BSc.",name:"Andrew",middleName:null,surname:"Novick",slug:"andrew-novick",fullName:"Andrew Novick"},{id:"146554",title:"MSc.",name:"Jamie",middleName:null,surname:"Scholl",slug:"jamie-scholl",fullName:"Jamie Scholl"},{id:"146555",title:"Dr.",name:"Michael",middleName:null,surname:"Watt",slug:"michael-watt",fullName:"Michael Watt"}]},{id:"58070",title:"MRI Medical Image Denoising by Fundamental Filters",slug:"mri-medical-image-denoising-by-fundamental-filters",totalDownloads:1907,totalCrossrefCites:8,totalDimensionsCites:13,book:{slug:"high-resolution-neuroimaging-basic-physical-principles-and-clinical-applications",title:"High-Resolution Neuroimaging",fullTitle:"High-Resolution Neuroimaging - Basic Physical Principles and Clinical Applications"},signatures:"Hanafy M. Ali",authors:[{id:"213318",title:"Dr.",name:"Hanafy",middleName:"M.",surname:"Ali",slug:"hanafy-ali",fullName:"Hanafy Ali"}]},{id:"63179",title:"Development Period of Prefrontal Cortex",slug:"development-period-of-prefrontal-cortex",totalDownloads:2590,totalCrossrefCites:5,totalDimensionsCites:5,book:{slug:"prefrontal-cortex",title:"Prefrontal Cortex",fullTitle:"Prefrontal Cortex"},signatures:"Merve Cikili Uytun",authors:[{id:"163607",title:"Ms.",name:"Merve",middleName:null,surname:"Cikili",slug:"merve-cikili",fullName:"Merve Cikili"}]},{id:"41582",title:"Traumatic Experiences Disrupt Amygdala – Prefrontal Connectivity",slug:"traumatic-experiences-disrupt-amygdala-prefrontal-connectivity",totalDownloads:4920,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"the-amygdala-a-discrete-multitasking-manager",title:"The Amygdala",fullTitle:"The Amygdala - A Discrete Multitasking Manager"},signatures:"Dong Hoon Oh",authors:[{id:"147834",title:"Prof.",name:"Dong Hoon",middleName:null,surname:"Oh",slug:"dong-hoon-oh",fullName:"Dong Hoon Oh"}]},{id:"52048",title:"Beta Amyloid Peptides: Extracellular and Intracellular Mechanisms of Clearance in Alzheimer’s Disease",slug:"beta-amyloid-peptides-extracellular-and-intracellular-mechanisms-of-clearance-in-alzheimer-s-disease",totalDownloads:1704,totalCrossrefCites:4,totalDimensionsCites:8,book:{slug:"update-on-dementia",title:"Update on Dementia",fullTitle:"Update on Dementia"},signatures:"Luis F. Hernández-Zimbrón, Elisa Gorostieta-Salas, Mei-Li Díaz-\nHung, Roxanna Pérez-Garmendia, Gohar Gevorkian and Hugo\nQuiroz-Mercado",authors:[{id:"75951",title:"BSc.",name:"Hugo",middleName:null,surname:"Quiroz-Mercado",slug:"hugo-quiroz-mercado",fullName:"Hugo Quiroz-Mercado"},{id:"181180",title:"Dr.",name:"Luis Fernando",middleName:null,surname:"Hernandez-Zimbron",slug:"luis-fernando-hernandez-zimbron",fullName:"Luis Fernando Hernandez-Zimbron"},{id:"181277",title:"Dr.",name:"Roxanna",middleName:null,surname:"Pérez-Garmendia",slug:"roxanna-perez-garmendia",fullName:"Roxanna Pérez-Garmendia"},{id:"181278",title:"BSc.",name:"Elisa",middleName:null,surname:"Gorostieta-Salas",slug:"elisa-gorostieta-salas",fullName:"Elisa Gorostieta-Salas"},{id:"181279",title:"MSc.",name:"Mei-Li",middleName:null,surname:"Díaz-Hung",slug:"mei-li-diaz-hung",fullName:"Mei-Li Díaz-Hung"},{id:"190226",title:"Dr.",name:"Gohar",middleName:null,surname:"Gevorkian-Markosian",slug:"gohar-gevorkian-markosian",fullName:"Gohar Gevorkian-Markosian"}]},{id:"51676",title:"Neuroinflammation and Neurodegeneration",slug:"neuroinflammation-and-neurodegeneration",totalDownloads:2687,totalCrossrefCites:4,totalDimensionsCites:7,book:{slug:"update-on-dementia",title:"Update on Dementia",fullTitle:"Update on Dementia"},signatures:"Inelia Morales, Gonzalo A. Farías, Nicole Cortes and Ricardo B.\nMaccioni",authors:[{id:"137002",title:"Dr.",name:"Gonzalo",middleName:null,surname:"Farias",slug:"gonzalo-farias",fullName:"Gonzalo Farias"},{id:"183194",title:"Dr.",name:"Ricardo",middleName:"Benjamín",surname:"Maccioni",slug:"ricardo-maccioni",fullName:"Ricardo Maccioni"},{id:"183196",title:"MSc.",name:"Inelia",middleName:null,surname:"Morales",slug:"inelia-morales",fullName:"Inelia Morales"},{id:"183197",title:"MSc.",name:"Nicole",middleName:null,surname:"Cortes",slug:"nicole-cortes",fullName:"Nicole Cortes"}]},{id:"41580",title:"Auditory Fear Circuits in the Amygdala – Insights from Computational Models",slug:"auditory-fear-circuits-in-the-amygdala-insights-from-computational-models",totalDownloads:2374,totalCrossrefCites:0,totalDimensionsCites:1,book:{slug:"the-amygdala-a-discrete-multitasking-manager",title:"The Amygdala",fullTitle:"The Amygdala - A Discrete Multitasking Manager"},signatures:"Satish S. Nair",authors:[{id:"147227",title:"Dr.",name:"Satish S.",middleName:null,surname:"Nair",slug:"satish-s.-nair",fullName:"Satish S. Nair"}]},{id:"57618",title:"Basics of Chemical Exchange Saturation Transfer (CEST) Magnetic Resonance Imaging",slug:"basics-of-chemical-exchange-saturation-transfer-cest-magnetic-resonance-imaging",totalDownloads:1234,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"high-resolution-neuroimaging-basic-physical-principles-and-clinical-applications",title:"High-Resolution Neuroimaging",fullTitle:"High-Resolution Neuroimaging - Basic Physical Principles and Clinical Applications"},signatures:"Kenya Murase",authors:[{id:"213859",title:"Prof.",name:"Kenya",middleName:null,surname:"Murase",slug:"kenya-murase",fullName:"Kenya Murase"}]},{id:"51705",title:"Non-Pharmacological Approaches in the Treatment of Dementia",slug:"non-pharmacological-approaches-in-the-treatment-of-dementia",totalDownloads:2096,totalCrossrefCites:0,totalDimensionsCites:7,book:{slug:"update-on-dementia",title:"Update on Dementia",fullTitle:"Update on Dementia"},signatures:"Grazia D’Onofrio, Daniele Sancarlo, Davide Seripa, Francesco\nRicciardi, Francesco Giuliani, Francesco Panza and Antonio Greco",authors:[{id:"184079",title:"Dr.",name:"Daniele",middleName:null,surname:"Sancarlo",slug:"daniele-sancarlo",fullName:"Daniele Sancarlo"},{id:"184080",title:"Dr.",name:"Grazia",middleName:null,surname:"D’Onofrio",slug:"grazia-d'onofrio",fullName:"Grazia D’Onofrio"},{id:"184081",title:"Dr.",name:"Antonio",middleName:null,surname:"Greco",slug:"antonio-greco",fullName:"Antonio Greco"}]}],onlineFirstChaptersFilter:{topicSlug:"cognitive-neuroscience",limit:3,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[{type:"book",id:"10176",title:"Microgrids and Local Energy Systems",subtitle:null,isOpenForSubmission:!0,hash:"c32b4a5351a88f263074b0d0ca813a9c",slug:null,bookSignature:"Prof. Nick Jenkins",coverURL:"https://cdn.intechopen.com/books/images_new/10176.jpg",editedByType:null,editors:[{id:"55219",title:"Prof.",name:"Nick",middleName:null,surname:"Jenkins",slug:"nick-jenkins",fullName:"Nick Jenkins"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:8,limit:8,total:1},route:{name:"chapter.detail",path:"/books/recent-advances-in-liver-diseases-and-surgery/hepatitis-c-overview-and-update-in-treatment",hash:"",query:{},params:{book:"recent-advances-in-liver-diseases-and-surgery",chapter:"hepatitis-c-overview-and-update-in-treatment"},fullPath:"/books/recent-advances-in-liver-diseases-and-surgery/hepatitis-c-overview-and-update-in-treatment",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()