Treatment modalities that have been used in patients with sickle cell disease and leg ulcers.
\\n\\n
More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n\n\n
\n'}],latestNews:[{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"},{slug:"intechopen-s-chapter-awarded-the-guenther-von-pannewitz-preis-2020-20200715",title:"IntechOpen's Chapter Awarded the Günther-von-Pannewitz-Preis 2020"},{slug:"suf-and-intechopen-announce-collaboration-20200331",title:"SUF and IntechOpen Announce Collaboration"}]},book:{item:{type:"book",id:"2238",leadTitle:null,fullTitle:"Pain in Perspective",title:"Pain in Perspective",subtitle:null,reviewType:"peer-reviewed",abstract:'Pain has been there since man has existed and whatever the method or technique of its relief, if successful will always lead to a special place in the heart of the person receiving it and also to the person delivering it. "Pain in Perspective" takes us into a journey of how it all began and then leads us to understand the various concepts of pain relief today. From musculoskeletal pain to complex shoulder pain and from neurological examination to charting out pain, this book describes new ideas and latest descriptions of pain concepts and their treatment.',isbn:null,printIsbn:"978-953-51-0807-8",pdfIsbn:"978-953-51-7037-2",doi:"10.5772/2627",price:119,priceEur:129,priceUsd:155,slug:"pain-in-perspective",numberOfPages:268,isOpenForSubmission:!1,isInWos:1,hash:"44376b5b3eb5a33870e0c842185ef477",bookSignature:"Subhamay Ghosh",publishedDate:"October 24th 2012",coverURL:"https://cdn.intechopen.com/books/images_new/2238.jpg",numberOfDownloads:28022,numberOfWosCitations:18,numberOfCrossrefCitations:14,numberOfDimensionsCitations:48,hasAltmetrics:1,numberOfTotalCitations:80,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"December 6th 2011",dateEndSecondStepPublish:"January 10th 2012",dateEndThirdStepPublish:"April 15th 2012",dateEndFourthStepPublish:"July 14th 2012",dateEndFifthStepPublish:"August 13th 2012",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,editors:[{id:"49582",title:"Mr.",name:"Subhamay",middleName:null,surname:"Ghosh",slug:"subhamay-ghosh",fullName:"Subhamay Ghosh",profilePictureURL:"https://mts.intechopen.com/storage/users/49582/images/3575_n.png",biography:"a",institutionString:null,position:"a",outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"1",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1116",title:"Algiatry",slug:"algiatry"}],chapters:[{id:"40394",title:"Introduction to Pain, Religion and Analgesia",doi:"10.5772/53922",slug:"introduction-to-pain-religion-and-analgesia",totalDownloads:2014,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Subhamay Ghosh",downloadPdfUrl:"/chapter/pdf-download/40394",previewPdfUrl:"/chapter/pdf-preview/40394",authors:[{id:"49582",title:"Mr.",name:"Subhamay",surname:"Ghosh",slug:"subhamay-ghosh",fullName:"Subhamay Ghosh"}],corrections:null},{id:"40392",title:"Work-Related Upper Limb Pain and Its Diagnosis: Contribution from the Neurological Examination",doi:"10.5772/50884",slug:"work-related-upper-limb-pain-and-its-diagnosis-contribution-from-the-neurological-examination",totalDownloads:1447,totalCrossrefCites:0,totalDimensionsCites:1,signatures:"Jørgen Riis Jepsen",downloadPdfUrl:"/chapter/pdf-download/40392",previewPdfUrl:"/chapter/pdf-preview/40392",authors:[{id:"143553",title:"Prof.",name:"Jørgen R",surname:"Jepsen",slug:"jorgen-r-jepsen",fullName:"Jørgen R Jepsen"}],corrections:null},{id:"40388",title:"Autonomic Regulation in Musculoskeletal Pain",doi:"10.5772/51086",slug:"autonomic-regulation-in-musculoskeletal-pain",totalDownloads:3398,totalCrossrefCites:0,totalDimensionsCites:2,signatures:"David M. Hallman and Eugene Lyskov",downloadPdfUrl:"/chapter/pdf-download/40388",previewPdfUrl:"/chapter/pdf-preview/40388",authors:[{id:"142718",title:"Ph.D. Student",name:"David",surname:"Hallman",slug:"david-hallman",fullName:"David Hallman"},{id:"148936",title:"Dr.",name:"Eugene",surname:"Lyskov",slug:"eugene-lyskov",fullName:"Eugene Lyskov"}],corrections:null},{id:"40391",title:"Work Related Musculoskeletal Pain and It’s Management",doi:"10.5772/51706",slug:"work-related-musculoskeletal-pain-and-it-s-management",totalDownloads:1916,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"David McBride and Helen Harcombe",downloadPdfUrl:"/chapter/pdf-download/40391",previewPdfUrl:"/chapter/pdf-preview/40391",authors:[{id:"139640",title:"Dr.",name:"David",surname:"McBride",slug:"david-mcbride",fullName:"David McBride"}],corrections:null},{id:"40386",title:"Management of Chronic Musculoskeletal Pain in the Elderly: Dilemmas and Remedies",doi:"10.5772/50780",slug:"management-of-chronic-musculoskeletal-pain-in-the-elderly-dilemmas-and-remedies",totalDownloads:2248,totalCrossrefCites:0,totalDimensionsCites:3,signatures:"Ayse Ozcan Edeer and Hulya Tuna",downloadPdfUrl:"/chapter/pdf-download/40386",previewPdfUrl:"/chapter/pdf-preview/40386",authors:[{id:"143831",title:"Ph.D.",name:"Ayse",surname:"Ozcan Edeer",slug:"ayse-ozcan-edeer",fullName:"Ayse Ozcan Edeer"},{id:"145522",title:"Dr.",name:"Hulya",surname:"Tuna",slug:"hulya-tuna",fullName:"Hulya Tuna"}],corrections:null},{id:"40389",title:"Shoulder Pain in Swimmers",doi:"10.5772/51013",slug:"shoulder-pain-in-swimmers",totalDownloads:5362,totalCrossrefCites:1,totalDimensionsCites:3,signatures:"Julio José Contreras Fernández, Rodrigo Liendo Verdugo, Matías Osorio Feito and Francisco Soza Rex",downloadPdfUrl:"/chapter/pdf-download/40389",previewPdfUrl:"/chapter/pdf-preview/40389",authors:[{id:"139621",title:"M.D.",name:"Julio",surname:"Contreras Fernández",slug:"julio-contreras-fernandez",fullName:"Julio Contreras Fernández"},{id:"144361",title:"Dr.",name:"Rodrigo",surname:"Liendo",slug:"rodrigo-liendo",fullName:"Rodrigo Liendo"},{id:"144362",title:"Dr.",name:"Francisco",surname:"Soza Rex",slug:"francisco-soza-rex",fullName:"Francisco Soza Rex"},{id:"155330",title:"Mr.",name:"Matías",surname:"Osorio Feito",slug:"matias-osorio-feito",fullName:"Matías Osorio Feito"}],corrections:null},{id:"40393",title:"The Epidemiology of Shoulder Pain: A Narrative Review of the Literature",doi:"10.5772/52931",slug:"the-epidemiology-of-shoulder-pain-a-narrative-review-of-the-literature",totalDownloads:3755,totalCrossrefCites:7,totalDimensionsCites:25,signatures:"Mario Pribicevic",downloadPdfUrl:"/chapter/pdf-download/40393",previewPdfUrl:"/chapter/pdf-preview/40393",authors:[{id:"141285",title:"Dr.",name:"Mario",surname:"Pribicevic",slug:"mario-pribicevic",fullName:"Mario Pribicevic"}],corrections:null},{id:"40387",title:"Knee Pain in Adults & Adolescents, Diagnosis and Treatment",doi:"10.5772/51077",slug:"knee-pain-in-adults-adolescents-diagnosis-and-treatment",totalDownloads:2726,totalCrossrefCites:1,totalDimensionsCites:1,signatures:"Sherif Hosny, W. McClatchie, Nidhi Sofat and Caroline B. Hing",downloadPdfUrl:"/chapter/pdf-download/40387",previewPdfUrl:"/chapter/pdf-preview/40387",authors:[{id:"67197",title:"Dr.",name:"Nidhi",surname:"Sofat",slug:"nidhi-sofat",fullName:"Nidhi Sofat"},{id:"142675",title:"Ms.",name:"Caroline",surname:"Hing",slug:"caroline-hing",fullName:"Caroline Hing"},{id:"155303",title:"Mr.",name:"Sherif",surname:"Hosny",slug:"sherif-hosny",fullName:"Sherif Hosny"},{id:"155304",title:"Mr.",name:"William",surname:"McClatchie",slug:"william-mcclatchie",fullName:"William McClatchie"}],corrections:null},{id:"40395",title:"Physical and Psychological Aspects of Pain in Obstetrics",doi:"10.5772/53923",slug:"physical-and-psychological-aspects-of-pain-in-obstetrics",totalDownloads:3534,totalCrossrefCites:1,totalDimensionsCites:8,signatures:"Longinus N. Ebirim, Omiepirisa Yvonne Buowari and Subhamay Ghosh",downloadPdfUrl:"/chapter/pdf-download/40395",previewPdfUrl:"/chapter/pdf-preview/40395",authors:[{id:"49582",title:"Mr.",name:"Subhamay",surname:"Ghosh",slug:"subhamay-ghosh",fullName:"Subhamay Ghosh"},{id:"151696",title:"Dr.",name:"Dabota",surname:"Buowari",slug:"dabota-buowari",fullName:"Dabota Buowari"}],corrections:null},{id:"40390",title:"A Novel Application of Virtual Reality for Pain Control: Virtual Reality-Mirror Visual Feedback Therapy",doi:"10.5772/51139",slug:"a-novel-application-of-virtual-reality-for-pain-control-virtual-reality-mirror-visual-feedback-thera",totalDownloads:1624,totalCrossrefCites:4,totalDimensionsCites:5,signatures:"Kenji Sato, Satoshi Fukumori, Kantaro Miyake, Daniel Obata, Akio Gofuku and Kiyoshi Morita",downloadPdfUrl:"/chapter/pdf-download/40390",previewPdfUrl:"/chapter/pdf-preview/40390",authors:[{id:"135353",title:"Prof.",name:"Kiyoshi",surname:"Morita",slug:"kiyoshi-morita",fullName:"Kiyoshi Morita"},{id:"143812",title:"Dr.",name:"Kenji",surname:"Sato",slug:"kenji-sato",fullName:"Kenji Sato"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},relatedBooks:[{type:"book",id:"3850",title:"Pain and Treatment",subtitle:null,isOpenForSubmission:!1,hash:"6df930f2bfb1fbedd1df37ee6b0f8d22",slug:"pain-and-treatment",bookSignature:"Gabor B. Racz and Carl E. Noe",coverURL:"https://cdn.intechopen.com/books/images_new/3850.jpg",editedByType:"Edited by",editors:[{id:"91492",title:"Dr.",name:"Gabor",surname:"Racz",slug:"gabor-racz",fullName:"Gabor Racz"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7897",title:"From Conventional to Innovative Approaches for Pain Treatment",subtitle:null,isOpenForSubmission:!1,hash:"b919454f06566215ea6a94c2d45239cc",slug:"from-conventional-to-innovative-approaches-for-pain-treatment",bookSignature:"Marco Cascella",coverURL:"https://cdn.intechopen.com/books/images_new/7897.jpg",editedByType:"Edited by",editors:[{id:"199335",title:"Dr.",name:"Marco",surname:"Cascella",slug:"marco-cascella",fullName:"Marco Cascella"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7289",title:"Pain Management in Special Circumstances",subtitle:null,isOpenForSubmission:!1,hash:"4043c5c08f3764c0de2d283a40d07c3c",slug:"pain-management-in-special-circumstances",bookSignature:"Nabil A. Shallik",coverURL:"https://cdn.intechopen.com/books/images_new/7289.jpg",editedByType:"Edited by",editors:[{id:"202782",title:"Dr.",name:"Nabil A.",surname:"Shallik",slug:"nabil-a.-shallik",fullName:"Nabil A. Shallik"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{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"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,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"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,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"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,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"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,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"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,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"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,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"}],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:"10786",leadTitle:null,title:"Squamous Cell Carcinoma",subtitle:null,reviewType:"peer-reviewed",abstract:"This book will be a self-contained collection of scholarly papers targeting an audience of practicing researchers, academics, PhD students and other scientists. The contents of the book will be written by multiple authors and edited by experts in the field.",isbn:null,printIsbn:null,pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,hash:"e143cb2e3fda9b3f4c97d7b6611f1b7c",bookSignature:"",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10786.jpg",keywords:null,numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 28th 2020",dateEndSecondStepPublish:"November 18th 2020",dateEndThirdStepPublish:"January 17th 2021",dateEndFourthStepPublish:"April 7th 2021",dateEndFifthStepPublish:"June 6th 2021",remainingDaysToSecondStep:"2 months",secondStepPassed:!0,currentStepOfPublishingProcess:1,editedByType:null,kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"16",title:"Medicine",slug:"medicine"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:null},relatedBooks:[{type:"book",id:"6550",title:"Cohort Studies in Health Sciences",subtitle:null,isOpenForSubmission:!1,hash:"01df5aba4fff1a84b37a2fdafa809660",slug:"cohort-studies-in-health-sciences",bookSignature:"R. Mauricio Barría",coverURL:"https://cdn.intechopen.com/books/images_new/6550.jpg",editedByType:"Edited by",editors:[{id:"88861",title:"Dr.",name:"René Mauricio",surname:"Barría",slug:"rene-mauricio-barria",fullName:"René Mauricio Barría"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{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"}}]},chapter:{item:{type:"chapter",id:"51543",title:"Leg Ulceration in Sickle Cell Disease: An Early and Visible Sign of End‐Organ Disease",doi:"10.5772/64234",slug:"leg-ulceration-in-sickle-cell-disease-an-early-and-visible-sign-of-end-organ-disease",body:'\n
The first patient with SCD described in the English medical literature more than 100 years ago suffered from leg ulceration [1, 2, 4–7, 9]; however, it was not until 1939 that the causal role of SCD in leg ulceration was established [3].
\nLeg ulcers are a frequent and debilitating complication of sickle cell disease, particularly of the SS genotype. The prevalence of leg ulcers in patients with sickle cell disease (SCD) varies geographically widely ranging from 75% in Jamaica to 1% in Saudi Arabia [4–5]. In the Cooperative Study of Sickle Cell Disease (CSSCD) in the United States, the overall prevalence was 2.5%, in persons 10 years of age and older and was higher in patients with SS disease (4.97%) and SS‐alpha thalassemia (3.92%) compared to patients with SC disease and SS‐beta thalassemia [6]. However, over 70% of the study population was under the age of 30 years, and along with improved survival of SCD patients, the prevalence of leg ulcers is likely to be much higher. In a sickle cell clinic in West Indies, 58% had a history of leg ulcers out of 102 patients who survived beyond 60 years of age [8]. About 20% of the 505 patients screened at the National Institutes of Health (NIH) recalled having had an ulcer [9]. The incidence of leg ulcers in sickle cell patients is hard to elucidate given the lack of any recent large prospective trials. The incidence of leg ulcers in patients with SS genotype was 9.97/100 persons in the Cooperative Study of Sickle Cell Disease [6]. In comparison, the prevalence of venous ulcers in the general population in the United States is approximately 600,000 annually [10] with 1% of the population is affected at any given time. Thus, the incidence of leg ulcers in patients with SCD exceeds that of the general population by more than tenfold and also occurs at a younger age.
\nThe striking geographic differences in leg ulcer prevalence may be attributed in part to the differing age structure of the studied populations; however, there does seem to be a difference even after adjusting for age. Different SCD haplotypes differ in their clinical severity. The Bantu haplotype usually has more severe clinical manifestations compared to others; however, there exists a considerable variation within haplotypes as well [11]. Leg ulcers have been reported to be more common in carriers of the CAR beta‐globin gene cluster haplotype [12]. Among patients who have the Asian haplotype, leg ulceration is rare among adults in both the eastern province of Saudi Arabia [5, 13] and central India [4, 14]. Though not yet defined, environmental, socioeconomic, and genetic factors are most likely responsible for the variations in incidence.
\nStudies from Jamaica and personal observations indicate that leg ulcers’ first occurrence is rare before 10 years of age, is most frequently seen between 10 and 25 years of age, and continues to increase in frequency after 30 years [2, 4]. In the CSSCD, incidence increased sharply after second decade of life, ranging from 14.59 to 19.17 in hemoglobin SS patients and from 7.57 to 11.13 in patients with hemoglobin SS‐alpha thalassemia [6].
\nSome studies found a male preponderance with the rates being 15 and 5/100 person‐years in men and women, respectively, in the CSSCD cohort [6]. Similar patterns were observed in Ghana [15]. However, no difference was seen in studies from Nigeria and Jamaica [4] nor in more recent reports [12].
\nThe prevalence of leg ulcers is higher in patients with SS and SS‐alpha thalassemia than among those with SC, SB+, or SB0 genotypes. Alpha thalassemia with two alpha gene deletions seems to be protective against development of leg ulcers in patients with sickle cell disease [6]. In CSSCD, incidence of leg ulcers was significantly lower in SS patients with two alpha gene deletions compared to patients with SS disease and SS patients with three alpha gene deletions. More recent data have shown that alpha thalassemia (one gene deletion) is not protective [12].
\nData from CSSCD suggest that higher hemoglobin level as well as higher fetal hemoglobin percentage is protective against development of leg ulcers in SS patients, whereas only fetal hemoglobin is protective in SS‐ alpha thalassemia patients [6].
\nIncidence of leg ulcers was 43.2 events per 100 person‐years in patients with hemoglobin levels <6 g and 2.4 events per 100 person‐years in patients with hemoglobin >12 g.
\nIn both genotypes, the incidence of leg ulcers decreased with an increase in fetal hemoglobin. Incidence was 0.7/100 person‐years in patients with HbF levels of >10% compared to 13/100 person‐years in patients with HbF levels of <5%. Most recent series [12, 16] did not show a relationship between HbF and leg ulcers. Of note is that the latter study included individuals that received hydroxyurea (HU) therapy and whose elevated HbF levels were not constitutional, but induced by the use of this drug. Patients did not enjoy its protecting effects since birth, as in the case of the older studies. Furthermore, hydroxyurea\'s other (negative) effects on angiogenesis could have blunted the benefits of high hemoglobin F.
\nSickle cell disease is characterized by vasoocclusion. The rigid deformed sickle cells get entrapped in the microcirculation leading to hyperviscosity, decreased blood flow through venules and capillaries, and chronic hemolysis resulting in anemia, ischemia‐reperfusion injury, and inflammation causing end‐organ damage [4]. Studies have shown that the hematocrit to viscosity ratio as well as red blood cell (RBC) deformability was reduced in sickle cell patients with leg ulcers [17, 18]. The marginal circulation of the malleoli is particularly susceptible to this obstruction of microcirculation, making them the most common site for sickle cell leg ulcers.
\nNitrogen oxide (NO) is a natural occurring free radical found in plasma. Receptors for NO present on the endothelium initiate relaxation of vascular smooth muscle causing vasodilation and increased blood flow along with reduced neutrophil adhesion. Chronic hemolysis is a hallmark of SCD and results in red blood cell (RBC) membrane damage, cell breakdown, and extrusion of free hemoglobin into plasma. This free hemoglobin scavenges NO, reducing its bioavailability and thus linked to hemolysis‐vascular dysfunction syndrome which is characterized by chronic vasoconstriction contributing to leg ulcers, priapism, and pulmonary hypertension [19, 20].
\nAn early study of 16 SCD patients with leg ulcers using manometry and the Doppler studies failed to demonstrate venous insufficiency as a primary factor in development of leg ulcers in SCD [21]. However, edema and pain often precede ulceration in these patients, and numerous studies since then have linked venous stasis with sickle cell leg ulcers [7]. Venous stasis in the calf muscles was suggested by the delayed clearance of 99mTc [22] and by magnetic resonance spectroscopy studies [23] in SS patients with leg ulcers as compared with those without.
\nMohan et al. described reduced venous refilling time and cutaneous red blood cell flux recovery time after exercise in patients with SS disease with leg ulcers compared to SS and AA patients without ulcers. They proposed incompetence in venous valves around the ankle resulting in venous hypertension and development as well as delayed healing of leg ulcers [24]. The Jamaican cohort study of 183 SS and 137 age‐ and sex‐matched AA controls showed significant association of venous incompetence and leg ulcers in SCD. Contributing factors were hypothesized to include sluggish circulation with dependency, turbidity and impaired linear flow at venous valves, hypoxia‐induced sickling, rheological effects of high white cell counts, and activation of coagulation cascade [25]. Cummings et al. obtained similar results in 2007 with venous incompetence significantly linked to development of leg ulcers in SCD [26]. Minniti et al. used laser speckle contrast imaging (LSCI) and infrared (IR) thermography to study regional blood flow of ulcer beds. The presence of venostasis was confirmed by their finding of increased number of blood vessels with fibrin thrombi and vascular occlusion [16]. Cutaneous hemosiderosis, dermatosclerosis, and prominent superficial veins are frequently found in SCD patients and further support the role of venostasis in the pathogenesis of leg ulcers. Further clinical evidence comes from the fact that ulcers tend to worsen on prolonged standing and improve with bed rest and compression therapy [7, 16, 25, 26].
\nMicroscopic analysis of skin biopsies. Evidence of increase in vascularity, chronic inflammation, vasculopathy with blood vessels occlusion, fibrin deposition in the intima, and microthrombi. Panel A: Scanning magnification view of the skin punch biopsy showing edge of an ulcer from the right ankle of patient MD. The epidermal changes adjacent to the ulcer are characterized by acanthosis, hyperkeratosis, and attenuated rete ridges. There are increased vascularity and inflammation in the dermis (H&E, 100× original magnification). Panel B: The histological changes subjacent to the ulcer bed are characterized by chronically inflamed granulation tissue with vasculopathic changes involving some of the small blood vessels (H&E, 200× original magnification). Panel C: High magnification view of the superficial dermal vessels peripheral to the ulcer shows proliferation of thick‐walled capillaries and venules, consistent with chronic stasis. There is a lymphoplasmacytic inflammatory infiltrate in the dermis (H&E, 400× original magnification). Panels D–F: Very high magnification view of involved vessels subjacent to the ulcer bed reveals eosinophilic fibrin deposits within the vessel wall and partial occlusion of the vascular lumen (H&E, 600× original magnification). Panel G: Scanning magnification view of the skin punch biopsy obtained from the right dorsal foot of patient DD shows vasculopathic changes involving a cluster of small blood vessel in the deep dermis (H&E, 40× original magnification). Panel H: High magnification view of the involved vessels reveals eosinophilic fibrin deposits within the vessel wall associated with intimal hyperplasia and narrowing of the vascular lumen (H&E, 400× original magnification). Reproduced with permission from Minniti et al. [16].
Ischemic injury caused by microvascular occlusion by sickle cells initiates a pro‐inflammatory and procoagulant cascade that is initiated by the upregulation of RBC integrins. This is followed by RBC adhesion to the endothelium, platelet aggregation, and granulocyte recruitment with the release of pro‐inflammatory cytokines [27]. The cycle of vessel obstruction and ischemic injury is hence perpetuated, culminating in further end‐organ damage. Minniti et al. provided histopathologic evidence of vasculopathy characterized by mural fibrin thrombi causing luminal narrowing and progressive vascular occlusion in small vessels in ulcer beds of SCD patients with leg ulcers [16] (Figure 1). Earlier studies also alluded to the procoagulant state in SCD patients including elevated levels of factor VIII and low levels of antithrombin III and prothrombin complexes [28, 29]. SCD ulcer patients have higher levels of soluble ICAM‐1 and the key inflammatory cytokine IL‐1 beta [30]. Oxidative stress has been shown to play a role in leg ulcer pathogenesis in sickle cell patients, and patients with glutathione S‐transferase polymorphism (GSTM1 and GSTT1 null phenotypes) have been shown to have a high risk of developing ulcers [31].
\nCardiac output is increased in patients with SS disease, and this may affect the distribution of peripheral blood flow and reflex vascular responses [4]. Normal microcirculation of the lower extremity (LE) is characterized by the venoarteriolar vasoconstriction reflex and the disappearance of vasomotion in the dependent position. It was noted that the venoarteriolar reflex was abolished and vasomotion preserved in the dependent position of the leg in SCD patients [32]. In addition to a high resting perfusion in patients with SCD to maintain normal integrity of cutaneous tissue, there occurs a pronounced vasoconstriction on dependency that exacerbates ischemia and pain, delays healing, and promotes recurrence of leg ulcers [7, 33].
\nThe role of bacteria in the pathogenesis of leg ulcers is uncertain. Secondary bacterial colonization is inevitable and usually not considered to be clinically significant. Commonly isolated bacteria in African reports include Staphylococcus aureus, beta‐hemolytic Streptococci, Pseudomonas aeruginosa, and Salmonella. Anaerobes comprised >50% of isolated bacteria in an African series, whereas bacterial flora is predominantly aerobic and polymicrobial in Jamaican reports. Bacterial colonization although unlikely to initiate ulceration may contribute to persistent inflammation of surrounding tissue that results in delayed healing [7]. Baum et al. reported improved healing with topical antibiotics; however, this carries the risks of bacterial resistance, contact sensitization, and disruption of wound moisture balance [7]. Researchers no longer rely solely on culture for identification of bacteria and are utilizing sophisticated sequencing techniques to elucidate the full diversity of microbial communities on the human body [34]. The ulcer skin microbiome, which has been thought only as a commensal on healthy skin, can contribute to delayed healing of ulcers in patients with sickle cell disease by causing excessive activation of both the innate and adaptive immune systems [35]. Emerging data from the study of diabetic wounds shows that the diversity of the skin microbiome correlates with ulcer characteristics [36], and it is likely that similar mechanisms are at play in sickle cell leg ulcers that may explain the variability in their occurrence.
\nStudies suggest that the expression of certain genes may contribute to the development of leg ulcers in SCD; however, the data on genetic associations with leg ulcers remains limited [12].
\nOfusu et al. published a study of 9 cases and 29 controls in 1987 suggesting a possible association of HLA‐B35 and CW14 alleles, with carriers of both alleles having a 17‐fold increased risk of developing leg ulcers. This study was limited due to its small size as well as the identified region being hard to study due to long‐range disequilibrium [12, 37].
\nAnother candidate gene study of 243 cases and 516 controls from the CSSCD by Nolan et al. identified associations with single nucleotide polymorphisms (SNPs) in Klotho (promotes endothelial NO production), TEK (involved in angiogenesis), and numerous genes in the transforming growth factor‐β (TGF‐β)/BMP pathway (modulates angiogenesis and wound healing) [38].
\nSome of the same SNPs have been reported to be associated with risk of stroke, pulmonary hypertension, and priapism, further supporting the observation that leg ulcers are often associated with other sickle cell sub‐phenotypes [12].
\nPreliminary results from genome‐wide association studies of 219 cases and 1180 controls from the CSSCD identified 30 SNPs associated with leg ulcer. It also showed that a cluster of genes in the MHC III region of chromosome 6 to be highly associated with leg ulcers [12]. A cross‐sectional study identified that an SNP in IL‐6, a pro‐inflammatory cytokine, was associated with higher likelihood of leg ulcer and retinopathy [39].
\nProposed simplified mechanism of sickle cell ulcer pathogenesis. Reproduced and modified with permission from Minniti et al. [2].
Minniti and Kato proposed a stepwise, multifactorial model for SCD ulcer pathogenesis (see Figure 2) that depicts an interplay between poor nutrition, low BMI, skin injury, inflammation, thrombosis, hemolysis, vasculopathy, neuropathy, and poor socioeconomic status [2, 9, 16, 29, 33, 40].
\nUlcer onset can be traumatic or spontaneous. Trauma accounts for approximately half the cases, which are incited by relatively insignificant physical damage such as scratches, abrasions, and animal or insect bites. In spontaneous ulcers, there is no history of trauma, but a lesion develops within the dermis often with surrounding induration and hyperpigmentation [7]. Initially, lesions may be covered by an intact epidermis, which then breaks down forming small, deep, and painful ulcers. Spontaneous ulcers are thought to originate from skin infarction. Ulcers occur initially in the second decade of life, around 18–20 years of age. The occurrence of a de novo ulcer in older patients is not common, unless the patient had an ulcer before.
\nLeg ulcers most frequently affect the skin around the medial or lateral malleoli but can also occur on the anterior shin or dorsum of the foot [4] and occasionally in the digits [Minniti, personal observation]. The predilection for the malleoli is likely multifactorial due to marginal blood flow at the site, high venous pressure, less subcutaneous fat, thin skin, and lymphedema [12, 27]. This is similar to other hematologic conditions including hereditary spherocytosis, β-thalassemia intermedia, and Felty\'s syndrome. While medial involvement was more common in two studies [41, 42], there was no such difference found for the medial, lateral, left, or right legs in the CSSCD [6].
\nLarge sickle cell leg ulcers associated with foot deformities (from author\'s personal collection).
In the CSSCD, ulcers ranged between 0.5, 5–10, 10–15, and >15 cm with equal frequency. Most Jamaican studies had ulcers <10 cm in size. However, large circumferential ulcers portend a poor prognosis due to inevitable damage to vessels and lymphatics [4]. Pain is not related to wound size, and often initial, small ulcers are extremely painful (see Figure 3). Purulence, poor granulation tissue, and nonhealing are frequently reported in ulcers >10 cm.
\nUlcers in individuals with sickle cell disease usually have a punched appearance with well‐defined margins and slightly raised edges. The base comprises granulation tissue, often covered by yellow slough. More than half of patients will have more than two ulcers that are present at the same time, and multiple small ulcers may then coalesce to form a large ulcer.
\nHistology of an early leg ulcer shows neovascularization, chronic inflammation, vasculopathy with blood vessel occlusion, fibrin deposition in the intima, and microthrombi [16] (see Figure 1). The epidermis adjacent to the ulcer reveals acanthosis, hyperkeratosis, and attenuated rete ridges. There is increased vascularity and inflammation in the dermis with a lymphoplasmacytic inflammatory infiltrate. Chronically inflamed granulation tissue with vasculopathic changes in small blood vessels is found subjacent to the ulcer bed [2, 4].
\nUlcers may be staged according to their depth as follows [12]:\n
Stage 1: Nonblanchable erythema of intact skin, which may present as skin discoloration, warmth, edema, or induration in darker skinned patients.
Stage 2: Partial‐thickness skin loss involving epidermis, dermis, or both, presenting as an abrasion, blister, or shallow crater.
Stage 3: Full‐thickness skin loss involving damage to or necrosis of subcutaneous tissue that may extend down to, but not through, underlying fascia. The ulcer presents clinically as a deep crater with or without undermining of adjacent tissue.
Stage 4: Full‐thickness skin loss with extensive tissue destruction or damage to muscle, bone, or supporting structures (tendon, joint capsule).
Leg ulcers can be classified as acute or chronic although there is no consensus as to a specific length of time to define chronicity. An acute ulcer usually heals in less than a month. Chronic ulcers usually persist for at least 6 months and may last for several years. As described above, ulcer healing is typically slow as the ulcer fills in with granulation tissue, and a bluish epithelium may be seen growing in from the ulcer margin. Healing rates of 3.3–8.1 mm2/d have been reported in SS disease [43, 44] compared with rates of 400 mm2/d in other types of leg ulcer [45]. Even after satisfactory healing, 25–52% recurred in the CSSCD [6]. It is generally accepted, and it is the author\'s experience that if an ulcer does not heal within 6 months, its chances of ever healing are slim.
\nMinniti et al. have proposed three patterns of leg ulcers in SCD [2]:\n
One‐time ulcer
One half of patients with SCDs will develop only one ulcer in their lifetime. It usually occurs in the second decade of life, heals within several months, and may recur during periods of stress. These patients often have infrequent pain crisis and have renal and pulmonary complications.
\nStuttering ulcer
Twenty‐five percent of SCD patients develop small ulcers that recur every 6–12 months for several years.
\nChronic, recurrent ulcer
Approximately 1% SCD patients in the United States develop an ulcer that persists for years or even decades and/or ulcers that recur in the same or nearby sites. These patients experience the most disabling chronic pain, unemployment, and depression. Amputation may need to be considered in rare cases to improve quality of life [2, 46]. These patients are often tall, undernourished, and severely anemic with high hemolytic rate. They may have nephropathy, have rare vasoocclusive crisis, and often have trouble with employment, social interaction, and depression.
\nLeg ulcer pain may be severe, excruciating, penetrating, sharp, and stinging. Patients often report a crescendo of localized pain just before new ulcers develop [2]. About 40–50% of patients recall prior trauma [15, 16], often trivial or pruritus that incites scratching and skin breakdown. The pain is often exacerbated by exposure to cold and to air. The size of the ulcer does not necessarily correlate with intensity of the pain, and very small ulcerations can be extremely painful as well. Most patients require opioids for pain control.
\nPatients should be specifically asked about history of ulcers, since many patients will report having leg ulcers at some point in their lifetime and may not volunteer the information themselves. History should also document prior ulcer therapies and other complications associated with leg ulcers in SCD including pulmonary hypertension, stroke, priapism, acute chest syndrome [38, 45], lower extremity venous thrombosis, and retinopathy [2].
\nPhysical exam should assess the wound size with ruler measurement as well as digital photography for greater accuracy [47]. Surrounding skin hypo‐ or hyperpigmentation, edema, and muscle atrophy should be noted. Although serous discharge and fibrinous material are common, periwound erythema, purulent discharge, and worsening pain may be signs of acute infection. Inguinal lymph nodes are often enlarged, especially during ulcer exacerbations and do not necessarily signify infection. Pulse oximetry as well as blood pressure may be low. Attention should be paid to the nutritional status of patients as many are malnourished [2].
\nSickle cell individuals with ulcers often have infrequent pain crises and may not have sought regular medical care prior to their presentation. Occasionally, this will be the first time a physician has evaluated them for end‐organ diseases. Complete blood count and chemistry panel often reveal markers of severe chronic hemolysis. A significant increase in LDH may be seen [48]. Urinalysis may show microalbuminuria. Serum C‐reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are often elevated. Patients may have low levels of antithrombin III, protein C or S, high level of factor VIII, or positive lupus anticoagulant. Wound cultures usually reveal only superficial colonizing bacteria and are rarely helpful. Nutritional status and exercise tolerance with 6‐minute walk test (6MWT) should be recorded. When interpreting 6MWT, be aware that shorter distances secondary to physical impairment and pain can be caused by the ulcer. Echocardiography should be obtained to evaluate tricuspid regurgitant velocity to screen for pulmonary hypertension. Imaging studies of bones commonly show demineralization and bone infarcts. MRI should be obtained when osteomyelitis is suspected, but the gold standard for diagnosis remains bone biopsy. Osteomyelitis in the underlying bone is a rare occurrence, but if not diagnosed and treated appropriately will prevent healing [2]. A Doppler ultrasound of the lower extremities should be obtained to rule out the presence of a DVT.
\nThe management of leg ulcers in SCD involves a multipronged and multidisciplinary approach (see Table 1) with involvement of the primary hematologist, wound care specialist, nutritionist, surgeon, and social worker [2]. There remains a paucity of data from randomized controlled trials to guide treatment [49]. Current practice relies mostly on data from small case reports and case series along with expert opinion.
\nLocal therapies | \nSystemic therapies | \n
---|---|
Topical antibiotics | \nZinc sulfate | \n
Skin grafts (autologous or bioengineered) | \nPentoxifylline | \n
RGD peptide matrix | \n|
Moist wound dressing | \nArginine butyrate | \n
Growth factors | \nEndothelin antagonists: bosentan | \n
Medical honey | \nHydroxyurea | \n
Allogeneic keratinocytes | \nRed blood cell transfusions | \n
Collagen matrix | \nSystemic antibiotics | \n
Autologous or allogeneic platelet gel | \nHyperbaric oxygen therapy | \n
Synthetic heparan sulfate | \n\n |
Topical sodium nitrite | \n\n |
Energy‐based modalities | \n\n |
Negative‐pressure wound therapy | \n\n |
Leg compression and leg elevation | \n\n |
Topical analgesics | \n\n |
MIST™ | \n\n |
Transdermal oxygen | \n\n |
Maggots | \n\n |
Surgical debridement | \n\n |
Treatment modalities that have been used in patients with sickle cell disease and leg ulcers.
A randomized controlled trial of a topical antibiotic preparation (neomycin, bacitracin, and polymyxin B) in 30 patients with SS disease and chronic leg ulceration showed a significant reduction in ulcer size over a period of 8 weeks in the treatment group compared to the control group [50]. However, this trial had a high risk of bias, and the majority of the literature since 1987 questions the role of bacterial infections in wound pathogenesis [7, 51].
La Grenade et al. conducted a randomized controlled trial, in 32 patients with SS disease, of Solcoseryl®, DuoDerm®, and conventional therapy, cleaning with Eusol® (a mild antiseptic) followed by wet dressing. Patients were randomized to one of three therapies and monitored for 12 weeks. DuoDerm® (ConvaTec, Greensboro, NC) hydrocolloid dressing was generally unacceptable, and two‐thirds of the patients defaulted from this treatment. Solcoseryl®, a deproteinized extract from calf\'s blood that is meant to improve the tissue utilization of oxygen, increased ulcer healing compared to the controls, but the difference was not significant [52].
\nA 2014 Cochrane review described single trial that used an arginine‐glycine‐aspartic acid matrix (RGD peptide matrix) that achieved noticeable benefit in the treatment of leg ulcers in SCD. The RGD peptide matrix is believed to act as a synthetic extracellular matrix to promote cell migration, keratinocyte layer formation, and wound strengthening. Chronic ulcers treated with RGD peptide matrix had a statistically significant decrease in surface area; however, further studies are needed to corroborate these findings [51, 53].
\nA small retrospective cohort study underscored the efficacy of simple moist wound‐healing approach in patients with chronic leg ulcers in SCD who had failed to heal despite treatments such as debridement, split‐thickness skin grafts, muscle flaps, wet‐to‐dry dressings, Unna boots, hydroxyurea, recombinant human erythropoietin, and arginine butyrate. Ultimately, all patients were treated with topical hydrocolloid dressing (DuoDerm CGF by ConvaTec). The eight patients who had not received surgical treatment healed completely within 2–16 months, with only one recurrence at 4 months. Of the ten patients who had previous surgical treatment, six healed without recurrence at 30 months, two experienced recurrence with resolution upon the reapplication of DuoDerm, and two did not heal though did not experience worsening of their ulcers [2, 54].
Several case reports have used topical growth factors as an approach to treating leg ulcers.
\nGranulocyte‐macrophage colony‐stimulating factor (GM‐CSF) has been used topically and via intracutaneous injection [55, 56]. The cytokine activates macrophages and induces the proliferation of keratinocytes and differentiation of myofibroblasts. While it was shown to be beneficial in wound healing [55–58], high cost, severe vasoocclusive, and even fatal events have discouraged its use [58].
\nThere are several skin substitutes that are available commercially. One of them, Apligraf® (Organogenesis, Canton, MA), is a bi‐layered bioengineered skin substitute that has been approved by the Food and Drug Administration (FDA) since 2000 for the treatment of diabetic foot ulcers and venous leg ulcers (VLUs) that have not responded within 4 weeks to standard of care (SOC) therapy [7]. Apligraf provides both cells and matrix for the nonhealing wound possibly via production of cytokines and growth factors similar to healthy human skin [59]. Several studies confirm the efficacy of Apligraf in treatment of VLUs, and the Society of Vascular Surgery approves the use of Apligraf for the treatment of VLUs [57, 60–62]. The optimal frequency of use is not known, and current clinical practice is for consideration of reapplication after at least 1–3 weeks of observation after initial application [7].
\nGordon and Bui examined the efficacy of Apligraf in their study of sickle cell patients with chronic ulcers. Prior to application, they used a 4‐week regimen of hydrogel, followed by 1 week of wet‐to‐dry dressings and 1 week of wet‐to‐dry dressings plus application of papain‐urea debriding ointment (Accuzyme). After 6 weeks, the ulcer was sufficiently optimized for closure. The use of Apligraf resulted in complete healing, and the ulcer remained healed at the last follow‐up (33 months) [63].
\nAllogeneic keratinocytes have been used to promote the migration of autologous keratinocytes from the peripheral wound bed. Sheets of cells applied twice per month successfully healed a chronic ulcer within 3 months, without recurrence at follow‐up at 8 months [64].
\nTwo patients with chronic ulcers were treated with Collistat (collagen matrix) every 4 weeks and experienced complete healing by 10 and 12 weeks [65].
\nA case series reported the use of an autologous platelet gel to treat leg ulcers in five SCD patients. Autologous platelet‐enriched plasma was applied to the wound margins and fibrin matrix clot to the wound bed, before covering with moist saline gauze. A significant local release of platelet‐derived growth factors (PDGFs), transforming growth factor‐β (TGF‐β), and vascular endothelial growth factor (VEGF) was noted. Three of the patients showed a reduction of the leg ulcer area by 85.7–100% within 6–10 weeks. Two patients with ulcers threefold to tenfold larger experienced 20.5% and 35.2% decreases in the leg ulcer area. The authors concluded that the use of autologous platelet gel offers a promising and cost‐effective adjuvant treatment for leg ulcers particularly in small ones [66].
\nA synthetic, bioengineered heparan sulfate solution, Cacipliq20, was used to treat a nonhealing leg ulcer. The solution is designed to function as a glycosaminoglycan mimetic, potentially restoring the extracellular matrix scaffold and enhancing growth factor recruitment to aid in collagen production and angiogenesis and to restore tissue homeostasis and protect the wound from further damage. The patient in this case report had failed to respond to several treatments, including moist wound therapy, grafting, and energy‐based modalities. The patient experienced complete healing after 8 weeks of twice‐weekly applications [67].
\nA phase 1 trial of escalating doses of topical sodium nitrite demonstrated a dose‐dependent improvement in ulcer healing and decreasing pain at the ulcer site [68]. Application of topical sodium nitrite twice weekly for 4 weeks was associated with a significant increase in periwound cutaneous blood flow measured by laser speckle contrast imaging. It appeared to be well tolerated with no grade 3–4 adverse events. The authors concluded that topical sodium nitrite 2% cream is suitable for additional clinical trials in adults with sickle cell anemia to promote healing of leg ulcers.
\nTopical honey has been utilized mostly in burns and postoperative wounds as a dressing providing a moist healing environment in addition to its natural anti‐inflammatory, healing, and antibacterial properties [69]. Its use has also been described in the sickle cell literature for treatment of leg ulcers [15].
\nLow‐frequency, noncontact ultrasound (e.g., MIST®) has been employed to accelerate healing of sickle cell ulcers. It is believed to act via effective removal of bacteria and biofilm along with reduction of chronic inflammation. It also appears to promote the release of NO and growth factors at the cellular level, thereby stimulating vasodilation, angiogenesis, and collagen deposition. This modality can also be used to optimally prepare the wound for grafting [70].
\nLow‐level laser therapy has been reported to result in 80% reduction in the area of a leg ulcer after just five 10–15‐minute sessions, leading to a marked improvement in the patient\'s quality of life [71]. Low‐level laser therapy has previously been reported to modulate wound healing by increasing mitotic activity, fibroblast production, collagen synthesis, and angiogenesis and may have a role in the apoptotic processes of wound healing [72].
\nPaggiaro et al. examined the use of negative‐pressure wound therapy (NPWT) in leg ulcers. Following surgical debridement and before grafting, three wounds were treated by different methods: a rayon and normal saline solution dressing, calcium alginate and gauze, and negative‐pressure therapy. Researchers found that the NPWT‐treated wounds had a more homogenous surface with better vascularization in comparison with the other two groups. All three wounds received a split‐thickness skin graft. While the other wounds experienced subsequent graft failure, the NPWT‐treated wound did not, and the ulcers had not recurred by the time of follow‐up (11 months) [73]. However, the painful nature of leg ulcers in SCD may be a limiting factor in the use of NPWT.
\nBed rest has been shown to promote ulcer healing. Patients who underwent 2–3 weeks of strict bed rest experienced complete closure of their wounds within 2–3 months. In addition to reducing venous back pressure and edema around the ankle, patients developed improvement in RBC deformability, possibly secondary to decreased plasma volume, which also aided healing [74]. However, this approach is not very practical.
\nThe use of compression devices has been shown to be effective in reducing edema and improves healing in other types of ulcers. Although there are no prospective studies evaluating their role in sickle cell‐related ulcers specifically, these were universally recommended in a survey of care providers treating these patients [75, 76]. The use of Unna boots is highly recommended by practitioners, as the zinc oxide‐impregnated boots are useful in treating lower extremity lesions exacerbated by venous insufficiency. Multicomponent compression systems have been shown to be the most effective in reducing edema and improving venous reflux [20].
\nAs venous insufficiency is often seen in SCD patients, the clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum are also applicable for treatment of leg ulcers in sickle cell with venous disease. The guidelines recommend compression therapy to increase VLU healing and to decrease the risk of ulcer recurrence. The use of multicomponent compression bandages is encouraged over single‐component bandages [62].
\nTopical opioids have been employed by dissolving oxycodone and meperidine tablets in water and applying them locally to provide topical analgesia. Total pain relief was reported likely because of modification of peripheral opioid receptors [77]. While this treatment is not commercially available, these findings warrant further research. Data in mice with SCD show that topical opioids such as morphine and fentanyl not only treat pain but also hasten healing [78]. Inhibition of neurogenic inflammation by topical opioids is advocated as the mechanism of action. A study of nitroglycerin applied above the ulcer demonstrated a significant reduction in ulcer‐associated pain, with increased ability to be able to manipulate the ulcer. Pain in fact is often so intense that bedside debridement is not possible, thus ultimately delaying ulcer healing.
\nHyperbaric oxygen therapy and its potential benefit in treatment of vasoocclusive crises and leg ulcers have been described in several case reports [76, 79, 80]. However, paucity of research, potential adverse side effects, lack of treatment protocols, limited availability, and economic factors restrict its use [7].
\nA case report described the use of transdermal continuous oxygen therapy using a portable device that delivers oxygen directly to the wound site. Two LE wounds received treatment for 15 weeks, and the authors noted that both healed without recurrence in the 42‐month follow‐up. The authors urge further studies utilizing this form of therapy [81].
\nMaggot therapy has had mixed results when studied in other types of ulcers. One study showed reduced time to debridement, but increased ulcer pain and no improvement in rate of healing [82]. In diabetic ulcers, maggot debridement provided outcomes equal to conventional surgical treatment [83]. At the NIH Clinical Center, Medical Maggots™ (disinfected Phaenicia sericata larvae; http://www.monarchlabs.com) has been utilized. Four patients with sickle cell disease received this therapy with mixed results. There was temporary improvement in ulcer appearance, quickly followed by relapse and unclear long‐term benefit [7, 16]. Pain has also been a limiting factor for the use of medicinal maggots in this population, and an opioid PCA may be required. This modality is currently reserved only for patients who are poor candidates for surgical debridement [76].
\nZinc supplementation has long been believed to promote healing in chronic wounds accompanied by serum zinc deficiency [84]. A placebo‐controlled trial reported that 220 mg of zinc sulfate administered orally three times a day significantly improved the healing of leg ulcers in sickle cell patients [43]. However, no further studies have been undertaken to confirm these results, and the results are hard to interpret as neither the length of supplementation with oral zinc or statistical analysis was provided [7].
\nPentoxifylline improves RBC and leukocyte deformability potentially decreasing blood viscosity, platelet aggregation, thrombus formation, and plasma fibrinogen levels [7]. This increases microcirculatory flow and tissue oxygenation making it a good modality for treatment of leg ulcers in sickle cell patients. One case report presented that 400 mg of oral pentoxifylline three times a day helped completely heal a leg ulcer in a sickle cell patient within 3 months [85]. In nine RCTs involving 572 patients, pentoxifylline combined with compression bandages improved ulcer healing [86, 87]. The 2014 clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum recommend the use of pentoxifylline for treatment of long‐standing or large VLUs [62]. As venous insufficiency is often present in SCD patients, pentoxifylline may be a good treatment option for them.
\nSystemic therapy of leg ulcers in SCD with
Arginine stimulates collagen production, improves immune function, and prevents vascular restenosis. Butyrate can stimulate PDGF production and downregulate inflammatory cytokines and enzymes that slow wound healing like TGF‐β, tumor necrosis factor‐alpha (TNF‐α), and matrix metalloproteinases [90]. A phase II controlled trial showed significant improvement in ulcer healing in the treatment arm after 3 months (78% vs. 24% in controls, P < 0.001). A limitation to this approach is the requirement of an IV catheter. Larger studies are needed to validate this potentially effective treatment modality.
\nA case report described complete healing of a leg ulcer in a patient with concomitant pulmonary hypertension. The ulcer had previously failed multiple therapies. The researchers attributed the healing to the blockade of the endothelin‐1 receptor and vasodilation in the patient with likely decreased NO availability [91]. However, concomitant transfusion therapy might have confounded the observations.
\nThe role of hydroxyurea (HU) in the development or in the treatment of leg ulcers in sickle cell patients is not clear with conflicting data to date [92–97]. HU increases fetal hemoglobin levels, decreasing the intracellular polymerization of HbS, the incidence of painful crises, and the need for transfusions in SCD patients [98]. Moreover, HU is a known NO donor and decreases WBC counts [99]. These effects should theoretically decrease the incidence of leg ulcers. However, leg ulcers observed in patients with chronic myeloproliferative disorders on HU often resolved several months after the discontinuation of this medication [100–103]. A case report suggested that HU causes an acquired blood dyscrasia that increases the risk of ulceration [104]. Other multicenter studies have seen no evidence of an association between hydroxyurea and leg ulceration [76]. There are no prospective trials that specifically address the effects of HU use on leg ulcer healing in the sickle cell population, and therefore, we discourage reflexively stopping HU in patients with leg ulcers who may be benefiting from it for other SCD complications like frequent pain crisis and acute chest syndrome.
\nThere are no prospective RCTs addressing the role of blood transfusions for treatment of leg ulcers in sickle cell patients. Transfusions increase the oxygen delivery to tissues by increasing total hemoglobin and decreasing the HbS concentration [76]. Some authors suggest target hemoglobin of 10 g/dl for successful surgical treatment, although a level between 8 and 9 g/dl may be more realistic and adequate for wound healing [20]. However, transfusions come with their own risks including iron overload, alloimmunization, and risk of transfusion reactions and infections. In recent clinical trials and in our clinical practice, we note that there are patients with chronic wounds who are treated with chronic transfusions, either for other indications or because of the ulcer, with no apparent benefit in decreasing the length of ulceration. The author recommends supporting skin grafts with transfusions for a limited time period, 4–6 months, in order to maximize graft success and decrease SCD‐related complications.
\nAs discussed above, bacterial colonization of leg ulcers appears to be common but of uncertain clinical significance. However, colonization may lead to infection or a chronic inflammation, and systemic antimicrobials with anti‐inflammatory properties like doxycycline, clindamycin, and metronidazole may improve ulcer healing along with adequate debridement [20].
\nSurgical treatments for leg ulcers often have high rates of failure and recurrence [7]. Scar tissue becomes denser and less vascular with each subsequent graft, shortening the ulcer‐free interval between recurrences [7, 105]. Microsurgical free flap transfers are popular since they include their own blood supply, which is a favorable attribute in these poorly vascular regions [106]. However, they are often limited by complications like thrombi, microemboli, and infection ultimately requiring debridement and split‐thickness skin grafts [7].
\nAiming to reduce the incidence of graft failure, some experts recommend perioperative and even chronic lifelong transfusions to decrease HbS levels to <30% [106, 107]. Some surgeons support the use of anticoagulation with heparin and/or aspirin, antibiotics, and the rinsing of flaps with heparinized solution prior to attachment [106]. Larger RCTs are required to address these important issues.
\nNutrition is known to be important in the management of ulcers, and patients should be assessed for nutritional deficiencies and treated appropriately. Zinc deficiency has been shown to be prevalent in SCD patients. The current recommendation is 220 mg of zinc sulfate thrice a day. Serum zinc levels should be remeasured 2 and 4 weeks after initiation of supplementation and therapy discontinued if levels normalize [7, 108]. Others and we have noted that the BMI of SCD patients with recurrent ulcers is lower than patients without leg ulcers [12, Ballas, unpublished data]. We have also noted that several of the most affected patients seem to be almost anorexic, and we speculate that the high state of inflammation that their ulcer causes could be responsible for the presence of TNF‐alpha, similar to cancer patients.
\nAssessment and treatment of occult deep venous thrombosis are essential. Anticoagulation may be necessary to treat known hypercoagulable disorder.
\nThe pain from leg ulcers in patients with sickle cell disease can be very severe and debilitating leading many patients to require therapy with chronic opioids. Moreover, severe pain may interfere with local therapies and further hinder healing. Nonsteroidal anti‐inflammatory agents are often inadequate for optimal pain control. Currently, there are no guidelines recommending topical analgesics in this patient population, but provocative data in sickle cell mice suggest that the application of topical opioids can treat both the pain and increase healing rates [78] although they should be explored in future studies. Some experts recommend regional nerve blocks with good results in pain control and also for secondary vasodilation via reduction of stress‐related catecholamine release. This approach is limited by the need for an indwelling catheter, the need for frequent clinic visit for pump refills, and the antecedent risks of infection [7].
\nLeg ulcers in SCD are often resistant to treatment and have a high rate of recurrence, making optimizing the wound bed a cornerstone of therapy. The ulcer must be adequately debrided to remove biofilm and necrotic, nonviable tissue from the base and edge of the wound in order to begin the healing process [109]. Various types of debridement techniques may be used including autolytic, enzymatic, biological, mechanical, and sharp, depending on its suitability to the patient, the type of wound, its location, and the extent of debridement required [110]. Regular weekly chronic debridements may be needed for improved healing although the optimal frequency is not established [111]. Sharp debridement can be very painful and may only be possible with some form of analgesia, topical, injectable, or general anesthesia.
\nAlthough a multitude of dressings exist, the most important principle of wound care remains maintenance of a moist healing environment. Energy‐based modalities like low‐frequency, noncontact ultrasound, electrical stimulation, and ultraviolet‐C light are good adjuvant treatment options for wounds that fail to respond positively to standard of care methods [7].
\nThe use of RGD peptide matrix, allogeneic keratinocytes, and autologous platelet gel are promising treatments for resistant ulcers, although more research is needed. These are not widely available as yet.
\nCompression therapy is encouraged for the management and prevention of edema, especially if venous insufficiency is present. Compression stockings are useful for prevention, while multilayer compression bandaging is recommended for treatment. An alternative is using a self‐applicable and adjustable short‐stretch Velcro band [62].
\nThe Society for Vascular Surgery and the American Venous Forum strongly advocate pentoxifylline for treatment of long‐standing or large VLUs since venous insufficiency is frequently found in these patients. Apligraf is recommended for ulcers not responding to standard of care therapies within 4–6 weeks.
\nMinimally, invasive ablation of superficial axial and perforator vein reflux in patients with active venous insufficiency and patent deep venous system is a relatively safe procedure and leads to faster healing and decreased ulcer recurrence when combined with compression therapy [112]. This also underscores prompt referral to a vascular specialist for evaluation and management of leg ulcers in SCD.
\nThe IDSA guidelines do not recommend treating an uninfected wound with antimicrobials since there is no evidence that this prevents infection or improves ulcer healing [113]. When there are clinical signs of infection, post‐debridement deep soft tissue or bone biopsy should be sent for culture. Superficial wound cultures are less reliable than tissue biopsies and should be avoided [114]. Hospitalized patients with more severe infections and signs of cellulitis and/or osteomyelitis typically receive intravenous antibiotic therapy at least initially. Finally, topical antibiotics do not significantly affect leg ulcers healing [7]. Further studies are needed to explore the immunomodulatory and anti‐inflammatory actions of tetracyclines on ulcer healing.
\nA previous history of leg ulcer is the greatest predictor of developing another leg ulcer in patients with sickle cell disease, increasing the risk up to 23‐fold in one study [84]. While spontaneous ulcers are unpredictable, traumatic ulcers may be preventable. Encouraging patients to regularly check their skin for signs of early ulcers and preventing local trauma by wearing properly fitting shoes and protecting themselves from insect bites may decrease the risk of developing leg ulcers. Wearing appropriately sized above‐the‐knee compression stockings can reduce edema and prevent new and recurrent ulcers [16].
\nEvidence suggests that SCD patients with hyper‐hemolysis phenotype (characterized by severe anemia and markers of hemolysis like high LDH) are at risk for leg ulcers as well as pulmonary hypertension, priapism, and renal disease [115]. Studies have shown that leg ulcers are more common in SCD patients with pulmonary hypertension [12, 116, 117]. Experts recommend that patients with HbS with leg ulcers should be screened for pulmonary hypertension.
\nThis epidemiological relationship between leg ulcers and pulmonary hypertension supports a common pathophysiologic mechanism. Sickle cell patients with leg ulcers have been shown to have higher rates of mortality that those without leg ulcers and are regarded as a marker of disease severity in sickle cell patients [9].
\nLeg ulcers of varying sizes (from author\'s personal collection).
Subcutaneous fibrosis impairing venous and lymphatic drainage may occur and can be severe enough to cause an equinus deformity [4] (Figure 4). Osteomyelitis is exceedingly rare but has been observed on occasion. Acute ankle arthritis complicates some cases of spontaneous leg ulceration, possibly as a result of associated ischemic synovial damage [118]. It resolves spontaneously with improvement of the leg ulcer.
\nLeg ulcers can have a profound impact on patients’ psychological well‐being. Patients often have social withdrawal at school and work places. They often suffer from depression, which may impair their ability to take care of their ulcers adequately and seek medical attention [4].
\nIn summary, sickle cell leg ulcers are a disabling complication of sickle cell disease, and despite being widely described in the medical literature, there remains a paucity of large randomized controlled data pertaining to their treatment. Current recommendations include a multifaceted approach utilizing a combination of topical, systemic, and surgical techniques. We describe a simplified algorithm to aid management of these complex patients (Figure 5). While a multidisciplinary team is essential, it is important to retain primary responsibility of the patient as hematologists, optimizing the health of the patient and facilitating plans of care made by various specialties. As we begin to understand more about the complex pathophysiology of these chronic wounds, more research is needed targeting these identified pathways to improve ulcer healing and prevent recurrence.
\nApproach to the management of patients with SCD and wounds.
Stress corrosion cracking (SCC) in chemical, petrochemical, and power plant industries is an insidious form of corrosion, which causes a lot of financial losses and human damages [1, 2, 3, 4, 5]. This phenomenon is associated with a combination of tensile stress, environment, and some metallurgical conditions as described in Figure 1.
The essential requirements for SCC.
During stress corrosion cracking, the metal or alloy is virtually unattacked over most of its surface, while fine and branch cracks progress through the bulk of material [6]. It is shown in Figure 2. This cracking phenomenon has serious consequences since it can occur under stresses much lower than design stresses and lead the equipment and structures to premature failures [7, 8, 9, 10, 11].
Crack development in carbon steel exposed to nitrate solution.
Stress corrosion cracking starts from corrosion sites at the material surfaces and progresses into a brittle manner. The process of cracking is not strictly a mechanical process, as the corrosivity of the environment strongly affects the fracture mode. Both intergranular and transgranular stress corrosion cracking are observed. Intergranular cracking proceeds along grain boundaries, while transgranular cracking advances without apparent preference for boundaries [12]. An example of stress corrosion cracking in which the crack has progressed in both intergranular and transgranular paths is shown in Figure 3. The development mode of cracking depends on the composition and microstructure of the material and environment.
Intergranular and transgranular stress corrosion cracking of the AISI 316L stainless steel at polythionic acid environment [8].
In this chapter, the conditions for the occurrence of SCC are first introduced. Then, the stress corrosion cracking mechanism for various materials in conditions that are susceptible is discussed in detail. The design of industrial structures and components is usually based on tensile properties, which have many disadvantages. So, the science of fracture mechanics applies in the situations prone to SCC because of the inevitability of manufacturing and service defects in materials and for considering the role of such imperfections. Methods of prevention based on corrosion science and empirical data are presented. Finally, practical examples are given to better understand the issue.
Not all metal-environment combinations are susceptible to cracking. In other words, the environment for occurrences of SCC for each metal or alloys is specific. Also, the resources of stress for each case of failure may be different.
Austenitic stainless steels suffer from SCC in chlorides, caustic, and polythionic acid. When austenitic stainless steels with sufficient carbon content (more than 0.03 wt.%) are heated in the range of 415–850°C, their microstructure becomes susceptible to precipitation of chromium carbides (M23C6) along grain boundaries known as sensitization [9, 12, 13]. Formation of Cr-rich carbides along grain boundaries may drastically deplete free chromium content in the area adjacent to the grain boundaries and render them susceptible to rapid preferential dissolution. Sensitized steels are most susceptible; the stress corrosion cracking of nonsensitized steels is also observed [14, 15]. Dissolution of grain boundaries in some corrosive environments aside from tensile stress led these types of materials to SCC.
Seasonal cracking of brass in the rainy season in an ammoniacal environment is another classical example of SCC. This was first identified on the brass cartridge used by the British Army in India. Since it is usually identified during the rainy season, it is also called seasonal cracking [12]. Alpha brass is an alloy of Cu-Zn. It can crack either intergranularly or transgranularly in nontarnishing ammonia solutions, depending on its zinc content [16, 17, 18]. Transgranular stress corrosion cracking, TGSCC, is observed in alloys with 20 or 30% Zn but not in alloys with 0.5 or 10% Zn [19, 20]. Stress corrosion cracking of Cu-Zn and Cu-A1 alloys in cuprous ammonia solutions can only occur when the parting limits for dealloying are exceeded. The parting limits are about 14 and 18 a/o for Cu-A1 and Cu-Zn, respectively [21]. Cu-A1 and Cu-Ga alloys have shown similar behaviors [19, 22].
Aluminum and all its alloys can fail by cracking along grain boundaries when simultaneously exposed to specific environments and stresses of sufficient magnitude [23, 24]. Of eight series of aluminum alloys, 2xxx, 5xxx, and 7xxx aluminum alloys are susceptible to SCC. Among them, 7xxx series aluminum alloys have a specific application in aerospace, military, and structural industries due to superior mechanical properties. In these high-strength 7xxx aluminum alloys, SCC plays a vital factor of consideration, as these failures are catastrophic during the service [25].
Carbon and low alloy steels have shown SCC in a wide range of environments that tend to form a protective passive or oxide film [26, 27, 28, 29, 30]. The environments that would passivate carbon steels have been found to cause SCC, including strong caustic solutions, phosphates, nitrates, carbonates, ethanol, and high-temperature water. The problems are important for both economic and safety reasons, due to the extensive use of carbon steels [31]. For example, nitrate cracking in an ammonium nitrate plant caused by catastrophic failures and a lot of financial losses. Caustic cracking of steam-generating boilers made of low alloy steels was a serious problem, which led an ammonia plant to repeated emergency shutdowns.
Stress corrosion cracking may be a problem whenever certain high-strength titanium alloys are exposed to aqueous and certain solvent environments [32, 33, 34, 35, 36]. For the first time, SCC of titanium was reported by Kiefer and Harple who describe the cracking phenomena with commercially pure titanium in red fuming nitric acid [37]. Hot salt cracking of titanium alloys was reported in turbine blades that operate at high temperature in the mid-1950s. The subject became very active in the early 1960s because of the SCC problem connected to these alloys in a transportation program [38].The first known report of stress corrosion cracking of titanium alloys in room temperature aqueous environments was that of Brown. He found that titanium alloys, 8% aluminum–1% molybdenum–1% vanadium alloy (Ti, 8–1–1), were susceptible to SCC in seawater [38].
Another requirement for SCC to occur is a corrosive environment. The environments for SCC are specific because not all environments promote SCC. For those alloys that develop a protective film, an aggressive ion is required to promote SCC. The aggressive media to passive layer of stainless steels are chlorides, caustic, and polythionic acid. The austenitic stainless steel series 300 is more susceptible in an environment containing chlorides. Chlorides will not cause SCC unless an aqueous phase is present. It appears that stress corrosion cracking in austenitic stainless steels in the presence of chlorides proceeds transgranularly and usually occurs at temperature above 70°C
Metal | Environment |
---|---|
Al alloys | NaCl-H2O2 solutions |
NaCl solutions | |
Seawater | |
Copper alloys | Ammonia vapor and solutions |
Amines | |
Water or water vapor | |
Gold alloys | FeCl3 solutions |
Acetic acid-salt solutions | |
Inconel | Caustic soda solutions |
Lead | Lead acetate solutions |
Magnesium alloys | NaCl-Na2CrO4 solutions |
Rural and coastal atmospheres | |
Seawater | |
Distilled water | |
Nickel | Fused caustic soda |
Steels | NaOH solutions |
NaOH-Na2SiO4 solutions | |
Calcium, ammonium, and sodium nitrite solutions | |
Mixed acids (H2SO4-HNO3) | |
Acidic H2S solutions | |
Seawater | |
Carbonate-bicarbonate solutions | |
Stainless steels | Acidic chloride solutions |
NaCl-H2O2 solutions | |
Seawater | |
H2S | |
NaOH-H2S solutions | |
Condensing steam from chloride waters | |
Titanium alloys | Red fuming nitric acid |
Seawater | |
Methanol-HCl |
The stress in the form of tensile (not compressive) plays a key role in the SCC fracture processes. In fact, SCC would never have occurred in the absence of stress. The required tensile stresses may be in the form of directly applied stresses, thermal, in the form of residual stresses, or a combination of all [8, 50]:
For SCC to occur alone by applied stress, it must have a very high magnitude. The welding and mechanical residual stresses are the main sources of stress attributed to the stress corrosion cracking. The welding residual stress is produced as a result of nonuniform temperature changes during welding operation and can be calculated from thermal strain vectors.
The thermal strain vector,
in which
The operational thermal stress can also be calculated from Eq. 2. Mechanical workings such as cold deformation and forming, machining, and grinding are the other sources, which introduce residual stresses [8, 51].
Extensive investigations have been devoted to find mechanisms of SCC for different materials and environments. An SCC failure illustrates the combined effects of mechanical, physical, and chemical/electrochemical factors causing the separation of metal bonds at the crack tip, thereby advancing the crack. Three mechanisms for SCC have been proposed through the investigations [52]:
This model supposes that there are pre-existing paths in an alloy that is susceptible to anodic dissolution. Because of precipitation or solute segregation of impurities like sulfur, phosphorus, and chromium carbides, the electrochemical properties of the matrix and segregates are changed. The area adjacent to the grain boundaries is depleted from one or more alloying elements, and so under such conditions, localized galvanic cells are created (Figure 4). Since precipitation or segregation is generally anodic to the matrix of the grains, dissolution under an anodic reaction occurs and provides active path for localized corrosions [53]. Also, the removal of the protective film at the pre-existing crack tips by plastic deformation would facilitate the onset of localized corrosion.
Galvanic cell mechanism [52].
This mechanism has been extensively studied in stress corrosion cracking of alpha brass in ammoniacal environment and also proposed for caustic cracking of boiler steel. The model is based on the idea of a strain-induced rupture of the protective film, and so plastic strains play a main role in failure processes [52, 55]. The theory assumes the existence of a passivation film on a metal surface. The passivation film protects the underlying metal against corrosive agents. The passivation film is ruptured by plastic strain due to mechanical workings. After the film is ruptured, the bare metal is exposed to the corrosive environment. The processes of disruptive strain (disruption of protective film) and film formation (due to repassivation) have occurred and alternate with each other. The crack propagates when the rate of rupture of oxide film is higher than the rate of repassivation of the film [52]. The mechanism is shown in Figure 5.
Strain-generated active path mechanisms. (A) Film rupture model and (B) slip-step dissolution model [52].
This model is based on the effects of environmental species on interatomic bond strength. The theoretical fracture stress required to separate two layers of atoms of spacing b is given by [56].
where E is the Young modulus, γ is the surface energy, and b is the spacing between atoms.
This theory implies that if surface energy is reduced, then
The design of steel structure and component based on tensile properties has many disadvantages that do not take into account the role of imperfections. Fracture mechanic introduces another material characteristic, namely, fracture toughness, KIC, which considered the role of cracks and imperfection in the form of cracks in designs. In its simplest form [57].
where
According to this equation, fracture occurs when stress intensity factor,
Effects of corrosive environment on fracture toughness [12].
Since the exact mechanism of SCC has not been completely understood, prevention methods are either general or empirical in nature. Appropriate strategy should be done in order to minimize this problem to ensure not only the safety of human life but also the safety of cost. The following general methods are recommended to overcome the SCC problems [12, 52, 58, 59]:
Lowering the tensile stress in the welded component using post weld heat treatment. The post weld heat treatment reduced or eliminated residual stress on surface and through the bulk of material. Plan and low alloy steels may be a stress relief at 1100–1200°F. The range of residual stress relief temperature for austenitic stainless steels is from 1500 to 1700°F. Reduction of tensile stresses by shot peening is also recommended. Shot peening introduces surface compressive stresses.
Eliminating aggressive agents from the environment by, for example, degasification, demineralization, or distillation.
Changing the alloy is one possible solution if neither the environment nor stress can be changed. For example, it is a common practice to use Inconel (raising the nickel content) when typ. 304 stainless steel is not satisfactory.
Applying cathodic protection: impressed current cathodic protection system has been successfully used to prevent SCC of steels.
Adding inhibitors to the system if feasible: high concentrations of phosphate have been successfully used.
Coatings are sometimes used, and they depend on keeping the environment away from the metal.
After only 3 years’ service of a circulation water heater (heat exchanger), it has been shown to sever leakage and has led a methanol plant to emergency shutdown. An on-site investigation revealed extensive cracking initiated at weld area and through the tube sheet holes as it is shown in Figure 7.
Failed area (a) cracks extending in the weld joint of tube sheet to plugs and (b) branched cracks in the surface of the tube sheet and through the holes [8].
The circulation water heater is a vertical U-type heat exchanger made of austenitic stainless steels. The equipment used to decline reforms gas temperature in a methanol plant. The hot reformed gas at approximately 385°C entered the tubes and is cooled down to 168°C by exchanging the heat with processed water in the shell. The gases that flow through the tubes are mainly CO2, CO, H2, CH4, and N2 and at a pressure of 3.9 MPa. At the shell cooling process, water flows with about 6 MPa pressure.
Deposits had formed on top of the tube sheet due to shutdown errors. AISI 316L materials overheated in service because of the insulation role of the deposits. Material sensitization occurs since overheating. The presence of sulfur in the process gas aside from moisture formed polythionic acid during shutdowns. Residual stress produced by heavy machining and welding aside from operational thermal stress provided tensile stress, which is needed for SCC. Stress corrosion cracking is induced by polythionic acid. Concentrated water with other aggressive agents such as caustic and chlorides leaked through the cracks aid the failures.
Cleaning of the shell by demineralized water after each shut down in order to prevent the forming of insulating deposits above the tube sheet
Reduction of sulfur in feeding gas
Reduction of caustic and chlorides in processed water
Carryover of caustic soda (NaOH) in the steam path caused catastrophic failure of superheater stainless steel tubes in a gas-fired heater and led to an unexpected shutdown after just 5 months of continuous service following the start of production. The failure areas are shown in Figure 8. Three types of cracks are identified in various regions of the tube: circumferential cracks adjacent to the seam weld, circumferential cracks at the ribbon of the seam weld, and longitudinal cracks on the U-bend. The path of cracks was complex on the surface or in the bulk metal; all had nucleated from inside the tubes. A visual inspection revealed a white deposit, high in sodium, around the cracks on the surface of the tubes.
(a and b) Circumferential cracks adjacent to the seam weld, (c and d) circumferential cracks at the ribbon of seam weld, and (e) longitudinal cracks on the U-bend [9].
The superheater tube material was made of AISI 304H austenitic stainless steel material.
The gas-fired steam heater (FH) generates high-pressure (HP) steam for turbines for the processing of methanol. Demineralized water for the boiler and subsequent steam path is prepared in the water treatment unit. Caustic soda is injected to demineralized water for pH control. The water is transferred to the preheat exchangers, is converted to saturated high-pressure steam at 325°C and 119 MPa, and is sent to the FH. Through the FH tubes, saturated steam converted to supersaturate steam at a temperature of 505°C and pressure of 119 MPa.
The main cause of crack initiation was the increase of pH due to the rise of caustic concentration in condensed drops. Sensitized austenite grains caused by chromium carbide depletion adjacent to the grain boundaries were attacked by concentrated caustic in the HAZ metal and U-bend area and led the heater to the caustic SCC failure.
Using A335 Grade P9, a low alloy steel tube shows higher resistance to SCC than AISI 304H stainless steel
Proper discharge of the tubes during shutdowns to prevent the formation of the concentrated deposits of caustic through the tubes
After a general overhaul of a thermal power plant in Serbia in November 2014, failure of hundreds of brass condenser tubes occurred during the hydrostatic test. Also, it was noted that some backing plates had fallen off from the tubes before this test. Fracture is observed only in condenser tubes of brass, as can be seen in Figure 9.
Failure of brass condenser tubes near joining location with backing plate.
The failed tube material of the condenser was made of brass CuZn28Sn1 (admiralty brass). The cooling water (roughly filtered river water) flows through the tubes, while the hot steam flows around the tubes.
Analysis of fracture surfaces using scanning electron microscopy (SEM) has shown the brittle transgranular fracture due to the occurrence of SCC. The condenser tubes are made of brass CuZn28Sn1. Ammonia and other nitrogen compounds in the cooling water through the tubes were found. These compounds are specific agents that cause stress corrosion cracking (SCC) in brass. In the joining region of condenser tubes to backing plates, there are residual tensile stresses. During the floods in May 2014, there was an increase in the concentration of ammonia and other nitrogen compounds in the river cooling water flowing through the condenser tubes. Failure of brass condenser tubes occurred due to SCC, because the necessary conditions for the SCC occurrence were fulfilled.
The risk of SCC in brass condenser tubes can be reduced if specific substances responsible for SCC occurrence are removed, as much as possible. This can be achieved by cleaning and drying the tubes immediately after the operation delay of the power plant.
Another way to reduce the risk of SCC occurrence in condenser tubes is the replacement of existing tubes (made of brass CuZn28Sn1, very susceptible to SCC) with tubes made of alloys of greater resistance to SCC, such as copper-nickel alloys or Bi-brass alloys [61].
Stress corrosion cracking is one of the main causes of unforeseen and dangerous destruction of industrial plants. The sensitized material, certain environments, and stress are three factors necessary for the occurrence of these types of failures. The environment prone to the cracking for each metal or alloy is specific because not all environments promote the SCC. Austenitic stainless steels suffer from SCC in chlorides, caustic, and polythionic acid. Copper alloys corrode in ammonia-containing environments. Well-known specific environments for the stress corrosion cracking in Al alloys include water vapor, aqueous solutions, organic liquids, and liquid metals. The SCC of Ti alloys in aqueous chloride and methanolic chloride environments has been widely reported. The tensile stress plays a key role in the stress corrosion cracking phenomenon. The required tensile stresses may be in the form of directly applied stresses, thermal, in the form of residual stresses, or a combination of all.
If one of these three components does not exist, this type of corrosion will not occur. Therefore, the solving methods should be based on the elimination of one of these three factors. Corrosive environment modification, the stress in the form of compression, and using proper material are three general proposed methods of prevention.
IntechOpen books are indexed by the following abstracting and indexing services:
",metaTitle:"Indexing and Abstracting",metaDescription:"IntechOpen was built by scientists, for scientists. We understand the community we serve, but to bring an even better service to the table for IntechOpen Authors and Academic Editors, we partnered with the leading companies and associations in the industry and beyond.",metaKeywords:null,canonicalURL:"/page/indexing-and-abstracting",contentRaw:'[{"type":"htmlEditorComponent","content":"Clarivate Web Of Science - Book Citation Index
\\n\\nCroatian Library (digital NSK)
\\n\\nOCLC (Online Computer Library Center) - WorldCat® Digital Collection Gateway
\\n\\n\\n\\n
\\n"}]'},components:[{type:"htmlEditorComponent",content:'
Clarivate Web Of Science - Book Citation Index
\n\nCroatian Library (digital NSK)
\n\nOCLC (Online Computer Library Center) - WorldCat® Digital Collection Gateway
\n\n\n\n
\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{sort:"featured,name"},profiles:[{id:"105746",title:"Dr.",name:"A.W.M.M.",middleName:null,surname:"Koopman-van Gemert",slug:"a.w.m.m.-koopman-van-gemert",fullName:"A.W.M.M. Koopman-van Gemert",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/105746/images/5803_n.jpg",biography:"Dr. Anna Wilhelmina Margaretha Maria Koopman-van Gemert MD, PhD, became anaesthesiologist-intensivist from the Radboud University Nijmegen (the Netherlands) in 1987. She worked for a couple of years also as a blood bank director in Nijmegen and introduced in the Netherlands the Cell Saver and blood transfusion alternatives. She performed research in perioperative autotransfusion and obtained the degree of PhD in 1993 publishing Peri-operative autotransfusion by means of a blood cell separator.\nBlood transfusion had her special interest being the president of the Haemovigilance Chamber TRIP and performing several tasks in local and national blood bank and anticoagulant-blood transfusion guidelines committees. Currently, she is working as an associate professor and up till recently was the dean at the Albert Schweitzer Hospital Dordrecht. She performed (inter)national tasks as vice-president of the Concilium Anaesthesia and related committees. \nShe performed research in several fields, with over 100 publications in (inter)national journals and numerous papers on scientific conferences. \nShe received several awards and is a member of Honour of the Dutch Society of Anaesthesia.",institutionString:null,institution:{name:"Albert Schweitzer Hospital",country:{name:"Gabon"}}},{id:"83089",title:"Prof.",name:"Aaron",middleName:null,surname:"Ojule",slug:"aaron-ojule",fullName:"Aaron Ojule",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Port Harcourt",country:{name:"Nigeria"}}},{id:"295748",title:"Mr.",name:"Abayomi",middleName:null,surname:"Modupe",slug:"abayomi-modupe",fullName:"Abayomi Modupe",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/no_image.jpg",biography:null,institutionString:null,institution:{name:"Landmark University",country:{name:"Nigeria"}}},{id:"94191",title:"Prof.",name:"Abbas",middleName:null,surname:"Moustafa",slug:"abbas-moustafa",fullName:"Abbas Moustafa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94191/images/96_n.jpg",biography:"Prof. Moustafa got his doctoral degree in earthquake engineering and structural safety from Indian Institute of Science in 2002. He is currently an associate professor at Department of Civil Engineering, Minia University, Egypt and the chairman of Department of Civil Engineering, High Institute of Engineering and Technology, Giza, Egypt. He is also a consultant engineer and head of structural group at Hamza Associates, Giza, Egypt. Dr. Moustafa was a senior research associate at Vanderbilt University and a JSPS fellow at Kyoto and Nagasaki Universities. He has more than 40 research papers published in international journals and conferences. He acts as an editorial board member and a reviewer for several regional and international journals. His research interest includes earthquake engineering, seismic design, nonlinear dynamics, random vibration, structural reliability, structural health monitoring and uncertainty modeling.",institutionString:null,institution:{name:"Minia University",country:{name:"Egypt"}}},{id:"84562",title:"Dr.",name:"Abbyssinia",middleName:null,surname:"Mushunje",slug:"abbyssinia-mushunje",fullName:"Abbyssinia Mushunje",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Fort Hare",country:{name:"South Africa"}}},{id:"202206",title:"Associate Prof.",name:"Abd Elmoniem",middleName:"Ahmed",surname:"Elzain",slug:"abd-elmoniem-elzain",fullName:"Abd Elmoniem Elzain",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Kassala University",country:{name:"Sudan"}}},{id:"98127",title:"Dr.",name:"Abdallah",middleName:null,surname:"Handoura",slug:"abdallah-handoura",fullName:"Abdallah Handoura",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"École Supérieure des Télécommunications",country:{name:"Morocco"}}},{id:"91404",title:"Prof.",name:"Abdecharif",middleName:null,surname:"Boumaza",slug:"abdecharif-boumaza",fullName:"Abdecharif Boumaza",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Abbès Laghrour University of Khenchela",country:{name:"Algeria"}}},{id:"105795",title:"Prof.",name:"Abdel Ghani",middleName:null,surname:"Aissaoui",slug:"abdel-ghani-aissaoui",fullName:"Abdel Ghani Aissaoui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/105795/images/system/105795.jpeg",biography:"Abdel Ghani AISSAOUI is a Full Professor of electrical engineering at University of Bechar (ALGERIA). He was born in 1969 in Naama, Algeria. He received his BS degree in 1993, the MS degree in 1997, the PhD degree in 2007 from the Electrical Engineering Institute of Djilali Liabes University of Sidi Bel Abbes (ALGERIA). He is an active member of IRECOM (Interaction Réseaux Electriques - COnvertisseurs Machines) Laboratory and IEEE senior member. He is an editor member for many international journals (IJET, RSE, MER, IJECE, etc.), he serves as a reviewer in international journals (IJAC, ECPS, COMPEL, etc.). He serves as member in technical committee (TPC) and reviewer in international conferences (CHUSER 2011, SHUSER 2012, PECON 2012, SAI 2013, SCSE2013, SDM2014, SEB2014, PEMC2014, PEAM2014, SEB (2014, 2015), ICRERA (2015, 2016, 2017, 2018,-2019), etc.). His current research interest includes power electronics, control of electrical machines, artificial intelligence and Renewable energies.",institutionString:"University of Béchar",institution:{name:"University of Béchar",country:{name:"Algeria"}}},{id:"99749",title:"Dr.",name:"Abdel Hafid",middleName:null,surname:"Essadki",slug:"abdel-hafid-essadki",fullName:"Abdel Hafid Essadki",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"École Nationale Supérieure de Technologie",country:{name:"Algeria"}}},{id:"101208",title:"Prof.",name:"Abdel Karim",middleName:"Mohamad",surname:"El Hemaly",slug:"abdel-karim-el-hemaly",fullName:"Abdel Karim El Hemaly",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/101208/images/733_n.jpg",biography:"OBGYN.net Editorial Advisor Urogynecology.\nAbdel Karim M. A. El-Hemaly, MRCOG, FRCS � Egypt.\n \nAbdel Karim M. A. El-Hemaly\nProfessor OB/GYN & Urogynecology\nFaculty of medicine, Al-Azhar University \nPersonal Information: \nMarried with two children\nWife: Professor Laila A. Moussa MD.\nSons: Mohamad A. M. El-Hemaly Jr. MD. Died March 25-2007\nMostafa A. M. El-Hemaly, Computer Scientist working at Microsoft Seatle, USA. \nQualifications: \n1.\tM.B.-Bch Cairo Univ. June 1963. \n2.\tDiploma Ob./Gyn. Cairo Univ. April 1966. \n3.\tDiploma Surgery Cairo Univ. Oct. 1966. \n4.\tMRCOG London Feb. 1975. \n5.\tF.R.C.S. Glasgow June 1976. \n6.\tPopulation Study Johns Hopkins 1981. \n7.\tGyn. Oncology Johns Hopkins 1983. \n8.\tAdvanced Laparoscopic Surgery, with Prof. Paulson, Alexandria, Virginia USA 1993. \nSocieties & Associations: \n1.\t Member of the Royal College of Ob./Gyn. London. \n2.\tFellow of the Royal College of Surgeons Glasgow UK. \n3.\tMember of the advisory board on urogyn. FIGO. \n4.\tMember of the New York Academy of Sciences. \n5.\tMember of the American Association for the Advancement of Science. \n6.\tFeatured in �Who is Who in the World� from the 16th edition to the 20th edition. \n7.\tFeatured in �Who is Who in Science and Engineering� in the 7th edition. \n8.\tMember of the Egyptian Fertility & Sterility Society. \n9.\tMember of the Egyptian Society of Ob./Gyn. \n10.\tMember of the Egyptian Society of Urogyn. \n\nScientific Publications & Communications:\n1- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Asim Kurjak, Ahmad G. Serour, Laila A. S. Mousa, Amr M. Zaied, Khalid Z. El Sheikha. \nImaging the Internal Urethral Sphincter and the Vagina in Normal Women and Women Suffering from Stress Urinary Incontinence and Vaginal Prolapse. Gynaecologia Et Perinatologia, Vol18, No 4; 169-286 October-December 2009.\n2- Abdel Karim M. El Hemaly*, Laila A. S. Mousa Ibrahim M. Kandil, Fatma S. El Sokkary, Ahmad G. Serour, Hossam Hussein.\nFecal Incontinence, A Novel Concept: The Role of the internal Anal sphincter (IAS) in defecation and fecal incontinence. Gynaecologia Et Perinatologia, Vol19, No 2; 79-85 April -June 2010.\n3- Abdel Karim M. El Hemaly*, Laila A. S. Mousa Ibrahim M. Kandil, Fatma S. El Sokkary, Ahmad G. Serour, Hossam Hussein.\nSurgical Treatment of Stress Urinary Incontinence, Fecal Incontinence and Vaginal Prolapse By A Novel Operation \n"Urethro-Ano-Vaginoplasty"\n Gynaecologia Et Perinatologia, Vol19, No 3; 129-188 July-September 2010.\n4- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Laila A. S. Mousa and Mohamad A.K.M.El Hemaly.\nUrethro-vaginoplasty, an innovated operation for the treatment of: Stress Urinary Incontinence (SUI), Detursor Overactivity (DO), Mixed Urinary Incontinence and Anterior Vaginal Wall Descent. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/ urethro-vaginoplasty_01\n\n5- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamed M. Radwan.\n Urethro-raphy a new technique for surgical management of Stress Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/\nnew-tech-urethro\n\n6- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamad A. Rizk, Nabil Abdel Maksoud H., Mohamad M. Radwan, Khalid Z. El Shieka, Mohamad A. K. M. El Hemaly, and Ahmad T. El Saban.\nUrethro-raphy The New Operation for the treatment of stress urinary incontinence, SUI, detrusor instability, DI, and mixed-type of urinary incontinence; short and long term results. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=urogyn/articles/\nurethroraphy-09280\n\n7-Abdel Karim M. El Hemaly, Ibrahim M Kandil, and Bahaa E. El Mohamady. Menopause, and Voiding troubles. \nhttp://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly03/el-hemaly03-ss\n\n8-El Hemaly AKMA, Mousa L.A. Micturition and Urinary\tContinence. Int J Gynecol Obstet 1996; 42: 291-2. \n\n9-Abdel Karim M. El Hemaly.\n Urinary incontinence in gynecology, a review article.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/abs-urinary_incotinence_gyn_ehemaly \n\n10-El Hemaly AKMA. Nocturnal Enuresis: Pathogenesis and Treatment. \nInt Urogynecol J Pelvic Floor Dysfunct 1998;9: 129-31.\n \n11-El Hemaly AKMA, Mousa L.A.E. Stress Urinary Incontinence, a New Concept. Eur J Obstet Gynecol Reprod Biol 1996; 68: 129-35. \n\n12- El Hemaly AKMA, Kandil I. M. Stress Urinary Incontinence SUI facts and fiction. Is SUI a puzzle?! http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly/el-hemaly-ss\n\n13-Abdel Karim El Hemaly, Nabil Abdel Maksoud, Laila A. Mousa, Ibrahim M. Kandil, Asem Anwar, M.A.K El Hemaly and Bahaa E. El Mohamady. \nEvidence based Facts on the Pathogenesis and Management of SUI. http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly02/el-hemaly02-ss\n\n14- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Mohamad A. Rizk and Mohamad A.K.M.El Hemaly.\n Urethro-plasty, a Novel Operation based on a New Concept, for the Treatment of Stress Urinary Incontinence, S.U.I., Detrusor Instability, D.I., and Mixed-type of Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/urethro-plasty_01\n\n15-Ibrahim M. Kandil, Abdel Karim M. El Hemaly, Mohamad M. Radwan: Ultrasonic Assessment of the Internal Urethral Sphincter in Stress Urinary Incontinence. The Internet Journal of Gynecology and Obstetrics. 2003. Volume 2 Number 1. \n\n\n16-Abdel Karim M. El Hemaly. Nocturnal Enureses: A Novel Concept on its pathogenesis and Treatment.\nhttp://www.obgyn.net/urogynecolgy/?page=articles/nocturnal_enuresis\n\n17- Abdel Karim M. El Hemaly. Nocturnal Enureses: An Update on the pathogenesis and Treatment.\nhttp://www.obgyn.net/urogynecology/?page=/ENHLIDH/PUBD/FEATURES/\nPresentations/ Nocturnal_Enuresis/nocturnal_enuresis\n\n18-Maternal Mortality in Egypt, a cry for help and attention. The Second International Conference of the African Society of Organization & Gestosis, 1998, 3rd Annual International Conference of Ob/Gyn Department � Sohag Faculty of Medicine University. Feb. 11-13. Luxor, Egypt. \n19-Postmenopausal Osteprosis. The 2nd annual conference of Health Insurance Organization on Family Planning and its role in primary health care. Zagaziz, Egypt, February 26-27, 1997, Center of Complementary Services for Maternity and childhood care. \n20-Laparoscopic Assisted vaginal hysterectomy. 10th International Annual Congress Modern Trends in Reproductive Techniques 23-24 March 1995. Alexandria, Egypt. \n21-Immunological Studies in Pre-eclamptic Toxaemia. Proceedings of 10th Annual Ain Shams Medical Congress. Cairo, Egypt, March 6-10, 1987. \n22-Socio-demographic factorse affecting acceptability of the long-acting contraceptive injections in a rural Egyptian community. Journal of Biosocial Science 29:305, 1987. \n23-Plasma fibronectin levels hypertension during pregnancy. The Journal of the Egypt. Soc. of Ob./Gyn. 13:1, 17-21, Jan. 1987. \n24-Effect of smoking on pregnancy. Journal of Egypt. Soc. of Ob./Gyn. 12:3, 111-121, Sept 1986. \n25-Socio-demographic aspects of nausea and vomiting in early pregnancy. Journal of the Egypt. Soc. of Ob./Gyn. 12:3, 35-42, Sept. 1986. \n26-Effect of intrapartum oxygen inhalation on maternofetal blood gases and pH. Journal of the Egypt. Soc. of Ob./Gyn. 12:3, 57-64, Sept. 1986. \n27-The effect of severe pre-eclampsia on serum transaminases. The Egypt. J. Med. Sci. 7(2): 479-485, 1986. \n28-A study of placental immunoreceptors in pre-eclampsia. The Egypt. J. Med. Sci. 7(2): 211-216, 1986. \n29-Serum human placental lactogen (hpl) in normal, toxaemic and diabetic pregnant women, during pregnancy and its relation to the outcome of pregnancy. Journal of the Egypt. Soc. of Ob./Gyn. 12:2, 11-23, May 1986. \n30-Pregnancy specific B1 Glycoprotein and free estriol in the serum of normal, toxaemic and diabetic pregnant women during pregnancy and after delivery. Journal of the Egypt. Soc. of Ob./Gyn. 12:1, 63-70, Jan. 1986. Also was accepted and presented at Xith World Congress of Gynecology and Obstetrics, Berlin (West), September 15-20, 1985. \n31-Pregnancy and labor in women over the age of forty years. Accepted and presented at Al-Azhar International Medical Conference, Cairo 28-31 Dec. 1985. \n32-Effect of Copper T intra-uterine device on cervico-vaginal flora. Int. J. Gynaecol. Obstet. 23:2, 153-156, April 1985. \n33-Factors affecting the occurrence of post-Caesarean section febrile morbidity. Population Sciences, 6, 139-149, 1985. \n34-Pre-eclamptic toxaemia and its relation to H.L.A. system. Population Sciences, 6, 131-139, 1985. \n35-The menstrual pattern and occurrence of pregnancy one year after discontinuation of Depo-medroxy progesterone acetate as a postpartum contraceptive. Population Sciences, 6, 105-111, 1985. \n36-The menstrual pattern and side effects of Depo-medroxy progesterone acetate as postpartum contraceptive. Population Sciences, 6, 97-105, 1985. \n37-Actinomyces in the vaginas of women with and without intrauterine contraceptive devices. Population Sciences, 6, 77-85, 1985. \n38-Comparative efficacy of ibuprofen and etamsylate in the treatment of I.U.D. menorrhagia. Population Sciences, 6, 63-77, 1985. \n39-Changes in cervical mucus copper and zinc in women using I.U.D.�s. Population Sciences, 6, 35-41, 1985. \n40-Histochemical study of the endometrium of infertile women. Egypt. J. Histol. 8(1) 63-66, 1985. \n41-Genital flora in pre- and post-menopausal women. Egypt. J. Med. Sci. 4(2), 165-172, 1983. \n42-Evaluation of the vaginal rugae and thickness in 8 different groups. Journal of the Egypt. Soc. of Ob./Gyn. 9:2, 101-114, May 1983. \n43-The effect of menopausal status and conjugated oestrogen therapy on serum cholesterol, triglycerides and electrophoretic lipoprotein patterns. Al-Azhar Medical Journal, 12:2, 113-119, April 1983. \n44-Laparoscopic ventrosuspension: A New Technique. Int. J. Gynaecol. Obstet., 20, 129-31, 1982. \n45-The laparoscope: A useful diagnostic tool in general surgery. Al-Azhar Medical Journal, 11:4, 397-401, Oct. 1982. \n46-The value of the laparoscope in the diagnosis of polycystic ovary. Al-Azhar Medical Journal, 11:2, 153-159, April 1982. \n47-An anaesthetic approach to the management of eclampsia. Ain Shams Medical Journal, accepted for publication 1981. \n48-Laparoscopy on patients with previous lower abdominal surgery. Fertility management edited by E. Osman and M. Wahba 1981. \n49-Heart diseases with pregnancy. Population Sciences, 11, 121-130, 1981. \n50-A study of the biosocial factors affecting perinatal mortality in an Egyptian maternity hospital. Population Sciences, 6, 71-90, 1981. \n51-Pregnancy Wastage. Journal of the Egypt. Soc. of Ob./Gyn. 11:3, 57-67, Sept. 1980. \n52-Analysis of maternal deaths in Egyptian maternity hospitals. Population Sciences, 1, 59-65, 1979. \nArticles published on OBGYN.net: \n1- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Laila A. S. Mousa and Mohamad A.K.M.El Hemaly.\nUrethro-vaginoplasty, an innovated operation for the treatment of: Stress Urinary Incontinence (SUI), Detursor Overactivity (DO), Mixed Urinary Incontinence and Anterior Vaginal Wall Descent. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/ urethro-vaginoplasty_01\n\n2- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamed M. Radwan.\n Urethro-raphy a new technique for surgical management of Stress Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/\nnew-tech-urethro\n\n3- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamad A. Rizk, Nabil Abdel Maksoud H., Mohamad M. Radwan, Khalid Z. El Shieka, Mohamad A. K. M. El Hemaly, and Ahmad T. El Saban.\nUrethro-raphy The New Operation for the treatment of stress urinary incontinence, SUI, detrusor instability, DI, and mixed-type of urinary incontinence; short and long term results. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=urogyn/articles/\nurethroraphy-09280\n\n4-Abdel Karim M. El Hemaly, Ibrahim M Kandil, and Bahaa E. El Mohamady. Menopause, and Voiding troubles. \nhttp://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly03/el-hemaly03-ss\n\n5-El Hemaly AKMA, Mousa L.A. Micturition and Urinary\tContinence. Int J Gynecol Obstet 1996; 42: 291-2. \n\n6-Abdel Karim M. El Hemaly.\n Urinary incontinence in gynecology, a review article.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/abs-urinary_incotinence_gyn_ehemaly \n\n7-El Hemaly AKMA. Nocturnal Enuresis: Pathogenesis and Treatment. \nInt Urogynecol J Pelvic Floor Dysfunct 1998;9: 129-31.\n \n8-El Hemaly AKMA, Mousa L.A.E. Stress Urinary Incontinence, a New Concept. Eur J Obstet Gynecol Reprod Biol 1996; 68: 129-35. \n\n9- El Hemaly AKMA, Kandil I. M. Stress Urinary Incontinence SUI facts and fiction. Is SUI a puzzle?! http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly/el-hemaly-ss\n\n10-Abdel Karim El Hemaly, Nabil Abdel Maksoud, Laila A. Mousa, Ibrahim M. Kandil, Asem Anwar, M.A.K El Hemaly and Bahaa E. El Mohamady. \nEvidence based Facts on the Pathogenesis and Management of SUI. http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly02/el-hemaly02-ss\n\n11- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Mohamad A. Rizk and Mohamad A.K.M.El Hemaly.\n Urethro-plasty, a Novel Operation based on a New Concept, for the Treatment of Stress Urinary Incontinence, S.U.I., Detrusor Instability, D.I., and Mixed-type of Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/urethro-plasty_01\n\n12-Ibrahim M. Kandil, Abdel Karim M. El Hemaly, Mohamad M. Radwan: Ultrasonic Assessment of the Internal Urethral Sphincter in Stress Urinary Incontinence. The Internet Journal of Gynecology and Obstetrics. 2003. Volume 2 Number 1. \n\n13-Abdel Karim M. El Hemaly. Nocturnal Enureses: A Novel Concept on its pathogenesis and Treatment.\nhttp://www.obgyn.net/urogynecolgy/?page=articles/nocturnal_enuresis\n\n14- Abdel Karim M. El Hemaly. Nocturnal Enureses: An Update on the pathogenesis and Treatment.\nhttp://www.obgyn.net/urogynecology/?page=/ENHLIDH/PUBD/FEATURES/\nPresentations/ Nocturnal_Enuresis/nocturnal_enuresis",institutionString:null,institution:{name:"Al Azhar University",country:{name:"Egypt"}}},{id:"113313",title:"Dr.",name:"Abdel-Aal",middleName:null,surname:"Mantawy",slug:"abdel-aal-mantawy",fullName:"Abdel-Aal Mantawy",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ain Shams University",country:{name:"Egypt"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:5681},{group:"region",caption:"Middle and South America",value:2,count:5161},{group:"region",caption:"Africa",value:3,count:1683},{group:"region",caption:"Asia",value:4,count:10200},{group:"region",caption:"Australia and Oceania",value:5,count:886},{group:"region",caption:"Europe",value:6,count:15610}],offset:12,limit:12,total:1683},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{topicId:"8"},books:[{type:"book",id:"10454",title:"Technology in Agriculture",subtitle:null,isOpenForSubmission:!0,hash:"dcfc52d92f694b0848977a3c11c13d00",slug:null,bookSignature:"Dr. Fiaz Ahmad and Prof. Muhammad Sultan",coverURL:"https://cdn.intechopen.com/books/images_new/10454.jpg",editedByType:null,editors:[{id:"338219",title:"Dr.",name:"Fiaz",surname:"Ahmad",slug:"fiaz-ahmad",fullName:"Fiaz Ahmad"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10502",title:"Aflatoxins",subtitle:null,isOpenForSubmission:!0,hash:"34fe61c309f2405130ede7a267cf8bd5",slug:null,bookSignature:"Dr. Lukman Bola Abdulra'uf",coverURL:"https://cdn.intechopen.com/books/images_new/10502.jpg",editedByType:null,editors:[{id:"149347",title:"Dr.",name:"Lukman",surname:"Abdulra'uf",slug:"lukman-abdulra'uf",fullName:"Lukman Abdulra'uf"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10504",title:"Crystallization",subtitle:null,isOpenForSubmission:!0,hash:"3478d05926950f475f4ad2825d340963",slug:null,bookSignature:"Dr. Youssef Ben Smida and Dr. Riadh Marzouki",coverURL:"https://cdn.intechopen.com/books/images_new/10504.jpg",editedByType:null,editors:[{id:"311698",title:"Dr.",name:"Youssef",surname:"Ben Smida",slug:"youssef-ben-smida",fullName:"Youssef Ben Smida"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10552",title:"Montmorillonite",subtitle:null,isOpenForSubmission:!0,hash:"c4a279761f0bb046af95ecd32ab09e51",slug:null,bookSignature:"Prof. Faheem Uddin",coverURL:"https://cdn.intechopen.com/books/images_new/10552.jpg",editedByType:null,editors:[{id:"228107",title:"Prof.",name:"Faheem",surname:"Uddin",slug:"faheem-uddin",fullName:"Faheem Uddin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10572",title:"Advancements in Chromophore and Bio-Chromophore Research",subtitle:null,isOpenForSubmission:!0,hash:"4aca0af0356d8d31fa8621859a68db8f",slug:null,bookSignature:"Dr. Rampal Pandey",coverURL:"https://cdn.intechopen.com/books/images_new/10572.jpg",editedByType:null,editors:[{id:"338234",title:"Dr.",name:"Rampal",surname:"Pandey",slug:"rampal-pandey",fullName:"Rampal Pandey"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10581",title:"Alkaline Chemistry and Applications",subtitle:null,isOpenForSubmission:!0,hash:"4ed90bdab4a7211c13cd432aa079cd20",slug:null,bookSignature:"Dr. Riadh Marzouki",coverURL:"https://cdn.intechopen.com/books/images_new/10581.jpg",editedByType:null,editors:[{id:"300527",title:"Dr.",name:"Riadh",surname:"Marzouki",slug:"riadh-marzouki",fullName:"Riadh Marzouki"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10582",title:"Chemical Vapor Deposition",subtitle:null,isOpenForSubmission:!0,hash:"f9177ff0e61198735fb86a81303259d0",slug:null,bookSignature:"Dr. Sadia Ameen, Dr. M. Shaheer Akhtar and Prof. Hyung-Shik Shin",coverURL:"https://cdn.intechopen.com/books/images_new/10582.jpg",editedByType:null,editors:[{id:"52613",title:"Dr.",name:"Sadia",surname:"Ameen",slug:"sadia-ameen",fullName:"Sadia Ameen"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10696",title:"Calorimetry",subtitle:null,isOpenForSubmission:!0,hash:"bb239599406f0b731bbfd62c1c8dbf3f",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10696.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10697",title:"Raman Spectroscopy",subtitle:null,isOpenForSubmission:!0,hash:"ab2446daed0caa4d243805387a2547ee",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10697.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10700",title:"Titanium Dioxide",subtitle:null,isOpenForSubmission:!0,hash:"c935253773c8ed0220e7b8a6fd90c4c6",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10700.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10702",title:"Polyimide",subtitle:null,isOpenForSubmission:!0,hash:"325bb1a83145389746e590eb13131902",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10702.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:9},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:17},{group:"topic",caption:"Business, Management and Economics",value:7,count:2},{group:"topic",caption:"Chemistry",value:8,count:7},{group:"topic",caption:"Computer and Information Science",value:9,count:10},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:5},{group:"topic",caption:"Engineering",value:11,count:14},{group:"topic",caption:"Environmental Sciences",value:12,count:2},{group:"topic",caption:"Immunology and Microbiology",value:13,count:5},{group:"topic",caption:"Materials Science",value:14,count:4},{group:"topic",caption:"Mathematics",value:15,count:1},{group:"topic",caption:"Medicine",value:16,count:60},{group:"topic",caption:"Nanotechnology and Nanomaterials",value:17,count:1},{group:"topic",caption:"Neuroscience",value:18,count:1},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:6},{group:"topic",caption:"Physics",value:20,count:2},{group:"topic",caption:"Psychology",value:21,count:3},{group:"topic",caption:"Robotics",value:22,count:1},{group:"topic",caption:"Social Sciences",value:23,count:3},{group:"topic",caption:"Technology",value:24,count:1},{group:"topic",caption:"Veterinary Medicine and Science",value:25,count:2}],offset:12,limit:12,total:11},popularBooks:{featuredBooks:[{type:"book",id:"9208",title:"Welding",subtitle:"Modern Topics",isOpenForSubmission:!1,hash:"7d6be076ccf3a3f8bd2ca52d86d4506b",slug:"welding-modern-topics",bookSignature:"Sadek Crisóstomo Absi Alfaro, Wojciech Borek and Błażej Tomiczek",coverURL:"https://cdn.intechopen.com/books/images_new/9208.jpg",editors:[{id:"65292",title:"Prof.",name:"Sadek Crisostomo Absi",middleName:"C. Absi",surname:"Alfaro",slug:"sadek-crisostomo-absi-alfaro",fullName:"Sadek Crisostomo Absi Alfaro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9139",title:"Topics in Primary Care Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ea774a4d4c1179da92a782e0ae9cde92",slug:"topics-in-primary-care-medicine",bookSignature:"Thomas F. Heston",coverURL:"https://cdn.intechopen.com/books/images_new/9139.jpg",editors:[{id:"217926",title:"Dr.",name:"Thomas F.",middleName:null,surname:"Heston",slug:"thomas-f.-heston",fullName:"Thomas F. Heston"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8697",title:"Virtual Reality and Its Application in Education",subtitle:null,isOpenForSubmission:!1,hash:"ee01b5e387ba0062c6b0d1e9227bda05",slug:"virtual-reality-and-its-application-in-education",bookSignature:"Dragan Cvetković",coverURL:"https://cdn.intechopen.com/books/images_new/8697.jpg",editors:[{id:"101330",title:"Dr.",name:"Dragan",middleName:"Mladen",surname:"Cvetković",slug:"dragan-cvetkovic",fullName:"Dragan Cvetković"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9785",title:"Endometriosis",subtitle:null,isOpenForSubmission:!1,hash:"f457ca61f29cf7e8bc191732c50bb0ce",slug:"endometriosis",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",editors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",slug:"courtney-marsh",fullName:"Courtney Marsh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9343",title:"Trace Metals in the Environment",subtitle:"New Approaches and Recent Advances",isOpenForSubmission:!1,hash:"ae07e345bc2ce1ebbda9f70c5cd12141",slug:"trace-metals-in-the-environment-new-approaches-and-recent-advances",bookSignature:"Mario Alfonso Murillo-Tovar, Hugo Saldarriaga-Noreña and Agnieszka Saeid",coverURL:"https://cdn.intechopen.com/books/images_new/9343.jpg",editors:[{id:"255959",title:"Dr.",name:"Mario Alfonso",middleName:null,surname:"Murillo-Tovar",slug:"mario-alfonso-murillo-tovar",fullName:"Mario Alfonso Murillo-Tovar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7831",title:"Sustainability in Urban Planning and Design",subtitle:null,isOpenForSubmission:!1,hash:"c924420492c8c2c9751e178d025f4066",slug:"sustainability-in-urban-planning-and-design",bookSignature:"Amjad Almusaed, Asaad Almssad and Linh Truong - Hong",coverURL:"https://cdn.intechopen.com/books/images_new/7831.jpg",editors:[{id:"110471",title:"Dr.",name:"Amjad",middleName:"Zaki",surname:"Almusaed",slug:"amjad-almusaed",fullName:"Amjad Almusaed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8468",title:"Sheep Farming",subtitle:"An Approach to Feed, Growth and Sanity",isOpenForSubmission:!1,hash:"838f08594850bc04aa14ec873ed1b96f",slug:"sheep-farming-an-approach-to-feed-growth-and-sanity",bookSignature:"António Monteiro",coverURL:"https://cdn.intechopen.com/books/images_new/8468.jpg",editors:[{id:"190314",title:"Prof.",name:"António",middleName:"Cardoso",surname:"Monteiro",slug:"antonio-monteiro",fullName:"António Monteiro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8816",title:"Financial Crises",subtitle:"A Selection of Readings",isOpenForSubmission:!1,hash:"6f2f49fb903656e4e54280c79fabd10c",slug:"financial-crises-a-selection-of-readings",bookSignature:"Stelios Markoulis",coverURL:"https://cdn.intechopen.com/books/images_new/8816.jpg",editors:[{id:"237863",title:"Dr.",name:"Stelios",middleName:null,surname:"Markoulis",slug:"stelios-markoulis",fullName:"Stelios Markoulis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9376",title:"Contemporary Developments and Perspectives in International Health Security",subtitle:"Volume 1",isOpenForSubmission:!1,hash:"b9a00b84cd04aae458fb1d6c65795601",slug:"contemporary-developments-and-perspectives-in-international-health-security-volume-1",bookSignature:"Stanislaw P. Stawicki, Michael S. Firstenberg, Sagar C. Galwankar, Ricardo Izurieta and Thomas Papadimos",coverURL:"https://cdn.intechopen.com/books/images_new/9376.jpg",editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",middleName:null,surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7769",title:"Medical Isotopes",subtitle:null,isOpenForSubmission:!1,hash:"f8d3c5a6c9a42398e56b4e82264753f7",slug:"medical-isotopes",bookSignature:"Syed Ali Raza Naqvi and Muhammad Babar Imrani",coverURL:"https://cdn.intechopen.com/books/images_new/7769.jpg",editors:[{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9279",title:"Concepts, Applications and Emerging Opportunities in Industrial Engineering",subtitle:null,isOpenForSubmission:!1,hash:"9bfa87f9b627a5468b7c1e30b0eea07a",slug:"concepts-applications-and-emerging-opportunities-in-industrial-engineering",bookSignature:"Gary Moynihan",coverURL:"https://cdn.intechopen.com/books/images_new/9279.jpg",editors:[{id:"16974",title:"Dr.",name:"Gary",middleName:null,surname:"Moynihan",slug:"gary-moynihan",fullName:"Gary Moynihan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7807",title:"A Closer Look at Organizational Culture in Action",subtitle:null,isOpenForSubmission:!1,hash:"05c608b9271cc2bc711f4b28748b247b",slug:"a-closer-look-at-organizational-culture-in-action",bookSignature:"Süleyman Davut Göker",coverURL:"https://cdn.intechopen.com/books/images_new/7807.jpg",editors:[{id:"190035",title:"Associate Prof.",name:"Süleyman Davut",middleName:null,surname:"Göker",slug:"suleyman-davut-goker",fullName:"Süleyman Davut Göker"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:5126},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"9208",title:"Welding",subtitle:"Modern Topics",isOpenForSubmission:!1,hash:"7d6be076ccf3a3f8bd2ca52d86d4506b",slug:"welding-modern-topics",bookSignature:"Sadek Crisóstomo Absi Alfaro, Wojciech Borek and Błażej Tomiczek",coverURL:"https://cdn.intechopen.com/books/images_new/9208.jpg",editors:[{id:"65292",title:"Prof.",name:"Sadek Crisostomo Absi",middleName:"C. Absi",surname:"Alfaro",slug:"sadek-crisostomo-absi-alfaro",fullName:"Sadek Crisostomo Absi Alfaro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9139",title:"Topics in Primary Care Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ea774a4d4c1179da92a782e0ae9cde92",slug:"topics-in-primary-care-medicine",bookSignature:"Thomas F. Heston",coverURL:"https://cdn.intechopen.com/books/images_new/9139.jpg",editors:[{id:"217926",title:"Dr.",name:"Thomas F.",middleName:null,surname:"Heston",slug:"thomas-f.-heston",fullName:"Thomas F. Heston"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8697",title:"Virtual Reality and Its Application in Education",subtitle:null,isOpenForSubmission:!1,hash:"ee01b5e387ba0062c6b0d1e9227bda05",slug:"virtual-reality-and-its-application-in-education",bookSignature:"Dragan Cvetković",coverURL:"https://cdn.intechopen.com/books/images_new/8697.jpg",editors:[{id:"101330",title:"Dr.",name:"Dragan",middleName:"Mladen",surname:"Cvetković",slug:"dragan-cvetkovic",fullName:"Dragan Cvetković"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9785",title:"Endometriosis",subtitle:null,isOpenForSubmission:!1,hash:"f457ca61f29cf7e8bc191732c50bb0ce",slug:"endometriosis",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",editors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",slug:"courtney-marsh",fullName:"Courtney Marsh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9343",title:"Trace Metals in the Environment",subtitle:"New Approaches and Recent Advances",isOpenForSubmission:!1,hash:"ae07e345bc2ce1ebbda9f70c5cd12141",slug:"trace-metals-in-the-environment-new-approaches-and-recent-advances",bookSignature:"Mario Alfonso Murillo-Tovar, Hugo Saldarriaga-Noreña and Agnieszka Saeid",coverURL:"https://cdn.intechopen.com/books/images_new/9343.jpg",editors:[{id:"255959",title:"Dr.",name:"Mario Alfonso",middleName:null,surname:"Murillo-Tovar",slug:"mario-alfonso-murillo-tovar",fullName:"Mario Alfonso Murillo-Tovar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8468",title:"Sheep Farming",subtitle:"An Approach to Feed, Growth and Sanity",isOpenForSubmission:!1,hash:"838f08594850bc04aa14ec873ed1b96f",slug:"sheep-farming-an-approach-to-feed-growth-and-sanity",bookSignature:"António Monteiro",coverURL:"https://cdn.intechopen.com/books/images_new/8468.jpg",editors:[{id:"190314",title:"Prof.",name:"António",middleName:"Cardoso",surname:"Monteiro",slug:"antonio-monteiro",fullName:"António Monteiro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8816",title:"Financial Crises",subtitle:"A Selection of Readings",isOpenForSubmission:!1,hash:"6f2f49fb903656e4e54280c79fabd10c",slug:"financial-crises-a-selection-of-readings",bookSignature:"Stelios Markoulis",coverURL:"https://cdn.intechopen.com/books/images_new/8816.jpg",editors:[{id:"237863",title:"Dr.",name:"Stelios",middleName:null,surname:"Markoulis",slug:"stelios-markoulis",fullName:"Stelios Markoulis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7831",title:"Sustainability in Urban Planning and Design",subtitle:null,isOpenForSubmission:!1,hash:"c924420492c8c2c9751e178d025f4066",slug:"sustainability-in-urban-planning-and-design",bookSignature:"Amjad Almusaed, Asaad Almssad and Linh Truong - Hong",coverURL:"https://cdn.intechopen.com/books/images_new/7831.jpg",editors:[{id:"110471",title:"Dr.",name:"Amjad",middleName:"Zaki",surname:"Almusaed",slug:"amjad-almusaed",fullName:"Amjad Almusaed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9376",title:"Contemporary Developments and Perspectives in International Health Security",subtitle:"Volume 1",isOpenForSubmission:!1,hash:"b9a00b84cd04aae458fb1d6c65795601",slug:"contemporary-developments-and-perspectives-in-international-health-security-volume-1",bookSignature:"Stanislaw P. Stawicki, Michael S. Firstenberg, Sagar C. Galwankar, Ricardo Izurieta and Thomas Papadimos",coverURL:"https://cdn.intechopen.com/books/images_new/9376.jpg",editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",middleName:null,surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7769",title:"Medical Isotopes",subtitle:null,isOpenForSubmission:!1,hash:"f8d3c5a6c9a42398e56b4e82264753f7",slug:"medical-isotopes",bookSignature:"Syed Ali Raza Naqvi and Muhammad Babar Imrani",coverURL:"https://cdn.intechopen.com/books/images_new/7769.jpg",editors:[{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"8468",title:"Sheep Farming",subtitle:"An Approach to Feed, Growth and Sanity",isOpenForSubmission:!1,hash:"838f08594850bc04aa14ec873ed1b96f",slug:"sheep-farming-an-approach-to-feed-growth-and-sanity",bookSignature:"António Monteiro",coverURL:"https://cdn.intechopen.com/books/images_new/8468.jpg",editedByType:"Edited by",editors:[{id:"190314",title:"Prof.",name:"António",middleName:"Cardoso",surname:"Monteiro",slug:"antonio-monteiro",fullName:"António Monteiro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9523",title:"Oral and Maxillofacial Surgery",subtitle:null,isOpenForSubmission:!1,hash:"5eb6ec2db961a6c8965d11180a58d5c1",slug:"oral-and-maxillofacial-surgery",bookSignature:"Gokul Sridharan",coverURL:"https://cdn.intechopen.com/books/images_new/9523.jpg",editedByType:"Edited by",editors:[{id:"82453",title:"Dr.",name:"Gokul",middleName:null,surname:"Sridharan",slug:"gokul-sridharan",fullName:"Gokul Sridharan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9785",title:"Endometriosis",subtitle:null,isOpenForSubmission:!1,hash:"f457ca61f29cf7e8bc191732c50bb0ce",slug:"endometriosis",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",editedByType:"Edited by",editors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",slug:"courtney-marsh",fullName:"Courtney Marsh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9018",title:"Some RNA Viruses",subtitle:null,isOpenForSubmission:!1,hash:"a5cae846dbe3692495fc4add2f60fd84",slug:"some-rna-viruses",bookSignature:"Yogendra Shah and Eltayb Abuelzein",coverURL:"https://cdn.intechopen.com/books/images_new/9018.jpg",editedByType:"Edited by",editors:[{id:"278914",title:"Ph.D.",name:"Yogendra",middleName:null,surname:"Shah",slug:"yogendra-shah",fullName:"Yogendra Shah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8816",title:"Financial Crises",subtitle:"A Selection of Readings",isOpenForSubmission:!1,hash:"6f2f49fb903656e4e54280c79fabd10c",slug:"financial-crises-a-selection-of-readings",bookSignature:"Stelios Markoulis",coverURL:"https://cdn.intechopen.com/books/images_new/8816.jpg",editedByType:"Edited by",editors:[{id:"237863",title:"Dr.",name:"Stelios",middleName:null,surname:"Markoulis",slug:"stelios-markoulis",fullName:"Stelios Markoulis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9585",title:"Advances in Complex Valvular Disease",subtitle:null,isOpenForSubmission:!1,hash:"ef64f11e211621ecfe69c46e60e7ca3d",slug:"advances-in-complex-valvular-disease",bookSignature:"Michael S. Firstenberg and Imran Khan",coverURL:"https://cdn.intechopen.com/books/images_new/9585.jpg",editedByType:"Edited by",editors:[{id:"64343",title:null,name:"Michael S.",middleName:"S",surname:"Firstenberg",slug:"michael-s.-firstenberg",fullName:"Michael S. Firstenberg"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10150",title:"Smart Manufacturing",subtitle:"When Artificial Intelligence Meets the Internet of Things",isOpenForSubmission:!1,hash:"87004a19de13702d042f8ff96d454698",slug:"smart-manufacturing-when-artificial-intelligence-meets-the-internet-of-things",bookSignature:"Tan Yen Kheng",coverURL:"https://cdn.intechopen.com/books/images_new/10150.jpg",editedByType:"Edited by",editors:[{id:"78857",title:"Dr.",name:"Tan Yen",middleName:null,surname:"Kheng",slug:"tan-yen-kheng",fullName:"Tan Yen Kheng"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9386",title:"Direct Numerical Simulations",subtitle:"An Introduction and Applications",isOpenForSubmission:!1,hash:"158a3a0fdba295d21ff23326f5a072d5",slug:"direct-numerical-simulations-an-introduction-and-applications",bookSignature:"Srinivasa Rao",coverURL:"https://cdn.intechopen.com/books/images_new/9386.jpg",editedByType:"Edited by",editors:[{id:"6897",title:"Dr.",name:"Srinivasa",middleName:"P",surname:"Rao",slug:"srinivasa-rao",fullName:"Srinivasa Rao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9139",title:"Topics in Primary Care Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ea774a4d4c1179da92a782e0ae9cde92",slug:"topics-in-primary-care-medicine",bookSignature:"Thomas F. Heston",coverURL:"https://cdn.intechopen.com/books/images_new/9139.jpg",editedByType:"Edited by",editors:[{id:"217926",title:"Dr.",name:"Thomas F.",middleName:null,surname:"Heston",slug:"thomas-f.-heston",fullName:"Thomas F. Heston"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9208",title:"Welding",subtitle:"Modern Topics",isOpenForSubmission:!1,hash:"7d6be076ccf3a3f8bd2ca52d86d4506b",slug:"welding-modern-topics",bookSignature:"Sadek Crisóstomo Absi Alfaro, Wojciech Borek and Błażej Tomiczek",coverURL:"https://cdn.intechopen.com/books/images_new/9208.jpg",editedByType:"Edited by",editors:[{id:"65292",title:"Prof.",name:"Sadek Crisostomo Absi",middleName:"C. Absi",surname:"Alfaro",slug:"sadek-crisostomo-absi-alfaro",fullName:"Sadek Crisostomo Absi Alfaro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"1366",title:"Operations Research",slug:"information-and-communication-operations-research",parent:{title:"Information and Communication",slug:"information-and-communication"},numberOfBooks:1,numberOfAuthorsAndEditors:12,numberOfWosCitations:3,numberOfCrossrefCitations:5,numberOfDimensionsCitations:8,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"information-and-communication-operations-research",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"4646",title:"Cutting Edge Research in Technologies",subtitle:null,isOpenForSubmission:!1,hash:"a0c6cc73cb98936693e6e4845a19dfcf",slug:"cutting-edge-research-in-technologies",bookSignature:"Constantin Volosencu",coverURL:"https://cdn.intechopen.com/books/images_new/4646.jpg",editedByType:"Edited by",editors:[{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:1,mostCitedChapters:[{id:"48912",doi:"10.5772/61080",title:"Possibilities of Applying ICT to Improve Safe Movement of Blind and Visually Impaired Persons",slug:"possibilities-of-applying-ict-to-improve-safe-movement-of-blind-and-visually-impaired-persons",totalDownloads:1450,totalCrossrefCites:4,totalDimensionsCites:5,book:{slug:"cutting-edge-research-in-technologies",title:"Cutting Edge Research in Technologies",fullTitle:"Cutting Edge Research in Technologies"},signatures:"Dragan Peraković, Marko Periša and Ante Bilić Prcić",authors:[{id:"13092",title:"Associate Prof.",name:"Dragan",middleName:null,surname:"Perakovic",slug:"dragan-perakovic",fullName:"Dragan Perakovic"},{id:"174543",title:"Dr.",name:"Marko",middleName:null,surname:"Periša",slug:"marko-perisa",fullName:"Marko Periša"},{id:"174901",title:"Prof.",name:"Ante",middleName:null,surname:"Bilic Prcic",slug:"ante-bilic-prcic",fullName:"Ante Bilic Prcic"}]},{id:"49017",doi:"10.5772/61091",title:"Weaving Complex Patterns — From Weaving Looms to Weaving Machines",slug:"weaving-complex-patterns-from-weaving-looms-to-weaving-machines",totalDownloads:3457,totalCrossrefCites:0,totalDimensionsCites:2,book:{slug:"cutting-edge-research-in-technologies",title:"Cutting Edge Research in Technologies",fullTitle:"Cutting Edge Research in Technologies"},signatures:"Stana Kovačević and Ivana Schwarz",authors:[{id:"97687",title:"Dr.",name:"Ivana",middleName:null,surname:"Schwarz",slug:"ivana-schwarz",fullName:"Ivana Schwarz"}]},{id:"49278",doi:"10.5772/61136",title:"Rapid Prototyping of Embedded Video Processing Systems in FPGA Devices",slug:"rapid-prototyping-of-embedded-video-processing-systems-in-fpga-devices",totalDownloads:1651,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"cutting-edge-research-in-technologies",title:"Cutting Edge Research in Technologies",fullTitle:"Cutting Edge Research in Technologies"},signatures:"Andrej Trost and Andrej Žemva",authors:[{id:"168194",title:"Dr.",name:"Andrej",middleName:null,surname:"Žemva",slug:"andrej-zemva",fullName:"Andrej Žemva"},{id:"178808",title:"Dr.",name:"Andrej",middleName:null,surname:"Trost",slug:"andrej-trost",fullName:"Andrej Trost"}]}],mostDownloadedChaptersLast30Days:[{id:"49017",title:"Weaving Complex Patterns — From Weaving Looms to Weaving Machines",slug:"weaving-complex-patterns-from-weaving-looms-to-weaving-machines",totalDownloads:3457,totalCrossrefCites:0,totalDimensionsCites:2,book:{slug:"cutting-edge-research-in-technologies",title:"Cutting Edge Research in Technologies",fullTitle:"Cutting Edge Research in Technologies"},signatures:"Stana Kovačević and Ivana Schwarz",authors:[{id:"97687",title:"Dr.",name:"Ivana",middleName:null,surname:"Schwarz",slug:"ivana-schwarz",fullName:"Ivana Schwarz"}]},{id:"48717",title:"An Analysis of Data Link Control Protocols",slug:"an-analysis-of-data-link-control-protocols",totalDownloads:1080,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"cutting-edge-research-in-technologies",title:"Cutting Edge Research in Technologies",fullTitle:"Cutting Edge Research in Technologies"},signatures:"Pinaki Mitra",authors:[{id:"89103",title:"Prof.",name:"Pinaki",middleName:null,surname:"Mitra",slug:"pinaki-mitra",fullName:"Pinaki Mitra"}]},{id:"48912",title:"Possibilities of Applying ICT to Improve Safe Movement of Blind and Visually Impaired Persons",slug:"possibilities-of-applying-ict-to-improve-safe-movement-of-blind-and-visually-impaired-persons",totalDownloads:1450,totalCrossrefCites:4,totalDimensionsCites:5,book:{slug:"cutting-edge-research-in-technologies",title:"Cutting Edge Research in Technologies",fullTitle:"Cutting Edge Research in Technologies"},signatures:"Dragan Peraković, Marko Periša and Ante Bilić Prcić",authors:[{id:"13092",title:"Associate Prof.",name:"Dragan",middleName:null,surname:"Perakovic",slug:"dragan-perakovic",fullName:"Dragan Perakovic"},{id:"174543",title:"Dr.",name:"Marko",middleName:null,surname:"Periša",slug:"marko-perisa",fullName:"Marko Periša"},{id:"174901",title:"Prof.",name:"Ante",middleName:null,surname:"Bilic Prcic",slug:"ante-bilic-prcic",fullName:"Ante Bilic Prcic"}]},{id:"49181",title:"3 DoF/6 DoF Localization System for Low Computing Power Mobile Robot Platforms",slug:"3-dof-6-dof-localization-system-for-low-computing-power-mobile-robot-platforms",totalDownloads:1155,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"cutting-edge-research-in-technologies",title:"Cutting Edge Research in Technologies",fullTitle:"Cutting Edge Research in Technologies"},signatures:"Carlos M. Costa, Héber M. Sobreira, Armando J. Sousa and\nGermano Veiga",authors:[{id:"97599",title:"Prof.",name:"Armando",middleName:null,surname:"Sousa",slug:"armando-sousa",fullName:"Armando Sousa"},{id:"174421",title:"M.Sc.",name:"Carlos",middleName:"Miguel Correeia Da",surname:"Costa",slug:"carlos-costa",fullName:"Carlos Costa"},{id:"174524",title:"Dr.",name:"Germano",middleName:null,surname:"Veiga",slug:"germano-veiga",fullName:"Germano Veiga"},{id:"177595",title:"Dr.",name:"Héber Miguel",middleName:null,surname:"Plácido Sobreira",slug:"heber-miguel-placido-sobreira",fullName:"Héber Miguel Plácido Sobreira"}]},{id:"49278",title:"Rapid Prototyping of Embedded Video Processing Systems in FPGA Devices",slug:"rapid-prototyping-of-embedded-video-processing-systems-in-fpga-devices",totalDownloads:1651,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"cutting-edge-research-in-technologies",title:"Cutting Edge Research in Technologies",fullTitle:"Cutting Edge Research in Technologies"},signatures:"Andrej Trost and Andrej Žemva",authors:[{id:"168194",title:"Dr.",name:"Andrej",middleName:null,surname:"Žemva",slug:"andrej-zemva",fullName:"Andrej Žemva"},{id:"178808",title:"Dr.",name:"Andrej",middleName:null,surname:"Trost",slug:"andrej-trost",fullName:"Andrej Trost"}]}],onlineFirstChaptersFilter:{topicSlug:"information-and-communication-operations-research",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:"profile.detail",path:"/profiles/279427/askia-m-mohammed",hash:"",query:{},params:{id:"279427",slug:"askia-m-mohammed"},fullPath:"/profiles/279427/askia-m-mohammed",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)}()