\\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:{caption:"IntechOpen Maintains",originalUrl:"/media/original/113"}},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-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"7850",leadTitle:null,fullTitle:"Mitochondria and Brain Disorders",title:"Mitochondria and Brain Disorders",subtitle:null,reviewType:"peer-reviewed",abstract:"The mitochondrion is a unique and ubiquitous organelle that contains its own genome, encoding essential proteins that are major components of the respiratory chain and energy production system. Mitochondria play a dominant role in the life and function of eukaryotic cells including neurons and glia, as their survival and activity depend upon mitochondrial energy production and supply. Besides energy production, mitochondria also play a vital role in calcium homeostasis and may induce apoptosis by excitotoxicity. Mitochondrial dysfunction is related to common neurological diseases, such as Parkinson's disease, Alzheimer's disease, Friedreich's ataxia, Huntington's disease, and Multiple Sclerosis. An efficient treatment of mitochondrial dysfunction would open new horizons in the therapeutic perspectives of a substantial number of inflammatory and degenerative neurological disorders.",isbn:"978-1-78985-532-6",printIsbn:"978-1-78985-531-9",pdfIsbn:"978-1-78985-653-8",doi:"10.5772/intechopen.77668",price:119,priceEur:129,priceUsd:155,slug:"mitochondria-and-brain-disorders",numberOfPages:124,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"e4cb9b34e45c6177ede9cf78fbda4b82",bookSignature:"Stavros Baloyannis",publishedDate:"March 11th 2020",coverURL:"https://cdn.intechopen.com/books/images_new/7850.jpg",numberOfDownloads:5569,numberOfWosCitations:0,numberOfCrossrefCitations:7,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:11,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:18,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 4th 2019",dateEndSecondStepPublish:"March 21st 2019",dateEndThirdStepPublish:"May 20th 2019",dateEndFourthStepPublish:"August 8th 2019",dateEndFifthStepPublish:"October 7th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"156098",title:"Emeritus Prof.",name:"Stavros J.",middleName:"J.",surname:"Baloyannis",slug:"stavros-j.-baloyannis",fullName:"Stavros J. Baloyannis",profilePictureURL:"https://mts.intechopen.com/storage/users/156098/images/system/156098.jpg",biography:"Stavros J. Baloyannis is Professor Emeritus of Neurology at Aristotelian University, Thessaloniki, Greece. He graduated from the School of Medicine, Aristotelian University. He trained in Neurology at the same university and at the Institute of Neurology, Queen Square, London. He also trained in Neuropathology and Electron Microscopy at the Institute of Neurology, London; Catholic University of Louvain, Belgium; University of Pennsylvania; and Yale University. He trained in Acoustic Neuropathology at Harvard University, and in Neuroimmunology at Yale University. Dr. Baloyannis has conducted research on the blood-brain barrier, mitochondria in Alzheimer’s disease, synaptogenesis, neurodegeneration, dendritic and synaptic pathology, and Golgi apparatus in dementias. His special interests include neuroethics, neurolinguistics, neurophilosophy, history of neurosciences, neurology and art, and the brain and music. He is a member of sixty-two scientific societies and an honorary member of the Academy of Hellenic Air Forces. He is also the president of the Society for the amelioration of the quality of life in neurological diseases and former president of the Orthodox Association for the medical mission. He is a visiting professor at Tufts University, Democritus University, School of Theology, School of Philosophy. Dr. Baloyannis is the author of 29 textbooks, 760 papers on neurology and neurosciences, and 3 books of poems. From 1992 to 2011, he was the head of the Department of Neurology and director of the Research Institute for Alzheimer’s disease.",institutionString:"Aristotle University of Thessaloniki",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"8",totalChapterViews:"0",totalEditedBooks:"5",institution:{name:"Aristotle University of Thessaloniki",institutionURL:null,country:{name:"Greece"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1049",title:"Mitochondrial Genetics",slug:"mitochondrial-genetics"}],chapters:[{id:"70996",title:"Introductory Chapter: Mitochondrial Alterations and Neurological Disorders",doi:"10.5772/intechopen.91051",slug:"introductory-chapter-mitochondrial-alterations-and-neurological-disorders",totalDownloads:775,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:null,signatures:"Stavros J. Baloyannis",downloadPdfUrl:"/chapter/pdf-download/70996",previewPdfUrl:"/chapter/pdf-preview/70996",authors:[{id:"156098",title:"Emeritus Prof.",name:"Stavros J.",surname:"Baloyannis",slug:"stavros-j.-baloyannis",fullName:"Stavros J. Baloyannis"}],corrections:null},{id:"69863",title:"Pathology Associated with Hormones of Adrenal Cortex",doi:"10.5772/intechopen.84815",slug:"pathology-associated-with-hormones-of-adrenal-cortex",totalDownloads:835,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Adrenal gland is an endocrine organ comprising of an outer cortex and inner medulla. These secrete various hormones that have a vital role in maintaining the normal homeostasis of the body. Lesions of adrenal cortex are quite common to encounter and most of these are related to the hormones secreted by three layers of adrenal cortex: the zona glomerulosa, the zona fasciculata, and the zona reticularis. Also it is very infrequent to encounter metastatic lesions in the adrenal glands too. So it is very important as a part of a clinician as well as a pathologist to know the pattern in which these hormones are secreted along with their physiological roles. Thus this chapter includes the disease that are related to excess as well as deficiencies of the hormones secreted by adrenal cortex. The chapter also includes various genetic syndromes that are associated with the disorders associated with hormones of adrenal cortex. The last part of the chapter includes a brief description of various benign as well as malignant lesions, the pathological as well as the etiological aspects and the hormonal abnormalities associated. This chapter thus mainly focuses on the pathology associated with the adrenal cortex and hormones secreted by the various layers of adrenal cortex.",signatures:"Lovelesh K. Nigam, Aruna V. Vanikar, Rashmi D. Patel, Kamal V. Kanodia and Kamlesh S. Suthar",downloadPdfUrl:"/chapter/pdf-download/69863",previewPdfUrl:"/chapter/pdf-preview/69863",authors:[{id:"228499",title:"Dr.",name:"Lovelesh K.",surname:"Nigam",slug:"lovelesh-k.-nigam",fullName:"Lovelesh K. Nigam"},{id:"239124",title:"Dr.",name:"Aruna V.",surname:"Vanikar",slug:"aruna-v.-vanikar",fullName:"Aruna V. Vanikar"},{id:"239127",title:"Dr.",name:"Rashmi",surname:"Dalsukhbhai Patel",slug:"rashmi-dalsukhbhai-patel",fullName:"Rashmi Dalsukhbhai Patel"},{id:"239128",title:"Dr.",name:"Kamal V.",surname:"Kanodia",slug:"kamal-v.-kanodia",fullName:"Kamal V. Kanodia"},{id:"282877",title:"Dr.",name:"Kamlesh",surname:"Suthar",slug:"kamlesh-suthar",fullName:"Kamlesh Suthar"}],corrections:null},{id:"67194",title:"PET Imaging of Mitochondrial Function in the Living Brain",doi:"10.5772/intechopen.86492",slug:"pet-imaging-of-mitochondrial-function-in-the-living-brain",totalDownloads:1016,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"In the last two and half decades, we have conducted research on brain functional imaging in nonhuman primates using animal positron emission tomography (PET) scanners with high spatial resolution. We recently designed and synthesized the novel PET probe [18F]BCPP-EF to quantitatively image mitochondria complex-I (MC-I) activity in the living brain. Brain MC-I activity, measured using [18F]BCPP-EF, was significantly lower in aged monkeys than that in young animals, while no significant reduction was observed in SV2A activity, a synaptic-specific parameter that was measured using [11C]UCB-J. Some aged monkeys exhibited increased amyloid-β deposition in the brain, measured using [11C]PiB, which induced neuroinflammation. A positive correlation was noted with neuroinflammation, measured using [11C]DPA-713 and a negative correlation with MC-I activity. Furthermore, a monkey model of Parkinson’s disease prepared by the chronic administration of MPTP revealed suppressed MC-I activity not only in the nigrostriatal dopamine pathway, measured using [11C]PE2I and [11C]6MemTyr, but also in cortical serotonergic neurons, measured using [11C]DASB. This review introduces the translational application of a novel PET probe for noninvasive MC-I imaging from preclinical to clinical PET measurements.",signatures:"Hideo Tsukada",downloadPdfUrl:"/chapter/pdf-download/67194",previewPdfUrl:"/chapter/pdf-preview/67194",authors:[{id:"179616",title:"Dr.",name:"Hideo",surname:"Tsukada",slug:"hideo-tsukada",fullName:"Hideo Tsukada"}],corrections:null},{id:"67264",title:"Mitochondrial Proteomic and Molecular Network Alterations in Human Ovarian Cancers",doi:"10.5772/intechopen.86493",slug:"mitochondrial-proteomic-and-molecular-network-alterations-in-human-ovarian-cancers",totalDownloads:868,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Mitochondrion is a multi-functional organelle, which plays important role in human ovarian cancers. Mitochondrial quantitative proteomics was used to detect, identify, and quantify proteins from mitochondrial samples prepared from ovarian cancer and normal control ovary tissues. A total of 5115 mitochondrial proteins and 1198 mitochondrial differentially expressed proteins (mtDEPs) were identified in human ovarian cancer compared to control tissues. Pathway network analysis revealed multiple pathway network changes to involve those mitochondrial proteins and mtDEPs. These findings provide the scientific data about the role of mitochondria plays in ovarian cancer, and offer the source for discovery of mitochondrial biomarker for ovarian cancers.",signatures:"Xianquan Zhan and Na Li",downloadPdfUrl:"/chapter/pdf-download/67264",previewPdfUrl:"/chapter/pdf-preview/67264",authors:[{id:"223233",title:"Prof.",name:"Xianquan",surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan"},{id:"318858",title:"Dr.",name:"Na",surname:"Li",slug:"na-li",fullName:"Na Li"}],corrections:null},{id:"68488",title:"Mitochondrial Dysfunction as a Key Event during Aging: From Synaptic Failure to Memory Loss",doi:"10.5772/intechopen.88445",slug:"mitochondrial-dysfunction-as-a-key-event-during-aging-from-synaptic-failure-to-memory-loss",totalDownloads:1239,totalCrossrefCites:6,totalDimensionsCites:10,hasAltmetrics:1,abstract:"Mitochondria are important cellular organelles with key regulatory functions in energy production, oxidative balance, and calcium homeostasis. This is especially important in the brain, since neurons require a large number of functional mitochondria to supply their high energy requirement, mainly for synaptic processes. A decrease in the activity and quality of mitochondria in the brain, particularly in the hippocampus, is associated with normal aging and a large number of neurodegenerative diseases compromising memory function. Although synaptic and cognitive dysfunction is multifactorial, growing evidence demonstrates that mitochondria play a key role in these processes and suggests that maintaining mitochondrial function could prevent these age-dependent alterations. In this chapter, we will discuss the hippocampal mitochondrial dysfunction present in aging and how these defects promote age-associated synaptic damage and cognitive impairment. We will summarize evidence that shows how neurodegeneration can be accelerated or attenuated during aging by modulating mitochondrial function.",signatures:"Claudia Jara, Angie K. Torres, Margrethe A. Olesen and Cheril Tapia-Rojas",downloadPdfUrl:"/chapter/pdf-download/68488",previewPdfUrl:"/chapter/pdf-preview/68488",authors:[{id:"183873",title:"Dr.",name:"Claudia",surname:"Jara",slug:"claudia-jara",fullName:"Claudia Jara"},{id:"299224",title:"Dr.",name:"Cheril",surname:"Tapia-Rojas",slug:"cheril-tapia-rojas",fullName:"Cheril Tapia-Rojas"},{id:"299227",title:"Ms.",name:"Angie K.",surname:"Torres",slug:"angie-k.-torres",fullName:"Angie K. Torres"},{id:"299230",title:"Ms.",name:"Margrethe",surname:"A. Olesen",slug:"margrethe-a.-olesen",fullName:"Margrethe A. Olesen"}],corrections:null},{id:"68330",title:"Coenzyme Q 10 and L-Carnitine Disturbances in Children with Mitochondrial Diseases",doi:"10.5772/intechopen.87950",slug:"coenzyme-q-sub-10-sub-and-l-carnitine-disturbances-in-children-with-mitochondrial-diseases",totalDownloads:836,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Coenzyme Q10 (CoQ10) and L-carnitine are very important biologically active compounds involved in energy metabolism. L-carnitine and coenzyme Q10 disturbances in mitochondrial diseases require the correction. Patients and methods: The levels of coenzyme Q10 and L-carnitine (total carnitine, free carnitine, and acylcarnitines) were determined in children with mitochondrial diseases (25 children and 16 children, respectively). High-performance liquid chromatography with UV detection (chromatograph Shimadzu Nexera LC-30) and chromatography-mass spectrometry (Agilent 6410 QQQ , USA) were used. As an additional parameter of possible coenzyme Q10 and carnitine insufficiency, the coenzyme Q10/cholesterol ratio and acylcarnitines/free carnitine ratio were calculated. Results: A significantly low ratio of coenzyme Q10/cholesterol in children with mitochondrial diseases was revealed—0.10 ± 0.01 vs. 0.19 ± 0.01 in the control group (p < 0.001). A lower absolute level of coenzyme Q10 and tendency toward a more pronounced decrease in the Q10/cholesterol ratio in older patients (6–16 years) were shown. The free carnitine blood level was within the normal range and averaged at 29.8 ± 2.6 μmol/l; however, the level was lower than that in the control group (44 ± 5.2 μmol/l, p < 0.05). A pronounced significant increase in the acylcarnitines/free carnitine ratio was determined—1.5 ± 0.05 (the normal range < 0.6).",signatures:"Ekaterina A. Nikolaeva, Ilgar S. Mamedov and Irina V. Zolkina",downloadPdfUrl:"/chapter/pdf-download/68330",previewPdfUrl:"/chapter/pdf-preview/68330",authors:[{id:"299513",title:"Dr.",name:"Ekaterina",surname:"Nikolaeva",slug:"ekaterina-nikolaeva",fullName:"Ekaterina Nikolaeva"},{id:"304282",title:"Dr.",name:"Ilgar",surname:"Mamedov",slug:"ilgar-mamedov",fullName:"Ilgar Mamedov"},{id:"304283",title:"Dr.",name:"Irina",surname:"Zolkina",slug:"irina-zolkina",fullName:"Irina Zolkina"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"6331",title:"Hypothalamus in Health and Diseases",subtitle:null,isOpenForSubmission:!1,hash:"d8943dda86e7f5eea7bb5afc1ff70cfe",slug:"hypothalamus-in-health-and-diseases",bookSignature:"Stavros J. Baloyannis and Jan Oxholm Gordeladze",coverURL:"https://cdn.intechopen.com/books/images_new/6331.jpg",editedByType:"Edited by",editors:[{id:"156098",title:"Emeritus Prof.",name:"Stavros J.",surname:"Baloyannis",slug:"stavros-j.-baloyannis",fullName:"Stavros J. Baloyannis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9638",title:"Cerebral and Cerebellar Cortex",subtitle:"Interaction and Dynamics in Health and Disease",isOpenForSubmission:!1,hash:"3770f481b045cb47025fe4f409c3e6c1",slug:"cerebral-and-cerebellar-cortex-interaction-and-dynamics-in-health-and-disease",bookSignature:"Stavros J. Baloyannis",coverURL:"https://cdn.intechopen.com/books/images_new/9638.jpg",editedByType:"Edited by",editors:[{id:"156098",title:"Emeritus Prof.",name:"Stavros J.",surname:"Baloyannis",slug:"stavros-j.-baloyannis",fullName:"Stavros J. Baloyannis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10222",title:"Demyelination Disorders",subtitle:null,isOpenForSubmission:!1,hash:"b6c26ceccacdde70c41c587361bd5558",slug:"demyelination-disorders",bookSignature:"Stavros J. Baloyannis, Fabian H. Rossi and Welwin Liu",coverURL:"https://cdn.intechopen.com/books/images_new/10222.jpg",editedByType:"Edited by",editors:[{id:"156098",title:"Emeritus Prof.",name:"Stavros J.",surname:"Baloyannis",slug:"stavros-j.-baloyannis",fullName:"Stavros J. Baloyannis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8296",title:"Multiple Sclerosis",subtitle:null,isOpenForSubmission:!1,hash:"ec14c3341208a441acbc52bc4b632c0c",slug:"multiple-sclerosis",bookSignature:"Stavros J. 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Crocci",authors:[{id:"94681",title:"MSc.",name:"Alexandre",middleName:null,surname:"Bitar",fullName:"Alexandre Bitar",slug:"alexandre-bitar"}]},{id:"31862",title:"The Problem of Contamination: Open vs. Closed vs. Semi-Closed Vitrification Systems",slug:"the-problem-of-contamination-open-vs-close-vs-semi-close-vitrification-systems",signatures:"Enrique Criado Scholz",authors:[{id:"108806",title:"Dr.",name:"Enrique",middleName:null,surname:"Criado Scholz",fullName:"Enrique Criado Scholz",slug:"enrique-criado-scholz"}]},{id:"31863",title:"Cryopreservation of Boar Spermatozoa: An Important Role of Antioxidants",slug:"cryopreservation-of-companion-and-livestock-animal-spermatozoa-an-important-role-of-antioxidants",signatures:"Kampon Kaeoket",authors:[{id:"92984",title:"Dr.",name:"Kampon",middleName:null,surname:"Kaeoket",fullName:"Kampon Kaeoket",slug:"kampon-kaeoket"}]},{id:"31864",title:"Cryopreservation of Rat Sperm",slug:"cryopreservation-of-rat-sperm",signatures:"Hideaki Yamashiro and Eimei Sato",authors:[{id:"92067",title:"Dr.",name:"Hideaki",middleName:null,surname:"Yamashiro",fullName:"Hideaki Yamashiro",slug:"hideaki-yamashiro"},{id:"97268",title:"Prof.",name:"Eimei",middleName:null,surname:"Sato",fullName:"Eimei Sato",slug:"eimei-sato"}]},{id:"31865",title:"Cryopreservation of Genetic Diversity in Rabbit Species (Oryctolagus cuniculus)",slug:"cryopreservation-of-genetic-diversity-in-rabbit-species",signatures:"Thierry Joly, Vanessa Neto and Pascal Salvetti",authors:[{id:"104423",title:"Dr.",name:"Thierry",middleName:null,surname:"Joly",fullName:"Thierry Joly",slug:"thierry-joly"}]},{id:"31866",title:"Review on Ovarian Cryopreservation in Large Animals and Non-Human Primates",slug:"research-on-ovarian-cryopreservation-in-large-animals-and-non-human-primates-",signatures:"Milan Milenkovic, Cesar Díaz-Garcia and Mats Brännström",authors:[{id:"92096",title:"Dr.",name:"Milan",middleName:null,surname:"Milenkovic",fullName:"Milan Milenkovic",slug:"milan-milenkovic"},{id:"99904",title:"Dr.",name:"Cesar",middleName:null,surname:"Díaz-García",fullName:"Cesar Díaz-García",slug:"cesar-diaz-garcia"},{id:"99906",title:"Prof.",name:"Mats",middleName:null,surname:"Brännström",fullName:"Mats Brännström",slug:"mats-brannstrom"}]},{id:"31867",title:"New Approaches of Ovarian Tissue Cryopreservation from Domestic Animal Species",slug:"new-approaches-of-ovarian-tissue-cryopreservation-from-domestic-animal-species",signatures:"Vanessa Neto, Thierry Joly, Loris Commin, Pierre Bruyère, Anne Baudot, Gérard Louis, Pierre Guérin and Samuel Buff",authors:[{id:"101281",title:"Dr.",name:"Vanessa",middleName:null,surname:"Neto",fullName:"Vanessa Neto",slug:"vanessa-neto"}]},{id:"31868",title:"Marine Fish Sperm Cryopreservation and Quality Evaluation in Sperm Structure and Function",slug:"marine-fish-sperm-cryopreservation-and-cryodamage-evaluation-in-sperm-viability-structure-antioxidan",signatures:"Qing Hua Liu, Zhi Zhong Xiao, Shi Hong Xu, Dao Yuan Ma, Yong Shuang Xiao and Jun Li",authors:[{id:"93000",title:"Prof.",name:"Jun",middleName:null,surname:"Li",fullName:"Jun Li",slug:"jun-li"},{id:"99827",title:"Prof.",name:"Qinghua",middleName:null,surname:"Liu",fullName:"Qinghua Liu",slug:"qinghua-liu"},{id:"99828",title:"Prof.",name:"Zhizhong",middleName:null,surname:"Xiao",fullName:"Zhizhong Xiao",slug:"zhizhong-xiao"},{id:"99830",title:"Prof.",name:"Shihong",middleName:null,surname:"Xu",fullName:"Shihong Xu",slug:"shihong-xu"}]},{id:"31869",title:"Sperm Cryopreservation of Two European Predator Fish Species, the Pikeperch (Sander lucioperca) and the Wels Catfish (Silurus glanis)",slug:"sperm-cryopreservation-of-two-european-predator-fish-species-the-pikeperch-sander-lucioperca-and-the",signatures:"Zoltán Bokor, Béla Urbányi, László Horváth, Tamás Müller and Ákos Horváth",authors:[{id:"74005",title:"Dr.",name:"Zoltán",middleName:null,surname:"Bokor",fullName:"Zoltán Bokor",slug:"zoltan-bokor"},{id:"84787",title:"Dr.",name:"Béla",middleName:null,surname:"Urbányi",fullName:"Béla Urbányi",slug:"bela-urbanyi"},{id:"84790",title:"Prof.",name:"László",middleName:null,surname:"Horváth",fullName:"László Horváth",slug:"laszlo-horvath"},{id:"84791",title:"Dr.",name:"Tamás",middleName:null,surname:"Müller",fullName:"Tamás Müller",slug:"tamas-muller"},{id:"84799",title:"Dr.",name:"Ákos",middleName:null,surname:"Horváth",fullName:"Ákos Horváth",slug:"akos-horvath"}]},{id:"31870",title:"Sperm Cryopreservation of Some Freshwater Fish Species in Malaysia",slug:"sperm-cryopreservation-of-some-freshwater-fish-species-in-malaysia",signatures:"Poh Chiang Chew and Abd. Rashid Zulkafli",authors:[{id:"90691",title:"Mrs.",name:"Poh Chiang",middleName:null,surname:"Chew",fullName:"Poh Chiang Chew",slug:"poh-chiang-chew"},{id:"135859",title:"Mr.",name:"Zulkafli",middleName:null,surname:"Abd. Rashid",fullName:"Zulkafli Abd. Rashid",slug:"zulkafli-abd.-rashid"}]},{id:"31871",title:"Cryopreservation of Brown Trout (Salmo trutta macrostigma) and Ornamental Koi Carp (Cyprinus carpio) Sperm",slug:"cryopreservation-of-brown-trout-salmo-trutta-macrostigma-and-ornamental-koi-carp-cyprinus-carpio-spe",signatures:"Yusuf Bozkurt, İlker Yavas and Fikret Karaca",authors:[{id:"90846",title:"Prof.",name:"Yusuf",middleName:null,surname:"Bozkurt",fullName:"Yusuf Bozkurt",slug:"yusuf-bozkurt"},{id:"119796",title:"Associate Prof.",name:"İlker",middleName:null,surname:"Yavaş",fullName:"İlker Yavaş",slug:"ilker-yavas"},{id:"120132",title:"Dr.",name:"Fikret",middleName:null,surname:"Karaca",fullName:"Fikret Karaca",slug:"fikret-karaca"}]},{id:"31872",title:"Cryopreservation of the Sperm of the African Catfish for the Thriving Aquaculture Industry in Nigeria",slug:"cryopreservation-of-the-sperm-of-the-african-giant-catfish-for-the-thriving-aquaculture-industry-in-",signatures:"Ofelia Galman Omitogun, Olanrewaju Ilori, Olawale Olaniyan, Praise Amupitan, Tijesunimi Oresanya, Sunday Aladele and Wasiu Odofin",authors:[{id:"95817",title:"Prof.",name:"Ofelia",middleName:"Galman",surname:"Omitogun",fullName:"Ofelia Omitogun",slug:"ofelia-omitogun"}]},{id:"31873",title:"Comparison of Cryopreservation Methods of Vegetatively Propagated Crops Based on Thermal Analysis",slug:"comparison-of-cryopreservation-methods-of-vegetatively-propagated-crops-based-on-thermal-analysis",signatures:"Jiří Zámečník, Miloš Faltus, Alois Bilavčík and Renata Kotková",authors:[{id:"93504",title:"Dr.",name:"Jiří",middleName:null,surname:"Zámečník",fullName:"Jiří Zámečník",slug:"jiri-zamecnik"},{id:"100928",title:"Dr.",name:"Miloš",middleName:null,surname:"Faltus",fullName:"Miloš Faltus",slug:"milos-faltus"},{id:"137342",title:"Dr.",name:"Alois",middleName:null,surname:"Bilavčík",fullName:"Alois Bilavčík",slug:"alois-bilavcik"},{id:"137343",title:"MSc.",name:"Renata",middleName:null,surname:"Kotková",fullName:"Renata Kotková",slug:"renata-kotkova"}]},{id:"31874",title:"Cryopreservation of Tropical Plant Germplasm with Vegetative Propagation - Review of Sugarcane (Saccharum spp.) and Pineapple (Ananas comusus (L.) Merrill) Cases",slug:"cryopreservation-of-tropical-plant-germplasm-with-vegetative-propagation-review-of-sugarcane-sacchar",signatures:"Marcos Edel Martinez-Montero, Maria Teresa Gonzalez Arnao and Florent Engelmann",authors:[{id:"89927",title:"Dr.",name:"Marcos Edel",middleName:null,surname:"Martinez-Montero",fullName:"Marcos Edel Martinez-Montero",slug:"marcos-edel-martinez-montero"},{id:"97246",title:"Dr.",name:"Florent",middleName:null,surname:"Engelmann",fullName:"Florent Engelmann",slug:"florent-engelmann"},{id:"99614",title:"Dr.",name:"María Teresa",middleName:null,surname:"González-Arnao",fullName:"María Teresa González-Arnao",slug:"maria-teresa-gonzalez-arnao"}]},{id:"31875",title:"Somatic Embryogenesis and Cryopreservation in Forest Species: The Cork Oak Case Study",slug:"somatic-embryogenesis-and-cryopreservation-in-forest-species-the-case-of-cork-oak-",signatures:"Conceição Santos",authors:[{id:"102191",title:"Prof.",name:"Conceição",middleName:null,surname:"Santos",fullName:"Conceição Santos",slug:"conceicao-santos"}]},{id:"31876",title:"Proline and the Cryopreservation of Plant Tissues: Functions and Practical Applications",slug:"proline-and-the-cryopreservation-of-plant-tissues-functions-and-practical-applications",signatures:"David J. 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The radial forearm flap is the most commonly used technique for phalloplasty. The goals of penile construction in a transgender man are to decrease the patient’s gender incongruence, obviate the use of an external prosthesis, give the patient the ability to orgasm, and to urinate through the constructed phallus if desired. Urethral strictures and fistulas are common complications following a phalloplasty with urethral lengthening that may be mitigated with a two-stage technique that utilizes a mucosa-only prelaminated neourethra. Sources of the mucosa may include vaginal and oral mucosa and less commonly, uterine, bladder, and colonic mucosa.
Transition of the trans man genitalia is commonly performed in multiple stages including a hysterectomy and oophorectomy primarily and if desired, followed by a vaginectomy with urethral diversion to the perineum or lengthening with a phalloplasty, scrotoplasty, and glansplasty. The ovaries may be preserved at the time of hysterectomy for possible egg preservation. If the decision is made to preserve the ovaries, it is crucial for the patient to be monitored for abnormalities through yearly routine surveillance.
First stage surgery may consist of a hysterectomy and oophorectomy (if not done prior) along with a vaginectomy with urethra lengthening using an anteriorly based vaginal flap with labia minora tissues along with prelamination of the nondominant radial forearm flap using vaginal mucosa, buccal mucosa, and less common skin grafts.
Second stage surgery, which commonly occurs 2–3 months following the first stage, consists of tubularization of the radial forearm tissue with free flap transfer, microvascular anastomosis, neurotization, urethroplasty, scrotoplasty, and glansplasty.
Given the large cutaneous surface of a native male phallus, autologous construction of a neophallus commonly will necessitate a large cutaneous donor site. Flaps, such as the tube-in-tube radial forearm flap, latissimus dorsi flap, scapular flap, deltoid flap, abdominal pedicled flap, and anterolateral thigh (ALT) flaps have all been used for phalloplasty [1]. Though many techniques have been described, the radial forearm free flap (RFFF) remains the most common for phalloplasty due to its long, reliable vascular pedicle, multiple nerve innervations for anastomosis to the recipient site, and pliability of the tissue facilitating eventual implant placement [2]. In addition, the radial forearm flap has a lower urethral and flap loss complication rate compared to the anterolateral thigh flap [3]. Harvest allows for simultaneous operative sites at the pelvis, upper extremity, and oral region if buccal mucosa is needed. This ability allows for decreased operative time, which can last from 5–12 hours. The RFFF technique makes it possible for patients to fulfill their desires of standing micturition, aesthetic acceptability, and erogenous and tactile sensation.
Erectile rigidity is another commonly reported goal of phalloplasty. To achieve an erection, radial bone can be utilized as an osteocutaneous flap at the time of neophallus creation, or a patient can opt to undergo insertion of a semirigid or hydraulic prosthesis at least 1 year after phalloplasty. It should be noted, however, that our practice prefers to no longer perform the osteocutaneous RFFF due to dyspareunia experienced by the patient post-surgery. This is due to the anchoring of the radius bone at the pubic symphysis. Additionally, most centers report a 30%+ extrusion rate necessitating implant removal at 2–3 years, and reoperation rates reach 100% at 5 years (Figure 1) [4]. There is a significant risk of complications following placement of penile prosthesis including mechanical failure, infection, and mal-positioning. It is critical to have a plastic surgeon trained in microvascular surgery present during the placement of the penile implant as the vascular pedicle may be readily injured during the dissection and subsequent dilation process required for placement of the cylinders. It is critical to avoid multiple passing of the dilators so that devascularization of the phallus does not ensue.
Radius bone exposure following radial forearm osteocutaneous flap phalloplasty.
Adding to the complexity of phalloplasty is the creation of a functional penile urethra. The urethra after neophallus construction can be divided into distinct segments, from proximal to distal: native (female) urethra, fixed or lengthened urethra, the anastomotic urethra, penile shaft urethra, and external meatus. The fixed urethra is the portion of the urethra formed after lengthening the native urethra via local vaginal or labial flaps, extragenital flaps, and grafts of skin or mucosa (Figure 2). The phallic urethra can be constructed by prelamination, tube-in-tube techniques, or pedicle flaps [2].
Patient 3 months following urethral lengthening using labia minora and anterior vaginal wall flaps.
The preoperative assessment begins with a physical examination. The patient is assessed for adequate perfusion to the lower extremities. Ideally, the patient should have a palpable pedal pulse bilaterally. If perfusion is in question especially when dealing with patients with peripheral arterial disease, one can obtain noninvasive studies such as arterial duplex or plethysmography to determine which side to use. Preoperative vein mapping can be performed to assess for deep venous thrombosis as well as the caliber and quality of the great saphenous vein. Ideally, the great saphenous vein should be 2.5–3 mm and free of sclerosis.
A branch of the profunda femoris artery is an option for inflow. The perfusion to the thigh is robust thus a branch of the profunda femoris artery can typically be sacrificed without significantly affecting thigh perfusion. To expose the profunda femoris artery, a longitudinal skin incision is made in the thigh overlying the femoral arteries. The femoral bifurcation is identified and the superficial femoral artery is preserved. The main trunk of the profunda femoris artery is identified and preserved. There are tributary branches of the profunda femoris vein that are ligated to facilitate exposure and hemostasis. The branches of the profunda femoris artery are identified and circumferentially dissected. Typically, the ascending branch is of adequate caliber and length to be used for the inflow. If this branch is not long enough or the caliber is too small, the remaining branches of the profunda can be explored.
An alternative source of inflow can be the superficial femoral artery or the common femoral artery. The great saphenous vein can be used as a conduit. An oblique incision is made in the medial groin overlying the femoral artery bifurcation as well as the saphenofemoral junction. The saphenous vein is identified first and preserved. The superficial femoral artery is then exposed that lies medial to the femoral vein. The artery is sequentially dissected and controlled, and the skin incision is extended distally along the course of the saphenous vein. The length of the vein needed to perform the loop transposition varies by patient. The length required can be estimated with a free tie. Ideally, the loop graft needs to be able to reach the pubis when is oriented medially. Once the saphenous vein is exposed, it is circumferentially dissected and its tributary branches are ligated and divided. Careful attention needs to be made when ligating the branches too close to the vein as it may cause stenosis. The saphenous vein is then transected distally, and the distal end is ligated. The vein is then cannulated and distended with heparinized saline solution. Any defects are identified and repaired. When the vein is distended, it is marked for orientation. To perform the loop configuration, the distal end of the vein is swung in a counterclockwise fashion toward the femoral artery. The patient is systemically heparinized. The femoral artery was clamped proximally and distally and an arteriotomy is made using 11 blades and then lengthened with Potts scissors. Alternatively, an aortic punch device can be used to enlarge the arteriotomy to the desired size. The anastomosis should be approximately 4 mm. An end-to-side anastomosis was performed between the femoral artery and the saphenous vein paying careful attention to maintaining the orientation of the vein to avoid twisting and kinking. Just prior to completing the last few sutures of the anastomosis, the femoral artery is forward and back-bled. The lumen of the artery and vein are flushed with heparinized saline solution to flush any thrombus. Once the anastomosis is completed, the clamps are released. The loop graft is assessed for orientation and flow. The patient’s leg and foot also need to be assessed to ensure there are no changes to baseline perfusion. One can expect a weak pulse and a thrill when palpating the graft. A Doppler can also be used to assess the presence of flow. If the loop graft is kinked or twisted, it may thrombose. When the loop graft is ready to be used, it is transected in the middle; the proximal end is the arterial inflow and the distal end is the venous outflow.
Complications of urinary stricture and fistula are prevalent. Variations of urethral lengthening techniques among centers have resulted from attempts to improve upon urologic complication rates, which range from 33 to 77% in large case series [5]. Urethral cutaneous fistulas following surgery may range from 22 to 75% [6]. Fistulas occur most commonly at or just proximal to the anastomosis between the phallic urethra and fixed urethra due to vascular insufficiency of the flap and decreased lumen of the phallic urethra. Rates of urethral strictures in female-to-male phalloplasty recipients range from 11 to 74% [7, 8, 9]. Since the plastic surgeon alone is not trained in the management of urethral strictures or fistulas, we believe it is essential to have a qualified reconstructive urologist involved in the management of these complications to optimize patient care.
The radial forearm flap may allow the patient to have penetrative sexual intercourse, has minimal donor site scarring, results in a cosmetically acceptable phallus, has tactile and erogenous sensitivity, and potentially creates a competent neourethra that allows for standing urination. These ideal characteristics, described by Hage et al, are mostly met by the RFFF (radial forearm free flap) [10].
Recognizing that urethral strictures and fistulas remain the most challenging complication we face, we have been able to decrease their occurrence with a staged technique. We have found that the radial forearm tube-within-a-tube technique not only requires electrolysis of the forearm to avoid hair growth within the urethra—a common cause of stricture—but also requires a larger donor site since flap skin is used to create the urethra. Minimizing the donor site and decreasing stricture rates have encouraged us to continue the two-stage technique with mucosal prelamination, which more closely mimics native urethra mucosa (Figure 3).
Cystoscopy of prelaminated neourethra prior to stage 2 phalloplasty revealing mucosa which mimics that of native urethral mucosa.
Given the potential morbidity associated with the complex phalloplasty procedure, an adequate preoperative evaluation is essential. The need for gender dysphoria evaluation and medical clearance is unique to this patient population. Gender identity disorder or gender incongruence is classified by the International Classification of Disease Manual as ICD-10-CM F64.9. The DSM-5 defines gender dysphoria as an incongruity between the patient’s experienced and expressed gender and their assigned gender, which causes clinically significant distress lasting at least 6 months, however, this has often lasted nearly the individual’s entire life [11]. According to the World Professional Association for Transgender Health (WPATH), a psychological evaluation and two letters recommending gender affirmation surgery from two psychiatrists or licensed mental health therapists, who independently assessed the patient, are required for the removal of reproductive organs and/or phalloplasty [12]. In addition, the patient must have taken hormone replacement therapy and lived as their true gender for at least 1 year. These prerequisites are not only required by most insurance companies for authorization of the procedure but also ensure that patients have a realistic understanding of the procedure and serve to minimize disappointment and patient regret.
The importance of a thorough preoperative psychosocial evaluation cannot be overstated. Adequate social support is encouraged to facilitate a successful recovery. The patient should be informed to expect frequent postoperative visits 1–2 months following surgery and should understand that the operation will impact their ability to work for 4–6 weeks. The surgeon should remain involved in all stages of the preoperative evaluation by corresponding with the patient’s mental health provider and urogynecologist.
A clear and candid discussion regarding the patient’s desired goals from surgery, including the length and circumference of the neophallus, allows the surgeon to determine whether expectations are realistic given the patient’s anatomy. The limitations, functional outcomes, recovery, risk of complications, timing of procedures, and cost of each surgery should be honestly discussed with the patient.
It is critical to accurately document current medications, including antiplatelet agents and hormones, in addition to the patient’s smoking history. Androgens such as testosterone must be discontinued 2 weeks prior to surgery to reduce the risk of thrombosis, and smoking cessation is required 4 weeks prior to surgery and up to 4 weeks after to ensure proper healing. Specific information regarding prior infections helps in selecting postoperative antibiotics, as postsurgical infection will delay healing and increase morbidity.
The microsurgical component of RFFF phalloplasty requires additional preoperative evaluation. Adequate recipient vessels will be needed for the microsurgical construction. If arterial inflow from the thigh will be used then pedal vessels should be assessed for adequate inflow. The abdominal wall should be examined for prior incisions particularly if the inferior epigastric vessels will be used as recipient’s vessels. We have used the inferior epigastric artery, descending branch of the lateral femoral circumflex or on occasion arterio-venous loops for recipient arteries and the inferior epigastric vein or saphenous veins for recipient venous outflow.
Allen’s test of the patient’s nondominant hand confirms that harvest of the RFFF flap will not compromise the blood supply to the hand. If the results of Allen’s test are poor, that is, the hand remains cool and pale after the release of ulnar artery occlusion, using another donor site should be considered or the dominant forearm. In addition, sensitive tattoos of the proposed forearm should be evaluated. Patients who live in cold climates may need reconstitution of their arterial anatomy with vein grafts after flap harvest.
Prior to surgery, it is also vital to assess patient sensation to determine if orgasm can be achieved through clitoral stimulation. The dorsal clitoral nerve (Figure 4), ilioinguinal nerve, and genitofemoral nerve co-apted to the medial and lateral antebrachial cutaneous nerves will provide both erogenous and protective sensation to the neophallus. If a patient has difficulty achieving orgasm prior to surgery, it is unlikely that the patient will be able to after surgery.
Clitoral nerves are exposed as recipient’s nerves at stage 2 RFFF phalloplasty.
It should also be noted that part of the patient population has forearm tattoos that will affect the cosmesis of the neophallus. Patient preference will dictate whether the presence of forearm tattoos on the neophallus is acceptable. Clear expectations should be set with the patient regarding the forearm donor site scar, which may be perceived as a stigma, however, we argue the scar is more acceptable than the anterolateral thigh flap scar (Figure 5).
Patient with urethral and flap-related complications following ALT phalloplasty from an outlying institution.
In our practice, we construct the penile urethra by forearm prelamination with mucosa, which obviates the need for forearm depilation (as would be the case in a tube-within-a-tube technique). The native urethra is a fibromuscular tube lined by urothelium, columnar epithelium, and nonkeratinizing squamous epithelium. Mucosal grafts have greater homology to the native urethra as they are also composed of nonkeratinized epithelium, which has led to less scar contracture and subsequent urethral strictures and fistulas following neourethral construction [1].
Prior to phalloplasty, a patient should have had a hysterectomy and oophorectomy. If he has not yet had these procedures, it is possible to have them performed during the first stage of our approach to staged phalloplasty. We have found that uterine mucosa is readily available if the patient is undergoing hysterectomy in the same operative setting as phalloplasty, and can be used to construct a patent, functional penile urethra [1]. If a patient is interested in egg harvesting prior to oophorectomy, this is performed before definitive and irreversible hysterectomy and oophorectomy.
The current sequence of surgery in our practice is first a subcutaneous mastectomy, followed by a hysterectomy and oophorectomy combined with a vaginectomy, scrotoplasty, and reconstruction of the horizontal part of the urethra, and later the actual phalloplasty.
We have found our two-stage technique allows for a urethral conduit which mimics that of a native urethra with no hair growth while minimizing the donor site on the forearm. Our decreased stricture rate has encouraged us to continue the use of this technique in patients pursuing phalloplasty with urethral lengthening.
The main procedures are as follows:
Vaginectomy with the harvest of vaginal mucosa tissue (combined with hysterectomy and oophorectomy if not already performed)—Procedure performed concurrently by urogynecologist or gynecologic oncologist
Urethral lengthening utilizing labia minora flaps and anteriorly based vaginal mucosa flap harvested at the time of vaginectomy
Occasional harvest of buccal mucosa if required for neo-urethra
Radial forearm flap elevation ulnarly for flap urethra prelamination
IV antibiotics against gram-positive, gram-negative organisms and anaerobes are administered to the patient 1 hour prior to incision.
The first stage entails flap prelamination during which the radial forearm flap is designed and the neourethra is formed using autologous tissue; mucosa is preferentially used in our practice. The markings for the planned flap are determined preoperatively following a normal Allen’s test on the patient’s nondominant upper extremity, ensuring that the patient’s hand can be perfused with the ulnar artery alone. The flap is elevated from the ulnar to radial direction in the supra-fascial plane to allow placement of the neourethra.
Prelamination of the patient’s eventual penile urethra is performed by grafting vaginal, and/or buccal mucosa in a suprafascial plane of the donor volar and ulnar forearm. The vaginal mucosa is harvested during the vaginectomy for the creation of the neourethra. We lengthen the native female urethra using labia minora tissues and an anterior pedicled vaginal flap. If a hysterectomy has not already been performed, it can be performed during this stage to provide additional mucosal tissue for the neourethra. The buccal mucosa is also harvested at this time if necessary (Figures 6 and 7). To allow for irrigation of the entire prelaminated neourethra, holes are cut into a 24-French Foley. After mucosal harvest, the mucosal grafts are cleansed with a betadine and normal saline solution and then sewed around the holed catheter construct, exteriorizing the sub-mucosal surface using a running, locking suture. Placing this construct lengthwise in the subcutaneous forearm (suprafascial plane) allows for the creation of a tubular graft, which will become the penile neourethra of the eventual phalloplasty. The patient is then immobilized in a splint for several days. Irrigation of the prelaminated flap is then performed twice daily beginning 1 week after surgery, a practice continued until flap transfer to prevent infection.
Markings of buccal mucosal graft. Avoid injury to Stenson’s duct.
Vaginal and buccal mucosa with mucosal surface toward the foley catheter in preparation for tubularization around the catheter.
Creating the urethra with mucosal tissue and not using forearm tissue decreases the width of the flap skin paddle compared to the traditional tube-within-a-tube urethra and yields a more aesthetically acceptable donor site scar. With this method, the patient can place his upper extremity across his chest with the flexor aspect against the chest and the scar will not be visible (Figure 8). Furthermore, with this technique, the patient does not need to undergo costly depilation treatments as there will be no hair growth within the urethra. Prelamination can also be completed with a skin graft from the thigh or abdomen when mucosal tissue is inadequate in patients who have undergone metoidioplasty with vaginectomy, however, this may lead to increased stricture rates.
Patient following staged radial forearm flap harvest revealing limited donor site secondary due to prelamination of the urethra.
Approximately 8–12 weeks after the first stage flap prelamination, creation of the neophallus can be performed. Although allowing more time between stages may be favorable, we have found that 8 weeks is long enough to achieve successful wound healing and favorable results and is a time frame that is tolerable for our patients [1].
One hour before incision is made, antibiotics against gram-positive, gram-negative, and anaerobic organisms should be intravenously administered to the patient. A tourniquet is used for flap harvest, in addition to a hand table. Separate surgical set-ups are used for the pelvic area and upper extremity to avoid cross-contamination. Two surgical teams can work simultaneously—one team performs the RFFF harvest and the second team performs the dissection of the recipient’s vessels (inferior epigastric artery and vein and/or descending branch of the lateral circumflex artery and saphenous vein), recipient nerves, preparation of the urethra for anastomosis and scrotoplasty.
The design of the radial forearm flap was defined in the first stage. A marking pen is used to delineate the dimensions of the flap, which will commonly measure 5.5–7.5 inches in length and 5.5–6.5 inches in width. Whereas the flap was elevated in the suprafascial plane for prelamination at Stage I, the flap is now elevated in the subfascial plane to avoid injury to the neourethra. The dissection begins on the ulnar side of the forearm and proceeds to the flexor carpi radialis and brachioradialis tendons for the RFFF harvest. The medial and lateral antebrachial cutaneous nerves are preserved during dissection of the radial forearm flap for coaptation to one dorsal nerve of the clitoris end-to-side for erogenous sensation and the ilioinguinal or genitofemoral nerve for tactile sensation. The radial artery and venae comitantes are ligated distally and proximally dissected for vascular anastomosis. Prior to distal ligation, the artery may be temporarily clamped to ensure blood flow to the hand. The basilic and/or cephalic veins are preserved and dissected with the flap. While the RFFF remains connected to its inherent blood supply, the flap is tubed into a phallus and sutured so that the neourethra is buried within the tubed phallus (Figure 9).
Tubed radial forearm flap at the donor site with the prelaminated urethra.
Using a modification of Monstrey’s scrotoplasty technique, the clitoris is dissected free from the lengthened urethra and denuded of skin [13]. The clitoral hood skin is removed and used for the coronaplasty using a technique described by Gottlieb [14] (Figure 10). The recipient arteries harvested for the vascular anastomoses are either the inferior epigastric artery or the descending branch of the lateral femoral circumflex artery. Of note, once we switched to using the descending branch of the lateral femoral circumflex artery as our recipient artery, we no longer had re-open procedures due to vascular compromise [2]. The thigh incision made for the lateral femoral circumflex is also used for the harvest of the great saphenous vein (Figure 11). Since we use the greater saphenous veins as recipient veins for the radial forearm flap, the proximal incision made to harvest the greater saphenous vein is also used for the gracilis muscle harvest. The distal free end of the muscle, harvested via a separate distal incision, is delivered through the proximal incision. Undermining of the soft tissues is performed from the proximal thigh incision to the level of the midline groin defect where the urethral anastomosis is to be performed.
Trans male patient during the harvest of clitoral (or T-dick) hood skin for coronaplasty using Gottlieb technique.
Descending branch of the lateral femoral circumflex artery as recipient artery and saphenous vein as recipient artery in preparation for free flap phalloplasty.
After vessel preparation with a microscope and confirming adequate outflow from the descending branch of the lateral femoral circumflex artery and inflow from the great saphenous vein, the RFFF is transferred to the pubic area. The forearm donor site can be covered with either an autologous split-thickness skin graft or the surgeon can apply a dermal substitute that can be grafted later. The first maneuver is to place the foley catheter, which is located in the neourethra, directly into the patient’s bladder. Absorbable sutures are used for the urethral anastomosis in two layers, which is the first anastomosis performed (Figure 12).
First of two-layered urethral anastomosis in staged radial forearm flap phalloplasty.
The arterial, venous, and neural anastomoses are performed next in that order and are all hand-sewn using 9-0 nylon suture with the aid of an operative microscope. The radial artery is connected end-to-end to the descending branch of the lateral circumflex artery. The venous anastomosis is performed between the cephalic or basilic vein and the greater saphenous vein. A second venous anastomosis can be performed between a radial venous comitante vein with the contralateral greater saphenous vein. Two to three nerve anastomoses may also be performed. The medial and lateral antebrachial cutaneous nerves are anastomosed end-to-end to the ilioinguinal nerves and to one of the dorsal clitoral nerves end-to-side. The ilioinguinal nerve is commonly found exiting the external inguinal ring. A cadaver nerve graft may be used as an interposition nerve graft when needed.
The gracilis muscle may be harvested in a minimally invasive fashion and wrapped around the urethral anastomosis, avoiding compression of the vascular pedicle, to provide vascularity to a minimally vascular urethral anastomosis (Figure 13). This maneuver also provides bulk to the neo-scrotum often obviating the need for scrotal implants. At our institution, we have been able to minimize urethral fistula rates using a gracliis muscle flap to augment the urethral anastomosis [15].
Gracilis muscle harvest via minimally invasive approach prior to alpha wrap around the urethral anastomosis.
A suprapubic tube is placed and used for urinary diversion if needed during urinary training of the neo-phallus.
Upon closure of all incisions, a Norfolk coronaplasty is performed with either a skin graft or labial graft obtained from the clitoral hood region by denuding the clitoris before transposition (Figure 10) [16].
Following surgery, patients are transferred to the intensive care unit for flap monitoring and will remain on strict bed rest for a minimum of 3 days. An implantable Doppler device has been very helpful in flap monitoring. Prophylaxis for microvascular thrombosis is typically subcutaneous heparin and aspirin. Strict monitoring of the free tissue transfer is performed by the intensive care unit and resident staff [17]. Patients whose forearm donor site was first covered with a dermal substitute are taken back to the operating room for definitive coverage with a skin graft after 2 weeks. Several days later the patient may be discharged home with both a penile catheter and suprapubic catheter (Figure 14). A pericatheter retrograde cystourethrogram can be planned 12 weeks post-surgery. If there is no extravasation of dye, indicating that there is no urinary fistula, the foley catheter can be removed and the suprapubic catheter can be clamped (Figure 15). Patients are encouraged to urinate through their neophallus with the suprapubic catheter clamped. We then check for residual urine in the bladder using a bladder scan if necessary. If the patient is successfully able to urinate from the phallus and adequately empty the bladder for several days the suprapubic tube can be discontinued.
Trans man following Stage II phalloplasty revealing suprapubic tube and penile foley catheter.
Pericatheter retrograde cystourethrogram 8 weeks following second stage phalloplasty operation in trans man. The study reveals no contrast extravasation indicating no fistula and no stricture noted.
If the patient desires, he can tattoo the glans and shaft of the neophallus for aesthetic enhancement, which is ideally performed before full tactile sensation has been achieved (typically 1-year postop). Similarly, the donor site can be tattooed to avoid the stigmata of a skin graft (Figure 16).
RFFF donor site with tattoo concealment.
Since the RFFF phalloplasty lacks bone, it may be too soft to allow for penetrative intercourse. Implantation of an erectile prosthesis is a definitive procedure, that may be performed after 8–12 months when tactile sensation is achieved at least ¾ distally of the penile shaft. A simple Tinel sign is often used to assess postoperative tactile sensation in the neo-phallus postoperatively. Both malleable dual or single cylinder penile prostheses or inflatable prostheses may be used for the erectile device commonly anchored to the ischial tuberosities. We strongly recommend plastic surgery involvement in placement of the prosthesis since knowledge of the location and preservation of the neo-phallus vascular supply is critical to successful placement. More technical details of the neo-phallus implant placement will be discussed in a separate chapter. Prior to implant placement, as the patient is awaiting neural sensation, patients may have successful penetrative intercourse by using an elastic 3M Coban wrap and a condom.
It is important that the patient is aware of the potential complications that may occur following surgery, included in the informed consent. Some complications may include partial or total flap loss, hematoma at the donor or recipient site, an insensate flap, anorgasmia, skin graft loss, chronic pain, numbness, urinary complications, hypertrophic scarring, infection, cold intolerance, vascular compromise, abdominal wall weakness or hernia, implant infection or malfunction, dyspareunia, tendon exposure, limited hand function, and persistent gender dysphoria.
Urethral fistulas and strictures are common untoward events following phalloplasty in the transgender male and may prevent the patient from voiding while standing. A meta-analysis of 665 patients drawn from 11 studies found that an average of 0.51 strictures and/or fistulas can be expected per free forearm flap phalloplasty [17]. The published rate of urologic complications following penile reconstruction ranges from 23 to 75% [18, 19]. The subsequent management of urethral fistulas and strictures can be challenging. Initially, conservative measures such as periodic urethral dilatation or internal urethrotomy can be employed as temporizing measures prior to definitive surgical management.
Most urethral fistulas occur at the anastomosis between the fixed urethra and phallic urethra, and often can occur proximal to a concomitant stricture. The techniques for fistula repair described are the simple fistula repair, the use of local tissue transfer, two-stage procedures with use of mesh graft, bladder, or buccal mucosa [20]. When the fistula is small with substantial overlying tissue, spontaneous resolution is likely. However, when a urethrocutaneous fistula is large and superficial, the abovementioned surgical repair is necessary.
Urethral strictures also primarily occur at the anastomotic urethra. The keystone surgical procedures for urethral stricture include urethroplasty (excision and primary anastomosis) and staged Johanson-type urethroplasty with additional skin grafts, preferentially buccal mucosa [21]. Surgical approaches are customized to the length of the stricture. A patient who has both a urethral fistula and stricture should have both problems addressed at the same time.
There are many variations of urethroplasty available owing to the considerable heterogeneity of phallic and neourethral construction techniques. Well-vascularized local flaps are utilized when available, as well as buccal mucosal grafts. A patient who has undergone several urethral fistula and/or stricture repair attempts will have progressively fewer options for reconstruction. At our institution, we have significantly decreased our fistula rates in transgender male phalloplasty by augmenting the paucity of vascularized tissue at this anastomosis using a pedicled gracilis flap at the time of flap transfer [15]. Prelamination with mucosal grafts may also decrease urethral stenosis and fistula formation [2].
The goals of phalloplasty include a sensate, cosmetically acceptable phallus with an incorporated neourethra, and the ability to place an implantable penile prosthesis to allow rigidity for penetrative intercourse. In the majority of cases, phalloplasty is the final stage of treatment for gender dysphoria.
While other donor sites may be used, the radial forearm free flap is a favorable technique due to its high vascularity, adequate sensation, sufficient tissue pliability, and good cosmetic outcome. We have found that our two-stage technique allows for a neourethra, which mimics a native urethra with no hair growth, while minimizing the donor site on the forearm compared to the previously used skin for a tube-within-a-tube radial forearm flap technique. Using a pre-laminated urethra our patients do not need to undergo electrolysis since the urethra is not created from forearm tissue, so we do not have the risk of hair growth in the urethra and its associated complications. Our decreased stricture rate has encouraged us to continue the use of this technique in patients pursuing phalloplasty with urethral lengthening. Although there have not been any blinded, randomized controlled trials comparing single-stage to two-stage phalloplasty, we believe that prelamination using mucosa for the construction of the trans male phallus urethra is a worthwhile technique that has demonstrated a reduction in the prevalence of complications with this already very challenging procedure.
The authors declare no conflict of interest.
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\n\nA Conflict of Interest is a situation in which a person's professional judgment may be influenced by a range of factors, including financial gain, material interest, or some other personal or professional interest. For IntechOpen as a publisher, it is essential that all possible Conflicts of Interest are avoided. Each contributor, whether an Author, Editor, or Reviewer, who suspects they may have a Conflict of Interest, is obliged to declare that concern in order to make the publisher and the readership aware of any potential influence on the work being undertaken.
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Despite its popularity in the field of statistics, Bayesian inference is barely known and used in psychology. Frequentist inference, and its null hypothesis significance testing (NHST), has been hegemonic through most of the history of scientific psychology. However, the NHST has not been exempt of criticisms. Therefore, the aim of this chapter is to introduce a Bayesian approach to hypothesis testing that may represent a useful complement, or even an alternative, to the current NHST. The advantages of this Bayesian approach over Frequentist NHST will be presented, providing examples that support its use in psychology and social sciences. 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He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. 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He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. 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He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. 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Dr. Aydin is currently a Fellow of Higher Education Academy, UK, a member of EPSRC College, a senior member of IEEE and a senior member of ACM. In addition to being a member of advisory committees of many international conferences, he is an Editorial Board Member of various peer-reviewed international journals. He has served as guest editor for a number of special issues of peer-reviewed international journals.",institutionString:null,institution:{name:"University of the West of England",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:20,paginationItems:[{id:"82526",title:"Deep Multiagent Reinforcement Learning Methods Addressing the Scalability Challenge",doi:"10.5772/intechopen.105627",signatures:"Theocharis Kravaris and George A. 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He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"117248",title:"Dr.",name:"Andrew",middleName:null,surname:"Macnab",slug:"andrew-macnab",fullName:"Andrew Macnab",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"322007",title:"Dr.",name:"Maria Elizbeth",middleName:null,surname:"Alvarez-Sánchez",slug:"maria-elizbeth-alvarez-sanchez",fullName:"Maria Elizbeth Alvarez-Sánchez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",country:{name:"Mexico"}}},{id:"337443",title:"Dr.",name:"Juan",middleName:null,surname:"A. Gonzalez-Sanchez",slug:"juan-a.-gonzalez-sanchez",fullName:"Juan A. Gonzalez-Sanchez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico System",country:{name:"United States of America"}}},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}}]}},subseries:{item:{id:"27",type:"subseries",title:"Multi-Agent Systems",keywords:"Collaborative Intelligence, Learning, Distributed Control System, Swarm Robotics, Decision Science, Software Engineering",scope:"Multi-agent systems are recognised as a state of the art field in Artificial Intelligence studies, which is popular due to the usefulness in facilitation capabilities to handle real-world problem-solving in a distributed fashion. The area covers many techniques that offer solutions to emerging problems in robotics and enterprise-level software systems. Collaborative intelligence is highly and effectively achieved with multi-agent systems. Areas of application include swarms of robots, flocks of UAVs, collaborative software management. Given the level of technological enhancements, the popularity of machine learning in use has opened a new chapter in multi-agent studies alongside the practical challenges and long-lasting collaboration issues in the field. It has increased the urgency and the need for further studies in this field. We welcome chapters presenting research on the many applications of multi-agent studies including, but not limited to, the following key areas: machine learning for multi-agent systems; modeling swarms robots and flocks of UAVs with multi-agent systems; decision science and multi-agent systems; software engineering for and with multi-agent systems; tools and technologies of multi-agent systems.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/27.jpg",hasOnlineFirst:!0,hasPublishedBooks:!1,annualVolume:11423,editor:{id:"148497",title:"Dr.",name:"Mehmet",middleName:"Emin",surname:"Aydin",slug:"mehmet-aydin",fullName:"Mehmet Aydin",profilePictureURL:"https://mts.intechopen.com/storage/users/148497/images/system/148497.jpg",biography:"Dr. Mehmet Emin Aydin is a Senior Lecturer with the Department of Computer Science and Creative Technology, the University of the West of England, Bristol, UK. His research interests include swarm intelligence, parallel and distributed metaheuristics, machine learning, intelligent agents and multi-agent systems, resource planning, scheduling and optimization, combinatorial optimization. Dr. Aydin is currently a Fellow of Higher Education Academy, UK, a member of EPSRC College, a senior member of IEEE and a senior member of ACM. In addition to being a member of advisory committees of many international conferences, he is an Editorial Board Member of various peer-reviewed international journals. 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Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. 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