\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
\n\n\n\n\n'}],latestNews:[{slug:"intechopen-signs-new-contract-with-cepiec-china-for-distribution-of-open-access-books-20210319",title:"IntechOpen Signs New Contract with CEPIEC, China for Distribution of Open Access Books"},{slug:"150-million-downloads-and-counting-20210316",title:"150 Million Downloads and Counting"},{slug:"intechopen-secures-indefinite-content-preservation-with-clockss-20210309",title:"IntechOpen Secures Indefinite Content Preservation with CLOCKSS"},{slug:"intechopen-expands-to-all-global-amazon-channels-with-full-catalog-of-books-20210308",title:"IntechOpen Expands to All Global Amazon Channels with Full Catalog of Books"},{slug:"stanford-university-identifies-top-2-scientists-over-1-000-are-intechopen-authors-and-editors-20210122",title:"Stanford University Identifies Top 2% Scientists, Over 1,000 are IntechOpen Authors and Editors"},{slug:"intechopen-authors-included-in-the-highly-cited-researchers-list-for-2020-20210121",title:"IntechOpen Authors Included in the Highly Cited Researchers List for 2020"},{slug:"intechopen-maintains-position-as-the-world-s-largest-oa-book-publisher-20201218",title:"IntechOpen Maintains Position as the World’s Largest OA Book Publisher"},{slug:"all-intechopen-books-available-on-perlego-20201215",title:"All IntechOpen Books Available on Perlego"}]},book:{item:{type:"book",id:"6662",leadTitle:null,fullTitle:"Trauma Surgery",title:"Trauma Surgery",subtitle:null,reviewType:"peer-reviewed",abstract:"Although trauma victims constitute around one-tenth to one-eighth of the total patient volume in hospital emergency departments, the burden of trauma on humankind is beyond these statistics. The twenty-first century is witnessing a growing threat on human beings imposed by many sources, namely natural disasters, terrorism and other conflicts, warfare, and transportation accidents; all of which ignite the rise of major trauma incidents worldwide. Physicians, therefore, get involved in trauma management more and more frequently in time. They need to evaluate, diagnose, treat, and stabilize victims and help them take part in active and productive life as soon as possible. Technological advances have provided many techniques to augment trauma care and resuscitation, fracture healing, wound care, casts and splints, sutures, and transfusions. However, the successful management of trauma warrants a collaboration of emergency medicine, surgical disciplines, intensive care medicine, and almost all the resources of a hospital. This work is an example of a multidisciplinary approach that is a must to maximize synergistic efforts to deliver contemporary care for trauma victims of all ages throughout the world.",isbn:"978-1-78923-757-3",printIsbn:"978-1-78923-756-6",pdfIsbn:"978-1-83881-371-0",doi:"10.5772/intechopen.71911",price:119,priceEur:129,priceUsd:155,slug:"trauma-surgery",numberOfPages:144,isOpenForSubmission:!1,isInWos:1,hash:"9721b9ac98bf237058cafd0a0303bdbc",bookSignature:"Ozgur Karcioglu and Hakan Topacoglu",publishedDate:"September 19th 2018",coverURL:"https://cdn.intechopen.com/books/images_new/6662.jpg",numberOfDownloads:6063,numberOfWosCitations:2,numberOfCrossrefCitations:1,numberOfDimensionsCitations:3,hasAltmetrics:0,numberOfTotalCitations:6,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 31st 2017",dateEndSecondStepPublish:"November 21st 2017",dateEndThirdStepPublish:"January 20th 2018",dateEndFourthStepPublish:"April 10th 2018",dateEndFifthStepPublish:"June 9th 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,editors:[{id:"221195",title:"Dr.",name:"Ozgur",middleName:null,surname:"Karcioglu",slug:"ozgur-karcioglu",fullName:"Ozgur Karcioglu",profilePictureURL:"https://mts.intechopen.com/storage/users/221195/images/system/221195.jpeg",biography:"Dr. Karcioglu graduated from his residency in Dokuz Eylul University Medical School, Department of Emergency Medicine, Turkey, in 1998. He attended the 'International Emergency Medicine” Fellowship in PennState University (2005). He is now the Chair of the Department of Emergency Medicine, Istanbul Education and Research Hospital. Since 1995, he has served as a founder and board member of the Emergency Medical Association of Turkey. He has had around 130 articles published in scientific journals, and has contributed in five books as an editor and authored 35 chapters. Recently, he published the books Trauma Surgery and Poisoning in the Modern World with the collaboration of IntechOpen. He is also an instructor of the Advanced Cardiac Life Support Course.",institutionString:"University of Health Sciences",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"4",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"229574",title:"Dr.",name:"Hakan",middleName:null,surname:"Topacoglu",slug:"hakan-topacoglu",fullName:"Hakan Topacoglu",profilePictureURL:"https://mts.intechopen.com/storage/users/229574/images/system/229574.JPG",biography:"Dr. Topacoglu completed his emergency medicine residency program at Dokuz Eylul University Medical School in 2002. He served as an assistant professor from 2002 to 2007, associate professor from 2007 to 2010 at university. During this period he worked as a member of many boards of the university. Besides, served as the manager of the Centre of the Emergency Medicine and Disaster Training from 2008 to 2010. He is currently working as head of emergency departments of the two hospitals in Istanbul. \n\nHe has more than 40 peer-reviewed articles published in international journals which have been cited over 400 times. He presented more than 80 abstracts at national and international symposia.\nH index is currently 11, i10 index is 13 and RG score is 26,85\nHe is board member of The Emergency Medical Association of Turkey and he contributed to two books as editor.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"994",title:"Traumatology",slug:"traumatology"}],chapters:[{id:"61270",title:"Fracture Repair: Its Pathomechanism and Disturbances",doi:"10.5772/intechopen.76252",slug:"fracture-repair-its-pathomechanism-and-disturbances",totalDownloads:566,totalCrossrefCites:0,totalDimensionsCites:2,signatures:"Grzegorz Szczęsny",downloadPdfUrl:"/chapter/pdf-download/61270",previewPdfUrl:"/chapter/pdf-preview/61270",authors:[{id:"232560",title:"Dr.",name:"Grzegorz",surname:"Szczęsny",slug:"grzegorz-szczesny",fullName:"Grzegorz Szczęsny"}],corrections:null},{id:"59356",title:"Management of Open Fracture",doi:"10.5772/intechopen.74280",slug:"management-of-open-fracture",totalDownloads:1131,totalCrossrefCites:1,totalDimensionsCites:1,signatures:"Alberto Jorge-Mora, Samer Amhaz-Escanlar, Iván Couto González,\nCristina López-Del Teso, Rodolfo Gómez, Teresa Jorge-Mora, José\nRamón Caeiro-Rey and Jesús Pino-Mínguez",downloadPdfUrl:"/chapter/pdf-download/59356",previewPdfUrl:"/chapter/pdf-preview/59356",authors:[{id:"34697",title:"Dr.",name:"Rodolfo",surname:"Gomez",slug:"rodolfo-gomez",fullName:"Rodolfo Gomez"},{id:"217172",title:"Ph.D.",name:"Alberto",surname:"Jorge-Mora",slug:"alberto-jorge-mora",fullName:"Alberto Jorge-Mora"},{id:"240642",title:"Prof.",name:"Jesus",surname:"Pino-Minguez",slug:"jesus-pino-minguez",fullName:"Jesus Pino-Minguez"},{id:"240643",title:"Dr.",name:"Teresa",surname:"Jorge-Mora",slug:"teresa-jorge-mora",fullName:"Teresa Jorge-Mora"},{id:"240644",title:"Dr.",name:"Samer",surname:"Amhaz-Escanlar",slug:"samer-amhaz-escanlar",fullName:"Samer Amhaz-Escanlar"},{id:"240645",title:"Dr.",name:"Iván",surname:"Couto Gonzalez",slug:"ivan-couto-gonzalez",fullName:"Iván Couto Gonzalez"},{id:"240646",title:"Dr.",name:"Cristina",surname:"López Del Teso",slug:"cristina-lopez-del-teso",fullName:"Cristina López Del Teso"}],corrections:null},{id:"60469",title:"Clinical and Radiological Assessment of Acetabular Fracture",doi:"10.5772/intechopen.76114",slug:"clinical-and-radiological-assessment-of-acetabular-fracture",totalDownloads:679,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Balaji Zacharia, Dhiyaneswaran Subramaniyam and Muhammed\nAyyub",downloadPdfUrl:"/chapter/pdf-download/60469",previewPdfUrl:"/chapter/pdf-preview/60469",authors:[{id:"31623",title:"Dr.",name:"Balaji",surname:"Zacharia",slug:"balaji-zacharia",fullName:"Balaji Zacharia"},{id:"236480",title:"Dr.",name:"Dhiyaneswaran",surname:"Subramaniam",slug:"dhiyaneswaran-subramaniam",fullName:"Dhiyaneswaran Subramaniam"},{id:"247419",title:"Dr.",name:"Muhammed",surname:"Ayyub",slug:"muhammed-ayyub",fullName:"Muhammed Ayyub"}],corrections:null},{id:"60520",title:"Maxillofacial Fractures: From Diagnosis to Treatment",doi:"10.5772/intechopen.76166",slug:"maxillofacial-fractures-from-diagnosis-to-treatment",totalDownloads:1878,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Mohammad Esmaeelinejad",downloadPdfUrl:"/chapter/pdf-download/60520",previewPdfUrl:"/chapter/pdf-preview/60520",authors:[{id:"172188",title:"Dr.",name:"Mohammad",surname:"Esmaeelinejad",slug:"mohammad-esmaeelinejad",fullName:"Mohammad Esmaeelinejad"}],corrections:null},{id:"63082",title:"Abdominal Trauma",doi:"10.5772/intechopen.76474",slug:"abdominal-trauma",totalDownloads:698,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Göksu Afacan",downloadPdfUrl:"/chapter/pdf-download/63082",previewPdfUrl:"/chapter/pdf-preview/63082",authors:[{id:"236854",title:"M.D.",name:"Göksu",surname:"Afacan",slug:"goksu-afacan",fullName:"Göksu Afacan"}],corrections:null},{id:"60091",title:"Emergency and Current Approaches to Thoracic Traumas",doi:"10.5772/intechopen.74713",slug:"emergency-and-current-approaches-to-thoracic-traumas",totalDownloads:593,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Turkan Dubus",downloadPdfUrl:"/chapter/pdf-download/60091",previewPdfUrl:"/chapter/pdf-preview/60091",authors:[{id:"233186",title:"Associate Prof.",name:"Turkan",surname:"Dubus",slug:"turkan-dubus",fullName:"Turkan Dubus"}],corrections:null},{id:"61857",title:"Geriatric Trauma",doi:"10.5772/intechopen.77151",slug:"geriatric-trauma",totalDownloads:520,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Banu Arslan",downloadPdfUrl:"/chapter/pdf-download/61857",previewPdfUrl:"/chapter/pdf-preview/61857",authors:[{id:"232986",title:"Dr.",name:"Banu",surname:"Arslan",slug:"banu-arslan",fullName:"Banu Arslan"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},relatedBooks:[{type:"book",id:"7111",title:"Poisoning in the Modern World",subtitle:"New Tricks for an Old Dog?",isOpenForSubmission:!1,hash:"08164f9300bc6bf4900c9166d960278b",slug:"poisoning-in-the-modern-world-new-tricks-for-an-old-dog-",bookSignature:"Ozgur Karcioglu and Banu Arslan",coverURL:"https://cdn.intechopen.com/books/images_new/7111.jpg",editedByType:"Edited by",editors:[{id:"221195",title:"Dr.",name:"Ozgur",surname:"Karcioglu",slug:"ozgur-karcioglu",fullName:"Ozgur Karcioglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8266",title:"Cardiac Diseases and Interventions in 21st Century",subtitle:null,isOpenForSubmission:!1,hash:"186b2840cf326729108f409cd8f30bcc",slug:"cardiac-diseases-and-interventions-in-21st-century",bookSignature:"Ozgur Karcioglu",coverURL:"https://cdn.intechopen.com/books/images_new/8266.jpg",editedByType:"Edited by",editors:[{id:"221195",title:"Dr.",name:"Ozgur",surname:"Karcioglu",slug:"ozgur-karcioglu",fullName:"Ozgur Karcioglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7908",title:"Emergency Medicine and Trauma",subtitle:null,isOpenForSubmission:!1,hash:"4d0e9d0c91eff59a61e29cd67cbb036b",slug:"emergency-medicine-and-trauma",bookSignature:"Ozgur Karcioglu and Müge Günalp Eneyli",coverURL:"https://cdn.intechopen.com/books/images_new/7908.jpg",editedByType:"Edited by",editors:[{id:"221195",title:"Dr.",name:"Ozgur",surname:"Karcioglu",slug:"ozgur-karcioglu",fullName:"Ozgur Karcioglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5290",title:"Wound Healing",subtitle:"New insights into Ancient Challenges",isOpenForSubmission:!1,hash:"a6c479ab3fea0a9b7051d2a8478c91c3",slug:"wound-healing-new-insights-into-ancient-challenges",bookSignature:"Vlad Adrian Alexandrescu",coverURL:"https://cdn.intechopen.com/books/images_new/5290.jpg",editedByType:"Edited by",editors:[{id:"66358",title:"Ph.D.",name:"Vlad",surname:"Alexandrescu",slug:"vlad-alexandrescu",fullName:"Vlad Alexandrescu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7046",title:"Wound Healing",subtitle:"Current Perspectives",isOpenForSubmission:!1,hash:"fa7b870ad29ce1dfcf6faeafdc060309",slug:"wound-healing-current-perspectives",bookSignature:"Kamil Hakan Dogan",coverURL:"https://cdn.intechopen.com/books/images_new/7046.jpg",editedByType:"Edited by",editors:[{id:"30612",title:"Prof.",name:"Kamil Hakan",surname:"Dogan",slug:"kamil-hakan-dogan",fullName:"Kamil Hakan Dogan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6069",title:"Essentials of Spinal Cord Injury Medicine",subtitle:null,isOpenForSubmission:!1,hash:"f0a49e24ebfbb9ed7d02f7daab9b30f6",slug:"essentials-of-spinal-cord-injury-medicine",bookSignature:"Yannis Dionyssiotis",coverURL:"https://cdn.intechopen.com/books/images_new/6069.jpg",editedByType:"Edited by",editors:[{id:"76883",title:"PhD.",name:"Yannis",surname:"Dionyssiotis",slug:"yannis-dionyssiotis",fullName:"Yannis Dionyssiotis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9066",title:"Wound Healing",subtitle:null,isOpenForSubmission:!1,hash:"a293ecd8c2655a402321dc30e0ffbf9a",slug:"wound-healing",bookSignature:"Muhammad Ahmad",coverURL:"https://cdn.intechopen.com/books/images_new/9066.jpg",editedByType:"Edited by",editors:[{id:"204257",title:"Dr.",name:"Muhammad",surname:"Ahmad",slug:"muhammad-ahmad",fullName:"Muhammad Ahmad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],ofsBooks:[]},correction:{item:{id:"76397",slug:"corrigendum-the-role-of-minimally-invasive-surgery-in-the-treatment-of-lung-cancer",title:"Corrigendum to: The Role of Minimally Invasive Surgery in the Treatment of Lung Cancer",doi:null,correctionPDFUrl:"https://cdn.intechopen.com/pdfs/76397.pdf\r\n",downloadPdfUrl:"/chapter/pdf-download/76397",previewPdfUrl:"/chapter/pdf-preview/76397",totalDownloads:null,totalCrossrefCites:null,bibtexUrl:"/chapter/bibtex/76397",risUrl:"/chapter/ris/76397",chapter:{id:"76313",slug:"the-role-of-minimally-invasive-surgery-in-the-treatment-of-lung-cancer",signatures:"Güntuğ Batihan",dateSubmitted:"November 10th 2020",dateReviewed:"March 20th 2021",datePrePublished:"April 16th 2021",datePublished:null,book:{id:"10437",title:"Lung Cancer - Modern Multidisciplinary Management",subtitle:null,fullTitle:"Lung Cancer - Modern Multidisciplinary Management",slug:null,publishedDate:null,bookSignature:"Dr. Henry S. Park",coverURL:"//cdnintech.com/web/frontend/www/assets/cover.jpg",licenceType:"CC BY 3.0",editedByType:null,editors:[{id:"96610",title:"Dr.",name:"Henry",middleName:"S.",surname:"Park",slug:"henry-park",fullName:"Henry Park"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"296216",title:"M.D.",name:"Guntug",middleName:null,surname:"Batihan",fullName:"Guntug Batihan",slug:"guntug-batihan",email:"gbatihan@hotmail.com",position:null,institution:{name:"Dr. Suat Seren Göğüs Hastalıkları Hastanesi",institutionURL:null,country:{name:"Turkey"}}}]}},chapter:{id:"76313",slug:"the-role-of-minimally-invasive-surgery-in-the-treatment-of-lung-cancer",signatures:"Güntuğ Batihan",dateSubmitted:"November 10th 2020",dateReviewed:"March 20th 2021",datePrePublished:"April 16th 2021",datePublished:null,book:{id:"10437",title:"Lung Cancer - Modern Multidisciplinary Management",subtitle:null,fullTitle:"Lung Cancer - Modern Multidisciplinary Management",slug:null,publishedDate:null,bookSignature:"Dr. Henry S. Park",coverURL:"//cdnintech.com/web/frontend/www/assets/cover.jpg",licenceType:"CC BY 3.0",editedByType:null,editors:[{id:"96610",title:"Dr.",name:"Henry",middleName:"S.",surname:"Park",slug:"henry-park",fullName:"Henry Park"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"296216",title:"M.D.",name:"Guntug",middleName:null,surname:"Batihan",fullName:"Guntug Batihan",slug:"guntug-batihan",email:"gbatihan@hotmail.com",position:null,institution:{name:"Dr. Suat Seren Göğüs Hastalıkları Hastanesi",institutionURL:null,country:{name:"Turkey"}}}]},book:{id:"10437",title:"Lung Cancer - Modern Multidisciplinary Management",subtitle:null,fullTitle:"Lung Cancer - Modern Multidisciplinary Management",slug:null,publishedDate:null,bookSignature:"Dr. Henry S. Park",coverURL:"//cdnintech.com/web/frontend/www/assets/cover.jpg",licenceType:"CC BY 3.0",editedByType:null,editors:[{id:"96610",title:"Dr.",name:"Henry",middleName:"S.",surname:"Park",slug:"henry-park",fullName:"Henry Park"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"10678",leadTitle:null,title:"Biostatistics",subtitle:null,reviewType:"peer-reviewed",abstract:"This book will be a self-contained collection of scholarly papers targeting an audience of practicing researchers, academics, PhD students and other scientists. The contents of the book will be written by multiple authors and edited by experts in the field.",isbn:null,printIsbn:null,pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,hash:"f63db439474a574454a66894db8b394c",bookSignature:"",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10678.jpg",keywords:null,numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 26th 2020",dateEndSecondStepPublish:"November 16th 2020",dateEndThirdStepPublish:"January 15th 2021",dateEndFourthStepPublish:"April 5th 2021",dateEndFifthStepPublish:"June 4th 2021",remainingDaysToSecondStep:"5 months",secondStepPassed:!0,currentStepOfPublishingProcess:1,editedByType:null,kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"15",title:"Mathematics",slug:"mathematics"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:null},relatedBooks:[{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"314",title:"Regenerative Medicine and Tissue Engineering",subtitle:"Cells and Biomaterials",isOpenForSubmission:!1,hash:"bb67e80e480c86bb8315458012d65686",slug:"regenerative-medicine-and-tissue-engineering-cells-and-biomaterials",bookSignature:"Daniel Eberli",coverURL:"https://cdn.intechopen.com/books/images_new/314.jpg",editedByType:"Edited by",editors:[{id:"6495",title:"Dr.",name:"Daniel",surname:"Eberli",slug:"daniel-eberli",fullName:"Daniel Eberli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2270",title:"Fourier Transform",subtitle:"Materials Analysis",isOpenForSubmission:!1,hash:"5e094b066da527193e878e160b4772af",slug:"fourier-transform-materials-analysis",bookSignature:"Salih Mohammed Salih",coverURL:"https://cdn.intechopen.com/books/images_new/2270.jpg",editedByType:"Edited by",editors:[{id:"111691",title:"Dr.Ing.",name:"Salih",surname:"Salih",slug:"salih-salih",fullName:"Salih Salih"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"872",title:"Organic Pollutants Ten Years After the Stockholm Convention",subtitle:"Environmental and Analytical Update",isOpenForSubmission:!1,hash:"f01dc7077e1d23f3d8f5454985cafa0a",slug:"organic-pollutants-ten-years-after-the-stockholm-convention-environmental-and-analytical-update",bookSignature:"Tomasz Puzyn and Aleksandra Mostrag-Szlichtyng",coverURL:"https://cdn.intechopen.com/books/images_new/872.jpg",editedByType:"Edited by",editors:[{id:"84887",title:"Dr.",name:"Tomasz",surname:"Puzyn",slug:"tomasz-puzyn",fullName:"Tomasz Puzyn"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"71654",title:"Personalized Care: Prevention of Lifestyle Diseases",doi:"10.5772/intechopen.92001",slug:"personalized-care-prevention-of-lifestyle-diseases",body:'
Personalized or individualized care, which includes personalized medicine, as well as personalized nutrition and even personalized exercise, is an individual (patient)-centric, integrative, and holistic approach for the treatment and management of lifestyle diseases. Personalized care, a term often used interchangeably with precision medicine (an essential piece of personalized care which specifically refers to the medical treatment of the patient) is a more comprehensive term (than personalized or precision medicine) that represents an overarching philosophy for patient care, taking the advantage of personalized medicine and pharmacogenomics, as well as personalized nutrition and exercise. Personalized medicine, as defined by Schleidgen et al. [1] as an emerging area of medical care seeking to improve stratification and timing of healthcare by utilizing biological information and biomarkers on the level of molecular disease pathways, genetics, proteomics, as well as metabolomics, is an essential piece of personalized care. The key issue of personalized or individualized medicine remains how a targeted therapy can be used to tackle rapidly increasing chronic health burden by maximizing therapeutic efficacy and minimizing drug toxicity risks for an individual. Since the completion of the human genome project in the year 2000, the field has continued to evolve over the years especially from pharmacogenetics to pharmacogenomics so as to effectively monitor the multigenic effect on drug response [2]. Realization of the limitation of pharmacogenetics leads to the emergence of pharmacogenomics, which determines how genes affect a person’s response to drugs. This has opened up avenues for individualized identification of genetic variants using wide genome approaches through the use of latest and most recent methods, thus providing ways for determining molecular targets with the help of available DNA-based diagnostic screening tools [3].
A growing body of evidence has shown that chronic human diseases and conditions such as type 2 diabetes (T2D), cardiovascular diseases (CVD), atherosclerosis, obesity, and metabolic syndrome are associated with unhealthy lifestyle, which includes bad eating habits, physical inactivity, smoking, and exposure to stress [4]. A lifestyle modification with personalized nutrition and personalized physical activity is believed to play a central role in the prevention, management, and treatment of these life-threatening conditions [5]. Currently over 2500 genetic tests are available for the detection of diseases [6]. Ongoing efforts are being made to determine genetic risk of individuals to some of these diet-related conditions, like T2D and obesity, through available testing and screening methods so as to minimize the public health burden [7, 8]. Newer methods involving nanodiagnostic tools such as the DNA-based bionanosensors have recently emerged and are presumed to be safe and cost-effective with high specificity for early detection of the disease [9]. There is a vital need to educate the patients by the physicians and healthcare workers including the dietitians on the benefits of a well-balanced diet since failure to meet the nutritional requirements results in an array of conditions that occur due to the deficiency of certain nutrients. For example, the deficiencies of vitamins and minerals such as zinc, selenium, magnesium, chromium, and iron deficiencies have been reported in conditions like diabetes [10] and cystic fibrosis [11], especially among children. More recently, boron is getting recognition as an important trace element that may contribute significantly by mitigating the harmful effects in at least some of these diseases by augmenting the innate immune response and other mechanisms, such as stabilizing the complex membrane and macromolecular structures. Nutrient, especially the micronutrient deficiencies in early childhood or at a later stage may result in great economic burden that can lower a country’s GDP [12]. Individualized nutrition and personalized care have the potential of a positive impact on the healthcare sector with certain changes in the system [13]. Some of the required changes may involve largely policy issues and healthcare infrastructural changes [14], as well as economic changes [15, 16] to lower the cost of medication.
Lifestyle factors such as bad eating habits, sedentary lifestyle, high-calorie diet and excessive alcohol intake increase the rate at which some or most chronic human diseases develop. Most of these diseases, which include cancer, diabetes and atherosclerosis, are a leading cause of death and pose great health and economic burden to the country [17]. Prevalence of diabetes, in particular, continues to increase in the world. Diabetes is projected to be the seventh leading cause of death by the year 2030 [18]. Lifestyle changes such as personalized exercise (physical activity), personalized diet (nutrigenomics), and relaxation techniques (meditation and yoga) can help prevent or at least minimize the occurrence, as well as the prevalence, of these diseases [4].
Lifestyle changes and somewhat drug intervention have profound effect on the development and progression of chronic human diseases, including the disease progress, for example, from the prediabetes stage to diabetes, or even diabetes-associated complications. However, it is not clear who may or may not respond appropriately to a particular therapy. This is because individuals are different. Lifestyle changes like healthy eating and physical activity can do a lot of wonder in preventing chronic diseases when coupled with individual awareness to disease through genetic risk testing and other methods. Personalized or individualized nutrition holds great promise in the future and can be used to identify associations between genes, nutrients, and a disease so as to improve public health [19].
Diet and (lack of) physical activity constitute some of the major contributory factors for the development of chronic illnesses, both noncommunicable and communicable, directly impacting the immune system of the body and metabolism. Diseases like tuberculosis fail to develop if an individual’s lifestyle is healthy with respect to diet and physical activity. In diet-related complications such as obesity and T2D, a complex interplay of several factors including both genetic predisposition and lifestyle of an individual has been reported [5, 19]. These factors can have serious devastating effects on health, as the appearance of one disease may increase the chance for another disease; for example, obesity alone may lead to an increase in T2D and CVD [20].
Diet-related diseases are generally chronic in nature and are often associated with age and type of diet (nutrition) [21]. Personalizing diet, i.e., increasing the nutritional quality of diet and genotyping (nutrigenomics), leads to achieving a better health [22]. Earlier, global guidelines on food, certain food groups, and other nutrient requirements of the population were recommended with the overall view of preventing or delaying the onset of diet-related diseases. Nowadays, with an increased understanding of genetic differences pertaining to nutritional requirements among individuals, scientists are making efforts to categorize these guidelines based on inter-individual variation in dietary response resulting in a personalized diet, thus preventing chronic diet-related conditions [21]. Over the years, a number of clinicians and researchers have tried to demonstrate the importance of dietary modifications to achieve healthy and sustainable weight loss among overweight and obese individuals. However, these attempts could not yield positive results because of different metabolic roles of macromolecules such as the lipid, protein and carbohydrate in energy homeostasis and differences in metabolism. These molecules have a great effect on metabolism, appetite, and thermogenesis, which support the idea of considering the fuel value provided by each macromolecule separately. At times, even when considered separately, nature and kind of food constituents matter. For example, a diet which can reduce the risk of T2D and CVD is important for people who already have the disease. In this case, a fiber-rich or nonstarch polysaccharide diet, like whole grain, legumes, fruits and vegetables, is the most appropriate diet.
A sedentary lifestyle equally contributes to lifestyle diseases. It has been identified as a link between obesity, diabetes, metabolic syndrome, CVD, and death [23]. Physical inactivity is widely believed to be the primary cause of most preventable chronic conditions including diabetes, obesity and CVD. Therefore, physical activity may delay or prevent these and other chronic conditions [24]. Weight loss is recognized as one of the baseline strategies employed to deal with chronic inflammatory diseases like diabetes and CVD [25]. Obese individuals are overweight and prone to develop chronic inflammatory diseases. A holistic approach focusing on changes in lifestyle including changes in diet to suit individual’s needs, and physical activity, together with compatible precision medicine and ridding of the bad habits is bound to have beneficial effect on the management and prevention of life-threatening diseases and associated complications.
Individuals with type 2 diabetes are often faced with insulin resistance (IR) challenge arising from an accumulation of triglycerides in adipose tissues. Studies have shown that weight loss can bring significant improvement in IR both in T2D and in those with impaired glucose tolerance [26]. Nonetheless, there is an array of inter-individual variations with regard to improvement in insulin sensitivity and glycemia because of the individual response to changes in lifestyle factors such as the weight, diet and physical activity [5].
Increasing evidence has shown that single-nucleotide polymorphisms (SNPs) exist in diabetes [27, 28], which gives a lot of scope for the treatment based on genetic characteristics of an individual. These genetic differences are considered as markers of diabetes risk as they can be used to predict the disease and also to determine diabetes onset [29]. Nearly 80 genetic loci are thought to influence genetic susceptibility to both types of diabetes. An integral part of diabetes management and self-management education, medical nutrition therapy (MNT), was designed to provide patients with specific care as well as guidelines on lifestyle changes an individual can make and maintain in order to improve health [30]. Once individuals’ basic nutritional requirements have been achieved, chances of developing disease are rare even for diabetics where nutrient supplementation may be an issue of concern [31].
Management of obesity consists of the ability to lose weight either through exercise or personalized nutrition (non-pharmacological), or may involve the use of drugs. Due to individual genetic makeup and myriad of environmental factors, different individuals respond differently to exercise; some may even show resistance [32, 33]. Personalized exercise may help prevent unwanted individual response. In addition, identification of specific polymorphisms such as obesity-related SNPs may help find differences in dietary response to caloric restriction. Personalized nutrition is, therefore, expected to play a role in determining the kind and nature of diet suitable for different individuals owing to the environmental and genetic differences. Many of the diet-associated health burdens have been linked to SNPs, which is used to predict individual response to drugs in a population [34]. The most common examples of these polymorphisms are leptin/leptin receptor polymorphism (related to obesity gene), apolipoprotein (E and A1), which is related to CVD, and methylenetetrahydrofolate reductase (MTHR) related to folate metabolism [35].
Cardiovascular diseases (CVDs) are a group of metabolic diseases arising from atherosclerosis [36]. CVDs account for the most common cause of morbidity and mortality in the world [36], with poorly controlled diabetes as one of the promoting factors. Newer technologies involving large-scale genotyping and sequencing have allowed for identification of heritable CVD risks which can be used in personalized treatment. Epigenetics and personalized attempts are increasingly proving beneficial and providing a new way to treat CVDs [37]. In the near future, it is hoped that the DNA sequence variants associated with CVD or which show association with the beneficial or adverse effects of medication and used to predict CVD risk may be identified and guide the decision of choosing the best medication and dose to individual patients.
Much of the successful personalized treatments have been recorded in the area of oncology with many tumors and cancers being targeted with individualized regimens. Today, the world is witnessing a rapid progress in the upcoming field of personalized medicine with the emergence of genotyping industry for screening/testing, leading to an increased use of of precision medicines for cancer therapy. Many of these drugs are already available in the market and include kinase inhibitors [38]. Imatinib, lapatinib and erlotinib are some selective kinase inhibitors which are used to target anaplastic lymphoma [38].
Genomic information is increasing our understanding of oral health by providing an understanding of the disease etiology, thereby allowing easier diagnostic and a chance to take preventive measures to avoid the onset of oral diseases [39]. This is possible when genome analysis and disease risk assessment is started at childhood, as it gives room for proper planning for individualized prevention and monitoring strategies. By doing so, oral health and related problems like dental caries, periodontitis, and oral cancers may be detected at the onset and treated.
Osteoporosis is a complicated preventable syndrome that affects millions of peoples, especially women, in the world. Several personalized medicine intervention procedures are being investigated to identify the individuals with a high tendency to the disease. For instance, FRAX(R) is an algorithm that enables physicians to calculate the tendency for an individual patient risk for osteoporosis for 10 years, as well as helps in the selection of appropriate drug taking into consideration the choice of the patient [40]. Prognosis, treatment, and prevention of fractures would be easier when gene variants associated with osteoporosis are identified, leading to a more personalized approach/therapy [41].
Personalized care is at the verge of a revolution in healthcare sector, with potential to revolutionize the treatment, care and prevention of a number of debilitating life threatening diseases, some of which have been discussed in this chapter (Figure 1). When fully implemented, the treatment of patients can be individualized in strict accordance with their individual genetic make-up, rather than traditional “one-size-fits-all” pharmacology. A person’s lifestyle, which decides the overall well-being of an individual, is crucial while implementing the approach of personalized care of patients suffering from long-term lifestyle debilitating and morbid diseases through individualized nutrition, personal hygiene/oral health, and individualized needs that may be combined with relaxation techniques, such as meditation and yoga.
Diet-related conditions where personalized care can revolutionize the treatment, control and prevention of lifestyle diseases in human.
TSS has been a recipient of the India Council for Cultural Relations (ICCR) scholarship award and acknowledges ICCR for providing fellowship to pursue PhD under the supervision of SA.
The human immune system is an intricate network of cell types and signaling pathways that act in a concerted effort to ensure that when an immune response is elicited, it is directly proportional to the severity of the attack. Although this network exists to protect the body from foreign invasion, an overactive immune response can lead to immunopathogenesis and autoimmunity, thus it is crucial that there are mechanisms set in place to ensure this system remains tightly regulated [1]. The immune system achieves this strict regulation by engaging a complex system of checkpoint control pathways. These checkpoints act as metaphorical gateways that require a specific key, in the form of a protein or a small molecule, in order to initiate tightly regulated signaling pathways that prevent over-reactivity of an immune response through the binding of specific cell surface receptors. This process is known as peripheral tolerance [2]. Certain checkpoint pathways, including those involving transmembrane protein receptors cytotoxic t-lymphocyte antigen 4 (CTLA-4) and programmed death 1 (PD-1), play pivotal inhibitory roles in T-cell activation. Specifically, the CTLA-4 checkpoint is designed to inhibit T-cells from becoming autoreactive during the beginning stages of T-cell activation, while the PD-1 checkpoint is part of a family of costimulatory receptors that, when bound to its ligand, inhibits T-cell proliferation [2].
Tumor cells exploit the process of peripheral tolerance as a way to evade immunological surveillance by mimicking inhibitory receptors that are normally expressed on the surface of antigen presenting cells [3]. Expressing these inhibitory receptors allows cancer cells to effectively downregulate an immune response by deactivating the T-cells they come into contact with. The development of genetically engineered immune checkpoint inhibitors (ICIs) to treat malignancies therefore has the potential to revive pre-existing immune responses that would have otherwise been suppressed by the cancer [4]. Immunotherapies have been developed over the past decade using monoclonal antibodies as checkpoint inhibitors, binding the inhibitory receptor on T-cells and blocking tumor cells from binding to these sites.
The first immune checkpoint inhibition therapies to enter clinical trials for patients with advanced cancer were two fully human CTLA-4 blocking antibodies, ipilimumab and tremelimumab. Clinical activity of the CTLA-4 blockade was most significant in advanced melanoma patients, leading to a 15% response rate that, for some patients, persisted for over 10 years after discontinuing therapy [5]. In 2010, a large Phase III trial was published showing ipilimumab to have significantly improved overall survival rates in patients with metastatic melanoma, compared to treatment with standard gp100, a synthetic peptide cancer vaccine, alone [6]. Ipilimumab has since been FDA approved in combination for the treatment of advanced renal cell carcinoma, microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer, hepatocellular carcinoma, non-small cell lung cancer (NSCLC), and malignant pleural mesothelioma.
The PD-1 checkpoint pathway was the next to be targeted with antibody therapy. Similar to ipilimumab, the first nivolumab trials were also shown to be most efficacious in melanoma patients, although it is now approved not only for the treatment of melanoma, but also of non-small cell lung cancer (NSCLC), small cell lung cancer, malignant pleural mesothelioma, renal cell carcinoma, Hodgkin lymphoma, squamous cell carcinoma of the head and neck, urothelial carcinoma, MSI-H or dMMR metastatic colorectal cancer, hepatocellular carcinoma, and esophageal squamous cell carcinoma. A study assessing the efficacy of anti-CTLA-4 and anti-PD-1 combined therapy in melanoma patients showed even more significant results, with 53% of patients achieving an objective response, and ≥ 80% tumor reduction was reported in all patients [7].
Thus far, the only two immune checkpoint inhibitors that have been successfully brought to market are those that involve the PD-1/PD-L1 checkpoint and CTLA-4 checkpoint. These targets are within the adaptive immune system, but scientists are looking at the potential anti-tumor effects of exploring checkpoint targets within the innate immune system. Another target currently being investigated involves immune checkpoint inhibition within natural killer (NK) cell-mediated immunity. Cancer cells frequently downregulate their MHC expression, rendering T-cell mediated immunotherapy insufficient for killing these tumor cells. NK cell-mediated treatment can, in theory, compensate for this. As a first line of defense within the immune surveillance system, NK cells are quicker to become activated and will indiscriminately induce apoptosis in any cell lacking MHC-receptors.
Similar to the immune system, a checkpoint control system is also used to control the distinct phases of the cell division cycle in order to regulate cellular proliferation. Unrestrained cell division is a fundamental characteristic of oncogenesis, therefore cell cycle checkpoint control is vital in preventing the development of cancer. The mechanism of action in this case of checkpoint control is site-specific protein phosphorylation executed largely by cyclin-dependent proline-directed protein kinases. For example, Cyclin D1 and CDK4/6 are downstream of growth-initiating signaling pathways which lead to cellular proliferation. Palbociclib, an inhibitor of cyclin-dependent kinases CDK4/CDK6 is approved for the treatment of HR-positive, HER2-negative advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine based therapy in postmenopausal women or fulvestrant in women with disease progression following endocrine therapy [8].
Another example of an executive cell cycle regulatory protein is the cyclin G1 protein, product of the CCNG1 proto-oncogene: (i) identified as the prime molecular driver of “Cell Competence” (to proliferate), (ii) needed for quiescent cells to enter the G1 phase, subject to oncogene-addiction as a molecular survival factor [9]. Tumor-targeted gene therapy involving CCNG1 blockade was tested in a number of clinical trials over a decade ago, and has recently been revived for clinical use, upon analysis of long-term cancer-free survival data, as the first clinically validated tumor-targeted gene therapy vector of this kind. This genetic medicine, known as DeltaRex-G (Former names: Mx-dnG1, dnG1, Rexin-G), is a “retroviral expression vector displaying a cryptic/designer collagen-binding motif on its gp70 surface envelope, designed specifically for targeting abnormal (anaplastic) Signature (SIG) proteins in the tumor microenvironment and encoding a dominant-negative mutant construct (dnG1) of human CCNG1 (Cyclin G1)oncogene/survival factor [10]. Once administered intravenously, the DeltaRex-G nanoparticles (~100 nm) accumulate in cancerous lesions, where the transgene is expressed, using the tumor cell’s replication machinery to translate a mutant, cytocidal protein that is specifically designed to block the Cyclin G1 pathways of cell competence and survival function, leading to active cancer cell death via apoptosis.
Herein, we discuss the current landscape of immune and cell cycle checkpoint inhibition by presenting a selected number of ongoing and past clinical research for advanced malignancies at the Cancer Center of Southern California (CCSC)/Sarcoma Oncology Research Center (SORC) in Santa Monica, California, in context and collaboration.
Ongoing clinical research is either investigator-initiated or company sponsored. In the case of investigator-initiated research, CCSC/SORC serves as the sponsor, conceives and designs the clinical protocol, and manages the entire clinical trial with or without funding by a pharmaceutical company, the FDA or the NIH. Company-sponsored research is developed, monitored, and funded by a pharmaceutical company.
Soft tissue sarcomas comprise a rare, heterogenous category of malignancies originating from connective tissue, blood vessels or lymphatic tissue [11]. This group accounts for only 1% of adult cancers in the United States, but it has a higher mortality rate than testicular cancer, thyroid cancer, and Hodgkin lymphoma combined [12]. The most commonly used modalities of treatment for sarcoma have been surgery, radiation and chemotherapy. Currently, chemotherapy treatment options have been shown to slow down disease progression but are ineffective in keeping most patients from eventually developing recurrent and metastatic disease [13]. Once unresectable or metastatic, the majority of soft tissue sarcomas remain incurable with chemotherapy. Immune checkpoint blockades do not act directly on the cancer cell, thus they can theoretically be applied to the treatment of any type of solid tumor, including the rarest and most aggressive malignancies. The precedent set by the approval of immune checkpoint inhibition for the treatment of numerous cancer types provides a strong rationale for studying their effects on soft tissue sarcoma. Studies with ipilimumab and nivolumab have since been done showing promising results when used in patients with advanced soft tissue sarcoma [14]. The third drug in this trial is a marine-derived alkaloid, trabectedin, an FDA approved chemotherapy treatment for leiomyosarcoma and liposarcoma [15]. A recently published retroactive analysis of 442 patients treated with trabectedin over a 10 year period confirms that trabectedin can prolong progression free survival (PFS) in patients with advanced sarcoma [16].
Gordon et al. designed the SAINT protocol based on the fact that sarcoma cells are most immunogenic early in the disease process [17] and prior to any other treatment, allowing immune checkpoint inhibitors to exploit this advantage and deploy the immune system to recognize and destroy them. This study was designed to evaluate the best objective response rates (BORR) assessed via CT scan or MRI and to assess the overall survival (OS) and progression-free survival (PFS) after 6 months of treatment.
Eligible patients for this Phase II clinical trial were treatment-naïve adult patients with advanced unresectable or metastatic soft tissue sarcoma. Trabectedin was administered to the study subjects at the maximum tolerated dose determined previously in the dose escalation phase of this trial. Ipilimumab and nivolumab were be administered at defined doses in order to assess the overall safety profile and potential efficacy of this treatment regimen. Patients continued on the treatment until they experienced significant disease progression or unmanageable toxicities. Best objective response was measured according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 using CT scan or MRI. Median progression-free survival (PFS) and overall survival (OS) were also measured in months. Adverse events were assessed and categorized as related or unrelated to the treatment and listed by severity according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Sixty subjects were evaluated using RECIST v1.1 for analysis of treatment efficacy. Twenty-five percent (25%) had either a complete response (11.7%) or a partial response (13.3%), and 37 patients (61.7%) had stable disease. Disease control rate was 86.6%. The median PFS was >6.7 months (6-month OS rate: 90%; 6-month PFS rate: 51%), while the median OS was >17.0 months.
Grade 3 TRAEs included fatigue (n = 6), adrenal insufficiency (n = 1), hyperglycemia (n = 1), dehydration (n = 1), hyponatremia (n = 2), bipedal edema (n = 2), increased AST (n = 6), increased ALT (n = 19), increased ALP (n = 1), port site infection (n = 2), psoriasis exacerbation (n = 1), anemia (n = 3), thrombocytopenia (n = 2), leukopenia (n = 1), and neutropenia (n = 3). Grade 4 TRAES include anemia (n = 1), neutropenia (n = 1), thrombocytopenia (n = 1), and increased CPK (n = 2). Grade 5 TRAES include rhabdomyolysis (n = 1). Therapy related AML occurred in one patient.
The positive results from this trial thus far strongly suggest that using combination therapy with ipilimumab, nivolumab, and trabectedin as first-line treatment in patients with advanced or metastatic sarcoma allows the treatments to engage synergistically without causing any additive toxicities. This combination may be superior to known therapies for STS. Overall, the adverse events experienced less severe than toxicities typically experienced with standard first line treatment (doxorubicin/ifosfamide) for metastatic soft tissue sarcoma. Future Phase 3 randomized studies are proposed to evaluate the safety and efficacy of first-line combinatorial therapy with ipilimumab, nivolumab and trabectedin in comparison to standard therapy for patients with advanced soft tissue sarcomas.
The significant immunotherapeutic potential of oncolytic virotherapy is due to its ability to induce a multifaceted anti-tumor response involving aspects of both the innate and adaptive immune systems [18]. A multitude of viral vectors have been explored for their potential oncolytic properties, particularly as a method of delivering targeted treatment to sites of malignant disease [19]. The ability to genetically modify these viruses to target and exploit essential oncogenic signaling pathways has kept them at the forefront of immuno-oncology research [20]. This particular vulnerability triggers selective replication of the viral genome and directly contributes to furthering the oncolytic process. Infected tumor cells secrete viral progeny composed in part by tumor-associated antigens and neoantigens in response to their infection, causing the innate immune system to activate an NK cell-mediated cytotoxic response. The tumor-associated antigens that are released into the tumor microenvironment are phagocytosed by antigen-presenting cells, thus initiating the process of T-cell-mediated adaptive anti-tumor immunity. In addition to the anti-tumor response, the presence of the oncolytic virus also triggers a concurrent anti-viral response, and regulatory mechanisms become crucial to ensuring a controlled immune response, including the upregulation of immune checkpoints [20].
Oncolytic viruses derived from Herpes simplex virus 1 (HSV-1) vectors are amongst the most frequently investigated in pre-clinical trials and have been shown to encompass the combined ability to induce oncolysis and anti-tumor immune responses simultaneously [21]. Talimogene Laherparepvec (T-VEC) is an injectable live, attenuated, oncolytic HSV-1 virus that has been genetically engineered to express human granulocyte-macrophage colony-stimulating factor (huGM-CSF), a known immune modulator and hematopoietic growth factor that stimulates the differentiation of multipotent progenitor cells and plays a key role in the functional abilities of many different circulating lymphocytes, including T-cells [22].
The objective of this ongoing study is to evaluate the potentially synergistic effects T-VEC may evoke when used in combination with anti-PD-L1 monoclonal antibody, nivolumab and marine derived alkaloid, trabectedin. The study is ongoing.
This open-label Phase II study is designed to assess the safety and efficacy of this combination treatment. This will be accomplished by determining the median month of progression-free survival, median duration of response, and best overall response rates based on each patients’ percent of change in their tumor sizes. This study plans to enroll 40 participants with advanced disease who have at least one tumor that is easily accessible for intratumoral injection with T-VEC. Regarding the statistical analysis, continuous variables will be summarized by the sample size (n) and measures of central tendency and variation will be calculated including mean, standard deviation, first and third quartiles, maximum and minimum. Categorical variables will be summarized by the sample and by the percent in each category. “Point estimates for efficacy endpoint incidences will be accompanied by a 2-sided 95% exact binomial CI. Time to event endpoints will be summarized descriptively using the KM method. Safety (incidence and severity of adverse events and significant laboratory abnormalities) will be performed on all patients (ITT population). Patient incidence of all treatment emergent AEs will be tabulated by system organ class and preferred term” [23].
Efficacy analysis (n = 31): There were 6.5% partial responses, 80.6% disease control rate, with 74.1% PFS rate and 92.6% OS rate at 4 months.
Safety Analysis (n = 41): Grade 3 TRAEs include fatigue (n = 2), decreased ejection fraction (n = 1), anasarca (n = 1), dehydration (n = 1), decreased cortisol (n = 1), anemia (n = 9), thrombocytopenia (n = 4), neutropenia (n = 4), gastroenteritis (n = 1), increased ALT (n = 8), increased AST (n = 1), and increased GGT (n = 1). Grade 4 TRAEs observed were thrombocytopenia (n = 2). There was no conversion from unresectable to resectable tumor. There were thirty-one evaluable subjects for efficacy analysis.
Second- or third- line combinatorial therapy with talimogene laherparepvec, nivolumab, and trabectedin.
may be equal or better than standard second/third line therapy in achieving disease control.
may be safer than standard therapy for patients with advanced soft tissue sarcoma with no unexpected toxicities.
Studies are proposed to evaluate the efficacy and safety of first, second/third line combinatorial therapy with talimogene laherparepvec, nivolumab and trabectedin vs. standard therapy (doxorubicin/ifosfamide) in randomized studies for advanced soft tissue sarcomas.
Aberrant mTOR signaling, typically due to either an activating mutation in oncogenes related to the mTOR pathway or a loss of function mutation in an upstream tumor suppressor gene, has been found to play a significant, multifaceted role in oncogenesis [24, 25]. Originally discovered while investigating the targets of the drug rapamycin, a potent immunosuppressive agent, in the early 1990’s, the protein kinase, mammalian target of rapamycin (mTOR), is a major signaling hub for directing cellular growth, metabolism, and proliferation [26]. While studying the mechanism of action behind rapamycin’s inhibitory effects on mTOR signaling, the drug was also found to be involved in the inhibition of T-cell proliferation, specifically between the G1 and S phases of the cell cycle. This finding launched a multitude of studies to better understand the role of mTOR signaling in T-cell activation and proliferation [27], culminating in the discovery that T-cells are also highly dependent on mTOR signaling to maintain normal T-cell activation and proliferation [28]. When t-cells receive immune stimuli, they then rely on signals from mTOR to promote t-helper cell differentiation while simultaneously inhibiting the induction of regulatory T-cells. Thus, mTOR exerts control over essential regulatory signals in both adaptive and innate immunity.
Initial clinical studies investigating the anti-cancer effects of single agent mTOR inhibitor, were disappointing, reporting its limited effects, thus leading to the investigation of rapamycin in combination with various chemotherapy agents where it was successful in inhibiting cancer growth in prostate cancer patients [29]. However, the experimental drug, ABI-009 or nab-sirolimus, a novel albumin-bound mTOR inhibitor, has been shown to be effective and safe for the treatment of malignant perivascular epithelioid cell tumors (PEComa) [30]. A phase 1/2 trial is currently ongoing to investigate the potential synergistic activity of nab-sirolimus when administered with an immune checkpoint inhibitor, nivolumab, in improving clinical outcomes for patients with advanced sarcoma.
The original objectives of the study are: (1) To investigate the maximum tolerated dose (MTD) of ABI-009 when given with nivolumab, a PD-1 inhibitor, in previously treated advanced undifferentiated pleomorphic sarcoma, liposarcoma, chondrosarcoma, osteosarcoma and Ewing sarcoma; (2) To investigate the disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) of this combination therapy in the aforementioned patient group, and (3) To correlate PFS with PD-L1 and other biomarker expression in patients’ tumors.
This is an IRB approved protocol with 2 parts. The phase 1 part is a dose-finding study using the “cohort of three design”, wherein a standard dose of nivolumab 240 mg is given IV every 3 weeks (day 1 of every 21-day cycle). Escalating doses of ABI-009 are given IV on days 8 and 15 of each cycle starting in Cycle 2 following the 2nd nivolumab dose. The starting dose of ABI-009 is 56 mg/m2, and sequentially escalating doses are 75, and 100 mg/m2. Phase 2 of the study will enroll 31 additional patients to further assess efficacy and safety at the MTD.
The Phase I part of study included 9 patients who were treated successfully at 3 dose levels. No dose-limiting toxicities (DLTs) were observed, the MTD was not reached, and 100 mg/m2 ABI-009 was designated as the recommended Phase II dose. Safety analysis: At Dose 1 (n = 3): Grade 3 treatment-related adverse events (TRAEs) included dyslipidemia (n = 1) and hyperglycemia (n = 1). At Dose 2 (n = 3): Grade 3 TRAEs included increased ALT (n = 1). At Dose 3 (n = 3): Grade 3 TRAEs included hypophosphatemia (n = 1).
The primary endpoint has been met with no DLTs, the MTD was not reached and Dose 3 (100 mg/m2) of ABI-009 has been designated as the phase 2 dose which is on-going.
The initiation of the extrinsic apoptosis pathway is mediated by several death domain receptors including death receptor 5 (DR5), a transmembrane protein receptor activated by the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) [31]. The DR5 apoptosis pathway naturally occurs to rid the body of neoplastic cells and is known to be crucial in immune system surveillance against cancer growth and metastasis. Normally, when an anchorage-dependent cell becomes detached, the cell will undergo a process of detachment-induced apoptosis called anoikis, initiated by a death receptor-mediated apoptotic pathway. A reduction in DR5 expression was found in melanoma tumor samples, strongly implying the TRAIL/DR5 pathway is associated with the prevention of tumor metastasis [32]. In 1999, Walczak et al. observed tumor cells to have a significantly higher sensitivity to TRAIL than normal cells, emphasizing its potential as a therapeutic cancer agent [33]. The subsequent development of agonistic antibodies against DR5 (i.e. recombinant human TRAIL proteins) was shown to be successful in stimulating apoptosis when tested in various tumor cell lines, and was later also shown to enhance the efficacy of chemotherapy and radiotherapy [34].
INBRX-109 is a tetravalent DR5 agonist antibody designed to initiate the DR5 apoptosis pathway and precisely engineered to avoid unnecessary crosslinking to lower the risk of hepatotoxicity.
This is the first in-human, open-label, non-randomized Phase I clinical trial for INBRX-109. Eligible patients had metastatic or unresectable solid tumors refractory to standard treatment or for which there is no FDA approved standard treatment. Phase I consists of two parts, part 1 being a 3 + 3 dose escalation cohort and part 2 being a dose expansion cohort. Safety, tolerability and dose-limiting toxicity were measured and analyzed using the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) criteria to assess the severity of adverse events experienced. This study’s exploratory objective is an assessment of anti-tumor activity and was reported according to RECIST v1.1 standard.
Overall, INBRX-109 was well tolerated and approximately 90% of patients showed no signs of hepatotoxicity. The pharmacokinetics of INBRX-109 were approximately dose proportional across all doses tested and thus support dosing every 3 weeks without administration of any premedications. All patients have thus far tested negative for anti-drug antibodies. Maximum tolerated dose was not reached in the dose escalation cohort and only one dose-limiting toxicity was experienced. Very few serious adverse events that occurred were attributable to the drug being studied. One patient with mesothelioma has been reported to have experienced acute hepatic failure leading to death that could possibly be related to the study drug. Evidence of anti-cancer effects were observed in patients with chondrosarcoma, resulting in durable partial responses and stable disease.
NBRX-109, a precisely engineered tetravalent DR5 agonist antibody, showed promising results that warrant further exploration. The pharmacokinetics of INBRX-109 were essentially dose-proportional across all three dose levels, supporting dosing every three weeks with no premedications necessary. Specifically, the chondrosarcoma cohort of this Phase I study has been expanded to include twenty patients and is currently ongoing.
Unregulated angiogenesis is one of the key characteristics of malignant tumors [35]. In addition to creating neovasculature, tumor angiogenesis plays a key role in creating an immunosuppressive tumor microenvironment by causing an accumulation of pro-tumor immune cells and a decrease in the abundance and function of anti-tumor immune cells. Anti-angiogenic cancer treatments have been shown to reverse this process, essentially ‘reprogramming’ the tumor microenvironment by converting it from an immunosuppressive to an immunogenic one. This has been accomplished by targeting and inhibiting vascular endothelial growth factor (VEGF), a well-known cell surface-signaling proangiogenic protein that becomes stimulated when bound to tyrosine kinase receptors. With the use of antiangiogenic small molecule tyrosine kinase inhibitors (TKIs), VEGF can be blocked from binding its receptor, stopping the tumor from being able to continue to create neovasculature [36]. However, cancer has been able to circumvent this blockade using multiple other pathways, suggesting the use of antiangiogenic therapies that inhibit more than one signaling pathway simultaneously.
The experimental drug, apatinib, is a highly selective VEGFR-2 TKI, administered orally, that has already been approved in China for ≥3rd-line treatment for advanced gastric cancer. The potential benefit of combining TKI and PD-1 therapies has been demonstrated in preclinical murine models, suggesting that combining ICIs with antiangiogenesis therapy could have the synergistic antitumor effects needed to enhance the efficacy of the individual therapies [37]. This phase 1 single-center clinical trial beginning in 2018 evaluated the safety and tolerability of TKI, apatinib, and PD-1 inhibitor, nivolumab, in patients with unresectable or metastatic cancer.
All subjects enrolled had cancer that was refractory to prior lines of treatment. Specifically, patients were required to already be at least three cycles into nivolumab treatment and must be planning to continue this treatment throughout the trial period. Thirty patients in total were enrolled, ten of which were in part 1 of this study, where they were treated with apatinib using a classic 3 + 3 dose escalation method in order to determine the maximum tolerated dose. Part 2 of this study included twenty subjects and was an expansion phase using the MTD. The percent of change in tumor responses and amount of time until progression were measured and analyzed using RECIST v1.1 and iRECIST criteria.
The overall response rate reported was 13.3% (95% CI: 3.8% to 30.7%) and the median PFS was 7.2 months (95% CI: 5.3 to 9.0 months). No complete responses occurred although four patients achieved a partial response and the majority of patients achieved stable disease. Seven patients from part 1 and six patients from part 2 experienced ≥ grade 3 treatment emergent adverse events including fatigue (10.0%), hypertension (10.0%), nausea (10.0%), anemia (16.7%) and asthenia (10.0%). Two patients experienced fatal adverse events, although there were no noted treatment related deaths. Nine patients eventually discontinued the study due to toxicity, and nine patients also received a dose reduction. No unexpected side effects were noted as a result of the combined treatment.
The results of this study demonstrate an acceptable safety profile and clinical benefit of combination treatment with nivolumab and apatinib that is worth exploring further in additional clinical studies.
Natural killer (NK) cells are the cytotoxic lymphocytes of the innate immune system [38]. As a rapid, first line of defense, NK cells are able to lyse tumor cells independent of the expression of tumor-associated antigens and/or the presence of major histocompatibility complex class I (MHC-I) molecules. This ability is crucial as cancer cells have been shown to downregulate the expression of MHC-I on their cell surface as a way to evade detection by immunosurveillance mechanisms [39]. Since the expression of MHC-I on cancer cells is needed for their detection and destruction by T-cells, evolving a loss of MHC-I expression has been a way for tumor cells to remain undetectable and this loss has therefore been reported “as a mechanism of resistance to anti–PD-1 therapy” [40]. In order to avoid the development of resistance to PD-1 checkpoint inhibition therapy, exploration of NK cell therapy is warranted, especially because of the NK cell’s specific role in the recognition and destruction of cancer cells that display a loss of MHC-I. Additionally, the broad ability of NK cells to destroy tumor cells irrespective of prior sensitization or immunization therapy make them ideal candidates for engineered cell therapies.
Discoveries regarding the NK cell’s role in anti-tumor immunity coupled with advancements in the field of hematopoietic stem cell transplantation have brought to light the potential in using NK cell-mediated immunotherapeutic strategies to fight cancer [41]. Adoptive immunotherapy using donor-derived autologous NK cell products can be engineered by using monoclonal antibodies alone, or in combination with in vivo and ex vivo NK cell activation techniques [42]. This is done by obtaining a patient’s NK cells and incubating them as highly active NK cells, giving them the ability to mass produce NK cells which are then infused back into the patient. This study explores the safety and tolerability of treating cancer with SNK01 (autologous natural killer cells).
This study is a nonrandomized, multicenter safety study of adoptively infused, ex vivo expanded autologous NK cells to treat male and female adult patients with advanced or metastatic, intractable cancer. Study subjects were placed in one of three cohorts and received SNK01 in an open-label fashion according to a 3 + 3 Phase 1 dose-escalation method. Patients received 5 weekly infusions for a period of 5 weeks, and restaging imaging was performed on week 6. The primary objective of this study was a safety assessment based on the incidence and severity of dose-limiting toxicities and other adverse events observed by evaluating vital signs, clinical laboratory findings and physical examination abnormalities. The adverse events were graded according to the CTCAE v5.0 criteria. Subjects’ performance status was assessed and recorded using ECOG criteria. The secondary objective is to evaluate the efficacy of the treatment by measuring the objective response rate of target lesions observed via CT scan using iRECIST criteria.
Not yet available.
In order to effectively achieve immune surveillance, immunosuppressive signals within the tumor microenvironment must be interrupted. The PD-1/PD-L1 signaling blockade was developed in accordance with this principle. Tumors have been shown to secrete cytokines associated with suppression of T-cells and NK cells, and past murine studies have shown circulating IL-18 in low levels originating from tumor cells can suppress NK anti-tumor activity [41]. The principles of checkpoint blockade can be applied here with the development of a neutralizing antibody to IL-18, suggesting the potential of checkpoint inhibition to improve in vivo NK cell activity.
NY-ESO-1 is a protein that is normally expressed in fetal and testicular tissues, although some solid malignancies have been known to express an abnormal NY-ESO-1 protein that has become a target for emerging antigen-directed cancer therapies [43, 44]. Previous studies looking at NY-ESO-1 expression in cancer cells have reported its presence in the majority of synovial sarcomas tested, as well as sporadic expression in a number of other sarcoma subsets [45]. The immunogenicity of NY-ESO-1 has been demonstrated by the discovery of receptors against NY-ESO-1 on CD8+ T-cells. A 2011 clinical trial conducted by the National Cancer Institute was the first to report promising anticancer effects of NY-ESO-1-targeted immunotherapy in patients with metastatic synovial sarcoma using adoptively transferred autologous T-cells containing a T-cell receptor against NY-ESO-1 [46], suggesting its potential to be effective in other sarcomas as well. Since then, numerous trials targeting NY-ESO-1 in various cancer types using both adoptive T-cell therapy and vaccination approaches have concluded that there is a clear clinical benefit in pursuing NY-ESO-1 as an immunotherapeutic target [47].
The drug being studied is CMB305, a prime-boost immunotherapeutic vaccine regimen developed to prime the immune system and enhance its subsequent response to immunotherapeutic agents. The priming component of CMB305 is an integration-deficient, replication-incompetent lentiviral vector containing RNA coding for NY-ESO-1. The boost component contains a recombinant E. coli-produced NY-ESO-1 protein that, as a single agent, can initiate anti-NY-ESO-1-specific CD4+ T-cell and antibody responses. The combination of the primer and the booster was designed with the intention of eliciting an enhanced T-cell response.
The goal of this study was to investigate the ability of a prime-boost immunotherapy regimen that is able to elicit NY-ESO-1-specific CD8+ T-cells to synergistically enhance the efficacy of PD-L1 checkpoint inhibition therapy in advanced or metastatic sarcoma patients whose tumors are positive for NY-ESO-1 expression.
The primary objective of this study was to compare the progression-free survival in locally advanced or metastatic sarcoma patients whose tumors expressed NY-ESO-1 when treated with CMB305 in combination with atezolizumab versus patients treated with atezolizumab alone. The secondary objectives of this study were to evaluate the safety of this combination treatment, as well as to evaluate the best overall response rate using RECIST v1.1 modified to use immune-related response criteria. The overall survival of the two groups will be evaluated.
Twelve patients were randomized 1:1 in a safety run-in evaluation. Next, 80 patients were randomized and stratified by disease. Tumor samples from all patients were tested for levels of PD-L1 and NY-ESO-1 expression prior to treatment, and again on Day 42 in order to assess the extent of successful immune cell invasion in the tumor. Re-staging imaging studies were performed every six weeks for the first twelve months, followed by staging every twelve weeks until the patient displayed symptomatic progression. CMB305 treatment was administered in seven doses over a three-month period, while atezolizumab was administered intravenously every three weeks, and was continued up to two years or until toxicities began to develop. An additional booster dose was also given every six weeks for the first year or until the patient displayed disease progression. Blood samples were collected to test for lentivirus vector persistence at baseline, six, twelve and twenty-four months following the initial treatment. Adverse events were recorded as related or unrelated to the study drug and graded based on CTCAE c4.03 criteria.
Not Available.
Phase I of this trial was the first of its kind to test a prime-boost vaccination regimen to treat patients with advanced cancer. In 2018, Immune Design released information stating that an early analysis of the Phase II clinical trial results showed the combination treatment of atezolizumab with CMB305 suggested that it is unlikely this regimen will show enhanced survival time of patients with recurrent synovial sarcoma [48]. A Phase III trial has not yet been pursued.
Advanced pancreatic adenocarcinoma is the third most common cancer type in the Unites States, although diagnostic tests are non-specific which leads to early-stage disease frequently going undetected [49, 50]. Once pancreatic adenocarcinoma reaches an advanced stage, it has likely become intractable and there is no cure. Previous targeted therapies revolved around the epidermal growth factor receptor (EGFR) signaling pathway, one of the most significant factors regulating cell growth, survival, differentiation and proliferation, making it a promising target for precision medicine [51]. EGFR signaling has been identified as an oncogenic driver in multiple cancer types, and EGFR inhibitors have been used as targeted therapy for pancreatic cancer [52].
DeltaRex-G is the first injectable tumor-targeted gene delivery system to be developed for cancer that blocks the G1 checkpoint of the cell division cycle of cancer cells by inhibiting the CCNG1 gene. DeltaRex-G includes a mutant construct of the CCNG1 gene that inhibits human cyclin G1, a proto-oncogene that promotes cell competence, cell survival, and stem cell proliferation. When administered systemically, DeltaRex-G seeks out and accumulates in tumor tissues by binding abnormal collagenous signature (SIG) proteins that are characteristically exposed as anaplasia during tumor invasion. Once the DeltaRex-G retrovector is incorporated in rapidly dividing cells, a cytocidal CCNG1 inhibitor protein is expressed that effectively blocks the cell division cycle, resulting in apoptosis and subsequent eradication of cancer cells, proliferative vasculature, and stroma.
Clinical data from DeltaRex-G trials conducted initially in the Philippines showed promising results for patients with advanced pancreatic adenocarcinoma. This prompted USFDA Orphan Drug status, leading to progressive clinical trials in the United States, using DeltaRex-G to treat chemotherapy-resistant advanced pancreatic adenocarcinoma, soft tissue sarcoma, osteosarcoma, and breast cancers. This study reports the results compiled from a Phase I-II clinical trial using intravenous infusions of DeltaRex-G as treatment for advanced pancreatic cancer.
Twenty patients with chemotherapy-resistant metastatic pancreatic cancer were enrolled in the trial. Target lesions were identified in each patient and changes in tumor size were measured using RECIST v1.0 criteria. Patients were grouped and treated at 3 escalating doses of DeltaRex-G, with six patients at Dose 0-I, seven patients at dose level II, and seven patients at dose level III. Fifteen patients completed at least one full 4-week treatment cycle and had a follow-up PET-CT scan. These fifteen subjects comprised the modified intent-to-treat (mITT) population and were evaluated in terms of their response to the treatment, months of progression-free survival and months of overall survival.
The safety analysis revealed no clinically significant dose-limiting toxicities at any of the 3 dose levels, with no serious adverse events related to the study drug. None of the patients tested positive for vector neutralizing antibodies, replication-competent retrovirus in peripheral blood lymphocytes, antibodies to gp70, or vector integration into the genomic DNA of peripheral blood lymphocytes. According to the RECIST v1.0 evaluations of tumor responses, one patient achieved a complete response, two patients, partial response, and 12 patients, stable disease with 100% disease control rate. The median progression free survival by RECIST v1.0 was 2.7 months, 4.0 months, and 5.6 months at Dose levels I, II, and III, respectively. Median overall survival was 4.3 months, 9.2 months, and 9.2 months at Dose levels I, II, and III, respectively. A dose response relationship was shown between duration of survival and DeltaRex-G dosage (p = 0.03). Consequently, fast track designation was given by the USFDA for a planned Phase 2/3 study using DeltaRex-G as second line therapy for advanced pancreatic adenocarcinoma.
DeltaRex-G is a potent cytotoxic cell cycle checkpoint inhibitor. Complete and partial responses were observed at dose levels II and III, suggesting a significant dose–response relationship between the dose of DeltaRex-G given and the level of response seen in the tumors. This relationship is further implied by the increase in months of progression free survival as the dosages were increased. Additionally, CCNG1 is expressed in over 50% of various different malignancies other than pancreatic cancer, suggesting DeltaRex-G’s potential efficacy in other cancer types [10].
Cell cycle checkpoint pathways that govern uninhibited cell proliferation can be rendered ineffective by a variety of cancer-induced immunosuppressive mechanisms [53]. The experimental cancer gene therapy, DeltaRex-G, is a pathotropic (disease-seeking) retrovector designed to disrupt the cell cycle machinery of proliferative tumor cells, forcing them to undergo apoptosis. This is accomplished through “precise” tumor-targeted gene delivery to block the Cyclin G1/Cdk/cMyc/Mdm2/p53 Axis, effectively arresting the dividing tumor cell in G1 phase of the cell cycle undermining CCNG1 oncogene addiction. Clinical trials using DeltaRex-G to treat cancers that are unresponsive to traditional therapy have shown remarkable efficacy in evoking long term cancer-free survival with monotherapy (>10 years) in a number of patients with pancreatic cancer, osteosarcoma, soft tissue sarcomas, breast cancer, and B-cell lymphoma [54]. Although DeltaRex-G is involved in cell cycle checkpoint inhibition, it has also been shown to reduce extracellular matrix production by tumor cells and increase immune cell entry into the tumor microenvironment, which raises the clinical potential for DeltaRex-G to work synergistically with specific immune checkpoint inhibitors.
One persistent thought is that blanket recruitment of immune cells to the tumor microenvironment may not always be advantageous in creating an effective anti-tumor response. Certain tumor-infiltrating immune cells of myeloid origin have been shown to aid in tumor metastasis [55]. Cancers often progress and metastasize using immunosuppressive mechanisms that includes production and secretion of molecules that recruit cells involved in immune responses to the tumor microenvironment, and by exploiting checkpoint altering pathways [56]. Alternatively, and plausibly, this is how the innate immune system works in a healthy individual, with its molecular start and stop switches to prevent exaggerated immune responses and autoimmune disease. This study reviews published literature on the specific tumor-infiltrating immune cells seen in tumors of patients treated with DeltaRex-G.
A review of published literature was conducted on articles pertaining to the efficacy of DeltaRex-G in influencing the tumor microenvironment. The tumor types identified throughout the literature review included pancreatic adenocarcinoma metastatic to the liver, melanoma metastatic to the inguinal lymph node, colorectal cancer metastatic to the lungs, pancreatic B-cell lymphoma metastatic to the liver and cervical lymph nodes, recurrent breast ductal adenocarcinoma, and non-small cell lung carcinoma metastatic to the adrenal gland. The presence of tumor-infiltrating lymphocytes in excised tumors of patients treated with DeltaRex-G was assessed using immunohistochemical staining, and anti-tumor immune cells were differentiated from pro-tumor immune cells by their cytological characteristics. Agents included in the category of anti-tumor immune cells included dendritic cells, helper T-cells, natural killer cells, and killer T-cells. Regulatory T-cells and B-cells have the ability to encourage tumor growth by preventing antigen presentation and killer T-cell activation, thus were categorized as possibly pro-tumor immune cells. M1 macrophages were categorized as anti-tumor, although M2-type tumor-associated macrophages can promote tumor pathogenicity by overpowering M1-type tumor-infiltrating macrophages that elicit anti-tumor inflammation and were therefore categorized as pro-tumor. Results were reported based on cancer type.
Killer T-cells were identified in the tumor microenvironment of all cancers analyzed and helper T-cells were identified in all tumor types except for pancreatic B-cell lymphoma metastatic to the liver and cervical lymph nodes. Dendritic cells were found in metastatic pancreatic adenocarcinoma, metastatic melanoma, breast ductal adenocarcinoma and metastatic non-small cell lung cancer. Natural killer cells were seen in metastatic pancreatic adenocarcinoma and metastatic non-small cell lung cancer. M1 macrophages were seen in breast ductal adenocarcinoma.
B-cells, possible pro-tumor cells, were seen in metastatic pancreatic adenocarcinoma, metastatic colorectal cancer, breast ductal adenocarcinoma and metastatic non-small cell lung cancer. Leukocyte common antigen was seen in metastatic pancreatic adenocarcinoma, metastatic melanoma, and non-small cell lung cancer. Pro-tumor macrophages were seen in breast ductal carcinoma.
Activating and optimizing the body’s own immune system is at the core of precision medicine. Pathologic review showed evidence of
Patients whose cancer has recurred or progressed after therapy have likely exhausted their treatment options [57]. This is where the need for research towards the development of personalized targeted treatments becomes both vital and urgent. The GeneVieve (Genes for Life) Protocol was a dose-seeking study for chemoresistant solid malignancies and B-cell lymphoma, that evaluated the efficacy and safety profile of a dual targeted gene therapy regimen using DeltaRex-G and DeltaVax (Former name: Reximmune-C), two personalized vaccination strategies aimed to augment immune cell trafficking within the tumor microenvironment for in situ autoimmunization. DeltaRex-G is a retrovector encoding a cytocidal “dominant-negative” mutant construct of the human CCNG1 (Cyclin G1) oncogene. This retrovector is designed to destroy cancer cells, its tumor vasculature and tumor associated fibroblasts, expose neoantigens created by the tumor debris, inhibit the production of the extracellular matrix and enable immune cells to safely enter the tumor microenvironment. DeltaVax is a retrovector encoding the human GM-CSF gene, used for evoking T-cell proliferation, dendritic cell maturation and polarization of M1 macrophages. United States- and Philippine-based Phase I/II studies using DeltaRex-G for sarcoma, pancreatic cancer, and breast cancer led to its accelerated approval in the Philippines for all chemoresistant solid malignancies and subsequent USFDA approved Orphan Drug status for pancreatic cancer, soft tissue sarcoma and osteosarcoma. In 2009, DeltaRex-G received Fast Track designation for a pivotal Phase II/III trial for pancreatic cancer in the United States. The GeneVieve protocol added a second retrovector strategically to the DeltaRex-G treatment that encoded a GM-CSF gene to examine the role localized GMCSF might play in further improving treatment outcomes and inducing long lasting anti-tumor immunity.
The patient population consisted of 16 adults with unresectable advanced or metastatic disease. All subjects had an ECOG score between 0 and 1, adequate hematological, kidney and hepatic function, and an estimated survival of 3 months or more. A chemistry panel and complete blood count were assessed weekly during treatment. DeltaRex-G was administered with escalating doses of DeltaVax, five patients at Dose Level I, four patients at Dose Level II, and seven patients at Dose Level III. All patients received a minimum of two cycles of treatment over an 8-week period. Toxicity was assessed prior to each infusion and subsequent treatment cycles using NCI CT-CAE version 3.0 criteria. A staging assessment was performed every 4 weeks with an FDG PET-CT scan. All images were performed and reviewed independently by the radiologists and RECIST v1.0 and International PET criteria were used to assess overall tumor response and progression-free survival.
No dose-limiting toxicities were observed at any of the three Dose Levels of DeltaVax, and no deaths that occurred were considered to be related to the treatment. None of the patients tested positive for vector neutralizing antibodies, replication-competent retrovirus in peripheral blood lymphocytes, antibodies to gp70 or vector integration into genomic DNA of peripheral blood lymphocytes. Using RECIST v1.0 criteria, three patients achieved a partial response, nine patients achieved stable disease, and two patients had progressive disease. The median progression free survival was 4.5, 9.0, and 13.0 months for Dose Levels I, II, and III respectively, and the median overall survival was 17, 13 and > 21 months for Dose Levels I, II, III respectively.
Histopathologic examination of patients’ residual tumor tissues showed vector localization as well as GM-CSF transgene expression in necrotic tissue, displaying the accuracy in delivery of both treatments. Safety and tolerability are displayed by the lack of adverse reactions associated with the study drugs. The one-year survival rate of 86% in patients who received higher doses of DeltaVax suggests that the combination regimen of DeltaRex-G and Deltavax has significant anti-tumor activity in patients with chemoresistant solid malignancies and B-cell lymphoma. In addition, the substantial increase in progression free survival with each increased dosage of DeltaVax suggests a trend towards a positive dose–response relationship between the two treatments.
DeltaRex-G has displayed through numerous clinical trials its cytocidal effect on cancer cells. This effect introduces neoantigens from the tumor into the tumor microenvironment to be recognized by the immune system and targeted for destruction through T-cell mediation. Nevertheless, these cytotoxic immune responses may not be significant enough to overcome the suppressive signals from surrounding regulatory T-cells that may also be recruited to the tumor microenvironment. The addition of DeltaVax is hypothesized to heighten the development of dendritic cells and increase proliferation and activation of T-cells, thereby improving the potency of tumor-targeted DeltaRex-G. These activated T-cells can then go on to recognize and destroy the newly introduced tumor neoantigens. This has the potential to further tumor regression and evoke long-lasting antitumor immunity.
This data therefore strongly suggests that the advancement of personalized cancer vaccination treatment has the potential to gain control of tumor growth and increase overall survival time in patients with advanced or malignant chemoresistant solid malignancies, as well as B-cell lymphomas.
Targeted Immunotherapy has revolutionized the way scientists and physicians conceptualize their approaches to cancer treatment and cancer checkpoint controls. Mechanistic understanding of innate and adaptive mechanisms of immunity are considered important aspects of both physiological cancer surveillance and tumor eradication, as seen in immune checkpoint control and in precision blockade of cell cycle control elements. The low immunogenicity of cancer cells, as well as the tendency of advanced cancers to create an immunosuppressive tumor microenvironment presents a technical problem of precision tumor-targeted drug delivery for both immune checkpoint antibodies and cell cycle control elements, which form a rational basis for emerging treatments. The precision of monoclonal antibodies as checkpoint inhibitors targeting cancer cells has allowed research to advance in a direction that moves away from the untoward toxicities associated with chemotherapy towards treatments that enhance the naturally powerful cytotoxic responses of the immune system. The use of checkpoint inhibitors as cancer immunotherapy has been validated in 16 indications; however, immune checkpoint inhibition is still only considered appropriate for a specific subset of patients [58], and is often confounded by serious immune-related Adverse Events (imAEs). The significance and durability of response to treatment with checkpoint inhibitor therapy is generally dependent on tumor cells having a high mutational burden or microsatellite instability that creates an increased amount of neoantigens to be recognized and eliminated by the adaptive immune system [59]. Based on the documented physiological tumor-seeking behavior and demonstrated survival value of the tumor-targeted gene therapy vectors, DeltaRex-G and DeltaVax, in treating advanced metastatic cancers, the successful adaptation of bioactive gene-targeting biotechnologies to (i) target FDA-approved off-the shelf checkpoint monoclonal antibodies to tumors, and/or (ii) recombinant “tumor-targeted” adaptor proteins have been developed, in anticipation of precisely targeting immune checkpoint inhibitors and immunostimulatory cytokines against tumors to improve clinical outcomes.
Another strategic approach is enhancing the anti-tumor properties of innate immunity. The innate immune system is also regulated by its own activating and inhibitory pathways that can be investigated as future targets for NK cell-based immunotherapy. One important characteristic to consider when making the case for focusing on boosting innate immunity is the fact that innate immune cells play a major role in immunosurveillance, acting as the first line of defense. Engaging the innate immune system is a necessary prerequisite for antigen-specific T-cells to respond, although innate immune cells such as NK cells do not require activation of T-cells to kill tumor cells [58]. NK cell activation occurs through their direct interaction with target cells, bypassing the need for antigen presentation and processing. Innate immunity is always activated prior to adaptive immunity, however, once activated, adaptive immunity has the advantage of higher specificity and lower probability of self-harm.
In recent years, the human Cyclin G1 (
Hence, DeltaRex-G eradicates cancer cells without causing immune-mediated adverse events, an unwanted complication of immune checkpoint inhibitors such as ipilimumab, nivolumab, pembrolizumab, atezolizumab, etc. Conceivably, DeltaRex-G could also be used in combination with reduced doses of immune checkpoint inhibitors to minimize off-target toxicity (imAEs) and maximize anticancer efficacy.
A second tumor-targeted retrovector, DeltaVax, displaying the same high-affinity tumor-targeting motif as DeltaRex-G, but this immuno-vector—encoding both the GM-CSF gene and the pro-drug regulated HSV-tk gene, and allowing for personalized “pulsed”
In the era of precision medicine, with tumor-targeted cancer gene therapy and immunotherapy coming of age, these recent advances bring great optimism to the medical and scientific communities around the world and the patients that they serve.
The authors are grateful to J Isaacs Charitable Trust (UK), Thomas Makin Family, James B. Finn Memorial, ArtistsforAveni, Capital Group, Trader Joes, Holmes Family Trust, Ronald and Linda Chelsky, Ritchie and Keri Tuazon, Lance S. Ostendorf, Norma Yaeger, Lawrence Yaeger Memorial, Martin Berwitt, Adolf Weinberger Foundation, Jun and Alice de Guzman, Dr. and Mrs. Antonio Ong for their generous donations..
Drs. Gordon and Hall are co-inventors of the targeted gene delivery system represented by DeltaRex-G and DeltaVax which was originally developed at the University of Southern California Keck School of Medicine, and are co-founders of Delta Next-Gene, LLC. Dr. Gordon is founder and president of the Aveni Foundation, a 501c3 public charity. NLA, TTK, DAB and SPC have no competing interest.
The clinical protocol was approved by the USFDA, the Western IRB, and the Institutional Biosafety Committee. A written informed consent was obtained from each patient prior to treatment with an investigational agent.
IntechOpen Compacts provide a mid-length publishing format which bridges the gap between journal articles, book chapters and monographs, and cover content across all scientific disciplines. Compacts are the preferred publishing option for brief research reports on new topics, in-depth case studies, dissertations, or essays exploring new ideas, issues or broader topics on the research subject.
",metaTitle:"IntechOpen Compacts",metaDescription:"IntechOpen Compacts present a mid-length publishing format which bridges the gap between journal articles, book chapters, and monographs and covers content across all scientific disciplines.",metaKeywords:null,canonicalURL:"/page/compacts",contentRaw:'[{"type":"htmlEditorComponent","content":"Without sacrificing the quality of carefully edited and produced peer-reviewed content, Compacts are published as part of IntechOpen’s book collection but on a faster schedule, typically 4-6 weeks after acceptance. With an average of 132,000 visitors per week, publishing in Compacts not only guarantees high visibility but also facilitates international content sharing. As a fully Open Access publisher, the utilization of a CC BY NC 4.0 license means that other researchers will never have to pay permission fees and can adapt, use, and further build upon the material published in Compacts, eliminating any barriers to the further development of scientific research.
\\n\\nCOMPACTS-SHORT FORM MONOGRAPH
\\n\\nCOST
\\n\\n4,000 GBP Compacts Monograph - Short Form
\\n\\nThe final price will depend on the volume of the publication and includes project management, editorial and peer-review services, technical editing, language copyediting, cover design, book layout, book promotion and ISBN assignment.
\\n\\n*The price does not include Value-Added Tax (VAT). Residents of European Union countries need to add VAT based on the specific rate applicable in their country of residence. Institutions and companies registered as VAT taxable entities in their own EU member state will not pay VAT by providing us with their VAT registration number. This is made possible by the EU reverse charge method.
\\n\\nOptional Services
\\n\\nIntechOpen has collaborated with Enago, through its sister company, Ulatus – one of the world’s leading providers of book translation services. The services are designed to convey the essence of your work seamlessly to readers from across the globe in their own language. Enago’s expert translators incorporate cultural nuances in translations to make the content relevant for local audiences while retaining the original meaning and style. With a high degree of linguistic and subject expertise, Enago translators are equipped to handle all complex and multiple overlapping themes encompassed in a single book to deliver a superior quality of translation.
\\n\\nIntechOpen Authors that wish to use this service will receive a 20% discount on all translation work. For more information or a quote, please visit: https://www.enago.com/intech.
\\n\\nFUNDING
\\n\\nWe feel that financial barriers should never prevent researchers from publishing their research. Please consult our Open Access Funding page to explore funding opportunities and learn more about how you can finance your IntechOpen publication.
\\n\\nBENEFITS
\\n\\nPUBLISHING PROCESS STEPS
\\n\\nSee a complete overview and description of the steps involved in the publishing process here.
\\n\\nSEND YOUR PROPOSAL
\\n\\nIf you are interested in publishing your book with IntechOpen, please submit your book proposal by completing the Publishing Proposal Form.
\\n\\nNot sure if this is the right option for you? Please refer back to the main Publish with IntechOpen page or feel free to contact us directly at book.department@intechopen.com
\\n"}]'},components:[{type:"htmlEditorComponent",content:'Without sacrificing the quality of carefully edited and produced peer-reviewed content, Compacts are published as part of IntechOpen’s book collection but on a faster schedule, typically 4-6 weeks after acceptance. With an average of 132,000 visitors per week, publishing in Compacts not only guarantees high visibility but also facilitates international content sharing. As a fully Open Access publisher, the utilization of a CC BY NC 4.0 license means that other researchers will never have to pay permission fees and can adapt, use, and further build upon the material published in Compacts, eliminating any barriers to the further development of scientific research.
\n\nCOMPACTS-SHORT FORM MONOGRAPH
\n\nCOST
\n\n4,000 GBP Compacts Monograph - Short Form
\n\nThe final price will depend on the volume of the publication and includes project management, editorial and peer-review services, technical editing, language copyediting, cover design, book layout, book promotion and ISBN assignment.
\n\n*The price does not include Value-Added Tax (VAT). Residents of European Union countries need to add VAT based on the specific rate applicable in their country of residence. Institutions and companies registered as VAT taxable entities in their own EU member state will not pay VAT by providing us with their VAT registration number. This is made possible by the EU reverse charge method.
\n\nOptional Services
\n\nIntechOpen has collaborated with Enago, through its sister company, Ulatus – one of the world’s leading providers of book translation services. The services are designed to convey the essence of your work seamlessly to readers from across the globe in their own language. Enago’s expert translators incorporate cultural nuances in translations to make the content relevant for local audiences while retaining the original meaning and style. With a high degree of linguistic and subject expertise, Enago translators are equipped to handle all complex and multiple overlapping themes encompassed in a single book to deliver a superior quality of translation.
\n\nIntechOpen Authors that wish to use this service will receive a 20% discount on all translation work. For more information or a quote, please visit: https://www.enago.com/intech.
\n\nFUNDING
\n\nWe feel that financial barriers should never prevent researchers from publishing their research. Please consult our Open Access Funding page to explore funding opportunities and learn more about how you can finance your IntechOpen publication.
\n\nBENEFITS
\n\nPUBLISHING PROCESS STEPS
\n\nSee a complete overview and description of the steps involved in the publishing process here.
\n\nSEND YOUR PROPOSAL
\n\nIf you are interested in publishing your book with IntechOpen, please submit your book proposal by completing the Publishing Proposal Form.
\n\nNot sure if this is the right option for you? Please refer back to the main Publish with IntechOpen page or feel free to contact us directly at book.department@intechopen.com
\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{sort:"featured,name"},profiles:[{id:"6700",title:"Dr.",name:"Abbass A.",middleName:null,surname:"Hashim",slug:"abbass-a.-hashim",fullName:"Abbass A. Hashim",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/6700/images/1864_n.jpg",biography:"Currently I am carrying out research in several areas of interest, mainly covering work on chemical and bio-sensors, semiconductor thin film device fabrication and characterisation.\nAt the moment I have very strong interest in radiation environmental pollution and bacteriology treatment. The teams of researchers are working very hard to bring novel results in this field. I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. I have served as the editor for many books, been a member of the editorial board in science journals, have published many papers and hold many patents.",institutionString:null,institution:{name:"Sheffield Hallam University",country:{name:"United Kingdom"}}},{id:"54525",title:"Prof.",name:"Abdul Latif",middleName:null,surname:"Ahmad",slug:"abdul-latif-ahmad",fullName:"Abdul Latif Ahmad",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"20567",title:"Prof.",name:"Ado",middleName:null,surname:"Jorio",slug:"ado-jorio",fullName:"Ado Jorio",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidade Federal de Minas Gerais",country:{name:"Brazil"}}},{id:"47940",title:"Dr.",name:"Alberto",middleName:null,surname:"Mantovani",slug:"alberto-mantovani",fullName:"Alberto Mantovani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"12392",title:"Mr.",name:"Alex",middleName:null,surname:"Lazinica",slug:"alex-lazinica",fullName:"Alex Lazinica",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12392/images/7282_n.png",biography:"Alex Lazinica is the founder and CEO of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his PhD studies in Robotics at the Vienna University of Technology. Here he worked as a robotic researcher with the university's Intelligent Manufacturing Systems Group as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and most importantly he co-founded and built the International Journal of Advanced Robotic Systems- world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career, since it was a pathway to founding IntechOpen - Open Access publisher focused on addressing academic researchers needs. Alex is a personification of IntechOpen key values being trusted, open and entrepreneurial. Today his focus is on defining the growth and development strategy for the company.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"19816",title:"Prof.",name:"Alexander",middleName:null,surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/19816/images/1607_n.jpg",biography:"Alexander I. Kokorin: born: 1947, Moscow; DSc., PhD; Principal Research Fellow (Research Professor) of Department of Kinetics and Catalysis, N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow.\r\nArea of research interests: physical chemistry of complex-organized molecular and nanosized systems, including polymer-metal complexes; the surface of doped oxide semiconductors. He is an expert in structural, absorptive, catalytic and photocatalytic properties, in structural organization and dynamic features of ionic liquids, in magnetic interactions between paramagnetic centers. The author or co-author of 3 books, over 200 articles and reviews in scientific journals and books. He is an actual member of the International EPR/ESR Society, European Society on Quantum Solar Energy Conversion, Moscow House of Scientists, of the Board of Moscow Physical Society.",institutionString:null,institution:{name:"Semenov Institute of Chemical Physics",country:{name:"Russia"}}},{id:"62389",title:"PhD.",name:"Ali Demir",middleName:null,surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62389/images/3413_n.jpg",biography:"Dr. Ali Demir Sezer has a Ph.D. from Pharmaceutical Biotechnology at the Faculty of Pharmacy, University of Marmara (Turkey). He is the member of many Pharmaceutical Associations and acts as a reviewer of scientific journals and European projects under different research areas such as: drug delivery systems, nanotechnology and pharmaceutical biotechnology. Dr. Sezer is the author of many scientific publications in peer-reviewed journals and poster communications. Focus of his research activity is drug delivery, physico-chemical characterization and biological evaluation of biopolymers micro and nanoparticles as modified drug delivery system, and colloidal drug carriers (liposomes, nanoparticles etc.).",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"61051",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"100762",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"St David's Medical Center",country:{name:"United States of America"}}},{id:"107416",title:"Dr.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Texas Cardiac Arrhythmia",country:{name:"United States of America"}}},{id:"64434",title:"Dr.",name:"Angkoon",middleName:null,surname:"Phinyomark",slug:"angkoon-phinyomark",fullName:"Angkoon Phinyomark",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/64434/images/2619_n.jpg",biography:"My name is Angkoon Phinyomark. I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. I had been a visiting research student at Faculty of Computer Science, University of Murcia, Murcia, Spain for three months.\n\nI have published over 40 papers during 5 years in refereed journals, books, and conference proceedings in the areas of electro-physiological signals processing and classification, notably EMG and EOG signals, fractal analysis, wavelet analysis, texture analysis, feature extraction and machine learning algorithms, and assistive and rehabilitative devices. I have several computer programming language certificates, i.e. Sun Certified Programmer for the Java 2 Platform 1.4 (SCJP), Microsoft Certified Professional Developer, Web Developer (MCPD), Microsoft Certified Technology Specialist, .NET Framework 2.0 Web (MCTS). I am a Reviewer for several refereed journals and international conferences, such as IEEE Transactions on Biomedical Engineering, IEEE Transactions on Industrial Electronics, Optic Letters, Measurement Science Review, and also a member of the International Advisory Committee for 2012 IEEE Business Engineering and Industrial Applications and 2012 IEEE Symposium on Business, Engineering and Industrial Applications.",institutionString:null,institution:{name:"Joseph Fourier University",country:{name:"France"}}},{id:"55578",title:"Dr.",name:"Antonio",middleName:null,surname:"Jurado-Navas",slug:"antonio-jurado-navas",fullName:"Antonio Jurado-Navas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/55578/images/4574_n.png",biography:"Antonio Jurado-Navas received the M.S. degree (2002) and the Ph.D. degree (2009) in Telecommunication Engineering, both from the University of Málaga (Spain). He first worked as a consultant at Vodafone-Spain. From 2004 to 2011, he was a Research Assistant with the Communications Engineering Department at the University of Málaga. In 2011, he became an Assistant Professor in the same department. From 2012 to 2015, he was with Ericsson Spain, where he was working on geo-location\ntools for third generation mobile networks. Since 2015, he is a Marie-Curie fellow at the Denmark Technical University. His current research interests include the areas of mobile communication systems and channel modeling in addition to atmospheric optical communications, adaptive optics and statistics",institutionString:null,institution:{name:"University of Malaga",country:{name:"Spain"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:5828},{group:"region",caption:"Middle and South America",value:2,count:5289},{group:"region",caption:"Africa",value:3,count:1765},{group:"region",caption:"Asia",value:4,count:10555},{group:"region",caption:"Australia and Oceania",value:5,count:909},{group:"region",caption:"Europe",value:6,count:15952}],offset:12,limit:12,total:119464},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{hasNoEditors:"0",sort:"dateEndThirdStepPublish"},books:[],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:29},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:8},{group:"topic",caption:"Business, Management and Economics",value:7,count:4},{group:"topic",caption:"Chemistry",value:8,count:9},{group:"topic",caption:"Computer and Information Science",value:9,count:10},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:10},{group:"topic",caption:"Engineering",value:11,count:29},{group:"topic",caption:"Environmental Sciences",value:12,count:4},{group:"topic",caption:"Immunology and Microbiology",value:13,count:4},{group:"topic",caption:"Materials Science",value:14,count:7},{group:"topic",caption:"Mathematics",value:15,count:3},{group:"topic",caption:"Medicine",value:16,count:51},{group:"topic",caption:"Neuroscience",value:18,count:3},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:3},{group:"topic",caption:"Physics",value:20,count:4},{group:"topic",caption:"Psychology",value:21,count:4},{group:"topic",caption:"Robotics",value:22,count:2},{group:"topic",caption:"Social Sciences",value:23,count:4},{group:"topic",caption:"Technology",value:24,count:1},{group:"topic",caption:"Veterinary Medicine and Science",value:25,count:2}],offset:0,limit:12,total:null},popularBooks:{featuredBooks:[{type:"book",id:"9154",title:"Spinal Deformities in Adolescents, Adults and Older Adults",subtitle:null,isOpenForSubmission:!1,hash:"313f1dffa803b60a14ff1e6966e93d91",slug:"spinal-deformities-in-adolescents-adults-and-older-adults",bookSignature:"Josette Bettany-Saltikov and Gokulakannan Kandasamy",coverURL:"https://cdn.intechopen.com/books/images_new/9154.jpg",editors:[{id:"94802",title:"Dr.",name:"Josette",middleName:null,surname:"Bettany-Saltikov",slug:"josette-bettany-saltikov",fullName:"Josette Bettany-Saltikov"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7030",title:"Satellite Systems",subtitle:"Design, Modeling, Simulation and Analysis",isOpenForSubmission:!1,hash:"b9db6d2645ef248ceb1b33ea75f38e88",slug:"satellite-systems-design-modeling-simulation-and-analysis",bookSignature:"Tien Nguyen",coverURL:"https://cdn.intechopen.com/books/images_new/7030.jpg",editors:[{id:"210657",title:"Dr.",name:"Tien M.",middleName:"Manh",surname:"Nguyen",slug:"tien-m.-nguyen",fullName:"Tien M. Nguyen"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8472",title:"Bioactive Compounds in Nutraceutical and Functional Food for Good Human Health",subtitle:null,isOpenForSubmission:!1,hash:"8855452919b8495810ef8e88641feb20",slug:"bioactive-compounds-in-nutraceutical-and-functional-food-for-good-human-health",bookSignature:"Kavita Sharma, Kanchan Mishra, Kula Kamal Senapati and Corina Danciu",coverURL:"https://cdn.intechopen.com/books/images_new/8472.jpg",editors:[{id:"197731",title:"Dr.",name:"Kavita",middleName:null,surname:"Sharma",slug:"kavita-sharma",fullName:"Kavita Sharma"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10201",title:"Post-Transition Metals",subtitle:null,isOpenForSubmission:!1,hash:"cc7f53ff5269916e3ce29f65a51a87ae",slug:"post-transition-metals",bookSignature:"Mohammed Muzibur Rahman, Abdullah Mohammed Asiri, Anish Khan, Inamuddin and Thamer Tabbakh",coverURL:"https://cdn.intechopen.com/books/images_new/10201.jpg",editors:[{id:"24438",title:"Prof.",name:"Mohammed Muzibur",middleName:null,surname:"Rahman",slug:"mohammed-muzibur-rahman",fullName:"Mohammed Muzibur Rahman"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10413",title:"A Collection of Papers on Chaos Theory and Its Applications",subtitle:null,isOpenForSubmission:!1,hash:"900b71b164948830fec3d6254b7881f7",slug:"a-collection-of-papers-on-chaos-theory-and-its-applications",bookSignature:"Paul Bracken and Dimo I. Uzunov",coverURL:"https://cdn.intechopen.com/books/images_new/10413.jpg",editors:[{id:"92883",title:"Prof.",name:"Paul",middleName:null,surname:"Bracken",slug:"paul-bracken",fullName:"Paul Bracken"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9515",title:"Update in Geriatrics",subtitle:null,isOpenForSubmission:!1,hash:"913e16c0ae977474b283bbd4269564c8",slug:"update-in-geriatrics",bookSignature:"Somchai Amornyotin",coverURL:"https://cdn.intechopen.com/books/images_new/9515.jpg",editors:[{id:"185484",title:"Prof.",name:"Somchai",middleName:null,surname:"Amornyotin",slug:"somchai-amornyotin",fullName:"Somchai Amornyotin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8148",title:"Investment Strategies in Emerging New Trends in Finance",subtitle:null,isOpenForSubmission:!1,hash:"3b714d96a68d2acdfbd7b50aba6504ca",slug:"investment-strategies-in-emerging-new-trends-in-finance",bookSignature:"Reza Gharoie Ahangar and Asma Salman",coverURL:"https://cdn.intechopen.com/books/images_new/8148.jpg",editors:[{id:"91081",title:"Dr.",name:"Reza",middleName:null,surname:"Gharoie Ahangar",slug:"reza-gharoie-ahangar",fullName:"Reza Gharoie Ahangar"}],equalEditorOne:{id:"206443",title:"Prof.",name:"Asma",middleName:null,surname:"Salman",slug:"asma-salman",fullName:"Asma Salman",profilePictureURL:"https://mts.intechopen.com/storage/users/206443/images/system/206443.png",biography:"Professor Asma Salman is a blockchain developer and Professor of Finance at the American University in the Emirates, UAE. An Honorary Global Advisor at the Global Academy of Finance and Management, USA, she completed her MBA in Finance and Accounting and earned a Ph.D. in Finance from an AACSB member, AMBA accredited, School of Management at Harbin Institute of Technology, China. Her research credentials include a one-year residency at the Brunel Business School, Brunel University, UK. Prof. Salman also served as the Dubai Cohort supervisor for DBA students under the Nottingham Business School, UK, for seven years and is currently a Ph.D. supervisor at the University of Northampton, UK, where she is a visiting fellow. She also served on the Board of Etihad Airlines during 2019–2020. One of her recent articles on “Bitcoin and Blockchain” gained wide visibility and she is an active speaker on Fintech, blockchain, and crypto events around the GCC. She holds various professional certifications including Chartered Fintech Professional (USA), Certified Financial Manager (USA), Women in Leadership and Management in Higher Education, (UK), and Taxation GCC VAT Compliance, (UK). She recently won an award for “Blockchain Trainer of the Year” from Berkeley Middle East. Other recognitions include the Women Leadership Impact Award by H.E First Lady of Armenia, Research Excellence Award, and the Global Inspirational Women Leadership Award by H.H Sheikh Juma Bin Maktoum Juma Al Maktoum.",institutionString:"American University in the Emirates",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"American University in the Emirates",institutionURL:null,country:{name:"United Arab Emirates"}}},equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"2160",title:"MATLAB",subtitle:"A Fundamental Tool for Scientific Computing and Engineering Applications - Volume 1",isOpenForSubmission:!1,hash:"dd9c658341fbd264ed4f8d9e6aa8ca29",slug:"matlab-a-fundamental-tool-for-scientific-computing-and-engineering-applications-volume-1",bookSignature:"Vasilios N. Katsikis",coverURL:"https://cdn.intechopen.com/books/images_new/2160.jpg",editors:[{id:"12289",title:"Prof.",name:"Vasilios",middleName:"N.",surname:"Katsikis",slug:"vasilios-katsikis",fullName:"Vasilios Katsikis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9385",title:"Renewable Energy",subtitle:"Technologies and Applications",isOpenForSubmission:!1,hash:"a6b446d19166f17f313008e6c056f3d8",slug:"renewable-energy-technologies-and-applications",bookSignature:"Tolga Taner, Archana Tiwari and Taha Selim Ustun",coverURL:"https://cdn.intechopen.com/books/images_new/9385.jpg",editors:[{id:"197240",title:"Associate Prof.",name:"Tolga",middleName:null,surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner"}],equalEditorOne:{id:"186791",title:"Dr.",name:"Archana",middleName:null,surname:"Tiwari",slug:"archana-tiwari",fullName:"Archana Tiwari",profilePictureURL:"https://mts.intechopen.com/storage/users/186791/images/system/186791.jpg",biography:"Dr. Archana Tiwari is Associate Professor at Amity University, India. Her research interests include renewable sources of energy from microalgae and further utilizing the residual biomass for the generation of value-added products, bioremediation through microalgae and microbial consortium, antioxidative enzymes and stress, and nutraceuticals from microalgae. She has been working on algal biotechnology for the last two decades. She has published her research in many international journals and has authored many books and chapters with renowned publishing houses. She has also delivered talks as an invited speaker at many national and international conferences. Dr. Tiwari is the recipient of several awards including Researcher of the Year and Distinguished Scientist.",institutionString:"Amity University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Amity University",institutionURL:null,country:{name:"India"}}},equalEditorTwo:{id:"197609",title:"Prof.",name:"Taha Selim",middleName:null,surname:"Ustun",slug:"taha-selim-ustun",fullName:"Taha Selim Ustun",profilePictureURL:"https://mts.intechopen.com/storage/users/197609/images/system/197609.jpeg",biography:"Dr. Taha Selim Ustun received a Ph.D. in Electrical Engineering from Victoria University, Melbourne, Australia. He is a researcher with the Fukushima Renewable Energy Institute, AIST (FREA), where he leads the Smart Grid Cybersecurity Laboratory. Prior to that, he was a faculty member with the School of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA. His current research interests include power systems protection, communication in power networks, distributed generation, microgrids, electric vehicle integration, and cybersecurity in smart grids. He serves on the editorial boards of IEEE Access, IEEE Transactions on Industrial Informatics, Energies, Electronics, Electricity, World Electric Vehicle and Information journals. Dr. Ustun is a member of the IEEE 2004 and 2800, IEC Renewable Energy Management WG 8, and IEC TC 57 WG17. He has been invited to run specialist courses in Africa, India, and China. He has delivered talks for the Qatar Foundation, the World Energy Council, the Waterloo Global Science Initiative, and the European Union Energy Initiative (EUEI). His research has attracted funding from prestigious programs in Japan, Australia, the European Union, and North America.",institutionString:"Fukushima Renewable Energy Institute, AIST (FREA)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"National Institute of Advanced Industrial Science and Technology",institutionURL:null,country:{name:"Japan"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"3568",title:"Recent Advances in Plant in vitro Culture",subtitle:null,isOpenForSubmission:!1,hash:"830bbb601742c85a3fb0eeafe1454c43",slug:"recent-advances-in-plant-in-vitro-culture",bookSignature:"Annarita Leva and Laura M. R. Rinaldi",coverURL:"https://cdn.intechopen.com/books/images_new/3568.jpg",editors:[{id:"142145",title:"Dr.",name:"Annarita",middleName:null,surname:"Leva",slug:"annarita-leva",fullName:"Annarita Leva"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"3560",title:"Advances in Landscape Architecture",subtitle:null,isOpenForSubmission:!1,hash:"a20614517ec5f7e91188fe8e42832138",slug:"advances-in-landscape-architecture",bookSignature:"Murat Özyavuz",coverURL:"https://cdn.intechopen.com/books/images_new/3560.jpg",editors:[{id:"93073",title:"Dr.",name:"Murat",middleName:null,surname:"Ozyavuz",slug:"murat-ozyavuz",fullName:"Murat Ozyavuz"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8511",title:"Cyberspace",subtitle:null,isOpenForSubmission:!1,hash:"8c1cdeb133dbe6cc1151367061c1bba6",slug:"cyberspace",bookSignature:"Evon Abu-Taieh, Abdelkrim El Mouatasim and Issam H. Al Hadid",coverURL:"https://cdn.intechopen.com/books/images_new/8511.jpg",editors:[{id:"223522",title:"Dr.",name:"Evon",middleName:"M.O.",surname:"Abu-Taieh",slug:"evon-abu-taieh",fullName:"Evon Abu-Taieh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:5331},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"9154",title:"Spinal Deformities in Adolescents, Adults and Older Adults",subtitle:null,isOpenForSubmission:!1,hash:"313f1dffa803b60a14ff1e6966e93d91",slug:"spinal-deformities-in-adolescents-adults-and-older-adults",bookSignature:"Josette Bettany-Saltikov and Gokulakannan Kandasamy",coverURL:"https://cdn.intechopen.com/books/images_new/9154.jpg",editors:[{id:"94802",title:"Dr.",name:"Josette",middleName:null,surname:"Bettany-Saltikov",slug:"josette-bettany-saltikov",fullName:"Josette Bettany-Saltikov"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7030",title:"Satellite Systems",subtitle:"Design, Modeling, Simulation and Analysis",isOpenForSubmission:!1,hash:"b9db6d2645ef248ceb1b33ea75f38e88",slug:"satellite-systems-design-modeling-simulation-and-analysis",bookSignature:"Tien Nguyen",coverURL:"https://cdn.intechopen.com/books/images_new/7030.jpg",editors:[{id:"210657",title:"Dr.",name:"Tien M.",middleName:"Manh",surname:"Nguyen",slug:"tien-m.-nguyen",fullName:"Tien M. Nguyen"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8472",title:"Bioactive Compounds in Nutraceutical and Functional Food for Good Human Health",subtitle:null,isOpenForSubmission:!1,hash:"8855452919b8495810ef8e88641feb20",slug:"bioactive-compounds-in-nutraceutical-and-functional-food-for-good-human-health",bookSignature:"Kavita Sharma, Kanchan Mishra, Kula Kamal Senapati and Corina Danciu",coverURL:"https://cdn.intechopen.com/books/images_new/8472.jpg",editors:[{id:"197731",title:"Dr.",name:"Kavita",middleName:null,surname:"Sharma",slug:"kavita-sharma",fullName:"Kavita Sharma"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10201",title:"Post-Transition Metals",subtitle:null,isOpenForSubmission:!1,hash:"cc7f53ff5269916e3ce29f65a51a87ae",slug:"post-transition-metals",bookSignature:"Mohammed Muzibur Rahman, Abdullah Mohammed Asiri, Anish Khan, Inamuddin and Thamer Tabbakh",coverURL:"https://cdn.intechopen.com/books/images_new/10201.jpg",editors:[{id:"24438",title:"Prof.",name:"Mohammed Muzibur",middleName:null,surname:"Rahman",slug:"mohammed-muzibur-rahman",fullName:"Mohammed Muzibur Rahman"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10413",title:"A Collection of Papers on Chaos Theory and Its Applications",subtitle:null,isOpenForSubmission:!1,hash:"900b71b164948830fec3d6254b7881f7",slug:"a-collection-of-papers-on-chaos-theory-and-its-applications",bookSignature:"Paul Bracken and Dimo I. Uzunov",coverURL:"https://cdn.intechopen.com/books/images_new/10413.jpg",editors:[{id:"92883",title:"Prof.",name:"Paul",middleName:null,surname:"Bracken",slug:"paul-bracken",fullName:"Paul Bracken"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9515",title:"Update in Geriatrics",subtitle:null,isOpenForSubmission:!1,hash:"913e16c0ae977474b283bbd4269564c8",slug:"update-in-geriatrics",bookSignature:"Somchai Amornyotin",coverURL:"https://cdn.intechopen.com/books/images_new/9515.jpg",editors:[{id:"185484",title:"Prof.",name:"Somchai",middleName:null,surname:"Amornyotin",slug:"somchai-amornyotin",fullName:"Somchai Amornyotin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8148",title:"Investment Strategies in Emerging New Trends in Finance",subtitle:null,isOpenForSubmission:!1,hash:"3b714d96a68d2acdfbd7b50aba6504ca",slug:"investment-strategies-in-emerging-new-trends-in-finance",bookSignature:"Reza Gharoie Ahangar and Asma Salman",coverURL:"https://cdn.intechopen.com/books/images_new/8148.jpg",editors:[{id:"91081",title:"Dr.",name:"Reza",middleName:null,surname:"Gharoie Ahangar",slug:"reza-gharoie-ahangar",fullName:"Reza Gharoie Ahangar"}],equalEditorOne:{id:"206443",title:"Prof.",name:"Asma",middleName:null,surname:"Salman",slug:"asma-salman",fullName:"Asma Salman",profilePictureURL:"https://mts.intechopen.com/storage/users/206443/images/system/206443.png",biography:"Professor Asma Salman is a blockchain developer and Professor of Finance at the American University in the Emirates, UAE. An Honorary Global Advisor at the Global Academy of Finance and Management, USA, she completed her MBA in Finance and Accounting and earned a Ph.D. in Finance from an AACSB member, AMBA accredited, School of Management at Harbin Institute of Technology, China. Her research credentials include a one-year residency at the Brunel Business School, Brunel University, UK. Prof. Salman also served as the Dubai Cohort supervisor for DBA students under the Nottingham Business School, UK, for seven years and is currently a Ph.D. supervisor at the University of Northampton, UK, where she is a visiting fellow. She also served on the Board of Etihad Airlines during 2019–2020. One of her recent articles on “Bitcoin and Blockchain” gained wide visibility and she is an active speaker on Fintech, blockchain, and crypto events around the GCC. She holds various professional certifications including Chartered Fintech Professional (USA), Certified Financial Manager (USA), Women in Leadership and Management in Higher Education, (UK), and Taxation GCC VAT Compliance, (UK). She recently won an award for “Blockchain Trainer of the Year” from Berkeley Middle East. Other recognitions include the Women Leadership Impact Award by H.E First Lady of Armenia, Research Excellence Award, and the Global Inspirational Women Leadership Award by H.H Sheikh Juma Bin Maktoum Juma Al Maktoum.",institutionString:"American University in the Emirates",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"American University in the Emirates",institutionURL:null,country:{name:"United Arab Emirates"}}},equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"2160",title:"MATLAB",subtitle:"A Fundamental Tool for Scientific Computing and Engineering Applications - Volume 1",isOpenForSubmission:!1,hash:"dd9c658341fbd264ed4f8d9e6aa8ca29",slug:"matlab-a-fundamental-tool-for-scientific-computing-and-engineering-applications-volume-1",bookSignature:"Vasilios N. Katsikis",coverURL:"https://cdn.intechopen.com/books/images_new/2160.jpg",editors:[{id:"12289",title:"Prof.",name:"Vasilios",middleName:"N.",surname:"Katsikis",slug:"vasilios-katsikis",fullName:"Vasilios Katsikis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9385",title:"Renewable Energy",subtitle:"Technologies and Applications",isOpenForSubmission:!1,hash:"a6b446d19166f17f313008e6c056f3d8",slug:"renewable-energy-technologies-and-applications",bookSignature:"Tolga Taner, Archana Tiwari and Taha Selim Ustun",coverURL:"https://cdn.intechopen.com/books/images_new/9385.jpg",editors:[{id:"197240",title:"Associate Prof.",name:"Tolga",middleName:null,surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner"}],equalEditorOne:{id:"186791",title:"Dr.",name:"Archana",middleName:null,surname:"Tiwari",slug:"archana-tiwari",fullName:"Archana Tiwari",profilePictureURL:"https://mts.intechopen.com/storage/users/186791/images/system/186791.jpg",biography:"Dr. Archana Tiwari is Associate Professor at Amity University, India. Her research interests include renewable sources of energy from microalgae and further utilizing the residual biomass for the generation of value-added products, bioremediation through microalgae and microbial consortium, antioxidative enzymes and stress, and nutraceuticals from microalgae. She has been working on algal biotechnology for the last two decades. She has published her research in many international journals and has authored many books and chapters with renowned publishing houses. She has also delivered talks as an invited speaker at many national and international conferences. Dr. Tiwari is the recipient of several awards including Researcher of the Year and Distinguished Scientist.",institutionString:"Amity University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Amity University",institutionURL:null,country:{name:"India"}}},equalEditorTwo:{id:"197609",title:"Prof.",name:"Taha Selim",middleName:null,surname:"Ustun",slug:"taha-selim-ustun",fullName:"Taha Selim Ustun",profilePictureURL:"https://mts.intechopen.com/storage/users/197609/images/system/197609.jpeg",biography:"Dr. Taha Selim Ustun received a Ph.D. in Electrical Engineering from Victoria University, Melbourne, Australia. He is a researcher with the Fukushima Renewable Energy Institute, AIST (FREA), where he leads the Smart Grid Cybersecurity Laboratory. Prior to that, he was a faculty member with the School of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA. His current research interests include power systems protection, communication in power networks, distributed generation, microgrids, electric vehicle integration, and cybersecurity in smart grids. He serves on the editorial boards of IEEE Access, IEEE Transactions on Industrial Informatics, Energies, Electronics, Electricity, World Electric Vehicle and Information journals. Dr. Ustun is a member of the IEEE 2004 and 2800, IEC Renewable Energy Management WG 8, and IEC TC 57 WG17. He has been invited to run specialist courses in Africa, India, and China. He has delivered talks for the Qatar Foundation, the World Energy Council, the Waterloo Global Science Initiative, and the European Union Energy Initiative (EUEI). His research has attracted funding from prestigious programs in Japan, Australia, the European Union, and North America.",institutionString:"Fukushima Renewable Energy Institute, AIST (FREA)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"National Institute of Advanced Industrial Science and Technology",institutionURL:null,country:{name:"Japan"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"3568",title:"Recent Advances in Plant in vitro Culture",subtitle:null,isOpenForSubmission:!1,hash:"830bbb601742c85a3fb0eeafe1454c43",slug:"recent-advances-in-plant-in-vitro-culture",bookSignature:"Annarita Leva and Laura M. R. Rinaldi",coverURL:"https://cdn.intechopen.com/books/images_new/3568.jpg",editors:[{id:"142145",title:"Dr.",name:"Annarita",middleName:null,surname:"Leva",slug:"annarita-leva",fullName:"Annarita Leva"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"9559",title:"Teamwork in Healthcare",subtitle:null,isOpenForSubmission:!1,hash:"0053c2ff8d9ec4cc4aab82acea46a41e",slug:"teamwork-in-healthcare",bookSignature:"Michael S. Firstenberg and Stanislaw P. Stawicki",coverURL:"https://cdn.intechopen.com/books/images_new/9559.jpg",editedByType:"Edited by",editors:[{id:"64343",title:null,name:"Michael S.",middleName:null,surname:"Firstenberg",slug:"michael-s.-firstenberg",fullName:"Michael S. Firstenberg"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7016",title:"Cardiovascular Risk Factors in Pathology",subtitle:null,isOpenForSubmission:!1,hash:"7937d2c640c7515de372282c72ee5635",slug:"cardiovascular-risk-factors-in-pathology",bookSignature:"Alaeddin Abukabda, Maria Suciu and Minodora Andor",coverURL:"https://cdn.intechopen.com/books/images_new/7016.jpg",editedByType:"Edited by",editors:[{id:"307873",title:"Ph.D.",name:"Alaeddin",middleName:null,surname:"Abukabda",slug:"alaeddin-abukabda",fullName:"Alaeddin Abukabda"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9873",title:"Strategies of Sustainable Solid Waste Management",subtitle:null,isOpenForSubmission:!1,hash:"59b5ceeeedaf7449a30629923569388c",slug:"strategies-of-sustainable-solid-waste-management",bookSignature:"Hosam M. Saleh",coverURL:"https://cdn.intechopen.com/books/images_new/9873.jpg",editedByType:"Edited by",editors:[{id:"144691",title:"Prof.",name:"Hosam M.",middleName:"M.",surname:"Saleh",slug:"hosam-m.-saleh",fullName:"Hosam M. Saleh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9893",title:"Automation and Control",subtitle:null,isOpenForSubmission:!1,hash:"09ba24f6ac88af7f0aaff3029714ae48",slug:"automation-and-control",bookSignature:"Constantin Voloşencu, Serdar Küçük, José Guerrero and Oscar Valero",coverURL:"https://cdn.intechopen.com/books/images_new/9893.jpg",editedByType:"Edited by",editors:[{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10405",title:"River Basin Management",subtitle:"Sustainability Issues and Planning Strategies",isOpenForSubmission:!1,hash:"5e5ddd0f2eda107ce19c4c06a55a8351",slug:"river-basin-management-sustainability-issues-and-planning-strategies",bookSignature:"José Simão Antunes Do Carmo",coverURL:"https://cdn.intechopen.com/books/images_new/10405.jpg",editedByType:"Edited by",editors:[{id:"67904",title:"Prof.",name:"José Simão",middleName:null,surname:"Antunes Do Carmo",slug:"jose-simao-antunes-do-carmo",fullName:"José Simão Antunes Do Carmo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9515",title:"Update in Geriatrics",subtitle:null,isOpenForSubmission:!1,hash:"913e16c0ae977474b283bbd4269564c8",slug:"update-in-geriatrics",bookSignature:"Somchai Amornyotin",coverURL:"https://cdn.intechopen.com/books/images_new/9515.jpg",editedByType:"Edited by",editors:[{id:"185484",title:"Prof.",name:"Somchai",middleName:null,surname:"Amornyotin",slug:"somchai-amornyotin",fullName:"Somchai Amornyotin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9021",title:"Novel Perspectives of Stem Cell Manufacturing and Therapies",subtitle:null,isOpenForSubmission:!1,hash:"522c6db871783d2a11c17b83f1fd4e18",slug:"novel-perspectives-of-stem-cell-manufacturing-and-therapies",bookSignature:"Diana Kitala and Ana Colette Maurício",coverURL:"https://cdn.intechopen.com/books/images_new/9021.jpg",editedByType:"Edited by",editors:[{id:"203598",title:"Ph.D.",name:"Diana",middleName:null,surname:"Kitala",slug:"diana-kitala",fullName:"Diana Kitala"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7030",title:"Satellite Systems",subtitle:"Design, Modeling, Simulation and Analysis",isOpenForSubmission:!1,hash:"b9db6d2645ef248ceb1b33ea75f38e88",slug:"satellite-systems-design-modeling-simulation-and-analysis",bookSignature:"Tien Nguyen",coverURL:"https://cdn.intechopen.com/books/images_new/7030.jpg",editedByType:"Edited by",editors:[{id:"210657",title:"Dr.",name:"Tien M.",middleName:"Manh",surname:"Nguyen",slug:"tien-m.-nguyen",fullName:"Tien M. Nguyen"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10413",title:"A Collection of Papers on Chaos Theory and Its Applications",subtitle:null,isOpenForSubmission:!1,hash:"900b71b164948830fec3d6254b7881f7",slug:"a-collection-of-papers-on-chaos-theory-and-its-applications",bookSignature:"Paul Bracken and Dimo I. Uzunov",coverURL:"https://cdn.intechopen.com/books/images_new/10413.jpg",editedByType:"Edited by",editors:[{id:"92883",title:"Prof.",name:"Paul",middleName:null,surname:"Bracken",slug:"paul-bracken",fullName:"Paul Bracken"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9154",title:"Spinal Deformities in Adolescents, Adults and Older Adults",subtitle:null,isOpenForSubmission:!1,hash:"313f1dffa803b60a14ff1e6966e93d91",slug:"spinal-deformities-in-adolescents-adults-and-older-adults",bookSignature:"Josette Bettany-Saltikov and Gokulakannan Kandasamy",coverURL:"https://cdn.intechopen.com/books/images_new/9154.jpg",editedByType:"Edited by",editors:[{id:"94802",title:"Dr.",name:"Josette",middleName:null,surname:"Bettany-Saltikov",slug:"josette-bettany-saltikov",fullName:"Josette Bettany-Saltikov"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"125",title:"Earth Science",slug:"earth-science",parent:{title:"Environmental Sciences",slug:"environmental-sciences"},numberOfBooks:36,numberOfAuthorsAndEditors:887,numberOfWosCitations:1057,numberOfCrossrefCitations:556,numberOfDimensionsCitations:1475,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"earth-science",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"9280",title:"Underwater Work",subtitle:null,isOpenForSubmission:!1,hash:"647b4270d937deae4a82f5702d1959ec",slug:"underwater-work",bookSignature:"Sérgio António Neves Lousada",coverURL:"https://cdn.intechopen.com/books/images_new/9280.jpg",editedByType:"Edited by",editors:[{id:"248645",title:"Dr.",name:"Sérgio António",middleName:null,surname:"Neves Lousada",slug:"sergio-antonio-neves-lousada",fullName:"Sérgio António Neves Lousada"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9879",title:"Geochemistry",subtitle:null,isOpenForSubmission:!1,hash:"aebccc07f8ffdf8a0043efc454024292",slug:"geochemistry",bookSignature:"Miloš René, Gemma Aiello and Gaafar El Bahariya",coverURL:"https://cdn.intechopen.com/books/images_new/9879.jpg",editedByType:"Edited by",editors:[{id:"142108",title:"Dr.",name:"Miloš",middleName:null,surname:"René",slug:"milos-rene",fullName:"Miloš René"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9864",title:"Hydrology",subtitle:null,isOpenForSubmission:!1,hash:"02925c63436d12e839008c793a253310",slug:"hydrology",bookSignature:"Theodore V. Hromadka II and Prasada Rao",coverURL:"https://cdn.intechopen.com/books/images_new/9864.jpg",editedByType:"Edited by",editors:[{id:"181008",title:"Dr.",name:"Theodore V.",middleName:"V.",surname:"Hromadka II",slug:"theodore-v.-hromadka-ii",fullName:"Theodore V. Hromadka II"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8974",title:"Current Topics in Tropical Cyclone Research",subtitle:null,isOpenForSubmission:!1,hash:"3bf6428d456edbadac595a8417045865",slug:"current-topics-in-tropical-cyclone-research",bookSignature:"Anthony Lupo",coverURL:"https://cdn.intechopen.com/books/images_new/8974.jpg",editedByType:"Edited by",editors:[{id:"18289",title:"Prof.",name:"Anthony",middleName:"Rocco",surname:"Lupo",slug:"anthony-lupo",fullName:"Anthony Lupo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8007",title:"Estuaries and Coastal Zones",subtitle:"Dynamics and Response to Environmental Changes",isOpenForSubmission:!1,hash:"ec140486c42d62e69ef428e6cf71b6d7",slug:"estuaries-and-coastal-zones-dynamics-and-response-to-environmental-changes",bookSignature:"Jiayi Pan and Adam Devlin",coverURL:"https://cdn.intechopen.com/books/images_new/8007.jpg",editedByType:"Edited by",editors:[{id:"179303",title:"Prof.",name:"Jiayi",middleName:null,surname:"Pan",slug:"jiayi-pan",fullName:"Jiayi Pan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7606",title:"Coastal and Marine Environments",subtitle:"Physical Processes and Numerical Modelling",isOpenForSubmission:!1,hash:"dd1227726856d58b88116129b0de8384",slug:"coastal-and-marine-environments-physical-processes-and-numerical-modelling",bookSignature:"José Simão Antunes Do Carmo",coverURL:"https://cdn.intechopen.com/books/images_new/7606.jpg",editedByType:"Edited by",editors:[{id:"67904",title:"Prof.",name:"José Simão",middleName:null,surname:"Antunes Do Carmo",slug:"jose-simao-antunes-do-carmo",fullName:"José Simão Antunes Do Carmo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7767",title:"Rainfall",subtitle:"Extremes, Distribution and Properties",isOpenForSubmission:!1,hash:"9f9b3b7d86cb46e2ce3653587805475d",slug:"rainfall-extremes-distribution-and-properties",bookSignature:"John Abbot and Andrew Hammond",coverURL:"https://cdn.intechopen.com/books/images_new/7767.jpg",editedByType:"Edited by",editors:[{id:"225780",title:"Dr.",name:"John",middleName:null,surname:"Abbot",slug:"john-abbot",fullName:"John Abbot"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6982",title:"Arctic Studies",subtitle:"A Proxy for Climate Change",isOpenForSubmission:!1,hash:"6545831965fb2dcef181c46d18fed1ba",slug:"arctic-studies-a-proxy-for-climate-change",bookSignature:"Masaki Kanao, Yoshihiro Kakinami and Genti Toyokuni",coverURL:"https://cdn.intechopen.com/books/images_new/6982.jpg",editedByType:"Edited by",editors:[{id:"51959",title:"Dr.",name:"Masaki",middleName:null,surname:"Kanao",slug:"masaki-kanao",fullName:"Masaki Kanao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8476",title:"Earth Crust",subtitle:null,isOpenForSubmission:!1,hash:"ebef9911d87b6db8cb55dad47250a6be",slug:"earth-crust",bookSignature:"Muhammad Nawaz, Farha Sattar and Sandeep Narayan Kundu",coverURL:"https://cdn.intechopen.com/books/images_new/8476.jpg",editedByType:"Edited by",editors:[{id:"269790",title:"Dr.",name:"Muhammad",middleName:null,surname:"Nawaz",slug:"muhammad-nawaz",fullName:"Muhammad Nawaz"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7484",title:"Topics in Hydrometerology",subtitle:null,isOpenForSubmission:!1,hash:"8d7e790445c691226a5778a32abd15cf",slug:"topics-in-hydrometerology",bookSignature:"Theodore V Hromadka II and Prasada Rao",coverURL:"https://cdn.intechopen.com/books/images_new/7484.jpg",editedByType:"Edited by",editors:[{id:"181008",title:"Dr.",name:"Theodore V.",middleName:"V.",surname:"Hromadka II",slug:"theodore-v.-hromadka-ii",fullName:"Theodore V. Hromadka II"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6836",title:"Groundwater",subtitle:"Resource Characterisation and Management Aspects",isOpenForSubmission:!1,hash:"7cad088c49e61c898abc7d7511de42f6",slug:"groundwater-resource-characterisation-and-management-aspects",bookSignature:"Modreck Gomo",coverURL:"https://cdn.intechopen.com/books/images_new/6836.jpg",editedByType:"Edited by",editors:[{id:"185450",title:"Dr.",name:"Modreck",middleName:null,surname:"Gomo",slug:"modreck-gomo",fullName:"Modreck Gomo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6973",title:"Advanced Evapotranspiration Methods and Applications",subtitle:null,isOpenForSubmission:!1,hash:"7c54751778dc2ff4a19cd84f1bf0c706",slug:"advanced-evapotranspiration-methods-and-applications",bookSignature:"Daniel Bucur",coverURL:"https://cdn.intechopen.com/books/images_new/6973.jpg",editedByType:"Edited by",editors:[{id:"50794",title:"Prof.",name:"Daniel",middleName:"G",surname:"Bucur",slug:"daniel-bucur",fullName:"Daniel Bucur"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:36,mostCitedChapters:[{id:"27305",doi:"10.5772/39363",title:"Water Stress in Plants: Causes, Effects and Responses",slug:"water-stress-in-plants-causes-effects-and-responses",totalDownloads:27795,totalCrossrefCites:43,totalDimensionsCites:124,book:{slug:"water-stress",title:"Water Stress",fullTitle:"Water Stress"},signatures:"Seyed Y. S. Lisar, Rouhollah Motafakkerazad, Mosharraf M. Hossain and Ismail M. M. Rahman",authors:[{id:"110740",title:"Dr.",name:"Ismail M. M.",middleName:null,surname:"Rahman",slug:"ismail-m.-m.-rahman",fullName:"Ismail M. M. Rahman"}]},{id:"53211",doi:"10.5772/66416",title:"Biofloc Technology (BFT): A Tool for Water Quality Management in Aquaculture",slug:"biofloc-technology-bft-a-tool-for-water-quality-management-in-aquaculture",totalDownloads:15412,totalCrossrefCites:36,totalDimensionsCites:85,book:{slug:"water-quality",title:"Water Quality",fullTitle:"Water Quality"},signatures:"Maurício Gustavo Coelho Emerenciano, Luis Rafael Martínez-\nCórdova, Marcel Martínez-Porchas and Anselmo Miranda-Baeza",authors:[{id:"146126",title:"Dr.",name:"Maurício Gustavo Coelho",middleName:null,surname:"Emerenciano",slug:"mauricio-gustavo-coelho-emerenciano",fullName:"Maurício Gustavo Coelho Emerenciano"},{id:"186970",title:"Prof.",name:"Marcel",middleName:null,surname:"Martínez-Porchas",slug:"marcel-martinez-porchas",fullName:"Marcel Martínez-Porchas"},{id:"186971",title:"Prof.",name:"Anselmo",middleName:null,surname:"Miranda-Baeza",slug:"anselmo-miranda-baeza",fullName:"Anselmo Miranda-Baeza"},{id:"195101",title:"Dr.",name:"Luis Rafael",middleName:null,surname:"Martínez-Córdoba",slug:"luis-rafael-martinez-cordoba",fullName:"Luis Rafael Martínez-Córdoba"}]},{id:"53194",doi:"10.5772/66561",title:"Impact of Wastewater on Surface Water Quality in Developing Countries: A Case Study of South Africa",slug:"impact-of-wastewater-on-surface-water-quality-in-developing-countries-a-case-study-of-south-africa",totalDownloads:6205,totalCrossrefCites:19,totalDimensionsCites:48,book:{slug:"water-quality",title:"Water Quality",fullTitle:"Water Quality"},signatures:"Joshua N. Edokpayi, John O. Odiyo and Olatunde S. Durowoju",authors:[{id:"187867",title:"Dr.",name:"Joshua",middleName:null,surname:"Edokpayi",slug:"joshua-edokpayi",fullName:"Joshua Edokpayi"},{id:"189690",title:"Prof.",name:"John",middleName:null,surname:"Odiyo",slug:"john-odiyo",fullName:"John Odiyo"},{id:"194678",title:"Dr.",name:"Olatunde",middleName:"Samod",surname:"Durowoju",slug:"olatunde-durowoju",fullName:"Olatunde Durowoju"}]}],mostDownloadedChaptersLast30Days:[{id:"24941",title:"Tsunami in Makran Region and Its Effect on the Persian Gulf",slug:"tsunami-in-makran-region-and-its-effect-on-the-persian-gulf",totalDownloads:4899,totalCrossrefCites:4,totalDimensionsCites:6,book:{slug:"tsunami-a-growing-disaster",title:"Tsunami",fullTitle:"Tsunami - A Growing Disaster"},signatures:"Mohammad Mokhtari",authors:[{id:"52451",title:"Dr.",name:"Mohammad",middleName:null,surname:"Mokhtari",slug:"mohammad-mokhtari",fullName:"Mohammad Mokhtari"}]},{id:"58138",title:"Water Pollution: Effects, Prevention, and Climatic Impact",slug:"water-pollution-effects-prevention-and-climatic-impact",totalDownloads:19558,totalCrossrefCites:8,totalDimensionsCites:16,book:{slug:"water-challenges-of-an-urbanizing-world",title:"Water Challenges of an Urbanizing World",fullTitle:"Water Challenges of an Urbanizing World"},signatures:"Inyinbor Adejumoke A., Adebesin Babatunde O., Oluyori Abimbola\nP., Adelani-Akande Tabitha A., Dada Adewumi O. and Oreofe Toyin\nA.",authors:[{id:"101570",title:"MSc.",name:"Babatunde Olufemi",middleName:null,surname:"Adebesin",slug:"babatunde-olufemi-adebesin",fullName:"Babatunde Olufemi Adebesin"},{id:"187738",title:"Dr.",name:"Adejumoke",middleName:"Abosede",surname:"Inyinbor",slug:"adejumoke-inyinbor",fullName:"Adejumoke Inyinbor"},{id:"188818",title:"Dr.",name:"Abimbola",middleName:null,surname:"Oluyori",slug:"abimbola-oluyori",fullName:"Abimbola Oluyori"},{id:"188819",title:"Mrs.",name:"Tabitha",middleName:null,surname:"Adelani-Akande",slug:"tabitha-adelani-akande",fullName:"Tabitha Adelani-Akande"},{id:"208501",title:"Dr.",name:"Adewumi",middleName:null,surname:"Dada",slug:"adewumi-dada",fullName:"Adewumi Dada"},{id:"208502",title:"Ms.",name:"Toyin",middleName:null,surname:"Oreofe",slug:"toyin-oreofe",fullName:"Toyin Oreofe"}]},{id:"53194",title:"Impact of Wastewater on Surface Water Quality in Developing Countries: A Case Study of South Africa",slug:"impact-of-wastewater-on-surface-water-quality-in-developing-countries-a-case-study-of-south-africa",totalDownloads:6205,totalCrossrefCites:19,totalDimensionsCites:48,book:{slug:"water-quality",title:"Water Quality",fullTitle:"Water Quality"},signatures:"Joshua N. Edokpayi, John O. Odiyo and Olatunde S. Durowoju",authors:[{id:"187867",title:"Dr.",name:"Joshua",middleName:null,surname:"Edokpayi",slug:"joshua-edokpayi",fullName:"Joshua Edokpayi"},{id:"189690",title:"Prof.",name:"John",middleName:null,surname:"Odiyo",slug:"john-odiyo",fullName:"John Odiyo"},{id:"194678",title:"Dr.",name:"Olatunde",middleName:"Samod",surname:"Durowoju",slug:"olatunde-durowoju",fullName:"Olatunde Durowoju"}]},{id:"57345",title:"Safe Drinking Water: Concepts, Benefits, Principles and Standards",slug:"safe-drinking-water-concepts-benefits-principles-and-standards",totalDownloads:4549,totalCrossrefCites:4,totalDimensionsCites:8,book:{slug:"water-challenges-of-an-urbanizing-world",title:"Water Challenges of an Urbanizing World",fullTitle:"Water Challenges of an Urbanizing World"},signatures:"Megersa Olumana Dinka",authors:[{id:"206964",title:"Dr.",name:"Megersa Olumana",middleName:null,surname:"Dinka",slug:"megersa-olumana-dinka",fullName:"Megersa Olumana Dinka"}]},{id:"53211",title:"Biofloc Technology (BFT): A Tool for Water Quality Management in Aquaculture",slug:"biofloc-technology-bft-a-tool-for-water-quality-management-in-aquaculture",totalDownloads:15412,totalCrossrefCites:36,totalDimensionsCites:85,book:{slug:"water-quality",title:"Water Quality",fullTitle:"Water Quality"},signatures:"Maurício Gustavo Coelho Emerenciano, Luis Rafael Martínez-\nCórdova, Marcel Martínez-Porchas and Anselmo Miranda-Baeza",authors:[{id:"146126",title:"Dr.",name:"Maurício Gustavo Coelho",middleName:null,surname:"Emerenciano",slug:"mauricio-gustavo-coelho-emerenciano",fullName:"Maurício Gustavo Coelho Emerenciano"},{id:"186970",title:"Prof.",name:"Marcel",middleName:null,surname:"Martínez-Porchas",slug:"marcel-martinez-porchas",fullName:"Marcel Martínez-Porchas"},{id:"186971",title:"Prof.",name:"Anselmo",middleName:null,surname:"Miranda-Baeza",slug:"anselmo-miranda-baeza",fullName:"Anselmo Miranda-Baeza"},{id:"195101",title:"Dr.",name:"Luis Rafael",middleName:null,surname:"Martínez-Córdoba",slug:"luis-rafael-martinez-cordoba",fullName:"Luis Rafael Martínez-Córdoba"}]},{id:"63043",title:"Desalination of Water",slug:"desalination-of-water",totalDownloads:2359,totalCrossrefCites:3,totalDimensionsCites:6,book:{slug:"desalination-and-water-treatment",title:"Desalination and Water Treatment",fullTitle:"Desalination and Water Treatment"},signatures:"Manish Thimmaraju, Divya Sreepada, Gummadi Sridhar Babu,\nBharath Kumar Dasari, Sai Kiran Velpula and Nagaraju Vallepu",authors:[{id:"249016",title:"Dr.",name:"Manish Kumar",middleName:null,surname:"Thimmaraju",slug:"manish-kumar-thimmaraju",fullName:"Manish Kumar Thimmaraju"},{id:"256566",title:"Mrs.",name:"Sreepada",middleName:null,surname:"Divya",slug:"sreepada-divya",fullName:"Sreepada Divya"}]},{id:"66437",title:"Detection of Underground Water by Using GPR",slug:"detection-of-underground-water-by-using-gpr",totalDownloads:1787,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"groundwater-resource-characterisation-and-management-aspects",title:"Groundwater",fullTitle:"Groundwater - Resource Characterisation and Management Aspects"},signatures:"Dalia N. Elsheakh and Esmat A. Abdallah",authors:[{id:"111813",title:"Dr.",name:"Dalia",middleName:null,surname:"Elsheakh",slug:"dalia-elsheakh",fullName:"Dalia Elsheakh"},{id:"111867",title:"Prof.",name:"Esmat",middleName:null,surname:"Abdallah",slug:"esmat-abdallah",fullName:"Esmat Abdallah"}]},{id:"68134",title:"Introductory Chapter: Earth Crust - Origin, Structure, Composition and Evolution",slug:"introductory-chapter-earth-crust-origin-structure-composition-and-evolution",totalDownloads:980,totalCrossrefCites:1,totalDimensionsCites:2,book:{slug:"earth-crust",title:"Earth Crust",fullTitle:"Earth Crust"},signatures:"Muhammad Nawaz",authors:[{id:"269790",title:"Dr.",name:"Muhammad",middleName:null,surname:"Nawaz",slug:"muhammad-nawaz",fullName:"Muhammad Nawaz"}]},{id:"61215",title:"Solar Desalination",slug:"solar-desalination",totalDownloads:1905,totalCrossrefCites:2,totalDimensionsCites:3,book:{slug:"desalination-and-water-treatment",title:"Desalination and Water Treatment",fullTitle:"Desalination and Water Treatment"},signatures:"Fadi Alnaimat, James Klausner and Bobby Mathew",authors:[{id:"151722",title:"Dr.",name:"Fadi",middleName:null,surname:"Alnaimat",slug:"fadi-alnaimat",fullName:"Fadi Alnaimat"},{id:"245337",title:"Prof.",name:"James",middleName:null,surname:"Klausner",slug:"james-klausner",fullName:"James Klausner"},{id:"245338",title:"Dr.",name:"Bobby",middleName:null,surname:"Mathew",slug:"bobby-mathew",fullName:"Bobby Mathew"}]},{id:"58862",title:"Aquifer, Classification and Characterization",slug:"aquifer-classification-and-characterization",totalDownloads:2155,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"aquifers-matrix-and-fluids",title:"Aquifers",fullTitle:"Aquifers - Matrix and Fluids"},signatures:"Salako Adebayo O and Adepelumi Abraham A",authors:[{id:"215811",title:"Mr.",name:"Adebayo",middleName:"Olayinka",surname:"Salako",slug:"adebayo-salako",fullName:"Adebayo Salako"},{id:"226469",title:"Prof.",name:"Adepelumi",middleName:null,surname:"Abraham A.",slug:"adepelumi-abraham-a.",fullName:"Adepelumi Abraham A."}]}],onlineFirstChaptersFilter:{topicSlug:"earth-science",limit:3,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[{type:"book",id:"10176",title:"Microgrids and Local Energy Systems",subtitle:null,isOpenForSubmission:!0,hash:"c32b4a5351a88f263074b0d0ca813a9c",slug:null,bookSignature:"Prof. Nick Jenkins",coverURL:"https://cdn.intechopen.com/books/images_new/10176.jpg",editedByType:null,editors:[{id:"55219",title:"Prof.",name:"Nick",middleName:null,surname:"Jenkins",slug:"nick-jenkins",fullName:"Nick Jenkins"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:8,limit:8,total:1},route:{name:"profile.detail",path:"/profiles/188025/mehmet-haluk-aksel",hash:"",query:{},params:{id:"188025",slug:"mehmet-haluk-aksel"},fullPath:"/profiles/188025/mehmet-haluk-aksel",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()