Newer biomarkers for diagnosis of active TB.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"6970",leadTitle:null,fullTitle:"The Universe of Escherichia coli",title:"The Universe of Escherichia coli",subtitle:null,reviewType:"peer-reviewed",abstract:'The title of the book "The Universe of Escherichia coli" aims to present and emphasize the huge diversity of this bacterial species and our efforts to prevent the E. coli infections. As it is part of the gut microbiota, E. coli is a well-known commensal species, and probiotic E. coli strains are successfully used for improving host\'s health. Also many "workhorse" E. coli strain exist that are employed in laboratory and biotechnology settings. But certain E. coli strains can cause intestinal and also extraintestinal infections at many anatomical sites. Therefore many efforts are undertaken to prevent E. coli infections, among them food safety, vaccines, but also new antimicrobial agents are searched for.',isbn:"978-1-83881-153-2",printIsbn:"978-1-83881-152-5",pdfIsbn:"978-1-83881-154-9",doi:"10.5772/intechopen.73717",price:119,priceEur:129,priceUsd:155,slug:"the-universe-of-escherichia-coli",numberOfPages:148,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"92027ca0bca1f8ae2971739a4ae6af84",bookSignature:"Marjanca Starčič Erjavec",publishedDate:"September 18th 2019",coverURL:"https://cdn.intechopen.com/books/images_new/6970.jpg",numberOfDownloads:7331,numberOfWosCitations:9,numberOfCrossrefCitations:13,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:17,numberOfDimensionsCitationsByBook:1,hasAltmetrics:0,numberOfTotalCitations:39,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"July 2nd 2018",dateEndSecondStepPublish:"July 23rd 2018",dateEndThirdStepPublish:"September 21st 2018",dateEndFourthStepPublish:"December 10th 2018",dateEndFifthStepPublish:"February 8th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"58980",title:"Dr.",name:"Marjanca",middleName:null,surname:"Starčič Erjavec",slug:"marjanca-starcic-erjavec",fullName:"Marjanca Starčič Erjavec",profilePictureURL:"https://mts.intechopen.com/storage/users/58980/images/system/58980.jpeg",biography:"Marjanca Starčič Erjavec, PhD, is a professor of Molecular Biology at the Department of Biology, Biotechnical faculty, University of Ljubljana, Slovenia, EU. She studied biology (undergraduate course) and biochemistry and molecular biology (graduate course) at the University of Ljubljana, Slovenia. She defended her PhD thesis in the field of bacterial molecular genetics at the University of Utrecht, Netherlands. She was a visiting professor at University of Maribor, Slovenia, University of Graz, Austria, University of Modena, Italy, Duke University, Durham, USA and at the Institute of Ecology and Genetics of Microorganisms, Perm, Russia. At the University of Ljubljana, she is involved in teaching different subjects for students of microbiology and molecular and functional biology. She conducts research on horizontal gene transfer, including plasmids, natural and clinical E. coli strains.",institutionString:"University of Ljubljana",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"University of Ljubljana",institutionURL:null,country:{name:"Slovenia"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"409",title:"Bacteriology",slug:"biochemistry-genetics-and-molecular-biology-microbiology-bacteriology"}],chapters:[{id:"68841",title:"Introductory Chapter: The Versatile Escherichia coli",doi:"10.5772/intechopen.88882",slug:"introductory-chapter-the-versatile-em-escherichia-coli-em-",totalDownloads:1080,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Marjanca Starčič Erjavec",downloadPdfUrl:"/chapter/pdf-download/68841",previewPdfUrl:"/chapter/pdf-preview/68841",authors:[{id:"58980",title:"Dr.",name:"Marjanca",surname:"Starčič Erjavec",slug:"marjanca-starcic-erjavec",fullName:"Marjanca Starčič Erjavec"}],corrections:null},{id:"64755",title:"Escherichia coli: A Versatile Platform for Recombinant Protein Expression",doi:"10.5772/intechopen.82276",slug:"-em-escherichia-coli-em-a-versatile-platform-for-recombinant-protein-expression",totalDownloads:919,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Among the living organisms, Escherichia coli has been the most common choice employed for recombinant protein expression. In addition to its well-characterized genetics, E. coli is fast growing, relatively cheap, and easy to handle. These fine properties, in conjunction with the success achieved in transforming plasmid DNA into E. coli, as well as the advent of various genetic engineering techniques in the 1970s, have enabled E. coli to be considered as the most favorable host for genetic manipulations. The recent advances in better comprehension of regulatory controls of gene expression and the availability of various novel approaches, which include both intracellular, e.g., through intein-mediated expression and self-cleavages, and extracellular, e.g., through the use of secretion signals, to achieve successful expression of the target proteins in E. coli further support the view that E. coli is the most promising host choice for heterologous protein expression.",signatures:"Wan-Keung Raymond Wong, Ka-Lun Ng, Thiyagarajan Sivakumar, Xiu-Hua Hu, Hao Wang and Lai-Cheuk Nelson Lai",downloadPdfUrl:"/chapter/pdf-download/64755",previewPdfUrl:"/chapter/pdf-preview/64755",authors:[{id:"269357",title:"Prof.",name:"Wan Keung Raymond",surname:"Wong",slug:"wan-keung-raymond-wong",fullName:"Wan Keung Raymond Wong"}],corrections:null},{id:"68887",title:"Enteropathogenic Escherichia coli",doi:"10.5772/intechopen.82861",slug:"enteropathogenic-em-escherichia-coli-em-",totalDownloads:779,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The term enteropathogenic Escherichia coli (EPEC) was first used in 1955 to describe a number of serogroup-defined E. coli strains associated with infantile diarrhea. EPEC are now defined as those that produce a characteristic intestinal histopathology known as attaching and effacing (A/E) and do not produce Shiga toxins. EPEC carry the locus for enterocyte effacement (LEE) pathogenicity island, which contains the eae gene that encodes an outer membrane protein called intimin. Typical EPEC (tEPEC) carry a virulence plasmid known as the pEAF (EPEC adhesion factor plasmid) which encodes the bundle-forming pilus (BFP) that mediate localized adherence to epithelial cells, whereas atypical EPEC (aEPEC) do not possess this plasmid. Typical EPEC strains have been associated with severe outbreaks of infant diarrhea in developing countries. Atypical EPEC strains have been linked to diarrhea outbreaks at all ages worldwide. Diarrhea due to aEPEC in children is not as severe as that caused by tEPEC.",signatures:"Isabel Cristina Affonso Scaletsky",downloadPdfUrl:"/chapter/pdf-download/68887",previewPdfUrl:"/chapter/pdf-preview/68887",authors:[{id:"269031",title:"Associate Prof.",name:"Isabel",surname:"Scaletsky",slug:"isabel-scaletsky",fullName:"Isabel Scaletsky"}],corrections:null},{id:"65564",title:"Insight into the mobilome of Escherichia coli",doi:"10.5772/intechopen.82799",slug:"insight-into-the-mobilome-of-em-escherichia-coli-em-",totalDownloads:807,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Mobilomes are all mobile genetic elements (plasmids, transposable elements, insertion sequences, gene cassettes, integrons, genomic islands, and bacteriophages) in a genome. Mobilome is one of the responsible agents for the bacterial evolution, virulence, and increasing antibiotic resistance. The mobile genetic elements in the Escherichia coli genome can carry antibiotic resistance genes and/or virulence genes. The acquisition of new mobile genetic elements can lead to the emergence of new pathotypes. The aim of this chapter is to gather knowledge about mobile genetic elements in E. coli strains. The method in this chapter depends on a literature survey, which scans reviews, research articles, and theses published about transposable elements, plasmids, bacteriophages, and genomic islands in E. coli strains.",signatures:"Elif Bozcal",downloadPdfUrl:"/chapter/pdf-download/65564",previewPdfUrl:"/chapter/pdf-preview/65564",authors:[{id:"203449",title:"Ph.D.",name:"Elif",surname:"Bozcal",slug:"elif-bozcal",fullName:"Elif Bozcal"}],corrections:null},{id:"65498",title:"Escherichia coli and Food Safety",doi:"10.5772/intechopen.82375",slug:"-em-escherichia-coli-em-and-food-safety",totalDownloads:1869,totalCrossrefCites:11,totalDimensionsCites:16,hasAltmetrics:0,abstract:"Foodborne pathogens are evaluated as an important risk factor in terms of public health in developed and developing countries due to their extensiveness all around the world. Escherichia coli and other coliform bacteria are important foodborne pathogens. Some of the most important sources of contamination for these groups of microorganisms are reported as: areas with unfavorable hygiene, contaminated waste water, meat products, cereal products and vegetables. Total coliform bacteria and E. coli count is known to be the indicator of unfavorable hygienic conditions and fecal contamination in foods. Foodborne diseases, however, are a global issue. A joint approach by all countries and related international organizations is a prerequisite for detection and control of foodborne problems that pose a threat to human health and international trade. Despite their complicated biology, epidemiology and analyses, most foodborne diseases are preventable. It is of vital importance for public health that consumers and food producers act in accordance with the principles regarding internationally accepted safety methods.",signatures:"Gözde Ekici and Emek Dümen",downloadPdfUrl:"/chapter/pdf-download/65498",previewPdfUrl:"/chapter/pdf-preview/65498",authors:[{id:"269684",title:"M.Sc.",name:"Gözde",surname:"Ekici",slug:"gozde-ekici",fullName:"Gözde Ekici"},{id:"269686",title:"Dr.",name:"Emek",surname:"Dümen",slug:"emek-dumen",fullName:"Emek Dümen"}],corrections:null},{id:"65326",title:"Human and Veterinary Vaccines against Pathogenic Escherichia coli",doi:"10.5772/intechopen.82835",slug:"human-and-veterinary-vaccines-against-pathogenic-em-escherichia-coli-em-",totalDownloads:1090,totalCrossrefCites:1,totalDimensionsCites:0,hasAltmetrics:0,abstract:"PathogenicEscherichia coli constitute an important current problem of public health and animal production. Efforts have been made to fight the infections caused by these bacteria, and in this chapter, we present the progress made up to date in the vaccines generated for this purpose. Different vaccines have been tested against the pathotypes responsible for human diseases such as diarrhea and urinary infections. Also, the poultry market has deserved the effort of the researchers to obtain a product that fights the E. coli strains that cause diseases in them. Finally, advances are also presented for the zoonotic enterohemorrhagic E. coli (EHEC), which are a different problem due to their low importance as a disease factor in cattle, but they are a very important pathogen in humans. In several of these fields, authorized products have been developed and are currently being marketed.",signatures:"Mariano Larzábal, Angel A. Cataldi and Daniel A. Vilte",downloadPdfUrl:"/chapter/pdf-download/65326",previewPdfUrl:"/chapter/pdf-preview/65326",authors:[{id:"269584",title:"Dr.",name:"Angel Adrian",surname:"Cataldi",slug:"angel-adrian-cataldi",fullName:"Angel Adrian Cataldi"},{id:"269585",title:"Dr.",name:"Mariano",surname:"Larzabal",slug:"mariano-larzabal",fullName:"Mariano Larzabal"}],corrections:null},{id:"64955",title:"Photodynamic Inactivation of Escherichia coli with Cationic Porphyrin Sensitizers",doi:"10.5772/intechopen.82645",slug:"photodynamic-inactivation-of-em-escherichia-coli-em-with-cationic-porphyrin-sensitizers",totalDownloads:790,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The activity of singlet-oxygen sensitizers for photodynamic inactivation (PDI) of microorganisms and photodynamic therapy of tumor cells has been evaluated using Escherichia coli, Saccharomyces cerevisiae, and human cancer cell lines. In this chapter, drug resistance of E. coli was examined based on the PDI activity of a variety of RPy-P-porphyrin sensitizers with different number of ionic valence and different hydrophobic characters. The PDI activities toward E. coli were evaluated using the minimum effective concentrations ([P]) of the porphyrin sensitizers. It was found that the [P] value for E. coli was larger than that for S. cerevisiae. E. coli has drug-resistance toward hydrophobic and mono-cationic porphyrins. However, E. coli has weak drug-resistance toward the porphyrins with both polycationic character and hydrophobicity. Since the outer membrane mainly consists of lipopolysaccharides and phospholipids that are negatively charged, cationic porphyrins are able to adsorb to the outer leaflet. Then the cationic porphyrins with hydrophobic character can interact with not only the outer leaflet but also inner leaflet of the outer membrane and the plasma membrane. Thus, porphyrins may be incorporated inside E. coli cells via the self-promoted uptake pathway. 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Finance",slug:"banking-and-finance",publishedDate:"December 23rd 2020",bookSignature:"Razali Haron, Maizaitulaidawati Md Husin and Michael Murg",coverURL:"https://cdn.intechopen.com/books/images_new/9534.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"206517",title:"Prof.",name:"Razali",middleName:null,surname:"Haron",slug:"razali-haron",fullName:"Razali Haron"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"11778",leadTitle:null,title:"Correctional Facilities and Correctional Treatment - International Perspectives",subtitle:null,reviewType:"peer-reviewed",abstract:"\r\n\tThe book “Correctional Facilities and Correctional Treatment - International Perspectives” will focus on current issues related to the correctional system in a broader international approach, revisiting some of the well-known problems that prison and community sentences embrace in different countries. The presentation of different correctional systems together with their underlying penal laws will help the reader to conceive how crime and criminals are approached globally.
\r\n\r\n\tThe book intends to revisit some of the typical prison problems (e.g., overcrowding, violence, mental health, drugs, sexuality, suicide, etc) in light of recent research, also providing international indicators of how recidivism is influenced by the way governments change their penal laws. The efficacy of correctional treatment programs and community-based programs on offenders’ recidivism rates will be also discussed. Studies concerning specific groups of the prison population – female prisoners, young prisoners, lifers, but also guards, and other staff members – will be considered to allow the implementation of tailored interventions.
\r\n\r\n\tFinally, the discussion about the future of the prison system and the alternatives related to community sentences or other diversion strategies will be considered, in light of corrections’ sustainability and under the therapeutic justice paradigm.
",isbn:"978-1-80356-615-3",printIsbn:"978-1-80356-614-6",pdfIsbn:"978-1-80356-616-0",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"a933550a6966a04e4677a4c0aea8f5b2",bookSignature:"Prof. Rui Abrunhosa Gonçalves",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11778.jpg",keywords:"Correctional Facilities, Correctional Laws, Correctional Treatment, Recidivism, Prison Sentences Efficacy, Community Sentences Efficacy, Corrections and Therapeutic Justice, Overcrowding, Violence, Mental Health, Future Challenges, Economic Sustainability",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 31st 2022",dateEndSecondStepPublish:"April 28th 2022",dateEndThirdStepPublish:"June 27th 2022",dateEndFourthStepPublish:"September 15th 2022",dateEndFifthStepPublish:"November 14th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"4 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"A longtime researcher and therapist in the field of forensic and criminal psychology in the University of Minho, and considered one of the most prominent forensic psychologists in Portugal.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"198691",title:"Prof.",name:"Rui",middleName:null,surname:"Abrunhosa Gonçalves",slug:"rui-abrunhosa-goncalves",fullName:"Rui Abrunhosa Gonçalves",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Minho",institutionURL:null,country:{name:"Portugal"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"23",title:"Social Sciences",slug:"social-sciences"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"247041",firstName:"Dolores",lastName:"Kuzelj",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/247041/images/7108_n.jpg",email:"dolores@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"6942",title:"Global Social Work",subtitle:"Cutting Edge Issues and Critical Reflections",isOpenForSubmission:!1,hash:"222c8a66edfc7a4a6537af7565bcb3de",slug:"global-social-work-cutting-edge-issues-and-critical-reflections",bookSignature:"Bala Raju Nikku",coverURL:"https://cdn.intechopen.com/books/images_new/6942.jpg",editedByType:"Edited by",editors:[{id:"263576",title:"Dr.",name:"Bala",surname:"Nikku",slug:"bala-nikku",fullName:"Bala Nikku"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6926",title:"Biological Anthropology",subtitle:"Applications and Case Studies",isOpenForSubmission:!1,hash:"5bbb192dffd37a257febf4acfde73bb8",slug:"biological-anthropology-applications-and-case-studies",bookSignature:"Alessio Vovlas",coverURL:"https://cdn.intechopen.com/books/images_new/6926.jpg",editedByType:"Edited by",editors:[{id:"313084",title:"Dr.",name:"Alessio",surname:"Vovlas",slug:"alessio-vovlas",fullName:"Alessio Vovlas"}],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:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],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:"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:"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:"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:"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:"117",title:"Artificial Neural Networks",subtitle:"Methodological Advances and Biomedical Applications",isOpenForSubmission:!1,hash:null,slug:"artificial-neural-networks-methodological-advances-and-biomedical-applications",bookSignature:"Kenji Suzuki",coverURL:"https://cdn.intechopen.com/books/images_new/117.jpg",editedByType:"Edited by",editors:[{id:"3095",title:"Prof.",name:"Kenji",surname:"Suzuki",slug:"kenji-suzuki",fullName:"Kenji Suzuki"}],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:"62126",title:"Latent Tuberculosis Infection: Patho-Biology and Treatment",doi:"10.5772/intechopen.76665",slug:"latent-tuberculosis-infection-patho-biology-and-treatment",body:'The medical, economic and social impact of the dual epidemics of human immunodeficiency virus (HIV) and tuberculosis (TB) will continue to remain one of the biggest public health challenges of the twenty-first century. According to the World Health Organization (WHO) Global Status Report, 11% of 10.4 million new cases of TB in 2015 were HIV-positive [1]. This is an increase in the number of new TB cases from 9.2 million in 2014 [1]. Sixty percent of the new TB cases are reported from India, Indonesia, China, Nigeria, Pakistan and South Africa [1]. It has been difficult to rein in the TB epidemic, and there are many reasons for it. One of the main reasons for spread of TB in low TB/HIV burden countries is the reactivation of latent tuberculosis. In high TB/HIV burden countries, the main factors are lack of accessible health facilities where timely and effective treatment of TB can be given and the burgeoning numbers of drug-resistant TB cases. Another significant factor in the failure of TB control programmes in the developing countries has been the ongoing HIV epidemic. HIV-infected patients are at increased risk of new TB infection as well as reactivation of latent TB infection (LTBI). Prevention of reactivation TB in those with LTBI is now considered as one of the key strategies of TB prevention and is one of the pillars for the WHO “End TB Strategy” [1]. The WHO aims to implement LTBI detection and treatment in the 30 high-TB burden countries first. In these countries, it has set out an ambitious target of bringing 90% of children under 5 years who are TB contacts and PLHA under the chemoprophylaxis programme by 2025 [1]. Biostatistical modeling shows that if 8% of persons with latent tuberculosis could be permanently protected each year, the global incidence in 2050 would be 14 times lower than incidence in 2013, with no other intervention needed [2].
Latent tuberculosis infection (LTBI) is a state of persistent immune response to
Operational constraints and unfounded fears of increased incidence of drug-resistant TB have been the two main reasons for the poor implementation of LTBI programme in high-TB burden countries. Only 87,236 children under 5 years age who were household contacts of TB cases were initiated on TB chemoprophylaxis in 2015 [1]. The best chemoprophylaxis coverage was from the Americas (67%, range 63–71%) and European Region (42%, range 40–44%). In high TB or HIV/TB burden countries, the figures ranged from 2.6% in Cameroon to 41% in Malawi. These numbers belie the actual magnitude of the problem. The total number of children on TB chemoprophylaxis (87236) is only 7.1% (range 6.9–7.4%) of the 1.2 million children who are eligible for treatment. PLHA have a higher coverage with TB chemoprophylaxis, especially in the African region. In 2015, TB chemoprophylaxis was being offered to PLHA enrolling for HIV care in 57 countries. These countries represent 61% of the global TB burden. These data are encouraging because in 2014 there were only 49 countries where TB preventive treatment was available. South Africa, Malawi, Mozambique and Kenya have the largest number of PLHA on TB chemoprophylaxis. Much more needs to be done. Of the 30 high TB/HIV burden countries, no preventive treatment was available in 21 countries. Even in nine that did report so, coverage of people newly enrolled in HIV care varied from 2% in Indonesia to 79% in Malawi. The National AIDS Control Organization (NACO) in India issued new TB management guidelines in 2016 [8]. TB care has now been integrated into the services provided by the ART centres and isoniazid preventive therapy (IPT) has also been included in it [8].
Ninety percent of people infected with Mtb are able to successfully contain the microbe and ward of clinical disease. It should be realized that Mtb infection cannot be eradicated but only contained even in healthy immune-competent people and a key pathological mechanism in this is formation of tubercular granuloma.
Mtb infection occurs via the respiratory tract and on entry, mycobacteria encounter alveolar macrophages in the airways and immediately infect them. Macrophages can provide an intracellular sanctuary for mycobacteria, and Mtb has evolved numerous mechanisms to survive within macrophages. A characteristic set of pro-inflammatory cytokines and chemotactic factors for macrophages are released and cause granuloma formation. The granuloma is composed of various cells including macrophages, lymphocytes, dendritic cells, neutrophils, and sometimes fibroblasts, often with a necrotic centre. This structure serves to contain the bacilli and acts as an immune microenvironment that limits
Structural or functional disruption of the granuloma is likely to lead to reactivation of latent
Depletion of CD4 cell population leads to an inability to mount an effective cell-mediated immune response against Mtb. Studies on macaques infected with simian immunodeficiency virus (SIV) have shown that reactivation of LTBI is directly associated with depletion of CD4+ T cells [10, 11, 12]. Critical decline in the number of CD4+ T cells is associated with a decrease in the number of memory CD4+ T cells (CD27+ CDRO45+) that can recognize Mtb antigens, decrease in polyfunctional antigen-specific CD4+ T cells and a relative increase in interferon gamma + CD 8+ T cells [10, 11, 12]. Other mechanisms include suppression of cell-mediated responses of regulatory T cells (Tregs) and impairment of TNF-α- mediated apoptosis of Mtb-infected cells [13].
Prior to putting people on chemoprophylaxis for LTBI, active TB has to be first excluded by standard case finding methods. Latent tuberculosis infection (LTBI) is most often diagnosed by the tuberculin skin test (TST), and the Mantoux TST is the standard method of determining
Classification of positive TST results
Induration size/Patient profile | ≥5 mm | ≥10 mm | ≥15 mm |
---|---|---|---|
HIV-infected persons
|
| Any person, including persons with no known risk factors for TB |
In interpreting a positive TST, it is important to consider much more than only the size of the induration. Rather, the TST should be considered according to three dimensions: size of induration, pre-test probability of infection and risk of disease if the person were truly infected [14]. There are two important causes of false-positive results: nontuberculous mycobacterial (NTM) infection and prior BCG vaccination [15]. NTMs are not a clinically important cause of false-positive TST results, except in populations with a high prevalence of NTM sensitization and a very low prevalence of TB infection [15]. The impact of BCG on TST specificity depends on when BCG is given and on how many doses are administered. If BCG is administered at birth or infancy and not repeated, then its impact on TST specificity is minimal and can be ignored while interpreting the results [15]. In contrast, if BCG is given after infancy (e.g., school entry) and/or given multiple times (i.e., booster shots), then TST specificity is compromised [15].
Tuberculin skin tests are subject to variability when repeated tuberculin tests are given. Chance variation should result in differences of less than 6 mm (representing two standard deviations) in 95% of subjects. This supports the adoption of 6 mm as a criterion to distinguish increases in reaction size due to random variation alone from true biologic phenomena, which could be either conversion or boosting [16]. Boosting is best distinguished from conversion on clinical grounds. One can attribute an increase in reaction size to boosting when the increase in reaction is seen after an interval of 1–5 weeks during which there has been no possibility of exposure, such as pre-employment testing of a health care worker [16]. Conversion can be confidently stated to have occurred when a previously tuberculin-negative individual becomes tuberculin test positive after receiving BCG vaccination, or following significant exposure such as during an outbreak or as a result of close contact with a highly contagious index case [17, 18]. Among subjects vaccinated in infancy, and tested after an interval of 5 years or more, prevalence of initial tuberculin reactions is the same in vaccinated and unvaccinated reference populations but prevalence of boosting was 7% higher in vaccinated than unvaccinated [19].
The other method of detecting LTBI is based on IFNγ release assays (IGRA). These tests detect a set of Mtb genes that are present in Mtb complex but not present in BCG immunized or in a setting of NTM infection. In this test, the sera of patients is incubated with Mtb specific T lymphocytes. The T cells respond to Mtb-specific gene products by secretion of pro-inflammatory cytokines that are detected. Two IGRAs are commercially available today. QuantiFERON-Gold In Tube test (QFT; Germany) uses whole blood and is ELISA based. The T-SPOT.TB test (Oxford Immunotec, Abingdon, UK) uses peripheral blood mononucleated cell (PBMC) and ELISPOT technique. Both IGRAs incorporate the region of difference 1 (RD1)-encoded 6 kDa early secretory antigenic target (ESAT-6) and 10 kDa culture filtrate protein (CFP10) antigens, whereas an additional single peptide from TB7.7, encoded in RD11, is added to the QFT [20]. The selections of antigens for these tests are critical. Natural immunity to
Various studies have evaluated the utility of IGRAs and TST. A study from Turkey published in 2007 seems relevant to countries like India as Turkey is also a country with high prevalence of TB and high BCG vaccination coverage [23]. The workers compared TST with QuantiFERON®-TB in three population groups: household contacts of smear-positive TB cases, community members who had been exposed to index smear-positive TB cases and healthcare workers dealing with TB cases or handling TB specimens. They did a Kappa analysis to look for agreement between the tests. They found that QuantiFERON®-TB values were higher in the first group of patients when compared to the other two groups. In case of TST, there was no difference among the three groups. Evaluation for agreement rates between the groups showed poor agreement in all three groups. The authors concluded that while Quantiferon Gold was more objective, practical and gave quantitative values, it was more expensive and required a well-equipped laboratory and thus did not have a programmatic role in detection of LTBI in a country will high TB prevalence and high BCG coverage [23].
In a Japanese study, the specificity of IGRA was studied in healthy low-risk individuals with history of BCG vaccination [24]. It was seen that TST was positive (≥ 10 mm) in 64.6% (specificity 35.4%) while QuantiFERON®-TB test was positive in 1.9% (specificity 98.1%,) [24]. Similar results were obtained in another study done in Korea [25].In this study, 273 participants were included, 220 (95.7%) had received BCG vaccine. Participants were grouped according to their risk of infection: group 1, no identifiable risk of
Both TST and IGRAs are acceptable but imperfect LTBI tests, with advantages and disadvantages [27]. In some situations, neither test is appropriate (e.g., active TB diagnosis in adults) and in some situations, both the tests may be necessary to detect
Population groups | Test | Quality of recommendation |
---|---|---|
PLHA, child contacts of TB cases, patients being initiated on anti-TNF treatment, patients receiving dialysis, patients preparing for organ/haemotologic transplant and patients of silicosis | IGRA/TST | Strong recommendation, low/very low quality evidence |
Prisoners, health-care workers, immigrants from high TB-burden countries, homeless persons and illicit drug users | IGRA/TST | Conditional recommendation, low/very low quality evidence |
In the long term, highly predictive biomarkers need to be identified. This is an active area of research, and future generations of LTBI tests should overcome the limitations of current assays. A great endeavor is on to discover reliable, low-cost biomarkers. Gene signatures can distinguish between active and latent TB [32]. A lot of works have been done to identify differential expression of cytokines and chemokines in active TB and LTBI. It has been shown that plasma levels of the CXC chemokine IP-10 and soluble TNF receptor type 2 (sTNFr2) can significantly differentiate active TB from the LTBI group, irrespective of HIV status [33]. Another study showed that serum IL-2, IL-9, IL-13, IL-17, TNF-α, sCD40L and VEGF-A levels may be adjunctive biomarkers for differential diagnosis of active TB, LTBI, and NTM disease [34]. Assessment of serum sCD40L and Mtb antigen-specific IFN-γ, TNF-α, and IL-2 levels could also help predict successful anti-TB treatment in conjunction with Mtb clearance [31]. Achkar et al. looked at biomarkers to distinguish active TB and LTBI from no TB infection in HIV positive and negative populations [35]. They did so because inflammatory response and repair are both blunted in PLHA. They identified a set of biomarkers which reliably predict active TB. The biomarkers identified are shown in Table 1 [32]:
Functional category | HIV-Positive TB | HIV-Negative TB |
---|---|---|
Immune response | CD14, SEPP1, SELL | CD14, SEPP1, PGL YR P2 |
Tissue development & repair | TNXB, LUM, PEPD, QSOX1, COMP | PFN1, VASN |
Lipid metabolism | APOC1 | |
Other | GP1BA | CPN2, TAGLN2, IGFBP6 |
Newer biomarkers for diagnosis of active TB.
SEPP, selenoprotein P; SELL, selectin L; TNXB, tenascin XB; LUM, lumican; PEPD-peptidase D; QSOX1, quiescin sulfhydryl oxidase 1; COMP, cartilage oligomeric matrix protein; APOC1, apolipoprotein C-I; GP1 BA-glycoprotein 1 BA; VASN, vasorin; PFN 1, profilin1; CPN 2, chaperon 2; TAGLN2, transgelin 2; IGFBP 6, insulin-like growth factor binding protein 6; PGLYRP2, peptidoglycan recognition protein 2.
Treatment of LTBI reduces the risk for active disease and hence various authorities have recommended treatment for this entity. Chemoprophylaxis for LTBI can prevent 60–90% of reactivation TB [36]. But chemoprophylaxis cannot be considered as a universal approach due to the inherent toxicity of all TB drugs. However, in vulnerable populations, the benefits far outweigh the risks [33].
The International Union against Tuberculosis (IUAT) trial, conducted in Eastern Europe, randomized approximately 28,000 individuals with positive tuberculin skin tests (TST) and fibronodular changes on chest X-ray [37]. Approximately 7000 participants each were randomized to placebo, 3, 6 or 12 months of INH. Compared to participants who took placebo, participants who completed 3 months INH had 31% reduction in TB; those who completed 6 months INH (6INH) 69% reduction and the subjects who completed 12 months INH (12INH) had 93% reduction in TB. The efficacy of 6INH and 12INH waned during 5 years of follow-up but remained significantly better than the placebo. It is to be noted that fewer people completed 12 INH regimens as compared to 6INH [34].
Concerns regarding the relatively low efficacy of 6INH, and equally serious concerns regarding the poor completion of 12INH resulted in recommendations for 9 months INH by the American Thoracic Society in 2000 [38]. The optimal duration of INH was recommended as 9 months, with estimated efficacy of 90% and no significant gain with extension to 12 months [35].
In another trial, in Hong Kong, people who had pulmonary silicosis with a positive TST were randomized to placebo, 6INH, 3 m INH + Rifampin, or 3 m Rifampin alone [39]. During 5 years of follow-up, 27% of those randomized to placebo arm developed active TB, compared to 16, 13, and 10% for the three regimens respectively [36]. The estimated effectiveness of 3-months rifampin was approximately 65%; this was better than the other regimens although the differences between active regimens were not significant, and all were significantly better than placebo [36].
A series of randomized trials have demonstrated that the efficacy of 3-4INH + RIF to be equivalent to that of 6INH (four studies) or 9INH (one study) although adverse events are significantly more frequent [40, 41].
For adults, the recommended duration of treatment is at least 6, and preferably 9, months. Children younger than 18 years and persons with HIV infection should be treated for 9 months [42]. In HIV TB setting, IPT has been shown to slow the progression to active disease. A Cochrane systematic review of 12 trials, published in 2010 among 8578 patients showed that IPT reduced the risk of active TB by 64% among TST positive HIV-infected participants [43]. WHO has recommended that in resource-limited countries and other middle-income countries, people living with HIV and children below 5 years of age who are household or close contacts of people with TB and who, after an appropriate clinical evaluation, are found not to have active TB but have LTBI should be treated. WHO has recommended the following regimens for the treatment of LTBI which are similar to current CDC guidelines [26, 44, 45, 46].
The 9-month regimen with isoniazid is preferred because it is more efficacious. However, treatment of LTBI for 6 months rather than 9 months may be more cost-effective and result in greater adherence by patients.
Regimen | Dose isoniazid | Dose rifapentine or rifampicin | Maximum dose |
---|---|---|---|
6 m or 9 m isoniazid daily | Adults = 5 mg/kg Children = 10 mg/kg | isoniazid - 300 mg | |
3 m rifapentine + isoniazid weekly | Adults & children isoniazid - 15 mg/kg | Rifapentine (wt band): 10.0–14.0 kg = 300 mg; 14.1–25.0 kg = 450 mg; 25.1–32.0 kg = 600 mg; 32.1–49.9 kg = 750 mg; ≥50.0 kg = 900 mg | isoniazid - 900 mg Rifapentine - 900 mg |
3 or 4 m isoniazid + rifampicin daily | Isoniazid: Adults - 5 mg/kg Children - 10 mg/kg | Rifampicin: Adults & children - 10 mg/kg | isoniazid-300 mg Rifampicin - 600 mg |
3 or 4 m rifampicin alone daily | Adults & children 10 mg/kg | Rifampicin - 600 mg |
Directly observed once-weekly regimen of isoniazid and rifapentine is recommended as an option equal to the standard INH 9-month daily regimen for treating LTBI. The regimen may be used in otherwise healthy HIV-infected persons, 12 years of age and older, who are not on antiretroviral medications. It may also be considered for children aged 2–11 years if completion of 9 months of INH is unlikely and hazard of TB disease is great.
The regimen using 4 months of rifampicin can be considered for persons who cannot tolerate INH or who have been exposed to INH-resistant TB. It should also not be used to treat HIV-infected persons taking some combinations of ART especially protease inhibitors.
The National Aids Control Organization guidelines for LTBI in PLHA published in 2016 recommends the following strategy [8]
Adults and adolescents living with HIV should be screened for TB with a clinical algorithm and those who do not report any one of the symptoms of current cough, fever, weight loss or night sweats are unlikely to have active TB and should be offered Isoniazid Preventive Therapy (IPT).
Children living with HIV (more than 12 months of age) who do not report poor weight gain, fever, current cough or history of contact with a TB case, are unlikely to have active TB and should be offered IPT.
Additional investigations will help in ruling out active TB (X-ray chest and tuberculin skin test) but are not mandatory.
The treatment recommended in adult and adolescent is Isoniazid 300 mg + Pyridoxine 50 mg (Vitamin B6) per day for 6 months and for children above 12 months is Isoniazid 10 mg/kg + Pyridoxine 25 mg (Vitamin B6) per day for 6 months.
Treatment of close contacts of drug-resistant active TB cases is difficult and yet is an increasingly common clinical problem. For contacts of INH-resistant index cases, INH will be ineffective, so 4RIF is recommended [47, 48].
In a prospective study, two of 41 children receiving tailored preventive therapy developed TB (confirmed and probable TB) compared to 13 of 64 children not receiving preventive treatment (OR 0.2, 95% CI 0.04–0.94) [49]. However, WHO has not recommended any form of preventive therapy for MDR contact cases. Based on the available evidence and the probability of increased likelihood to develop active TB disease following recent infection, strict clinical observation and close monitoring for the development of active TB disease for at least 2 years is preferred over the provision of preventive treatment for contacts of MDR-TB cases [1].
Clinical management of latent tuberculosis infection should also address such concomitant risk factors as illicit-drug use, alcohol abuse, and smoking through opioid-substitution treatment and counseling about alcohol and smoking cessation, respectively. Acceptance of and adherence to the full course of latent tuberculosis treatment must be encouraged. In a study conducted in the United States and Canada, 17% of persons who were offered treatment for latent infection refused it [1]. Treatment completion varies widely (from 19 to 96%), and the reasons for non-completion need to be fully assessed [1]. The use of various incentives to promote treatment initiation and adherence, depending on the specific need of the person being treated, should be considered. Peer education, counseling, people-friendly services, and properly trained service providers boost confidence and may improve adherence to treatment [1].
The lengthy duration of treatment reduces patient compliance, while the potential occurrence of serious adverse events such as hepatitis, further discourages patients’ and providers’ acceptance of this therapy [50, 51, 52].
INH has the major disadvantage of potential serious adverse events. Of particular concern is hepatotoxicity, as this is difficult to detect, and can be fatal. Surveillance studies have confirmed that hepatotoxicity is quite common in patients taking INH and can be severe resulting in up to 1 per cent mortality in older patients [53].The relative risk for developing hepatotoxicity associated with isoniazid compared with placebo were 3.45 (95% CI, 1.49–7.99) for 12 weeks of treatment, 4.59 (95% CI, 2.03–10.39) for 24 weeks of treatment, and 6.21 (95% CI, 2.79–13.79) for 52 weeks of treatment in the IUAT trial [34].
In another randomized trial, rates of grade 3 and 4 adverse events were significantly lower with 4RIF than 9INH [54]. Grade 3–4 hepatotoxicity occurred in 4% of patients taking 9INH compared to less than 1% in those taking 4RIF [54].
Comparison of drug toxicity of INH and Rifampicin has been studied in many trials. Rates of hepatotoxicity among patients receiving isoniazid were 5.2, 3.7, 34 and 11.4% compared to rates among patients treated with rifampicin (0.0, 0.7 and 4.4%, respectively) [55, 56].
In PREVENT TB study, rates of grade 3 and 4 hepatotoxicity were 4.9 and 1.0% in the rifapentine plus isoniazid arm and 5.5 and 1.1% in the isoniazid-only arm, respectively [57]. The RR for grade 3 or 4 hepatotoxicity was 0.90 (95% CI, 0.75–1.08). Mortality from hepatotoxicity was reported to be 1.0% among patients on isoniazid and 0.8% on those on isoniazid plus rifapentine (RR, 0.83 [95% CI, 0.51–1.35]) [57]. Therefore, unless the index TB case has INH-resistant TB or an abbreviated regimen is required in a special situation, there is no reason not to use INH for LTBI chemoprophylaxis.
Identification and early chemoprophylaxis for LTBI can prevent reactivation TB and thus reduce both TB morbidity and transmission of TB in the community. In low TB-burden countries LTBI detection and IPT are important strategies for TB eradication. Diagnosis of LTBI is based on either TST or TB IGRA. The test preferred usually depends on the financial support available for public health programmes. In high TB- burden countries, LTBI detection and treatment can contribute to decreasing TB burden and transmission and also emergence of drug resistant TB. Here the guidelines are pretty straightforward and IPT should be offered to all children less than 5 years who have contact with pulmonary TB cases or HIV-positive individuals. INH is the preferred drug for LTBI and a 9-month regimen is considered optimal. However, careful clinical monitoring is required to detect drug induced liver injury early and also to ensure adherence to therapy. Clinical trials in different parts of the world have shown that this effort is worth it.
N-of-1 trials or single-patient trials focus on one patient and their main goal is to evaluate whether the treatment is effective for the individual. The main motivation for such trials is that each patient serves as his or her own control, and another is that each patient is different from another and there is no average patient. This is in contrast to conventional clinical trials where the aim is to optimize treatment for the average patients. Consequently, their aims are different, and conventional clinical trials are not appropriate for N-of-1 trials. These trials may appear new but they are not, except that they probably were given short shrift and not well publicized. In the last decade or so, there is increasing interest in N-of-1 trials. Duan et al. [1] raised awareness among clinicians and epidemiologists that N-of-1 trials are potentially useful for informing personalized treatment decisions for patients with chronic conditions. A monograph on this topic in healthcare is [2], where their applications to behavioral sciences and many medical settings are discussed, including the economics, ethics, statistical analysis of running such trials, and how to report results to professional audiences. Scuffham et al. [3] showed how N-of-1 trials can improve patient management and save costs and Kravitz and Duan [4] provided a user’s handbook on implementing such trials. A systematic review of the use of N-of-1 trials in the medical literature is given in [5]. There are many ways to analyze and compare results from N-of-1 trials; see for example, [6].
Interestingly, and perhaps, not unexpectedly, results from N-of-1 trials can be combined to generate group mean effects, as [7, 8] demonstrated how it can be done using systematic reviews and meta-analyses on the effects of amphetamine and methylphenidate for attention-deficit hyperactivity disorder. Li et al. [9] provided a systematic review of quality N-of-1 trials published between 1985 and 2013 in the medical literature based on the CONSORT extension for N-of-1 Trials (CENT) where they examined factors that influence reporting quality in these trials. In palliative care, Senior et al. [10] designed a N-of-1 trial of a psychostimulant, methylphenidate hydrochloride (MPH) (5 mg bd), compared to placebo as a treatment for fatigue, with a population estimate of the benefit by the aggregation of multiple SPTs. Forty patients who had advanced cancer was enrolled through specialist palliative care services in Australia.
Multi-crossover single-patient trials are often employed when the focus is to make the best possible treatment decision for an individual patient [2, 11, 12]. From a clinician’s perspective, having clear evidence of the value of one treatment over another (or no treatment) is more useful than knowing the average response. The average response gives the clinician the probability that a treatment will be effective, whereas N-of-1 trials give more certainty about whether the treatment for a particular patient will work or not.
In what is to follow, we assume that there are predetermined p periods in the crossover study, and in each period only one of the treatments is administrated. The same treatment may be used in other periods. We first discuss the case when there are two treatments and two periods for N-of-1 trials before extending them to aggregated N-of-1 trials to evaluate the effects of treatments for the average patients. Treatment groups are generically denoted by
Many researchers studied the optimality of crossover designs [13, 14, 15, 16, 17, 18]. Optimal designs have been constructed under a variety of statistical models to provide the most accurate inference of the treatment effects. It is known that the two-treatment design
A direct application of this two-treatment optimal design results from the literature with
However, design issues are not always as straightforward to address. For example, Carriere and Li [21] showed that constructing N-of-1 trials for individualized care from sequences in these repeated measurement designs is not always optimal for estimating individual-based treatment effects. Likewise, Guyatt et al. [22] showed that aggregating a series of N-of-1 trials that are optimal for individual patients can also provide an optimal estimate of the treatment effects for the average patient. For example, in a multi-clinic setting in three
The traditional crossover design model assumes that the carryover effects last for only one period. The patient effects are considered fixed in the model. The traditional model assumes no carryover effects for the observations in the first period. An alternative model which has carryover effects in the first period as well is built by giving patients a pre-period or baseline period [23, 24]. More complex models have also been considered. Some models incorporate higher-order carryover effects [25]; some consider carryover effects are proportional to the treatment effects [26], some include the interaction effects between the treatment effects and carryover effects [27], and others have random patient effects [28, 29, 30].
We first focus on the traditional model, frequently used to analyze repeated measures crossover data:
The model assumes that the carryover effects only depend on the treatment assigned in the previous period but not on the treatment in the current period, which may be unrealistic. Taking the interaction into account without introducing too many parameters, Kunert and Stufken [17] presented a model with self and mixed carryover effects. The self carryover effect occurs when the treatments administered in the current and the previous periods are the same; otherwise, we have a mixed carryover effect. The model with the self and mixed carryover effects is given by
where
In an N-of-1 trial with
For models (1) and (2), we define the contrast of the direct treatment effects by
To construct a model-based optimal design, we commonly use design criteria such as
Specifically, we first partition the design matrix
Following [13], a design is universally optimal if (i) its information matrix is completely symmetric, and (ii) it maximizes the trace of the information matrix. To study the universal optimality of treatment effects in the
We first discuss how to find N-of-1 designs for comparing two treatments by minimizing the variance of the estimated direct treatment effect contrast,
For N-of-1 trials involving two treatments, the design sequences consist of crossover pairs,
Further, if an
When we define
h | s | m |
---|---|---|
0 | p-1 | |
1 | p-2 | |
2 | p-3 | |
−1 |
Feature parameters of a sequence in a 2-treatment N-of-1 design.
For a particular
Sequence | Alternation | |||
---|---|---|---|---|
−7 | 0 | 0 | 7 | |
−5 | 1 | 1 | 6 | |
1 | 6 | |||
1 | 6 | |||
−3 | 2 | 2 | 5 | |
2 | 5 | |||
2 | 5 | |||
−1 | 3 | 3 | 4 |
Sequences for
Note:
In the next section, we show that the information matrix of the parameters of interest are only dependent on the feature parameters. That is, sequences with the same
Let
In 2-treatment N-of-1 trials, the
under model (1) for
under model (2) for
Since the information matrices can be further simply expressed in terms of
Under an equi-correlated error assumption, the optimal N-of-1 trial for
Under the equi-correlated errors, the optimal N-of-1 trial for estimating the direct treatment contrast is the sequence with only
To summarize, the optimal N-of-1 trials for estimating direct treatment effects are determined by the three feature parameters
It can be shown that under the traditional model, the optimal trial for the direct treatment effect uses the sequence with
In addition to the interest in the patient-based evidence of a treatment contrast, it may also be desirable to obtain a population average effect of treatments. Aggregating the series of N-of-1 trials can give such an estimate of the average effect [7]. Using the one sequence that was found optimal for N-of-1 trial to all patients seems to be an obvious choice. However, it might not optimize the trial for estimating the effects on the average patient and therefore, using the one sequence that is optimal for a single individual patient to all patients might not serve this purpose.
The optimal designs for aggregated N-of-1 trials can also be derived from the information matrices we obtained, similarly as for N-of-1 trials for one patient, by allowing
To find the optimal design, we typically choose
As noted earlier for Table 1, designs with the same value of
For example, the optimal design for aggregated six-period N-of-1 trials is the two-sequence design using sequences
For example, the optimal aggregated 6-period N-of-1 trials for multi-clinic setting is to use the two-sequence design
From each sequence, we obtain individual patient specific treatment effects and by aggregating these one sequence of N-of-1 trials, we can quantify the average treatment effects.
To appreciate the practical performance of the optimal N-of-1 trials we constructed, we compare the efficiencies of selected designs for estimating the treatment and carryover effects under the two models. We also investigate their performances in some aggregation for estimating the average treatment effect. We limit the comparison to the models with independent and equi-correlation errors. In our comparisons, we also reference many designs, labeled with an A or S at the beginning, like A65 and S83, that were investigated in [31].
Recall that the optimal N-of-1 trials are either to alternate between
Design | h | Traditional model | Self and mixed model | |||
---|---|---|---|---|---|---|
S61: ABABAB | −5 | 1.208 | 1.500 | 1.208 | NE | 1.500 |
S62: ABABBA | −3 | 0.242 | 0.300 | 1.250 | 3.000 | 1.500 |
S63: ABBAAB | −1 | 0.173 | 0.214 | 1.214 | 1.714 | 1.714 |
S64: ABBABA | −3 | 0.242 | 0.300 | 1.250 | 3.000 | 1.500 |
A61 = S61 + dual | 1.208 | 1.500 | 1.208 | NE | 1.500 | |
A62 = S62 + dual | 0.242 | 0.300 | 1.250 | 3.000 | 1.500 | |
A63 = S63 + dual | 0.173 | 0.214 | 1.214 | 1.714 | 1.714 | |
A64 = S63 + S62 + duals | 0.193 | 0.240 | 1.210 | 2.063 | 1.563 | |
A65 = S61:S64 + duals | 0.242 | 0.300 | 1.214 | 2.535 | 1.521 | |
S81: ABABABAB | −7 | 1.146 | 1.333 | 1.146 | NE | 1.333 |
S82: ABABBABA | −5 | 0.229 | 0.267 | 1.167 | 2.667 | 1.333 |
S83: ABBAABBA | −1 | 0.127 | 0.148 | 1.150 | 1.600 | 1.400 |
S84: ABBABAAB | −3 | 0.150 | 0.174 | 1.147 | 1.647 | 1.412 |
A81 = S81 + dual | 1.146 | 1.333 | 1.146 | NE | 1.333 | |
A82 = S82 + dual | 0.229 | 0.267 | 1.167 | 2.667 | 1.333 | |
A83 = S83 + dual | 0.127 | 0.148 | 1.150 | 1.600 | 1.400 | |
A84 = S82 + S84 + dual | 0.176 | 0.205 | 1.147 | 1.945 | 1.358 | |
A85 = S81:84 + dual | 0.176 | 0.205 | 1.147 | 1.945 | 1.358 |
Variances of the estimators of treatment and carryover effects in six- and eight-period designs.
Note: NE means “Not Estimable.” For
Based on these single sequence trials, we also consider aggregated N-of-1 trials to numerically justify Propositions 1 and 2. We constructed 5 aggregated N-of-1 trials for
A61.
A62.
A63.
A64.
A65. All 8 sequences, S61–S64 and their duals with 4 patients in each sequence
A81.
A82.
A83.
A84.
A85. All 8 sequences, S81–S84 and their duals with 4 patients in each sequence
The design A63 uses the optimal sequence S63 under the traditional model; the design A61 uses the optimal sequence S61 under the self and mixed model although the self carryover effect is not estimable; the design A62 is a slight rearrangement of designs A61 and A63; the design A64 is a combination of designs A62 and A63; the design A65 contains all 8 possible sequences of a 6-period design. Designs A81–A85 are also similarly constructed from various N-of-1 trials. We compare these designs under the traditional model and the self and mixed model. Table 3 displays the comparison results under the two models and reports the variances of the estimated
Table 3 shows that under the traditional model, the design A63 with the optimal sequence
When using the self and mixed effects model, Design A61 provides the best precision for estimating the direct treatment effect and the mixed carryover effect. However, the self carryover effect is not estimable. Overall, A63 is the optimal choice even in this case. However, all designs performed rather similar with over 95
A similar observation is possible for 8-period designs and their sequences. In summary, it appears that there is no discernable advantage to distinguish among the two models and various error structures.
Overall, S63 and S83 for single N-of-1 trials or designs A63 and A83 in aggregation of S63, S83 and their duals seem to be the best under both models. They are optimal for estimating direct treatment and mixed carryover effects. Further, they are optimal for estimating both the treatment and carryover effects under the traditional model. Hence, we conclude that the optimal six-period aggregated N-of-1 trials is
We close this section with a summary note. Our numerical work suggests that alternating
Oftentimes, N-of-1 trials deal with comparing
Li [31] showed that Kiefer’s conditions could not be satisfied with designs in the class No1(t,t). However, if we consider a slightly different class of designs, then universally optimal designs can be obtained. Li [31] used No1(t,t+) to denote the new class of designs, which consist of designs with one extra treatment to the last period in No1(t,t). For instance, a design in No1(3,3+) could be
One disadvantage of the universally optimal designs for
Li [31] showed some practical universally optimal designs for three-, four- and five-treatment in blocks of size 2. In each block, two different treatments are assigned such as a crossover pair. For
No1(3,2) with
No1(4,2+) for
and
No1(5,2) for
In this Chapter, we discussed and reviewed construction of universally optimal N-of-1 designs and how they may be aggregated to estimate treatment effects for the average patients. Originally, Kiefer [13] proposed the concept of universal optimality with zero row and column sums in the information matrices. We examined conditions when such universally optimal designs exist with special application to N-of-1 trial designs that will make them optimal no matter what criteria are applied. In particular, we first presented a sufficient condition that ensures N-of-1 designs are universally optimal for the traditional model that accommodates the carryover effects. Additionally, we discussed extensions of our work to finding optimal aggregated N-of-1 designs. Using numerical results from our simulation for comparing the estimated precision of several six- and eight-period designs, we were able to obtain realistic guidelines for the practitioners.
Overall, there are three key conclusions from this chapter. The first is that alternating between
Another take home message is that when an experiment has been carried out with the optimal N-of-1 trial and additional patients are accrued in the trial, we can aggregate these N-of-1 trials optimally by allocating the same number of patients to its dual sequence, thereby optimizing the trial for both the individual and average patients.
Lastly, we also provided a strategy for finding N-of-1 trials with more than 2 treatments. By restricting the class of designs and utilizing each subsequence, we constructed universally optimal N-of-1 trial designs when there are
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Various technical variants of this test can detect antigen (native or foreign) or antibody, determine the intensity of the immune response whether pathological or not; the type of induced immune response as well as the innate immunity potential; and much more. These capabilities, as well as the high sensitivity and robustness of the test and a small price, make it possible to quickly and reliably diagnose diseases in most laboratories. Besides, ELISA is a test that is also used in veterinary medicine, toxicology, allergology, food industry, etc. Despite the fact that it has existed for almost 50 years, different ELISA tests with different technical solutions are still being developed, which improves and expands the application of the this exceptional test. The aim of this chapter is to empower the rider to optimize, standardize and validate an enzyme linked immunosorbent assay.",book:{id:"9850",slug:"norovirus",title:"Norovirus",fullTitle:"Norovirus"},signatures:"Rajna Minic and Irena Zivkovic",authors:[{id:"325806",title:"Ph.D.",name:"Irena",middleName:null,surname:"Zivkovic",slug:"irena-zivkovic",fullName:"Irena Zivkovic"},{id:"325839",title:"Dr.",name:"Rajna",middleName:null,surname:"Minic",slug:"rajna-minic",fullName:"Rajna Minic"}]},{id:"56750",title:"Laboratory Approach to Anemia",slug:"laboratory-approach-to-anemia",totalDownloads:6255,totalCrossrefCites:2,totalDimensionsCites:4,abstract:"Anemia is a major cause of morbidity and mortality worldwide and can be defined as a decreased quantity of circulating red blood cells (RBCs). The epidemiological studies suggested that one-third of the world’s population is affected with anemia. Anemia is not a disease, but it is instead the sign of an underlying basic pathological process. However, the sign may function as a compass in the search for the cause. Therefore, the prediagnosis revealed by thorough investigation of this sign should be supported by laboratory parameters according to the underlying pathological process. We expect that this review will provide guidance to clinicians with findings and laboratory tests that can be followed from the initial stage in the anemia search.",book:{id:"5942",slug:"current-topics-in-anemia",title:"Current Topics in Anemia",fullTitle:"Current Topics in Anemia"},signatures:"Ebru Dündar Yenilmez and Abdullah Tuli",authors:[{id:"183998",title:"Ph.D.",name:"Ebru",middleName:null,surname:"Dündar Yenilmez",slug:"ebru-dundar-yenilmez",fullName:"Ebru Dündar Yenilmez"},{id:"209103",title:"Prof.",name:"Abdullah",middleName:null,surname:"Tuli",slug:"abdullah-tuli",fullName:"Abdullah Tuli"}]},{id:"33133",title:"Waist Circumference in Children and Adolescents from Different Ethnicities",slug:"waist-circumference-in-children-and-adolescents-from-different-ethnicities",totalDownloads:8023,totalCrossrefCites:4,totalDimensionsCites:7,abstract:null,book:{id:"642",slug:"childhood-obesity",title:"Childhood Obesity",fullTitle:"Childhood Obesity"},signatures:"Peter Schwandt and Gerda-Maria Haas",authors:[{id:"29867",title:"Prof.",name:"Peter",middleName:null,surname:"Schwandt",slug:"peter-schwandt",fullName:"Peter Schwandt"}]},{id:"54411",title:"Isolation and Characterization of Escherichia coli from Animals, Humans, and Environment",slug:"isolation-and-characterization-of-i-escherichia-coli-i-from-animals-humans-and-environment",totalDownloads:6182,totalCrossrefCites:5,totalDimensionsCites:8,abstract:"Working on a diverse species of bacteria that have hundreds of pathotypes representing hundreds of strains and many closely related family members is a challenge. Appropriate research design is required not only to achieve valid desired outcome but also to minimize the use of resources, including time to outcome and intervention. This chapter outlines basics of Escherichia coli isolation and characterization strategies that can assist in research designing that matches the set objectives. Types of samples to be collected, collection and storage strategies, and processing of samples are described. Different approaches to isolation, confirmation and concentration of various E. coli strains are summarized in this chapter. Characterization and typing of E. coli isolates by biochemical, serological, and molecular methods have been explained so that an appropriate choice is made to suite a specific E. coli strain/pathotype. Some clues on sample and isolate preservation for future use are outlined, and general precautions regarding E. coli handling are also presented to the researcher to avoid improper planning and execution of E. coli-related research. 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A pregnant woman has an increased risk (up to four times) of getting malaria and twice the chances of dying from malaria, compared to a non‐pregnant adult, becuase the immune system is partially suppressed during pregnancy. Malaria in pregnancy not only affects the mother but also has a dangerous sequel for the developing foetus, resulting in premature delivery or intrauterine growth retardation. Diagnosis of malaria in pregnancy remains a challenge due to the low parasite density and placental sequestration of Plasmodium falciparum. Thus, there is an urgent need for new diagnostic methods to detect malarial parasites in the pregnant women. Though antimalarial drugs are available, which can be safely given in the pregnancy, increasing drug resistance of malarial parasite may pose a big problem in the future. In this chapter, we review the burden of pregnancy‐associated malaria (PAM), its pathogenesis, diagnostic issues during pregnancy and recent guidelines for chemoprophylaxsis and treatment.",book:{id:"5270",slug:"current-topics-in-malaria",title:"Current Topics in Malaria",fullTitle:"Current Topics in Malaria"},signatures:"Kapil Goyal, Alka Sehgal, Chander S. 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The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"13",title:"Veterinary Medicine and Science",doi:"10.5772/intechopen.73681",issn:"2632-0517",scope:"Paralleling similar advances in the medical field, astounding advances occurred in Veterinary Medicine and Science in recent decades. 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A dynamic career research platform which is based on the thematic areas of comparative vertebrate physiology, stress endocrinology, reproductive endocrinology, animal health and welfare, and conservation biology. \nEdward has supervised 40 research students and published over 60 peer reviewed research.",institutionString:null,institution:{name:"University of Queensland",institutionURL:null,country:{name:"Australia"}}},editorTwo:null,editorThree:null},{id:"20",title:"Animal Nutrition",coverUrl:"https://cdn.intechopen.com/series_topics/covers/20.jpg",isOpenForSubmission:!0,editor:{id:"175967",title:"Dr.",name:"Manuel",middleName:null,surname:"Gonzalez Ronquillo",slug:"manuel-gonzalez-ronquillo",fullName:"Manuel Gonzalez Ronquillo",profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",biography:"Dr. Manuel González Ronquillo obtained his doctorate degree from the University of Zaragoza, Spain, in 2001. He is a research professor at the Faculty of Veterinary Medicine and Animal Husbandry, Autonomous University of the State of Mexico. He is also a level-2 researcher. He received a Fulbright-Garcia Robles fellowship for a postdoctoral stay at the US Dairy Forage Research Center, Madison, Wisconsin, USA in 2008–2009. He received grants from Alianza del Pacifico for a stay at the University of Magallanes, Chile, in 2014, and from Consejo Nacional de Ciencia y Tecnología (CONACyT) to work in the Food and Agriculture Organization’s Animal Production and Health Division (AGA), Rome, Italy, in 2014–2015. He has collaborated with researchers from different countries and published ninety-eight journal articles. He teaches various degree courses in zootechnics, sheep production, and agricultural sciences and natural resources.\n\nDr. Ronquillo’s research focuses on the evaluation of sustainable animal diets (StAnD), using native resources of the region, decreasing carbon footprint, and applying meta-analysis and mathematical models for a better understanding of animal production.",institutionString:null,institution:{name:"Universidad Autónoma del Estado de México",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null},{id:"28",title:"Animal Reproductive Biology and Technology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/28.jpg",isOpenForSubmission:!0,editor:{id:"177225",title:"Prof.",name:"Rosa Maria Lino Neto",middleName:null,surname:"Pereira",slug:"rosa-maria-lino-neto-pereira",fullName:"Rosa Maria Lino Neto Pereira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9wkQAC/Profile_Picture_1624519982291",biography:"Rosa Maria Lino Neto Pereira (DVM, MsC, PhD and) is currently a researcher at the Genetic Resources and Biotechnology Unit of the National Institute of Agrarian and Veterinarian Research (INIAV, Portugal). 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She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. 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He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:{name:"Association for Computing Machinery",country:{name:"United States of America"}}},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:"Manufacturing and Technology Integrated Campus – SENAI CIMATEC",institution:null},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:'"Politechnica" University Timişoara',institution:null},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"426586",title:"Dr.",name:"Oladunni A.",middleName:null,surname:"Daramola",slug:"oladunni-a.-daramola",fullName:"Oladunni A. Daramola",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Federal University of Technology",country:{name:"Nigeria"}}},{id:"357014",title:"Prof.",name:"Leon",middleName:null,surname:"Bobrowski",slug:"leon-bobrowski",fullName:"Leon Bobrowski",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Bialystok University of Technology",country:{name:"Poland"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"354126",title:"Dr.",name:"Setiawan",middleName:null,surname:"Hadi",slug:"setiawan-hadi",fullName:"Setiawan Hadi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Padjadjaran University",country:{name:"Indonesia"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"332603",title:"Prof.",name:"Kumar S.",middleName:null,surname:"Ray",slug:"kumar-s.-ray",fullName:"Kumar S. Ray",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Statistical Institute",country:{name:"India"}}},{id:"415409",title:"Prof.",name:"Maghsoud",middleName:null,surname:"Amiri",slug:"maghsoud-amiri",fullName:"Maghsoud Amiri",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Allameh Tabataba'i University",country:{name:"Iran"}}},{id:"357085",title:"Mr.",name:"P. Mohan",middleName:null,surname:"Anand",slug:"p.-mohan-anand",fullName:"P. Mohan Anand",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356696",title:"Ph.D. Student",name:"P.V.",middleName:null,surname:"Sai Charan",slug:"p.v.-sai-charan",fullName:"P.V. Sai Charan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"357086",title:"Prof.",name:"Sandeep K.",middleName:null,surname:"Shukla",slug:"sandeep-k.-shukla",fullName:"Sandeep K. Shukla",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}}]}},subseries:{item:{id:"18",type:"subseries",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11414,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. 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