Simulation result, Example 1.
\\n\\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\\n\\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\nFeel free to share this news on social media and help us mark this memorable moment!
\\n\\n\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/237"}},components:[{type:"htmlEditorComponent",content:'
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\nIntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\n\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\nFeel free to share this news on social media and help us mark this memorable moment!
\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"7617",leadTitle:null,fullTitle:"Electromagnetic Fields and Waves",title:"Electromagnetic Fields and Waves",subtitle:null,reviewType:"peer-reviewed",abstract:"In this book, a variety of topics related to electromagnetic fields and waves are extensively discussed. The topics encompass the physics of electromagnetic waves, their interactions with different kinds of media, and their applications and effects.",isbn:"978-1-78923-956-0",printIsbn:"978-1-78923-955-3",pdfIsbn:"978-1-83880-653-8",doi:"10.5772/intechopen.77420",price:119,priceEur:129,priceUsd:155,slug:"electromagnetic-fields-and-waves",numberOfPages:192,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"d87c09ddaa95c04479ffa2579e9f16d2",bookSignature:"Kim Ho Yeap and Kazuhiro Hirasawa",publishedDate:"May 15th 2019",coverURL:"https://cdn.intechopen.com/books/images_new/7617.jpg",numberOfDownloads:15054,numberOfWosCitations:12,numberOfCrossrefCitations:17,numberOfCrossrefCitationsByBook:1,numberOfDimensionsCitations:35,numberOfDimensionsCitationsByBook:1,hasAltmetrics:1,numberOfTotalCitations:64,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 6th 2018",dateEndSecondStepPublish:"September 27th 2018",dateEndThirdStepPublish:"November 26th 2018",dateEndFourthStepPublish:"February 14th 2019",dateEndFifthStepPublish:"April 15th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"126825",title:"Dr.",name:"Kim Ho",middleName:null,surname:"Yeap",slug:"kim-ho-yeap",fullName:"Kim Ho Yeap",profilePictureURL:"https://mts.intechopen.com/storage/users/126825/images/system/126825.jpeg",biography:"Kim Ho Yeap is an associate professor at Universiti Tunku Abdul Rahman, Malaysia. He is an Institute of Electrical and Electronics Engineers (IEEE) senior member, a professional engineer registered with the Board of Engineers, Malaysia, and a chartered engineer registered with the UK Engineering Council. He is the external examiner and external course assessor of Wawasan Open University. From 2017 to 2022, he was editor-in-chief of the Journal on Digital Signal Processing. He has also been a guest editor for the Journal of Applied Environmental and Biological Sciences and Journal of Fundamental and Applied Sciences. He has also been a recipient of the university teaching excellence award and twenty-too research grants. He has published more than 100 research articles in electromagnetics, including refereed journal papers, conference proceedings, books, and book chapters.",institutionString:"Universiti Tunku Abdul Rahman",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Universiti Tunku Abdul Rahman",institutionURL:null,country:{name:"Malaysia"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"268165",title:"Dr.",name:"Kazuhiro",middleName:null,surname:"Hirasawa",slug:"kazuhiro-hirasawa",fullName:"Kazuhiro Hirasawa",profilePictureURL:"https://mts.intechopen.com/storage/users/268165/images/system/268165.jpeg",biography:"Kazuhiro Hirasawa is a professor (Tsukuba University), Japan (2005–present), and an international collaborative partner (Universiti Tunku Abdul Rahman), Malaysia (2013–present). He received his BEng in 1964, his MEng in 1966 (Keio University), and his PhD in 1971 (Syracuse University). He was at the University of Tsukuba (1978–2005), Tokyo University of Agriculture and Technology (2005–2007), MIT (USA) (1991), and Institute for Infocomm Research (Singapore) (2002). He was an editor of the International Journal on Wireless and Optical Communications (2003–2007). He has published about 200 research articles (journal papers, international conference proceedings, books, book chapters, and US government reports) in electromagnetic waves and antennas. He is an IEEE Life Fellow. He obtained the best paper award at IEEE EMC International Symposium with Dr. Morioka (2010).",institutionString:"University of Tsukuba",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Institute of Electrical and Electronics Engineers",institutionURL:null,country:{name:"United States of America"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"737",title:"Electromagnetism",slug:"electrical-and-electronic-engineering-electromagnetism"}],chapters:[{id:"66104",title:"Introductory Chapter: Electromagnetism",doi:"10.5772/intechopen.85155",slug:"introductory-chapter-electromagnetism",totalDownloads:1188,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:null,signatures:"Kim Ho Yeap and Kazuhiro Hirasawa",downloadPdfUrl:"/chapter/pdf-download/66104",previewPdfUrl:"/chapter/pdf-preview/66104",authors:[{id:"126825",title:"Dr.",name:"Kim Ho",surname:"Yeap",slug:"kim-ho-yeap",fullName:"Kim Ho Yeap"},{id:"268165",title:"Dr.",name:"Kazuhiro",surname:"Hirasawa",slug:"kazuhiro-hirasawa",fullName:"Kazuhiro Hirasawa"}],corrections:null},{id:"65544",title:"Vacuum Microwave Sources of Electromagnetic Radiation",doi:"10.5772/intechopen.83734",slug:"vacuum-microwave-sources-of-electromagnetic-radiation",totalDownloads:1219,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This chapter contains new simulation results concerning the physical foundations of how microwave tubes operate based on Cherenkov’s mechanism of radiation (interaction with slow electromagnetic wave) and some experimental results connected with improving the output characteristics of the magnetrons (a mm band surface wave magnetron and a magnetron with two RF outputs of energy), as well as results of computer modeling of a 320-GHz band traveling wave tube (TWT). The results of analytical calculations and computer modeling, a phase bunching process in the mm band surface wave magnetron, are considered. It is shown that the process of phase focusing has two features associated with a concentration of RF wave energy close to the vanes of an anode block and higher electron hub of a space charge as compared to the classical magnetrons. The features and examples of practical application of the magnetron with two RF outputs of energy are presented. It is shown that the main advantage of the magnetrons is its extended functionalities (for example, possibility of frequency tuning including electronic tuning of a frequency from a pulse to pulse). The presented materials will be of interest not only for starting researchers but also for those who have microwave tube experience.",signatures:"Gennadiy Churyumov, Jinghui Qiu and Nannan Wang",downloadPdfUrl:"/chapter/pdf-download/65544",previewPdfUrl:"/chapter/pdf-preview/65544",authors:[{id:"18100",title:"Prof.",name:"Jinghui",surname:"Qiu",slug:"jinghui-qiu",fullName:"Jinghui Qiu"},{id:"216155",title:"Prof.",name:"Gennadiy I.",surname:"Churyumov",slug:"gennadiy-i.-churyumov",fullName:"Gennadiy I. Churyumov"},{id:"282701",title:"Dr.",name:"Nannan",surname:"Wang",slug:"nannan-wang",fullName:"Nannan Wang"}],corrections:null},{id:"64949",title:"Design of Radial Power Combiners Based on TE 01 Circular Waveguide Mode",doi:"10.5772/intechopen.82840",slug:"design-of-radial-power-combiners-based-on-te-01-circular-waveguide-mode",totalDownloads:1563,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Modern microwave and millimeter-wave systems require high-power amplifiers in very diverse fields such as communications or plasma physics. Although amplification technology has significantly evolved in the last decades, a single module is not enough for achieving the required power level. The solution in this case is the combination of several individual modules with power combiners. In this chapter, this concept is shown with two E-plane radial power combiners, both carrying a high-power signal with the circular waveguide TE01 mode. The first design is a 16-way Ku-band combiner with an excellent experimental performance: return loss better than 30 dB, with a balance for the amplitudes of ±0.15 dB and ±2.5o for the phases, in a 16.7% fractional bandwidth (2 GHz centered at 12 GHz), and efficiency better than 95% in this band. The second design is a 5-way W-band combiner, showing excellent characteristics as well: the experimental prototype has a return loss better than 20 dB, with a balance for the amplitudes of ±0.4 dB and ±3.5o for the phases, in a 12.8% fractional bandwidth (12 GHz centered at 94 GHz), and efficiency better than 85% in this whole band. The experimental results obtained in both designs are the state of the art in the area of radial power combiners.",signatures:"José R. Montejo-Garai, Jorge A. Ruiz-Cruz and Jesús M. Rebollar",downloadPdfUrl:"/chapter/pdf-download/64949",previewPdfUrl:"/chapter/pdf-preview/64949",authors:[{id:"4535",title:"Dr.",name:"Jorge A.",surname:"Ruiz-Cruz",slug:"jorge-a.-ruiz-cruz",fullName:"Jorge A. Ruiz-Cruz"},{id:"124755",title:"Prof.",name:"José",surname:"Montejo-Garai",slug:"jose-montejo-garai",fullName:"José Montejo-Garai"},{id:"124756",title:"Prof.",name:"Jesus",surname:"Rebollar",slug:"jesus-rebollar",fullName:"Jesus Rebollar"}],corrections:null},{id:"65168",title:"Energy Transfer from Electromagnetic Fields to Materials",doi:"10.5772/intechopen.83420",slug:"energy-transfer-from-electromagnetic-fields-to-materials",totalDownloads:1876,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Electromagnetic fields are complex phenomena, which transport energy and information across space. Information can be imposed onto electromagnetic waves by human ingenuity, through various forms of modulation; however, this chapter will focus on the acquisition of information as electromagnetic waves are generated by materials or pass through materials. The chapter will also consider how energy is transferred to materials by electromagnetic fields.",signatures:"Graham Brodie",downloadPdfUrl:"/chapter/pdf-download/65168",previewPdfUrl:"/chapter/pdf-preview/65168",authors:[{id:"14683",title:"Dr.",name:"Graham",surname:"Brodie",slug:"graham-brodie",fullName:"Graham Brodie"}],corrections:null},{id:"65958",title:"Two Systems of Maxwell’s Equations and Two Corresponding Systems of Wave Equations in a Rotating Dielectric Medium",doi:"10.5772/intechopen.82595",slug:"two-systems-of-maxwell-s-equations-and-two-corresponding-systems-of-wave-equations-in-a-rotating-die",totalDownloads:910,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In this chapter, on the base of two basic systems of Maxwell’s equations for electromagnetic field vectors E→ and B→ in a uniformly rotating dielectric medium, the two corresponding systems of wave equations have been derived (to the first order in an angular velocity Ω). From their comparative analysis, it can be seen that the structure of the wave equations for electromagnetic field vectors in the first system is asymmetrical with respect to Ω, while the structure of such equations in the second one is symmetrical. On this basis, it can be concluded that if the principle of symmetry is accepted as a criterion for selection, then second system of wave equations (and, therefore, corresponding the second set of Maxwell’s equations) for vectors E→ and B→ may be preferred.",signatures:"Evgeny A. Bondarenko",downloadPdfUrl:"/chapter/pdf-download/65958",previewPdfUrl:"/chapter/pdf-preview/65958",authors:[{id:"279165",title:"Dr.",name:"Evgeny",surname:"Bondarenko",slug:"evgeny-bondarenko",fullName:"Evgeny Bondarenko"}],corrections:null},{id:"66294",title:"The Interaction of Microwaves with Materials of Different Properties",doi:"10.5772/intechopen.83675",slug:"the-interaction-of-microwaves-with-materials-of-different-properties",totalDownloads:3424,totalCrossrefCites:5,totalDimensionsCites:10,hasAltmetrics:1,abstract:"Electromagnetic radiation, such as microwaves, are all the time reflected, transmitted, and/or absorbed by any kind of matter, glasses, conductors, water, ferrites, and so forth. Magnetic materials absorb greatly microwaves. The more magnetic, the more microwaves are absorbed. The aim of this chapter is to present the fundamental physics of the absorption of microwave power (energy per unit time) by ferrimagnetic and ferromagnetic matter in the nano and micro size scale. The magnetic moments and their collective modes are the basic microscopic absorbers under in-resonance and out-of-resonance conditions. Experimental setups and measurement techniques are described. The profiles of microwave absorption are described and connected to the micromagnetic environment that elicits such absorption. Section by section and the overall microwave power absorption profiles are related to the micromagnetic structures. Emphasis is made on nano- and micromagnets. These interactions of microwaves with nano- and micromagnets serve to infer microscopic magnetic information.",signatures:"Rafael Zamorano Ulloa, Ma. Guadalupe Hernandez Santiago\nand Veronica L. Villegas Rueda",downloadPdfUrl:"/chapter/pdf-download/66294",previewPdfUrl:"/chapter/pdf-preview/66294",authors:[{id:"176210",title:"Dr.",name:"Rafael",surname:"Zamorano Ulloa",slug:"rafael-zamorano-ulloa",fullName:"Rafael Zamorano Ulloa"},{id:"289450",title:"Mrs.",name:"María G.",surname:"Hernández",slug:"maria-g.-hernandez",fullName:"María G. Hernández"},{id:"289451",title:"Ms.",name:"Verónica L.",surname:"Villegas",slug:"veronica-l.-villegas",fullName:"Verónica L. Villegas"}],corrections:null},{id:"65654",title:"Electromagnetic Field Interaction with Metamaterials",doi:"10.5772/intechopen.84170",slug:"electromagnetic-field-interaction-with-metamaterials",totalDownloads:1623,totalCrossrefCites:4,totalDimensionsCites:10,hasAltmetrics:0,abstract:"It is well known that constitutive parameters, namely, the electrical permittivity, ε, and the magnetic permeability, μ, in a medium determine the response and reaction of such medium or material when exposed to external time-varying electromagnetic fields. Furthermore, most materials are lossy and dispersive, that is, both permittivity and permeability are complex and frequency-dependent. Interestingly, by controlling the sign of real parts of ε and μ in a medium, unique electromagnetic properties can be achieved that are not readily available in nature. Recently, subwavelength composite engineered structures, also known as metamaterials, have evolved in many engineering and optical applications, due to their unique electromagnetic properties that are not found in nature, including but not limited to negative refractive index, backward wave propagation, subwavelength focusing and super lenses, and invisibility cloaking. The main aims of this chapter are to provide an overview of electromagnetic field behavior and interaction with metamaterials and to explore such behavior in various metamaterials both analytically and numerically.",signatures:"Mohammed M. Bait-Suwailam",downloadPdfUrl:"/chapter/pdf-download/65654",previewPdfUrl:"/chapter/pdf-preview/65654",authors:[{id:"188899",title:"Dr.",name:"Mohammed",surname:"Bait-Suwailam",slug:"mohammed-bait-suwailam",fullName:"Mohammed Bait-Suwailam"}],corrections:null},{id:"65910",title:"Metamaterial: Smart Magnetic Material for Microwave Absorbing Material",doi:"10.5772/intechopen.84471",slug:"metamaterial-smart-magnetic-material-for-microwave-absorbing-material",totalDownloads:1871,totalCrossrefCites:4,totalDimensionsCites:8,hasAltmetrics:0,abstract:"Metamaterial is an artificial, advanced material that has properties such as electromagnetic waves (EM), namely isotropic materials with permittivity and permeability in a single phase at a certain frequency. Smart magnetics is one of the metamaterials that is a modified magnetic material that has a single-phase permeability and permittivity as a function of frequency depending on the type of magnetic material used. Smart magnetics in this study include perovskite, ferrite, hexagonal ferrite, and composite systems. Research that has been carried out on perovskite, ferrite, hexagonal ferrite and composite smart magnetic system materials are La0.8Ba0.2FexMn½(1-x)Ti½(1-x)O3, NixFe3-xO4, and Ba(1-x)SrxFe2O4, Ba0.6Sr0.4Fe12-zMnzO19 and composite silicon rubber—iron oxide. The four smart magnetic material systems have an average microwave absorption in the X-band frequency range. Very varied reflection loss characteristics depend on the smart magnetic material system formed. It was concluded that smart magnetic material is a microwave absorbent that has reflection loss values in the X-band frequency range. Smart magnetic material is certainly not able to absorb microwaves on all band frequencies because each smart magnetic material has different resonance characteristics, so the maximum effort that can be done is to find the right composition of smart magnetic material which is expected to have the maximum wave absorption capability.",signatures:"Wisnu Ari Adi, Yunasfi Yunasfi, Mashadi Mashadi, Didin Sahidin Winatapura,\nAde Mulyawan, Yosef Sarwanto, Yohanes Edi Gunanto and Yana Taryana",downloadPdfUrl:"/chapter/pdf-download/65910",previewPdfUrl:"/chapter/pdf-preview/65910",authors:[{id:"266181",title:"Dr.",name:"Wisnu",surname:"Adi",slug:"wisnu-adi",fullName:"Wisnu Adi"},{id:"295417",title:"Dr.",name:"Didin Sahidin",surname:"Winatapura",slug:"didin-sahidin-winatapura",fullName:"Didin Sahidin Winatapura"},{id:"295418",title:"Dr.",name:"Ade",surname:"Mulyawan",slug:"ade-mulyawan",fullName:"Ade Mulyawan"},{id:"295419",title:"Dr.",name:"Yosef",surname:"Sarwanto",slug:"yosef-sarwanto",fullName:"Yosef Sarwanto"},{id:"295420",title:"Dr.",name:"Yohanes Edi",surname:"Gunanto",slug:"yohanes-edi-gunanto",fullName:"Yohanes Edi Gunanto"},{id:"295421",title:"Dr.",name:"Yana",surname:"Taryana",slug:"yana-taryana",fullName:"Yana Taryana"},{id:"295430",title:"Dr.",name:"Yunasfi",surname:"Yunasfi",slug:"yunasfi-yunasfi",fullName:"Yunasfi Yunasfi"},{id:"295431",title:"Dr.",name:"Mashadi",surname:"Mashadi",slug:"mashadi-mashadi",fullName:"Mashadi Mashadi"}],corrections:null},{id:"66579",title:"Effects of Electromagnetic Field on the Development of Chick Embryo: An In Vivo Study",doi:"10.5772/intechopen.84704",slug:"effects-of-electromagnetic-field-on-the-development-of-chick-embryo-an-in-vivo-study",totalDownloads:1387,totalCrossrefCites:3,totalDimensionsCites:3,hasAltmetrics:0,abstract:"This study was conducted to explore the effects of electromagnetic waves on a developing chick embryo. The radiofrequency electromagnetic waves (RFW) emitted by different smart phones was measured by using a TriField meter. Chick fertilized eggs were placed in an egg incubator, divided into control and exposed groups. In the exposed group, a mobile phone was placed inside an incubator in call receiving mode, while in the control group, the mobile phone was not used. Studies were conducted at low and high exposure (dose) of RFW. Chick embryos were sacrificed at day 10 and day 15, and embryos were examined for mortality, gross malformation, weight, and length. Histology, electron microscopy, and Hsp 70 of liver were done for the high dose group. No mortality was observed in the low dose group; however, in the high dose group, the mortality was 14%, and deformities of the limbs and skin abnormalities were observed. Weight and length in the exposed groups were significantly lower than the control at higher dose. Histology and ultrastructure of liver revealed fatty infiltration, increase number of mitochondria, deformation, and disappearance of its cristae. Hsp 70 and mRNA levels were elevated in the exposed groups for high dose group.",signatures:"Najam Siddiqi and Nasser Al Nazwani",downloadPdfUrl:"/chapter/pdf-download/66579",previewPdfUrl:"/chapter/pdf-preview/66579",authors:[{id:"278673",title:"Dr.",name:"Najam",surname:"Siddiqi",slug:"najam-siddiqi",fullName:"Najam Siddiqi"},{id:"291777",title:"Prof.",name:"Nasser",surname:"Al Nazwani",slug:"nasser-al-nazwani",fullName:"Nasser Al Nazwani"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"83",title:"Properties and Applications of Silicon Carbide",subtitle:null,isOpenForSubmission:!1,hash:"7e94cc189847633076ad5b2d23117c2f",slug:"properties-and-applications-of-silicon-carbide",bookSignature:"Rosario Gerhardt",coverURL:"https://cdn.intechopen.com/books/images_new/83.jpg",editedByType:"Edited by",editors:[{id:"19005",title:"Prof.",name:"Rosario",surname:"Gerhardt",slug:"rosario-gerhardt",fullName:"Rosario Gerhardt"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"166",title:"Electromagnetic Waves",subtitle:null,isOpenForSubmission:!1,hash:"6561a39a2e8aaffc6cde23ecd65cdfde",slug:"electromagnetic-waves",bookSignature:"Vitaliy Zhurbenko",coverURL:"https://cdn.intechopen.com/books/images_new/166.jpg",editedByType:"Edited by",editors:[{id:"3721",title:"Prof.",name:"Vitaliy",surname:"Zhurbenko",slug:"vitaliy-zhurbenko",fullName:"Vitaliy Zhurbenko"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2431",title:"Dielectric Material",subtitle:null,isOpenForSubmission:!1,hash:"70942e6b7ab8fb1bfa75537709d3910d",slug:"dielectric-material",bookSignature:"Marius Alexandru Silaghi",coverURL:"https://cdn.intechopen.com/books/images_new/2431.jpg",editedByType:"Edited by",editors:[{id:"128198",title:"Dr.",name:"Marius Alexandru",surname:"Silaghi",slug:"marius-alexandru-silaghi",fullName:"Marius Alexandru Silaghi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3706",title:"Wave Propagation in Materials for Modern Applications",subtitle:null,isOpenForSubmission:!1,hash:null,slug:"wave-propagation-in-materials-for-modern-applications",bookSignature:"Andrey Petrin",coverURL:"https://cdn.intechopen.com/books/images_new/3706.jpg",editedByType:"Edited by",editors:[{id:"7760",title:"Dr.",name:"Andrey",surname:"Petrin",slug:"andrey-petrin",fullName:"Andrey Petrin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1647",title:"Trends in Electromagnetism",subtitle:"From Fundamentals to Applications",isOpenForSubmission:!1,hash:"2c0ce5e84f67194c32ed9659512218c3",slug:"trends-in-electromagnetism-from-fundamentals-to-applications",bookSignature:"Victor Barsan and Radu P. 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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"}}]},chapter:{item:{type:"chapter",id:"69832",title:"Conjugate Gradient Approach for Discrete Time Optimal Control Problems with Model-Reality Differences",doi:"10.5772/intechopen.89711",slug:"conjugate-gradient-approach-for-discrete-time-optimal-control-problems-with-model-reality-difference",body:'\nOptimal control problems are existing in engineering and natural sciences for so long, and the applications of the optimal control have been well defined in the literature [1, 2, 3, 4]. With the rapid evolution of computer technology, the development of the optimal control techniques is reached a mature level, from classical control to modern control, from proportional-integral-derivative (PID) control to feedback control, and from adaptive control to intelligent control [5, 6, 7, 8]. The studies in the optimal control field are still progressing, and attract the interest of, not only engineers and applied mathematicians but also biologists and financialists, to investigate and contribute to the optimal control theory.
\nIn particular, the optimal control algorithm, which integrates system optimization and parameter estimation, gives a new insight into the control community. This algorithm is known as the integrated system optimization and parameter estimation (ISOPE), and its dynamic version is called the dynamic ISOPE (DISOPE). Both of these algorithms were introduced by Robert [9, 10, 11], and Robert and Becerra [12, 13, 14], respectively. The basic idea of DISOPE is applying the model-based optimal control, which has different structures and parameters compared to the original optimal control problem, to obtain the correct optimal solution of the original optimal control problem, in spite of model-reality differences. Recently, this algorithm has been extended to cover both deterministic and stochastic versions, and it is known as an integrated optimal control and parameter estimation (IOCPE) algorithm [15, 16]. On the other hand, the application of the optimization techniques, particularly, using the conjugate gradient method for solving the optimal control problem [17, 18, 19] has also been studied, where the open-loop control strategy is concerned [3, 8].
\nIn this chapter, the conjugate gradient approach [17, 19] is employed to solve the linear model-based optimal control problem for obtaining the optimal solution of the original optimal control problem. In our approach, the simplified model, which is adding the adjusted parameters, is formulated initially. Then, an expanded optimal control problem, which combines the system dynamic and the cost function from the original optimal control problem into the simplified model, is introduced. By defining the Hamiltonian function and the augmented cost function, the corresponding necessary conditions for optimality are derived. Among these necessary conditions, a set of necessary conditions is for the modified model-based optimal control problem, a set of necessary conditions defines the parameter estimation problem, and a set of necessary conditions calculates the multipliers [15].
\nBy virtue of the modified model-based optimal control problem, an equivalence optimization problem is defined, and the related gradient function is determined. With an initial control sequence, the initial gradient and the initial search direction are computed. Then, the control sequences are updated through the line search technique, where the gradient and search direction would satisfy the conjugacy condition [17, 18]. During the iteration, the state and the costate are updated by the control sequence obtained from the conjugate gradient approach. When the convergence is achieved within a tolerance given, the iterative solution approximates to the correct optimal solution of the original optimal control problem, in spite of model-reality differences. For illustration, examples of linear and nonlinear cases, which are damped harmonic oscillator [7] and continuous stirred-tank chemical tank [8], are studied.
\nThe chapter is organized as follows. In Section 2, the problem statement is described in detail, where the original optimal control problem and the simplified model are discussed. In Section 3, the methodology used is further explained. The necessary conditions for optimality are derived, and the use of the conjugate gradient method is delivered in solving the equivalence optimization problem. In Section 4, examples of a damped harmonic oscillator and a continuous stirred-tank chemical reactor are studied. The results show the efficiency of the algorithm proposed. Finally, concluding remarks are made.
\nConsider a general class of the discrete-time nonlinear optimal control problem, given by
\nwhere \n
This problem, which is referred to as Problem (P), is regarded as the real optimal control problem. Due on the complex and nonlinear structure, solving Problem (P) actually requires the efficient computation techniques. For this reason, the simplified model of Problem (P) is identified to be solved such that the true optimal solution of Problem (P) could be approximated. Hence, this simplified model-based optimal control problem is defined as follows:
\nwhere \n
Let this problem is referred to as Problem (M). It can be seen that, because of the different structures and parameters, only solving Problem (M) would not obtain the optimal solution of Problem (P) for not taking the adjusted parameters into account. Notice, adding the adjusted parameters into Problem (M) could let us calculate the differences between the real plant and the model used. On this basis, Problem (M) would be solved iteratively to give the correct optimal solution of Problem (P), in spite of model-reality differences.
\nNow, an expanded optimal control problem, which combines the real plant and the cost function in Problem (P) into Problem (M) and is referred to as Problem (E), is introduced by
\nwhere \n
Define the Hamiltonian function for Problem (E), given by:
\nwhere \n
where \n
Applying the calculus of variation [7, 9, 11, 13, 15] to the augmented cost function in (5), the following necessary conditions for optimality are obtained:
\n(a) Stationary condition:
\n(b) Co-state equation:
\n(c) State equation:
\n(d) Boundary conditions:
\n(e) Adjusted parameter equations:
\n(f) Modifier equations:
\nwith \n
(g) Separable variables:
\nNotice that for the optimality necessary conditions obtained above, they are divided into three sets of necessary conditions. The first set of necessary conditions in (6)–(9) is the necessary conditions for the system optimization problem. The second set of necessary conditions in (10)–(12) defines the parameter estimation problem. The third set of necessary conditions in (13)–(15) provides the computation of multipliers. In fact, the necessary conditions, which are defined in (6)–(9), are the optimality for the modified model-based optimal control problem, and the adjusted parameters, which are calculated from the necessary conditions in (10)–(12), measure the differences between the real plant and the model used.
\nAs a consequence, the modified model-based optimal control problem, which is referred to as Problem (MM), is defined by
\nwith the specified \n
It is obvious that Problem (MM), which is derived from Problem (E), is a modification of optimal control problem and is also known as a modified linear quadratic regular problem. Importantly, the set of the necessary conditions in (6)–(9) for Problem (E) is the necessary conditions that are satisfied by Problem (MM). In addition, due to the quadratic criterion feature of the objective function, the conjugate gradient method [17, 18], which is one of the numerical optimization techniques, could be applied to solve Problem (MM).
\nFor simplicity [19], establish Problem (MM) as a nonlinear optimization problem with the initial control given by \n
Let this problem as Problem (Q). Moreover, the Hamiltonian function defined in (4) is taken into consideration as an equivalent objective function. Hence, this Hamiltonian function allows the evaluation of the gradient function, which is the stationary condition in (6), and by using the iterative solution \n
Define the gradient function \n
which is represented by the stationary condition in (6). For arbitrary initial control \n
The following line search equation is applied to update the control sequence:
\nwhere \n
After that, the gradient and the search direction are updated by
\nwith
\nfor
From the discussion above, we present the result as a proposition given as follows:
\nProposition 1.
\n
The conjugate gradient algorithm is summarized below:
\nData: Choose the arbitrary initial control \n
Step 0: Compute the initial gradient \n
Step 1: Solve the state Eq. (8) forward in time from \n
Step 2: Solve the costate Eq. (7) backward in time from \n
Step 3: Calculate the value of the cost functional \n
Step 4: Solve (23) to obtain the step size \n
Step 5: Calculate the control \n
Step 6: Evaluate the gradient \n
Step 0 is the preliminary step for setting the initial search direction based on the gradient direction in using the conjugate gradient algorithm.
Steps 1, 2, and 3 are performed to solve the system optimization by using the corresponding control sequence \n
Steps 4, 5, and 6 are the computation steps in implementing the conjugate direction.
Accordingly, Problem (Q) is solved by using the conjugate gradient algorithm. Indeed, the solution procedure for system optimization with parameter estimation could be described by joining the conjugate gradient algorithm with the parameters estimated. A summary of the calculation procedure including the principle of model-reality differences is listed as follows:
\nData: \n
Step 0: Compute a nominal solution. Assume that \n
Step 1: Compute the parameters \n
Step 2: Compute the modifiers \n
Step 3: With \n
Step 4: Test the convergence and update the optimal solution of Problem (P). In order to provide a mechanism for regulating convergence, a simple relaxation method is employed:
\nwhere \n
In Step 0, the nominal solution could be obtained by using the standard procedure of the linear quadratic regulator approach, where the feedback gain and the Riccati equation are calculated offline.
In Step 3, applying the conjugate gradient algorithm to obtain the new control sequence will give a good effect if the conjugacy of the search direction is satisfied.
In Step 4, the simple relaxation method in (27)–(29) is used, so that the matching scheme for the parameters and the optimal solution can be established.
In this section, two examples are studied. The first example is for optimizing and controlling a damped harmonic oscillator [7], and the second example is related to optimal control of a continuous stirred-tank chemical reactor [8]. The mathematical models of these examples are discussed, and their optimal solution is obtained by using the algorithm discussed in Section 3. Here, the algorithm is implemented in the Octave 5.1.0 environment.
\nConsider a damped harmonic oscillator [7] given by
\nwith the natural frequency \n
is minimized. This problem is a continuous-time linear optimal control problem, and the equivalence discrete time optimal control problem, which is regarded as Problem (P), is given by:
\nwith the initial state \n
Consider the model-based optimal control problem, which is regarded as Problem (M), given by:
\nwith the initial state \n
By using the algorithm proposed, the simulation result is shown in Table 1. Notice that the minimum cost for Problem (M) is 546.05 units without adding the adjusted parameters. Once the adjusted parameters are taken into consideration, the iterative solution approximates to the true optimal solution of the original optimal control problem, in spite of model-reality differences. It is highlighted that there is a 99% of the cost reduction to obtain the final cost of 128.50 units.
\nNumber of iteration | \nInitial cost | \nFinal cost | \nElapsed time (s) | \n
---|---|---|---|
20 | \n17053.11 | \n128.50 | \n1.38021 | \n
Simulation result, Example 1.
\nFigures 1 and 2 show the trajectories of control and state, respectively. With this control effort, the state reaches at the steady state after 4 units of time, which presents the oscillator stopped from moving. Figure 3 shows the changes of the costate at the first 2 units of time. The optimal solution obtained is verified by satisfying the stationary condition as shown in Figure 4. Figures 5 and 6 show the adjusted parameters after the convergence is achieved, where the model-reality differences are measured during the iterative procedure.
\nFinal control u(k), Example 1.
Final state x(k), Example 1.
Final costate p(k), Example 1.
Stationary Hu(k), Example 1.
Adjusted parameter α(k), Example 1.
Adjusted parameter γ(k), Example 1.
Therefore, this damped harmonic oscillator is controlled, and the cost function is minimized as desired.
\nConsider a continuous stirred-tank chemical reactor, which consists of two state equations [8]. The flow of a coolant through a coil inserted in the reactor is to control the first order, irreversible exothermic reaction taking place in the reactor. Assume that \n
with the initial state \n
Here, the desired objective is to maintain the temperature and the concentration close to their respective steady-state values without expending large amounts of the control effort.
\nThis problem is a continuous time nonlinear optimal control problem. For doing the discretization transform, the sampling time \n
with the initial state \n
By applying the algorithm proposed to obtain the optimal solution for Problem (P), the following model, which is referred to as Problem (M), is introduced,
\nwith the initial state \n
\nTable 2 shows the simulation result obtained by using the algorithm proposed. It is mentioned that the minimum cost for the linear model-based optimal control problem is 5.9589 units. At the beginning of the iteration calculation procedure, the initial cost is 0.147463 unit, and a 90% of cost reduction is addressed to give the final cost of 0.014167 unit.
\nNumber of iteration | \nInitial cost | \nFinal cost | \nElapsed time (s) | \n
---|---|---|---|
9 | \n0.147463 | \n0.014167 | \n4.60934 | \n
Simulation result, Example 2.
The trajectories of the final control and the final state are, respectively, shown in Figures 7 and 8. It is noted that the state reaches to the steady state after 40 units of time by associating the control effort taken. This situation indicates that the temperature and the concentration are maintained at their steady state. Thus, the desired objective is confirmed. Figure 9 shows the costate behavior, which is reduced gradually to zero at the terminal time, and Figure 10 shows the stationary condition, which examines the existing of the optimal solution. The adjusted parameters, which are shown in Figures 11 and 12, respectively, measure the differences between the model used and the real plant.
\nFinal control u(k), Example 2.
Final state x(k), Example 2.
Final costate p(k), Example 2.
Stationary Hu(k), Example 2.
Adjusted parameter α(k), Example 2.
Adjusted parameter γ(k), Example 2.
Hence, the correct optimal solution of Problem (P) is approximated successfully by solving the model in Problem (M), and the efficiency of the algorithm proposed is demonstrated.
\nThe approach, which integrates system optimization and parameter estimation, was discussed in this chapter. The use of the conjugate gradient method in solving the model-based optimal control problem has been examined, and the applicability of the conjugate gradient approach in associating the principle of model-reality differences was identified. Definitely, many computational approaches could be used to solve the model-based optimal control; however, the algorithm proposed in this chapter gives a tractable solution procedure for handling the optimal control problems with different structures and parameters, especially for obtaining the optimal solution for the nonlinear optimal control problem. In conclusion, the efficiency of the algorithm is highly recommended. In future research, it is strongly suggested to investigate the application of optimization techniques in stochastic optimization and control.
\nThe authors would like to acknowledge the Universiti Tun Hussein Onn Malaysia (UTHM) and the Ministry of Higher Education (MOHE) for the financial support for this study under the research grant FRGS VOT. 1561.
\nThe authors declare no conflict of interest.
Chronic myeloproliferative disorders are a group of clonal diseases of the stem cell. It is a group of several diseases with some common features. They derive from a multipotential hematopoietic stem cell. A clone of neoplastic cells in all these neoplams is characterized by a lower proliferative activity than that of acute myeloproliferative diseases. In each of these diseases, leukocytosis, thrombocythemia, and polyglobulia may appear at some stage, depending on the diagnosis [1, 2].
The research on interferon has been going on since the 1950s [3]. Then, the attention was paid to its influence on the immune system. It has been noted that it can exert an antiproliferative effect by stimulating cells of the immune system [4]. In 1987, a publication by Ludwig et al. was published, which reported the effectiveness of interferon alpha in the treatment of chronic myeloproliferative disorders [5].
More and more new studies have been showing the effectiveness of interferon alpha in reducing the number of platelets, reducing the need for phlebotomies in patients with polycythemia vera and also in reducing the number of leukocytes. Moreover, interferon reduced the symptoms of myeloproliferative disorders such as redness and itching of the skin. Additionally, it turned out to be effective in reducing the size of the spleen.
Further studies on the assessment of remission using molecular-level response assessments indicate that the interferon action in chronic myeloproliferation diseases targets cells from the mutant clone with no effect on normal bone marrow cells [6].
Over the years, interferon alpha-2a and interferon alpha-2b have been introduced into the treatment of chronic myeloproliferation, followed by their pegylated forms. The introduction of pegylated forms allowed for a reduction in the number of side effects and less frequent administration of the drug to patients. In recent years, monopegylated interferon alpha-2b has been used to further increase the interval between drug administrations while maintaining its antiproliferative efficacy.
The exact mechanism of action of interferon alpha in the treatment of chronic myeloproliferative disease is still not fully understood, but it has an impact on JAK2 (Janus Kinase) signal transducers and activates the STAT signal pathway (Janus Kinase/SignalTransducer and Activator of Transcription).
Interferon alpha binds to IFNAR1 and IFNAR2c, which are type I interferon receptors. Interferon alpha has an impact on JAK2(Janus Kinase) signal transducers and activates the STAT signal pathway. The disturbances in this signaling pathway are observed in chronic myeloproliferative disorders [7].
Interferon inhibits the JAK-STAT signaling pathway by directly inhibiting the action of thrombopoietin in this pathway [8].
So far, three driver mutations have been described in the course of chronic myeloproliferative diseases that affect the functioning of the JAK-STAT pathway.
JAK2 kinase and JAK1, JAK3, and TYK2 kinases belong to the family of non-receptor tyrosine kinases. They are involved in the intracellular signal transduction of the JAK-STAT pathway. It is a system of intracellular proteins used by growth factors and cytokines to express genes that regulate cell activation, proliferation, and differentiation. The mechanism of JAK activation is based on the autophosphorylation of tyrosine residues that occurs after ligand binds to the receptor. JAK2 kinase transmits signals from the hematopoietic cytokine receptors of the myeloid lineage (erythropoietin, granulocyte-colony stimulating factor thrombopoietin, and lymphoid lineage [9].
A somatic G/T point mutation in exon 14 of the JAK2 kinase gene converts valine to phenylalanine at position 617 (V617F) in the JAK2 pseudokinase domain, which allows constitutive, ligand-independent activation of the receptor to trigger a proliferative signal [10].
Mutation of the MPL gene, which encodes the receptor for thrombopoietin, increases the sensitivity of magekaryocytes to the action of thrombopoietin, which stimulates their proliferation [11].
Malfunction of calreticulin as a result of mutation of the CARL gene leads to the activation of the MPL-JAK/STAT signaling pathway, which is independent of the ligand, as calreticulin is responsible, for the proper formation of the MPL receptor. Consequently, there is a clonal proliferation of hematopoietic stem cells [12].
Below, we provide an overview of some clinical studies on the efficacy of interferon in chronic myeloproliferative disorders.
Polycythemia vera (PV) is characterized by an increase in the number of erythrocytes in the peripheral blood.
Polycythemia vera is caused by a clonal mutation in the multipotential hematopoietic stem cell of the bone marrow. The mutation leads to an uncontrolled proliferation of the mutated cell clone, independent of erythropoietin and other regulatory factors. As the mutation takes place at an early stage of hematopoiesis, an increase of the number of erythrocytes as well as of leukocytes and platelets is observed in the peripheral blood. The cause of proliferation in PV independent from external factors is a mutation in the Janus 2 (JAK2) tyrosine kinase gene. The V617F point mutation in the JAK2 gene is responsible for about 96% mutation, and in the remaining cases the mutation arises in exon 12. Both mutations lead to constitutive activation of the JAK-STAT signaling pathway [13].
As a result of the uncontrolled proliferation, blood viscosity increases, which generates symptoms such as headaches and dizziness, visual disturbances, or erythromelalgia. As the number of all hematopoietic cells, including the granulocytes ones, increases, the difficult to control symptoms of their hyperdegranulation may appear, among which gastric ulcer or skin itching is often observed. During the disease progression, the spleen and liver become enlarged.
The most common complication of the disease is episodes of thrombosis, especially arterial one. During the course of the disease, it can also evolve into myelofibrosis or acute myeloid leukemia.
The treatment of PV is aimed at preventing thromboembolic complications, relieving the general symptoms, the appearance of hepatosplenomegaly as well as preventing its progression.
Each patient should receive an antiplatelet drug chronically, and usually acetylsalicylic acid is the choice. Most often, the treatment is started with phlebotomy in order to rapidly lower the hematocrit level. If cytoreductive therapy is necessary, the drugs of first choice are hydroxycarbamide and interferon [2].
However, the research on the mechanism of the action of interferons is still ongoing. In vitro studies with CD34+ cells from peripheral blood of patients diagnosed with polycythemia vera showed that interferon inhibits clonal changed cells selectively. It was found that interferon alpha-2b and pegylated interferon alpha-2a reduce the percentage of cells with JAK2 V617F mutation by about 40%. Pegylated interferon alpha-2a works by activating mitogen-activated protein kinase P38. It affects CD34+ cells of patients with polycythemia vera by increasing the rate of their apoptosis [6].
A case of a patient with PV with a confirmed chromosomal translocation t(6;8) treated with interferon alpha-2b, which resulted in a reduction of the clone with translocation by 50% from the baseline value, was also described [14].
In 2019, the results of a phase II multicenter study were published, which aimed at assessing the effectiveness of recombinant pegylated interferon alpha-2a in cases of refractory to previously hydroxycarbamide therapy. The study included 65 patients with essential thrombocythemia (ET) and 50 patients with polycythemia vera. All patients had previously been treated with hydroxycarbamide and showed resistance to this drug or its intolerance.
The assessment of the response was performed after 12 months of treatment. Overall response rate to interferon was higher in patients diagnosed with ET than in patients with polycythemia vera. In essential thrombocythemia, the percentage of achieved complete remissions was 43 and 26% of partial remissions. The remission rate in ET patients was higher if calreticulin CALR gene mutation was present. Patients with polycythemia vera achieved complete remission in 22% of cases and partial remission in 38% of cases.
Treatment-related side effects that follow to discontinuation of treatment were reported in almost 14% of patients [15].
The duration of response to treatment with pegylated interferon alpha-2a and the assessment of its safety in long-term use in patients with chronic myeloproliferative disorders was the goal of a phase II of the single-center study. Forty-three adult patients with polycythemia vera and 40 patients with essential thrombocythemia were enrolled in the study. The complete hematological response was defined as a decrease in hemoglobin concentration below 15.0 g/l, without phlebotomies, a resolution of splenomegaly, and no thrombotic episodes in the case of PV, and for essential thrombocythemia—a decrease platelet count below 440,000/μl and two other conditions as above. The assessment of the hematological response was performed every 3–6 months. The median follow-up was 83 months.
The hematological response was obtained in 80% of cases for the entire group. In patients with polycythemia vera, 77% of patients achieved a complete response (CR) while 7% a partial response (PR). The duration of response averaged 65 months for CR and 35 months for PR. In the group of patients diagnosed with essential thrombocythemia, CR was achieved in 73% and PR in 3%. The durance of CR was 58 months and PR was 25 months.
The molecular response for the entire group was achieved in 63% of cases.
The overall analysis showed that the duration of hematological remission and its achievement with pegylated interferon alpha-2a treatment is not affected neither by baseline disease characteristics nor JAK2 allele burden and disease molecular status. There was also no effect on age, sex, or the presence of splenomegaly.
During the course of the study, 22% of patients discontinued the treatment, because of toxicity. Toxicity was the greatest at the beginning of treatment. The starting dose was 450 μg per week and was gradually tapered off.
Thus, on the basis of the above observations, the researchers established that pegylated interferon alpha-2a may give long-term hematological and molecular remissions [16].
The assessment of pegylated interferon alpha-2a in group of patients diagnosed with polycythemia vera only was performed. The evaluation was carried out on a group of 27 patients. Interferon decreased the JAK2 V617F allele burden in 89% of cases. In three patients who were JAK2 homozygous at baseline, after the interferon alpha-2a treatment wild-type of JAK2 reappeared. The reduction of the JAK2 allele burden was estimated from 49% to an average 27%, and additional in one patient the mutant JAK2 allele was not detectable after treatment. It can therefore be postulated that the action of pegylated interferon alpha-2a is directed to cells of the polycythemia vera clone [17].
In 2005, the results of treatment by pegylated interferon alpha-2b of 21 patients diagnosed with polycythemia vera and 21 patients diagnosed with essential thrombocythemia were published. In the case of polycythemia vera in 14 patients, PRV-1 gene mutation was initially detected. In 36% of cases, PRV-1 expression normalized after treatment with pegylated interferon alpha-2b. For the entire group of 42 patients, the remission assessment showed that complete remission was achieved in 69% cases after 6 months of treatment. However, only in 19 patients remission was still maintained 2 years after the start of the study. Pegylated interferon alpha-2b was equally effective in patients with PV and ET. The use and the type of prior therapy did not affect the achievement of remission [18].
Another study with enrolled only PV patients included 136 patients. They were divided into two arms. One group received interferon alpha-2b and the other group received hydroxycarbamide. Interferon dosage was administered in 3 million units three times a week for 2 years and then 5 million units two times a week. Hydroxycarbamide was administered at a dose between 15 and 20 mg/kg/day.
In the group of patients treated with interferon, a significantly lower percentage of patients developed erythromelalgia (9.4%) and distal parasthesia (14%) compared with the group treated with hydroxycarbamide, for whom these percentages were respectively: 29 and 37.5%. Interferon alpha-2b was found to be more effective in inducing a molecular response, which was achieved in 54.7% of cases, in comparison with hydroxycarbamide—19.4% of cases, despite the fact that the percentage of achieved general hematological responses did not differ between the groups and amounted about 70%. The 5-year progression free period in the interferon group was achieved in a higher percentage (66%) than in the hydroxycarbamide group (46.7%) [19].
The most recent form of interferon approved by the
Thanks to these changes to the structure of the molecule, it was possible to achieve a significant increase in its half-life. Ropeginterferon can be administered subcutaneously to patients every 14 days. The clinical trials conducted so far have assessed the ropeginterferon dose from 50 micrograms to a maximum dose of 500 microgams administered as standard every 2 weeks. The possible dose change in case of side effects includes not only the reduction of the drug dose itself, but also the extension of the interval between doses. The extension of the dosing interval up to 4 weeks was assessed.
Ropeginterforn was approved in 2019 by the EMA for the use in patients diagnosed with polycythemia vera without splenomegaly, as monotherapy.
Ropeginterferon, like the previous forms of interferons used in treatment, is contraindicated in patients with severe mental disorders, such as severe depression. It is also a contraindication in patients with noncompensatory standard treatment of disorders of the thyroid gland as well as severe forms of autoimmune diseases. The safety profile of ropeginterferon is similar to that of other forms of alpha interferons. The most common side effects are flu-like symptoms [20].
Ropeginterferon has been shown to exhibit in vitro activity against JAK2-mutant cells. The activity of ropeginterferon against JAK2-positive cells is similar to that of other forms of interferons used actually for standard therapy. Ropeginterferon has an inhibitory effect on erythroid progenitor cells with a mutant JAK2 gene. At the same time, it has almost no effect on progenitor cells without the mutated allele (JAK2-wile-type) and normal CD34+ cells. A gradual decrease of JAK2-positive cells was observed in patients with PV during ropeginterferon treatment. The examination was performed after 6 and 12 months of treatment. In comparison, the reduction in the percentage of JAK2 positive cells in patients treated with hydroxycarbamide was significantly lower.
These results may suggest that ropeginterferon may cause elimination of the mutant clone, but further prospective clinical trials are needed to confirm this theory. The evaluation was performed on a group of patients enrolled in the PROUD-PV study who were treated in France [21].
In 2017, a multicenter study was opened in Italy. The study was of the second phase. In total, 127 patients with polycythemia vera were included in the study. All patients enrolled on the study had low-risk PV. The clinical trial consisted of two arms. Patients received phlebotomies and low-dose aspirin in one arm and ropeginterferon in the other arm. The aim of the study was to achieve a hematocrit of 45% or lower without any evidence of disease progression. Ropeginterferon was administered every 2 weeks at a constant dose of 100 μg.
The response to the treatment was assessed after 12 months. The reduction of hematocrit to the assumed level was achieved in significantly higher percentage of patients in the ropeginterferon group than of patients who received only phlebotomies and aspirin. In addition, none of the patients treated with ropeginterferon experienced disease progression during the course of the study, while among those treated with phlebotomies, 8% of patients progressed.
Grade 4 or 5 adverse events were not observed in patients treated with ropeginterferon, and the incidence of remaining adverse event (AE) was small and comparable in both arms. The most common side effects in the ropeginterferon group were flu-like symptoms and neutropenia; however, the third-grade neutropenia was the most common (8% of cases) [22].
One of the most important clinical studies on the use of ropeginterferon was the PROUD-PV study and its continuation: the CONTINUATION-PV study. These were three-phase, multicenter studies. The aim of the study was to compare the effectiveness of ropeginterferon in relation to hydroxycarbamide. The study included adult patients diagnosed with polycythemia vera treated with hydroxycarbamide for less than 3 years and no cytoreductive treatment at all. In total, 257 patients received this treatment. The patients were divided into two groups: those receiving ropeginterferon or the other being given hydroxycarbamide.
During the PROUD-study, drug doses were increased until the hematocrit was achieved below 45% without the use of phlebotomies, and the normalization of the number of leukocytes and platelets was reached.
The PROUD-PV study lasted 12 months. After this time, the patients continued the treatment under the CONTINUATION-PV study for further 36 months. After the final analysis performed in the 12th month at the end of PROUD study, it was found that the hematological response rates did not differ between the ropeginterferon and hydroxycarbamide treatment groups. These were consecutively 43% in the ropeginterferon arm and 46% in the control arm.
However, after analyzing the CONTINUATION- PV study, it turned out that after 36 months of treatment, the rates of hematological responses begin to prevail in the group of patients receiving ropeginterferon, 53% versus 38% in the control group. Thus, from the above data, it can be seen that the response rate to ropeginterferon increases with the duration of treatment [23].
Another analysis of patients participating in the PROUD and CONTINUATION studies was based on the assessment of treatment results after 24 months, dividing patients into two groups according to age (under and over 60 years).
The initial comparison of both groups of patients showed that older patients had a more aggressive course of the disease. Patients over 60 years of age had a higher percentage of cells with a mutant JAK2 allele. They experienced both general symptoms and some complications, such as thrombosis, more frequently. Both patients under 60 years of age and over 60 years of age in the ropeginterferon arm had a higher rate of molecular response, namely 77.1 and 58.7% compared with the HU remission: 33.3 and 36.1%, respectively. Significantly higher reductions in the JAK2 allele were observed in both groups of patients after ropeginterferon treatment: it was 54.8% for younger patients and 35.1% for elderly patients. For comparison, this difference in the group of patients treated with HU was 4.5 and 18.4%, respectively.
What is more, the age did not affect the frequency of ropeginterferon side effects. In addition, the incidence of adverse ropeginterferon disorders was similar to that observed in the hydroxycarbamide group [24].
Essential thrombocythemia is a clonal growth of multipotential stem cells in the bone marrow. The consequence of this is increased proliferation of megakaryocytes in the bone marrow and an increase in the number of platelets in the peripheral blood. The level of platelets above 450,000/μl is considered a diagnostic criterion.
Essential thrombocythemia may progress over time to a more aggressive form of myeloproliferation, i.e., myelofibrosis. The disease can also evolve into acute myeloid leukemia or myelodysplastic syndrome, both with very poor prognosis. Thromboembolic complications are serious, and they concern over 20% of patients. Thrombosis occurs in the artery and venous area. Moreover, in patients with a very high platelet count, above 1,000,000/μl, bleeding may occur as a result of secondary von Willebrand syndrome [1, 2].
The treatment of ET is primarily aimed to prevent thrombotic complications.
In low-risk patients, only acetylsalicylic acid is used. In cases of high-risk patients, hydroxycarbamide is the first-line drug for most patients. Anagrelide and interferon are commonly used as second-line drugs.
Due to the possible effects of hydroxycarbamide of cytogenetic changes in the bone marrow cells after long-lasting usage, some experts recommend the use of interferon in younger patients in the first line. Interferon is also used as the drug of choice in patients planning a pregnancy [25].
The efficacy of pegylated interferon alpha-2a was assessed on the basis of the group of 39 patients with essential thrombocythemia and 40 patients with polycythemia vera.
Of the overall group, 81% of patients were previously treated prior to the study entry. The patients received pegylated interferon alpha-2a in a dose of 90 μg once a week. The dose of 450 μg was associated with a high percentage of intolerance.
In patients with essential thrombocythemia, the complete remission was achieved in 76%, while the overall hematological response rate brought 81%. Moreover, the molecular remission was achieved in 38%, in 14% of cases, JAK2 transcript became not detectable.
Patients diagnosed with polycythemia vera achieved 70% complete hematological remission and 80% general hematological response to treatment. JAK2 transcript was undetectable in 6% of patients. Molecular remission was achieved in 54% of cases.
Pegylated interferon alpha-2a at the dose of 90 μg per week was very well tolerated. In total, 20% of patients experienced a grade of 3 or 4 of adverse reaction, which was neutropenia. In addition, an increase in liver function tests was observed. Grade 4 of AE was not observed among patients who started the treatment with 90 μg/week while grade 3 neutropenia was an adverse event in only 7% of cases [26].
The effect of interferon alpha-2b treatment in patients with ET and PV was investigated. The study was prospective. Some of the results concerning the group of patients with polycythemia vera are presented in the subsection on polycythemia vera. In total, 123 patients with diagnosed essential thrombocythemia participated in the study. All of them received interferon alpha-2b. The patients were divided into two groups depending on the presence of the JAK2 V617F mutation. The enrolled patients were between 18 and 65 years of age. The treatment they received was, sequentially, interferon alpha-2b in the dose of 3 million units three times a week for the first 2 years, after which time the dose was changed into a maintenance dose, which amounted to 5 million units two times a week.
The analysis showed that the patients with the JAK2 V617F mutation present in a higher percentage achieved an overall hematological response as well as a complete hematological response. The overall hematological response was achieved in 83% of patients with JAK2 mutation, and the complete hematological remission was achieved in 23 cases. In the group of ET patients without the JAK2 V617F mutation, overall hematological response was achieved in 61.4%, while the complete hematological remission was achieved in 12 patients. The 5-year progression-free survival was obtained in 75.9% in the JAKV617F group and only in 47.6% without the mutation.
A significant proportion of patients experienced mild side effects. Grade 3 and 4 of adverse events were severe, most of them being a fever. The isolated cases of elevated liver tests and nausea have also been reported [19].
Pegylated interferon alpha-2b in patients with essential thrombocythemia who were previously treated with hydroxycarbamide, anagrelide, and other forms of interferon alpha, however, due to the lack of efficacy or toxicity, the patients required a change of treatment, was assessed. Pegylated interferon alpha-2b turned out to be effective in these cases. It led to the complete hematological remission in 91% of patients after 2 months of therapy, and in 100% of patients after 4 months. However, merely 11 patients participated in the study. Also only two patients required treatment discontinuation due to the side effects such as depression and general fatigue grade 3 [27].
In case of pregnant patients, interferon is currently considered the only safe cytoreductive drug. Over the years, several analyses of the results of interferon treatment during pregnancy have been carried out.
The assessment of 34 pregnancies in 23 women diagnosed with ET was performed retrospectively. All the pregnancies included in the analysis were of high risk. This high risk was associated with a high platelet count above 1,500,000/μl, a history of thrombotic episode, severe microcirculation disorders, or a history of major hemorrhage.
It turned out that the use of interferon allowed the birth of an alive child in 73.5% of cases. There was no difference in efficacy between the basic and pegylated forms of interferon alpha. In pregnancies without interferon treatment, the percentage of live births was only 60%. Moreover, it was not found if the presence of the JAK2 V617F mutation had any influence on the course of pregnancy [28].
An analysis of the course of pregnancy in patients with ET was assessed in Italy. Data from 17 centers were taken into account. Data from 122 pregnancies were collected from 92 women. In patients diagnosed with essential thrombocythemia, the risk of the spontaneous loss of pregnancy is about 2.5 times higher than among the general population. In the contrary to the study quoted above, it was found that the presence of the JAK2 mutation increases the risk of pregnancy loss. The proportion of live births in patients exposed to interferon during pregnancy was 95%, compared with 71.6% in the group of patients not treated with interferon.
The multivariate analysis also showed that the use of acetylsalicylic acid during pregnancy had no effect on the live birth rate of patients with ET [29].
Whatever its form, interferon is the drug of first choice in pregnancy. Hydroxycarbamide and anagrelide should be withdrawn for about 6 months, and at least for 3 months, before the planned conception. Experts recommend the use of interferon in high-risk pregnancies [30]. A Japanese analysis of 10 consecutive pregnancies in ET patients showed 100% live births in patients who received interferon [31].
In myelofibrosis (MF), monoclonal megakaryocytes produce cytokines that stimulate the proliferation of normal, non-neoplastic fibroblasts and stimulate angiogenesis. The consequence of this is the gradual fibrosis of the bone marrow, impaired hematopoiesis in the bone marrow, and the formation of extramedullary location mainly in the sites of fetal hematopoiesis, i.e., in the spleen and the liver.
The production of various cytokines by neoplastic megakaryocytes leads to the proliferation of normal, noncancerous fibroblasts as well as to increased angiogenesis.
Progressive bone marrow fibrosis leads to worsening anemia and thrombocytopenia. On the other hand, the production of proinflammatory cytokines by megakaryoblasts leads to the general symptoms such as weight loss, fever, joint pain, night sweats, and consequently, progressive worsening of general condition.
The prognosis for myelofibrosis is poor. In about 20% of patients, myelofibrosis evolves into acute myeloid leukemia with poor prognosis.
Currently, the only effective method of treatment that gives a chance to prolong the life is allogeneic bone marrow transplantation. However, this method is only available to younger patients.
The goal of treatment of patients who have not been qualified for allotranspalntation is to reduce the symptoms and to improve the patient’s quality of life. In case of leukocytosis cytoreducing drugs, such as hydroxycarbamide, melphalan, or cladribine can be used. They cause a reduction in the number of leukocytes and may, to some extent, inhibit splenomegaly. Interferon alpha has been used successfully for the treatment of myelofibrosis for many years. The results of its effectiveness will be presented below [2].
Currently, the JAK2 inhibitor ruxolitinib is approved for the treatment of myelofibrosis with enlarged spleen in intermediate and high-risk patients. Ruxolitinib reduces the size of the spleen, reduces general symptoms, and improves the quality of life; however, it does not prolong the overall survival of patients [32].
In 2015, the results of a retrospective study were published to compare the histological parameters of the bone marrow before and after interferon treatment. Twelve patients diagnosed with primary myelofibrosis as well as post-PV MF and post-ET MF were enrolled in the study. Patients were treated with pegylated recombinant interferon alpha-2a or recombinant interferon alpha-2b in standard doses. The time of treatment was from 1 to 10 years. Some patients had previously been treated with hydroxycarbamide or anagrelide. In all cases, karyotype was normal. The prognostic factor of Dynamic International Prognostic Scoring System (DIPSS) was assessed at the beginning as well as during the treatment.
Bone marrow cellularity decreased in cases with increased bone marrow cellularity before the treatment. After the interferon treatment, a reduction in the degree of bone marrow fibrosis was found. The parameters, such as the density of naked nuclei and the density of megakaryocytes in the bone marrow, also improved.
It proves that if the JAK2 V617F mutation had been present, DIPSS was decreased after interferon treatment. This relationship was not observed in patients without the JAK2 V617F mutation. The improvement in peripheral blood morphological parameters and the overall clinical improvement correlated with the improvement in the assessed histological parameters of the bone marrow.
Before the initiation of interferon, seven patients had splenomegaly. During the treatment with interferon, the complete resolution of splenomegaly was achieved in 17% of patients (two cases), and its size decreased in 25% (three cases). A good clinical response was achieved in 83% during interferon therapy. There was no significant difference in response between the two types of interferon used [33].
A prospective study was also conducted in patients with low and intermediate-1 risk group myelofibrosis. Seventeen patients were enrolled. Patients received interferon alpha-2b (0.5–3 milion units/three times a week) or pegylated interferon alpha-2a (45–90 μg/week). The duration of therapy was on average 3.3 years.
Most of the patients responded to the treatment. Partial remission was found in seven patients and complete remission in two patients. Moreover, in four cases, the disease was stabilized and in one case the clinical improvement was achieved. Three patients did not respond to treatment at all and progressed to myelofibrosis. Additionally, the assessment in reducing spleen size was performed. At baseline, 15 patients have splenomegaly, nine of them achieved the compete regression of spleen size [34].
However, the efficacy of interferon in the treatment of myelofibrosis appears to be limited only to a less advanced form, when the bone marrow still has an adequate percentage of normal hemopoiesis and the marrow stroma is not significantly fibrotic. In more advanced stages, interferon was not shown to have any significant effect on the regression of the fibrosis process [35].
In 2020, the results of the COMBI study were published. That was a two-phase, multicenter, single-arm study that investigated the efficacy and safety of the combination of ruxolitinib and pegylated interferon alpha. Thirty-two patients with PV and 18 patients with primary and secondary myelofibrosis participated in the study. The patients were at age 18 and older. Remission was achieved in 44% of myelofibrosis cases, including 28% (5 patients) of complete remission. In patients with PV, the results were slightly worse: 31% of remissions, including 9% of complete remissions. Patients received pegylated interferon alpha-2a (45 μg/week) or pegylated interferon alpha-2b (35 μg/week) in low doses and ruxolitinib in doses of 5–20 mg twice a day.
For the entire group of patients (with PV and MF), the initial JAK2 allele burden was 47% at baseline, and after 2 years of treatment with interferon and ruxolitinib, it decreased to 12%.
The treatment toxicity was low. The highest incidence of side effects occurred at initiation of therapy. It was mostly anemia and thrombocytopenia.
The observations from the COMBI study show that, for the combination of interferon in lower doses with ruxolitinib, it may be effective and well tolerated even in the group of patients who had intolerance to interferon used as the only drug in higher doses. The combined treatment improved the bone marrow in terms of fibrosis and its cellularity. It also allowed to improve the value of peripheral blood counts [36].
It is currently known that some of the additional mutations are associated with a worse prognosis in patients with myelorpoliferation, including patients with myelofibrosis. Some of these mutations have been identified as high-risk molecular mutations. These are ASXL1, EZH2, IDH1/2, or SRSF2. Earlier studies have shown their association with a more aggressive course of the disease, worse prognosis, and shorter survival of patients, as well as a poorer response to treatment. Due to their importance, they have been included in the diagnostic criteria of myelofibrosis [37].
It is also known that the presence of driver mutations, i.e., JAK2, CALR, and MPL or triple negativity, may affect the course of myeloproliferation, including the incidence of thromboembolic complications.
The assessment of the influence of driver mutations and a panel of selected additional mutations on the effectiveness of interferon treatment in patients with myelofibrosis was performed on a group of 30 patients. Only the patients with low- and intermediate-1-risk were enrolled in the study. The treatment with pegylated interferon alpha-2a or interferon alpha-2b resulted in a complete remission in two patients and partial remission in nine patients. The disease progressed in three cases. One patient relapsed and four died. The remaining patients achieved a clinical improvement or disease stabilization. In the studied group, it was not found if the effectiveness of interferon treatment was influenced by the lack of driver mutations. Among the group of four patients with additional mutations, two died and one had disease progression. It was a mutation of ASXL1 and SRSF2. The treatment with interferon in patients without additional molecular mutations in the early stages of the disease may prevent further progression of the disease [38].
The side effects of interferon in the group of patients with myelofibrosis are similar to those occurring after the treatment of other chronic myeloproliferative diseases. The most frequently described are hematological toxicity- anemia and thrombocytopenia, less often is the appearance of leukopenia. Hematological toxicity usually resolves with dose reduction or extension of the dose interval. The most frequently nonhematological toxicity was fatigue, muscle pain, weakness, and depression symptoms. All symptoms are usually mild and do not exceed grade 2 [38].
However, the use of interferon in the treatment of myelofibrosis has not been recommended as a standard therapy. Interferon is still being evaluated in clinical trials, or it is used in selected patients as a nonstandard therapy in this diagnosis.
Mastocytosis is characterized by an excessive proliferation of abnormal mast cells and their accumulation in various organs.
The basis for the development of mastocytosis is ligand-independent activation of the KIT receptor, resulting from mutations in the KIT proto-oncogene. The KIT receptor is a trans membrane receptor with tyrosine kinase’s activity. Its activation stimulates the proliferation of mast cells. That excessive numbers of mast cells infiltrate tissues and organs and release mediators such as histamine, interleukine-6, tryptase, heparin, and others, which are responsible for the appearance of symptoms typical of mastocytosis. In addition, the infiltration of tissues for mast cells itself causes damage to the affected organs.
The prognosis of mastocytosis depends on the type of the disease. In the case of cutaneous mastocytosis (CM), in the majority of cases prognosis is good and the disease does not shorten the patient’s life, but in aggressive systemic mastocytosis (ASM), the average follow-up is about 40 months. Mast cell leukemia has a poor prognosis with a median follow-up of approximately 1 year.
Systemic mastocytosis usually requires the implementation of cytoreductive therapy. The first line of therapy is interferon alone or its combination with corticosteroids. In aggressive systemic mastocytosis, the first line in addition to interferon 2-CdA can be used. An effective drug turned out to be midostaurin in the case of the present KIT mutation. In patients without the KIT D816V mutation, treatment with imatinib may be effective. In the case of mast cell leukemia, multidrug chemotherapy is most often required, as in acute leukemias, followed by bone marrow transplantation [39].
Systemic mastocytosis requiring treatment is a rare disease, this is why the studies available in the literature evaluating various therapies concern mostly small groups of patients.
In 2002, the French authors presented their experiences on the use of interferon in patients with systemic mastocytosis. They included 20 patients. The patients received interferon alpha-2b in gradually increased doses.
The patients were assessed after 6 months. In cases in which bone marrow was infiltrated for mast cells at baseline, it still remained infiltrated after 6 months of treatment.
However, the responses were obtained in terms of symptoms related to mast cell degranulation. Partial remission was achieved in 35% of patients and minor remission in 30%. It concerns mainly skin lesions and vascular congestion. Moreover, the assessment of the histamine level in the plasma revealed a decrease of it in patients who previously presented symptoms related to the degranulation of mast cells, such as gastrointestinal disorders and flushing.
A high percentage of side effects were found during treatment. They concerned 35% of patients. Depression and cytopenia were most frequent ones [40].
Another analysis was a report of five patients with systemic mastocytosis treated with interferon and prednisolone. All patients received interferon alpha-2b in a dose of 3 million units three times a week and four patients additionally received prednisolone. Four patients responded to interferon treatment at varying degrees. One patient, who at baseline had bone marrow involvement by mast cells in above 10%, progressed to mast cell leukemia. In two patients, the symptoms C resolved completely and in one of them they partially disappeared. In one case, stabilizing disease was achieved [41].
In 2009, a retrospective analysis of patients treated with cytoreductive therapy due to mastocytosis was published. The authors collected data from 108 patients treated at the Mayo Clinic. This analysis allowed for the comparison of the efficacy of four drugs used in systemic mastocytosis. There were interferon alpha alone or in the combination with prednisone—among 40 patients, hydroxycarbamide—among 26 ones, imatinib—among 22 persons, and 2-chlorodeoxyadenosine (2-CdA)—among 22 patients.
After dividing the patients into three additional groups on the basis of the type of mastocytosis—indolent systemic mastocytosis, aggressive systemic mastocytosis, and systemic mastocytosis associated with another clonal hematological nonmast cell lineage disease (SM-AHNMD)—the effectiveness of each of type of therapy was assessed.
The highest response rates in indolent and aggressive mastocytosis were achieved with interferon treatment. They were 60% of the responses in both groups, and in the SM-AHNMD group of patients, the percentage was also one of the highest and amounted to 45%. The second most effective drug was 2-CdA. The response rates were 56% for indolent MS, 50% for aggressive MS, and 55% for SM-AHNMD. The patients treated with imatinib achieved response in 14, 50, and 9% by following groups, respectively. In contrast, patients with indolent and aggressive systemic mastocytosis did not respond to hydroxycarbamide treatment at all. The response rate in both groups was 0%. However, patients with MS associated with another clonal hematological nonmast cell lineage disease achieved 21% response to hydroxycarbamide. Additionally, it was found that only interferon relieved symptoms caused by the release of inflammatory mediators by mast cells.
The additional analysis showed no influence of the TET 2 mutation on the response to treatment [42].
In the literature, there are also single cases of mastocytosis presenting trials of nonstandard treatment. That is description of a patient with systemic mastocytosis with mast cell bone marrow involvement. Mutation of c-kit Asp816Val was present. Patient progressed despite treatment with dasatinib and 2-chlorodeoxyadenosine. The patient developed symptoms related to the degranulation of mast cells and increased ascites.
The patient was treated with pranlukast, which is an anti-leukotriene receptor antagonist due to an asthma episode. The rate of ascites growth decreased significantly after one administration. The patient required paracentesis every 10 days and not every 3 days, as before starting to take the drug. After 15 days of treatment with pranlukast, the patient received interferon alpha, which resulted in complete regression of ascites, resolution of pancytopenia, and complete disappearance of the c-kit mutation clone. The infiltration of mast cells in the bone marrow significantly decreased [43].
Interferon alpha was also effective in a patient with systemic mastocytosis associated with myelodysplastic syndrome with the c-kit D816V mutation, which was refractory to imatinib treatment [44].
Interferon alpha also proved to be effective in the treatment of osteoporotic lesions appearing in the course of mastocytosis.
The series of 10 cases with resolved mastocytosis and osteoporosis-related fractures was presented in 2011. The patients received interferon alpha in a dose of 1.5 million units three times a week as well as pamindronic acid. The patients were treated for an average of 60 months. For the first 2 years, pamindronate was given at a dose of 1 mg/kg every month, and then every 3 months.
During the course of the study, no patient had a new-bone fracture. The level of alkaline phosphatase decreased by 25% in relation to the value before treatment and tryptase by 34%. Bone density increased during treated with interferon and pamindronate. The increase was on average 12% in the spine bones and 1.9% in the hip bones. At the same time, there was no increase in the density of the hip bone and a minimal increase in the density of the spine in patients treated with pamindronate alone.
The results of this observation suggest that it is beneficial to add low doses of interferon alpha to pamindronate treatment in terms of bone density increase [45].
That experiences show that interferon used in systemic mastocytosis significantly improves the quality of life of patients by inhibiting the symptoms caused by degranulation of mast cells. They prevent bone fractures and, in some patients, they cause remission of bone marrow infiltration by mast cells.
Chronic neutrophilic leukemia (CNL) is a very rare disease. It is characterized by the clonal proliferation of mature neutrophils.
The diagnostic criteria proposed by the World Health Organization (WHO) comprise leukocyte counts above 25,000/μl (including more than 80% of rod and segmented
Physical examination often shows enlargement of the liver and spleen, moreover, patients complain on weight loss and weakness [1].
The prognosis varies. The average survival time for patients with CNL is less than 2 years.
Only few descriptions of chronic neutrophilic leukemia are available in the literature, and these are mostly single case reports.
Because it is an extremely rare disease, there are no established and generally accepted treatment standards. In most cases, patients are given hydroxycarbamide or interferon. Patients who are eligible for a bone marrow transplant may benefit from this treatment. Bone marrow allotransplantation remains the only method that gives a chance for a significant extension of life.
The German authors presented a series of 14 cases of chronic neutrophilic leukemia. The group of patients consisted of eight women and six men. The average age was 64.7 years. From the entire group of patients, longer survival was achieved only in three cases. One of these patients was treated with interferon alpha and achieved hematological remission, the other underwent bone marrow allotransplantation from a family donor, and the third one was treated with hydroxycarbamide and transfusions as needed. The follow-up period of the patient after allogeneic matched related donor transplantation (allo-MRD) was 73 months, and for the patient after interferon treatment it was 41 months.
The remaining patients died within 2 years of diagnosis. Six patients, the largest group, died due to intracranial bleeding, three patients died because of leukemia cell tissue infiltration, one patient because of the disease transformation into leukemia, and one patient because of pneumonia [46].
It can be seen from these experiences that treatment with interferon alpha can significantly extend the survival time of patients.
The case of a 40-year-old woman diagnosed with chronic neutrophilic leukemia is presented by Yassin and coauthors. Initially, the patient had almost 41,000 leukocytes in the peripheral blood. In a physical examination, splenomegaly and hepatomegaly were not present. Patient received pegylated interferon alpha-2a. The initially dose was 50 μg once a week for the first 2 weeks, then the dose was increased to 135 μg weekly for 6 weeks, and then the dose interval was extended to another 2 weeks. As a result of the treatment, the general condition of the patient improved and the parameters of peripheral blood counts were normalized [47].
Another case report presented in the literature describes a 41-year-old woman diagnosed with CNL accompanied by focal segmental glomerulosclerosis (FSGS). The patient had increasing leukocytosis for several months. On the admission to the hospital, leukocytosis was 94,000/μl. Moreover, the number of platelets in the morphology exceeded 1,000,000/μl. More than a year earlier, the patient had splenectomy due to splenomegaly and spleen infraction.
Additionally, JAK2 V617F mutation was found. Some authors suggest that the presence of JAK2 mutation may be associated with longer survival in CNL.
The patient received hydroxycarbamide for 3 months and reduction in the number of leukocytes was achieved. After this time, interferon alpha-2b was added to hydroxycarbamide. As a result, focal segmental glomerulosclerosis disappeared and the renal tests improved [48].
Another case of chronic neutrophilic leukemia with a JAK2 gene mutation concerns a 53-year-old man. The patient’s baseline leukocytosis was 33,500/μl, including the neutrophil count of 29,700/μl. The patient also had splenomegaly.
The treatment with interferon alpha-2b at a dose of 3 million units every other day was started. After a month of treatment, the number of leukocytes was reduced to less than 10,000/μl. Then the patient was treated chronically with interferon alpha-2b in doses of 3 million units every 2 weeks. As a result of the therapy, the number of leukocytes remains between 8 and 10,000/μl. The patient remains in general good condition [49].
A series of two CNL cases are also shown. The first patient was a 70-year-old woman with stable leukocytosis of about 35,000/μl and the remaining morphology parameters in normal range. The patient was only observed for 5 years until hepasplenomegaly progressed rapidly. Then, interferon alpha-2b was included. Due to the treatment, the rapid regression of hepatosplenomegaly was achieved.
The second case is a 68-year-old woman with baseline leukocytosis of almost 14,000/μl. In this case, the treatment with hydroxycarbamide was started immediately. However, no improvement was achieved. After 6 weeks of HU treatment, interferon alpha-2b 3 million units 3 times a week was implemented and leukocytosis decreased. Due to the interferon treatment, the disease stabilized for a long time. Because the patient experienced an adverse reaction, a severe flu-like syndrome, interferon was discontinued. After interferon withdrawal, the disease progressed gradually and the treatment attempts by busulfan and 6-mercaptopurine were unsuccessful. Therefore, interferon was readministered and the disease went into remission. Interferon treatment was continued at a reduced dose. The disease regression was achieved again.
Additionally, the patient showed an improvement in the function of granulocytes in terms of phagocytosis and an improvement in neutral killer (NK) cell function after treatment with interferon [50].
The above examples show that interferon alpha is effective in the treatment of chronic neutrophilic leukemia. The side effects are rare and can be managed with dose reductions. Moreover, in these cases, interferon is also effective in a reduced dose. Disease remission or regression can be achieved without typical of CNL complications, such as intracranial bleeding.
Interferon has been used in the past to treat chronic myeloid leukemia. The treatment with tyrosine kinase inhibitors is now a standard practice. However, in a small number of patients, they are ineffective or exhibit unmanageable toxicity. Therefore, the attempts are underway to use interferon in combination with TKI in lower doses, which is to ensure the enhancement of the antiproliferative effect while reducing the toxicity.
There are ongoing attempts to use ropeginterferon in patients diagnosed with chronic myeloid leukemia, in whom treatment with imatinib alone has not led to deep molecular response (DMR). The first phase study was conducted in a small group of patients with chronic myeloid leukemia. The patients in first chronic phase treated with imatinib who did not achieve DMR, but in complete hematologic remission and complete cytogenetic remission, were included in the study. Patients have been treated with imatinib for at least 18 months. Twelve patients were enrolled in the study, and they completed the study according to the protocol. These patients received additional ropeginterferon to imatinib and four achieved DMR. Low toxicity was observed during the treatment. Among the hematological toxicities, neutropenia was the most common. There was no nonhematological toxicity with a degree higher than 1/2 during the treatment. Moreover, it has been found that better effects and fewer side effects are obtained when ropeginterferon is administered for a longer time, but in lower doses. The comparison of the effectiveness of interferon in chronic myeloproliferative disorders based on selected articles is presented in Table 1 [51].
Source | Type of trial | Interferon | Diagnosis | No. | Prior treatment status | Response rate |
---|---|---|---|---|---|---|
Yacoubet al. [15] | Phase II, multicenter | Pegylated IFN alfa-2a | PV | 50 | Resistance to HU or HU intolerance | CR:22% PR:38% |
ET | 65 | CR:43% PR:26% | ||||
Masarova et al. [16] | Phase II, single-center | Pegylated IFN alfa-2a | PV | 43 | Untreated or previously treated with cytoreductive therapy | CR:77% PR:7% |
ET | 40 | CR:73% PR:3% | ||||
Samuelsson et al. [18] | Phase II | Pegylated IFN alfa-2b | PV | 21 | Untreated or previously treated with cytoreductive therapy | CR: 69% for the entire group |
ET | 21 | |||||
Huang BT et al. [19] | Open label, multicenter | IFN alfa-2b | PV | 136 | Untreated or previously treated with cytoreductive therapy | OHR:70% Molecular response:54.7% |
ET | 123 | OHR (JAK2+ patients):83% CHR:23 cases OHR (JAK2-patients): 61.4% CHR:12 cases | ||||
Gisslinger et al. [23] | phase III, multicenter | Ropeginterferon | PV | 257 | Previously treated | OHR:53% |
Quintás-Cardama et al. [26] | phase II | Pegylated IFN alfa-2a | PV | 40 | Untreated or previously treated with cytoreductive therapy | OHR:80% CR:70% Molecular remission:54% |
ET | 39 | OHR:81% CR:76% Molecular remission:38% | ||||
Sørensen et al. [36] | Phase III, multicenter, COMBI | Pegylated IFN alfa-2a with ruxolitinib or Pegylated IFN alfa-2b with ruxolitinib | PV | 32 | Untreated or previously treated with cytoreductive therapy | OHR:44% CR:28% |
MF | 18 | OHR:31% CR:9% | ||||
Casassus et al. [40] | Open label, multicenter | IFN alpha-2b | Mastocytosis | 20 | Untreated and previously treated | PR:35% Minor remission: 30% |
Comparison of the effectiveness of interferon in chronic myeloproliferative disorders.
PV: polycythemia vera; ET: essential thrombocythemia; MF: myelofibrosis; HU: hydroxycarbamide/hydroxyurea; CR: complete remission; PR: partial remission; and OHR: overall hematological response.
Interferon alpha appears to be an effective and safe drug in the most type of chronic myeloproliferative disorders. Nowadays, all forms of its using have similar effectiveness. Interferon alpha can be effective even in cases of resistance for first-line treatment. Trial research is currently underway to combine it with some new drugs, such as ruxolitinib, and to add it to the already well-established therapy, it is a promising option for patients with refractory disease.
From time to time, new forms of interferon, such as ropeginterferon, are introduced, which gives hope for better effectiveness, better safety profile, and greater comfort in its use for patients who have to be treated for many years. In the case of the use of interferons alpha in the treatment of chronic myeloproliferative diseases, there are still opportunities to extend its use and to study its combination with newly introduced drugs.
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Due to rapid depletion of agricultural areas and soil quality by means of ever-increasing population and an excessive addition of chemical fertilizers, a rehabilitated attention is a need of the hour to maintain sustainable approaches in agricultural crop production. Biochar is the solid, carbon-rich material obtained by pyrolysis using different biomasses. It has been widely documented in previous studies that, the crop growth and yield can be increased by using biochar. This chapter exclusively summarizes the properties of biochar, its interaction with soil microflora, and its role in plant growth promotion when added to the soil.",book:{id:"7305",slug:"biochar-an-imperative-amendment-for-soil-and-the-environment",title:"Biochar",fullTitle:"Biochar - An Imperative Amendment for Soil and the Environment"},signatures:"Jyoti Rawat, Jyoti Saxena and Pankaj Sanwal",authors:null},{id:"46355",doi:"10.5772/57469",title:"Phytoremediation of Soils Contaminated with Metals and Metalloids at Mining Areas: Potential of Native Flora",slug:"phytoremediation-of-soils-contaminated-with-metals-and-metalloids-at-mining-areas-potential-of-nativ",totalDownloads:8605,totalCrossrefCites:14,totalDimensionsCites:87,abstract:null,book:{id:"3854",slug:"environmental-risk-assessment-of-soil-contamination",title:"Environmental Risk Assessment of Soil Contamination",fullTitle:"Environmental Risk Assessment of Soil Contamination"},signatures:"Paulo J.C. Favas, João Pratas, Mayank Varun, Rohan D’Souza and\nManoj S. Paul",authors:[{id:"169746",title:"Dr.",name:"Paulo",middleName:null,surname:"Favas",slug:"paulo-favas",fullName:"Paulo Favas"},{id:"169747",title:"Dr.",name:"Manoj",middleName:"Stephen",surname:"Paul",slug:"manoj-paul",fullName:"Manoj Paul"},{id:"169952",title:"Dr.",name:"Joao",middleName:null,surname:"Pratas",slug:"joao-pratas",fullName:"Joao Pratas"},{id:"169953",title:"Dr.",name:"Mayank",middleName:null,surname:"Varun",slug:"mayank-varun",fullName:"Mayank Varun"},{id:"169954",title:"Dr.",name:"Rohan",middleName:null,surname:"D'Souza",slug:"rohan-d'souza",fullName:"Rohan D'Souza"}]},{id:"61845",doi:"10.5772/intechopen.77987",title:"Montmorillonite: An Introduction to Properties and Utilization",slug:"montmorillonite-an-introduction-to-properties-and-utilization",totalDownloads:5518,totalCrossrefCites:45,totalDimensionsCites:78,abstract:"Clay mineral is an important material available in nature. With an increasing understanding of clay structure, montmorillonite is realized viable for an enhanced performance in a variety of materials and products in the areas of catalysis, food additive, antibacterial function, polymer, sorbent, etc. Significant development in the use and application of montmorillonite is seen in recent time. This chapter provides an overview of montmorillonite, structure, and properties and particularly discusses its recent utilization in important materials. Montmorillonite is introduced in terms of its natural sources, chemical structure, physical and chemical properties, and functional utilization. The important physical and chemical properties are summarized as particle and layered structure, molecular structure and cation exchange effect, barrier property, and water sorption. This is followed by the important functional utilizations of montmorillonite based on the effects of its chemical structure. The important functional utilization of montmorillonite includes food additive for health and stamina, for antibacterial activity against tooth and gum decay, as sorbent for nonionic, anionic, and cationic dyes, and the use as catalyst in organic synthesis. The environment concerns, to date, do not indicate the adversity for particles used as additive. Studies will be useful which are clearly based on any montmorillonite structure to describe environmental effects.",book:{id:"6561",slug:"current-topics-in-the-utilization-of-clay-in-industrial-and-medical-applications",title:"Current Topics in the Utilization of Clay in Industrial and Medical Applications",fullTitle:"Current Topics in the Utilization of Clay in Industrial and Medical Applications"},signatures:"Faheem Uddin",authors:[{id:"228107",title:"Prof.",name:"Faheem",middleName:null,surname:"Uddin",slug:"faheem-uddin",fullName:"Faheem Uddin"}]}],mostDownloadedChaptersLast30Days:[{id:"46032",title:"Soil Contamination, Risk Assessment and Remediation",slug:"soil-contamination-risk-assessment-and-remediation",totalDownloads:14030,totalCrossrefCites:22,totalDimensionsCites:62,abstract:null,book:{id:"3854",slug:"environmental-risk-assessment-of-soil-contamination",title:"Environmental Risk Assessment of Soil Contamination",fullTitle:"Environmental Risk Assessment of Soil Contamination"},signatures:"Muhammad Aqeel Ashraf, Mohd. Jamil Maah and Ismail Yusoff",authors:[{id:"25185",title:"Dr.",name:"Muhammad Aqeel",middleName:null,surname:"Ashraf",slug:"muhammad-aqeel-ashraf",fullName:"Muhammad Aqeel Ashraf"},{id:"101988",title:"Dr.",name:"Ismail",middleName:null,surname:"Yusoff",slug:"ismail-yusoff",fullName:"Ismail Yusoff"},{id:"169931",title:"Prof.",name:"Mohd Jamil",middleName:null,surname:"Maah",slug:"mohd-jamil-maah",fullName:"Mohd Jamil Maah"},{id:"169932",title:"Dr.",name:"Ng Tham",middleName:null,surname:"Fatt",slug:"ng-tham-fatt",fullName:"Ng Tham Fatt"}]},{id:"71931",title:"Open Pit Mining",slug:"open-pit-mining",totalDownloads:1767,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Open pit mining method is one of the surface mining methods that has a traditional cone-shaped excavation and is usually employed to exploit a near-surface, nonselective and low-grade zones deposits. It often results in high productivity and requires large capital investments, low operating costs, and good safety conditions. The main topics that will be discussed in this chapter will include an introduction into the general features of open pit mining, ore body characteristics and configurations, stripping ratios and stripping overburden methods, mine elements and parameters, open pit operation cycle, pit slope angle, stability of mine slopes, types of highwall failures, mine closure and reclamation, and different variants of surface mining methods including opencast mining, mountainous mining, and artisan mining.",book:{id:"8620",slug:"mining-techniques-past-present-and-future",title:"Mining Techniques",fullTitle:"Mining Techniques - Past, Present and Future"},signatures:"Awwad H. Altiti, Rami O. Alrawashdeh and Hani M. Alnawafleh",authors:[{id:"313182",title:"Prof.",name:"Rami",middleName:null,surname:"Alrawashdeh",slug:"rami-alrawashdeh",fullName:"Rami Alrawashdeh"},{id:"313522",title:"Dr.",name:"Awwad",middleName:null,surname:"Altiti",slug:"awwad-altiti",fullName:"Awwad Altiti"},{id:"313523",title:"Prof.",name:"Hani",middleName:null,surname:"Alnawafleh",slug:"hani-alnawafleh",fullName:"Hani Alnawafleh"}]},{id:"64027",title:"Stages of a Integrated Geothermal Project",slug:"stages-of-a-integrated-geothermal-project",totalDownloads:4511,totalCrossrefCites:3,totalDimensionsCites:4,abstract:"A geothermal project constitutes two big stages: the exploration and the exploitation. Each one has a single task whose results allow defining the feasibility of a geothermal project, until achieving the construction and operation stage of the power generation plant. The first stage contains the area recognition, its limitation to the target, and elimination of external factors until defining a geothermal zone with characteristics to be commercially exploited. The main studies and analysis that can be applied during the exploration stage are listed, and the major indicator to continue with the project or suspend is the prefeasibility report. The major risks in the exploration stage are due to studies that are carried out on the surface; at this stage, the costs can be considered low. The main results of the exploration are the selection of sites to drill three or four initial wells. Each well provides a direct overview of the reservoir: depth, production thicknesses, thermodynamic parameters, and production characteristics. The drilling of three to four exploratory wells is recommended, as far as there is certainty of the feasibility of the project, and the development of the field begins with drilling of sufficient wells to feed the plant. In this stage, the cost increases, but the risks decrease.",book:{id:"7504",slug:"renewable-geothermal-energy-explorations",title:"Renewable Geothermal Energy Explorations",fullTitle:"Renewable Geothermal Energy Explorations"},signatures:"Alfonso Aragón-Aguilar, Georgina Izquierdo-Montalvo,\nDaniel Octavio Aragón-Gaspar and Denise N. Barreto-Rivera",authors:[{id:"258358",title:"Dr.",name:"Alfonso",middleName:null,surname:"Aragón-Aguilar",slug:"alfonso-aragon-aguilar",fullName:"Alfonso Aragón-Aguilar"}]},{id:"65070",title:"Biochar: A Sustainable Approach for Improving Plant Growth and Soil Properties",slug:"biochar-a-sustainable-approach-for-improving-plant-growth-and-soil-properties",totalDownloads:6979,totalCrossrefCites:61,totalDimensionsCites:101,abstract:"Soil is the most important source and an abode for many nutrients and microflora. Due to rapid depletion of agricultural areas and soil quality by means of ever-increasing population and an excessive addition of chemical fertilizers, a rehabilitated attention is a need of the hour to maintain sustainable approaches in agricultural crop production. Biochar is the solid, carbon-rich material obtained by pyrolysis using different biomasses. It has been widely documented in previous studies that, the crop growth and yield can be increased by using biochar. This chapter exclusively summarizes the properties of biochar, its interaction with soil microflora, and its role in plant growth promotion when added to the soil.",book:{id:"7305",slug:"biochar-an-imperative-amendment-for-soil-and-the-environment",title:"Biochar",fullTitle:"Biochar - An Imperative Amendment for Soil and the Environment"},signatures:"Jyoti Rawat, Jyoti Saxena and Pankaj Sanwal",authors:null},{id:"39170",title:"Study of Impacts of Global Warming on Climate Change: Rise in Sea Level and Disaster Frequency",slug:"study-of-impacts-of-global-warming-on-climate-change-rise-in-sea-level-and-disaster-frequency",totalDownloads:6708,totalCrossrefCites:14,totalDimensionsCites:32,abstract:null,book:{id:"2206",slug:"global-warming-impacts-and-future-perspective",title:"Global Warming",fullTitle:"Global Warming - Impacts and Future Perspective"},signatures:"Bharat Raj Singh and Onkar Singh",authors:[{id:"26093",title:"Dr.",name:"Bharat Raj",middleName:null,surname:"Singh",slug:"bharat-raj-singh",fullName:"Bharat Raj Singh"},{id:"118426",title:"Prof.",name:"Onkar",middleName:null,surname:"Singh",slug:"onkar-singh",fullName:"Onkar Singh"}]}],onlineFirstChaptersFilter:{topicId:"10",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82490",title:"Precision Agriculture for Sustainable Soil and Crop Management",slug:"precision-agriculture-for-sustainable-soil-and-crop-management",totalDownloads:3,totalDimensionsCites:null,doi:"10.5772/intechopen.101759",abstract:"Precision agriculture (PA) transforms traditional practices into a new world of production of agriculture. It uses a range of technologies or diagnostic tools such as global navigation satellite system (GNSS), geographic information systems (GIS), yield monitors, near-infrared reflectance sensing, and remote sensing in collecting and analyzing the in-field spatial variability data, thereby enabling farmers to monitor and make site-specific management decisions for soils and crops. PA technology enables visualization of spatial and temporal variations of production resources and supports spatially varying treatments using variable rate application technologies installed on farm agricultural field machinery. The demand for PA is driven by recognition within-field variability and opportunities for treating areas within a field or production unit differently. PA can be applied to multiple cultural practices including tillage, precision seeding, variable rate fertilizer application, precision irrigation and selective pesticide application; and facilitates other management decisions making, for example, site-specific deep tillage to remove soil compaction. PA technology ensures optimal use of production inputs and contributes to a significant increase in farm profitability. By reducing crop production inputs and managing farmland in an environmentally sensible manner, PA technology plays a vital role in sustainable soil and crop management in modern agriculture.",book:{id:"10952",title:"Soil Science - Emerging Technologies, Global Perspectives and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/10952.jpg"},signatures:"Md. Rayhan Shaheb, Ayesha Sarker and Scott A. Shearer"},{id:"82272",title:"Landslide Movement Monitoring with InSAR Technologies",slug:"landslide-movement-monitoring-with-insar-technologies",totalDownloads:6,totalDimensionsCites:0,doi:"10.5772/intechopen.105058",abstract:"Synthetic aperture radar interferometry (InSAR) is a technology that has been widely used in many areas, such as topographic mapping, land and resource survey, geological exploration, disaster prevention and mitigation, volcanic and seismic monitor and so on. Landslide, as a representative geohazard, include a wide range of phenomena involving downhill ground movement. InSAR, a technology which can measure surface deformation at the millimeter level over serveral days or years, is suitable to detect landslides with chronical and widespread movements. In this chapter, we introduce main process methods of InSAR data, including Persistent Scatter Interferometry (PSInSAR) and Distributed Scatter Interferometry (DSInSAR). A study area, Daguan County Town, one of the most landslide-prone areas in China is induced to demonstrate the practicability of InSAR in detecting landslides. Combined InSAR results with geological, geotechnical and meterological data, the distribution of landslide in Daguan County in spatial and temporal dimensions would be displayed. We also coupling numerical modeling and InSAR for characterizing landslide movements under multiple loads. The numerical results revealed that body loads dominated the cumulative downhill movements by squeezing water and air from voids, and precipitation caused seasonal movements with the direction perpendicular to the slope surface.",book:{id:"10950",title:"Landslides",coverURL:"https://cdn.intechopen.com/books/images_new/10950.jpg"},signatures:"Peifeng Ma, Yifei Cui, Weixi Wang, Hui Lin, Yuanzhi Zhang and Yi Zheng"},{id:"82823",title:"The Metropolitan Transformation of Ioannina City from 1940 to 2015",slug:"the-metropolitan-transformation-of-ioannina-city-from-1940-to-2015",totalDownloads:6,totalDimensionsCites:0,doi:"10.5772/intechopen.105884",abstract:"The chapter presents the urban and regional changes in the city of Ioannina, Greece. This city is located in the periphery of Epirus, which is in the western Balkans, Eastern Europe. The chapter examines, with the tools of aerial photos and QGIS software, the spatial transformation of Ioannina city from 1940 to 2015. Map science is a field through which the users could observe and compare maps from past to future. The plans and the planning were formed under the values, standards, and fundamentals of the mosaic of politics, good practices, urban rules, and citizen level. The urban space has already changed until nowadays. The chapter examines the reasons for urban politics and social–economic moments that became the epitome of these urban and regional changes. The results show the comparative spatial study from each historical period.",book:{id:"11488",title:"GIS and Spatial Analysis",coverURL:"https://cdn.intechopen.com/books/images_new/11488.jpg"},signatures:"Efthymios-Spyridon Georgiou"},{id:"83032",title:"Introductory Chapter: Solar Photovoltaic Energy",slug:"introductory-chapter-solar-photovoltaic-energy",totalDownloads:7,totalDimensionsCites:0,doi:"10.5772/intechopen.106259",abstract:null,book:{id:"9862",title:"Solar Radiation - Measurements, Modeling and Forecasting for Photovoltaic Solar Energy Applications",coverURL:"https://cdn.intechopen.com/books/images_new/9862.jpg"},signatures:"Mohammadreza Aghaei, Amir Nedaei, Aref Eskandari and Jafar Milimonfared"},{id:"82963",title:"Evolution of Radio Source Components and the Quasar/Galaxy Unification Scheme",slug:"evolution-of-radio-source-components-and-the-quasar-galaxy-unification-scheme",totalDownloads:5,totalDimensionsCites:0,doi:"10.5772/intechopen.106244",abstract:"In this work, a theoretical model is developed for explanation of temporal evolution of extragalactic radio sources via beaming, orientation effects and asymmetries. Equation of the form D≈P±q1+z−m is used to account for the D ∼ P/z relation. Also, D≈D01+z−1+z1+z2 accounted properly for Ω0=1 cosmology than the Ω0=0 counterpart in linear size versus redshift of radio sources. Similarly, D=Dc1∓lnPPc1/2 model explained redshift-luminosity relationship of extragalactic radio sources. The results from the regression analyses are q = +0.003 (r = 0.04) for sources with z < 1 and q = −1.59 (r = −0.6) for all z≥1 sources. A critical linear size, Dc of 316kpc which matches the maximum theoretical linear size, Dmax of 0.15D0 at a critical redshift zc∼1 and a critical luminosity Pc=26.33WHz−1 are obtained. The indication of all these results is that the linear size of radio sources evolves up to a certain limit in D–P plane and thereafter decreases with increasing luminosity as predicted in this work.",book:{id:"11737",title:"Astronomy",coverURL:"https://cdn.intechopen.com/books/images_new/11737.jpg"},signatures:"Costecia Ifeoma Onah, Augustine A. Ubachukwu and Finbarr C. Odo"},{id:"82981",title:"Wood Quality and Pulping Process Efficiency of Elite Eucalyptus spp. Clones Field-Grown under Seasonal Drought Stress",slug:"wood-quality-and-pulping-process-efficiency-of-elite-eucalyptus-spp-clones-field-grown-under-seasona",totalDownloads:9,totalDimensionsCites:0,doi:"10.5772/intechopen.106341",abstract:"The objective of the present study is to evaluate the wood quality of five elite Eucalyptus spp. clones at 4 years of age from a clonal test installed in a region of seasonal drought stress in central-western Brazil focusing on pulp production. A total of 25 trees were systematically felled and disks and logs were obtained along the trunk. Wooden disks were used for density and fiber analyses and the logs were converted into chips for application in the pulping process. For the denser genotype, clone D (E. grandis x E. urophylla x Eucalyptus tereticornis), a thicker cell wall associated to thinner fibers results in a negative effect on the fiber quality. In contrast, clone B (Eucalyptus pellita x E. grandis), which has relatively inferior pulping performance, displayed the lowest wood density associated to wider lumen and fibers. 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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:"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:"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:null,institution:null},{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:"417317",title:"Mrs.",name:"Chiedza",middleName:null,surname:"Elvina Mashiri",slug:"chiedza-elvina-mashiri",fullName:"Chiedza Elvina Mashiri",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Midlands State University",country:{name:"Zimbabwe"}}},{id:"352140",title:"Dr.",name:"Edina",middleName:null,surname:"Chandiwana",slug:"edina-chandiwana",fullName:"Edina Chandiwana",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Midlands State University",country:{name:"Zimbabwe"}}},{id:"342259",title:"B.Sc.",name:"Leonard",middleName:null,surname:"Mushunje",slug:"leonard-mushunje",fullName:"Leonard Mushunje",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Midlands State University",country:{name:"Zimbabwe"}}},{id:"347042",title:"Mr.",name:"Maxwell",middleName:null,surname:"Mashasha",slug:"maxwell-mashasha",fullName:"Maxwell Mashasha",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Midlands State University",country:{name:"Zimbabwe"}}},{id:"2941",title:"Dr.",name:"Alberto J.",middleName:"Jorge",surname:"Rosales-Silva",slug:"alberto-j.-rosales-silva",fullName:"Alberto J. Rosales-Silva",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"437913",title:"Dr.",name:"Guillermo",middleName:null,surname:"Urriolagoitia-Sosa",slug:"guillermo-urriolagoitia-sosa",fullName:"Guillermo Urriolagoitia-Sosa",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"435126",title:"Prof.",name:"Joaquim",middleName:null,surname:"José de Castro Ferreira",slug:"joaquim-jose-de-castro-ferreira",fullName:"Joaquim José de Castro Ferreira",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Aveiro",country:{name:"Portugal"}}},{id:"437899",title:"MSc.",name:"Miguel Angel",middleName:null,surname:"Ángel Castillo-Martínez",slug:"miguel-angel-angel-castillo-martinez",fullName:"Miguel Angel Ángel Castillo-Martínez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"289955",title:"Dr.",name:"Raja",middleName:null,surname:"Kishor Duggirala",slug:"raja-kishor-duggirala",fullName:"Raja Kishor Duggirala",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Jawaharlal Nehru Technological University, Hyderabad",country:{name:"India"}}}]}},subseries:{item:{id:"5",type:"subseries",title:"Parasitic Infectious Diseases",keywords:"Blood Borne Parasites, Intestinal Parasites, Protozoa, Helminths, Arthropods, Water Born Parasites, Epidemiology, Molecular Biology, Systematics, Genomics, Proteomics, Ecology",scope:"Parasitic diseases have evolved alongside their human hosts. In many cases, these diseases have adapted so well that they have developed efficient resilience methods in the human host and can live in the host for years. Others, particularly some blood parasites, can cause very acute diseases and are responsible for millions of deaths yearly. Many parasitic diseases are classified as neglected tropical diseases because they have received minimal funding over recent years and, in many cases, are under-reported despite the critical role they play in morbidity and mortality among human and animal hosts. The current topic, Parasitic Infectious Diseases, in the Infectious Diseases Series aims to publish studies on the systematics, epidemiology, molecular biology, genomics, pathogenesis, genetics, and clinical significance of parasitic diseases from blood borne to intestinal parasites as well as zoonotic parasites. We hope to cover all aspects of parasitic diseases to provide current and relevant research data on these very important diseases. In the current atmosphere of the Coronavirus pandemic, communities around the world, particularly those in different underdeveloped areas, are faced with the growing challenges of the high burden of parasitic diseases. At the same time, they are faced with the Covid-19 pandemic leading to what some authors have called potential syndemics that might worsen the outcome of such infections. Therefore, it is important to conduct studies that examine parasitic infections in the context of the coronavirus pandemic for the benefit of all communities to help foster more informed decisions for the betterment of human and animal health.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11401,editor:{id:"67907",title:"Dr.",name:"Amidou",middleName:null,surname:"Samie",slug:"amidou-samie",fullName:"Amidou Samie",profilePictureURL:"https://mts.intechopen.com/storage/users/67907/images/system/67907.jpg",biography:"Dr. Amidou Samie is an Associate Professor of Microbiology at the University of Venda, in South Africa, where he graduated for his PhD in May 2008. He joined the Department of Microbiology the same year and has been giving lectures on topics covering parasitology, immunology, molecular biology and industrial microbiology. 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