Comparison of the effectiveness of interferon in chronic myeloproliferative disorders.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"9322",leadTitle:null,fullTitle:"Hybrid Nanomaterials - Flexible Electronics Materials",title:"Hybrid Nanomaterials",subtitle:"Flexible Electronics Materials",reviewType:"peer-reviewed",abstract:"Two of the hottest research topics today are hybrid nanomaterials and flexible electronics. As such, this book covers both topics with chapters written by experts from across the globe. Chapters address hybrid nanomaterials, electronic transport in black phosphorus, three-dimensional nanocarbon hybrids, hybrid ion exchangers, pressure-sensitive adhesives for flexible electronics, simulation and modeling of transistors, smart manufacturing technologies, and inorganic semiconductors.",isbn:"978-1-83880-338-4",printIsbn:"978-1-83880-337-7",pdfIsbn:"978-1-78985-651-4",doi:"10.5772/intechopen.83326",price:119,priceEur:129,priceUsd:155,slug:"hybrid-nanomaterials-flexible-electronics-materials",numberOfPages:148,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"beff6cce44f54582ee8a828759d24f19",bookSignature:"Rafael Vargas-Bernal, Peng He and Shuye Zhang",publishedDate:"June 10th 2020",coverURL:"https://cdn.intechopen.com/books/images_new/9322.jpg",numberOfDownloads:6669,numberOfWosCitations:7,numberOfCrossrefCitations:14,numberOfCrossrefCitationsByBook:1,numberOfDimensionsCitations:25,numberOfDimensionsCitationsByBook:1,hasAltmetrics:0,numberOfTotalCitations:46,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 12th 2019",dateEndSecondStepPublish:"September 23rd 2019",dateEndThirdStepPublish:"November 22nd 2019",dateEndFourthStepPublish:"February 10th 2020",dateEndFifthStepPublish:"April 10th 2020",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"182114",title:"D.Sc.",name:"Rafael",middleName:null,surname:"Vargas-Bernal",slug:"rafael-vargas-bernal",fullName:"Rafael Vargas-Bernal",profilePictureURL:"https://mts.intechopen.com/storage/users/182114/images/system/182114.jpeg",biography:"Rafael Vargas-Bernal received a bachelor's degree in Communications and Electronics Engineering from the University of Guanajuato in 1995, and the degrees of Master of Science and Doctorate in Sciences with Specialty in Electronics from the National Institute of Astrophysics, Optics and Electronics (INAOE) in 1997 and 2000, respectively. Since January 2002, he has been a professor-researcher at the Higher Technological Institute of Irapuato (ITESI) and, particularly since 2006, he has worked in the Department of Materials Engineering where he has established himself as a senior researcher. He has authored 1 book, 16 articles in journals, 42 chapters in books, and about 150 conference articles. He is a member of the National System of Researchers (SNI-Mexico). He regularly serves as a reviewer of scientific articles in RSC Advances, Royal Society Open Science, Materials Science and Engineering B, New Journal of Chemistry, Sensors and Actuators B: Chemical, Applied Surface Science, Journal of Alloys and Compounds, Materials Today Communications, Sensors, Aggregate, Advances in Polymer Technology, Advances in Materials Science and Engineering, IET Circuits, Devices and Systems, Nanoscale, SoftwareX, IEEE Electron Device Letters, IEEE Transactions on Nanotechnology, as well as reviewer of standards in Semiconductor Equipment and Materials International (SEMI). His research interests include telecommunications, two-dimensional materials, nanomaterials, aerospace materials, composite materials, MEMS, advanced materials, gas sensors, and biosensors.",institutionString:null,position:null,outsideEditionCount:null,totalCites:0,totalAuthoredChapters:"9",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Instituto Tecnológico Superior de Irapuato",institutionURL:null,country:{name:"Mexico"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"297762",title:"Dr.",name:"Peng",middleName:null,surname:"He",slug:"peng-he",fullName:"Peng He",profilePictureURL:"https://mts.intechopen.com/storage/users/297762/images/system/297762.jpeg",biography:"Prof. Peng He is the Duty Director of the State Key Laboratory of Advanced Welding and Joining, China. He has been an Executive Member of the ISO-Welding Standard Committee from 2014 and has been an Executive Member of the International Materials Science & Joining Technologies Committee from 2012. Up to now, he has written 292 papers and 7 books, developed 39 patents, and received 13 awards in materials science. He is currently researching materials processing, micro-joining, and reliability.",institutionString:"Harbin Institute of Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Harbin Institute of Technology",institutionURL:null,country:{name:"China"}}},coeditorTwo:{id:"255004",title:"Dr.",name:"Shuye",middleName:null,surname:"Zhang",slug:"shuye-zhang",fullName:"Shuye Zhang",profilePictureURL:"https://mts.intechopen.com/storage/users/255004/images/system/255004.jpeg",biography:"Dr. Zhang has been a lecturer at State Key Lab of Advanced Welding and Joining since 2017. He is focusing on novel and advanced materials for nanofabrication and nanodevices. He has published forty SCI&EI indexed papers, including ten IEEE conference papers, in IEEE Transactions on Components, Packaging and Manufacturing Technology, Journal of Materials Science: Materials in Electronics, Journal of Alloys and Compounds, and Advanced Materials. Dr. Zhang is the session chair of IEEE NANO 2019 and co-session chair of IEEE 3M NANO 2018 and 2019.",institutionString:"Harbin Institute of Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Harbin Institute of Technology",institutionURL:null,country:{name:"China"}}},coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"17",title:"Nanotechnology and Nanomaterials",slug:"nanotechnology-and-nanomaterials"}],chapters:[{id:"71831",title:"Introductory Chapter: Hybrid Nanomaterials",doi:"10.5772/intechopen.92012",slug:"introductory-chapter-hybrid-nanomaterials",totalDownloads:915,totalCrossrefCites:3,totalDimensionsCites:5,hasAltmetrics:0,abstract:null,signatures:"Rafael Vargas-Bernal",downloadPdfUrl:"/chapter/pdf-download/71831",previewPdfUrl:"/chapter/pdf-preview/71831",authors:[{id:"182114",title:"D.Sc.",name:"Rafael",surname:"Vargas-Bernal",slug:"rafael-vargas-bernal",fullName:"Rafael Vargas-Bernal"}],corrections:null},{id:"69106",title:"Electronic Transport in Few-Layer Black Phosphorus",doi:"10.5772/intechopen.89149",slug:"electronic-transport-in-few-layer-black-phosphorus",totalDownloads:685,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Subjected to an adequately high magnetic field, Landau levels (LLs) form to alter the electronic transport behavior of a semiconductor. Especially in two-dimensional (2D) limit, quantum Hall effect sheds light on a variety of intrinsic properties of 2D electronic systems. With the raising quality of field effect transistors (FET) based on few-layer black phosphorus (BP), electronic transport in quantum limit (quantum transport) has been extensively studied in literatures. This chapter investigates the electronic transport in few-layer BP, especially in quantum limit. At the beginning of this chapter, a brief introduction to the background of LL, edge state, and quantum Hall effect will be delivered. We then examine the fabrication of high-quality FET based on BP and their electronic performances followed by exploring the magnetoresistances of these high-quality devices which reveal Shubnikov-de Haas (SdH) oscillations and quantum Hall effect in BP. Intrinsic parameters like effective mass, Landé g-factor, and so on are discussed based on quantum transport.",signatures:"Gen Long, Xiaolong Chen, Shuigang Xu and Ning Wang",downloadPdfUrl:"/chapter/pdf-download/69106",previewPdfUrl:"/chapter/pdf-preview/69106",authors:[{id:"302575",title:"Dr.",name:"Gen",surname:"Long",slug:"gen-long",fullName:"Gen Long"},{id:"302576",title:"Dr.",name:"Ning",surname:"Wang",slug:"ning-wang",fullName:"Ning Wang"},{id:"302807",title:"Dr.",name:"Xiaolong",surname:"Chen",slug:"xiaolong-chen",fullName:"Xiaolong Chen"},{id:"309794",title:"Dr.",name:"Shuigang",surname:"Xu",slug:"shuigang-xu",fullName:"Shuigang Xu"}],corrections:null},{id:"69619",title:"Synthesis of Three-Dimensional Nanocarbon Hybrids by Chemical Vapor Deposition",doi:"10.5772/intechopen.89671",slug:"synthesis-of-three-dimensional-nanocarbon-hybrids-by-chemical-vapor-deposition",totalDownloads:817,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Carbon nanomaterials such as graphene, carbon nanotube (CNT), and carbon nanofiber (CNF) have received tremendous attentions in the past two decades due to their extraordinary mechanical strength and thermal and electrical properties. Recently, it indicates that three-dimensional (3D) nanocarbon hybrids overcome the weakness of individual low-dimensional nanocarbon materials and exhibit unique properties among carbon nanomaterials. Efforts have thus been made to acquire synergistic integration of one-dimensional (1D) and two-dimensional (2D) carbon nanomaterials. Meanwhile, chemical vapor deposition (CVD) is a widespread and effective method of fabricating three-dimensional nanocarbon hybrids compared with other synthetic methods. In this case, a number of 3D nanocarbon hybrids are synthesized by using different precursors at diverse temperature, and the nanocarbon hybrids are expected to be a promising choice for various application areas in the future.",signatures:"Hua-Fei Li, Shuguang Deng and Gui-Ping Dai",downloadPdfUrl:"/chapter/pdf-download/69619",previewPdfUrl:"/chapter/pdf-preview/69619",authors:[{id:"247902",title:"Prof.",name:"GuiPing",surname:"Dai",slug:"guiping-dai",fullName:"GuiPing Dai"},{id:"304258",title:"Prof.",name:"Shuguang",surname:"Deng",slug:"shuguang-deng",fullName:"Shuguang Deng"},{id:"310484",title:"Mr.",name:"Hua-Fei",surname:"Li",slug:"hua-fei-li",fullName:"Hua-Fei Li"}],corrections:null},{id:"71932",title:"Hybrid Ion Exchangers",doi:"10.5772/intechopen.92116",slug:"hybrid-ion-exchangers",totalDownloads:637,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Hybrid ion exchangers are of recent origin in the field of ion exchange chemistry. They have shown excellent chemical, mechanical and thermal stability conversant to both organic and inorganic counterparts. Very recently, new classes of ion exchangers have been studied by combining surfactants and inorganic metal phosphates. This article highlights the salient features of metal phosphates as ion exchangers, various development stages with the modifications, with an emphasis on the recent developments in the field of analytical chemistry, particularly surfactant-based hybrid fibrous and non-fibrous metal phosphates as ion exchangers. Surfactants or surface-active agents when present in the matrix of inorganic metal phosphates not only enhance their ion-exchange capacity but, also the selective adsorption of metal ions. Therefore, these materials are of great importance in industrial and environmental applications.",signatures:"Amita Somya",downloadPdfUrl:"/chapter/pdf-download/71932",previewPdfUrl:"/chapter/pdf-preview/71932",authors:[{id:"267347",title:"Dr.",name:"Amita",surname:"Somya",slug:"amita-somya",fullName:"Amita Somya"}],corrections:null},{id:"70587",title:"Pressure-Sensitive Adhesives for Flexible Display Applications",doi:"10.5772/intechopen.90619",slug:"pressure-sensitive-adhesives-for-flexible-display-applications",totalDownloads:901,totalCrossrefCites:3,totalDimensionsCites:6,hasAltmetrics:0,abstract:"Pressure-sensitive adhesives (PSA) have been used in electronics for not only attachment of two materials but also shock absorption, thermal and electrical conductivity, electromagnetic shielding, and optical property. Optically clear adhesives (OCA) have been used as a core material for optical performance of display. In addition to basic properties of OCA such as adhesion strength, transmittance, haze, and reliability, it has required dielectric constant, gap filling, and anticorrosion according to a substrate. However, the structural and functional changes of flexible display bring challenges to OCA that protects vulnerable components such as thin-film transistor, OLED, and thin-film encapsulation by stress dispersion and adjustment of a neutral plane. At the same time, flexibility and existing properties are essential. In this chapter, the development of components and performance of OCA, and evaluation methods will be discussed.",signatures:"Tae-Hyung Lee, Ji-Soo Kim, Jung-Hun Lee and Hyun-Joong Kim",downloadPdfUrl:"/chapter/pdf-download/70587",previewPdfUrl:"/chapter/pdf-preview/70587",authors:[{id:"189738",title:"Prof.",name:"Hyun-Joong",surname:"Kim",slug:"hyun-joong-kim",fullName:"Hyun-Joong Kim"},{id:"312227",title:"Mr.",name:"Jung-Hun",surname:"Lee",slug:"jung-hun-lee",fullName:"Jung-Hun Lee"},{id:"312228",title:"Ms.",name:"Ji-Soo",surname:"Kim",slug:"ji-soo-kim",fullName:"Ji-Soo Kim"},{id:"315617",title:"Mr.",name:"Tae-Hyung",surname:"Lee",slug:"tae-hyung-lee",fullName:"Tae-Hyung Lee"}],corrections:null},{id:"70330",title:"Numerical Simulation and Compact Modeling of Thin Film Transistors for Future Flexible Electronics",doi:"10.5772/intechopen.90301",slug:"numerical-simulation-and-compact-modeling-of-thin-film-transistors-for-future-flexible-electronics",totalDownloads:751,totalCrossrefCites:5,totalDimensionsCites:6,hasAltmetrics:0,abstract:"In this chapter, we present a finite element method (FEM)-based numerical device simulation of low-voltage DNTT-based organic thin film transistor (OTFT) by considering field-dependent mobility model and double-peak Gaussian density of states model. Device simulation model is able to reproduce output characteristics in linear and saturation region and transfer characteristics below and above threshold region. We also demonstrate an approach for compact modeling and compact model parameter extraction of organic thin film transistors (OTFTs) using universal organic TFT (UOTFT) model by comparing the compact modeling results with the experimental results. Results obtained from technology computer-aided design (TCAD) simulation and compact modeling are compared and contrasted with experimental results. Further we present simulations of voltage transfer characteristic (VTC) plot of polymer P-channel thin film transistor (PTFT)-based inverter to assess the compact model against simple logic circuit simulation using SmartSpice and Gateway.",signatures:"Arun Dev Dhar Dwivedi, Sushil Kumar Jain, Rajeev Dhar Dwivedi and Shubham Dadhich",downloadPdfUrl:"/chapter/pdf-download/70330",previewPdfUrl:"/chapter/pdf-preview/70330",authors:[{id:"153167",title:"Dr.",name:"Arun Dev Dhar",surname:"Dwivedi",slug:"arun-dev-dhar-dwivedi",fullName:"Arun Dev Dhar Dwivedi"},{id:"322076",title:"Dr.",name:"Sushil Kumar",surname:"Jain",slug:"sushil-kumar-jain",fullName:"Sushil Kumar Jain"},{id:"322077",title:"Dr.",name:"Rajeev Dhar",surname:"Dwivedi",slug:"rajeev-dhar-dwivedi",fullName:"Rajeev Dhar Dwivedi"},{id:"322078",title:"Dr.",name:"Shubham",surname:"Dadhich",slug:"shubham-dadhich",fullName:"Shubham Dadhich"}],corrections:null},{id:"69281",title:"Smart Manufacturing Technologies for Printed Electronics",doi:"10.5772/intechopen.89377",slug:"smart-manufacturing-technologies-for-printed-electronics",totalDownloads:1087,totalCrossrefCites:3,totalDimensionsCites:8,hasAltmetrics:0,abstract:"Fabrication of electronic devices on different flexible substrates is an area of significant interest due to low cost, ease of fabrication, and manufacturing at ambient conditions over large areas. Over the time, a number of printing technologies have been developed to fabricate a wide range of electronic devices on nonconventional substrates according to the targeted applications. As an increasing interest of electronic industry in printed electronics, further expansion of printed technologies is expected in near future to meet the challenges of the field in terms of scalability, yield, and diversity and biocompatibility. This chapter presents a comprehensive review of various printing electronic technologies commonly used in the fabrication of electronic devices, circuits, and systems. The different printing techniques based on contact/noncontact approach of the printing tools with the target substrates have been explored. These techniques are assessed on the basis of ease of operation, printing resolutions, processability of materials, and ease of optimization of printed structures. The various technical challenges in printing techniques, their solutions with possible alternatives, and the potential research directions are highlighted. The latest developments in assembling various printing tools for enabling high speed and batch manufacturing through roll-to-roll systems are also explored.",signatures:"Saleem Khan, Shawkat Ali and Amine Bermak",downloadPdfUrl:"/chapter/pdf-download/69281",previewPdfUrl:"/chapter/pdf-preview/69281",authors:[{id:"308939",title:"Dr.",name:"Saleem",surname:"Khan",slug:"saleem-khan",fullName:"Saleem Khan"},{id:"310184",title:"Dr.",name:"Shawkat",surname:"Ali",slug:"shawkat-ali",fullName:"Shawkat Ali"},{id:"310185",title:"Prof.",name:"Amine",surname:"Bermak",slug:"amine-bermak",fullName:"Amine Bermak"}],corrections:null},{id:"71199",title:"Plastic Inorganic Semiconductors for Flexible Electronics",doi:"10.5772/intechopen.91195",slug:"plastic-inorganic-semiconductors-for-flexible-electronics",totalDownloads:876,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Featured with bendability and deformability, smartness and lightness, flexible materials and devices have wide applications in electronics, optoelectronics, and energy utilization. The key for flexible electronics is the integration of flexibility and decent electrical performance of semiconductors. It has long been realized that high-performance inorganic semiconductors are brittle, and the thinning-down-induced flexibility does not change the intrinsic brittleness. This inconvenient fact severely restricts the fabrication and service of inorganic semiconductors in flexible and deformable electronics. By contrast, flexible and soft polymers can be readily deformed but behave poorly in terms of electrical properties. Recently, Ag2S was discovered as the room-temperature ductile inorganic semiconductor. The intrinsic flexibility and plasticity of Ag2S are attributed to multicentered chemical bonding and solid linkage among easy slip planes. Furthermore, the electrical and thermoelectric properties of Ag2S can be readily optimized by Se/Te alloying while the ductility is maintained, giving birth to a high-efficiency full inorganic flexible thermoelectric device. This chapter briefly reviews this big discovery, relevant backgrounds, and research advances and tries to demonstrate a clear structure-performance correlation between crystal structure/chemical bonding and mechanical/electrical properties.",signatures:"Tian-Ran Wei, Heyang Chen, Xun Shi and Lidong Chen",downloadPdfUrl:"/chapter/pdf-download/71199",previewPdfUrl:"/chapter/pdf-preview/71199",authors:[{id:"312244",title:"Dr.",name:"Lidong",surname:"Chen",slug:"lidong-chen",fullName:"Lidong Chen"},{id:"312245",title:"Dr.",name:"Xun",surname:"Shi",slug:"xun-shi",fullName:"Xun Shi"},{id:"322080",title:"Dr.",name:"Tian-Ran",surname:"Wei",slug:"tian-ran-wei",fullName:"Tian-Ran Wei"},{id:"322081",title:"Dr.",name:"Heyang",surname:"Chen",slug:"heyang-chen",fullName:"Heyang Chen"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"5884",title:"Unraveling the Safety Profile of Nanoscale Particles and Materials",subtitle:"From Biomedical to Environmental Applications",isOpenForSubmission:!1,hash:"5e5811aa0f15ab9d8b6a235e8408875d",slug:"unraveling-the-safety-profile-of-nanoscale-particles-and-materials-from-biomedical-to-environmental-applications",bookSignature:"Andreia C. 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Holistic Principles to Transform Cities for Sustainability",doi:"10.5772/23957",slug:"what-is-green-urbanism-holistic-principles-to-transform-cities-for-sustainability",body:'This book chapter first looks at the timeline of important publications on sustainable design that emerged from different schools of thought, and how gradually the notion of
Over the last thirty-five years or so, an international debate on eco-city theory has emerged and has developed as a relevant research field concerning the future of urbanism and the city itself. During that time, a number of architectural schools of thought have been implemented worldwide. One such school is
In 1972, the
At the end of the 20th century, Tokyo, Sao Paulo, Mexico-City, Mumbai, Calcutta, Shanghai and Beijing have grown to become endless urban landscapes. They are new types of mega-cities, which express an impossibility of orderly planning and strategic regulation. In his 1994 essay, Rem Koolhaas rightly asked `What ever happened to urbanism?’. In 2000, the term `Climate Change’ has been getting widely introduced. We find emerging Green Urbanism theory for the 21st century, which aims to transform existing cities from fragmentation to compaction. Eco-city theory focuses on adjusting the relationship between city and nature. Leading sociologists and urban theorists, including Ulrich Beck, Saskia Sassen, Richard Sennett, Jan Gehl, Manuel Castells, Anthony Giddens, Herbert Girardet, Thomas Sieverts, to name just a few, are exploring wider areas such as globalization, urban sustainability, ecology, network systems, information and communication technologies, and other related fields. Federico Butera, Ken Yeang, Richard Burdett, Jaime Lerner and Jeffrey Kenworthy also made some important contributions to the discussion of sustainable urban planning. Solar cities in Linz-Pichling (Austria), Freiburg-Vauban and the Solar District Freiburg-Schlierberg (Germany), Hanover-Kronsberg (Germany), Stockholm Hammarby-Sjöstad (Sweden), the BedZED Development in Sutton (South of London, UK), and the green district EVA Lanxmeer in Culemborg (The Netherlands) represent some of the built milestones in sustainable urban development at the beginning of the 21st century. The Swedish city of Vaexjö has been very successful in reducing its CO2 emissions and will be, by 2015, entirely independent from fossil fuels. The industrial park in Kalundborg (Denmark) is often cited as a model for industrial ecology, while the city of Waitakere, in the Western part of the greater Auckland urban region, is New Zealand’s first eco-city. More recently, excellent compilations of research on sustainable cities have been published by
Satterthwaite, Wheeler and Beatley. In the meantime, `Sustainability Science’ has emerged as a conceptual and theoretical basis for a new planning paradigm. Today, we can probably recognize two major breaks in the continuous development of cities. The first is connected to the introduction of the automobile, which made possible an entirely different, dispersed city model (the de-compacted `Functional City’ of the 20th century). The second, the full awareness of climate change, is of equal importance and just as far-reaching, raising the possibility of entirely new city models and typologies that are likely to emerge: Green Urbanism.
Cities can and must become the most environmentally-friendly model for inhabiting our earth. It is more important than ever to re-conceptualize existing cities and their systems of infrastructure, to be compact, mixed-use and polycentric cities.
This part introduces the
With all this technological progress, we should not lose sight of the fact that a key component in any society’s sustainability is more than its carbon footprint. The future of our societies is not just merely a technical matter of finding more eco-friendly energy solutions, but a question of holistic social sustainability and identifying principles for healthy communities.
The three pillars of Green Urbanism, and the interaction between these pillars. Diagram: courtesy the author, 2007.
The districts and cities where
respond well to their climate, location, orientation and context, optimizing natural assets such as sunlight and wind flow,
are quiet, clean and effective, with a healthy microclimate,
have reduced or have no CO2 emissions, as they are self-sufficient energy producers, powered by renewable energy sources,
eliminate the concept of waste, as they are based on a closed-loop ecosystem with significant recycling, reusing, remanufacturing and composting,
have high water quality, practicing sensitive urban water management,
The holistic concept of Eco-City has again a balanced relationship between the urban (city) and the rural (countryside). Diagram: courtesy the author, 2008.
integrate landscape, gardens and green roofs to maximize urban biodiversity and mitigate the urban heat island effect,
take only their fair share of the earth’s resources, using principles of urban ecology,
apply new technologies such as co-generation, solar cooling and electric-mobility,
provide easy accessibility and mobility, are well inter-connected, and provide an efficient low-impact public transport system,
use regional and local materials and apply prefabricated modular construction systems,
create a vibrant sense of place and authentic cultural identity, where existing districts are densified and make use of urban mixed-use infill projects,
are generally more compact communities around transport nodes (`green TODs’), with a special concern for affordable housing and mixed-use programs,
use deep green passive design strategies and solar architecture concepts for all buildings, with compact massing for reduced heat gain in summer,
are laid-out and oriented in a way that keeps the buildings cool in summer, but which catches the sun in winter,
have a local food supply through community gardens and urban farming and which achieve high food security and reduced `food miles’, and
use multi-disciplinary approach, best practice for urban governance and sustainable procurement methods.
All these criteria make it clear that our design focus should be on the neighbourhood and district scale, with projects on urban infill or redevelopment (brownfield) sites, adjacent to existing developed areas and transport nodes (avoiding further greenfield sites or master planned developments in non-urban areas). The following
The following is a short list of the principles; for full discussion, see my book ‘The Principles of Green Urbanism. Transforming the City for Sustainability’ (2010). It must be noted, though, that in order to enable sustainable urban development and to ensure that eco-districts are successful on many levels, all urban design components need to work interactively and cannot be looked at separately. The principles are based on the triple-zero framework (triple-bottom line) of:
zero fossil-fuel energy use
zero waste
zero emissions (aiming for low-to-no-carbon emissions).
`Zero waste’ means that buildings are fully demountable and fully recyclable at the end of their life-cycle, so that the site can return to being a greenfield site after use. Understandably, it requires a holistic approach to put the principles in action and to guide the available know-how to the advantage of the city. The principles describe the strategies necessary for eco-districts, although they need to be adapted to the location, context and scale of the urban development. It may be difficult at first to achieve some of the principles, but all are important; they can potentially save money, reach early payback, improve livability and increase opportunities for social interaction of residents. The principles offer practical steps on the path to sustainable cities, harmonizing growth and usage of resources. The truly `carbon-neutral’ city has not yet been built, but all projects introduced in this book are important steps towards turning this vision into a reality.
The sustainability matrix – the
Principle 1 Climate and context
The city based on its climatic conditions, with appropriate responses to location and site context. What are the unique site constraints, climatic conditions and opportunities?
Every site or place has its own unique individual conditions in regard to orientation, solar radiation, rain, humidity, prevailing wind direction, topography, shading, lighting, noise, air pollution and so on. The various aspects of this principle include: Climatic conditions, which are seen as the fundamental influence for form-generation in the design of any project; understanding the site and its context, which is essential at the beginning of every sustainable design project; optimizing orientation and compactness to help reduce the city district’s heat gain or losses; achieving a city with minimized environmental footprint by working with the existing landscape, topography and resources particular to the site, and the existing micro-climate of the immediate surroundings. Maintaining complexity in the system is always desirable (be it biodiversity, eco-system or neighbourhood layout), and a high degree of complexity is always beneficial for society. Enhancing the opportunities offered by topography and natural setting leads to a city well adapted to the local climate and its eco-system. We can use the buildings’ envelope to filter temperature, humidity, light, wind and noise. Due to the different characteristics of every location, each city district has to come up with its own methods and tailored strategies to reach sustainability and to capture the spirit of the place. Each site or city is different and the drivers for re-engineering existing districts will need to understand how to take full advantage of each location’s potential, and how to fine-tune the design concept to take advantage of local circumstances. As an aim, all urban development must be in harmony with the specific characteristics, various site factors and advantages of each location and be appropriate to its societal setting and contexts (cultural, historical, social, geographical, economical, environmental and political). In future, all buildings will have climate-adapted envelope technologies, with facades that are fully climate-responsive.
Principle 2 Renewable energy for zero CO2 emissions
The city as a self-sufficient on-site energy producer, using decentralized district energy systems. How can energy be generated and supplied emission-free and in the most effective way?
The various aspects of this principle include: Energy supply systems and services, as well as energy efficient use and operation, promoting increased use of renewable power, and perhaps natural gas as a transition fuel in the energy mix, but always moving quickly away from heavy fossil-fuels such as coal and oil; and the transformation of the city district from an energy consumer to an energy producer, with local solutions for renewables and the increasing de-carbonizing of the energy supply. The supply of oil will last shorter than the life-expectancy of most buildings. The local availability of a renewable source of energy is the first selection criteria for deciding on energy generation. In general, a
well-balanced combination of energy sources can sensibly secure future supply. A necessary aim is also to have a distributed energy supply through a decentralized system, utilizing local renewable energy sources. This will transform city districts into local power stations of renewable energy sources, which will include solar PV, solar thermal, wind (on- and off-shore), biomass, geothermal power, mini-hydro energy and other new technologies. Some of the most promising technologies are in building-integrated PV, urban wind turbines, micro CHP and solar cooling. That is to say, there should be on-site electrical generation and energy storage in combination with a smart grid, which integrates local solar and wind generation, utilizing energy-efficiency in all its forms. Solar hot water systems would be compulsory. Co-generation technology utilizes waste heat through CHP combined-heat-and-power plants. Energy-efficiency programs are not enough. Too often we find that savings from energy-efficiency programs are absorbed by a rise in energy use. Genuine action on climate change means that coal-fired power stations cease to operate and are replaced by renewable energy sources. Eco-districts will need to operate on renewable energy sources as close to 100 per cent as possible. As a minimum, at least 50 per cent of on-site renewable energy generation should be the aim of all urban planning, where the energy mix comes from decentralized energy generation and takes into account the resources that are locally available, as well as the cost and the availability of the technology. Optimizing the energy balance can be achieved by using exchange, storage and cascading (exergy) principles. It is, therefore, essential that the fossil-fuel powered energy and transportation systems currently supporting our cities are rapidly turned into systems that are supplied by renewable energy sources. High building insulation, high energy-efficiency standards and the use of smart metering technology is essential, so that if a part of an office building is not in use, the intelligent building management system will shut down lights and ventilation.
Principle 3 Zero-waste city
The zero-waste city as a circular, closed-loop eco-system. How to avoid the creation of waste in the first place – changing behaviour of consumption?
Sustainable waste management means to turn waste into a resource. All cities should adopt nature’s zero-waste management system. Zero-waste urban planning includes reducing, recycling, reusing and composting waste to produce energy. All material flows need to be examined and fully understood, and special attention needs to be given to industrial waste and e-waste treatment. We need to plan for recycling centres, for zero landfill and ‘eliminating the concept of waste’ and better understanding nutrient flows (Braungart, 2002). Eco-districts are neighbourhoods where we reuse and recycle materials and significantly reduce the volume of solid waste and toxic chemical releases. All construction materials as well as the production of goods (and building components) need to be healthy and fully-recyclable. Waste prevention is always better than the treatment or cleaning-up after waste is formed. Some other systems that need to be put in place are: the remanufacturing of metals, glass, plastics, paper into new products needs to be a routine (without down-grading the product); waste-to-energy strategies are needed for residual waste; and an `extended producer responsibility’ clause is needed for all products. In this context of waste, better management of the nitrogen cycle has emerged as an important topic: to restore the balance to the nitrogen cycle by developing improved fertilization technologies, and technologies in capturing and recycling waste. Controlling the impact of agriculture on the global cycle of nitrogen is a growing challenge for sustainable development. Essentially, we need to become (again) a `recycling society’, where it is common that around 60 to 90 per cent of all waste is recycled and composted. In future, optimizing waste streams and material flows in regard to urban development will be guided by resource recovery and supply chains that use local materials, for achieving closed-cycle urban ecology and reduced material consumption.
Principle 4 Water
The city with closed urban water management and a high water quality. What is the situation in regard to the sustainable supply of potable drinking water?
The various aspects of this principle include, in general, reducing water consumption, finding more efficient uses for water resources, ensuring good water quality and the protection of aquatic habitats. The city can be used as a water catchment area by educating the population in water efficiency, promoting rainwater collection and using wastewater recycling and storm water harvesting techniques (e.g. solar-powered desalination plants). Storm water and flood management concepts need to be adopted as part of the urban design, and this includes storm water run-offs and improved drainage systems and the treatment of wastewater. As part of the eco-district’s adequate and affordable health care provisions, it needs to ensure the supply of safe water and sanitation. This includes such things as algae and bio-filtration systems for grey water and improving the quality of our rivers and lakes so that they are fishable and swimmable again. An integrated urban water cycle planning and management system that includes a high-performance infrastructure for sewage recycling (grey and black water recycling), storm water retention and harvesting the substantial run-off through storage, must be a routine in all design projects. On a household level we need to collect rain water and use it sparingly for washing and install dual-water systems and low-flush toilets. On a food production level we need to investigate the development of crops that need less water and are more drought resistant.
Principle 5 Landscape, gardens and urban biodiversity
The city that integrates landscapes, urban gardens and green roofs to maximize biodiversity. Which strategies can be applied to protect and maximize biodiversity and to re-introduce landscape and garden ideas back in the city, to ensure urban cooling?
A sustainable city takes pride in its many beautiful parks and public gardens. This pride is best formed through a strong focus on local biodiversity, habitat and ecology, wildlife rehabilitation, forest conservation and the protecting of regional characteristics. Ready access to these public parks, gardens and public spaces, with opportunities for leisure and recreation, are essential components of a healthy city. As is arresting the loss of biodiversity by enhancing the natural environment and landscape, and planning the city using ecological principles based on natural cycles (not on energy-intensive technology) as a guide, and increasing urban vegetation. A city that preserves and maximizes its open spaces, natural landscapes and recreational opportunities is a more healthy and resilient city. The sustainable city also needs to introduce inner-city gardens, urban farming/agriculture and green roofs in all its urban design projects (using the city for food supply). It needs to maximize the resilience of the eco-system through urban landscapes that mitigate the `urban heat island’ (UHI) effect, using plants for air-purification and urban cooling. Further, the narrowing of roads, which calms traffic and lowers the UHI effect, allows for more (all-important) tree planting. Preserving green space, gardens and farmland, maintaining a green belt around the city, and planting trees everywhere (including golf courses), as trees absorb CO2, is an important mission. As is conserving natural resources, respecting natural energy streams and restoring stream and river banks, maximizing species diversity. At home, we need to de-pave the driveway or tear up parking lots. In all urban planning, we need to maintain and protect the existing eco-system that stores carbon (e.g. through a grove or a park), and plan for the creation of new carbon storage sites by increasing the amount of tree planting in all projects. The increase in the percentage of green space as a share of total city land is to be performed in combination with densification activities.
Principle 6 Sustainable transport and good public space: compact and poly-centric cities
The city of eco-mobility, with a good public space network and an efficient low-impact public transport system for post-fossil-fuel mobility. How can we get people out of their cars, to walk, cycle, and use public transport?
Good access to basic transport services is crucial, as it helps to reduce automobile dependency, as does reducing the need to travel. We need to see integrated non-motorized transport, such as cycling or walking, and, consequently, bicycle/pedestrian-friendly environments, with safe bicycle ways, free rental bike schemes and pleasant public spaces. It is important to identify the optimal transport mix that offers inter-connections for public transport and the integration of private and public transport systems. Some ideas here include: eco-mobility concepts and smart infrastructure (electric vehicles); integrated transport systems (bus transit, light railway, bike stations); improved public space networks and connectivity, and a focus on transport-oriented development (`green TODs’). It is a fact that more and wider roads result in more car and truck traffic, and CO2 emissions, and also allows for sprawling development and suburbs that increases electricity-demand and provides less green space. The transport sector is responsible for causing significant greenhouse-gas emissions (over 20 per cent). To combat this effect we need to change our lifestyles by, for example, taking public transport, driving the car less, or car-pooling. Alternatively, we can ride a bike or walk, if the city district has been designed for it. Personal arrangements have the potential to reduce commuting and to boost community spirit. We want a city district which is well-connected for pedestrians, a city with streetscapes that encourage a healthy, active lifestyle and where residents travel less and less by car. `Green TODs’ are the future, as these developments can create a range of medium-density housing typologies and provide a variety of transportation choices, achieving a balance of residences and employment.
Principle 7 Local and sustainable materials with less embodied energy
City construction using regional, local materials with less embodied energy and applying prefabricated modular systems. What kind of materials are locally available and appear in regional, vernacular architecture?
The various aspects of this principle include: advanced materials technologies, using opportunities for shorter supply chains, where all urban designs focus on local materials and technological know-how, such as regional timber in common use. Affordable housing can be achieved through modular prefabrication. Prefabrication has come and gone several times in modern architecture, but this time, with closer collaboration with manufacturers of construction systems and building components in the design phase, the focus will be on sustainability. We need to support innovation and be aware of sustainable production and consumption, the embodied energy of materials and the flow of energy in closing life-cycles. We need to emphasize green manufacturing and an economy of means, such as process-integrated technologies that lead to waste reduction. It is more environmentally friendly to use lightweight structures, enclosures and local materials with less embodied energy, requiring minimal transport. We need improved material and system specifications, supported by research in new materials and technological innovation; reduced material diversity in multi-component products to help facilitate the design for resource recovery, disassembly, value retention, and the possibility of reusing entire building components. Success in this area will increase the long-term durability of buildings, reduce waste and minimize packaging.
Principle 8 Density and retrofitting of existing districts
The city with retrofitted districts, urban infill, and densification/intensification strategies for existing neighbourhoods. What are the opportunities to motivate people to move back to the city, closer to workplaces in the city centre?
The various aspects of this principle include: encouraging the densification of the city centre through mixed-use urban infill, centre regeneration and green TODs; increasing sustainability through density and compactness (compact building design means developing buildings vertically rather than horizontally); promoting business opportunities around green transit-oriented developments; optimizing the relationship between urban planning and transport systems; retrofitting inefficient building stock and systematically reducing the city district’s carbon footprint. Consideration will need to be given to better land-use planning to reduce the impact of urban areas on agricultural land and landscape; to increasing urban resilience by transforming city districts into more compact communities and designing flexible typologies for inner-city living and working. Special strategies for large metropolitan areas and fast-growing cities are required. Here, examples of rapid development are being provided by Asian cities. Special strategies are also needed for small and medium-sized towns due to their particular milieu, and creative concepts are needed for the particular vulnerabilities of Small Island States and coastal cities. Public space upgrading through urban renewal programs will bring people back to the city centre. This will need some strategic thinking about how to use brownfield and greyfield developments and also the adaptive reuse of existing buildings. Remodeling and re-energizing existing city centres to bring about diverse and vibrant communities requires people to move back into downtown areas. This can be achieved through mixed-use urban infill projects, building the `city above the city’ by converting low density districts into higher density communities; and by revitalizing underutilized land for community benefit and affordable housing. In the compact city, every neighbourhood is sustainable and self-sufficient; and uses ESCo principles for self-financing energy efficiency and in all retrofitting programs.
Principle 9 Green buildings and districts, using passive design principles
The city that applies deep green building design strategies and offers solar access for all new buildings. How can we best apply sustainable design and passive design principles in all their forms and for all buildings?
The various aspects of this principle include: low-energy, zero-emission designs, applying best practice for passive design principles, for all buildings and groups of buildings; dramatically reducing building energy use; introducing compact solar architecture; and renovating and retrofitting the entire building stock. New design typologies need to be developed at low cost, and we need to produce functionally neutral buildings that last longer. We need to apply facade technology with responsive building skins for bio-climatic architecture, to take advantage of cooling breezes and natural cross-ventilation, maximizing cross-ventilation, day-lighting and opportunities for night-flush cooling; we need to focus on the low consumption of resources and materials, including the reuse of building elements; and design for disassembly. Other ideas include: mixed-use concepts for compact housing typologies; adaptive reuse projects that rejuvenate mature estates; solar architecture that optimizes solar gain in winter and sun shading technology for summer, catching the low winter sun and avoiding too much heat gain in summer. It is important to renew the city with energy-efficient green architecture, creating more flexible buildings of long-term value and longevity. Flexibility in plan leads to a longer life for buildings. Technical systems and services have a shorter life-cycle. This means, first of all, applying technical aids sparingly and making the most of all passive means provided by the building fabric and natural conditions. Buildings that generate more energy than they consume, and collect and purify their own water, are totally achievable. We need to acknowledge that the city as a whole is more important than any individual building.
Principle 10 Livability, healthy communities and mixed-use programs
The city with a special concern for affordable housing, mixed-use programs, and a healthy community. How does urban design recognize the particular need for affordable housing, to ensure a vibrant mix of society and multi-functional mixed-use programs?
Land use development patterns are the key to sustainability. A mixed-use (and mixed-income) city delivers more social sustainability and social inclusion, and helps to repopulate the city centre. Demographic changes, such as age, are a major issue for urban design. It is advantageous for any project to maximize the diversity of its users. Different sectors in the city can take on different roles over a 24 hours cycle; for example, the CBD is used for more than just office work. In general we want connected, compact communities, for a livable city, applying mixed-use concepts and strategies for housing affordability, and offering different typologies for different housing needs. To this end we need affordable and livable housing together with new flexible typologies for inner-city living. These mixed-use neighbourhoods (of housing types, prices and ownership forms) have to avoid gentrification and provide affordable housing with districts inclusive for the poor and the rich, young and old, and workers of all walks of life, and also provide secure tenure (ensuring ‘aging in place’). Housing typologies need to deal with demographic changes. We have to understand migration and diversity as both an opportunity and a challenge. Mixed land uses are particularly important as it helps reduce traffic. Master plans should require all private developments to contain 40 to 50 per cent of public (social) housing, and have it integrated with private housing. Higher densities should centre on green TODs. Essentially, these changes will aim to introduce more sustainable lifestyle choices, with jobs, retail, housing and a city campus being close by with IT and tele-working from home significantly helping to reduce the amount of travel (motto: `Don’t commute to compute’). By integrating a diverse range of economic and cultural activities, we avoid mono-functional projects, which generate a higher demand for mobility. Green businesses would be supported through the use of ethical investments to generate funding. The question is: how specific or adaptable should buildings be to their use?
Principle 11 Local food and short supply chains
The city for local food supply, with high food security and urban agriculture.
Which strategies can be applied to grow food locally in gardens, on roof tops and on small spaces in the city?
The various aspects of this principle include: local food production; regional supply; an emphasis on urban farming and agriculture, including `eat local’ and `slow food’ initiatives. The sustainable city makes provision for adequate land for food production in the city, a return to the community and to the allotment gardens of past days, where roof gardens become an urban market garden. It is essential that we bridge the urban-rural disconnect and move cities towards models that deal in natural eco-systems and healthy food systems. The people of the eco-city would garden and farm locally, sharing food, creating compost with kitchen scraps and garden clippings and growing `community’ vegetables. Buying and consuming locally will be necessary to cut down on petrol-based transport. Such things as re-using paper bags and glass containers, paper recycling and the cost of food processing will need reconsideration. We will need to reduce our consumption of meat and other animal products, especially shipped-in beef, as the meat cycle is very intensive in terms of energy and water consumption and herds create methane and demand great quantities of electricity. Perhaps as much as 50 per cent of our food will need to be organically produced, without the use of fertilizers or pesticides made from oil, and grown in local allotments.
Principle 12 Cultural heritages, identity and sense of place
The city of public health and cultural identity: a safe and healthy city, which is secure and just. How to maintain and enhance a city’s or region’s identity, unique character and valued urban heritage, avoiding interchangeable design that makes all cities look the same?
All sustainable cities aim for air quality, health and pollution reduction, to foster resilient communities, to have strong public space networks and modern community facilities. This is the nature of sustainable cities. However, each city has its own distinct environment, whether it be by the sea, a river, in a dessert, a mountain; whether its climate is tropical, arid, temperate, etc, each situation is unique. The design of the city will take all these factors into consideration, including materials, history and population desires. The essence of place is the up-swelling of grassroots strategies, the protection of its built heritage and the maintenance of a distinct cultural identity, e.g. by promoting locally owned businesses, supporting creativity and cultural development. New ideas require affordable and flexible studio space in historic buildings and warehouses. Cities will grow according to the details and unique qualities of localities, demographic qualities of the populace and the creativity of the authorities and citizens. The aim of a city is to support the health, the activities and the safety of its residents. It is, therefore, incumbent on city councils to protect the city by developing a master plan that balances heritage with conservation and development; fostering distinctive places with a strong sense of place, where densities are high enough to support basic public transit and walk-to retail services.
Principle 13 Improved urban governance, leadership and best practice
The city applying best practice for urban governance and sustainable procurement methods. Which networks and skills can be activated and utilized through engaging the local community and key stakeholders, to ensure sustainable outcomes?
Good urban governance is extremely important if we want to transform existing cities into sustainable compact communities. It has to provide efficient public transport, good public space and affordable housing, high standards of urban management, and without political support change will not happen. City councils need strong management and political support for their urban visions to be realized. They need strong support for a strategic direction in order to manage sustainability through coherent combined management and governance approaches, which include evolutionary and adaptive policies linked to a balanced process of review, and to public authorities overcoming their own unsustainable consumption practices and changing their methods of urban decision-making. A city that leads and designs holistically, that implements change harmoniously, and where decision-making and responsibility is shared with the empowered citizenry, is a city that is on the road to sustainable practices. In balancing community needs with development, public consultation exercises and grassroots participation are essential to ensuring people-sensitive urban design and to encouraging community participation. Citizens need to participate in community actions aimed at governments and big corporations, by writing letters and attending city-council hearings. Empowering and enabling people to be actively involved in shaping their community and urban environment is one of the hallmarks of a democracy. Cities are a collective responsibility. As far as bureaucratic urban governance and best practice is concerned, authorities could consider many of the following: updating building code and regulations; creating a database of best practice and worldwide policies for eco-cities; revising contracts for construction projects and integrated public management; raising public awareness; improving planning participation and policy-making; creating sustainable subdivisions, implementing anti-sprawl land-use and growth boundary policies; legislating for controls in density and supporting high-quality densification; arriving at a political decision to adopt the
Principle 14 Education, research and knowledge
The city with education and training for all in sustainable urban development.
How to best raise awareness and change behaviour?
The various aspects of this principle include: technical training and up-skilling, research, exchange of experiences, knowledge dissemination through research publications about ecological city theory and sustainable design. Primary and secondary teaching programs need to be developed for students in such subjects as waste recycling, water efficiency and sustainable behaviour. Changes in attitude and personal lifestyles will be necessary. The city is a hub of institutions, such as galleries and libraries and museums, where knowledge can be shared. We must provide sufficient access to educational opportunities and training for the citizenry, thus increasing their chances of finding green jobs. Universities can act as `think tanks’ for the transformation of their cities. We also need to redefine the education of architects, urban designers, planners and landscape architects. Research centres for sustainable urban development policies and best practice in eco-city planning could be founded, where assessment tools to measure environmental performance are developed and local building capacity is studied.
Principle 15 Strategies for cities in developing countries
Particular sustainability strategies for cities in developing countries, harmonizing the impacts of rapid urbanization and globalization. What are the specific strategies and measurements we need to apply for basic low-cost solutions appropriate to cities in the developing world?
Developing and emerging countries have their own needs and require particular strategies, appropriate technology transfers and funding mechanisms. Cities in the developing world cannot have the same strategies and debates as cities in the developed world. Similarly, particular strategies for emerging economies and fast-growing cities are required, as is the problem of informal settlements and urban slums and slum upgrading programs. Low-cost building and mass housing typologies for rapid urbanization are required in cooperation with poverty reduction programs. It is essential that we train local people to empower communities, creating new jobs and diversifying job structures, so as not to focus on only one segment of the economy (e.g. tourism). Achieving more sustainable growth for Asian metropolitan cities is a necessity. Combating climate change, which was mainly caused through the emissions by industrialized nations and which is having its worst effect in poorer countries in Africa, Asia and Latin America, with a focus on Small Island States, is a priority.
The presented principles are about holistic strategies and integrated approaches: The most successful solutions are now the highly effective combination of passive design principles with some well considered
Before electrical heating, cooling and illumination became common, architects used a combination of passive design principles to ensure that interiors were well lit and ventilated through passive means, without any use of mechanical equipment. However, since the early 1950s most architects and engineers have simply employed air-conditioning systems for cooling, as energy from fossil fuels was cheap and plentiful, and air-conditioning systems allowed for deep-plan buildings, internalized shopping mall complexes and other highly inefficient air-conditioning dependent building typologies.
The biggest energy consumers in buildings are technical installations for cooling interiors and lighting. The extensive use of glass surfaces in the facades of buildings (especially in hot, tropical or subtropical climates) and materials that easily store the heat in summer
The outlined 15 principles of Green Urbanism aim to guide urban designers and decision-makers. Diagram: courtesy the author, 2008.
frequently lead to solar overheating, which has led to the widespread use of mechanical systems (air-conditioning systems) (Aynsley, 2006). Buildings in the tropics are a particular challenge due to the high humidity and temperatures. However, the tropics are home to almost two-thirds of the world’s population, so practical and achievable solutions are of particular relevance. With more careful building design, energy-hungry air-conditioning systems could be avoided in almost any climate. Instead of the use of mechanical air-conditioning systems, substantial improvements in comfort can be achieved by the informed choice of materials appropriate to basic passive energy principles and the optimization of natural ventilation (cross-ventilation, night-flush cooling, mixed-mode systems), summer shading and winter solar heat gain. Solar and wind energy can provide heating, cooling and electric power.
On the other hand, buildings from a pre-air-conditioning era frequently display a convincing application of passive design principles, such as their optimized orientation, the use of evaporative cooling, strategic use of thermal mass, trompe walls, ingenious sun-shading devices for the western facade, solar chimneys, courtyards allowing for cross-ventilation of hot air at the highest point in the room, and natural cross-ventilation adjustable to the changing directions of a breeze. Sub-slab labyrinths for fresh air intake, activating the thermal mass, have recently seen a comeback in many projects. Such underground air chambers, called thermal labyrinths, are frequently used to ventilate rooms, with air cooled naturally by travelling a long distance underground through channels in the earth. Energy savings from the use of thermal labyrinths can be significant (Daniels, 1995, 2000). In addition, the use of local materials with less embodied energy (combined with local workforce and locally available technical know-how) has recently led to regional ‘styles’ in architecture.
Successful buildings of the future will increasingly rely on the critical examination of, and learning from, buildings of the past (Vale and Vale, 1991, 2000; Hyde, 2000). There is so much we can learn from such studies, e.g. which passive design principles have delivered the most
The average German household produces around 43.5 tonnes of greenhouse gas emissions per year. Diagram: courtesy Umweltbundesamt, Germany, 2009.
energy savings? How has adequate active and passive thermal storage mass been provided? There is a good reason why passive design principles have traditionally been preferred to (and are now once again being chosen over) active systems. ‘We need solutions for buildings that can do more with less technology’, argues engineer Gerhard Hausladen, adding: ‘The optimization of the building layout and detailing of the facade system are essential for an integrated approach to the design of low-energy consuming buildings and cities’ (Hausladen et al., 2005; 41). Just optimizing buildings through the application of passive design principles can deliver energy savings of up to 80 per cent (Hausladen et al., 2005).
A building’s location and its surroundings play a key role in regulating its indoor temperature, the illumination of space and the capacity to minimize energy use. For example, trees and landscaping can provide shade or block wind, while neighbouring buildings can overshadow a building and thus increase the need for illumination during daytime. This is why the designer needs to understand the site conditions and the effective application of passive design principles fully (Hall and Pfeiffer, 2000; Gauzin-Mueller, 2002; Treberspurg, 2008).
For buildings to have the minimum adverse impact on the natural and built environment, energy-efficient building design needs to balance a whole range of requirements from various inter-linked issues, including (but not limited to):
design strategies based on a deep understanding of site and context
strategies for energy efficiency (operational and embodied)
strategies for water efficiency
material efficiency: focusing on material flows and embodied energy (life cycle)
overall material and waste streams during construction, operation and demolition
integrating passive design principles, such as optimizing the building’s shape and orientation, employing natural ventilation, use of daylight, thermal mass, sun shading, solar gains, the use of courtyard typologies, etc.
reducing overall greenhouse gas emissions from construction, operation and demolition
integrating community well-being and sundry social dimensions
health and quality of indoor environment (occupants’ comfort).
The need to minimize non-renewable resource consumption and reduce waste poses significant challenges for the building designer as well as construction companies, and for building operators during the period of building use. It is obvious that some of the earliest design decisions have a significant impact on energy efficiency and opportunities to use passive solar power or natural ventilation, such as decisions on: building orientation, placement on site, compactness and geometry, typology, material choices, facade openings, etc.
While recognizing that using more electricity from non-fossil fuels (such as solar and wind power) will help to address climate change, the building designer is likely to focus primarily on cutting energy consumption (Keeler and Burke, 2009). Reducing energy consumption with energy-efficient building design strategies is vital because it helps to preserve finite resources, lowers costs for businesses and consumers and can often be accomplished relatively quickly (again, the
Buildings using passive design principles are usually naturally ventilated (or use mixed-mode systems, which is a combination of natural ventilation and additional mechanical cooling during summer months) and are well day-lit to minimize the need for active systems of climate control and artificial lighting (Daniels and Hindrichs, 2007). Green roofs help to cut energy consumption by providing insulation to the building and by acting as filtration for the rainwater capture system, and at the same time increasing the city’s biodiversity.
Studying the built heritage plays an important role in the shift towards a low-carbon society. It offers a large resource of knowledge about design principles and how architects have operated for hundreds of years within the challenges of hot, arid or tropical climates. This knowledge has not been sufficiently discussed, taught and researched. In the light of globalization, it is increasingly necessary for the existing authentic built heritage to be a significant contributor to local identity, helping to define the unique character of a location, supporting local people to achieve social outcomes and as a memory of a place. The diversity and rich complexity of tangible and intangible heritage is a constant inspiration that deserves to be better maintained and protected.
Research in pre-air-conditioning built heritage is particularly relevant for the future of the Asia-Pacific region, where we can find rapid urbanization, sometimes combined with too much reliance on outdated models of urban growth and building designs, thus further increasing energy demands. This can include an unusually high dependency on mechanical (air-conditioning) systems, thereby creating large CO2 emissions and high operating costs in both residential and commercial building stock. In current discussions about sustainability and climate change, we can observe a re-appreciation and evaluation of the built heritage in harmony with its climatic conditions and geographic location. The Asia-Pacific region’s humid tropical climate poses a particularly difficult problem. It has temperatures often around 30 degrees Celsius during the daytime and around 25 degrees Celsius at night, and has a high relative humidity of about 90 per cent. This is typical for Singapore, Hong Kong, Bangkok, Jakarta, Manila and other large tropical cities suffering from the Urban Heat Island (UHI) effect. Such conditions leave little scope for night-flush cooling, and refreshing breezes (air flow) are often lacking for long periods (Aynsley, 2006). Serious climate engineering strategies are needed, and the de-humidification of the air as part of a cooling process is a preferable option. There are some particularly exciting developments in the innovative area of ‘solar cooling’. So far, around 400 installations worldwide already use such innovative solar cooling technology (Kohlenbach, 2010).
The UHI effect has been particularly difficult for large cities located in tropical regions. Hong Kong, for instance, has a very high population density and is always praised for its efficient public transport systems (Owens, 1986; Newman and Kenworthy, 1989). But the city has an extremely high dependency on air-conditioning and the lack of natural air ventilation in the city has emerged as a serious planning issue. Most buildings are not insulated and lack any external sun shading of their facades.
Brooks and Hyde have pointed out how a site’s micro-climate can be modified through careful site planning, leading to improved thermal comfort of outdoor spaces, increased capacity for natural ventilation and sun control in buildings, and therefore reduced cooling loads (Brooks, 1988; Hyde, 2000). Traditionally, in cities in Asia and the Middle East, there has always existed a large repertoire of climatically adaptive and culturally sensitive urban form, which is found in the traditional use of courtyard typologies and low-rise housing, even in high-density districts, with narrow, shaded laneways. In addition, there is a variety of passive cooling techniques that can be utilized for particular climate types, such as shaded spaces with courtyards and atria for effective cross-ventilation, open circulation with breezeways and verandahs, roof ventilation, solar chimneys and similar techniques.
The main principles of material and energy-efficient design include:
optimal orientation, appropriate window size and sun control (effective shading)
compact building form (building geometry with less facade surface)
building mass modified to increase natural air flow through site (catching breezes)
cross-ventilation and day lighting, with effective external sun shading (e.g. a louver system for sun control, using vertical shading louvers at the eastern and western facades; these have the advantage of retaining the outside view and are more effective than horizontal louvers)
passive solar heating for winter months
evaporative cooling systems
strategic selection of materials for use of thermal mass (e.g. choice of lightweight or heavy construction materials, with exposed, ‘activated’ concrete surface)
rooftop vegetation, gardens and water surfaces for improved micro-climate and reduced heat load
night-flush cooling through openings, activating thermal mass (using night purge)
sub-slab labyrinths, bringing in outside air through underground, cool air channels beneath the slab
white (not dark) facade and roof colouring
optimal sun shading devices, with wide roof overhangs to shade windows
landscaping for westerly facade protection
high insulation of external walls and roofs.
These strategies are often combined to make them work together as a system; for instance, by linking high thermal capacity (thermal mass) for heat sink effects with passive solar heating, or with cross-ventilation for night-flush cooling (summer cooling). The use of lightweight exterior facade construction elements with low thermal capacity can help to avoid the accumulation, storage and re-radiation of heat.
Deep building plans, beyond a maximum of 15 metres in depth, have disadvantages, as these can significantly reduce the effectiveness of day lighting and natural ventilation, leading to greater dependency on air-conditioning systems, thereby negatively impacting on the occupants’ health, thermal comfort, productivity and overall working conditions. Therefore, four of the most applicable and widely used passive design strategies are:
avoiding large glazing that receives direct sunlight and is without shading (design of high quality external shading)
reducing the surface-to-volume ratio as much as possible through compact building massing
using window sizing strategically in the design of the building (depending on orientation)
maximizing day lighting and natural cross-ventilation through slim building plans.
A widely recognized green urbanism model district is \'Hammarby Sjöstad\', an inner-city district of the Swedish capital city of Stockholm. It occupies an area of about 200 hectares, which, according to the masterplan, will comprise 11,000 apartments, for about 20,000 residents, and an additional 200,000 sqm area of commercial space by the year 2018. The project, which was started in the mid 1990s, expands the inner city centre towards to the waterfront, having water as a central focus for the development. It is the conversion of an old industrial and harbour area (brownfield site) into a modern, sustainable neighbourhood.
Hammarby Sjöstad has a strong emphasis on design principles of ecology and environmental sustainability. The development links the city centre with the new urban district by using same street dimensions, block lengths, building heights, density and mix of uses as can be found in the city centre, delivering a high quality neighbourhood. One could say that the new district has a traditional Swedish structure, which it has combined with a modern architectural language that responds to the specific waterside context. The design promotes sustainability and follows modern architectural principles, such as maximising light and views of the water and green spaces. It follows standard dimensions of street width (18 m), block sizes (70x100 m), density, and land use. Public transport and the creation of new road and tram infrastructure make the area easily accessible.
The scale of the development varies from four to five storeys along the canal and 6 to 8 storeys along the inner area. The spine of the new district is a 37.5 m wide boulevard, which connects key transport nodes and public focal points, creating a natural focus for activity and retail. The ground floors of nearly all the buildings along this boulevard have been designed as flexible spaces, suitable for commerce, leisure or community use. Many residents work in the neighbourhood which allows them to walk to work.
The residential districts adjacent to the main spine follow a grid structure with a semi-open block form, which delivers maximum daylight and long views, as well as providing open access to the courtyards of residential blocks. Most apartments have balconies overlooking the streets and waterfront. An inter-connected network of varied parks, green spaces and walkways runs through the district as well as pedestrian paths, quays and linear parks across the waterfront, offering access to the residents towards the boat moorings in the summer. Community provisions include a modern church building, two public schools, one private school, one pre-school and nursery, a health centre, a library, a sports centre, a football pitch and basketball court and other amenities.
Example of Green Urbanism in practice: The green district Hammarby Sjöstad in Stockholm, built 1995-2008 on land formerly used by the port (to be fully completed in 2018). It is widely accepted as a best practice model for sustainable urban development, having included in its urban development innovative principles of water and waste management and reduction of car dependency. Image: courtesy City of Stockholm, Sweden, 2008.
Stockholm’s green district Hammarby Sjöstad includes on-site energy generation with solar cells and green roofs, as well as principles for sensitive urban water management. Image: courtesy City of Stockholm, Sweden, 2008. See also:
It is important to note, that a couple of innovative engineering solutions will not deliver a vibrant city. All the technology in the world cannot achieve sustainability and vitality by
Moving from a non sustainable linear metabolism towards a more sustainable, circular metabolism, requires the looping and re-use of materials and products. Less required input and less waste generation are the characteristics of such a healthier city structure. Diagram: courtesy the author, 2010 (after: H. Girardet, 1999).
itself. The problem of urban design is far more complex. Designing a city requires holistic, multi-dimensional approaches, and each time the adaptation of strategies to a unique context: the integration and combination of qualitative and quantitative knowledge.
There is now a growing interest in understanding the complex interactions and feedbacks between urbanization, material consumption, energy and water efficiency and the depletion of our resources. The question how far urban form and population density impact on resource consumption is important but still not fully understood.
Much of Green Urbanism is common sense urbanism. In the future,
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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Applying FMEA in clinical approaches can lead to a significant reduction of the risk priority number (RPN).",book:{id:"9808",slug:"contemporary-topics-in-patient-safety-volume-1",title:"Contemporary Topics in Patient Safety",fullTitle:"Contemporary Topics in Patient Safety - Volume 1"},signatures:"Hoda Sabati, Amin Mohsenzadeh and Nooshin Khelghati",authors:[{id:"340486",title:"M.Sc.",name:"Hoda",middleName:null,surname:"Sabati",slug:"hoda-sabati",fullName:"Hoda Sabati"},{id:"348872",title:"M.Sc.",name:"Amin",middleName:null,surname:"Mohsenzadeh",slug:"amin-mohsenzadeh",fullName:"Amin Mohsenzadeh"},{id:"348874",title:"MSc.",name:"Nooshin",middleName:null,surname:"Khelghati",slug:"nooshin-khelghati",fullName:"Nooshin Khelghati"}]},{id:"69876",title:"Leadership Styles in Nursing",slug:"leadership-styles-in-nursing",totalDownloads:3212,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Recent developments in the field of management-organization and organizational behavior and new concepts have also led to the emergence of new leadership styles in leadership. 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The task-focused leadership style is explored under the headings of transactional and autocratic leadership, laissez-faire leadership, and instrumental leadership.",book:{id:"9047",slug:"nursing-new-perspectives",title:"Nursing",fullTitle:"Nursing - New Perspectives"},signatures:"Serpil Çelik Durmuş and Kamile Kırca",authors:null},{id:"58916",title:"Factors Affecting the Attitudes of Women toward Family Planning",slug:"factors-affecting-the-attitudes-of-women-toward-family-planning",totalDownloads:8553,totalCrossrefCites:9,totalDimensionsCites:18,abstract:"Everyone has the right to decide on the number and timing of children without discrimination, violence and oppression, to have the necessary information and facilities for it, to access sexual and reproductive health services at the highest standard. Deficient or incorrect family planning methods, wrong attitudes and behaviors toward the methods and consequent unplanned pregnancies, increased maternal and infant mortality rates are the main health problems in most countries. Individuals’ learning modern family planning methods and having positive attitude for these methods may increase the usage of these methods and contributes the formation of healthy communities. It is considered important to examine the current attitudes and determinants in order to spread the choice of effective method.",book:{id:"6142",slug:"family-planning",title:"Family Planning",fullTitle:"Family Planning"},signatures:"Nazli Sensoy, Yasemin Korkut, Selcuk Akturan, Mehmet Yilmaz,\nCanan Tuz and Bilge Tuncel",authors:[{id:"216377",title:"Prof.",name:"Nazli",middleName:null,surname:"Sensoy",slug:"nazli-sensoy",fullName:"Nazli Sensoy"},{id:"216589",title:"Dr.",name:"Yasemin",middleName:null,surname:"Korkut",slug:"yasemin-korkut",fullName:"Yasemin Korkut"},{id:"216595",title:"Dr.",name:"Selcuk",middleName:null,surname:"Akturan",slug:"selcuk-akturan",fullName:"Selcuk Akturan"},{id:"216596",title:"Dr.",name:"Canan",middleName:null,surname:"Tuz",slug:"canan-tuz",fullName:"Canan Tuz"},{id:"216598",title:"Dr.",name:"Bilge",middleName:null,surname:"Tuncel",slug:"bilge-tuncel",fullName:"Bilge Tuncel"},{id:"216599",title:"Dr.",name:"Mehmet",middleName:null,surname:"Yilmaz",slug:"mehmet-yilmaz",fullName:"Mehmet Yilmaz"}]},{id:"69631",title:"Cultural Practices and Health Consequences: Health or Habits, the Choice Is Ours",slug:"cultural-practices-and-health-consequences-health-or-habits-the-choice-is-ours",totalDownloads:918,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Human beings are social animals with an innate desire to conform to socially accepted norms and values. Over periods of time, some of these norms become standards that all members of the community are expected to adhere to. Deviance from these standards is seen as absurd, wrong, or frankly abnormal. However, many of these cultural mores have no scientific basis and, some of them actually promote behaviors with negative health consequences. This chapter examines the cultural practices of some communities in Africa and their health consequences and, explores ways to address the challenges.",book:{id:"9138",slug:"public-health-in-developing-countries-challenges-and-opportunities",title:"Public Health in Developing Countries",fullTitle:"Public Health in Developing Countries - Challenges and Opportunities"},signatures:"Radiance Ogundipe",authors:[{id:"302308",title:"Dr.",name:"Radiance",middleName:null,surname:"Ogundipe",slug:"radiance-ogundipe",fullName:"Radiance Ogundipe"}]},{id:"55808",title:"The Role of Legumes in Human Nutrition",slug:"the-role-of-legumes-in-human-nutrition",totalDownloads:5446,totalCrossrefCites:64,totalDimensionsCites:110,abstract:"Legumes are valued worldwide as a sustainable and inexpensive meat alternative and are considered the second most important food source after cereals. Legumes are nutritionally valuable, providing proteins (20–45%) with essential amino acids, complex carbohydrates (±60%) and dietary fibre (5–37%). Legumes also have no cholesterol and are generally low in fat, with ±5% energy from fat, with the exception of peanuts (±45%), chickpeas (±15%) and soybeans (±47%) and provide essential minerals and vitamins. In addition to their nutritional superiority, legumes have also been ascribed economical, cultural, physiological and medicinal roles owing to their possession of beneficial bioactive compounds. Research has shown that most of the bioactive compounds in legumes possess antioxidant properties, which play a role in the prevention of some cancers, heart diseases, osteoporosis and other degenerative diseases. Because of their composition, legumes are attractive to health conscious consumers, celiac and diabetic patients as well as consumers concerned with weight management. The incorporation of legumes in diets, especially in developing countries, could play a major role in eradicating protein-energy malnutrition especially in developing Afro-Asian countries. Legumes could be a base for the development of many functional foods to promote human health.",book:{id:"5963",slug:"functional-food-improve-health-through-adequate-food",title:"Functional Food",fullTitle:"Functional Food - Improve Health through Adequate Food"},signatures:"Yvonne Maphosa and Victoria A. Jideani",authors:[{id:"201151",title:"Ph.D. Student",name:"Yvonne",middleName:null,surname:"Maphosa",slug:"yvonne-maphosa",fullName:"Yvonne Maphosa"}]}],onlineFirstChaptersFilter:{topicId:"200",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82616",title:"The Quantum Theory of Reproduction – How Unique is an Individual?",slug:"the-quantum-theory-of-reproduction-how-unique-is-an-individual",totalDownloads:14,totalDimensionsCites:0,doi:"10.5772/intechopen.105769",abstract:"Our understanding of nature’s way is founded on quantum mechanics. In its existence of over 80 years, quantum theory has been describing the physical world. The attraction of studying quantum mechanics is the perception of the conceptual structure of nature. This is aided by the mathematical structure that exposes the internal logic of the subject by inventing a notation that embeds the philosophy of the question. To describe how unique each individual is. A calculation method was applied. The uniqueness of an individual is one in two nonillion, octillion, septillion, sextillion, quintillion, quadrillion, trillion, billion, million and thousand. Individuals are indefinitely unique.",book:{id:"11284",title:"Studies in Family Planning",coverURL:"https://cdn.intechopen.com/books/images_new/11284.jpg"},signatures:"Zouhair O. Amarin"},{id:"81930",title:"Smoking and Its Consequences on Male and Female Reproductive Health",slug:"smoking-and-its-consequences-on-male-and-female-reproductive-health",totalDownloads:14,totalDimensionsCites:0,doi:"10.5772/intechopen.104941",abstract:"Smoking contributes to the death of around one in 10 adults worldwide. Specifically, cigarettes are known to contain around 4000 toxins and chemicals that are hazardous in nature. The negative effects of smoking on human health and interest in smoking-related diseases have a long history. Among these concerns are the harmful effects of smoking on reproductive health. Thirteen percent of female infertility is due to smoking. Female smoking can lead to gamete mutagenesis, early loss of reproductive function, and thus advance the time to menopause. It has been also associated with ectopic pregnancy and spontaneous abortion. Even when it comes to assisted reproductive technologies cycles, smokers require more cycles, almost double the number of cycles needed to conceive as non-smokers. Male smoking is shown to be correlated with poorer semen parameters and sperm DNA fragmentation. Not only active smokers but also passive smokers, when excessively exposed to smoking, can have reproductive problems comparable to those seen in smokers. In this book chapter, we will approach the effect of tobacco, especially tobacco smoking, on male and female reproductive health. This aims to take a preventive approach to infertility by discouraging smoking and helping to eliminate exposure to tobacco smoke in both women and men.",book:{id:"11284",title:"Studies in Family Planning",coverURL:"https://cdn.intechopen.com/books/images_new/11284.jpg"},signatures:"Amor Houda, Jankowski Peter Michael, Micu Romeo and Hammadeh Mohamad Eid"},{id:"81468",title:"The Knowledge and Use of Intra-Uterine Device by Women Attending Ante-Natal Clinic at Enugu State Teaching Hospital, Parklane",slug:"the-knowledge-and-use-of-intra-uterine-device-by-women-attending-ante-natal-clinic-at-enugu-state-te",totalDownloads:24,totalDimensionsCites:0,doi:"10.5772/intechopen.104097",abstract:"Intrauterine contraception has been recognized globally as one of the modern long-term reversible contraceptive methods suitable for women of all reproductive ages. It represents the most cost-effective method for preventing unwanted pregnancies, scientifically proven for its safety, efficacy and cost-effectiveness and is known to last longer in preventing pregnancy than other methods. This study assessed the knowledge of mothers attending ESUT teaching hospital, Parklane on intrauterine contraceptive device, the use as well as the common side effects experienced by the users. A descriptive survey research design was used to sample 175 mothers. A structured researcher developed questionnaire was used for data collection. The findings revealed that more than half of the respondents have good knowledge of intrauterine device but only 23 (14%) respondents make use of it. The commonly experienced side effects identified were irregular bleeding (75%) and vaginal discharge (62.5%). Although, the respondents had good knowledge of intrauterine device, their uptake of the method was poor. Therefore, there is a need to improve contraceptive counseling to ensure that women understand the relative effectiveness of IUDS. The study also recommended the need for better education for both clients and providers to improve the accessibility and acceptability of intrauterine device.",book:{id:"11284",title:"Studies in Family Planning",coverURL:"https://cdn.intechopen.com/books/images_new/11284.jpg"},signatures:"Chukwuasokam Caleb Aniechi and Uloma Cynthia Ezuma"},{id:"81003",title:"Perspective Chapter: Modern Birth Control Methods",slug:"perspective-chapter-modern-birth-control-methods",totalDownloads:43,totalDimensionsCites:0,doi:"10.5772/intechopen.103858",abstract:"This chapter focuses on various modern birth control methods, including combined oral contraceptives, progestogen-only pills, progestogen-only injectables, progestogen-only implants, intrauterine devices, barrier contraceptives, and emergency contraceptive pills. Each contraceptive method is covered in detail, including mechanism of action, effectiveness, health benefits, advantages, disadvantages, risks, and side-effects.",book:{id:"11284",title:"Studies in Family Planning",coverURL:"https://cdn.intechopen.com/books/images_new/11284.jpg"},signatures:"Rahma Al Kindi, Asma Al Salmani, Rahma Al Hadhrami, Sanaa Al Sumri and Hana Al Sumri"},{id:"80084",title:"Contraceptive Implants",slug:"contraceptive-implants",totalDownloads:174,totalDimensionsCites:0,doi:"10.5772/intechopen.101999",abstract:"Contraceptive implants or implantable contraceptive are five subdermal implants, rods the size of pencil lead that are embedded just under the skin on the inside of the upper arm. The rods contain etonogestrel, the metabolite of desogestrel, an equivalent progestin. Implants are often used during breastfeeding without an impact on milk production. It was identified that age does not affect the use of contraceptive implants but educational status is significant to its usage; there is an association between the age at first birth and the use of contraceptive implants; the number of liveborn children has a significant impact or influence on the use of implants; etc. This chapter focuses on types of contraceptive implants and its mechanism of action; global statistics on contraceptive implants; side effects; health benefits and positive characteristics of contraceptive implants; those who can and cannot use contraceptive implants; reasons women are not interested in contraceptive implants and factors influencing its usage.",book:{id:"11284",title:"Studies in Family Planning",coverURL:"https://cdn.intechopen.com/books/images_new/11284.jpg"},signatures:"Paul Hassan Ilegbusi"}],onlineFirstChaptersTotal:5},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:11,numberOfPublishedChapters:91,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:333,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:11,numberOfPublishedChapters:144,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:125,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:23,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:12,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"August 17th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:33,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:6,paginationItems:[{id:"22",title:"Applied Intelligence",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",isOpenForSubmission:!0,editor:{id:"27170",title:"Prof.",name:"Carlos",middleName:"M.",surname:"Travieso-Gonzalez",slug:"carlos-travieso-gonzalez",fullName:"Carlos Travieso-Gonzalez",profilePictureURL:"https://mts.intechopen.com/storage/users/27170/images/system/27170.jpeg",biography:"Carlos M. Travieso-González received his MSc degree in Telecommunication Engineering at Polytechnic University of Catalonia (UPC), Spain in 1997, and his Ph.D. degree in 2002 at the University of Las Palmas de Gran Canaria (ULPGC-Spain). He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",isOpenForSubmission:!0,editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",isOpenForSubmission:!0,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. Papakostas has received a diploma in Electrical and Computer Engineering in 1999 and the M.Sc. and Ph.D. degrees in Electrical and Computer Engineering in 2002 and 2007, respectively, from the Democritus University of Thrace (DUTH), Greece. Dr. Papakostas serves as a Tenured Full Professor at the Department of Computer Science, International Hellenic University, Greece. Dr. Papakostas has 10 years of experience in large-scale systems design as a senior software engineer and technical manager, and 20 years of research experience in the field of Artificial Intelligence. Currently, he is the Head of the “Visual Computing” division of HUman-MAchines INteraction Laboratory (HUMAIN-Lab) and the Director of the MPhil program “Advanced Technologies in Informatics and Computers” hosted by the Department of Computer Science, International Hellenic University. He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. Dr Ventura also holds the positions of Affiliated Professor at Virginia Commonwealth University (Richmond, USA) and Distinguished Adjunct Professor at King Abdulaziz University (Jeddah, Saudi Arabia). Additionally, he is deputy director of the Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI) and heads the Knowledge Discovery and Intelligent Systems Research Laboratory. He has published more than ten books and over 300 articles in journals and scientific conferences. Currently, his work has received over 18,000 citations according to Google Scholar, including more than 2200 citations in 2020. In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. He is a Senior Member of the IEEE Computer, the IEEE Computational Intelligence, and the IEEE Systems, Man, and Cybernetics Societies, and the Association of Computing Machinery (ACM). Finally, his main research interests include data science, computational intelligence, and their applications.",institutionString:null,institution:{name:"University of Córdoba",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"26",title:"Machine Learning and Data Mining",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",isOpenForSubmission:!0,editor:{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",biography:"Dr. Marco Antonio Aceves Fernandez obtained his B.Sc. (Eng.) in Telematics from the Universidad de Colima, Mexico. 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Prof. Emeje’s several international fellowships include the prestigious Raman fellowship. He has published more than 150 articles and patents. He is also the head of R&D at NIPRD and holds a visiting professor position at Nnamdi Azikiwe University, Nigeria. He has a postgraduate certificate in Project Management from Walden University, Minnesota, as well as a professional teaching certificate and a World Bank certification in Public Procurement. Prof. Emeje was a national chairman of academic pharmacists in Nigeria and the 2021 winner of the May & Baker Nigeria Plc–sponsored prize for professional service in research and innovation.",institutionString:"National Institute for Pharmaceutical Research and Development",institution:{name:"National Institute for Pharmaceutical Research and Development",country:{name:"Nigeria"}}},{id:"436430",title:"Associate Prof.",name:"Mesut",middleName:null,surname:"Işık",slug:"mesut-isik",fullName:"Mesut Işık",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/436430/images/19686_n.jpg",biography:null,institutionString:null,institution:{name:"Bilecik University",country:{name:"Turkey"}}},{id:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a scientist and Principal Investigator at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering the lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via artificial intelligence-based analyses of exosomal Raman signatures. Dr. Paul also works on spatial multiplex immunofluorescence-based tissue mapping to understand the immune repertoire in lung cancer. Dr. Paul has published in more than sixty-five peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award and the 2022 AAISCR-R Vijayalaxmi Award for Innovative Cancer Research. He is a senior member of the Institute of Electrical and Electronics Engineers (IEEE) and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/system/329795.png",biography:"Dr. Mohd Aftab Siddiqui is an assistant professor in the Faculty of Pharmacy, Integral University, Lucknow, India, where he obtained a Ph.D. in Pharmacology in 2020. He also obtained a BPharm and MPharm from the same university in 2013 and 2015, respectively. His area of research is the pharmacological screening of herbal drugs/natural products in liver cancer and cardiac diseases. He is a member of many professional bodies and has guided many MPharm and PharmD research projects. Dr. Siddiqui has many national and international publications and one German patent to his credit.",institutionString:"Integral University",institution:null}]}},subseries:{item:{id:"8",type:"subseries",title:"Bioinspired Technology and Biomechanics",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11404,editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",slug:"adriano-andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",biography:"Dr. Adriano de Oliveira Andrade graduated in Electrical Engineering at the Federal University of Goiás (Brazil) in 1997. He received his MSc and PhD in Biomedical Engineering respectively from the Federal University of Uberlândia (UFU, Brazil) in 2000 and from the University of Reading (UK) in 2005. He completed a one-year Post-Doctoral Fellowship awarded by the DFAIT (Foreign Affairs and International Trade Canada) at the Institute of Biomedical Engineering of the University of New Brunswick (Canada) in 2010. Currently, he is Professor in the Faculty of Electrical Engineering (UFU). He has authored and co-authored more than 200 peer-reviewed publications in Biomedical Engineering. He has been a researcher of The National Council for Scientific and Technological Development (CNPq-Brazil) since 2009. He has served as an ad-hoc consultant for CNPq, CAPES (Coordination for the Improvement of Higher Education Personnel), FINEP (Brazilian Innovation Agency), and other funding bodies on several occasions. He was the Secretary of the Brazilian Society of Biomedical Engineering (SBEB) from 2015 to 2016, President of SBEB (2017-2018) and Vice-President of SBEB (2019-2020). He was the head of the undergraduate program in Biomedical Engineering of the Federal University of Uberlândia (2015 - June/2019) and the head of the Centre for Innovation and Technology Assessment in Health (NIATS/UFU) since 2010. He is the head of the Postgraduate Program in Biomedical Engineering (UFU, July/2019 - to date). He was the secretary of the Parkinson's Disease Association of Uberlândia (2018-2019). Dr. Andrade's primary area of research is focused towards getting information from the neuromuscular system to understand its strategies of organization, adaptation and controlling in the context of motor neuron diseases. 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