Emission factors considered for the LD fleet and fuel power plants and average unit energy consumption.
\\n\\n
Dr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\\n\\nSeeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\\n\\nOver these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\\n\\nWe are excited about the present, and we look forward to sharing many more successes in the future.
\\n\\nThank you all for being part of the journey. 5,000 times thank you!
\\n\\nNow with 5,000 titles available Open Access, which one will you read next?
\\n\\nRead, share and download for free: https://www.intechopen.com/books
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Preparation of Space Experiments edited by international leading expert Dr. Vladimir Pletser, Director of Space Training Operations at Blue Abyss is the 5,000th Open Access book published by IntechOpen and our milestone publication!
\n\n"This book presents some of the current trends in space microgravity research. The eleven chapters introduce various facets of space research in physical sciences, human physiology and technology developed using the microgravity environment not only to improve our fundamental understanding in these domains but also to adapt this new knowledge for application on earth." says the editor. Listen what else Dr. Pletser has to say...
\n\n\n\nDr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\n\nSeeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\n\nOver these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\n\nWe are excited about the present, and we look forward to sharing many more successes in the future.
\n\nThank you all for being part of the journey. 5,000 times thank you!
\n\nNow with 5,000 titles available Open Access, which one will you read next?
\n\nRead, share and download for free: https://www.intechopen.com/books
\n\n\n\n
\n'}],latestNews:[{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"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"10134",leadTitle:null,fullTitle:"Organic Agriculture",title:"Organic Agriculture",subtitle:null,reviewType:"peer-reviewed",abstract:"Organic crop production is the science and art of growing field crops, fruits, vegetables, and flowers by adopting the essential principles of organic agriculture in soil building and conservation, pest management, and heirloom variety conservation. This book provides detailed insights into organic farming in agriculture, biological efficacy in the management of plant diseases, organic nutrient management, socio-economic dimensions of adoption of conservation practices, nonchemical weed control, plant growth promoting fungi for phytostimulation, nanotechnological approaches, and finally vermicomposting. The book primarily focuses on research and development based organic agriculture and horticulture production technologies, and has attempted to abridge information on organic crop production of the major food grain crops. The book also contains comprehensive information on the various related dimensions of organic crop production.",isbn:"978-1-78984-669-0",printIsbn:"978-1-78984-668-3",pdfIsbn:"978-1-78984-720-8",doi:"10.5772/intechopen.89775",price:119,priceEur:129,priceUsd:155,slug:"organic-agriculture",numberOfPages:168,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"a9866f9df52191cc505b27fb2abdc687",bookSignature:"Shaon Kumar Das",publishedDate:"December 2nd 2020",coverURL:"https://cdn.intechopen.com/books/images_new/10134.jpg",numberOfDownloads:6247,numberOfWosCitations:4,numberOfCrossrefCitations:19,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:39,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:62,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 9th 2019",dateEndSecondStepPublish:"February 12th 2020",dateEndThirdStepPublish:"April 12th 2020",dateEndFourthStepPublish:"July 1st 2020",dateEndFifthStepPublish:"August 30th 2020",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"182210",title:"Dr.",name:"Shaon Kumar",middleName:null,surname:"Das",slug:"shaon-kumar-das",fullName:"Shaon Kumar Das",profilePictureURL:"https://mts.intechopen.com/storage/users/182210/images/system/182210.jpg",biography:"Shaon Kumar Das is working as a Scientist SS (Agricultural Chemistry) at ICAR RC for NEH Region, Sikkim Centre, Tadong, Gangtok under the Indian Council of Agricultural Research, New Delhi. He received his M.Sc. in 2010 from IARI, New Delhi along with a gold medal for his outstanding contribution. He joined the Agricultural Research Service (ARS) in 2011 as a scientist. He completed his Ph.D in 2020 from Visva Bharati University in Soil Science and Agricultural Chemistry and worked on integrated organic nutrient management. He has published 27 national and 40 international research articles, 10 review articles in national and international journals, 30 popular articles, 28 extension folders, 2 books, and 25 book chapters in edited books. He received a DST-INSPIRE fellowship in 2010 from DST, Govt. of India. He has been awarded the best scientist award by the ICAR RC for the NEH Region, Umiam, Meghalaya in 2018. He received six young scientist awards and 3 best oral presentation awards from different reputable societies. He was the Principal Investigator (PI) of different externally funded projects like DST, DBT, NMHS, ICAR etc. He has been involved in the research on carbon sequestration, soil fertility management, soil acidity reclamation, and organic nutrient standardization of major hill crops.",institutionString:"Indian Council of Agricultural Research (ICAR)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"307",title:"Agroecology",slug:"agroecology"}],chapters:[{id:"72994",title:"Role of Organic Farming in Agriculture",doi:"10.5772/intechopen.93431",slug:"role-of-organic-farming-in-agriculture",totalDownloads:704,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Organic farming could be an all-encompassing generation administration framework that empowers and improves agroecosystem wellbeing, counting biodiversity, natural cycles, and soil biological activity. It stresses the role of management activities in preference to the use of off-farm data, considering that regional conditions require locally adapted systems. This can be achieved using agronomic, biological, and mechanical methods, in equal share to synthetic materials, to carry out any specific role inside the organization. Organic farming is still only a small industry, which represents only 2% of global food sales. However, it is growing in importance in the world. It is hard to get information due to lack of official statistics and the level of confidentiality of systems of organic produce. Soil practices such as crop rotations, organic fertilizers, symbiotic associations, cover crops, inter-cropping, and minimum tillage are central to organic practices. The static arrangements of soil are achieved by soil fauna and vegetation. Besides, cycling of nutrients and energy is enhanced by increasing the retentive abilities of the soil for nutrients and water.",signatures:"Muthuraman Yuvaraj, Peyandi Paraman Mahendran and Eman Tawfik Hussien",downloadPdfUrl:"/chapter/pdf-download/72994",previewPdfUrl:"/chapter/pdf-preview/72994",authors:[{id:"280193",title:"Dr.",name:"Muthuraman",surname:"Yuvaraj",slug:"muthuraman-yuvaraj",fullName:"Muthuraman Yuvaraj"}],corrections:null},{id:"72269",title:"Nanotechnological Approaches in Sustainable Agriculture and Plant Disease Management",doi:"10.5772/intechopen.92463",slug:"nanotechnological-approaches-in-sustainable-agriculture-and-plant-disease-management",totalDownloads:735,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Every year approximately 30–50% of crops suffer with different kinds of biotic stresses. Rapidly growing agrochemical industries and their diverse products make the environment more toxic and simultaneously hazardous for plant heath and soil health. Such types of agrochemicals are toxic, hazardous, carcinogenic, non-eco-friendly. Therefore, this is the ideal time to think about some more effective alternatives against those problems. Nanotechnological approaches bring the alternatives in the form of decreasing toxicity, improving shelf-life, increasing solubility for poorly water-soluble agrochemicals, minimum use with maximum effect, slow leaching efficiency with long-term effect with coupling of eco-friendly naturalistic way. The way of nanoparticle application in agriculture, specifically disease management, is unique, where it can be used singly or by coupling with fungicidal, herbicidal, insecticidal, RNA-interference molecules. Though it has such a positive impact, very few products will be commercially available in our market due to high price of particular products and well-established long field trial efficacy detection among insect, pest-pathogen, and environment. Application of nanomolecules in other progressive fields has been emerging, whereas advancement in agricultural applications needs to be boosted up through skilled knowledge transfer and basic understanding of its fundamental aspect.",signatures:"Siddhartha Das and Sudeepta Pattanayak",downloadPdfUrl:"/chapter/pdf-download/72269",previewPdfUrl:"/chapter/pdf-preview/72269",authors:[{id:"320136",title:"Dr.",name:"Siddhartha",surname:"Das",slug:"siddhartha-das",fullName:"Siddhartha Das"},{id:"320228",title:"Ms.",name:"Sudeepta",surname:"Pattanayak",slug:"sudeepta-pattanayak",fullName:"Sudeepta Pattanayak"}],corrections:null},{id:"71681",title:"Packages of Organic Nutrient Management as Soil Policy for Upgrading Cropping System to Restore Soil Productivity",doi:"10.5772/intechopen.91928",slug:"packages-of-organic-nutrient-management-as-soil-policy-for-upgrading-cropping-system-to-restore-soil",totalDownloads:609,totalCrossrefCites:8,totalDimensionsCites:11,hasAltmetrics:0,abstract:"The indigenous farming systems are, by and large, organically practiced. Organic farming systems facilitate the buildup of soil organic matter, reducing risk of erosion and runoff and enhancing nutrient storehouse in soils for plants. Rapid developments in organic farming promotion necessitated continuous flow of technology to meet day-to-day challenges. Farmyard manure (FYM), compost, and green manure are the most important and widely used bulky organic manures. Manuring with different short-duration legumes is suitable for maintenance of soil quality in terms of adding nitrogen to soil. Sustainable quantity of potassium can be maintained by vegetative mulching with crop residues. The use of balanced dosages of mixed compost at 5–10 t/ha along with 2 t/ha dolomite increases yield of maize, rice, mustard, and soybean. This article briefly describes about the integrated organic nutrient management as soil policy for upgrading cropping system to restore soil productivity.",signatures:"Shaon Kumar Das and Ravikant Avasthe",downloadPdfUrl:"/chapter/pdf-download/71681",previewPdfUrl:"/chapter/pdf-preview/71681",authors:[{id:"182210",title:"Dr.",name:"Shaon Kumar",surname:"Das",slug:"shaon-kumar-das",fullName:"Shaon Kumar Das"}],corrections:null},{id:"71592",title:"Vermicomposting: An Effective Option for Recycling Organic Wastes",doi:"10.5772/intechopen.91892",slug:"vermicomposting-an-effective-option-for-recycling-organic-wastes",totalDownloads:1437,totalCrossrefCites:2,totalDimensionsCites:9,hasAltmetrics:0,abstract:"Urbanization and industrialization resulted in rapid increase in volume of solid waste; its management has become one of the biggest problems today. Solid wastes can be disposed off by methods like land filling, incineration, conversion into biogas, recycling, and composting, but its overproduction has led to inappropriate disposal practices such as their indiscriminate and inappropriately timed application to agricultural fields that ultimately leads to water and soil pollution. However, if handled properly, these organic wastes can be used for vermicomposting; it is an effective recycling technology that improves the quality of the products which is disinfected, detoxified, and highly nutritive. It is a low cost, eco-biotechnological process of waste management in which earthworms are used to cooperate with microorganisms in order to convert biodegradable wastes into organic fertilizer. Earthworms excreta (vermicast) is a nutritive organic fertilizer rich in humus, NPK, micronutrients, beneficial soil microbes; nitrogen-fixing, phosphate solubilizing bacteria, actinomycets, and growth hormones auxins, gibberlins and cytokinins, is a suitable alternative to chemical fertilizers, being an excellent growth promoter and protector for crop plants. Thus, vermiculture not only results in management of soild waste but also produces excellent nutrient enriched vermicompost. Vermicompost is beneficial for sustainable organic agriculture and maintaining balanced ecosystem.",signatures:"Tamanreet Kaur",downloadPdfUrl:"/chapter/pdf-download/71592",previewPdfUrl:"/chapter/pdf-preview/71592",authors:[{id:"317164",title:"Dr.",name:"Tamanreet",surname:"Kaur",slug:"tamanreet-kaur",fullName:"Tamanreet Kaur"}],corrections:null},{id:"72075",title:"Application and Mechanisms of Plant Growth Promoting Fungi (PGPF) for Phytostimulation",doi:"10.5772/intechopen.92338",slug:"application-and-mechanisms-of-plant-growth-promoting-fungi-pgpf-for-phytostimulation",totalDownloads:1276,totalCrossrefCites:6,totalDimensionsCites:13,hasAltmetrics:0,abstract:"Plant growth-promoting fungi (PGPF) constitute diverse genera of nonpathogenic fungi that provide a variety of benefits to their host plants. PGPF show an effective role in sustainable agriculture. Meeting increasing demand for crop production without damage to the environment is the biggest challenge nowadays. The use of PGPF has been recognized as an environmentally friendly way of increasing crop production. These fungi have proven to increase crop yields by improving germination, seedling vigor, plant growth, root morphogenesis, photosynthesis, and flowering through either a direct or indirect mechanism. The mechanisms of PGPF involve solubilizing and mineralizing nutrients for easy uptake by plants, regulating hormonal balance, producing volatile organic compounds and microbial enzyme, suppressing plant pathogens and ameliorating abiotic stresses. Successful colonization is an intrinsic factor for most PGPF to exert their beneficial effects on plants. A certain level of specificity exists in the interactions between plant species and PGPF for root colonization and growth promoting effects. There is a gap between the number of reported efficacious PGPF and the number of PGPF as biofertilizer. Efforts should be strengthened to improve the efficacy and commercialization of PGPF. Hence, this chapter summarizes valuable information regarding the application and mechanisms of PGPF in sustainable agriculture.",signatures:"Md. Motaher Hossain and Farjana Sultana",downloadPdfUrl:"/chapter/pdf-download/72075",previewPdfUrl:"/chapter/pdf-preview/72075",authors:[{id:"318381",title:"Dr.",name:"Md. Motaher",surname:"Hossain",slug:"md.-motaher-hossain",fullName:"Md. Motaher Hossain"},{id:"318383",title:"Dr.",name:"Farjana",surname:"Sultana",slug:"farjana-sultana",fullName:"Farjana Sultana"}],corrections:null},{id:"71029",title:"Biological Efficacy of Trichoderma spp. and Bacillus spp. in the Management of Plant Diseases",doi:"10.5772/intechopen.91043",slug:"biological-efficacy-of-em-trichoderma-em-spp-and-em-bacillus-em-spp-in-the-management-of-plant-disea",totalDownloads:685,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This chapter will cover topics about the microbial antagonists Trichoderma spp. and Bacillus spp. from the perspective of use as potential biological control agents on plant diseases. Results obtained in the laboratory about from their isolation, microbial strain collections for both genera, taxonomic identification, antifungal activity in in vitro tests, obtained evaluation of the antifungal effect of secondary metabolites from microbial antagonists will be shown. Besides, results obtained from bioassays in the greenhouse and field are used as biopesticides in the control of diseases in fruit trees and vegetables and their effects on the promotion of plant growth and increased crop yield.",signatures:"Francisco Daniel Hernández-Castillo, Francisco Castillo-Reyes, Marco Antonio Tucuch-Pérez and Roberto Arredondo-Valdes",downloadPdfUrl:"/chapter/pdf-download/71029",previewPdfUrl:"/chapter/pdf-preview/71029",authors:[{id:"76348",title:"Dr.",name:"Francisco Daniel",surname:"Hernandez Castillo",slug:"francisco-daniel-hernandez-castillo",fullName:"Francisco Daniel Hernandez Castillo"},{id:"187441",title:"Dr.",name:"Francisco",surname:"Castillo",slug:"francisco-castillo",fullName:"Francisco Castillo"},{id:"314111",title:"M.Sc.",name:"Marco Antonio",surname:"Tucuch Pérez",slug:"marco-antonio-tucuch-perez",fullName:"Marco Antonio Tucuch Pérez"},{id:"317252",title:"Dr.",name:"Roberto",surname:"Arredondo Valdes",slug:"roberto-arredondo-valdes",fullName:"Roberto Arredondo Valdes"}],corrections:null},{id:"71318",title:"Nonchemical Weed Control in Winter Oilseed Rape Crop in the Organic Farming System",doi:"10.5772/intechopen.91044",slug:"nonchemical-weed-control-in-winter-oilseed-rape-crop-in-the-organic-farming-system",totalDownloads:433,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"A field experiment was conducted during the 2014–2017 period at Aleksandras Stulginskis University (now—Vytautas Magnus University Agriculture Academy) on a Endocalcaric Endogleyic Luvisol (LV-can.gln) according to the WRB 2014. The three nonchemical weed control methods were explored: (1) thermal (using wet water steam), (2) mechanical (interrow loosening), and (3) self-regulation (smothering). In the thermal and mechanical weed control treatments, winter oilseed rape was grown with an interrow spacing of 48.0 cm and in weed smothering (self-regulation) treatment with an interrow spacing of 12.0 cm. Winter oilseed rape was grown in the soil with a regular humus layer (23–25 cm) and with a thickened humus layer (45–50 cm). Annual weeds predominated in the winter oilseed rape crop. In the soil with both humus layers, regular and thickened, the most efficient weed control method was mechanical weed management both during the autumn (efficacy 26.7–75.1%) and spring (efficacy 37.1–76.7%) growing seasons. Thermal and mechanical weed control in combination with the bio-preparations in droughty years significantly reduced the number of weed seedlings. Dry matter mass of weeds most markedly decreased through the application of the mechanical weed management method.",signatures:"Aušra Marcinkevičienė, Marina Keidan, Rita Pupalienė, Rimantas Velička, Zita Kriaučiūnienė, Lina Marija Butkevičienė and Robertas Kosteckas",downloadPdfUrl:"/chapter/pdf-download/71318",previewPdfUrl:"/chapter/pdf-preview/71318",authors:[{id:"313789",title:"Dr.",name:"Rita",surname:"Pupalienė",slug:"rita-pupaliene",fullName:"Rita Pupalienė"}],corrections:null},{id:"72832",title:"Socio-Economic Dimensions of Adoption of Conservation Practices: What Is Needed to Be Done?",doi:"10.5772/intechopen.93198",slug:"socio-economic-dimensions-of-adoption-of-conservation-practices-what-is-needed-to-be-done-",totalDownloads:370,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Promoting sustainable agricultural production requires farmers to adopt new technologies such as organic farming to increase the agricultural productivity, while conserving the environment. Adoption and diffusion of new technologies need a long process, as experienced in the past. There are social and economic factors, identified in the literature, and those could cause delays in farmers’ use of new technologies. Hence, technology adoption and diffusion are important policy issues in agriculture. For that reason, this paper provides a literature review including factors influencing the adoption and diffusion of technology in agriculture and aims to contribute to the future studies and policies, especially focusing on the social capital or the social aspects, which are proven not to be analyzed by the previous studies comprehensively. The results show that interaction with neighbors and relatives, and membership in a group or organization, which represent the social aspects, has a positive influence on adoption and diffusion of new technologies. Hence, policy-makers should incorporate the social aspects when designing the policies, such as cost sharing programmes, to promote adoption and diffusion of new technologies.",signatures:"Nisa Sansel Tandogan and Haluk Gedikoglu",downloadPdfUrl:"/chapter/pdf-download/72832",previewPdfUrl:"/chapter/pdf-preview/72832",authors:[{id:"318014",title:"Associate Prof.",name:"Haluk",surname:"Gedikoglu",slug:"haluk-gedikoglu",fullName:"Haluk Gedikoglu"},{id:"323357",title:"Ph.D. Student",name:"Nisa Sansel",surname:"Tandogan",slug:"nisa-sansel-tandogan",fullName:"Nisa Sansel Tandogan"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"4566",title:"Agroecology",subtitle:null,isOpenForSubmission:!1,hash:"9e35a4ff7bee4ab82eab2c6b3f441789",slug:"agroecology",bookSignature:"Vytautas Pilipavičius",coverURL:"https://cdn.intechopen.com/books/images_new/4566.jpg",editedByType:"Edited by",editors:[{id:"169359",title:"Dr.",name:"Vytautas",surname:"Pilipavicius",slug:"vytautas-pilipavicius",fullName:"Vytautas Pilipavicius"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6952",title:"Irrigation in Agroecosystems",subtitle:null,isOpenForSubmission:!1,hash:"1afe3f365612ea9b4f35942c69792f63",slug:"irrigation-in-agroecosystems",bookSignature:"Gabrijel Ondrašek",coverURL:"https://cdn.intechopen.com/books/images_new/6952.jpg",editedByType:"Edited by",editors:[{id:"46939",title:"Prof.",name:"Gabrijel",surname:"Ondrasek",slug:"gabrijel-ondrasek",fullName:"Gabrijel Ondrasek"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6301",title:"Vegetation",subtitle:null,isOpenForSubmission:!1,hash:"5c1b7f22f2f926f8d59ea56f2fe84c6f",slug:"vegetation",bookSignature:"Allan Sebata",coverURL:"https://cdn.intechopen.com/books/images_new/6301.jpg",editedByType:"Edited by",editors:[{id:"143409",title:"Dr.",name:"Allan",surname:"Sebata",slug:"allan-sebata",fullName:"Allan Sebata"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6485",title:"Sustainability of Agroecosystems",subtitle:null,isOpenForSubmission:!1,hash:"4ed7b8c6bce44bfaddb83c0365793742",slug:"sustainability-of-agroecosystems",bookSignature:"Alexandre Bosco de Oliveira",coverURL:"https://cdn.intechopen.com/books/images_new/6485.jpg",editedByType:"Edited by",editors:[{id:"77880",title:"Dr.",name:"Alexandre",surname:"De Oliveira",slug:"alexandre-de-oliveira",fullName:"Alexandre De Oliveira"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9345",title:"Sustainable Crop Production",subtitle:null,isOpenForSubmission:!1,hash:"5135c48a58f18229b288f2c690257bcb",slug:"sustainable-crop-production",bookSignature:"Mirza Hasanuzzaman, Marcelo Carvalho Minhoto Teixeira Filho, Masayuki Fujita and Thiago Assis Rodrigues Nogueira",coverURL:"https://cdn.intechopen.com/books/images_new/9345.jpg",editedByType:"Edited by",editors:[{id:"76477",title:"Prof.",name:"Mirza",surname:"Hasanuzzaman",slug:"mirza-hasanuzzaman",fullName:"Mirza Hasanuzzaman"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6560",title:"Plant Competition in Cropping Systems",subtitle:null,isOpenForSubmission:!1,hash:"664e0a97f4494932f6c0461f9a6e7bd6",slug:"plant-competition-in-cropping-systems",bookSignature:"Daniel Dunea",coverURL:"https://cdn.intechopen.com/books/images_new/6560.jpg",editedByType:"Edited by",editors:[{id:"180202",title:"Associate Prof.",name:"Daniel",surname:"Dunea",slug:"daniel-dunea",fullName:"Daniel Dunea"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10499",title:"Next-Generation Greenhouses for Food Security",subtitle:null,isOpenForSubmission:!1,hash:"456f82c97eafad5734cd36c48e167781",slug:"next-generation-greenhouses-for-food-security",bookSignature:"Redmond R. 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In the last decades, the energy use for electricity production and for the transportation sector have more than duplicated (IEA - WEO, 2007) and today face a number of challenges related to reliability, security and environmental sustainability. The scientific evidence on climate change (IPCC, 2007) has been calling for urgent cross-sector emission cutting and electrified transportation is in the portfolio of the technology options that may help to solve the problem (IEA - ETP, 2008). In most of OCDE countries the transportation and electric power systems contribute to the majority of CO2 emissions (IEA - WEO, 2008) and most of the fossil fuels (coal, natural gas and oil) used to produce electricity and for transportation are, in many of these countries, imported. Oil accounts to the majority of this primary energy imports and more than 60% of it, is used for transportation (mainly road transportation) and so is responsible for the majority of emissions associated to the transport sector. All these facts are pressing decision makers/manufacturers to act on the road transportation sector, introducing more efficient vehicles on the market and diversifying the energy sources.
\n\t\t\tThe technological evolution of the Electric Drive Vehicles (EDV) of different types: Hybrid Vehicles (HEV), Battery Electric Vehicles (BEV) and Fuel Cell Vehicles (FCV), will lead to a progressive penetration of EDV´s in the transportation sector taking the place of Internal Combustion Engine Vehicles (ICEV). The next step in EDV technological development, already announced by some of the main automakers, (EV World, 2009) is the possibility of plugging into a standard electric power outlet so that they can charge batteries with electric energy from the grid. A lot of companies including many key and niche players worldwide are reported to have been developing models for the coming years in the segments of battery powered electric vehicles, Plug-In Hybrid Electric Vehicles (PHEVs), and fuel cell electric vehicles (EV ReportLinker, 2007).
\n\t\t\tBy shifting currently non-electric loads to the grid, electric vehicles might play a crucial role in the integration of these two critical elements of the whole energy system: power generation and transportation. In a scenario where a commitment is made to reduce emissions from power generation, the build-up of new intermittent power capacity is problematic for the electric systems operation (Skea, J, et al., 2008) and usually needs large investments in energy storage. The addition of extra load from electric vehicles in the electricity system can be challenging, if together both systems are more efficient and able to reduce overall emissions.
\n\t\t\tFurthermore, for future energy systems, with a high electrification of transportation, Vehicle to Grid (V2G) concepts can offer a potential storage capacity and use stored energy in batteries to support the grid in periods of shortage. By itself, each vehicle is small in its impact on the power system, but a large number of vehicles could have a significant impact either as an additional charge or a source of distributed generating capacity (Kempton and Tomic, 2005a; Kempton and Tomic, 2005b).
\n\t\t\tThis chapter is concerned with studying the potential impacts of the electric vehicles on the electricity systems, with a focus on the additional power demand, power generation emissions associated with EVs and the role of demand side management (DSM) strategies in supporting their penetration as well as the economic impacts of EVs on electric utilities.
\n\t\t\tThe analysis of the impact on the electric utilities of large-scale adoption of plug-in electric vehicles from the perspective of electricity demand, CO2 and other green house gas emissions and energy costs can be studied for two different electric utility´s environments: A big electric system synchronized with similar systems within the same Continent, and a small Island, a lower electric isolated system. Each case has very different characteristics the most important ones are the robustness of the systems, the isolated system needs more backup power installed and usually has less variety in the production technologies. Other major difference is that in a small Island, due to its dimension and apartness, there is no room to run an electricity market, so that the whole service of electricity supply is provided by a regulated monopoly. These differences have influence on the final electricity price formation.
\n\t\t\tMany studies regarding battery electric vehicles and Plug in hybrids are being performed in different countries. In the US, for instance, the capacity of the electric power infrastructure in different regions was studied for the supply of the additional load due to PHEV penetration (Kintner-Meyer et al., 2007) and the economic assessment of the impacts of PHEV adoption on vehicles owners and on electric utilities (Scott et al., 2007). Other studies (Hadley, 2006) considered the scenario of one million PHEVs added to a US sub-region and analyzed the potential changes in demand, impacts on generation adequacy, transmission and distribution and later the same analysis was extended to 13 US regions with the inclusion of GHG estimation for each of the seven scenarios performed for each region (Hadley, 2008). The ability to schedule both charging and very limited discharging of PHEVs could significantly increase power system utilization. The evaluation of the effects of optimal PHEV charging, under the assumption that utilities will indirectly or directly control when charging takes place, providing consumers with the absolute lowest cost of driving energy by using low-cost off-peak electricity, was also studied (Denholm and Short, 2006). This study was based on existing electricity demand and driving patterns, six geographic regions in the United States were evaluated and found that when PHEVs derive 40% of their miles from electricity, no new electric generation capacity was required under optimal dispatch rules for a 50% PHEV penetration. A similar study was made also by NREL (National Renewable Energy Laboratory) but here the analysis focused only one specific region and four scenarios for charging were evaluated in terms of grid impact and also in terms of GHG emissions (Parks et al., 2007). The results showed that off-peak charging would be more efficient in terms of grid stress and energy costs and a significant reduction on CO2 emissions was expected thought an increase in SO2 emissions was also expected due to the off peak charging being composed of a large amount of coal generation.
\n\t\t\tThe results obtained in one place on earth cannot be used in other regions only the methodologies. Apart from reasons that are related to car use habits and roads’ topology, there is the electricity production source mix that is different from place to place, more expensive in some places and with more use of renewable sources in others. These differences will also be focused on this chapter and the way they contribute to the EVs’ fuel/energy costs and the emissions balance between the power generation and the road transportation sectors with electric mobility.
\n\t\tIn this section, a description of the electric power systems demand is done emphasizing its evolution along a day and the contribution that electric vehicles may have for leveling the power consumption diagram. Examples of the typical load profiles filled with the different technologies available (renewable sources, big hydro and thermal units) are presented, as well as the possible percentage of renewable in the electricity production. Then, the emissions associated with the electric vehicles’ recharging are accounted.
\n\t\t\tTo study the economic impacts for the two case studies, the different rules for technology dispatch are described in a market environment and in the case of a traditional integrated electric system. In this section an explanation of how the price for end consumers (where electric cars are included) is formed will be done with examples taken from a market environment and from a vertically integrated company in an isolated Island.
\n\t\tNowadays, electric power systems are designed to respond to instantaneous consumer demand. One of the main features of power consumption is the difference in demand along the day hours, the week days and seasons. Fig. 1 shows, as an example, the hourly demand profiles of the Portuguese electric system. Each curve represents a week of worth data from four different seasons in 2008 and illustrates the variation in electricity demand. It can be observed that, in this country, the annual peak demand occurs during winter months (December or January), in the evening.
\n\t\t\tPower demand profiles in Portugal for different seasons
This variation in daily and seasonal demand could mean that there is always some underutilized capacity that could be used during off peak hours. Looking at average values, Fig. 2 presents the evolution of the hourly average power consumption in Portugal over the 24 hours of the day during the whole year 2008. This evolution along the day has nevertheless a valley during the night that represents about 60% of the peak consumption and so has great financial consequences with the need of having several power plants that are useless and an underutilized network during the night. This situation gives the opportunity for electric vehicles contribution for levelling the power consumption diagram.
\n\t\t\tExample hourly average power consumption during (weekdays in Portugal mainland year 2008)
As an example, Fig. 3 shows the estimated contribution for the power consumption diagram levelling when considering different levels of the electric vehicles penetration. Portugal mainland was used as an example and it was considered that 85% of the electric vehicle charging happens uniformly during the valley hours (from 11pm to 8am) with the rest charge happening uniformly during the other 14 hours of the day. The extra energy that each electric vehicle should charge from the grid in average was considered about 2.5MWh per year, more or less 7kWh per day plus a 10% in transmission losses.
\n\t\t\tElectric vehicles contribution to the consumption diagram leveling
As can be observed in Fig.3 only with a high penetration of vehicles like ca. 1million units (almost ¼ of the country’s light duty fleet), the impacts are visible in the consumption profile. The main question is how to incentivise off-peak charging?
\n\t\t\tIt is easy to foresee major congestion problems in already heavily loaded grids and voltage profile problems in predominantly radial networks, particularly if the peak load periods coincide with EV charging periods. Hence, if no load management strategies are defined, significant technical problems will occur and their drawbacks might even be larger than the economic/environmental benefits arising from electric vehicles usage (Fig.4).
\n\t\t\tLoad profile simulation of the peak demand weak for year 2015 with 4, 9 and 17% light duty fleet replacement with EV’s that recharge at peak hours in Portugal mainland.
The management strategies to prevent peak recharge can be adopted in two ways:
\n\t\t\tBy developing a dynamic price signal approach such that EV will charge predominantly during low energy price/demand moments or
By developing a technical management system such that charging can be distributed during valley hour periods and at times when there is large renewable power generation.
In a scenario of mass EVs penetration, the recharging profiles are important for the electric utility system’s sake and their effects on peak consumption, electricity prices and grid congestion should be carefully foreseen and studied.
\n\t\tThe hourly average power consumption during a day presented in Fig. 2 has an equivalent diagram when analyzing the distribution during the 24 hours of the day of the annual energy consumed. Fig. 5 presents this distribution and also the different power technologies that generated this energy demand.
\n\t\t\tThe great difference between the consumption at valley and at off-valley hours represents a barrier to the penetration of generation technologies that need to work more hours per year in order to became economically viable (usually with low unit variable costs but with large fixed costs) or non dispatchable units (renewable energies).
\n\t\t\tThe effective use of the country´s power plant fleet can be illustrated by the load duration curve (LDC), where the hourly average power over the whole year is sorted by decreasing order constituting a curve that begins with the year peak at hour 1 and the smallest demand at hour 8760 as illustrated in Fig. 6. In this example, the unutilized capacity could be annually 4000 GWh. Nowadays some of this capacity is used in pumping during off-peak hours. In 2008, about 700GWh were used for pumping to provide energy storage in reservoirs available for the peak hours. Without increasing capacity it would be possible to account with around 3000 GWh a year for extra off-peak loads that could be used in plug-in electric vehicles’ recharging. Considering a 3MWh/year of extra energy needed to charge an EV, it is possible to have one million EVs charging their batteries during valley hours, without any more investments in power installed and transmission lines.
\n\t\t\tExample of hourly energy consumption with used power plants technologies
Load duration curve for Portugal in year 2007
In addition to the fixed costs associated with underutilized capacity, the significant cycling that occurs on a daily basis creates additional costs for plants due to the constantly varying loads that could require generators to operate well below the “design point” of optimum efficiency. Power plant cycling also increases operation and maintenance requirements.
\n\t\t\tThis last situation is more visible for instance at St. Miguel Island in Azores, where the geothermal energy production (renewable energy without CO2 emissions that should be used as base load due to its impossibility of production variation) penetration is limited by the valley consumption. If base load electricity generation is much higher than actual demand, excess electricity will be wasted unless it is coupled to a storage system. This is an example, where the use of EVs, charged during off-peak hours, allow the development of a production technology from a renewable, endogenous source, with no CO2 emissions, against the systematic fuel imports (for vehicles and for electricity production).
\n\t\t\tS. Miguel has 27MW of existing geothermal capacity and the government wants to expand this capacity to meet future demand. Expanding existing capacity would mean that geothermal production will meet 40MW (EDA 2009). Current base load electricity demand is nowadays less than 40MW (Fig.7).
\n\t\t\tThere is the possibility of increasing the geothermal capacity in 3MW by 2011 and 10MW in 2013, but these investments are limited by the off-peak demand. Even considering a demand increase of 4% for years 2010 to 2013, there is not enough off-peak demand to fill the valley and at the same time assure at least a 10% of fuel power to prevent any shortage of the renewable energy sources.
\n\t\t\tTypical Winter Power consumption diagram at the S. Miguel Island, Azores, Portugal
As stated in last section, the fact that the valley demand, in this case, is about half the value of peak demand, gives the opportunity for electric vehicles contribution for levelling the power consumption diagram. The extra demand for charging the vehicles at each hour of the day is computed using equation 1.
\n\t\t\tWhere
Considering that 85% of the vehicles will uniformly recharge at night, the introduction of these vehicles will create and additional electricity demand that, in the context of today’s electricity generation mix, will be fulfilled by the running fuel oil power plants (Fig. 8).
\n\t\t\tAs expected, the percentage of renewable energy decreases and in terms of marginal emissions, they are simply being transferred from the tail pipes to the fuel power plants chimneys.
\n\t\t\tConsidering an emissions rate of 830gCO2/kWh for the fuel power plants, the additional CO2 emissions to daily charge EVs (an extra energy of 86MWh), should be 71.4 tons of CO2.
\n\t\t\tThe TTW daily emissions avoided if these same vehicles were conventional was about 120 tons.
\n\t\t\tLoad profile in S. Miguel for Winter season with EVs extra demand (30% of Light Duty fleet replaced for EVs)
However, if additional renewable electricity installed capacity is deployed, then the vehicles will also be running on renewable electricity. It can be considered that these EVs charged during off-peak hours are charged 100% with renewable energy. In fact there are three possible approaches:
\n\t\t\tIt is considered the EVs as marginal load and as stated in Fig. 8, the energy and emissions associated with EVs charging would be mainly on fuel.
It is considered the EVs as a base load because they justify the increase in renewable base load generation and the energy and emissions associated with EVs are from renewable sources (zero emissions).
It is considered the EVs equal to the other load and the energy and emissions associated to EVs charging would be an average of the production mix. In this case the emissions associated with EVs recharging is as stated by equation 2\n\t\t\t\t\t
These different approaches will lead to different CO2 emissions associated to EVs’ recharge (in this example, 8% of total daily electricity consumption).
\n\t\t\tIn the first case, a daily 71.4 tons of CO2 emissions for EVs recharge under the considered scenario of EV penetration, in the second case, a daily zero emissions for EVs recharge and in the third case a 37 tons.
\n\t\t\tIt is possible to see in Fig. 9, for instance for the typical Spring load profile that the new geothermal plus wind power penetration are not possible unless they increase valley consumption.
\n\t\t\tExpected load profile in S. Miguel for Spring (2013), 4% demand increase, 9 MW of wind, 13MW of new geothermal power and 30% LD fleet replacement by EVs.
The CO2 emissions factors, unit consumption and daily usage of vehicles considered in this analysis are resumed in Table 1.
\n\t\t\t\n\t\t\t\t\t\t | CO2 Emissions | \n\t\t\t\t\t\tUnit Consumption | \n\t\t\t\t\t\tDaily | \n\t\t\t\t\t|||
\n\t\t\t\t\t\t | kg/litre | \n\t\t\t\t\t\tkg/kWh | \n\t\t\t\t\t\tlitres/100km | \n\t\t\t\t\t\tkWh/100km | \n\t\t\t\t\t\tkg/kWh | \n\t\t\t\t\t\tkm | \n\t\t\t\t\t
ICEV Gasoline | \n\t\t\t\t\t\t2.31 | \n\t\t\t\t\t\t\n\t\t\t\t\t\t | 7 | \n\t\t\t\t\t\t\n\t\t\t\t\t\t | \n\t\t\t\t\t\t | 32 | \n\t\t\t\t\t
ICEV Diesel | \n\t\t\t\t\t\t2.68 | \n\t\t\t\t\t\t\n\t\t\t\t\t\t | 6 | \n\t\t\t\t\t\t\n\t\t\t\t\t\t | \n\t\t\t\t\t\t | 32 | \n\t\t\t\t\t
Fuel Plants | \n\t\t\t\t\t\t\n\t\t\t\t\t\t | 0.83 | \n\t\t\t\t\t\t\n\t\t\t\t\t\t | \n\t\t\t\t\t\t | 0.25 | \n\t\t\t\t\t\t\n\t\t\t\t\t |
EV | \n\t\t\t\t\t\t\n\t\t\t\t\t\t | \n\t\t\t\t\t\t | \n\t\t\t\t\t\t | 123 | \n\t\t\t\t\t\t\n\t\t\t\t\t\t | 32 | \n\t\t\t\t\t
Emission factors considered for the LD fleet and fuel power plants and average unit energy consumption.
It is easy to see that even considering that EVs are recharged by fuel, there are advantages in the CO2 emissions balance, as the daily 120 tons from the car tail pipes, are replaced by 72 tons in the fuel power plants chimneys. Although the correct mode is to attribute emissions for the percentage of electricity consumption to EVs’ recharge, and that is only 37 tons.
\n\t\tElectricity supply is considered a service of general economic interest. In the past, the electricity industry was organized as vertically integrated state-owned monopolies and consequently not subjected to the normal rules of competition. The liberalization process was put into force in many countries including in the European community (EC) in 1996 by Directive 96/92/EC, and led to the unbundling of activities. This directive defined common rules for the gradual liberalization of the electricity industry with the objective of establishing one common European market. Vertically integrated utilities have been vertically separated or unbundled and barriers to entry in generation and retailing were being removed to create competition.
\n\t\t\tIn the two case studies presented in this chapter, two situations are analyzed: In the case of a small isolated system, a vertically integrated company is considered and the average unit production costs are used to define the merit order for technology dispatch. In the case of a continental European country, the marginal production costs are used to provide a supply curve and schedule the technology dispatch and find the wholesale price by market simulation.
\n\t\t\tThe unit average cost for each technology is an average value that contains many simplifications. The cost functions are not linear and the average costs depend highly on the performance points in which the plants usually work. There are also the start-up costs (higher if there is a cold start) that should increase unit average cost if the plants don’t work in a continuous state. In a monopoly context, the unit commitment service is centrally provided by the system operator as all the units belonged to the same company. In a market context this decisions are private and individual companies will predict the price of energy for the time under consideration and will then incur the cost of starting up if they expect to make a profit.
\n\t\t\t\tIn this case, simple empirical rules are applied to distribute the energy source technologies to provide for the different scenarios of daily load profile. The rules used to order the power technologies that support expected demand plus EVs consider:
\n\t\t\t\tThe special producers either renewable or thermal (special producers like cogeneration) are the first in order;
The cheaper technologies follow afterwards. For each case, the cheaper technologies enter in increasing cost order until a certain percentage of the power installed is used and only then follows the next technology;
Production from reservoirs are used only in peak hours;
In any case the technical limits of each group committed to electricity production should be taken into account. In this case the imposed limitation is made by the power installed in each technology.
\n\t\t\t\tIn the S. Miguel (Azores) case study, as a volcanic Island, the renewable source is mainly geothermal. Geothermal power plants are characterized by high capital investments for exploration, drilling wells and plant installation but low cost for operation and maintenance, so that they should be considered base load plants.
\n\t\t\t\tThe unit costs per technology, considered in this example are described in Table 2 and the unit average production cost depends on the electricity mix. In table 2 there are two examples of electricity production mix and the associated average production costs. It is easy to see that the use of more fuel power plants instead of geothermal ones makes the unit variable costs higher due to fuel cost. Fuel prices tend to increase because of world oil demand increase and it must also not be forgotten that, associated to fuel plants use, there are the CO2 emission costs that also tend to increase due to increasing environmental concerns.
\n\t\t\t\tIt is also easy to see that the available technologies for electricity production make electricity costs expensive in S. Miguel Island. This has to be added to the fact that, an isolated system needs more redundancy and power installed in thermal plants to assure a high level of security of supply. This also increases fixed costs (the cost of power assurance).
\n\t\t\t\tProduction Technology | \n\t\t\t\t\t\t\tUnit costs €/MWh | \n\t\t\t\t\t\t\tProduction scenario 1 | \n\t\t\t\t\t\t\tProduction scenario 2 | \n\t\t\t\t\t\t
Geothermal | \n\t\t\t\t\t\t\t33 | \n\t\t\t\t\t\t\t37% | \n\t\t\t\t\t\t\t51% | \n\t\t\t\t\t\t
Wind | \n\t\t\t\t\t\t\t82 | \n\t\t\t\t\t\t\t4% | \n\t\t\t\t\t\t\t4% | \n\t\t\t\t\t\t
Hydro | \n\t\t\t\t\t\t\t80 | \n\t\t\t\t\t\t\t3% | \n\t\t\t\t\t\t\t3% | \n\t\t\t\t\t\t
Fuel | \n\t\t\t\t\t\t\t100 | \n\t\t\t\t\t\t\t56% | \n\t\t\t\t\t\t\t42% | \n\t\t\t\t\t\t
Average unit prod. cost (€/MWh) | \n\t\t\t\t\t\t\t74 | \n\t\t\t\t\t\t\t65 | \n\t\t\t\t\t\t
Unit average costs per technology, percentage of production scenarios and unit average production costs.
Added to the production costs there are also the costs associated to transmission lines use. Customers have to pay for the net’s investments and maintenance and at the end for the service of distribution, accounting and billing. As all these services are supplied for the same vertically integrated company in a monopoly context, the final prices that end customers have to pay for electricity supply are regulated.
\n\t\t\t\tThe impact EVs have on overall costs, depend on the additional variable cost associated with generating more electricity to serve the Plug-in vehicles’ charging. Average variable costs may rise with increased electricity sales because higher cost generation plants are brought to service. Assuming though, no new infrastructure investment, average fixed costs will decrease, because the existing debt-service obligation is spread over more energy sold.
\n\t\t\t\tThe time of vehicles charging is crucial for this analysis. An off-peak recharge can, in this example increase the penetration of geothermal power, decrease variable unit costs and fixed unit costs while at the same time reduces emissions and fuel oil consumption and imports.
\n\t\t\tTo use the marginal production costs to schedule technologies to the expected load, a market simulation can be done with the demand and supply curves interception. A supply curve per technology should be generated. These curves should be added to generate a whole supply curve. Supply curves per technology are generated based on the expected power installed per technology and the supply curves verified in the past. As an example it can be observed the supply curves for the Portuguese units for the different technologies that play in the Iberian Electricity (MIBEL) spot market. In Fig.10 is an example of the supply curves per technology that occurred in two winter days, (2009/01/12) at 12h and (2010/01/19) at 22h.
\n\t\t\t\tSupply curves per technology for day 22 Jan 2009 at 12h and 19 Jan 2010 at 22h in the Portuguese market
The supply curves in 2010 (the right hand side graphic in Fig. 10) show very low priced bids in hydro due to climate influence and also some low priced bids in natural gas due to more available supply (860MW were installed in the production system during the year 2009).
\n\t\t\t\tThe supply curves to be generated would represent different scenarios according to the expected power installed per technology, a dry or wet year scenario and the season. There are in the majority of the cases, 2 steps in the supply curves for each technology. The amplitude of the slops depends on the hydrologic conditions of the hydro resources and the natural gas availability. If there is too much of these resources, low priced platforms are expected at the beginning of the supply curves as observed for year 2010 in Fig. 10. The power where the steps occur and its amplitude depends on the power installed in the technology, the climate conditions scenarios, season and hour of the day. The rules for supply curves generation are the following:
\n\t\t\t\tThere are four cases of supply curves per technology associated with each season (Spring, Summer, Autumn or Winter);
The expected power installed in each technology in the year in study is an input that limits power generation;
The scenarios to be studied (a dry year with high priced hydro resources or a wet year with low priced hydro and natural gas offers) are inputs that lead to different supply curves shape;
Two or three slops are generated for each technology with more or less the same shape of the past supply curves observed as seen in Fig. 10.
According to the scenario studied, the season and power installed, the slops of the supply curves are generated with the same shapes of past technology’s supply curves observed in similar conditions. A small randomness that represents the observed variations is also programmed.
The supply curves generated for each technology are added in ascending order of price to form a global supply curve that will intersect demand.
An example of supply curves for year 2020 in Portugal mainland can be seen in Fig. 11.
\n\t\t\t\tIn this case, the rules for technologies dispatch are:
\n\t\t\t\tThe special producers either renewable or thermal (special producers like cogeneration) are the first in order;
The technologies with lower marginal costs follow afterwards. For each hour, according to demand level, the intersection gives market price and quantity per technology that will fulfill the daily load profile.
In this case, the wholesale electricity price is formed by supply and demand curves intersection. An increase in demand makes demand curve shift to the right and so electricity prices rise as the curves intersection occurs at a higher point in the slop. As an example, it is possible to see price formation for instance in hour 5, in the Portuguese sub-market, for the 23th Jan 2008 with the real data available at Market operator (OMEL 2009) site. It is possible to see the effects of an increase in off-peak load to plug-in vehicles recharging, in the market prices. As an example, considering that a huge amount of EVs were charging at this hour (5 a.m.) with an extra 800 kW power demand. The demand curve shifts to the right (Fig. 12). The price rises for almost three cents and some of the previous low cost clients (the pumping charges) were not supplied because they had lower priced buying bids.
\n\t\t\t\tScenario of supply curves per technology for year 2020 in the Portuguese market
Price formation in the Portuguese sub-market at hour 5 (economic simulation) and the effect of an extra 800MW of power for EV off peak recharge has in the market price.
The leveling of load profile may have the consequences of making the hydro-pumping less profitable. In fact, the reversible hydro plants’ profits come from the discharging and selling at peak prices revenues less the costs from pumping with energy bought with off-peak prices. The following relation must occur:
\n\t\t\t\tWhere
Over the wholesale prices, there come the net access prices. The national regulator establishes the access and pricing rules of the transmission and distribution activities. The revenues for transmission and distribution network’s operators are assured by the payment of a use tariff. The transmission and distribution network use tariffs are established by the regulator. In Table 3 there is the peak and off peak low voltage net access tariffs imposed in Portugal in the last years.
\n\t\t\t\tLow voltage net access tariffs | \n\t\t\t\t\t\t\t2008 | \n\t\t\t\t\t\t\t2009 | \n\t\t\t\t\t\t\t2010 | \n\t\t\t\t\t\t\t2011 | \n\t\t\t\t\t\t
Peak [cents/kWh] Off peak [cents/kWh] | \n\t\t\t\t\t\t\t7.45 3.28 | \n\t\t\t\t\t\t\t5.39 0.68 | \n\t\t\t\t\t\t\t9.09 3.76 | \n\t\t\t\t\t\t\t8.92 3.86 | \n\t\t\t\t\t\t
Evolution of low voltage net access regulated tariffs in Portugal
Apart from the networks access regulated tariffs and wholesale prices, consumers should have to pay also retailing electricity costs. These activities work in competition as the established model imposed the existence of electricity wholesale and retail markets and the possibility for any customer to choose between different retailers. Depending on the retailer that each end consumer chooses, the cost of electricity to be paid by consumers should include the cost that the retailer paid for the energy at the wholesale electricity market plus the value of the regulated net access tariffs plus the revenue for the retailer. Considering a 4% on the wholesale electricity cost for the retailer revenue and the values presented in Table 3, Fig. 13 depicts the evolution of the final cost of energy that a low voltage domestic consumer should pay along the day.
\n\t\t\t\tAverage daily evolution for final costs of energy for a domestic consumer in 2009
This difference in costs that is reflected more or less in the regulated prices between peak and off-peak consumption should influence EVs’ recharging profiles.
\n\t\t\tElectric drive vehicles with the plug-in capability are only beginning to be commercially available. It would be necessary to have an idea of the capability of mass production and market penetration of these vehicles depending on their critical components development phases (namely the most critical element – the battery). The type of mobility provided by the plug in vehicles will be an important aspect because it influences vehicle´s charging needs. The demand side of the transportation sector needs to be studied and it is inevitable that the consumer/passenger behavior will deeply affect future mobility. Each country´s fleet profile is largely dependent on economical and political/taxation aspects, for instance, Portugal has a relatively new fleet, but it is very difficult to access the fleet´s renovation rate because there are few incentives to disposal. However, these will be crucial aspects, as they will be relevant to the new vehicle technologies market penetration.
\n\t\t\tThe EV’s energy requirements and the expected power capacity in terms of the charging circuit and the capacity of the batteries are important requisites that define the time needed for charging and the all-electric autonomy of the vehicle.
\n\t\t\tThe expected evolution of the grid capacity to support recharge at any time and the energy production technologies are important to compute EVs energy use and emissions associated. In isolated regions, such as Islands the introduction of intermittent renewable has more problems because it is not connected to a robust large Continental grid. How to benefit from using off-peak capacity and the possibility of the charging coincides with renewable energy sources?
\n\t\tHow much power can be provided to an EV or a PHEV and during how much time?
\n\t\t\tThe power demand on the grid will be a function of the voltage and current of the connection point to the grid. The capacity of the battery will then determine the length of time it will take to recharge the battery, given the connection strength. EPRI has conducted several studies on PHEV capabilities (EPRI, 2006), (Duvall, 2006) and several options are possible. Adapting to the European mainland reality, it is possible to charge the vehicles at 230 volts AC with 2,5 mm2 wire’s section (16 A circuit current) that would be about 3,5kW or with 4 mm2 wire’s section (25 A circuit current) and that would be about 5kW.
\n\t\t\tIt is also possible to charge fast in stations, and this at a higher power level that may go till 50kW. While a slow charge can last 6-8 hours at 100% state of charge (SOC), a fast charge can last 15-30 minutes but only allows 80% SOC and with less battery efficiency (while a slow charge can have an efficiency of 80% a fast charge’s is reduced to 55%).
\n\t\t\tThe average daily energy needs to charge an EV depends on the daily mileage expected for the vehicle. The time and power of the recharge will define the EV’s charging profile and the aggregation of all EVs, the extra load the electric system has to supply. A few EVs have no effect in the power grids but a mass penetration of plug-in vehicles should be simulated so that the electric utilities are prepared with the best strategies for a synergetic combination of the transportation and electricity production systems.
\n\t\tThere are many factors regarding user preference for electric vehicle technology. The most pragmatic and objective causes that may a rational potential vehicle buyer decide not to choose this technology are:
\n\t\t\tFuel availability (the availability of charging infrastructures)
Range limitations for the BEV configurations
Acquisition costs
PHEVs and BEVs are designed such that they can be plugged into a home garage at night for fuelling. Garages are most frequently lacking in dense urban areas, the very places where an electric vehicle is an ideal solution for personal transportation. For example, in Lisbon only one in six cars are parked in private garages and these include apartment and condominiums with a parking place with need to plug-in (CML 2002).
\n\t\t\t\tIn addition to the lack of garage access, the limited electricity-only range of plug-in vehicles will prompt the desire for drivers to “top off” their batteries when away from their normal overnight charging location. Electric vehicles must be plugged into the grid to refuel, but a public infrastructure to provide this service does not yet exist. Prospective plug-in car owners want the assurance that they can charge their vehicles at home, while at work, or parked anywhere for extended periods. There is a need for parking/charging points for slow charge and fast charging stations.
\n\t\t\t\tOn average, cars are parked roughly 23 hours per day in home garages, apartments, condominiums and hotel garages, employee parking locations, public lots and curbside. To meet driver demand for convenient charging, these are the locations in which charging points should be installed.
\n\t\t\tThe limited driving range of pure EVs creates what is known as “range anxiety”, which affect drivers as soon as the battery charge falls below 50%. Fast charging could alleviate “range anxiety” by supplementing home slow charging with convenient on-road charging at opportunistic charging points. In one 10-minute charge cycle, fast charge technology can provide enough energy to allow an EV to operate for another 60 km (Szczepanek A., Botsford C., 2009). With a network of fast chargers, consumers could charge anytime, anywhere – practical infrastructure akin to the gasoline fill-up model. This fast charge capability can help to enable rapid growth of the EV market by minimizing vehicle downtime. Fleets can fast charge during opportunistic breaks to maximize productive drive.
\n\t\t\t\tBattery manufacturers believe that they could develop a battery that could cope with fast charging although the priority is to mass produce batteries at low costs, while maintaining high quality standards, safety requirements and guaranteeing a life time of more than ten years rather than introducing batteries with super fast charging capabilities.
\n\t\t\t\tThe successful launch of Li-Ion batteries for electronic goods such as laptops and mobile phones opened the door to further developments and it may be assumed that Li-Ion batteries will be the key technology for PHEVs and EVs in the coming decade. Regardless of the future development in the area of battery based energy storage it can be concluded that the current level of performance is now so good that the automotive industry has decided to include partly or fully electrical drivelines and traction batteries in many of their near future products.
\n\t\t\t\tWhen fast charge with safe batteries become available with increased capacity at competitive prices, the pure BEV can cover a wide range of the transport needs, especially in urban areas, and be a strong alternative to conventional transport powered by liquid fuels.
\n\t\t\t\tThe challenge lies in setting up a commercially viable, convenient system for end customers. The difficulty is how to change drivers’ mobility behavior, so that instead of going to a gas station just before the tank is empty, drivers need to charge their cars every other time they park.
\n\t\t\t\tThere is also a third alternative for recharging EVs, the battery swapping service. This can be done in recharging stations and the change can be done in about 10 minutes for a full charged battery. This would relieve “range anxiety” giving the customer three different modes for recharge:
\n\t\t\t\tSlow charge (7/8 hours for 100%);
Fast charge (30 minutes for 80%);
Batteries change (5 minutes for 100%).
The recharge service price should increase as time decreases. A fair price for each of these recharging models should be established, and this would both be high enough to infrastructure´s investment recovery and low enough to be advantage to customer. This service should increase the cost of electricity to recharge.
\n\t\t\tDespite growing environmental awareness in society, studies have repeatedly shown that customers are only willing to pay a limited price for being “green”. This means that EVs and PHEVs must be attractively priced, not only in terms of initial purchase price, but also the ongoing costs each month. The costs of EVs are still much higher than for conventional cars due to a low production volume and expensive battery packs. This reflects directly the manufacturing costs. On the other hand, the expenses per travelled km are quite attractive comparatively to gasoline use, for EV technological solution it is around 1/4. With present prices pure electric vehicles pay off in terms of cost only if long distances are driven (higher than 200 000 km) (Baptista, 2009). This fact is important when calculating eventual tax incentives to purchase these kinds of technologies, having in mind that the final consumer is extremely sensitive to the “km for breakthrough”. These limitations force Governments incentives to push the penetration of electric vehicles. There are predictions on the evolution of EVs’ batteries capacity, density and price for the coming years. According to some consultancy analysis (Roland Berger, 2008) battery costs are expected to decrease to half the price from 2010 to 2020.
\n\t\t\tThere are many possibilities of vehicles charging profiles. Some could be more likely to happen but the uncertainty is high as it depends on vehicles charging requirements and drivers mobility patterns. Many studies performed included different charging scenarios.
\n\t\t\tUnder this charging profile it is considered that each EV begins charging as soon as it is plugged in, and stops when the battery is fully charged in case of normal time charge or 80% SOC in case of fast charge. This can be considered a reference case without any intelligent control of how and when charging occurs, or incentives (such as time-of-use rates) to influence individual consumer behavior. The majority of charging is home charging though a little services charging is also considered. The uncontrollable charge could be as depicted in Fig. 14.
\n\t\t\t\tExpected charging profile for uncontrolled charging scenario
This charging scenario assumes that almost all charging occurs at home in the overnight hours. Given existing incentives for off-peak energy use it attempts to better optimize the use of low cost off peak energy by delaying initiation of household charging until 10 pm (Fig. 15) or 11pm according to the utility policy to promote off-peak demand.
\n\t\t\t\tExpected charging profile for off-peak charging scenario
Under this recharging profile, a peak at 10 pm should be expected in a high EV penetration scenario. This peak could be smoothed with scheduled strategies for off-peak recharge (Fig. 16).
\n\t\t\tThis charging scenario also assumes that almost all charging occurs at home during the off-peak hours, however it attempts to provide the most optimal low cost charging electricity by assuming that the vehicle charging can be controlled directly by the local utility. This allows the utility to precisely match the vehicle charging to periods of minimum demand, allowing the use of lowest cost electricity, and improving overall utility system performance.
\n\t\t\t\tExpected charging profile for a smothing off-peak charging scenario
The impacts of EVs and PHEVs charge on the electric utilities depend on the first place of the combination of vehicles’ penetration and charging profile scenarios. The case studies considered in this chapter arise from the combination of different scenarios of electric vehicle penetration and recharging operation. For each scenario, the following variables should be analyzed:
\n\t\t\tPrimary energy needs for the electric and transportation sector working as separate systems (BAU) and working together (EVs scenarios);
Effects in electricity load profiles.
Impacts on overall energy and CO2 emissions
Impacts on electricity costs.
Impacts on fossil fuels use and imports.
Energy consumption, fossil fuels use and CO2 emissions from electricity production and transportation (the light duty fleet segment) can suffer great reductions with the integration of these two sectors by transport electrification. The replacement of a great amount of ICEVs by EVs in a country in which power generation accounts with more than 50% of renewable sources has great impacts in fossil fuels use and CO2 emissions reductions.
\n\t\t\tIn terms of electricity production mix, with plenty renewable sources for generation, two extreme cases can be considered:
\n\t\t\tA dry year, with high prices offers for hydro and natural gas production, the supply curves per technology could have the following forms considered a certain power installed per technology (Fig. 17a).
A wet year, with low prices offers for hydro and also natural gas production, the supply curves per technology could have the forms depicted in Fig. 17b.
The expected load profiles for 2020 in a dry year hypothesis for a 2 million EVs scenario (about 1/3 of LD fleet replacement) should be as depicted in Fig. 18. A peak effect in load diagram in an uncontrollable recharge profile can be observed. By transport electrification, even in the worst situation of uncontrollable recharge, a 2% decrease in primary energy use, 9% in fossil fuels use (due to great reductions in the transportation sector) and 8% in CO2 emissions can be achieved by transport electrification when compared with the case without EVs. An off-peak recharge profile with mass EVs penetration has more effects in energy, fossil fuels use and emissions reductions. In fact it was verified a 4%, 10% and 9% reduction respectively.
\n\t\t\tExample of supply curves per technology with a) high prices for hydro and natural gas production; b) low prices for hydro and natural gas production
Example of the expected Winter demand profile for a dry year 2020 in an EVs’ peak and off-peak recharge scenario
Expected Winter spot prices in a peak and off-peak recharge scenarios for 2M EVs in Portugal mainland
In any situation the integration of the electricity generation and transportation sectors has energy and environmental advantages. The decrease of fossil fuel use brings also economic advantages in the trading balance as all fossil fuels are imported in this example country.
\n\t\t\tIn terms of the electricity wholesale prices, in a high EV penetration scenario, the leveling of the spot prices follow the leveling of the load profile (Fig. 19).
\n\t\t\tIt is expectable that the peak effect of uncontrollable charging would cause price sparks at the peak hours. A time of use price for EVs recharge must be done to avoid this situation.
\n\t\t\tIn the Island example as stated in sections 2.2 and 2.3.1, uncontrollable EVs recharge has worse consequences in renewable penetration and production prices.
\n\t\tAs stated in section 2.3., electricity costs for EVs’ recharge, either in a market context or as a vertically owned company is a sum of different costs related to production, net use and retailing of the product to the final client. To illustrate the differences, we have two case studies, the mainland, where there is competition in the production and retailing markets and S. Miguel Island where the same company monopolises all activities.
\n\t\t\tAdding all the costs associated to electricity supply service, for the mainland case, in a scenario of low hydro production the price could reach 17 cents/kWh, for 2 Million EVs charging mainly at peak hours, this includes the whole sale price (8c€/kWh) plus the net access tariff (the 2010 regulated tariff was used in this example, 9.09c€/kWh) plus the retailer revenue (a 4% of the wholesale, 0.32c€/kWh). In a high hydro production and low wholesale prices, an off peak recharge could reach the 5.6 cents/kWh. In these extreme conditions EV energy prices could be between 0.9€ to 2.8€ per 100 km. Compared with the most efficient ICEV cars and the present gasoline and Diesel prices in Portugal that can spend between 4.5€ and 8.2€ per 100 km, there are great advantages in charging EVs during off-peak hours. These simulations were made considering for the vehicles a slow recharge at low voltage at home or at service and no extra charge is considered to pay for the parking/charging service.
\n\t\t\tFor the Island case study, an uncontrollable recharge must be forbidden, as the final electricity costs would reach the 20 cents/kWh, with all the environmental consequences as EVs would be recharged mainly with fuel oil. An off-peak recharge could cost only 8 cents/kWh, considered the regulated tariffs imposed (ERSE, 2011). In the Island EVs energy costs can be between 1.3€ and 3€ per 100 km.
\n\t\tElectric vehicles (EVs) and plug-in hybrid electric vehicles (PHEVs), which obtain their fuel from the grid by charging a battery, are set to be introduced into the mass market and expected to contribute to oil consumption reduction. PHEVs and EVs can also provide a good opportunity to reduce CO2 emissions from transport activities if the electricity they use to charge their batteries is generated through low carbon technologies. In addition to the environmental issue, EVs bring techno-economical challenges for utilities as well, because EVs will have great load flexibility as they are parked 93% of their lifetime, making it easy for them to charge either at home, at work, or at parking facilities, hence implying that the time of day in which they charge, can easily vary.
\n\t\t\tThe replacement of a great amount of ICEVs by EVs in a country in which power generation accounts with more than 50% of renewable sources has great impacts in fossil fuels use and CO2 emissions. The results obtained from the simulations show that, a mass penetration of electric vehicles in Portugal, contributes to decrease energy consumption, fossil fuels’ use (mainly oil) and CO2 emissions from the two sectors (electricity production and transportation) that nowadays most contribute to the emissions from fossil fuels burning.
\n\t\t\tThe pressure to generate electricity from endogenous low carbon resources in the majority of the countries makes naturally transport electrification a solution to lower emissions and fossil energy use from the transportation sector also. The cost and range of the vehicle remain the main bottlenecks for EVs penetration.
\n\t\t\tThe cost of the energy to charge the EV is highly dependent on the electricity generation technologies in the first place, the electricity market structure (whether there is concurrence or not) and the time of recharge (peak or valley recharge) makes the rest influence on final costs.
\n\t\t\tIn the examples used in this chapter, scenarios of EV penetration (energy needed) and recharge profile (hourly power demand) combined with the extreme cases of expected electricity production lead to different wholesale prices and hourly price profile, as well as fossil fuels use and emissions associated to charge the EVs, leading to different costs of the EV fuel per km.
\n\t\t\tFacing the increasing oil prices, the cost of energy per km of the EVs became even more advantageous when compared to ICEVs fuel costs and enough to overcome the initial purchase costs difference.
\n\t\tThanks are due to the MIT Portugal Program and Fundação para a Ciência e Tecnologia for the PhD financial support (SFRH/BD/35191/2007) POS_Conhecimento. The authors would like to acknowledge FCT- Fundação para a Ciência e Tecnologia through the national project MMSAFU - Microssimulation Model to Simulate Alternative Fuel Usage (POCI/ENR/57450/2004), and national project Power demand estimation and power system impacts resulting of fleet penetration of electric/plug-in vehicles (MIT-Pt/SES-GI/0008/2008).
\n\t\tAntiphospholipid syndrome (APS) was first described in 1983 with steadily improving clinical and scientific refinements since that time. It was initially recognized with the discovery of lupus anticoagulant immunoglobulin that binds to phospholipids and proteins associated with the cell membrane and its association with other autoimmune conditions. Over the years, the clinical manifestations of APS were further delineated, followed by the discovery of other antiphospholipid antibodies. Currently, APS is defined as an autoimmune condition characterized by the presence of venous or arterial thrombosis and/or pregnancy-related complications in patients with antiphospholipid antibodies [1]. Notably, APS can occur as a
Clinically, APS can manifest in a variety of ways and affect multiple organ systems. Presenting symptoms can range from relatively benign to severe. One subtype (to be discussed in Section 2) termed catastrophic APS (CAPS) is defined as APS that affects >3 organs in a short period of time (<7 days) with pathologic evidence of small-vessel occlusion. The most common venous manifestation of APS is deep vein thrombosis, while stroke is the most common arterial manifestation of this disease [4]. Obstetric complications include placental insufficiency and recurrent pregnancy loss, typically after 10 weeks of gestation. There are, however, a multitude of other manifestations including cardiac valvular disease, coronary artery disease, livedo reticularis, renal small artery vasculopathy, and thrombocytopenia, which are
Antiphospholipid antibodies (aPL) are a serological marker for APS and their presence is key to the definition and classification for APS. Phospholipids are molecules found in the blood that aid in clot formation. They form complexes with other plasma proteins and are the target of aPL antibodies; thus, one may expect to clinically see a bleeding disorder when phospholipids are disrupted. However, these autoantibodies primarily cause endothelial dysfunction and disruption of coagulation factors as they compete with coagulation factors for available phospholipids, thereby leading to a procoagulant state and clot formation [6]. The pathophysiology of aPL antibodies is not fully elucidated, but the current thought is that of a “two-hit” hypothesis. The first hit being a patient-specific susceptibility, and the second hit being a trigger or inciting event. This theory is based on the idea that about 1–5% of the population may have positive aPL antibodies without any clinical manifestations, indicating the need for a trigger that leads to the pathologic state [2, 4]. In a patient carrying aPL antibodies, endothelial cell activation occurs in the setting of oxidative stress in conditions such as infection, surgery, and pregnancy. This is thought to subsequently lead to a series of events including complement activation, cytokine release, increased expression of tissue factor on endothelial cells, increased platelet adhesiveness, and impairment of thrombolysis [2, 4]. Overall, this creates a procoagulant state leading to the range of clinical manifestations as described.
aPL antibodies are a heterogeneous group of autoantibodies that primarily include
There are a variety of antiphospholipid antibodies associated with APS, as detected with different methods, some are overlapping, but each has distinct properties. Image adapted from Misita et al. [
The presence of LA alone is thought to hold the highest risk for thrombosis among all antiphospholipid antibodies. Thrombotic risk is much lower in patients who have only a positive aCL or anti-B2GPI antibody [1, 3]. The risk is thought to be much higher however in patients with multiple positive antibodies, especially those found to be “triple positive” [3]. Thrombotic risk is also much higher in patients who have secondary APS is associated with SLE and in patients with primary APS with concurrent vascular comorbidities including hypertension, hypercholesterolemia, tobacco, and oral contraceptive use [7].
The initial classification criteria for APS, called the Sapporo criteria, was first developed in 1999 and most recently updated in 2006 [1]. As shown in Table 1, the criteria currently require one clinical manifestation of thrombosis or pregnancy complication, and one laboratory criteria present on two occasions at least 12 weeks apart.
Antiphospholipid antibody syndrome (APS) is present if at least one of the clinical criteria and one of the laboratory criteria that follow arc met* clinical criteria |
1. Vascular thrombosis† One or more clinical episodes‡ of arterial, venous, or small vessel thrombosis§, in any tissue or organ. Thrombosis must be confirmed by objective validated criteria (i.e. unequivocal findings of appropriate imaging studies or histopathology). For histopathologic confirmation, thrombosis should be present without significant evidence of inflammation in the vessel wall. |
2. Pregnancy morbidity
|
Laboratory criteria** 1. Lupus anticoagulant (LA) present in plasma, on two or more occasions at least 12 weeks apart, detected according to the guidelines of the International Society on Thrombosis and Hemostasis (Scientific Subcommittee on LAs/phospholipid-dependent antibodies) [10, 11]. |
2. Anticardiolipin (aCL) antibody of IgG and/or IgM isotype in scrum or plasma, present in medium or high titer (i.e. >40 GPL or MPL, or >the 99th percentile), on two or more occasions, at least 12 weeks apart, measured by a standardized ELISA. |
3. Anti-β2 glycoprotein-I antibody of IgG and/or IgM isotype in scrum or plasma (in titer > the 99th percentile), present on two or more occasions, at least 12 weeks apart, measured by a standardized ELISA, according to recommended procedures. |
The classification criteria for APS [1].
Classification of APS should be avoided if less than 12 weeks or more than 5 years separate the positive aPL test and the clinical manifestation.
Coexisting inherited or acquired factors for thrombosis arc, not reasons for excluding patients from APS trials. However, two subgroups of APS patients should be recognized, according to (a) the presence, and (b) the absence of additional risk factors for thrombosis. Indicative (but not exhaustive) such eases include: age (>55 in men, and >65 in women), and the presence of any of the established risk factors for cardiovascular disease (hypertension, diabetes mellitus, elevated LDL or low HDL cholesterol, cigarette smoking, family history of premature cardiovascular disease, body mass index ≥30 kg m–2, microalbuminuria, estimated GFR < 60 ml min−1), inherited thrombophilias, oral contraceptives, nephrotic syndrome, malignancy, immobilization, and surgery. Thus, patients who fulfill criteria should be stratified according to contributing causes of thrombosis.
A thrombotic episode in the past could be considered as a clinical criterion, provided that thrombosis is proved by appropriate diagnostic means and that no alternative diagnosis or cause of thrombosis is found.
Superficial venous thrombosis is not included in the clinical criteria.
Generally accepted features of placental insufficiency include: (i) abnormal or non-reassuring fetal surveillance test(s), e.g. a non-reactive non-stress test, suggestive of fetal hypoxemia, (ii) abnormal Doppler flow velocimetry waveform analysis suggestive of fetal hypoxemia, e.g. absent end-diastolic flow in the umbilical artery, (iii) oligohydramnios, e.g. an amniotic fluid index of 5 cm or less, or (iv) a postnatal birth weight less than the 10th percentile for the gestational age.
Investigators arc strongly advised classifying APS patients in studies into one of the following categories: I, more than one laboratory criteria present (any combination): IIa, LA present alone; IIb, aCL antibody present alone; IIc, anti-β2 glycoprotein-I antibody present alone.
As mentioned, there are other autoantibodies implicated in APS that are not yet included in the classification criteria. The remainder of this chapter will discuss the clinical manifestations, epidemiology, pathophysiology, diagnosis, and treatment in more detail.
APS can present as a wide range of clinical manifestations with the major clinical features consisting of arterial and venous thromboses, and obstetrical complications. The most common obstetrical manifestations of APS are recurrent early miscarriage, placental insufficiency, early pre-eclampsia, and fetal death, all of which should prompt evaluation for the presence of aPL [12].
Thrombotic events in APS may occur in virtually any vascular bed, with the cerebral circulation being the arterial territory most commonly affected, usually in the form of stroke or transient ischemic attack [13]. APS has also been associated with many other clinical features including livedo reticularis, epilepsy, thrombocytopenia, and cognitive dysfunction, however, the strength of association is not sufficiently high to include them in the syndrome definition. The clinical characteristics of a cohort of 1000 patients with APS (Euro-Phospholipid Project) are displayed in Table 2 [14].
As described in Section 1, the first set of criteria for APS was established in Sapporo, Japan in 1999 after an expert workshop [9]. This was modified, including the addition of anti-β2GPI antibodies in Sydney, Australia in 2006. The revised APS classification criteria strongly recommend investigating coexisting inherited and acquired thrombosis risk factors in patients with APS [1]. A recent assessment of the 2006 revised APS classification criteria has shown that only 59% of the patients meeting the 1999 APS Sapporo classification criteria met the revised criteria [15]. In addition, many of the older studies evaluated for only a few of the specific aPL antibodies now thought to be important in stroke risk, accepted low positive titers and many looked at only one-time point, hence it is difficult to apply the results of those studies [16]. While the purpose of the criteria was to help choose patients for clinical trials, it is the best available tool to avoid over-diagnosis of APS in clinical practice [17].
CAPS is a rare and potentially fatal complication of APS. As described in Table 3, the clinical presentation is characterized by acute multi-organ failure due to thromboses of three or more organs within 1 week, associated with the presence of aPL and thrombocytopenia [16]. CAPS can be seen as the first presentation of APS or can be triggered by infection, surgery, or trauma in patients with known APS [19].
Manifestation | No. (%) of patients |
---|---|
Deep vein thrombosis | 389 (38.9%) |
Other peripheral thrombi | 248 (24.8%) |
Migraine | 202 (20.2%) |
Stroke | 198 (19.8%) |
Transient ischemic attack | 111 (11.1%) |
Epilepsy | 70 (7.0%) |
Multi-infarct dementia | 25 (2.5%) |
Chorea | 13 (1.3%) |
Acute encephalopathy | 11 (1.1%) |
Transient amnesia | 7 (0.7%) |
Cerebral venous thrombosis | 7 (0.7%) |
Cerebellar ataxia | 7 (0.7%) |
Transverse myelopathy | 4 (0.4%) |
Hemiballismus | 3 (0.3%) |
Pulmonary embolism | 141 (14.1%) |
Other pulmonary manifestations | 56 (5.6%) |
Valve thickening/dysfunction | 116 (11.6%) |
Other cardiac manifestations | 153 (15.3%) |
Renal manifestations | 27 (2.7%) |
Gastrointestinal manifestations | 42 (4.2%) |
Livedo reticularis | 241 (24.1%) |
Other cutaneous manifestations | 155 (15.5%) |
Arthralgia | 387 (38.7%) |
Other osteoarticular manifestations | 295 (29.5%) |
Amaurosis fugax | 54 (5.4%) |
Other ophthalmological manifestations | 34 (3.4%) |
8 (0.8%) | |
Thrombocytopenia | 296 (29.6%) |
Hemolytic anemia | 97 (9.7%) |
Preeclampsia | 56 (9.5%) |
Other obstetric manifestations | 41 (7.1%) |
Live birth | 753 (47.7%) |
Other fetal manifestations (fetal loss, premature births) | 827 (52.3%) |
Cumulative clinical features during the evolution of the disease in 1000 patients with APS (adapted [14]).
1. Evidence of involvement of three or more organs, systems, and/or tissues. |
2. Development of manifestations simultaneously or in less than a week. |
3. Confirmation by histopathology of small vessel occlusion in at least one organ or tissue. |
4. Laboratory confirmation of the presence of antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies, and/or anti-beta2-glycoprotein I antibodies). |
Requires all four criteria |
All four criteria, except for only two organs, systems, and/or sites of tissue involvement |
All four criteria, except for the laboratory confirmation at least six weeks apart due to the early death of a patient never tested for aPL before the catastrophic APS |
Criteria 1, 2, and 4 above |
1, 3, and 4 and the development of the third event in more than a week but less than a month, despite anticoagulation. |
In the setting of pregnancy, Obstetric APS (OAPS) is diagnosed if at least one of the clinical criteria and one of the laboratory criteria are met as outlined in Table 4 [1, 20].
Clinical criteria | Laboratory criteria |
---|---|
|
|
Although up to 5% of the population might be positive for aPL antibodies, only a small fraction is diagnosed with APS as per the mentioned criteria [21]. Based on the analysis of 120 full-text papers, the overall estimated aPL frequency in stroke patients of all ages is 13.5% [22]. Sciascia et al. [7], in a systematic review of data from 5217 patients concluded that the overall aPL frequency was estimated as 17.2% for stroke and 11.7% for the transient ischemic attack, and the presence of aPL seems to confer a five-fold higher risk for stroke or TIA when compared with controls. The cumulative prevalence in the Euro-Phospholipid Project Study was 19.8% for stroke and 11.1% for TIA [14], making it the most common and severe arterial complication of APS.
Notably, it has been suggested that more than 20% of strokes in patients younger than 45 years are associated with APS [23], although this estimate may be inflated by referral bias [24]. The presence and magnitude of the ischemic stroke risk associated with aPL in the older population are more evenly split between finding an increased risk and no increased risk. This suggests that aPL may be a more important stroke mechanism in young people whereas, in older populations, other stroke risk factors take on a greater importance.
aPL associated strokes pose a higher risk for women. The Framingham cohort and offspring study found an increased risk of strokes and TIAs for women with high anticardiolipin but not in men [25]. In another study of 34 women under 45 years of age with ischemic strokes and no traditional vascular risk factors, 35% were found to have anticardiolipin antibodies [26].
Another study demonstrated that high serum concentrations of aPL, regardless of other cardiovascular risk factors, were an important predictor of the risk of future stroke and TIA in only females [27]. The presence of anti-β2GP1 antibodies in young women may increase the stroke risk 2.3-fold according to the RATIO study [28].
In terms of traditional vascular risk factors in APS patients, it is debated whether these or the circulating aPL antibodies are responsible for the accelerated atherosclerosis seen in APS. Hypertension is more prevalent in SLE and APS than in the general population. A study showed that hypertension was the only independent risk factor for arterial manifestations, mainly stroke, in APS [29]. The risk of stroke for LA-positive patients was two-fold in smokers and six-fold in smokers receiving oral contraceptives [25]. The Italian Project on Stroke in Young Adults, a prospective study of 1867 patients showed that family history of strokes, migraines with auras, aPL, discontinuation of antiplatelet or antihypertensive medications and increase in at least one traditional vascular risk factor were independent predictors for thromboembolic events [30]. Overall, this emphasizes the importance of aggressively treating all modifiable stroke risk factors like hypertension, diabetes, hypercholesterolemia, obesity, OCP use, and tobacco use to reduce additional thrombotic risks.
A summary of factors that warrant an evaluation of APS in stroke patients is listed in Table 5.
Patient age < 50 years of age |
Female gender |
Lack of traditional vascular risk factors |
Positive family history for arterial or venous thromboses |
Recurrent strokes |
Thrombocytopenia, obstetric complications, venous thromboses, or other arterial thromboses |
SLE or presence of other connective tissue diseases |
Key factors warranting evaluation of antiphospholipid syndrome.
Stroke subtypes in APS may be either thrombotic or cardioembolic depending on the location and size of the occluded vessel [31]. Intracranial stem or branch arterial occlusions and stenosis were reported in 50% of APS patients with stroke [32]. Narrowing of multiple intracranial arteries may occur in APS and indicates vasculopathy rather than vasculitis. Occasionally, there is involvement of the extracranial carotid artery. In a small case series of 17 patients, 32% had extracranial arterial abnormalities [33]. Cardioembolic strokes in APS are associated with left cardiac valvular abnormalities, including irregular thickening of leaflets, non-bacterial vegetations, and valve dysfunction [32]. Stroke subtypes in APS can also vary according to the types of antibodies [34]. Saidi et al. [35], in an analysis of 208 patients with their first stroke, reported that antiphosphatidylserine IgG was associated with cardioembolic strokes, lupus anticoagulant with lacunar strokes, and anticardiolipin IgG and IgM with lacunar, atherosclerotic and cardioembolic strokes. The severity of the thromboembolic event does not relate to the aPL antibody titer.
The type of antibodies present also appears to have an association with increased thrombotic risk. The presence of antiphosphatidylserine antibodies had the highest risk for clinical manifestations of APS, and IgG antiphosphatidylserine antibodies correlated strongly with the presence of lupus anticoagulant. The presence of antiphosphatidylserine antibodies (IgG or IgM) or anti-b2GP-1 (IgG, IgM, or IgA) antibodies improved the specificity for APS over anticardiolipin antibodies alone [36]. In another study, the positive predictive value for antiphosphatidylserine and anti-b2GP-1 antibodies was stronger for arterial thromboses than for venous thromboses [37]. Another study of pregnant women with APS reported that patients with triple aPL positivity (LA, aCL, and anti-B2GPI) and/or previous thromboembolism had an increased likelihood of poor neonatal outcomes than patients with double or single aPL positivity and no thrombosis history [38].
The recurrent risk of stroke in APS patients has been less widely studied as compared to other types of thromboses. Pezzini et al. calculated a cumulative risk of 14% for brain ischemia at 10 years [30]. Recurrent strokes and other thromboembolic events in patients with aPL antibodies have been reported both early (within the first year of an index stroke event) and late (5–10 years) [39]. The initial type of thromboembolic event (i.e. arterial, venous, miscarriage) appears to be the most likely type of event to recur in a given patient according to some studies [40]. The Euro-Phospholipid Project Group reported thrombotic events in 16.6% of patients in the first 5 years of follow-up and in 14.4% in the second 5-year follow-up period. The most common events during follow-up were strokes, TIAs, DVTs, and pulmonary emboli with survival probability at 10 years being 90.7% [14].
The first model to develop a predictive model for aPL associated thrombosis risk in SLE patients was modified in 2013 by Sciascia et al. to include data on clinical manifestations, and risk factors forming a quantitative score called the Global Antiphospholipid Syndrome Score (GAPSS) [41]. This was further modified in 2019 to form the aGAPSS (Adjusted Global Antiphospholipid Syndrome Score) as outlined in Table 6 [42]. The goal of the aGAPSS is to risk-stratify patients based on the likelihood of developing recurrent thrombosis in the setting of APS.
Factor | Point value |
---|---|
Anticardiolipin Antibody IgG/IgM | 5 |
Anti-B2-glycoprotein I IgG/IGM | 4 |
Lupus anticoagulant | 4 |
Hyperlipidemia | 3 |
Arterial hypertension | 1 |
Taken together, screening for APS is indicated in stroke patients who meet even some of the clinical and laboratory criteria and those with recurrent strokes despite maximal medical management and no clear etiology. The goal of these scoring systems is to further refine the risk of recurrent thromboses associated with APS.
Cerebral venous sinus thrombosis (CVST) usually presents with headaches, nausea, vomiting, often associated with seizures, and focal neurological deficits. Papilledema, coma, and death also occasionally contribute to the clinical manifestation of CVST. In patients with CVST, reported frequency of aCL positivity ranges from 7 to 22% [43], and predisposes to CVST at a relatively younger age and to a more extensive cerebral venous involvement [44]. In addition, a higher rate of post-cerebral venous sinus thrombosis headache and more infarctions on brain imaging studies are seen in patients with aPL antibodies than in those without them [45].
While intracranial hemorrhage (ICH) is not a common manifestation of APS, there have been reports of reversible vasoconstriction syndrome (RCVS) [46] which is characterized by thunderclap headaches (severe pain peaking in seconds), and focal neurologic deficits.
Moyamoya disease, a progressive narrowing of cerebral vasculature with collateralization, has also been reported to have associations with APS. Of the 16 cases reported in a small series of moyamoya and aPL, 21% fulfilled APS criteria [47].
Sneddon syndrome is a rare entity that may be considered during workup for APS. It is a chronic disorder, usually non-inflammatory, notable for generalized livedo racemosa (which may be confused with livedo reticularis seen in APS), and recurrent strokes [48]. Livedo racemosa is characterized by a violaceous netlike patterning of the skin similar to the familiar livedo reticularis, although it differs by its location (more generalized and widespread, found not only on the limbs but also on the trunk and/or buttocks). Approximately 40–50% of patients with Sneddon’s syndrome present aPL antibodies, suggesting that some patients should be classified as APS [49].
Cognitive dysfunction has been reported 19–40% in aPL-positive patients [50]. While many believe that the cognitive decline is due to multiple subcortical infarcts, there have been theories that it is multifactorial, with genetic predisposition, antibody specificity, and direct antibody effects as potential contributors [51].
Migraines are the most prevalent neurologic manifestation in APS, estimated prevalence of around 20% [52].
Other rare clinical manifestations of APS include seizures, acute ischemic encephalopathy, transverse myelitis, amaurosis fugax, optic neuropathy, and other neuropsychiatric disorders.
APS has been a recognized cause of cerebrovascular events (CVE) especially in those without classic cardiovascular risk factors. Traditionally, it has been estimated that one in five strokes in patients younger than 45 could be associated with APS, but there have been concerns that this is an over-estimate due to referral bias [53]. Systematic reviews have provided much of our current knowledge on the prevalence of aPL in patients with vascular events, however broad population studies are lacking. One large study evaluating stroke, pregnancy morbidity, myocardial infarction, and deep vein thrombosis estimated that aPL antibodies were present in ∼14% of stroke patients [22].
APS, either primary or secondary, garners consideration especially in young patients with CVE. To address events in the young, the previous study [21] was repeated for those less than 50 years of age and positive aPL was found in 17.4% of cases [54]. Regardless of diagnosis, the presence of any aPL increased the risk of CVE by 5.48-fold for those under the age of 50, and the risk of thrombosis progressively increases with the increasing number of positive antibodies [54]. It has also been reported that patients with stroke and aPL positivity are younger and more likely to be female than patients with strokes who are aPL negative [51]. A similar risk for CVE has been recently reported in another study, where persistently positive aPL increased the risk of CVE by 4.62-fold and where the positive criteria and non-criteria aPL was found in 20/89 (22%) CVE patients [55].
The Euro-Phospholipid Project cataloged the largest group of patients with APS. At the initiation of this study, prevalence data were obtained with 13.1% of patients having a stroke as their presenting manifestation [52]. Stroke was the fourth most common presenting symptom behind deep vein thrombosis, thrombocytopenia, and livedo reticularis. Of the 1000 patients, 204 (about 20%) experienced a stroke at some point during their disease course [52]. Cervera et al. [52] made a delineation regarding age-of-onset, defining “older-onset” APS as diagnosis after the age of 50. Comparatively, the over-50 patients were more likely to have strokes (30%) and were more likely to be male (34%), and were more likely to experience angina pectoris (9%) [52]. These patients were followed over a 10-year time period, and over that time period, 5.3% of the patients experienced a stroke. Stroke was the most prevalent thrombotic event. It was also the 4th leading cause of death in these patients following bacterial infection, myocardial infarction, and malignancy [14].
Patients with APS hospitalized with a stroke also have increased mortality compared to patients without APS [55]. APS has also been identified as an independent risk factor for hemorrhagic transformation of ischemic stroke (OR 2.57, 95%CI 1.14–5.81, p = 0.0228) and extended hospital length of stay [56].
One of the unique aspects of APS is the diversity of types of vasculature involved—arteries and veins, small vessels, and large vessels. Multiple mechanisms of the prothrombotic state have been theorized and will be discussed in Section 4 of this chapter. APS has been implicated in multiple stroke etiologic subtypes including large-artery atherosclerosis, cardio-embolism, and small-vessel occlusion. However, the percentage breakdown between these etiologies has not been consistently reported.
As previously stated, APS is responsible for venous events as well as arterial events. In the cerebrovascular system, these include CVST. APS has been implicated in 6–17% of all cases of CVST and tends to predispose to CVST at a relatively younger age [44].
Vasculopathies, described in detail in Section 2, including Moyamoya and Sneddon’s syndrome, overlap with APS at a rate of 21% and 50% respectively. Reversible cerebral vasoconstriction syndrome (RCVS) has also been described in patients with APS [46].
Other neurologic manifestations of the antiphospholipid syndrome include headache (20%), seizures (8%), and chorea (1.3–4.5%), with less frequent neurological manifestations including parkinsonism (especially progressive supranuclear palsy), dystonia, ballismus, myoclonus, cerebella ataxia, transverse myelitis, cognitive impairments, psychiatric symptoms, and peripheral neuropathy [4, 57].
As outlined in Table 7, some aPL are associated with a higher risk of ischemic stroke than others. Isolated LA positivity induces the greatest individual antibody risk for ischemic stroke [58]. Anti- β2-GPI were also associated with increased risk but to a lesser degree [58]. aCL and antiprothrombin antibodies have been reported variably with some studies showing no increased risk as an independent risk factor [27] while others reported to be independent risk when considering young patients exclusively [58]. As mentioned, triple positivity with positive LA, β2-GPI antibodies and aCL antibodies confers the highest risk [58].
High risk | Moderate risk | Low risk |
---|---|---|
Triple positivity (LA + aCL + anti-β2-GPI) | Isolated aCL when persistently positive in patients with SLE | Isolated anti-β2-GPI positivity |
Isolated LA positivity | Inconsistent and low titer isolated aCL positivity |
Risk for cerebrovascular event based on serologic profile. Adapted [58].
Traditional cardiovascular risk factors also play a role in outcomes for patients with APS. Studies reveal that hypertension and smoking are the risk factors most associated with repeat thrombotic arterial events [59]. Combinations of risk factors have also been shown to increase the risk of repeat events [60]. Prospective studies evaluating the results of risk factor control have yet to be reported.
The RATIO study (Risk of Arterial Thrombosis In relation to Oral contraceptives) identified that the use of oral contraceptives (OCPs) and smoking carried an extremely high risk for women with APS in terms of risk for myocardial infarction and ischemic stroke [28]. The data revealed that the relative risk for ischemic stroke was higher in those who were smoking and in women with OCPs. The odds ratio for ischemic stroke was 43.1 (95%CI 12.2–152.0), which increased to 201.0 (95%CI 22.1–1828.0) in women who used oral contraceptives and 87.0 (14.5–523.0) in those who smoked. In women who had anti- β2-GPI, the risk of ischemic stroke was 2.3 (95%CI 1.4–3.7), but the risk of myocardial infarction was not increased (OR 0.9, 95%CI 0.5–1.6). Neither aCL nor anti-prothrombin antibodies affected the risk of myocardial infarction or ischemic stroke [28].
Vascular thrombosis in APS can affect a wide variety of organ systems, but cerebrovascular thrombosis leading to stroke and transient ischemic attack is the most prevalent and perhaps the most consequential arterial event [61]. In a retrospective study of 135 APS patients, the highest morbidity was linked to neurologic involvement especially due to arterial thrombosis [62]. APS is also an important cause of stroke in the young, but as described can also affect older individuals [60]. The mechanisms of stroke in APS are diverse and include thrombosis in arteries, veins, and the microvasculature, as well as cardioembolism from non-bacterial thrombotic endocarditis.
The pathophysiology of vascular thrombosis in APS is not completely understood, but several studies suggest multiple converging pathways involving not only antibodies but also endothelial cells, platelets, monocytes, coagulation cascade proteins, and complements [63] producing a systemic thrombo-inflammatory state. The presence of aPL is not the sole cause for the significant clinical manifestations of APS as there can be asymptomatic “carriers” [17, 60]. Therefore, as previously mentioned, a “two-hit” hypothesis has been theorized, where the first-hit involves the presence of circulating aPL and associated endothelial dysfunction, and the second-hit presents an inflammatory insult such as trauma, surgery, or infection, leading to upregulation of β2GPI receptors on endothelial cells, as schematically demonstrated in Figure 2.
The pathophysiology of vascular thrombosis in APS is not completely understood, but a 2-hit hypothesis is widely proposed. The first hit involves the presence of circulating aPL and endothelial injury, while the second hit requires an inflammatory insult such as trauma, surgery, or infection, leading to upregulation of beta-2 glycoprotein 1 (β2-GP1) receptors on endothelial cells. The aPLs-β2-GP1 receptor interaction unleashes multiple converging downstream pathways culminating in a thrombo-inflammatory state. VEGF: vascular endothelial growth factor; neutrophil extracellular traps (NETosis); GP: glycoprotein; TF: tissue factor (adapted [
Even though aPL can be detected either by clotting tests, such as LA, or by an ELISA, such as aCL and anti-β2GPI, they are predominantly directed against β2GPI [17] and prothrombin [64]. Other important antigens recognized by aPL are annexin V, phosphatidylethanolamine, and phosphatidylserine [65]. Mechanistically these autoantibodies target phospholipid-binding plasma proteins bound to the surface of vascular endothelial cells and thrombocytes [60]. Plasma proteins predominantly bind to phosphatidylserine [17]. Normally located in the inner surface of cell membranes, phosphatidylserine becomes externalized when endothelial cells, platelets, and monocytes are activated. The avidity with which β2GPI binds to phosphatidylserine is further enhanced by the ‘β2GPI’- ‘β2GPI antibody dimerization’ [66]. The downstream effect of β2GPI antibodies on endothelial cells and monocytes includes increased expression of tissue factor and thromboxane A2 which trigger the extrinsic coagulation pathway [64, 67]. Furthermore, the antibody binding inhibits the tissue factor pathway inhibitor and protein C activity [64, 67]. Taken together, the net effect is the synergistic production of a prothrombotic state. Endothelial cells, upon stimulation with aPL, also downregulate their nitric oxide production and increase the surface expression of adhesion molecules such as E-selectin leading to pro-inflammatory and pro-coagulation endothelial phenotype [17, 57, 67, 68]. This antibody-induced endothelial injury can lead to intimal hyperplasia, micro-vasculopathy, and accelerated atherosclerosis [69]. Activated platelets increase their surface expression of GPIIb-IIIa, synthesis of thromboxane A2 and platelet factor-4a, all acting to facilitate thrombosis [67]. Activation of neutrophils with accompanying release of Neutrophil Extracellular Traps (NETosis) and IL-8 may also play a role [67]. Annexin V, a natural anticoagulant, binds to phosphatidylserine (a procoagulant) forming an anticoagulant shield in the physiologic state in APS, this shield is disrupted tipping the system in favor of coagulation [70]. Upregulation in the mTOR (mechanistic target of rapamycin) pathway on endothelial cells may partly explain the microvascular thrombosis seen in APS.
In addition to vascular thrombosis, up to one-third of patients with APS develop non-bacterial thrombotic endocarditis (NBTE) in which there is a deposition of sterile platelet thrombi on heart valves, particularly the mitral and aortic valves, which can be a source of cardioembolic strokes [66].
Population and family studies, as well as animal studies, have suggested genetic disposition may be relevant to the development of APS. Like many autoimmune disorders, predisposition to APS has been mapped to genes in the major histocompatibility complex (MHC), among others. Also, epigenetic phenomena such as altered microRNA biogenesis in neutrophils, leading to accelerated atherosclerosis, have been implicated in APS [63].
The initial workup for stroke in the setting of APS is consistent with that of other stroke etiologies. Specifically, a multisystem approach evaluating from “
What raises the suspicion for APS in stroke? When should it be considered that more information and studies are needed besides the typical workup usually undertaken? The most pertinent situation would be when a younger patient (<50 years) presented with a thrombotic stroke without identified classic risk factors for ischemic/embolic stroke [71]. Initial workup may reveal exam and laboratory findings that may raise the concern for APS as listed in Table 8. Notably, subtle renal, cardiac, hematologic, and dermatologic system alterations can be indicative. Further, a family history of early-onset stroke, clotting, or other systemic features should be queried. Absence of typical risk factors including hypertension, diabetes, atrial fibrillation, or known history of coagulopathy (e.g. protein C deficiency, protein S deficiency, antithrombin III), among others, further increases the consideration for APS. Notably, as many as 17% of cardiovascular events in those under 50 reveal aPL antibodies and up to 22% including anticardiolipin antibodies [54].
1. Hematologic |
2. Neurologic
|
3. Dermatologic
|
4. Cardiac
|
5. Renal
|
Other important clinical signs of APS not noted in Sapporo criteria, by body system. Adapted [63].
Of note, without suggestion of underlying coagulopathy or clinical findings (see Table 8) a young patient without classic risk factors, testing for many coagulopathies is not routinely performed. When performed, there is also the question of whether this workup needs to occur in the inpatient setting, during the patient’s admission for stroke, or if it can be done post-discharge. When considering this, the most important question is: Will any findings acutely change management? It should also be noted that for a positive diagnosis APS testing needs to occur multiple times over a 3 month or longer time period. If considering the APS diagnosis, formal hematology and/or rheumatology consult is recommended. In general, the recommendation for inpatient vs. outpatient is that some workup may be deferred if necessary, to the outpatient setting, either under the care of the patient’s primary physician/provider, neurologist, hematologist, or rheumatologist.
Consistent with all stroke patients, every patient should receive standard stroke workup testing including brain imaging (CT brain, MRI brain), vessel imaging of the head, neck, and great vessels of the chest (CTA, MRA), cardiac imaging including a transthoracic echocardiogram (TTE) and laboratory testing (CMP, CBC, PT/INR, aPTT, TSH, HgbA1C, lipid profile). A bubble study with the TTE should be considered if a paradoxical embolus from a DVT is on the differential. It is also recommended to obtain basic inflammatory markers such as sedimentation rate (ESR) and C-reactive protein (CRP) to evaluate for suggestion of diffuse inflammatory disease [24].
Transesophageal echocardiogram (TEE) should also be considered if the etiology remains uncertain, this is due to the increased frequency of valvular abnormalities in the setting of APS that may include irregular nodules/vegetations most commonly on the atrial side of the mitral valve or vascular side of the aortic valve, or if thickening of the valves is noted on TTE. Most commonly, the left side of the heart is the affected side with the mitral valve more commonly affected compared to the aortic valve. These cardiac changes are postulated to be due to immune complex damage and fibrosis [72].
If APS is being considered, it is recommended that while inpatient with the acute stroke the patient should have all antiphospholipid antibodies checked, according to the revised Sapporo laboratory criteria (see Table 1). Notably, this includes ELISA IgM/IgG for anticardiolipin (aCL) with a positive test showing medium to high titers (>40 GPL/MPL units or >99th percentile), which will need to be confirmed on at least two or more occasions, 12-weeks apart. Lupus anticoagulant (LA) should also be checked by two tests including dilute Russell viper venom time (dRVVT) and LA-sensitive PTT (PTT-LA)), again conformed on at least two occasions, 12-weeks apart. Lastly, an ELISA IgM/IgG for anti-beta2-glycoprotein I (β2GPI) should also be tested, with a positive value determined by titer in the 99th percentile, and again, should be tested on at least two occasions 12-weeks apart.
At least one clinical criterion (in the context of this chapter, most likely stroke) and one laboratory criterion should be met to diagnosis APS. As described, these tests are done 12-weeks apart, so the first set of lab tests will be performed inpatient and then the second 12-weeks later, typically performed in the outpatient setting. As outlined in Table 8, if the patient does not meet revised Sapporo criteria, APS may still be diagnosed if clinical suspicion remains high based on multi-system abnormalities and if further etiologies are not identified [64].
If a patient inconsistently tests positive for APS, it may be warranted to also check for other autoimmune diseases, namely systemic lupus erythematosus (SLE), as up to 36% of those with APS will be positive for SLE. Having both APS and SLE increases the risk for stroke beyond having only one or the other [31].
As described above, there are 3 primary antibody tests for APS including aCL, LA, and β2GPI. Anticardiolipin (aCL) testing was first developed as a test for syphilis in the 1900s [71]. The aCL antibody was found not to be specific to just syphilis, thus its utility as a test for APS was also found after many false-positive syphilis tests showed an increased risk for thrombotic events. The tests presently use tissue derived from bovine tissue. Both IgG and IgM are evaluated by ELISA for the presence of aCL antibodies. Notably, due to cross-reactivity as discussed with syphilis, the presence of aCL does not alone confirm APS.
Lupus anticoagulant (LA) is a test for immunoglobulins that while associated with thrombosis, are associated with preventing coagulation in vivo. The process for testing LA is three tests including screening (usually with aPTT or dRVVT, clotting of phospholipid factors), mixing (correct with normal plasma), and confirmation (shortening prolongation with added phospholipid) [67]. Once again, LA by itself cannot confirm APS due to cross-reactivity. LA testing is outlined in Figure 3.
Testing for lupus anticoagulant (Adapted [
Anti-β2 glycoprotein I (β2GPI) enzyme-linked immunosorbent assay (ELISA) testing is the last of the trio of tests for APS. There are 5 main domains of the β2GPI, labeled DI through DV. Anti-β2GPI largely targets domain I (DI). When this domain is targeted, it has been shown an association with thrombosis. The other domains DII through DV being targeted have not been shown to have as strong a connection for promoting thrombosis. Of note, there are some more rare entities that may also raise anti-β2GPI levels, such as leishmaniasis, leptospirosis, or leprosy. For APS, the associated antibodies are against the IgG form, whereas other elevates of anti-β2GPI may be directed towards the IgM variety [73].
Unless the patient presents with a prior history of APS, the diagnosis of APS will likely be in question during the acute and subacute stroke window. This is because APS by laboratory criteria needs to be performed 12-weeks apart with two positive tests to confirm. That said, a patient that presents with a stroke and has one or more laboratory results that are concerning for APS (positive LA, aCL, anti-β2GPI), there is a question if confirming APS would change acute management. Oftentimes, the answer is yes; this even in the setting of likely APS, because thrombosis can be multifactorial and can progress between confirmatory APS testing [67]. As such, management should focus on appropriate treatment for the source of the stroke. For example, if the source is cardioembolic, the timing of initiation of anticoagulation should be considered, weighing the risk of a second embolic event while not on indicated therapy versus the risk of hemorrhagic conversion of the primary infarct.
Once the workup for APS is complete, and if positive, the next logical step is to address treatment. However, prior to addressing treatment, let us first consider if APS is a primary risk factor for stroke risk. Numerous studies have been performed to address this question, culminating with a meta-analysis evaluating 15 different studies in aggregate [54]. In this evaluation, 13 of the 15 studies reported a significant association between a CVE and aPL antibodies with a cumulative odds ratio of 5.48 [54]. While this study provides insight into primary event risk, a follow-up question relates to the risk of APS with recurrent stroke. A second meta-analysis was completed looking at 8 studies to answer this question, demonstrating no statistically significant risk of recurrent ischemic stroke among APS patients [74]. Understanding why one meta-analysis demonstrated a link between aPL antibodies and single ischemic events, while another did not show a link with recurrent events remains challenging to understand. One hypothesis used to explain these incongruent findings is that clinical events do not occur frequently occur despite the presence of the antibodies, suggesting that treatment and/or lifestyle modifications after a first stroke affect the chance of a second event [74, 75]. Therefore, an understanding that APS is associated with the single cerebral vascular event, and that treatment affects the chance of a second event, indicates that secondary prevention is highly warranted.
Knowing that therapy is indicated, we can now evaluate various treatments on the risk of thrombosis in the setting of APS. In those individuals without any other risk factors, the risk of thrombosis is less than 1% per year [76, 77]. In this group, when they do present with a thrombus, it is normally in the setting of another thrombotic risk factor, such as cancer, surgery, pregnancy, estrogen use, acute infection, smoking, and hypertension. On the other hand, the risk of thrombosis can be as high as 5% per year in individuals with a persistent moderate high-risk profile including aPL antibodies and a systemic autoimmune disease [78]. Therefore, with the risk of thrombosis being so variable, sometimes as low as 1% or other times as high as 5%, the question of optimal prevention strategies can be challenging.
Regarding primary prevention (before a stroke or vascular event) the answer remains controversial with only scant data based on prospective trials [79]. Some of these trials have demonstrated a decrease in thrombosis with the use of aspirin. For example, a meta-analysis of 11 mostly observational studies demonstrated a 2-fold risk reduction in the first thrombotic event with a more significant effect in those with arterial thrombosis [79]. Post subgroup analysis of only prospective trials demonstrated there was no significant difference between aspirin and those not treated [79]. Therefore, with conflicting data on aspirin, one may ask could there be a benefit with the use of anticoagulation as well as aspirin for primary prevention. While the data was limited, one primary prevention study evaluated the use of aspirin alone vs. aspirin plus anticoagulation in 166 patients, demonstrating no significant difference in terms of the amount of thrombotic events between groups, with an increased risk of bleeding in the aspirin plus warfarin arm [80]. Therefore, given the increased bleeding risk, the use of aspirin and warfarin in combination is not recommended for primary prevention, with the question of aspirin use in isolation remaining. Many agencies have weighed in on this subject including the 13th International Congress on Antiphospholipid Antibodies as well as the European League Against Rheumatism making recommendations suggesting the use of aspirin in high-risk antiphospholipid profiles, those with other thrombotic risk factors, as well as those with SLE [58, 81]. Even with these recommendations, one must also consider the risk of bleeding with the use of aspirin. One meta-analysis looking at six randomized control trials showed an association of increased annual risk of major bleeding in those patients using aspirin with hypertension, age > 65, diabetes, and male sex being the most significant associated risk factors [82].
In summary, the decision to use primary prevention remains an individualized choice based on a patient-centric decision. Overall, though one should consider the use of primary prevention with aspirin in those with cardiac risk factors, high risk antiphospholipid antibody profile, presence of other thrombotic risk factors and in the presence of other autoimmune disease always ensuring a thorough risk benefit analysis is done with concern for bleeding. See Figure 4 for breakdown of treatment option algorithm.
Treatment options algorithm (adapted [
Knowing the indications for the use of primary prophylaxis we now consider secondary prophylaxis. Data regarding the need for secondary prophylaxis specifically in previous arterial thrombi remains scant without any consensus. For example, one study demonstrated the use of warfarin with a goal INR of 1.4–2.8 was not superior to full dose aspirin 325 mg alone for stroke prevention, with concerns that this study was flawed due to transient positivity of aPL antibodies [27]. Another study evaluating 20 patients with ischemic stroke demonstrated that the use of low-dose aspirin and warfarin with a goal INR of 2–3 was superior to low-dose aspirin alone in the prevention of further arterial thrombi [11]. While two other studies demonstrated that for older patients with stroke, and a single test showing low titers of anticardiolipin antibodies, that aspirin may be as effective as warfarin [27, 83]. With this conflicting data, there remains no consensus statement on secondary prophylaxis with many agencies weighing in on this subject. For example, the 13th International Congress on Antiphospholipid Antibodies as well as the European League Against Rheumatism both recommended secondary prophylaxis with high-intensity warfarin with an INR > 3 or low dose aspirin combined with moderate-intensity warfarin with an INR from 2 to 3 [58, 81]. Both agencies decided on using a goal INR of >3 for warfarin because in previous studies evaluating different doses of warfarin in treating thrombi, relatively few patients with arterial thrombi were enrolled [84, 85]. Overall, data remains scarce and guidelines are based upon a consensus of expert opinion. In those with recurrent arterial events, some recommend increasing target INR level and or switching to low molecular weight heparin with the addition of other adjective therapies to include statins [86].
In summary, the decision on which patient to treat and which agent to use for secondary prophylaxis with arterial thrombi remains a patient-centric decision. Those with high-risk aPL profiles, presence of other systemic autoimmune diseases, and or other risk factors for thrombus would likely benefit from treatment with either aspirin and warfarin with a goal 2–3 or warfarin alone with a goal INR 3–4. Those with recurrent events would likely benefit from increasing the INR goal or if not feasible switching to low molecular weight heparin. Moving forward it would be beneficial to validate a risk stratification model to identify those with arterial thrombosis who would benefit from more aggressive treatment [67]. See Figure 5 demonstrates a treatment options algorithm.
Arterial versus venous thrombus treatment options algorithm (adapted [
Now knowing the indications and treatment options for the use in secondary arterial prophylaxis we now move on to secondary venous prophylaxis, which in the case of stroke would be beneficial in treating paradoxical emboli. Much different from that in arterial secondary prophylaxis, there is more of a consensus regarding the treatment of secondary venous prophylaxis using warfarin with a goal INR of 2–3 showing a decrease in recurrent venous events of 80–90% [57, 87]. Some studies have evaluated the use of higher intensity anticoagulation with a goal INR of 3.1–4.5 showing no reduced risk in thrombosis, but a significant excess of minor bleeding [84, 85].
Therefore, with the above data, we can safely say in summary for secondary prevention for venous thrombi in those with a chance of paradoxical emboli treatment with warfarin with a goal INR of 2–3 is indicated. See Figure 5 for a treatment options algorithm.
Following the basics of both primary and secondary prevention, one may question other anticoagulation options as adjuvant therapies. Regarding the use of direct oral anticoagulants (DOACs) there remains insufficient evidence with data suggesting an increased risk of thrombosis [88]. For example, two studies demonstrated no difference in the rate of venous thromboembolism and an increased risk of arterial thrombotic with the use of rivaroxaban over warfarin [89, 90]. Looking at this data more closely, a meta-analysis of these two studies did not find an increased risk of thrombosis in patients treated with rivaroxaban over warfarin at a 6 month follow up, however for unclear reasons, almost 3/4 of the thrombi occurred post the 6 months follow up [39]. Given the lack of prospective data, the utility of DOACs in the treatment of thrombus formation remains uncertain.
Beyond DOACs, other adjuvant therapies have been studied including statins and hydroxychloroquine. With statins being a mainstay of treatment post-stroke, it would not be unreasonable to think that they may be beneficial in APS, potentially exhibiting pleiotropic effects including anti-inflammatory, antithrombotic, and as well as the expected lipid-lowering potential [13]. To date, there have been no randomized controlled trials looking at the efficacy in this group of patients. One study however did look at the levels of pro-inflammatory and prothrombotic markers post use of Fluvastatin, which were significantly decreased suggesting their benefit in APS [91]. At this time without a randomized control trial, the 15th International Congress on Antiphospholipid Antibodies has recommended the use of statins in those with high cardiovascular risks and or recurrent thrombosis despite adequate AC [88]. Regarding the use of hydroxychloroquine, similar to statins in addition to its immunomodulatory effect, it also has antithrombotic properties making it a good candidate as adjunctive therapy [88]. Two studies have been performed demonstrating differing results regarding treatment with hydroxychloroquine plus aspirin vs. aspirin alone. The first demonstrated no difference between rates of thrombosis between both groups [92]. The other demonstrated a significantly lower thrombotic rate compared to standard of care alone, in addition to down-trending antibody titers [93]. These data suggest that both statins and hydroxychloroquine could be beneficial as adjunctive therapies in specific situations, although more data is needed for consensus.
Throughout this section, we have addressed the need for primary and secondary prevention, but one question left unanswered is safety as associated with therapy cessation. Unfortunately, there remains a multitude of answers to this question, hence each case should be considered independently. In those with a history of arterial thrombotic events, the risk of repeat thrombus formation off anticoagulation is too high and therefore indefinite anticoagulation is warranted [94]. In those with a history of transient positivity of antiphospholipid antibodies who eventually become negative based on two separate studies, one can consider stopping anticoagulation [95, 96]. Specifically, this would be associated with those who only have primary APS with persistently negative antibodies where if there was a thrombotic event it occurred in association with a transient risk factor including pregnancy or immobilization as examples [96]. In these cases, it is thought that the antibodies do not play a pathogenic role, but rather are a “phenomenon”. Therefore, some have recommended a 3–6-month course of anticoagulation with consideration to look for residual thrombus, which has been shown to increase the rate of recurrence by 50% [94]. Notably, the data and recommendations regarding stopping anticoagulation are based upon two small case series. Therefore, with such insufficient data, unless the risk of anticoagulation outweighs the benefit it would not be recommended to stop anticoagulation in those that become persistently negative.
Throughout this section we have addressed both preventions of stroke in APS, but what if someone should fail prevention and come in with an acute stroke. The answer to this question unlike many of the other is simple. Acute management is no different than those with or without APS [97]. Lastly, as described, APS often requires treatment with anticoagulant medications such as heparin to reduce the risk of further episodes of thrombosis and improve the prognosis of pregnancy. Warfarin (brand name Coumadin) should not be used during pregnancy because it crosses the placenta and is teratogenic. Unfractionated heparin (UFH) and low molecular weight heparin do not cross the placenta and are safe for the fetus, but long-term treatment with UFH is problematic because of its inconvenient administration, the need to monitor anticoagulant activity, and because of its potential side effects, such as heparin-induced thrombocytopenia and osteoporosis [98].
Thromboses of the cerebral arterial and venous systems are a common manifestation of APS leading to ischemic and/or hemorrhagic stroke. APS has been a recognized cause of CVE especially in those without classic cardiovascular risk factors. It has been estimated that one in five strokes and patients younger than 45 could be associated with APS and some newer studies show that APL antibodies are present in approximately 14% of stroke patients. Persistently elevated APL seems to increase the risk for CV by at least fourfold. Stroke is the fourth most common presenting symptom behind deep venous thrombosis, thrombocytopenia, and livedo reticularis. The recurrent risk of stroke in APS patients has been less widely studied as compared to other types of thromboses, however, cumulative risk of 14% for brain ischemia at 10 years has been reported. APS increases stroke risk via many mechanisms including hypercoagulability, inflammation, accelerated atherosclerosis, and cardiac manifestations, among others. Mechanistically these lead to in-situ clot formation and/or embolic phenomena. Physicians must carefully consider all these potential mechanisms when evaluating and treating stroke patients to achieve both optimal short- and long-term outcomes. While the exact underlying pathophysiology of APS remains uncertain, underlying genetics in the setting of a triggering event (e.g., surgery, trauma, infection) is believed to play a key role in the development of the disease. While primary and secondary prevention recommendations continue to evolve, each case should be considered independently to achieve optimal results. Results from more randomized control trials are needed to further infer upon the ever-evolving consensus guidelines. For the time being, the decision to use primary and/or secondary prevention therapies, and of which type, will continue to be an individualized patient-centric decision requiring careful interpretation of test results with multispecialty (neurology, hematology, rheumatology) input.
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\\n\\nIn the case of Retraction or removal of the Work, the publisher will be under no obligation to refund the APC.
\\n\\nThe general principles set out above apply to Retractions and Corrections issued in all IntechOpen publications.
\\n\\nAny suggestions or comments on this Policy are welcome and may be sent to permissions@intechopen.com.
\\n\\nPolicy last updated: 2017-09-11
\\n"}]'},components:[{type:"htmlEditorComponent",content:'IntechOpen’s Retraction and Correction Policy has been developed in accordance with the Committee on Publication Ethics (COPE) publication guidelines relating to scientific misconduct and research ethics:
\n\n1. RETRACTIONS
\n\nA Retraction of a Chapter will be issued by the Academic Editor, either following an Author’s request to do so or when there is a 3rd party report of scientific misconduct. Upon receipt of a report by a 3rd party, the Academic Editor will investigate any allegations of scientific misconduct, working in cooperation with the Author(s) and their institution(s).
\n\nA formal Retraction will be issued when there is clear and conclusive evidence of any of the following:
\n\nPublishing of a Retraction Notice will adhere to the following guidelines:
\n\n1.2. REMOVALS AND CANCELLATIONS
\n\n2. STATEMENTS OF CONCERN
\n\nA Statement of Concern detailing alleged misconduct will be issued by the Academic Editor or publisher following a 3rd party report of scientific misconduct when:
\n\nIntechOpen believes that the number of occasions on which a Statement of Concern is issued will be very few in number. In all cases when such a decision has been taken by the Academic Editor the decision will be reviewed by another editor to whom the author can make representations.
\n\n3. CORRECTIONS
\n\nA Correction will be issued by the Academic Editor when:
\n\n3.1. ERRATUM
\n\nAn Erratum will be issued by the Academic Editor when it is determined that a mistake in a Chapter originates from the production process handled by the publisher.
\n\nA published Erratum will adhere to the Retraction Notice publishing guidelines outlined above.
\n\n3.2. CORRIGENDUM
\n\nA Corrigendum will be issued by the Academic Editor when it is determined that a mistake in a Chapter is a result of an Author’s miscalculation or oversight. A published Corrigendum will adhere to the Retraction Notice publishing guidelines outlined above.
\n\n4. FINAL REMARKS
\n\nIntechOpen wishes to emphasize that the final decision on whether a Retraction, Statement of Concern, or a Correction will be issued rests with the Academic Editor. The publisher is obliged to act upon any reports of scientific misconduct in its publications and to make a reasonable effort to facilitate any subsequent investigation of such claims.
\n\nIn the case of Retraction or removal of the Work, the publisher will be under no obligation to refund the APC.
\n\nThe general principles set out above apply to Retractions and Corrections issued in all IntechOpen publications.
\n\nAny suggestions or comments on this Policy are welcome and may be sent to permissions@intechopen.com.
\n\nPolicy last updated: 2017-09-11
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Both forms of IBD involve an uncontrolled inflammatory process in the intestines, leading to worsening quality of life and requiring long-term medical and/or surgical intervention. Epidemiological and clinical studies suggest that the pathogenesis of inflammatory bowel disease is strongly linked to genetic predisposition. CD and UC are considered polygenic diseases in which familial clustering is observed in 5–10% of patients. Among genetic factors associated with IBD development, it has been found that many single nucleotide polymorphisms are associated with susceptibility to IBD progression. SNP can affect the production or function of a protein and thus affect the development of the disease. However, although the overall role of genes involved in the development of IBD is already in most cases known, as of today it is unclear how the SNPs in these genes affect cellular function, or how such changed cellular functions would contribute to the development of IBD. In the present work several selected polymorphisms in genes involved in IBD development are discussed.",book:{id:"7947",slug:"the-recent-topics-in-genetic-polymorphisms",title:"The Recent Topics in Genetic Polymorphisms",fullTitle:"The Recent Topics in Genetic Polymorphisms"},signatures:"Ewa Dudzińska",authors:null}],onlineFirstChaptersFilter:{topicId:"61",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},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:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:99,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:289,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:104,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:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{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"}}}},{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"}}}}]},series:{item:{id:"10",title:"Physiology",doi:"10.5772/intechopen.72796",issn:"2631-8261",scope:"Modern physiology requires a comprehensive understanding of the integration of tissues and organs throughout the mammalian body, including the cooperation between structure and function at the cellular and molecular levels governed by gene and protein expression. While a daunting task, learning is facilitated by identifying common and effective signaling pathways mediated by a variety of factors employed by nature to preserve and sustain homeostatic life. \r\nAs a leading example, the cellular interaction between intracellular concentration of Ca+2 increases, and changes in plasma membrane potential is integral for coordinating blood flow, governing the exocytosis of neurotransmitters, and modulating gene expression and cell effector secretory functions. 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His primary area of interest is physiology and pathophysiology of the gastrointestinal (GI) tract, with the major focus on the mechanism of GI mucosal defense, protection, and ulcer healing. He was a postdoctoral NIH fellow at the University of California and the Gastroenterology VA Medical Center, Irvine, Long Beach, CA, USA, and at the Gastroenterology Clinics Erlangen-Nuremberg and Munster in Germany. He has published 290 original articles in some of the most prestigious scientific journals and seven book chapters on the pathophysiology of the GI tract, gastroprotection, ulcer healing, drug therapy of peptic ulcers, hormonal regulation of the gut, and inflammatory bowel disease.",institutionString:null,institution:{name:"Jagiellonian University",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"10",title:"Animal Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/10.jpg",isOpenForSubmission:!0,annualVolume:11406,editor:{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. 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From\r\n1964 to 1974, he worked as Assistant in Biochemistry at the School of MedicineUniversidad Nacional de La Plata, Argentina. From 1974 to 1976, he was a Fellowof the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor oBiochemistry at the Universidad Nacional de La Plata, Argentina. He is Member ofthe National Research Council (CONICET), Argentina, and Argentine Society foBiochemistry and Molecular Biology (SAIB). His laboratory has been interested for manyears in the lipid peroxidation of biological membranes from various tissues and different species. Professor Catalá has directed twelve doctoral theses, publishedover 100 papers in peer reviewed journals, several chapters in books andtwelve edited books. Angel Catalá received awards at the 40th InternationaConference Biochemistry of Lipids 1999: Dijon (France). W inner of the Bimbo PanAmerican Nutrition, Food Science and Technology Award 2006 and 2012, South AmericaHuman Nutrition, Professional Category. 2006 award in pharmacology, Bernardo\r\nHoussay, in recognition of his meritorious works of research. Angel Catalá belongto the Editorial Board of Journal of lipids, International Review of Biophysical ChemistryFrontiers in Membrane Physiology and Biophysics, World Journal oExperimental Medicine and Biochemistry Research International, W orld Journal oBiological Chemistry, Oxidative Medicine and Cellular Longevity, Diabetes and thePancreas, International Journal of Chronic Diseases & Therapy, International Journal oNutrition, Co-Editor of The Open Biology Journal.",institutionString:null,institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}},editorTwo:null,editorThree:null},{id:"12",title:"Human Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/12.jpg",isOpenForSubmission:!0,annualVolume:11408,editor:{id:"195829",title:"Prof.",name:"Kunihiro",middleName:null,surname:"Sakuma",slug:"kunihiro-sakuma",fullName:"Kunihiro Sakuma",profilePictureURL:"https://mts.intechopen.com/storage/users/195829/images/system/195829.jpg",biography:"Professor Kunihiro Sakuma, Ph.D., currently works in the Institute for Liberal Arts at the Tokyo Institute of Technology. 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Additionally, to understand how to maintain and improve physical function in older adults, to conduct studies about the mechanism of sarcopenia and determine when possible interventions are needed.",institutionString:null,institution:{name:"Ritsumeikan University",institutionURL:null,country:{name:"Japan"}}}},{id:"13",title:"Plant Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/13.jpg",isOpenForSubmission:!0,annualVolume:11409,editor:{id:"332229",title:"Prof.",name:"Jen-Tsung",middleName:null,surname:"Chen",slug:"jen-tsung-chen",fullName:"Jen-Tsung Chen",profilePictureURL:"https://mts.intechopen.com/storage/users/332229/images/system/332229.png",biography:"Dr. Jen-Tsung Chen is currently a professor at the National University of Kaohsiung, Taiwan. He teaches cell biology, genomics, proteomics, medicinal plant biotechnology, and plant tissue culture. 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(Eng.) in Telematics from the Universidad de Colima, Mexico. He obtained both his M.Sc. and Ph.D. from the University of Liverpool, England, in the field of Intelligent Systems. He is a full professor at the Universidad Autonoma de Queretaro, Mexico, and a member of the National System of Researchers (SNI) since 2009. Dr. Aceves Fernandez has published more than 80 research papers as well as a number of book chapters and congress papers. He has contributed in more than 20 funded research projects, both academic and industrial, in the area of artificial intelligence, ranging from environmental, biomedical, automotive, aviation, consumer, and robotics to other applications. He is also a honorary president at the National Association of Embedded Systems (AMESE), a senior member of the IEEE, and a board member of many institutions. 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He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. 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He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:"Polytechnic University of Timişoara",institution:{name:"Polytechnic University of Timişoara",institutionURL:null,country:{name:"Romania"}}}]},{type:"book",id:"9963",title:"Advances and Applications in Deep Learning",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/9963.jpg",slug:"advances-and-applications-in-deep-learning",publishedDate:"December 9th 2020",editedByType:"Edited by",bookSignature:"Marco Antonio Aceves-Fernandez",hash:"0d51ba46f22e55cb89140f60d86a071e",volumeInSeries:4,fullTitle:"Advances and Applications in Deep Learning",editors:[{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. 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