Comparison of the effectiveness of interferon in chronic myeloproliferative disorders.
\\n\\n
IntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\\n\\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\\n\\nLaunching 2021
\\n\\nArtificial Intelligence, ISSN 2633-1403
\\n\\nVeterinary Medicine and Science, ISSN 2632-0517
\\n\\nBiochemistry, ISSN 2632-0983
\\n\\nBiomedical Engineering, ISSN 2631-5343
\\n\\nInfectious Diseases, ISSN 2631-6188
\\n\\nPhysiology (Coming Soon)
\\n\\nDentistry (Coming Soon)
\\n\\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\\n\\nNote: Edited in October 2021
\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/132"}},components:[{type:"htmlEditorComponent",content:'With the desire to make book publishing more relevant for the digital age and offer innovative Open Access publishing options, we are thrilled to announce the launch of our new publishing format: IntechOpen Book Series.
\n\nDesigned to cover fast-moving research fields in rapidly expanding areas, our Book Series feature a Topic structure allowing us to present the most relevant sub-disciplines. Book Series are headed by Series Editors, and a team of Topic Editors supported by international Editorial Board members. Topics are always open for submissions, with an Annual Volume published each calendar year.
\n\nAfter a robust peer-review process, accepted works are published quickly, thanks to Online First, ensuring research is made available to the scientific community without delay.
\n\nOur innovative Book Series format brings you:
\n\nIntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\n\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\n\nLaunching 2021
\n\nArtificial Intelligence, ISSN 2633-1403
\n\nVeterinary Medicine and Science, ISSN 2632-0517
\n\nBiochemistry, ISSN 2632-0983
\n\nBiomedical Engineering, ISSN 2631-5343
\n\nInfectious Diseases, ISSN 2631-6188
\n\nPhysiology (Coming Soon)
\n\nDentistry (Coming Soon)
\n\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\n\nNote: Edited in October 2021
\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"8871",leadTitle:null,fullTitle:"Renewable Energy - Resources, Challenges and Applications",title:"Renewable Energy",subtitle:"Resources, Challenges and Applications",reviewType:"peer-reviewed",abstract:"The demand for secure, affordable and clean energy is a priority call to humanity. Challenges associated with conventional energy resources, such as depletion of fossil fuels, high costs and associated greenhouse gas emissions, have stimulated interests in renewable energy resources. For instance, there have been clear gaps and rushed thoughts about replacing fossil-fuel driven engines with electric vehicles without long-term plans for energy security and recycling approaches. This book aims to provide a clear vision to scientists, industrialists and policy makers on renewable energy resources, predicted challenges and emerging applications. It can be used to help produce new technologies for sustainable, connected and harvested energy. A clear response to economic growth and clean environment demands is also illustrated.",isbn:"978-1-78984-284-5",printIsbn:"978-1-78984-283-8",pdfIsbn:"978-1-83962-155-0",doi:"10.5772/intechopen.81765",price:159,priceEur:175,priceUsd:205,slug:"renewable-energy-resources-challenges-and-applications",numberOfPages:540,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"e00c59554fb355c16623c62064ecc3bb",bookSignature:"Mansour Al Qubeissi, Ahmad El-kharouf and Hakan Serhad Soyhan",publishedDate:"September 9th 2020",coverURL:"https://cdn.intechopen.com/books/images_new/8871.jpg",numberOfDownloads:17074,numberOfWosCitations:23,numberOfCrossrefCitations:40,numberOfCrossrefCitationsByBook:2,numberOfDimensionsCitations:82,numberOfDimensionsCitationsByBook:3,hasAltmetrics:1,numberOfTotalCitations:145,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 4th 2018",dateEndSecondStepPublish:"March 1st 2019",dateEndThirdStepPublish:"October 2nd 2019",dateEndFourthStepPublish:"March 14th 2019",dateEndFifthStepPublish:"May 13th 2020",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!0,featuredMarkup:null,editors:[{id:"241686",title:"Dr.",name:"Mansour",middleName:null,surname:"Al Qubeissi",slug:"mansour-al-qubeissi",fullName:"Mansour Al Qubeissi",profilePictureURL:"https://mts.intechopen.com/storage/users/241686/images/system/241686.png",biography:"Dr. Al Qubeissi is a Chartered Engineer, Fellow of the Higher Education Academy, member of several engineering organisations (including UnICEG, IAENG–ISME, IMechE and the Institute for Future Transport and Cities), and Senior Lecturer and Course Director for Master of Engineering programmes at CU. He is experienced in computational thermo-fluids, biofuels and energy systems. Other relevant expertise includes turbine combustion, PV/T and battery thermal management. His research efforts have been disseminated via 10s of publications in high impact refereed journals, conference proceedings and books. Since joining CU in 2015, Dr. Al Qubeissi has been involved in leading 10s of research projects and PhD theses. Prior to that role, he was a Lecturer at the University of Brighton, UK.",institutionString:"Coventry University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Coventry University",institutionURL:null,country:{name:"United Kingdom"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"296147",title:"Dr.",name:"Ahmad",middleName:null,surname:"El-Kharouf",slug:"ahmad-el-kharouf",fullName:"Ahmad El-Kharouf",profilePictureURL:"https://mts.intechopen.com/storage/users/296147/images/system/296147.jpeg",biography:"Dr. El-kharouf is a Research Fellow at the Centre for Fuel Cell and Hydrogen Research, School of Chemical Engineering, UoB, UK. He is the manager of the EPSRC Centre for Doctoral Training in Fuel Cells and their Fuels; a collaborative consortium of UoB, UCL, Imperial College London, University of Nottingham and Loughborough University. His primary research is focussed on the development of next generation automotive Polymer Electrolyte Fuel Cells (PEFCs), aiming for an operation temperature of up to 120˚C and increasing the stack volumetric and gravimetric power density. Dr El-kharouf’s other research activities include the development and testing of materials for PEM electrolysers, solid oxide fuel cell development and the integration of fuel cell and hydrogen technologies in transport and stationary applications.",institutionString:"University of Birmingham",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Birmingham",institutionURL:null,country:{name:"United Kingdom"}}},coeditorTwo:{id:"172226",title:"Associate Prof.",name:"Hakan Serhad",middleName:null,surname:"Soyhan",slug:"hakan-serhad-soyhan",fullName:"Hakan Serhad Soyhan",profilePictureURL:"https://mts.intechopen.com/storage/users/172226/images/system/172226.jpeg",biography:"Professor Soyhan has been a member of the Department of Mechanical Engineering, SU since 1992. He received his BEng (1992), MSc (1995) and PhD (2000) from Istanbul Technical University and undertook post-doctoral research in chemical kinetics at the Combustion Physics Division, Lund University, Sweden and on HCCI engines and chemical kinetics at Shell Global Solutions, Chester, UK. Currently, he is working on fuels and combustion studies in transport. He is the Head of Local Energy Research Association and Head of the Combustion Institute, Turkey. Professor Soyhan is the Founder and Director of TeamSan Co, a member of the Turkish Society of Mechanical Engineers, and an associate member of TUBITAK USETEG Committee on R&D projects of the Transportation, Defence and Energy Technologies Group.",institutionString:"Sakarya University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Sakarya University",institutionURL:null,country:{name:"Turkey"}}},coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"770",title:"Renewable Energy",slug:"engineering-energy-engineering-renewable-energy"}],chapters:[{id:"71531",title:"For Sustainable Development: Future Trends in Renewable Energy and Enabling Technologies",doi:"10.5772/intechopen.91842",slug:"for-sustainable-development-future-trends-in-renewable-energy-and-enabling-technologies",totalDownloads:1508,totalCrossrefCites:6,totalDimensionsCites:18,hasAltmetrics:1,abstract:"Energy demand in the world is nowadays growing further out of limits of installable generation capacity. Therefore, future energy demands should be met and improved efficiently and securely. Energy solutions should be supported by utilizing renewable energy sources. At present, the contribution of renewable energy to the world primary energy is not high to meet the primary energy and electricity supplies. Both developed and developing nations will necessarily continue to rely on fossil fuels in the coming decades. In developing countries, the situation is more inconvenient than that for developed countries. Many developing countries have been apparently trying to restructure their energy sectors. It seems that it is difficult to realize innovations. Cost, market share and policy are the main barriers for the development of renewable energy. In the strategy plans of many countries, the sustainable development in relation to the parameters such as economic, social and industrial is supported by their energy policies. New enabling technologies related to renewable energies will also help to reduce environmental costs, and thus the energy systems will be operated as both securely and economically without environmental problems. New renewable energy markets are surely required in both the wholesale and retail markets.",signatures:"Mustafa Seckin Salvarli and Huseyin Salvarli",downloadPdfUrl:"/chapter/pdf-download/71531",previewPdfUrl:"/chapter/pdf-preview/71531",authors:[{id:"294122",title:"Prof.",name:"Huseyin",surname:"Salvarli",slug:"huseyin-salvarli",fullName:"Huseyin Salvarli"},{id:"294228",title:"Mr.",name:"Mustafa Seckin",surname:"Salvarli",slug:"mustafa-seckin-salvarli",fullName:"Mustafa Seckin Salvarli"}],corrections:null},{id:"71552",title:"Energy Security and Renewable Energy: A Geopolitical Perspective",doi:"10.5772/intechopen.91848",slug:"energy-security-and-renewable-energy-a-geopolitical-perspective",totalDownloads:1181,totalCrossrefCites:7,totalDimensionsCites:9,hasAltmetrics:1,abstract:"This chapter examines the role of renewable energy in shaping energy security against the backdrop of global geopolitical, socioeconomic, and technological uncertainties. The evolving definition of energy security during the twentieth and early twenty-first centuries is discussed initially. The dimensions, components, and metrics of energy security are reviewed, including the 4A definition of energy security that comprises physical availability; economic affordability; accessibility from a sociopolitical standpoint; and environmental acceptability. A novel energy security index is proposed, with the following components: physical availability; technology development; economic affordability; social accessibility; governance; unconventional threats; and natural environment. Of these, physical availability followed by technology development, economic affordability, and governance was rated as the most important, and the environment was rated as the least important by a small panel of experts. The roles of wind and solar energy are highlighted, with an emphasis on the social acceptance of renewable energy in an energy security context. Other energy security indexes are discussed, focusing on sustainability and renewable energy. Denmark, Germany, China, Russia, and the United States are examined as case studies that help understand the transition to renewable energy in the context of coopetition among states. As these countries face different political concerns, geopolitical realities, and energy security issues, they consider different policy approaches to address them.",signatures:"John A. Paravantis and Nikoletta Kontoulis",downloadPdfUrl:"/chapter/pdf-download/71552",previewPdfUrl:"/chapter/pdf-preview/71552",authors:[{id:"297889",title:"Prof.",name:"John",surname:"Paravantis",slug:"john-paravantis",fullName:"John Paravantis"},{id:"297898",title:"M.Sc.",name:"Nikoletta",surname:"Kontoulis",slug:"nikoletta-kontoulis",fullName:"Nikoletta Kontoulis"}],corrections:null},{id:"72448",title:"Evaluating Biogas Technology in South Africa: Awareness and Perceptions towards Adoption at Household Level in Limpopo Province",doi:"10.5772/intechopen.92834",slug:"evaluating-biogas-technology-in-south-africa-awareness-and-perceptions-towards-adoption-at-household",totalDownloads:426,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Despite the enormous advantages associated with biogas technology, the level of awareness and perceptions still remain very dismay. The level of adoption is relatively low compared to the potential of the technology. This chapter therefore aimed at unravelling the awareness and perceptions of the technology at household level in Limpopo Province of South Africa. In this study, 200 households were sampled; 72 households with biogas digesters and 128 without digesters. Primary data collection was elicited with the use of open- and closed-ended questionnaires. A non-parametric test of Spearman rank correlation coefficient and chi-square were employed to show the association between the variables. Empirically, the results revealed that income earned, cost of digester, lack of awareness programmes, water and feedstock availability, technical availability and assistance, and private sector participation are among the factors limiting the dissemination, awareness and perception of the technology in the province. The study recommends interventions through more elaborate awareness and promotion programmes in disseminating the technology as well as provision of technical assistance, loans, credits and subsidies to households willing to adopt the technology.",signatures:"Solomon Eghosa Uhunamure, Nthaduleni Samuel Nethengwe and David Tinarwo",downloadPdfUrl:"/chapter/pdf-download/72448",previewPdfUrl:"/chapter/pdf-preview/72448",authors:[{id:"297407",title:"Ph.D. Student",name:"Solomon",surname:"Uhunamure",slug:"solomon-uhunamure",fullName:"Solomon Uhunamure"},{id:"322082",title:"Dr.",name:"Nthaduleni Samuel",surname:"Nethengwe",slug:"nthaduleni-samuel-nethengwe",fullName:"Nthaduleni Samuel Nethengwe"},{id:"322083",title:"Dr.",name:"David",surname:"Tinarwo",slug:"david-tinarwo",fullName:"David Tinarwo"}],corrections:null},{id:"68202",title:"Evaluating the Success of Renewable Energy and Energy Efficiency Policies in Ghana: Matching the Policy Objectives against Policy Instruments and Outcomes",doi:"10.5772/intechopen.88278",slug:"evaluating-the-success-of-renewable-energy-and-energy-efficiency-policies-in-ghana-matching-the-poli",totalDownloads:884,totalCrossrefCites:1,totalDimensionsCites:9,hasAltmetrics:0,abstract:"Advancement in energy policies has stimulated the adoption of instruments used in the renewable energy sector and climate change mitigation. Renewable energy policies play a crucial role in the abatement of greenhouse gas emissions, by providing access to modern energy and energy security by diversifying energy supply. There have been numerous policies developed in Ghana to improve the uptake of renewable energy for electricity production and to ensure efficient use of electrical energy. Some of the specific government policy objectives include reducing technical and commercial losses in power supply, support the modernization and expansion of the energy infrastructure to meet the growing demands, ensure reliability and accelerate the development and utilisation of renewable energy and energy-efficient technologies. These policies have defined targets and period to be implemented. This chapter outlined the renewable energy and energy efficiency policies in Ghana by matching the policy objectives against policy instruments and outcomes to measure what has been achieved. A comparative analysis was made with South Africa and Morocco’s renewable energy sectorial policies on the basis of various strategies adopted to their achievements and what Ghana can learn from.",signatures:"Margaret Adobea Oduro, Samuel Gyamfi, Samuel Asumadu Sarkodie and Francis Kemausuor",downloadPdfUrl:"/chapter/pdf-download/68202",previewPdfUrl:"/chapter/pdf-preview/68202",authors:[{id:"247286",title:"Dr.",name:"Samuel",surname:"Asumadu-Sarkodie",slug:"samuel-asumadu-sarkodie",fullName:"Samuel Asumadu-Sarkodie"},{id:"294752",title:"Ms.",name:"Margaret Adobea",surname:"Oduro",slug:"margaret-adobea-oduro",fullName:"Margaret Adobea Oduro"},{id:"294753",title:"Dr.",name:"Samuel",surname:"Gyamfi",slug:"samuel-gyamfi",fullName:"Samuel Gyamfi"},{id:"294754",title:"Dr.",name:"Francis",surname:"Kemausuor",slug:"francis-kemausuor",fullName:"Francis Kemausuor"}],corrections:null},{id:"67908",title:"Energy Policy Decision in the Light of Energy Consumption Forecast by 2030 in Zimbabwe",doi:"10.5772/intechopen.87249",slug:"energy-policy-decision-in-the-light-of-energy-consumption-forecast-by-2030-in-zimbabwe",totalDownloads:609,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Sustainable energy, environmental protection, and global warming are the most discussed topics in today’s world. Demand forecasting is paramount for the design of energy generation systems to meet the increasing energy demand. In this chapter, an examination of the causal nexus between energy consumption, total population, greenhouse gas emissions, and per capita GDP was carried out to forecast Zimbabwe’s energy consumption by 2030. A time series data from 1980 to 2012 were employed alongside econometric techniques to explore the causal relationship among the variables under review. The stationary test revealed the integration of all the data series of interest of order one ∼ I(1). The autoregressive integrated moving average (ARIMA) model forecasted Zimbabwe’s 2030 energy demand around 0.183 quadrillion Btu as against the current 0.174 quadrillion Btu. The empirical finding is indicative for policy- and decision makers who design the energy policy framework geared towards achieving the universal access to modern energy technologies in Zimbabwe.",signatures:"Remember Samu, Samuel Asumadu Sarkodie, Murat Fahrioglu and Festus Victor Bekun",downloadPdfUrl:"/chapter/pdf-download/67908",previewPdfUrl:"/chapter/pdf-preview/67908",authors:[{id:"247286",title:"Dr.",name:"Samuel",surname:"Asumadu-Sarkodie",slug:"samuel-asumadu-sarkodie",fullName:"Samuel Asumadu-Sarkodie"},{id:"232865",title:"Mr.",name:"Remember",surname:"Samu",slug:"remember-samu",fullName:"Remember Samu"},{id:"232874",title:"Prof.",name:"Murat",surname:"Fahrioglu",slug:"murat-fahrioglu",fullName:"Murat Fahrioglu"},{id:"298741",title:"Mr.",name:"Festus Victor",surname:"Bekun",slug:"festus-victor-bekun",fullName:"Festus Victor Bekun"}],corrections:null},{id:"71838",title:"Renewable Energy in Ukraine-Poland Region: Comparison, Critical Analysis, and Opportunities",doi:"10.5772/intechopen.91686",slug:"renewable-energy-in-ukraine-poland-region-comparison-critical-analysis-and-opportunities",totalDownloads:424,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Fundamental and applied research on renewable energy is actively supported for the development of world science and maintaining the energy independence and security of different countries. This section analyzes the publications of scientists from two countries—Ukraine and Poland—in the field of “thermoelectricity,” “photoelectricity,” and “bioenergy” to find regularities in each state and to determine the prospects for joint research. Ukraine and Poland share a common border and have similar climatic conditions and historical heritage, but Poland is a member of the EU, and its legislation in the field of renewable energy complies with the regulations of the European Community. Ukraine is making every effort to develop renewable energy. Comparison of the state of research in these countries is also an example of the analysis of the situation at the borders of EU countries and may answer questions related to sustainable development, the mass transition to renewable energy, and the refusal to use fossil fuels and nuclear power plants. The analysis is based on the results of data published in the international scientific databases Web of Science and Scopus. The most advanced areas of research in each country are identified, analyzed, and aimed at practical application.",signatures:"Lyubomyr Nykyruy, Valentyna Yakubiv, Grzegorz Wisz, Iryna Hryhoruk, Zhanna Zapukhlyak and Rostyslaw Yavorskyi",downloadPdfUrl:"/chapter/pdf-download/71838",previewPdfUrl:"/chapter/pdf-preview/71838",authors:[{id:"231005",title:"Dr.",name:"Lyubomyr",surname:"Nykyruy",slug:"lyubomyr-nykyruy",fullName:"Lyubomyr Nykyruy"},{id:"297731",title:"Dr.",name:"Grzegorz",surname:"Wisz",slug:"grzegorz-wisz",fullName:"Grzegorz Wisz"},{id:"297732",title:"Prof.",name:"Valentyna",surname:"Yakubiv",slug:"valentyna-yakubiv",fullName:"Valentyna Yakubiv"},{id:"297733",title:"MSc.",name:"Iryna",surname:"Hryhoruk",slug:"iryna-hryhoruk",fullName:"Iryna Hryhoruk"},{id:"297796",title:"MSc.",name:"Rostyslav",surname:"Yavorskyi",slug:"rostyslav-yavorskyi",fullName:"Rostyslav Yavorskyi"},{id:"312346",title:"MSc.",name:"Zhanna",surname:"Zapukhlyak",slug:"zhanna-zapukhlyak",fullName:"Zhanna Zapukhlyak"}],corrections:null},{id:"71811",title:"Operational Challenges towards Deployment of Renewable Energy",doi:"10.5772/intechopen.92041",slug:"operational-challenges-towards-deployment-of-renewable-energy",totalDownloads:552,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:0,abstract:"This chapter focuses on the feasibility analysis and different challenges toward deployment of renewable energy to achieve global sustainability. The analysis emphasizes that the technological advancement, cost, and efficiency are the basic elements for mass adaptation of renewable energy. At the same time, huge available resources, favorable economies, and large social-economic benefits attract major parts of the globe toward the transition from conventional to renewable energy. The proposed chapter also indicates the major options and barriers toward the deployment of different renewable energies in India, which will act as a catalyst to achieve the India’s dream renewable energy target of 175 GW by 2022. In the current era of modern technologies, highly CO2 releasing countries like India and China demand a wide range of renewable energy integration into their power generation portfolios to meet the requirements of global sustainability. Therefore, the proposed chapter will also provide a strong base of energy security for upcoming generations.",signatures:"Pankaj Kumar, Kumar Avinash Chandra, Sanjay Patel, Nitai Pal, Mohit Kumar and Himanshu Sharma",downloadPdfUrl:"/chapter/pdf-download/71811",previewPdfUrl:"/chapter/pdf-preview/71811",authors:[{id:"221309",title:"Dr.",name:"Himanshu",surname:"Sharma",slug:"himanshu-sharma",fullName:"Himanshu Sharma"},{id:"230824",title:"Mr.",name:"Pankaj",surname:"Kumar",slug:"pankaj-kumar",fullName:"Pankaj Kumar"},{id:"297307",title:"Dr.",name:"Nitai",surname:"Pal",slug:"nitai-pal",fullName:"Nitai Pal"},{id:"312624",title:"Mr.",name:"Kumar Avinash",surname:"Chandra",slug:"kumar-avinash-chandra",fullName:"Kumar Avinash Chandra"},{id:"312740",title:"Mr.",name:"Sanjay",surname:"Patel",slug:"sanjay-patel",fullName:"Sanjay Patel"},{id:"312741",title:"Mr.",name:"Mohit",surname:"Kumar",slug:"mohit-kumar",fullName:"Mohit Kumar"}],corrections:null},{id:"72521",title:"Bioinspired Nanocomposites: Functional Materials for Sustainable Greener Technologies",doi:"10.5772/intechopen.92876",slug:"bioinspired-nanocomposites-functional-materials-for-sustainable-greener-technologies",totalDownloads:495,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"This chapter presents a broad overview of the current advancements in bioplastics and bioinspired nanocomposites with nanoscale reinforcements that are being applied for a broad range of applications, that is, biomedical, electronics, durable goods and packaging materials. The production of nanocomposites by completely and/or partially renewable and biodegradable materials has helped in a range of different applications. Several drawbacks of conventional materials such as hydrophilicity, low-heat deflection, poor conductivity, and barrier properties can be efficiently overcome using biohybrid nanomaterials. Nano-reinforcements in composite materials deliver remarkably improved properties such as decrease in hydrophilicity and increase in mechanical properties as compared with neat biopolymer, which fails to exhibit these properties on its own. This approach can be used for other natural polymers to induce desired functionalities. This chapter covers the recent trends in nano-functional materials, renewable materials that are being applied for the production of nanobiocomposites and their applications especially in biomedical and healthcare sectors, which are discussed in detail. This emerging concept will definitely enhance the scope of nanohybrid materials for sustainable products development with improved properties than previously applied synthetic polymer-based or natural polymer-based materials.",signatures:"Sarmad Ahmad Qamar, Muhammad Asgher and Nimrah Khalid",downloadPdfUrl:"/chapter/pdf-download/72521",previewPdfUrl:"/chapter/pdf-preview/72521",authors:[{id:"274804",title:"Dr.",name:"Sarmad Ahmad",surname:"Qamar",slug:"sarmad-ahmad-qamar",fullName:"Sarmad Ahmad Qamar"},{id:"316379",title:"Dr.",name:"Nimrah",surname:"Khalid",slug:"nimrah-khalid",fullName:"Nimrah Khalid"},{id:"319732",title:"Prof.",name:"Muhammad",surname:"Asgher",slug:"muhammad-asgher",fullName:"Muhammad Asgher"}],corrections:null},{id:"72639",title:"Road Transportation Industry Facing the Energy and Climate Challenges",doi:"10.5772/intechopen.92299",slug:"road-transportation-industry-facing-the-energy-and-climate-challenges",totalDownloads:519,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"On a worldwide scale, vehicles, which constitute the transportation sector, play a major role in supporting the other productive sectors. In addition, the automobiles help promoting the living standards of human beings by satisfying the needs of most people in their daily activities. Nowadays, for the traction or repulsion of vehicles, the overwhelming majority of these automobiles are equipped with internal combustion engines (ICE); however, the automotive industry is moving steadily toward the adoption of new technologies because of the rapid depletion of fossil fuels and climate challenges caused by the transport sector, which accounts for the 27% of global energy consumption and for 33.7% of pollutant emissions and green house gas (GHG). For road transportation sector, the fuel-cell electric vehicle is one of the promising solutions advocated by car manufacturers and research entities to replace gradually conventional vehicles.",signatures:"Brahim Mebarki, Belkacem Draoui, Boumediene Allaoua and Abdelghani Draoui",downloadPdfUrl:"/chapter/pdf-download/72639",previewPdfUrl:"/chapter/pdf-preview/72639",authors:[{id:"15376",title:"Dr.",name:"Boumediene",surname:"Allaoua",slug:"boumediene-allaoua",fullName:"Boumediene Allaoua"},{id:"238688",title:"Dr.",name:"Brahim",surname:"Mebarki",slug:"brahim-mebarki",fullName:"Brahim Mebarki"}],corrections:null},{id:"71480",title:"Solid Green Biodiesel Catalysts Derived from Coal Fly Ash",doi:"10.5772/intechopen.91703",slug:"solid-green-biodiesel-catalysts-derived-from-coal-fly-ash",totalDownloads:583,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:1,abstract:"Coal fly ash (CFA) is generated during the combustion of coal for energy production. Many studies are based on its utilization as the most abundant, cheap aluminosilicate industrial residue, which is recognized as a risk for the environment and human health. The present review is focused on CFA origin, chemical properties, and its catalytic application for biodiesel production. The aluminosilicate nature and the presence of rare earth elements make CFA suitable for different adsorption, catalytic, and extraction processes for obtaining valuable products including alternative fuels and pure elements. However, the presence of toxic elements is a potential environmental problem, which should be solved in order to avoid soil, water, and air pollution. The most used modification methods are alkali activation, hydrothermal, and thermal treatment that improve the structural, morphological, and textural properties. The active catalytic form could be obtained by impregnation or ion exchange method. It was found that such synthesized materials have significant catalytic potential in the biofuel chemistry. In the case of biodiesel production, the high values of conversion or yield can be achieved under mild low-energy reaction conditions in the presence of low-cost waste-based catalysts.",signatures:"Miroslav Stanković, Stefan Pavlović, Dalibor Marinković, Marina Tišma, Margarita Gabrovska and Dimitrinka Nikolova",downloadPdfUrl:"/chapter/pdf-download/71480",previewPdfUrl:"/chapter/pdf-preview/71480",authors:[{id:"189814",title:"Dr.",name:"Miroslav",surname:"Stanković",slug:"miroslav-stankovic",fullName:"Miroslav Stanković"},{id:"294962",title:"Dr.",name:"Pavlović",surname:"Stefan",slug:"pavlovic-stefan",fullName:"Pavlović Stefan"},{id:"294963",title:"Dr.",name:"Dalibor",surname:"Marinković",slug:"dalibor-marinkovic",fullName:"Dalibor Marinković"},{id:"314777",title:"Dr.",name:"Marina",surname:"Tišma",slug:"marina-tisma",fullName:"Marina Tišma"},{id:"314778",title:"Dr.",name:"Margarita",surname:"Gabrovska",slug:"margarita-gabrovska",fullName:"Margarita Gabrovska"},{id:"314779",title:"Dr.",name:"Dimitrinka",surname:"Nikolova",slug:"dimitrinka-nikolova",fullName:"Dimitrinka Nikolova"}],corrections:null},{id:"70472",title:"Biomass Carbonization",doi:"10.5772/intechopen.90480",slug:"biomass-carbonization",totalDownloads:1061,totalCrossrefCites:4,totalDimensionsCites:7,hasAltmetrics:0,abstract:"Carbonization is the art of reinventing the waste biomass into a carbon−/energy-rich charcoal. It redefines the principles of renewable energy and power generation. Char is produced by a pyrolysis process in which the biomass is heated in an inert atmosphere to high temperatures until absorbed volatiles are expelled thus enriching its heating value and energy content. Carbonization itself is an old process that is being used till now, but the renewed interest in it especially with biomass is because it opens new doors for commercial and scientific applications. The carbon can be extracted from the produced char to form the precious graphite and graphene. This chapter provides a general overview about slow pyrolysis processes including carbonization and the torrefaction process which is a mild carbonization process. The characterization of different biomass species and their effect on the carbonization process and the final product will be also discussed. Different carbonization processes and methodologies which vary in the process parameters will be addressed, and the most promising ones will be highlighted. An important addition to this chapter is the general design parameters, methodologies, and factors that must be taken into consideration when designing carbonization reactors for lab and industrial designs.",signatures:"Mahmoud Amer and Ahmed Elwardany",downloadPdfUrl:"/chapter/pdf-download/70472",previewPdfUrl:"/chapter/pdf-preview/70472",authors:[{id:"290877",title:"Dr.",name:"Ahmed",surname:"Elwardany",slug:"ahmed-elwardany",fullName:"Ahmed Elwardany"},{id:"290878",title:"Dr.",name:"Mahmoud",surname:"Amer",slug:"mahmoud-amer",fullName:"Mahmoud Amer"}],corrections:null},{id:"69326",title:"Aviation Fuels and Biofuels",doi:"10.5772/intechopen.89397",slug:"aviation-fuels-and-biofuels",totalDownloads:1023,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Aviation industry consumes about 177 billion liters of kerosene, moving more than 25,000 aircraft and 6 billion passengers. To achieve that, civil aviation in 2015 generated about 781 million tons of CO2 corresponding to 2% anthropogenic emissions of this greenhouse gas, and all required energy is derived from fossil sources. To reduce the environmental impact and to create alternative energy sources to bring energy security, it is of great importance to increase researching and development, so that it becomes viable to produce biokerosene. This chapter aims to present some varieties of biomass and its derivatives being studied as raw materials for new aviation fuels such as ethanol, butanol, fatty acid methyl esters, and fusel oil.",signatures:"Jonathan Baumi, Caroline Milani Bertosse and Carmen Luisa Barbosa Guedes",downloadPdfUrl:"/chapter/pdf-download/69326",previewPdfUrl:"/chapter/pdf-preview/69326",authors:[{id:"37458",title:"Associate Prof.",name:"Carmen Luisa",surname:"Guedes",slug:"carmen-luisa-guedes",fullName:"Carmen Luisa Guedes"},{id:"275606",title:"MSc.",name:"Jonathan",surname:"Baumi",slug:"jonathan-baumi",fullName:"Jonathan Baumi"},{id:"296577",title:"Ms.",name:"Caroline Milani",surname:"Bertosse",slug:"caroline-milani-bertosse",fullName:"Caroline Milani Bertosse"}],corrections:null},{id:"72194",title:"Hydrogen Technologies for Mobility and Stationary Applications: Hydrogen Production, Storage and Infrastructure Development",doi:"10.5772/intechopen.91676",slug:"hydrogen-technologies-for-mobility-and-stationary-applications-hydrogen-production-storage-and-infra",totalDownloads:1196,totalCrossrefCites:4,totalDimensionsCites:6,hasAltmetrics:1,abstract:"The present chapter focuses on hydrogen technologies for both stationary and mobility/transportation applications. Hydrogen production from sustainable resources for the generation of pure and low cost hydrogen is described in the chapter. Several potential hydrogen production techniques are introduced and analyzed. The challenges and the advantages of each production method will be discussed. Furthermore, the chapter will introduce hydrogen infrastructure development for mobility applications and will discuss hydrogen storage challenges. Hydrogen production for fuel cell technologies requires an improvement regarding sustainability of the hydrogen supply and an improvement regarding decentralized hydrogen production. Moreover, hydrogen economy as far requires a large scale and long term storage solution to meet the increasing demand.",signatures:"Martin Khzouz and Evangelos I. Gkanas",downloadPdfUrl:"/chapter/pdf-download/72194",previewPdfUrl:"/chapter/pdf-preview/72194",authors:[{id:"288364",title:"Dr.",name:"Martin",surname:"Khzouz",slug:"martin-khzouz",fullName:"Martin Khzouz"},{id:"312860",title:"Dr.",name:"Evangelos",surname:"Gkanas",slug:"evangelos-gkanas",fullName:"Evangelos Gkanas"}],corrections:null},{id:"66716",title:"The PV/Wind System for Sustainable Development and Power Generation with Real Dynamic Input Datasets in the Distribution Power Systems",doi:"10.5772/intechopen.85878",slug:"the-pv-wind-system-for-sustainable-development-and-power-generation-with-real-dynamic-input-datasets",totalDownloads:557,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Rapid population growth and industrialization in developing countries cause an increase in demand for energy. In order to meet this energy demand, two types of resources are used: renewable energy and nonrenewable energy. Nonrenewable sources, also called fossil fuels, cause environmental problems in serious and dangerous dimensions. For this reason, it is a necessity to find alternatives. It is a renewable energy source that can be used as an alternative to fossil fuels. This chapter deals with power control of a PV/wind system for power generation with dynamic input dataset. The main contribution of this chapter is that it is the first time to use real data from PV/wind system and observe the system reliability with real-time simulation results. The proposed system consists of doubly fed induction-based wind generator, rotor-side converter (RSC), grid-side converter (GSC), solar arrays, DC-DC converter and grid-side converter, and grid and dynamic loads. The aim of the proposed strategy is to use wind and solar energies with maximum efficiency by simulating the real condition of wind and insolation with input datasets. The modeling and the validation of the operation of the system and its controllers are done by using PSCAD/EMTDC.",signatures:"Emel Bakmaz, Kemal Aygul, Burak Esenboga, Tugce Demirdelen and Mehmet Tumay",downloadPdfUrl:"/chapter/pdf-download/66716",previewPdfUrl:"/chapter/pdf-preview/66716",authors:[{id:"201009",title:"Dr.",name:"Tuğçe",surname:"Demirdelen",slug:"tugce-demirdelen",fullName:"Tuğçe Demirdelen"},{id:"293301",title:"BSc.",name:"Kemal",surname:"Aygul",slug:"kemal-aygul",fullName:"Kemal Aygul"},{id:"294204",title:"MSc.",name:"Emel",surname:"Bakmaz",slug:"emel-bakmaz",fullName:"Emel Bakmaz"},{id:"294205",title:"BSc.",name:"Burak",surname:"Esenboga",slug:"burak-esenboga",fullName:"Burak Esenboga"},{id:"294206",title:"Prof.",name:"Mehmet",surname:"Tumay",slug:"mehmet-tumay",fullName:"Mehmet Tumay"}],corrections:null},{id:"68091",title:"Recovery of Photovoltaic Module Heat Using Thermoelectric Effect",doi:"10.5772/intechopen.87989",slug:"recovery-of-photovoltaic-module-heat-using-thermoelectric-effect",totalDownloads:526,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The growing demand for renewable energy sources, in particular for solar technologies, requires more detailed studies to increase power and efficiency. Among them, thermoelectric energy conversion is a well-known technology used for decades including solar thermal generators (STEG), radioisotope thermoelectric generators (RTG), automotive thermoelectric generators (ATG) and thermoelectric generators (TEG). This chapter aims to demonstrate that the thermoelectric effect (Seebeck effect) can be used to harness the thermal energy retained in photovoltaic panels to increase their overall efficiency with its direct conversion into electrical energy and vice versa. It is also observed that solar radiation can be converted directly into electric energy, as in photovoltaic modules, or yet can be converted directly into electricity, as in thermoelectric modules. It is emphasised that although the energy conversion by thermoelectric effect still has low electrical efficiency, this source is characterised by a high degree of reliability, low maintenance, appreciable durability and absence of moving parts, and it allows generating electric energy through recovery of the thermal energy from several industrial processes. At the end of this chapter is presented a case study related to the thermal energy absorbed by a polycrystalline photovoltaic module to illustrate their increased efficiency and power in thermoelectric-photovoltaic cogeneration.",signatures:"Felix A. Farret and Emanuel A. Vieira",downloadPdfUrl:"/chapter/pdf-download/68091",previewPdfUrl:"/chapter/pdf-preview/68091",authors:[{id:"276270",title:"MSc.",name:"Emanuel",surname:"Vieira",slug:"emanuel-vieira",fullName:"Emanuel Vieira"},{id:"277685",title:"Ph.D.",name:"Felix",surname:"Farret",slug:"felix-farret",fullName:"Felix Farret"}],corrections:null},{id:"69352",title:"Renewable Energy Application for Solar Air Conditioning",doi:"10.5772/intechopen.89462",slug:"renewable-energy-application-for-solar-air-conditioning",totalDownloads:519,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"This chapter presents an overview of various solar air conditioning technologies such as solar PV, absorption, desiccant, and adsorption cooling systems. It includes feasibility and comparative analysis of numerous standalone and hybrid configurations of solar cooling systems, which were investigated in past. In addition, recent developments in use of solar energy as a regeneration source to dehumidify desiccant wheel in different applications are also discussed. Details of system technologies and climate-based performance comparison in terms of various performance factors, for example, COPth, Qlatent, Qsensible, COPsolar, SF, PES, and Ƞcollector for solar-assisted configurations are highlighted. It is observed that hybridization of solar solid desiccant system results more efficient and cost-effective cooling system as latent and sensible loads are treated independently, especially when regeneration process of desiccant wheel is integrated with solar energy. This review will help to explore further improvements in solar-assisted cooling systems.",signatures:"Rubeena Kousar, Muzaffar Ali, Nadeem Ahmed Sheikh, Faik Hamad and Muhammad Kamal Amjad",downloadPdfUrl:"/chapter/pdf-download/69352",previewPdfUrl:"/chapter/pdf-preview/69352",authors:[{id:"303859",title:"Dr.",name:"Faik",surname:"Hamad",slug:"faik-hamad",fullName:"Faik Hamad"},{id:"304611",title:"Dr.",name:"Muzaffar",surname:"Ali",slug:"muzaffar-ali",fullName:"Muzaffar Ali"},{id:"304613",title:"MSc.",name:"Rubina",surname:"Kamal",slug:"rubina-kamal",fullName:"Rubina Kamal"},{id:"304617",title:"Prof.",name:"Nadeem",surname:"Ahmed Sheikh",slug:"nadeem-ahmed-sheikh",fullName:"Nadeem Ahmed Sheikh"}],corrections:null},{id:"71671",title:"Thermal and Hydraulic Analysis of Transfer Medium Motion Regime in Flat Plate Solar Collector",doi:"10.5772/intechopen.90451",slug:"thermal-and-hydraulic-analysis-of-transfer-medium-motion-regime-in-flat-plate-solar-collector",totalDownloads:420,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In the research herein, we have considered the thermal and hydraulic analysis of transfer media motion mode in the flat solar collector. We have substantiated the thermal and hydraulic parameters of the flat plate solar collector. Heat absorbing flat solar collector tubes hydraulic analysis has shown, that using the heat transfer standard size there might be located the pipeline, the length of which 2.5 times more than of the collector’s body, sufficiently increasing at that insolation time on the transfer media.",signatures:"Yedilkhan Amirgaliyev, Murat Kunelbayev, Kalizhanova Aliya, Ainur Kozbakova, Omirlan Auelbekov and Nazbek Katayev",downloadPdfUrl:"/chapter/pdf-download/71671",previewPdfUrl:"/chapter/pdf-preview/71671",authors:[{id:"236034",title:"Associate Prof.",name:"Murat",surname:"Kunelbayev",slug:"murat-kunelbayev",fullName:"Murat Kunelbayev"}],corrections:null},{id:"71361",title:"Offshore Renewable Energy",doi:"10.5772/intechopen.91662",slug:"offshore-renewable-energy",totalDownloads:868,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:1,abstract:"Offshore renewable technologies hold the potential to satisfy a considerable amount of the global energy demand in the coming years. In this chapter, the main sources of renewable energy related to the oceans (waves, tides, and offshore winds) will be characterized and discussed, with reference to the challenges related to their use. Thus, the main devices capable of exploiting these resources will be presented. Their working principal, together with operational and technological requirements, will be described, highlighting strengths and weaknesses of each technology and providing examples of the past and current experiences. The elements of project management, as well as environmental impact and public perception, will be included. Finally, conclusions on the current viability of ocean energy devices will be drawn, together with guidelines for their future exploitation.",signatures:"Giovanni Rinaldi",downloadPdfUrl:"/chapter/pdf-download/71361",previewPdfUrl:"/chapter/pdf-preview/71361",authors:[{id:"296632",title:"Dr.",name:"Giovanni",surname:"Rinaldi",slug:"giovanni-rinaldi",fullName:"Giovanni Rinaldi"}],corrections:null},{id:"71575",title:"Wind Speed Analysis Using Signal Processing Technique",doi:"10.5772/intechopen.91840",slug:"wind-speed-analysis-using-signal-processing-technique",totalDownloads:426,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In this study, wind energy, the formation of this energy, and the necessary stages for the production of electrical energy will be discussed. Then, the countries’ investments in wind energy will be mentioned. In the mathematical background, statistical methods and signal processing methods are used in the calculation of wind energy efficiency. In this chapter, a detailed analysis of the use of wind speed data with signal processing techniques will be made using the hourly wind speed data of Istanbul for the last 10 years. This data will be analyzed by the Fourier method. Afterward, analyses will be made with short-time Fourier transform (STFT) and bi-spectrum analysis method, and these results will be compared. The data obtained from the study can be considered as a framework for the wind farms to be constructed.",signatures:"Omer Akgun and T. Cetin Akinci",downloadPdfUrl:"/chapter/pdf-download/71575",previewPdfUrl:"/chapter/pdf-preview/71575",authors:[{id:"303541",title:"Associate Prof.",name:"T. Cetin",surname:"Akinci",slug:"t.-cetin-akinci",fullName:"T. Cetin Akinci"},{id:"314167",title:"Dr.",name:"Omer",surname:"Akgun",slug:"omer-akgun",fullName:"Omer Akgun"}],corrections:null},{id:"71418",title:"Wind Turbine Integration to Tall Buildings",doi:"10.5772/intechopen.91650",slug:"wind-turbine-integration-to-tall-buildings",totalDownloads:747,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:1,abstract:"Having a far distance from the ground levels exposed to turbulent wind conditions, tall buildings have the potential of generating wind energy. However, there are many challenges to incorporating wind generation into urban areas. These include planning issues besides visual impacts. So, as to integration, there is a need for a combined approach that considers wind energy harvesting besides these issues. At this point, a multidisciplinary approach can fill the gap between the architectural design and the wind engineering processes. Based on this approach, this chapter presents design strategies from the literature to integrate wind energy to tall buildings using computational fluid dynamics (CFD) simulation. It is intended to guide further researches on wind energy and consequently to contribute to the environmental quality of urban areas and sustainable development of the cities.",signatures:"Ilker Karadag and Izzet Yuksek",downloadPdfUrl:"/chapter/pdf-download/71418",previewPdfUrl:"/chapter/pdf-preview/71418",authors:[{id:"186397",title:"Dr.",name:"İzzet",surname:"Yüksek",slug:"izzet-yuksek",fullName:"İzzet Yüksek"},{id:"295400",title:"Dr.",name:"İlker",surname:"Karadağ",slug:"ilker-karadag",fullName:"İlker Karadağ"}],corrections:null},{id:"71602",title:"Thermal Energy Storage for Solar Energy Utilization: Fundamentals and Applications",doi:"10.5772/intechopen.91804",slug:"thermal-energy-storage-for-solar-energy-utilization-fundamentals-and-applications",totalDownloads:1148,totalCrossrefCites:1,totalDimensionsCites:5,hasAltmetrics:1,abstract:"Solar energy increases its popularity in many fields, from buildings, food productions to power plants and other industries, due to the clean and renewable properties. To eliminate its intermittence feature, thermal energy storage is vital for efficient and stable operation of solar energy utilization systems. It is an effective way of decoupling the energy demand and generation, while plays an important role on smoothing their fluctuations. In this chapter, various types of thermal energy storage technologies are summarized and compared, including the latest studies on the thermal energy storage materials and heat transfer enhancements. Then, the most up-to-date developments and applications of various thermal energy storage options in solar energy systems are summarized, with an emphasis on the material selections, system integrations, operational characteristics, performance assessments and technological comparisons. The emerging and future trends are finally outlined. This chapter will be a useful resource for relevant researchers, engineers, policy-makers, technology users, and engineering students in the field.",signatures:"Kai Wang, Zhen Qin, Wei Tong and Chenzhen Ji",downloadPdfUrl:"/chapter/pdf-download/71602",previewPdfUrl:"/chapter/pdf-preview/71602",authors:[{id:"309117",title:"Dr.",name:"Chenzhen",surname:"Ji",slug:"chenzhen-ji",fullName:"Chenzhen Ji"},{id:"309341",title:"Dr.",name:"Zhen",surname:"Qin",slug:"zhen-qin",fullName:"Zhen Qin"},{id:"310907",title:"Dr.",name:"Wei",surname:"Tong",slug:"wei-tong",fullName:"Wei Tong"},{id:"313563",title:"Prof.",name:"Kai",surname:"Wang",slug:"kai-wang",fullName:"Kai Wang"}],corrections:null},{id:"72474",title:"A Thermoelectric Energy Harvesting System",doi:"10.5772/intechopen.92088",slug:"a-thermoelectric-energy-harvesting-system",totalDownloads:482,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Thermoelectric generators (TEGs) and their applications have gained momentum for their ability to use waste thermal energy. More contemporary technology must offer more exceptional energy-efficient applications at a lower cost. New technology must also have an ability to generate electric power through the conversion of wasted heat. The TEG has demonstrated its efficiency and how it can offer increased potential by adding an MPPT algorithm to increase the power flow while decreasing the cost of operation. The limitations can be offset by the use of lower cost manufacturing materials and automated systems in the TEG units. It is also important to note the cost per watt found in using a thermoelectric generator is estimated to be $1/W for an installed device. To achieve this goal, the optimum operating point should be monitored by DC to DC converters. The DC to DC converters should also be driven through a generated pulse using an MPPT algorithm.",signatures:"Khalid Yahya, Mohammed Salem, Nassim Iqteit and Sajjad Ahmad Khan",downloadPdfUrl:"/chapter/pdf-download/72474",previewPdfUrl:"/chapter/pdf-preview/72474",authors:[{id:"254056",title:"Dr.",name:"Mohamed",surname:"Salem",slug:"mohamed-salem",fullName:"Mohamed Salem"},{id:"270815",title:"Dr.",name:"Khalid",surname:"Yahya",slug:"khalid-yahya",fullName:"Khalid Yahya"},{id:"315602",title:"Dr.",name:"Nassim",surname:"Iqteit",slug:"nassim-iqteit",fullName:"Nassim Iqteit"},{id:"319848",title:"Dr.",name:"Sajjad",surname:"Khan",slug:"sajjad-khan",fullName:"Sajjad Khan"}],corrections:null},{id:"71506",title:"Optimization Techniques of Islanded Hybrid Microgrid System",doi:"10.5772/intechopen.91841",slug:"optimization-techniques-of-islanded-hybrid-microgrid-system",totalDownloads:453,totalCrossrefCites:5,totalDimensionsCites:6,hasAltmetrics:0,abstract:"The utilization of energy is increasing day by day, it is an unavoidable truth. This large demand for energy cannot be satisfied by the conventional power sources alone. Sustainable power sources, for example, solar and wind turbine-based energy system are the most effective and both economically and environmentally feasible. The Hybrid renewable energy system (HRES) is a recent concept in the field of sustainable development which joins at least two renewable power sources like wind turbine, solar module and other inexhaustible sources such as ocean energy, fuel cell etc. This chapter starts with an audit by addressing the possible difficulties that can occur while a solar power plant and the wind farm will be integrated together to supply power to the main grid or in a islanded manner. This chapter gives an overview of the optimization techniques that can improve the integration of the hybrid systems to the grid as well as with the islanded load. This review also sheds significant light on the techniques to improve the equality of a grid integrated solar-wind hybrid energy system. It also includes the critical findings on the strategies that are necessary to build an efficient grid-connected and islanded solar-wind hybrid energy system.",signatures:"Sk. Shezan Arefin",downloadPdfUrl:"/chapter/pdf-download/71506",previewPdfUrl:"/chapter/pdf-preview/71506",authors:[{id:"245333",title:"Dr.",name:"Shezan",surname:"Arefin",slug:"shezan-arefin",fullName:"Shezan Arefin"}],corrections:null},{id:"71431",title:"Performances Analysis of a Micro-Grid Connected Multi-Renewable Energy Sources System Associated with Hydrogen Storage",doi:"10.5772/intechopen.91673",slug:"performances-analysis-of-a-micro-grid-connected-multi-renewable-energy-sources-system-associated-wit",totalDownloads:467,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"This work highlights the modeling and simulation of a micro-grid connected renewable energy system. It comprises of wind turbine (WT) based on doubly fed induction generator (DFIG), photovoltaic generator (PV), fuel cell (FC) generator, a Hydrogen tank, a water electrolyzer used for long-term storage, and a battery bank energy storage system (BBESS) utilized for short-term storage. In this paper, a global control strategy and an energy management strategy are proposed for the overall system. This strategy consists in charging the BBESS and producing hydrogen from the water electrolyzer in case of power excess provided from WT-DFIG and photovoltaic generators. Therefore, the FC and the BBESS will be used as a backup generator to supply the demand required power, when the WT-DFIGs and the PV energy are deficient. The effectiveness of this contribution is verified through computer simulations under Matlab/Simulink, where very satisfactory results are obtained.",signatures:"Salah Tamalouzt, Nabil Benyahia, Abdelmounaim Tounzi and Amar Bousbaine",downloadPdfUrl:"/chapter/pdf-download/71431",previewPdfUrl:"/chapter/pdf-preview/71431",authors:[{id:"53131",title:"Dr.",name:"Amar",surname:"Bousbaine",slug:"amar-bousbaine",fullName:"Amar Bousbaine"},{id:"233294",title:"Prof.",name:"Nabil",surname:"Benyahia",slug:"nabil-benyahia",fullName:"Nabil Benyahia"},{id:"282360",title:"Ph.D.",name:"Salah",surname:"Tamalouzt",slug:"salah-tamalouzt",fullName:"Salah Tamalouzt"},{id:"310286",title:"Prof.",name:"Abdelmounaim",surname:"Tounzi",slug:"abdelmounaim-tounzi",fullName:"Abdelmounaim Tounzi"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"7514",title:"Biofuels",subtitle:"Challenges and opportunities",isOpenForSubmission:!1,hash:"e8346cbab8dc0782736f2976dd8889f8",slug:"biofuels-challenges-and-opportunities",bookSignature:"Mansour Al Qubeissi",coverURL:"https://cdn.intechopen.com/books/images_new/7514.jpg",editedByType:"Edited by",editors:[{id:"241686",title:"Dr.",name:"Mansour",surname:"Al Qubeissi",slug:"mansour-al-qubeissi",fullName:"Mansour Al Qubeissi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3633",title:"Solar Energy",subtitle:null,isOpenForSubmission:!1,hash:null,slug:"solar-energy",bookSignature:"Radu D Rugescu",coverURL:"https://cdn.intechopen.com/books/images_new/3633.jpg",editedByType:"Edited by",editors:[{id:"8615",title:"Prof.",name:"Radu",surname:"Rugescu",slug:"radu-rugescu",fullName:"Radu Rugescu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4479",title:"Solar Cells",subtitle:"New Approaches and Reviews",isOpenForSubmission:!1,hash:"f6907a79a7d35f34d0c719d6297a2667",slug:"solar-cells-new-approaches-and-reviews",bookSignature:"Leonid A. 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Priority will be given to research work with experimental validation and/or with the development of fundamental and original control techniques and methods. The first section will concern the research’s work devoted to developing optimal and intelligent techniques of speed and torque control. The second part relates to generators control systems used in various applications such as renewable energies, electric/hybrid vehicles, embedded systems, multi-sources systems, etc. The last part will cover the torque control for special machines used in various fields as well as computational tools and methods based on the reduction and the elimination of machine faults and noises, etc.
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Down through centuries, efforts have been made to use local anesthesia for treatments. In the ancient times, the Assyrians applied pressure over the carotid artery in order to obtain a certain degree of anesthesia, explaining why this artery is called “the artery of sleep” in the Greek literature. In 1532, the Indians of Peru chewed the leaves of coca shrubs to relieve fatigue and hunger and to produce a feeling of exhilaration. A chemical with some anesthetic property was first introduced in the nineteenth century. A German chemist in 1859, however, reported the anesthetic properties of the coca leaf. In 1859, cocaine was first extracted in its pure form by Albert Neimann, a German chemist. In the mid-1860s, Sir Benjamin Ward Richardson introduced the effect of ether spray for skin anesthesia. Around the same time the adverse effects of cocaine on the mood and psyche were demonstrated. As known today, side effects of cocaine include cardiac stimulation, peripheral vasoconstriction, excitation of the central nervous system (CNS) and addiction. In 1943, lidocaine-the first amide local anesthetic was introduced with greater potency, more rapid onset and less allergenicity as compared to the previously introduced esters.
Management of pain in dentistry requires knowledge about the fifth cranial nerve anatomy-the trigeminal nerve. It is the largest of the cranial nerves and has three major divisions: ophthalmic, maxillary and mandibular.
The branches of the maxillary nerve are given off in four regions:
The branch entering the cranium –the middle meningeal nerve– travels with the middle meningeal artery to provide sensory innervation of the dura mater.
Several branches are given off in the pterygopalatine fossa namely the zygomatic nerve, the pterygopalatine nerve and the posterior superior alveolar nerve.
The superficial branches of the trigeminal nerve
Branches of the trigeminal nerve
At the mental foramen, the inferior alveolar nerve branches into its terminal branches-- the incisive and the mental nerves:
There is a great variety of techniques for anesthetizing different regions of the mandible, the most common and useful ones are described in this section.
The inferior alveolar nerve block (IANB) is one of the most important and commonly used techniques in dentistry. Unfortunately it is also the most frustrating with the highest percentage of failure even when properly administrated [1].The IANB anesthetizes the IAN (a branch of mandibular division of the trigeminal), incisive nerve, mental nerve and commonly (but not always) the lingual nerve of the injected side. This block effects the sensation of all the teeth on one side of mandible, the bone from the inferior portion of ramus to the midline, the lingual soft tissue and periosteum of the mandible, buccal soft tissues anterior to the mental foramen and anterior two thirds of the tongue and floor of the oral cavity [2].
In one technique, the patient is positioned supine (recommended) or semi-supine. The thumb of the free hand is placed on the coronoid notch retracting the soft tissues. The insertion point of the needle is about 6 to 10 mm above the occlusal plane and at the 3/4 of the anterior posterior distance from the coronoid notch to the pterygomandibular raphe (visual in the oral cavity). The syringe is advanced from across the lower premolar teeth of the opposite side. A long dental needle is used; the bone must be touched while advancing about 25mm of the 35 mm needle into the tissue. After contacting bone the needle is withdrawn slightly, aspiration performed and if negative in two directions 1.5 to 1.8 ml of solution is deposited over a minimum of 60 seconds (Figure 3).. [1]
The Inferior Alveolar Nerve Block
Two problems occur very commonly with this technique [7]:
Contacting the bone too soon: to solve this problem the needle is withdrawn halfway, still remaining in the soft tissue, then the barrel of the syringe is swung over the mandibular teeth of the side being anesthetized, then the needle is advanced about 2.5 mm and the solution is deposited. This is a modification of IANB (the indirect technique) [8].
The bone is not contacted after 30 mm of needle insertion: the needle should be withdrawn halfway back then the barrel of the syringe is swung over the molar teeth of the opposite side being anesthetized, and then advanced to touch the bone and then continued as described. When the bone is not touched the solution should not be deposited because the needle could be in the parotid gland near the facial nerve and an injection there could lead to transient paralysis of the facial nerve [1].
One of the most common causes of failure of IANB is depositing the solution too low (below the mandibular foramen) in this case it can be corrected by re-injecting at a higher site, approximately 5 to 10 mm above the previous site.
Mylohyoid nerve is the most common nerve which provides mandible teeth with accessory sensory innervation (most commonly the mesial portion of mandibular first molar). A supplemental injection at the apical region of the tooth in question on the lingual side will solve the problem [9].
Incomplete anesthesia of the central and lateral incisors is due to overlapping fibers of the contralateral inferior alveolar nerve. In this case a supplemental injection with infiltration technique or PDL injection should be done [1].
Olsen reported that in children the mandibular foramen is situated at a level lower than the occlusal plane [10]. Therefore in pediatric patients the injection must be made slightly lower and more posteriorly than for an adult patient.
Dr. Joseph Akinosi described a close-mouth approach in 1977 [11]. This technique became a successful alternative for inferior alveolar and Gow-Gates mandibular nerve blocks. In 1960 a very similar technique was described by Vazirani, there for the term “Vazirani-Akinosi” is used for the approach. It is also known as “Close-mouth mandibular nerve block” and “Tuberosity approach”. Although this technique can be used whenever mandibular anesthesia is desired, its primary indication is in situations where the patient has a limited mouth opening range such as patients with trismus or when spasm of the masticatory muscles on one side of the mandible occur due to several unsuccessful attempt to anesthetize it with IANB, the Vazirani-Akinosi anesthesia approach provides successful anesthesia and a motor blockade (of V3 division of trigeminal nerve) to relieve trismus if it is produced secondary to muscle spasm.
In 1992, Wolfe described a modification of the Vazirani-Akinosi technique, in which the needle is bent at a 45 degree angle to adapt better with the lingual aspect of the ramus. But due to the increase risk of needle breakage this technique cannot be recommended [12]. If the Vazirani-Akinosi technique administered successfully anesthesia of inferior alveolar, incisive, mental, buccal, lingual and mylohyoid nerves is obtained.
For administration of this technique a 25 or 27 gage needle is used. The patient should be positioned supine or semisupine. The index finger or thumb is placed on the coronoid notch reflecting the tissue on the medial side of the ramus laterally. The patient is asked to occlude gently with cheeks and muscles of masticatory relaxed. The syringe is held parallel to the maxillary occlusal plane, with the needle at the mucogingival junction of maxillary third molar (or second molar). The bevel of the needle should be held toward the bone. The needle is inserted to the soft tissue overlying the medial border of the mandible ramus at the point described, and is advanced 25mm (for an average-sized adult) posteriorly and slightly laterally. After negative aspiration in two planes the anesthesia solution can be deposited. Motor nerve paralysis is the first sign to occur so a patient with trismus will notice increased ability to open the jaw. After 1 to 1.5 minute anesthesia of the lip and tongue is noted, and the dental procedure usually can start within 5 minutes.
It is shown in studies that the Vazirani-Akinosi technique has the same success rate of conventional IANB. But with fewer complications and a lower aspiration rate (<10%) [1].
In 1973, George Albert Edwards Gow-Gates described a new approach to mandibular anesthesia which he had experience with and reported a success rate of 99% [13]. In this technique the anesthesia solution is deposited on the medial side of the condylar neck just below the insertion of the lateral pterygoid muscles and truly anesthetizes the entire distribution of V3, including the inferior alveolar, lingual, mylohyoid, mental, incisive, auriculotemporal and buccal nerves (in 75% of patients). The Gow-gates technique has a higher success rate and a lower incidence of positive aspiration in comparison to IANB.
In this technique the patient is positioned supine or semisupine and is asked to open his mouth widely, then the syringe, fitted with a long needle, is introduced into the mouth through the corner of the mouth on the opposite side. Insertion point is distal to the second molar and in a height of the mesiopalatal cusp of the second molar. The needle is inserted into the tissue and aligned with the plane extending from the corner of the mouth on the opposite side to the intertragus notch on the side of injection, then advanced about 25mm (two third of the needle) until the bone is touched. Then it is withdrawn about 1mm and after negative aspiration in two directions about 1.8 ml of the solution is deposited. If the bone is not contacted, either the patient has partially closed his mouth or the needle is deflected medially (most common cause). In this situation ask the patient to hold his mouth completely open and after withdrawing the needle half way realign the needle anteriorly by swinging the barrel of the syringe somewhat more distally and then advance the needle to contact the bone and continue the process of anesthesia [1, 9](Figure 4).
Due to greater diameter of the mandibular nerve it may require a larger volume of the anesthesia solution, so if the depth of the anesthesia is inadequate after the first injection deposit up to 1.8 ml in the second injection [9].
The Gow-Gates technique
The buccal nerve provides sensory innervation to the buccal gingiva, mucosa and part of the cheek in mandibular molar region. This nerve is consequently not anesthetized during IANB, so if required this nerve most be separately anesthetized. Because the buccal nerve lies immediately beneath the mucous membrane it can be anesthetized easily by depositing about 0.5ml of solution at the coronoid notch (the area distal and buccal to the last molar in the arch). And this nerve block has a success rate of approximately 100% [9].
The mental nerve and incisive nerve are the terminal branches of the inferior alveolar nerve and provide sensory innervation to the buccal soft tissues lying anterior to the foramen and the soft tissues of the lower lip and chin and those teeth located anterior to the foramen (premolar, canine and incisors) on the injection side. To administer this technique the mental foramen should be located with finger palpation near the apex of the second premolar. The bone immediately around the foramen is rougher to the touch and the patient might feel some soreness when you press your finger against the mental nerve. The needle bevel should be directed toward the bone and the mucosa is penetrated near the mucobuccal fold and the needle is advanced until it reaches the mental foramen, then about 0.6 ml of solution (one third of a cartridge) is deposited. After injection the tissue should be massaged to facilitate entry of the solution into the mental foramen. In the early literature it was emphasized to enter the foramen for a successful nerve block but now it has been shown that this action is completely unnecessary and only increases the risk of damaging the nerve or vessels of the area. Bilateral mental block is very useful when procedures are to be done on anterior or premolar teeth on both sides. [1]
Different regional blocks and infiltration injections can be used for anesthetizing the maxilla. Some are described herein.
This is the most common technique used for obtaining pulpal anesthesia and is more commonly known as local infiltration. In this technique the patient is asked to partially open his mouth and the syringe is held parallel to the long axis of the tooth. The needle is inserted in the mucobuccal fold above the apex of the tooth and advanced until it touches the bone then withdrawn a little and the solution is deposited at a rate of 30 s/ml (Figure 5). If the solution is deposited while the needle touches the bone the solution is injected below the periosteum which is more painful and may cause post injection discomfort.
The infiltration technique
This is a very easy technique and has a high success rate but when several teeth require anesthesia or there is an infection or acute inflammation in the area of the injection regional nerve blocks are preferred. In pediatric patients infiltration technique can also be used for anesthetizing mandibular primary teeth and in several studies it has been shown that in these patients infiltration technique has a comparable effectiveness to mandibular nerve block for dental procedures [14].
The patient is positioned supine or semisupine and the patient’s mouth partially open, the mandible is pulled toward the side of the injection and the soft tissues are retracted with the index finger. Then injection is done into the mucobuccal fold distal to the second molar at an angle of 45 degrees; next the needle is advanced posteriorly, superiorly and medially about 30mm and the solution is deposited [9].
In this approach we attend to insert the needle to the pterygopalatine fissure through the greater palatine foramen and affect the maxillary nerve as it passes through the fossa. We ask the patient to hold his mouth wide open. Palpate the greater palatine foramen medial to the distal aspect of the second molar. Insert the needle at an angle of 45 degree superiorly and distally to the foramen. After advancement about 30mm we deposit the anesthesia solution. This technique is painful and may be dangerous is rarely needed if ever and thus, is not recommended.
By blocking the posterior superior alveolar (PSA) nerve the molar teeth of maxilla, the associated bone and buccal gingiva will be anesthetized. It is shown that only in 28% of patients the middle superior alveolar nerve provides the mesiobuccal root of the first molar with sensory innervation, in this situation an extra injection (usually infiltration) is necessary to anesthetize the accessory innervations.
To block the PSA, we partially open the patient’s mouth and pull the mandible to the side of injection. A short needle is used to prevent distal insertion of the needle which can produce a temporary (10 to 14 days) hematoma. The needle is inserted into the mucobuccal fold over the second molar and advanced about 16mm upwards, inwards and backwards. Then, the anesthesia solution is slowly deposited (Figure 6). [1]
The PSA nerve block
In pediatric patients with primary or early mixed dentition, the thick bone of zygomatic process lies over the buccal roots of the second primary and first permanent molars, attenuating the effectiveness of infiltration injection in this region. So in this situations a PSA nerve block may be used instead [15].
As mentioned before the MSA exist only in 28% of people and provides sensory innervation to maxillary premolars and mesiobuccal root of the first molar. The MSA block is performed by delivering a buccal infiltration at the apex of the second premolar tooth.
The Anterior Superior Alveolar nerve (ASA) supplies the maxillary incisors and canine teeth on one side and the soft and hard tissue adjacent to it. On the other hand the infraorbital nerve provides sensory innervation to the mucosa and skin surface of one half of the upper lip and part of the skin on lateral aspect of the nose; but because these two nerves can be anesthetized with one approach, the technique is either known as “ASA block” or “Infraorbital nerve block”.
To perform this technique we locate the infraorbital foramen; to do so the infraorbital notch is palpated with the index finger then moved downward from the notch, the bone immediately inferior to the notch is convex, which is the roof of the infraorbital foramen, as we continue inferiorly a concavity is felt, this is the infraorbital foramen. When we press against it the patient senses a mild soreness. After the foramen is located we retract the lip and cheek of the patient, a syringe with a long needle is inserted into the mucobuccal fold at the apex of the first premolar. The syringe is held parallel to the long axis of the tooth and is advanced till it reaches near the foramen. The average depth of insertion into the tissue is 16mm (half of the length of a long needle) for an adult of average height. When the needle is in the target area, slowly deposit 0.9 to 1.2ml of the solution. You would be able to “feel” the anesthesia solution as it is deposited beneath the finger on the foramen. Maintain firm pressure with your finger over the injection site for 1 or 2 more minutes to increase the diffusion of the solution into the infraorbital foramen. For decreasing the pain on insertion of the needle and tearing of the periosteum insert the needle with an angled position (away from the bone) and solution is deposit while the needle is advanced through soft tissue [1].It is in no way necessary to enter the foramen.
It is possible to anesthetize palatine tissue by palatal infiltration technique at any place needed but by performing a greater palatine nerve block the posterior portion of the hard palate and the overlying soft tissue anteriorly as far as the first premolar on one side will be anesthetized. The foramen creates a depression in the palate usually distal to the maxillary second molar, which can be located by palpating the area. Deposition of 0.5ml of anesthesia solution in the region of the greater palatine foramen will block the nerve [9].
A very rare complication is ischemia and necrosis of soft tissue of the injection region and it only happens when highly concentrated vasoconstrictor solution is used for hemostasis over a prolonged period [1]. It is in no way necessary to enter the foramen.
This block anesthetizes the anterior portion of the hard palate (soft and hard tissue) bilaterally mesial to the first premolars. The technique can be performed by depositing 0.2 to 0.5 ml of anesthetic solution adjacent to the incisive papilla. Because the soft tissue in this area is dense, firmly adherent to underlying bone, and quite sensitive the injection in this area is very painful, so several methods are suggested to decrease the pain. One is anesthetizing the dental papilla between centrals labially and inserting the needle through it to the palatal side near the foramen and depositing a little solution to partially anesthetize the soft tissue overlying the nasopalatine nerve before the main injection [1].
This is a relatively new technique, first demonstrated by Friedman and Hochman during development of a computer-controlled local anesthetic delivery (C-CLAD) system [16, 17]. This technique relies on the slow delivery and penetration of anesthetic solution through the porous cortical bone and the nutrient canals.
About 1.4 to 1.8ml of solution (one cartridge) should be deposited very slowly (0.5ml per minute) into the tissue halfway between the palatal midline and the premolar palatal gingival margin. This method is best performed with a C-CLAD. This method blocks the ASA and MSA so it anesthetizes the palate and the teeth anterior to the first molar and adjacent buccal attached gingiva. In studies the AMSA block is shown as effective as multiple maxillary infiltrations [18].
This method like the AMSA block relies on slow delivery of anesthetic solution via a C-CLAD system and was defined by Friedman and Hochman in the mid1990s [8, 17, 19]. In this approach 1.4 to 1.8ml of solution is deposited in the incisive canal at a rate of 0.5 ml per minute. This block anesthetize the pulp of the incisors and canine bilaterally, facial periodontal tissue associated with these same teeth and anterior hard palate. You should keep in mind that also the injection with a C-CLAD system is not painful but it will take about 3 or 4 minutes which some patients may be reluctant to tolerate.
These techniques include intraosseous, intrapulpal, intraseptal and intraligamentary methods.
Intraligamentary (PDL) technique
Intraseptal technique
EMLA
SYRIJET needle-free injection.
Transcutaneous electronic nerve stimulation
The complications of the injection of local anesthetic drugs can be divided into two parts namely systemic and local complications, explained below.
Broken needle shown in the panoramic radiograph
After injection, children often bite their lips and cheeks, because of numbness in these areas.
Osteonecrosis following the intraosseous injection
Chronic myeloproliferative disorders are a group of clonal diseases of the stem cell. It is a group of several diseases with some common features. They derive from a multipotential hematopoietic stem cell. A clone of neoplastic cells in all these neoplams is characterized by a lower proliferative activity than that of acute myeloproliferative diseases. In each of these diseases, leukocytosis, thrombocythemia, and polyglobulia may appear at some stage, depending on the diagnosis [1, 2].
The research on interferon has been going on since the 1950s [3]. Then, the attention was paid to its influence on the immune system. It has been noted that it can exert an antiproliferative effect by stimulating cells of the immune system [4]. In 1987, a publication by Ludwig et al. was published, which reported the effectiveness of interferon alpha in the treatment of chronic myeloproliferative disorders [5].
More and more new studies have been showing the effectiveness of interferon alpha in reducing the number of platelets, reducing the need for phlebotomies in patients with polycythemia vera and also in reducing the number of leukocytes. Moreover, interferon reduced the symptoms of myeloproliferative disorders such as redness and itching of the skin. Additionally, it turned out to be effective in reducing the size of the spleen.
Further studies on the assessment of remission using molecular-level response assessments indicate that the interferon action in chronic myeloproliferation diseases targets cells from the mutant clone with no effect on normal bone marrow cells [6].
Over the years, interferon alpha-2a and interferon alpha-2b have been introduced into the treatment of chronic myeloproliferation, followed by their pegylated forms. The introduction of pegylated forms allowed for a reduction in the number of side effects and less frequent administration of the drug to patients. In recent years, monopegylated interferon alpha-2b has been used to further increase the interval between drug administrations while maintaining its antiproliferative efficacy.
The exact mechanism of action of interferon alpha in the treatment of chronic myeloproliferative disease is still not fully understood, but it has an impact on JAK2 (Janus Kinase) signal transducers and activates the STAT signal pathway (Janus Kinase/SignalTransducer and Activator of Transcription).
Interferon alpha binds to IFNAR1 and IFNAR2c, which are type I interferon receptors. Interferon alpha has an impact on JAK2(Janus Kinase) signal transducers and activates the STAT signal pathway. The disturbances in this signaling pathway are observed in chronic myeloproliferative disorders [7].
Interferon inhibits the JAK-STAT signaling pathway by directly inhibiting the action of thrombopoietin in this pathway [8].
So far, three driver mutations have been described in the course of chronic myeloproliferative diseases that affect the functioning of the JAK-STAT pathway.
JAK2 kinase and JAK1, JAK3, and TYK2 kinases belong to the family of non-receptor tyrosine kinases. They are involved in the intracellular signal transduction of the JAK-STAT pathway. It is a system of intracellular proteins used by growth factors and cytokines to express genes that regulate cell activation, proliferation, and differentiation. The mechanism of JAK activation is based on the autophosphorylation of tyrosine residues that occurs after ligand binds to the receptor. JAK2 kinase transmits signals from the hematopoietic cytokine receptors of the myeloid lineage (erythropoietin, granulocyte-colony stimulating factor thrombopoietin, and lymphoid lineage [9].
A somatic G/T point mutation in exon 14 of the JAK2 kinase gene converts valine to phenylalanine at position 617 (V617F) in the JAK2 pseudokinase domain, which allows constitutive, ligand-independent activation of the receptor to trigger a proliferative signal [10].
Mutation of the MPL gene, which encodes the receptor for thrombopoietin, increases the sensitivity of magekaryocytes to the action of thrombopoietin, which stimulates their proliferation [11].
Malfunction of calreticulin as a result of mutation of the CARL gene leads to the activation of the MPL-JAK/STAT signaling pathway, which is independent of the ligand, as calreticulin is responsible, for the proper formation of the MPL receptor. Consequently, there is a clonal proliferation of hematopoietic stem cells [12].
Below, we provide an overview of some clinical studies on the efficacy of interferon in chronic myeloproliferative disorders.
Polycythemia vera (PV) is characterized by an increase in the number of erythrocytes in the peripheral blood.
Polycythemia vera is caused by a clonal mutation in the multipotential hematopoietic stem cell of the bone marrow. The mutation leads to an uncontrolled proliferation of the mutated cell clone, independent of erythropoietin and other regulatory factors. As the mutation takes place at an early stage of hematopoiesis, an increase of the number of erythrocytes as well as of leukocytes and platelets is observed in the peripheral blood. The cause of proliferation in PV independent from external factors is a mutation in the Janus 2 (JAK2) tyrosine kinase gene. The V617F point mutation in the JAK2 gene is responsible for about 96% mutation, and in the remaining cases the mutation arises in exon 12. Both mutations lead to constitutive activation of the JAK-STAT signaling pathway [13].
As a result of the uncontrolled proliferation, blood viscosity increases, which generates symptoms such as headaches and dizziness, visual disturbances, or erythromelalgia. As the number of all hematopoietic cells, including the granulocytes ones, increases, the difficult to control symptoms of their hyperdegranulation may appear, among which gastric ulcer or skin itching is often observed. During the disease progression, the spleen and liver become enlarged.
The most common complication of the disease is episodes of thrombosis, especially arterial one. During the course of the disease, it can also evolve into myelofibrosis or acute myeloid leukemia.
The treatment of PV is aimed at preventing thromboembolic complications, relieving the general symptoms, the appearance of hepatosplenomegaly as well as preventing its progression.
Each patient should receive an antiplatelet drug chronically, and usually acetylsalicylic acid is the choice. Most often, the treatment is started with phlebotomy in order to rapidly lower the hematocrit level. If cytoreductive therapy is necessary, the drugs of first choice are hydroxycarbamide and interferon [2].
However, the research on the mechanism of the action of interferons is still ongoing. In vitro studies with CD34+ cells from peripheral blood of patients diagnosed with polycythemia vera showed that interferon inhibits clonal changed cells selectively. It was found that interferon alpha-2b and pegylated interferon alpha-2a reduce the percentage of cells with JAK2 V617F mutation by about 40%. Pegylated interferon alpha-2a works by activating mitogen-activated protein kinase P38. It affects CD34+ cells of patients with polycythemia vera by increasing the rate of their apoptosis [6].
A case of a patient with PV with a confirmed chromosomal translocation t(6;8) treated with interferon alpha-2b, which resulted in a reduction of the clone with translocation by 50% from the baseline value, was also described [14].
In 2019, the results of a phase II multicenter study were published, which aimed at assessing the effectiveness of recombinant pegylated interferon alpha-2a in cases of refractory to previously hydroxycarbamide therapy. The study included 65 patients with essential thrombocythemia (ET) and 50 patients with polycythemia vera. All patients had previously been treated with hydroxycarbamide and showed resistance to this drug or its intolerance.
The assessment of the response was performed after 12 months of treatment. Overall response rate to interferon was higher in patients diagnosed with ET than in patients with polycythemia vera. In essential thrombocythemia, the percentage of achieved complete remissions was 43 and 26% of partial remissions. The remission rate in ET patients was higher if calreticulin CALR gene mutation was present. Patients with polycythemia vera achieved complete remission in 22% of cases and partial remission in 38% of cases.
Treatment-related side effects that follow to discontinuation of treatment were reported in almost 14% of patients [15].
The duration of response to treatment with pegylated interferon alpha-2a and the assessment of its safety in long-term use in patients with chronic myeloproliferative disorders was the goal of a phase II of the single-center study. Forty-three adult patients with polycythemia vera and 40 patients with essential thrombocythemia were enrolled in the study. The complete hematological response was defined as a decrease in hemoglobin concentration below 15.0 g/l, without phlebotomies, a resolution of splenomegaly, and no thrombotic episodes in the case of PV, and for essential thrombocythemia—a decrease platelet count below 440,000/μl and two other conditions as above. The assessment of the hematological response was performed every 3–6 months. The median follow-up was 83 months.
The hematological response was obtained in 80% of cases for the entire group. In patients with polycythemia vera, 77% of patients achieved a complete response (CR) while 7% a partial response (PR). The duration of response averaged 65 months for CR and 35 months for PR. In the group of patients diagnosed with essential thrombocythemia, CR was achieved in 73% and PR in 3%. The durance of CR was 58 months and PR was 25 months.
The molecular response for the entire group was achieved in 63% of cases.
The overall analysis showed that the duration of hematological remission and its achievement with pegylated interferon alpha-2a treatment is not affected neither by baseline disease characteristics nor JAK2 allele burden and disease molecular status. There was also no effect on age, sex, or the presence of splenomegaly.
During the course of the study, 22% of patients discontinued the treatment, because of toxicity. Toxicity was the greatest at the beginning of treatment. The starting dose was 450 μg per week and was gradually tapered off.
Thus, on the basis of the above observations, the researchers established that pegylated interferon alpha-2a may give long-term hematological and molecular remissions [16].
The assessment of pegylated interferon alpha-2a in group of patients diagnosed with polycythemia vera only was performed. The evaluation was carried out on a group of 27 patients. Interferon decreased the JAK2 V617F allele burden in 89% of cases. In three patients who were JAK2 homozygous at baseline, after the interferon alpha-2a treatment wild-type of JAK2 reappeared. The reduction of the JAK2 allele burden was estimated from 49% to an average 27%, and additional in one patient the mutant JAK2 allele was not detectable after treatment. It can therefore be postulated that the action of pegylated interferon alpha-2a is directed to cells of the polycythemia vera clone [17].
In 2005, the results of treatment by pegylated interferon alpha-2b of 21 patients diagnosed with polycythemia vera and 21 patients diagnosed with essential thrombocythemia were published. In the case of polycythemia vera in 14 patients, PRV-1 gene mutation was initially detected. In 36% of cases, PRV-1 expression normalized after treatment with pegylated interferon alpha-2b. For the entire group of 42 patients, the remission assessment showed that complete remission was achieved in 69% cases after 6 months of treatment. However, only in 19 patients remission was still maintained 2 years after the start of the study. Pegylated interferon alpha-2b was equally effective in patients with PV and ET. The use and the type of prior therapy did not affect the achievement of remission [18].
Another study with enrolled only PV patients included 136 patients. They were divided into two arms. One group received interferon alpha-2b and the other group received hydroxycarbamide. Interferon dosage was administered in 3 million units three times a week for 2 years and then 5 million units two times a week. Hydroxycarbamide was administered at a dose between 15 and 20 mg/kg/day.
In the group of patients treated with interferon, a significantly lower percentage of patients developed erythromelalgia (9.4%) and distal parasthesia (14%) compared with the group treated with hydroxycarbamide, for whom these percentages were respectively: 29 and 37.5%. Interferon alpha-2b was found to be more effective in inducing a molecular response, which was achieved in 54.7% of cases, in comparison with hydroxycarbamide—19.4% of cases, despite the fact that the percentage of achieved general hematological responses did not differ between the groups and amounted about 70%. The 5-year progression free period in the interferon group was achieved in a higher percentage (66%) than in the hydroxycarbamide group (46.7%) [19].
The most recent form of interferon approved by the
Thanks to these changes to the structure of the molecule, it was possible to achieve a significant increase in its half-life. Ropeginterferon can be administered subcutaneously to patients every 14 days. The clinical trials conducted so far have assessed the ropeginterferon dose from 50 micrograms to a maximum dose of 500 microgams administered as standard every 2 weeks. The possible dose change in case of side effects includes not only the reduction of the drug dose itself, but also the extension of the interval between doses. The extension of the dosing interval up to 4 weeks was assessed.
Ropeginterforn was approved in 2019 by the EMA for the use in patients diagnosed with polycythemia vera without splenomegaly, as monotherapy.
Ropeginterferon, like the previous forms of interferons used in treatment, is contraindicated in patients with severe mental disorders, such as severe depression. It is also a contraindication in patients with noncompensatory standard treatment of disorders of the thyroid gland as well as severe forms of autoimmune diseases. The safety profile of ropeginterferon is similar to that of other forms of alpha interferons. The most common side effects are flu-like symptoms [20].
Ropeginterferon has been shown to exhibit in vitro activity against JAK2-mutant cells. The activity of ropeginterferon against JAK2-positive cells is similar to that of other forms of interferons used actually for standard therapy. Ropeginterferon has an inhibitory effect on erythroid progenitor cells with a mutant JAK2 gene. At the same time, it has almost no effect on progenitor cells without the mutated allele (JAK2-wile-type) and normal CD34+ cells. A gradual decrease of JAK2-positive cells was observed in patients with PV during ropeginterferon treatment. The examination was performed after 6 and 12 months of treatment. In comparison, the reduction in the percentage of JAK2 positive cells in patients treated with hydroxycarbamide was significantly lower.
These results may suggest that ropeginterferon may cause elimination of the mutant clone, but further prospective clinical trials are needed to confirm this theory. The evaluation was performed on a group of patients enrolled in the PROUD-PV study who were treated in France [21].
In 2017, a multicenter study was opened in Italy. The study was of the second phase. In total, 127 patients with polycythemia vera were included in the study. All patients enrolled on the study had low-risk PV. The clinical trial consisted of two arms. Patients received phlebotomies and low-dose aspirin in one arm and ropeginterferon in the other arm. The aim of the study was to achieve a hematocrit of 45% or lower without any evidence of disease progression. Ropeginterferon was administered every 2 weeks at a constant dose of 100 μg.
The response to the treatment was assessed after 12 months. The reduction of hematocrit to the assumed level was achieved in significantly higher percentage of patients in the ropeginterferon group than of patients who received only phlebotomies and aspirin. In addition, none of the patients treated with ropeginterferon experienced disease progression during the course of the study, while among those treated with phlebotomies, 8% of patients progressed.
Grade 4 or 5 adverse events were not observed in patients treated with ropeginterferon, and the incidence of remaining adverse event (AE) was small and comparable in both arms. The most common side effects in the ropeginterferon group were flu-like symptoms and neutropenia; however, the third-grade neutropenia was the most common (8% of cases) [22].
One of the most important clinical studies on the use of ropeginterferon was the PROUD-PV study and its continuation: the CONTINUATION-PV study. These were three-phase, multicenter studies. The aim of the study was to compare the effectiveness of ropeginterferon in relation to hydroxycarbamide. The study included adult patients diagnosed with polycythemia vera treated with hydroxycarbamide for less than 3 years and no cytoreductive treatment at all. In total, 257 patients received this treatment. The patients were divided into two groups: those receiving ropeginterferon or the other being given hydroxycarbamide.
During the PROUD-study, drug doses were increased until the hematocrit was achieved below 45% without the use of phlebotomies, and the normalization of the number of leukocytes and platelets was reached.
The PROUD-PV study lasted 12 months. After this time, the patients continued the treatment under the CONTINUATION-PV study for further 36 months. After the final analysis performed in the 12th month at the end of PROUD study, it was found that the hematological response rates did not differ between the ropeginterferon and hydroxycarbamide treatment groups. These were consecutively 43% in the ropeginterferon arm and 46% in the control arm.
However, after analyzing the CONTINUATION- PV study, it turned out that after 36 months of treatment, the rates of hematological responses begin to prevail in the group of patients receiving ropeginterferon, 53% versus 38% in the control group. Thus, from the above data, it can be seen that the response rate to ropeginterferon increases with the duration of treatment [23].
Another analysis of patients participating in the PROUD and CONTINUATION studies was based on the assessment of treatment results after 24 months, dividing patients into two groups according to age (under and over 60 years).
The initial comparison of both groups of patients showed that older patients had a more aggressive course of the disease. Patients over 60 years of age had a higher percentage of cells with a mutant JAK2 allele. They experienced both general symptoms and some complications, such as thrombosis, more frequently. Both patients under 60 years of age and over 60 years of age in the ropeginterferon arm had a higher rate of molecular response, namely 77.1 and 58.7% compared with the HU remission: 33.3 and 36.1%, respectively. Significantly higher reductions in the JAK2 allele were observed in both groups of patients after ropeginterferon treatment: it was 54.8% for younger patients and 35.1% for elderly patients. For comparison, this difference in the group of patients treated with HU was 4.5 and 18.4%, respectively.
What is more, the age did not affect the frequency of ropeginterferon side effects. In addition, the incidence of adverse ropeginterferon disorders was similar to that observed in the hydroxycarbamide group [24].
Essential thrombocythemia is a clonal growth of multipotential stem cells in the bone marrow. The consequence of this is increased proliferation of megakaryocytes in the bone marrow and an increase in the number of platelets in the peripheral blood. The level of platelets above 450,000/μl is considered a diagnostic criterion.
Essential thrombocythemia may progress over time to a more aggressive form of myeloproliferation, i.e., myelofibrosis. The disease can also evolve into acute myeloid leukemia or myelodysplastic syndrome, both with very poor prognosis. Thromboembolic complications are serious, and they concern over 20% of patients. Thrombosis occurs in the artery and venous area. Moreover, in patients with a very high platelet count, above 1,000,000/μl, bleeding may occur as a result of secondary von Willebrand syndrome [1, 2].
The treatment of ET is primarily aimed to prevent thrombotic complications.
In low-risk patients, only acetylsalicylic acid is used. In cases of high-risk patients, hydroxycarbamide is the first-line drug for most patients. Anagrelide and interferon are commonly used as second-line drugs.
Due to the possible effects of hydroxycarbamide of cytogenetic changes in the bone marrow cells after long-lasting usage, some experts recommend the use of interferon in younger patients in the first line. Interferon is also used as the drug of choice in patients planning a pregnancy [25].
The efficacy of pegylated interferon alpha-2a was assessed on the basis of the group of 39 patients with essential thrombocythemia and 40 patients with polycythemia vera.
Of the overall group, 81% of patients were previously treated prior to the study entry. The patients received pegylated interferon alpha-2a in a dose of 90 μg once a week. The dose of 450 μg was associated with a high percentage of intolerance.
In patients with essential thrombocythemia, the complete remission was achieved in 76%, while the overall hematological response rate brought 81%. Moreover, the molecular remission was achieved in 38%, in 14% of cases, JAK2 transcript became not detectable.
Patients diagnosed with polycythemia vera achieved 70% complete hematological remission and 80% general hematological response to treatment. JAK2 transcript was undetectable in 6% of patients. Molecular remission was achieved in 54% of cases.
Pegylated interferon alpha-2a at the dose of 90 μg per week was very well tolerated. In total, 20% of patients experienced a grade of 3 or 4 of adverse reaction, which was neutropenia. In addition, an increase in liver function tests was observed. Grade 4 of AE was not observed among patients who started the treatment with 90 μg/week while grade 3 neutropenia was an adverse event in only 7% of cases [26].
The effect of interferon alpha-2b treatment in patients with ET and PV was investigated. The study was prospective. Some of the results concerning the group of patients with polycythemia vera are presented in the subsection on polycythemia vera. In total, 123 patients with diagnosed essential thrombocythemia participated in the study. All of them received interferon alpha-2b. The patients were divided into two groups depending on the presence of the JAK2 V617F mutation. The enrolled patients were between 18 and 65 years of age. The treatment they received was, sequentially, interferon alpha-2b in the dose of 3 million units three times a week for the first 2 years, after which time the dose was changed into a maintenance dose, which amounted to 5 million units two times a week.
The analysis showed that the patients with the JAK2 V617F mutation present in a higher percentage achieved an overall hematological response as well as a complete hematological response. The overall hematological response was achieved in 83% of patients with JAK2 mutation, and the complete hematological remission was achieved in 23 cases. In the group of ET patients without the JAK2 V617F mutation, overall hematological response was achieved in 61.4%, while the complete hematological remission was achieved in 12 patients. The 5-year progression-free survival was obtained in 75.9% in the JAKV617F group and only in 47.6% without the mutation.
A significant proportion of patients experienced mild side effects. Grade 3 and 4 of adverse events were severe, most of them being a fever. The isolated cases of elevated liver tests and nausea have also been reported [19].
Pegylated interferon alpha-2b in patients with essential thrombocythemia who were previously treated with hydroxycarbamide, anagrelide, and other forms of interferon alpha, however, due to the lack of efficacy or toxicity, the patients required a change of treatment, was assessed. Pegylated interferon alpha-2b turned out to be effective in these cases. It led to the complete hematological remission in 91% of patients after 2 months of therapy, and in 100% of patients after 4 months. However, merely 11 patients participated in the study. Also only two patients required treatment discontinuation due to the side effects such as depression and general fatigue grade 3 [27].
In case of pregnant patients, interferon is currently considered the only safe cytoreductive drug. Over the years, several analyses of the results of interferon treatment during pregnancy have been carried out.
The assessment of 34 pregnancies in 23 women diagnosed with ET was performed retrospectively. All the pregnancies included in the analysis were of high risk. This high risk was associated with a high platelet count above 1,500,000/μl, a history of thrombotic episode, severe microcirculation disorders, or a history of major hemorrhage.
It turned out that the use of interferon allowed the birth of an alive child in 73.5% of cases. There was no difference in efficacy between the basic and pegylated forms of interferon alpha. In pregnancies without interferon treatment, the percentage of live births was only 60%. Moreover, it was not found if the presence of the JAK2 V617F mutation had any influence on the course of pregnancy [28].
An analysis of the course of pregnancy in patients with ET was assessed in Italy. Data from 17 centers were taken into account. Data from 122 pregnancies were collected from 92 women. In patients diagnosed with essential thrombocythemia, the risk of the spontaneous loss of pregnancy is about 2.5 times higher than among the general population. In the contrary to the study quoted above, it was found that the presence of the JAK2 mutation increases the risk of pregnancy loss. The proportion of live births in patients exposed to interferon during pregnancy was 95%, compared with 71.6% in the group of patients not treated with interferon.
The multivariate analysis also showed that the use of acetylsalicylic acid during pregnancy had no effect on the live birth rate of patients with ET [29].
Whatever its form, interferon is the drug of first choice in pregnancy. Hydroxycarbamide and anagrelide should be withdrawn for about 6 months, and at least for 3 months, before the planned conception. Experts recommend the use of interferon in high-risk pregnancies [30]. A Japanese analysis of 10 consecutive pregnancies in ET patients showed 100% live births in patients who received interferon [31].
In myelofibrosis (MF), monoclonal megakaryocytes produce cytokines that stimulate the proliferation of normal, non-neoplastic fibroblasts and stimulate angiogenesis. The consequence of this is the gradual fibrosis of the bone marrow, impaired hematopoiesis in the bone marrow, and the formation of extramedullary location mainly in the sites of fetal hematopoiesis, i.e., in the spleen and the liver.
The production of various cytokines by neoplastic megakaryocytes leads to the proliferation of normal, noncancerous fibroblasts as well as to increased angiogenesis.
Progressive bone marrow fibrosis leads to worsening anemia and thrombocytopenia. On the other hand, the production of proinflammatory cytokines by megakaryoblasts leads to the general symptoms such as weight loss, fever, joint pain, night sweats, and consequently, progressive worsening of general condition.
The prognosis for myelofibrosis is poor. In about 20% of patients, myelofibrosis evolves into acute myeloid leukemia with poor prognosis.
Currently, the only effective method of treatment that gives a chance to prolong the life is allogeneic bone marrow transplantation. However, this method is only available to younger patients.
The goal of treatment of patients who have not been qualified for allotranspalntation is to reduce the symptoms and to improve the patient’s quality of life. In case of leukocytosis cytoreducing drugs, such as hydroxycarbamide, melphalan, or cladribine can be used. They cause a reduction in the number of leukocytes and may, to some extent, inhibit splenomegaly. Interferon alpha has been used successfully for the treatment of myelofibrosis for many years. The results of its effectiveness will be presented below [2].
Currently, the JAK2 inhibitor ruxolitinib is approved for the treatment of myelofibrosis with enlarged spleen in intermediate and high-risk patients. Ruxolitinib reduces the size of the spleen, reduces general symptoms, and improves the quality of life; however, it does not prolong the overall survival of patients [32].
In 2015, the results of a retrospective study were published to compare the histological parameters of the bone marrow before and after interferon treatment. Twelve patients diagnosed with primary myelofibrosis as well as post-PV MF and post-ET MF were enrolled in the study. Patients were treated with pegylated recombinant interferon alpha-2a or recombinant interferon alpha-2b in standard doses. The time of treatment was from 1 to 10 years. Some patients had previously been treated with hydroxycarbamide or anagrelide. In all cases, karyotype was normal. The prognostic factor of Dynamic International Prognostic Scoring System (DIPSS) was assessed at the beginning as well as during the treatment.
Bone marrow cellularity decreased in cases with increased bone marrow cellularity before the treatment. After the interferon treatment, a reduction in the degree of bone marrow fibrosis was found. The parameters, such as the density of naked nuclei and the density of megakaryocytes in the bone marrow, also improved.
It proves that if the JAK2 V617F mutation had been present, DIPSS was decreased after interferon treatment. This relationship was not observed in patients without the JAK2 V617F mutation. The improvement in peripheral blood morphological parameters and the overall clinical improvement correlated with the improvement in the assessed histological parameters of the bone marrow.
Before the initiation of interferon, seven patients had splenomegaly. During the treatment with interferon, the complete resolution of splenomegaly was achieved in 17% of patients (two cases), and its size decreased in 25% (three cases). A good clinical response was achieved in 83% during interferon therapy. There was no significant difference in response between the two types of interferon used [33].
A prospective study was also conducted in patients with low and intermediate-1 risk group myelofibrosis. Seventeen patients were enrolled. Patients received interferon alpha-2b (0.5–3 milion units/three times a week) or pegylated interferon alpha-2a (45–90 μg/week). The duration of therapy was on average 3.3 years.
Most of the patients responded to the treatment. Partial remission was found in seven patients and complete remission in two patients. Moreover, in four cases, the disease was stabilized and in one case the clinical improvement was achieved. Three patients did not respond to treatment at all and progressed to myelofibrosis. Additionally, the assessment in reducing spleen size was performed. At baseline, 15 patients have splenomegaly, nine of them achieved the compete regression of spleen size [34].
However, the efficacy of interferon in the treatment of myelofibrosis appears to be limited only to a less advanced form, when the bone marrow still has an adequate percentage of normal hemopoiesis and the marrow stroma is not significantly fibrotic. In more advanced stages, interferon was not shown to have any significant effect on the regression of the fibrosis process [35].
In 2020, the results of the COMBI study were published. That was a two-phase, multicenter, single-arm study that investigated the efficacy and safety of the combination of ruxolitinib and pegylated interferon alpha. Thirty-two patients with PV and 18 patients with primary and secondary myelofibrosis participated in the study. The patients were at age 18 and older. Remission was achieved in 44% of myelofibrosis cases, including 28% (5 patients) of complete remission. In patients with PV, the results were slightly worse: 31% of remissions, including 9% of complete remissions. Patients received pegylated interferon alpha-2a (45 μg/week) or pegylated interferon alpha-2b (35 μg/week) in low doses and ruxolitinib in doses of 5–20 mg twice a day.
For the entire group of patients (with PV and MF), the initial JAK2 allele burden was 47% at baseline, and after 2 years of treatment with interferon and ruxolitinib, it decreased to 12%.
The treatment toxicity was low. The highest incidence of side effects occurred at initiation of therapy. It was mostly anemia and thrombocytopenia.
The observations from the COMBI study show that, for the combination of interferon in lower doses with ruxolitinib, it may be effective and well tolerated even in the group of patients who had intolerance to interferon used as the only drug in higher doses. The combined treatment improved the bone marrow in terms of fibrosis and its cellularity. It also allowed to improve the value of peripheral blood counts [36].
It is currently known that some of the additional mutations are associated with a worse prognosis in patients with myelorpoliferation, including patients with myelofibrosis. Some of these mutations have been identified as high-risk molecular mutations. These are ASXL1, EZH2, IDH1/2, or SRSF2. Earlier studies have shown their association with a more aggressive course of the disease, worse prognosis, and shorter survival of patients, as well as a poorer response to treatment. Due to their importance, they have been included in the diagnostic criteria of myelofibrosis [37].
It is also known that the presence of driver mutations, i.e., JAK2, CALR, and MPL or triple negativity, may affect the course of myeloproliferation, including the incidence of thromboembolic complications.
The assessment of the influence of driver mutations and a panel of selected additional mutations on the effectiveness of interferon treatment in patients with myelofibrosis was performed on a group of 30 patients. Only the patients with low- and intermediate-1-risk were enrolled in the study. The treatment with pegylated interferon alpha-2a or interferon alpha-2b resulted in a complete remission in two patients and partial remission in nine patients. The disease progressed in three cases. One patient relapsed and four died. The remaining patients achieved a clinical improvement or disease stabilization. In the studied group, it was not found if the effectiveness of interferon treatment was influenced by the lack of driver mutations. Among the group of four patients with additional mutations, two died and one had disease progression. It was a mutation of ASXL1 and SRSF2. The treatment with interferon in patients without additional molecular mutations in the early stages of the disease may prevent further progression of the disease [38].
The side effects of interferon in the group of patients with myelofibrosis are similar to those occurring after the treatment of other chronic myeloproliferative diseases. The most frequently described are hematological toxicity- anemia and thrombocytopenia, less often is the appearance of leukopenia. Hematological toxicity usually resolves with dose reduction or extension of the dose interval. The most frequently nonhematological toxicity was fatigue, muscle pain, weakness, and depression symptoms. All symptoms are usually mild and do not exceed grade 2 [38].
However, the use of interferon in the treatment of myelofibrosis has not been recommended as a standard therapy. Interferon is still being evaluated in clinical trials, or it is used in selected patients as a nonstandard therapy in this diagnosis.
Mastocytosis is characterized by an excessive proliferation of abnormal mast cells and their accumulation in various organs.
The basis for the development of mastocytosis is ligand-independent activation of the KIT receptor, resulting from mutations in the KIT proto-oncogene. The KIT receptor is a trans membrane receptor with tyrosine kinase’s activity. Its activation stimulates the proliferation of mast cells. That excessive numbers of mast cells infiltrate tissues and organs and release mediators such as histamine, interleukine-6, tryptase, heparin, and others, which are responsible for the appearance of symptoms typical of mastocytosis. In addition, the infiltration of tissues for mast cells itself causes damage to the affected organs.
The prognosis of mastocytosis depends on the type of the disease. In the case of cutaneous mastocytosis (CM), in the majority of cases prognosis is good and the disease does not shorten the patient’s life, but in aggressive systemic mastocytosis (ASM), the average follow-up is about 40 months. Mast cell leukemia has a poor prognosis with a median follow-up of approximately 1 year.
Systemic mastocytosis usually requires the implementation of cytoreductive therapy. The first line of therapy is interferon alone or its combination with corticosteroids. In aggressive systemic mastocytosis, the first line in addition to interferon 2-CdA can be used. An effective drug turned out to be midostaurin in the case of the present KIT mutation. In patients without the KIT D816V mutation, treatment with imatinib may be effective. In the case of mast cell leukemia, multidrug chemotherapy is most often required, as in acute leukemias, followed by bone marrow transplantation [39].
Systemic mastocytosis requiring treatment is a rare disease, this is why the studies available in the literature evaluating various therapies concern mostly small groups of patients.
In 2002, the French authors presented their experiences on the use of interferon in patients with systemic mastocytosis. They included 20 patients. The patients received interferon alpha-2b in gradually increased doses.
The patients were assessed after 6 months. In cases in which bone marrow was infiltrated for mast cells at baseline, it still remained infiltrated after 6 months of treatment.
However, the responses were obtained in terms of symptoms related to mast cell degranulation. Partial remission was achieved in 35% of patients and minor remission in 30%. It concerns mainly skin lesions and vascular congestion. Moreover, the assessment of the histamine level in the plasma revealed a decrease of it in patients who previously presented symptoms related to the degranulation of mast cells, such as gastrointestinal disorders and flushing.
A high percentage of side effects were found during treatment. They concerned 35% of patients. Depression and cytopenia were most frequent ones [40].
Another analysis was a report of five patients with systemic mastocytosis treated with interferon and prednisolone. All patients received interferon alpha-2b in a dose of 3 million units three times a week and four patients additionally received prednisolone. Four patients responded to interferon treatment at varying degrees. One patient, who at baseline had bone marrow involvement by mast cells in above 10%, progressed to mast cell leukemia. In two patients, the symptoms C resolved completely and in one of them they partially disappeared. In one case, stabilizing disease was achieved [41].
In 2009, a retrospective analysis of patients treated with cytoreductive therapy due to mastocytosis was published. The authors collected data from 108 patients treated at the Mayo Clinic. This analysis allowed for the comparison of the efficacy of four drugs used in systemic mastocytosis. There were interferon alpha alone or in the combination with prednisone—among 40 patients, hydroxycarbamide—among 26 ones, imatinib—among 22 persons, and 2-chlorodeoxyadenosine (2-CdA)—among 22 patients.
After dividing the patients into three additional groups on the basis of the type of mastocytosis—indolent systemic mastocytosis, aggressive systemic mastocytosis, and systemic mastocytosis associated with another clonal hematological nonmast cell lineage disease (SM-AHNMD)—the effectiveness of each of type of therapy was assessed.
The highest response rates in indolent and aggressive mastocytosis were achieved with interferon treatment. They were 60% of the responses in both groups, and in the SM-AHNMD group of patients, the percentage was also one of the highest and amounted to 45%. The second most effective drug was 2-CdA. The response rates were 56% for indolent MS, 50% for aggressive MS, and 55% for SM-AHNMD. The patients treated with imatinib achieved response in 14, 50, and 9% by following groups, respectively. In contrast, patients with indolent and aggressive systemic mastocytosis did not respond to hydroxycarbamide treatment at all. The response rate in both groups was 0%. However, patients with MS associated with another clonal hematological nonmast cell lineage disease achieved 21% response to hydroxycarbamide. Additionally, it was found that only interferon relieved symptoms caused by the release of inflammatory mediators by mast cells.
The additional analysis showed no influence of the TET 2 mutation on the response to treatment [42].
In the literature, there are also single cases of mastocytosis presenting trials of nonstandard treatment. That is description of a patient with systemic mastocytosis with mast cell bone marrow involvement. Mutation of c-kit Asp816Val was present. Patient progressed despite treatment with dasatinib and 2-chlorodeoxyadenosine. The patient developed symptoms related to the degranulation of mast cells and increased ascites.
The patient was treated with pranlukast, which is an anti-leukotriene receptor antagonist due to an asthma episode. The rate of ascites growth decreased significantly after one administration. The patient required paracentesis every 10 days and not every 3 days, as before starting to take the drug. After 15 days of treatment with pranlukast, the patient received interferon alpha, which resulted in complete regression of ascites, resolution of pancytopenia, and complete disappearance of the c-kit mutation clone. The infiltration of mast cells in the bone marrow significantly decreased [43].
Interferon alpha was also effective in a patient with systemic mastocytosis associated with myelodysplastic syndrome with the c-kit D816V mutation, which was refractory to imatinib treatment [44].
Interferon alpha also proved to be effective in the treatment of osteoporotic lesions appearing in the course of mastocytosis.
The series of 10 cases with resolved mastocytosis and osteoporosis-related fractures was presented in 2011. The patients received interferon alpha in a dose of 1.5 million units three times a week as well as pamindronic acid. The patients were treated for an average of 60 months. For the first 2 years, pamindronate was given at a dose of 1 mg/kg every month, and then every 3 months.
During the course of the study, no patient had a new-bone fracture. The level of alkaline phosphatase decreased by 25% in relation to the value before treatment and tryptase by 34%. Bone density increased during treated with interferon and pamindronate. The increase was on average 12% in the spine bones and 1.9% in the hip bones. At the same time, there was no increase in the density of the hip bone and a minimal increase in the density of the spine in patients treated with pamindronate alone.
The results of this observation suggest that it is beneficial to add low doses of interferon alpha to pamindronate treatment in terms of bone density increase [45].
That experiences show that interferon used in systemic mastocytosis significantly improves the quality of life of patients by inhibiting the symptoms caused by degranulation of mast cells. They prevent bone fractures and, in some patients, they cause remission of bone marrow infiltration by mast cells.
Chronic neutrophilic leukemia (CNL) is a very rare disease. It is characterized by the clonal proliferation of mature neutrophils.
The diagnostic criteria proposed by the World Health Organization (WHO) comprise leukocyte counts above 25,000/μl (including more than 80% of rod and segmented
Physical examination often shows enlargement of the liver and spleen, moreover, patients complain on weight loss and weakness [1].
The prognosis varies. The average survival time for patients with CNL is less than 2 years.
Only few descriptions of chronic neutrophilic leukemia are available in the literature, and these are mostly single case reports.
Because it is an extremely rare disease, there are no established and generally accepted treatment standards. In most cases, patients are given hydroxycarbamide or interferon. Patients who are eligible for a bone marrow transplant may benefit from this treatment. Bone marrow allotransplantation remains the only method that gives a chance for a significant extension of life.
The German authors presented a series of 14 cases of chronic neutrophilic leukemia. The group of patients consisted of eight women and six men. The average age was 64.7 years. From the entire group of patients, longer survival was achieved only in three cases. One of these patients was treated with interferon alpha and achieved hematological remission, the other underwent bone marrow allotransplantation from a family donor, and the third one was treated with hydroxycarbamide and transfusions as needed. The follow-up period of the patient after allogeneic matched related donor transplantation (allo-MRD) was 73 months, and for the patient after interferon treatment it was 41 months.
The remaining patients died within 2 years of diagnosis. Six patients, the largest group, died due to intracranial bleeding, three patients died because of leukemia cell tissue infiltration, one patient because of the disease transformation into leukemia, and one patient because of pneumonia [46].
It can be seen from these experiences that treatment with interferon alpha can significantly extend the survival time of patients.
The case of a 40-year-old woman diagnosed with chronic neutrophilic leukemia is presented by Yassin and coauthors. Initially, the patient had almost 41,000 leukocytes in the peripheral blood. In a physical examination, splenomegaly and hepatomegaly were not present. Patient received pegylated interferon alpha-2a. The initially dose was 50 μg once a week for the first 2 weeks, then the dose was increased to 135 μg weekly for 6 weeks, and then the dose interval was extended to another 2 weeks. As a result of the treatment, the general condition of the patient improved and the parameters of peripheral blood counts were normalized [47].
Another case report presented in the literature describes a 41-year-old woman diagnosed with CNL accompanied by focal segmental glomerulosclerosis (FSGS). The patient had increasing leukocytosis for several months. On the admission to the hospital, leukocytosis was 94,000/μl. Moreover, the number of platelets in the morphology exceeded 1,000,000/μl. More than a year earlier, the patient had splenectomy due to splenomegaly and spleen infraction.
Additionally, JAK2 V617F mutation was found. Some authors suggest that the presence of JAK2 mutation may be associated with longer survival in CNL.
The patient received hydroxycarbamide for 3 months and reduction in the number of leukocytes was achieved. After this time, interferon alpha-2b was added to hydroxycarbamide. As a result, focal segmental glomerulosclerosis disappeared and the renal tests improved [48].
Another case of chronic neutrophilic leukemia with a JAK2 gene mutation concerns a 53-year-old man. The patient’s baseline leukocytosis was 33,500/μl, including the neutrophil count of 29,700/μl. The patient also had splenomegaly.
The treatment with interferon alpha-2b at a dose of 3 million units every other day was started. After a month of treatment, the number of leukocytes was reduced to less than 10,000/μl. Then the patient was treated chronically with interferon alpha-2b in doses of 3 million units every 2 weeks. As a result of the therapy, the number of leukocytes remains between 8 and 10,000/μl. The patient remains in general good condition [49].
A series of two CNL cases are also shown. The first patient was a 70-year-old woman with stable leukocytosis of about 35,000/μl and the remaining morphology parameters in normal range. The patient was only observed for 5 years until hepasplenomegaly progressed rapidly. Then, interferon alpha-2b was included. Due to the treatment, the rapid regression of hepatosplenomegaly was achieved.
The second case is a 68-year-old woman with baseline leukocytosis of almost 14,000/μl. In this case, the treatment with hydroxycarbamide was started immediately. However, no improvement was achieved. After 6 weeks of HU treatment, interferon alpha-2b 3 million units 3 times a week was implemented and leukocytosis decreased. Due to the interferon treatment, the disease stabilized for a long time. Because the patient experienced an adverse reaction, a severe flu-like syndrome, interferon was discontinued. After interferon withdrawal, the disease progressed gradually and the treatment attempts by busulfan and 6-mercaptopurine were unsuccessful. Therefore, interferon was readministered and the disease went into remission. Interferon treatment was continued at a reduced dose. The disease regression was achieved again.
Additionally, the patient showed an improvement in the function of granulocytes in terms of phagocytosis and an improvement in neutral killer (NK) cell function after treatment with interferon [50].
The above examples show that interferon alpha is effective in the treatment of chronic neutrophilic leukemia. The side effects are rare and can be managed with dose reductions. Moreover, in these cases, interferon is also effective in a reduced dose. Disease remission or regression can be achieved without typical of CNL complications, such as intracranial bleeding.
Interferon has been used in the past to treat chronic myeloid leukemia. The treatment with tyrosine kinase inhibitors is now a standard practice. However, in a small number of patients, they are ineffective or exhibit unmanageable toxicity. Therefore, the attempts are underway to use interferon in combination with TKI in lower doses, which is to ensure the enhancement of the antiproliferative effect while reducing the toxicity.
There are ongoing attempts to use ropeginterferon in patients diagnosed with chronic myeloid leukemia, in whom treatment with imatinib alone has not led to deep molecular response (DMR). The first phase study was conducted in a small group of patients with chronic myeloid leukemia. The patients in first chronic phase treated with imatinib who did not achieve DMR, but in complete hematologic remission and complete cytogenetic remission, were included in the study. Patients have been treated with imatinib for at least 18 months. Twelve patients were enrolled in the study, and they completed the study according to the protocol. These patients received additional ropeginterferon to imatinib and four achieved DMR. Low toxicity was observed during the treatment. Among the hematological toxicities, neutropenia was the most common. There was no nonhematological toxicity with a degree higher than 1/2 during the treatment. Moreover, it has been found that better effects and fewer side effects are obtained when ropeginterferon is administered for a longer time, but in lower doses. The comparison of the effectiveness of interferon in chronic myeloproliferative disorders based on selected articles is presented in Table 1 [51].
Source | Type of trial | Interferon | Diagnosis | No. | Prior treatment status | Response rate |
---|---|---|---|---|---|---|
Yacoubet al. [15] | Phase II, multicenter | Pegylated IFN alfa-2a | PV | 50 | Resistance to HU or HU intolerance | CR:22% PR:38% |
ET | 65 | CR:43% PR:26% | ||||
Masarova et al. [16] | Phase II, single-center | Pegylated IFN alfa-2a | PV | 43 | Untreated or previously treated with cytoreductive therapy | CR:77% PR:7% |
ET | 40 | CR:73% PR:3% | ||||
Samuelsson et al. [18] | Phase II | Pegylated IFN alfa-2b | PV | 21 | Untreated or previously treated with cytoreductive therapy | CR: 69% for the entire group |
ET | 21 | |||||
Huang BT et al. [19] | Open label, multicenter | IFN alfa-2b | PV | 136 | Untreated or previously treated with cytoreductive therapy | OHR:70% Molecular response:54.7% |
ET | 123 | OHR (JAK2+ patients):83% CHR:23 cases OHR (JAK2-patients): 61.4% CHR:12 cases | ||||
Gisslinger et al. [23] | phase III, multicenter | Ropeginterferon | PV | 257 | Previously treated | OHR:53% |
Quintás-Cardama et al. [26] | phase II | Pegylated IFN alfa-2a | PV | 40 | Untreated or previously treated with cytoreductive therapy | OHR:80% CR:70% Molecular remission:54% |
ET | 39 | OHR:81% CR:76% Molecular remission:38% | ||||
Sørensen et al. [36] | Phase III, multicenter, COMBI | Pegylated IFN alfa-2a with ruxolitinib or Pegylated IFN alfa-2b with ruxolitinib | PV | 32 | Untreated or previously treated with cytoreductive therapy | OHR:44% CR:28% |
MF | 18 | OHR:31% CR:9% | ||||
Casassus et al. [40] | Open label, multicenter | IFN alpha-2b | Mastocytosis | 20 | Untreated and previously treated | PR:35% Minor remission: 30% |
Comparison of the effectiveness of interferon in chronic myeloproliferative disorders.
PV: polycythemia vera; ET: essential thrombocythemia; MF: myelofibrosis; HU: hydroxycarbamide/hydroxyurea; CR: complete remission; PR: partial remission; and OHR: overall hematological response.
Interferon alpha appears to be an effective and safe drug in the most type of chronic myeloproliferative disorders. Nowadays, all forms of its using have similar effectiveness. Interferon alpha can be effective even in cases of resistance for first-line treatment. Trial research is currently underway to combine it with some new drugs, such as ruxolitinib, and to add it to the already well-established therapy, it is a promising option for patients with refractory disease.
From time to time, new forms of interferon, such as ropeginterferon, are introduced, which gives hope for better effectiveness, better safety profile, and greater comfort in its use for patients who have to be treated for many years. In the case of the use of interferons alpha in the treatment of chronic myeloproliferative diseases, there are still opportunities to extend its use and to study its combination with newly introduced drugs.
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\n\nThe Open Access Publishing Fee (OAPF) is payable only after your book chapter, monograph or journal article is accepted for publication.
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\n\nDuring the launching phase journals do not charge an APC, rather they will be funded by IntechOpen.
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