Summary of contemporary randomized trials on LD‐EBRT of painful heel spurs: tested schedules, results, and conclusions.
\\n\\n
These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\\n\\n\\n\\n\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\nInitially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\nThese books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\n\n\n\n\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"9974",leadTitle:null,fullTitle:"E-Learning and Digital Education in the Twenty-First Century",title:"E-Learning and Digital Education in the Twenty-First Century",subtitle:null,reviewType:"peer-reviewed",abstract:"E-learning and digital education approaches are evolving and changing the landscape of teaching and learning at all levels of education throughout the world. Innovation of emerging learning technologies is assisting e-learning and digital education to meet the needs of the 21st century. Due to the digital transformation of everyday practice, the process of learning and education has become more self-paced and accessible at any time from anywhere. The new generations of digital natives are growing up with a set of skills through their engagement with the digital world. In this context, this book includes a collection of chapters to facilitate continuous improvements including flexibility and accessibility in e-learning and digital education by exploring the challenges and opportunities of innovative approaches through the lenses of current theories, policies, and practices.",isbn:"978-1-83962-590-9",printIsbn:"978-1-83962-589-3",pdfIsbn:"978-1-83962-591-6",doi:"10.5772/intechopen.87797",price:139,priceEur:155,priceUsd:179,slug:"e-learning-and-digital-education-in-the-twenty-first-century",numberOfPages:308,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"88b58d66e975df20425fc1dfd22d53aa",bookSignature:"M. Mahruf C. Shohel",publishedDate:"May 18th 2022",coverURL:"https://cdn.intechopen.com/books/images_new/9974.jpg",numberOfDownloads:3768,numberOfWosCitations:0,numberOfCrossrefCitations:4,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:8,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:12,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 12th 2020",dateEndSecondStepPublish:"July 3rd 2020",dateEndThirdStepPublish:"September 1st 2020",dateEndFourthStepPublish:"November 20th 2020",dateEndFifthStepPublish:"January 19th 2021",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"94099",title:"Dr.",name:"M. Mahruf C.",middleName:null,surname:"Shohel",slug:"m.-mahruf-c.-shohel",fullName:"M. Mahruf C. Shohel",profilePictureURL:"https://mts.intechopen.com/storage/users/94099/images/system/94099.png",biography:"Dr. M. Mahruf C. Shohel is currently working at the Doctoral College, University of Surrey, United Kingdom. Prior to his current role, Dr. Shohel worked for several British universities since completing his doctoral studies at the University of Manchester. He is an academic researcher with special interests in education, childhood studies, international development, teachers’ professional development, technology-enhanced learning, and social science research methods. Most recently, he has taught “Digital Learning in Emergencies” for postgraduates at the University of Geneva, Switzerland. He has written extensively on development issues in the Global South and conducted research on disadvantaged children including socioeconomically deprived children, street children, sex workers’ children, and displaced refugee children. Currently, Dr. Shohel is engaged in the fields of education in emergencies, education for sustainable development and global citizenship, emerging technologies in education, students\\' learning journeys and their engagement, and teaching and learning in higher education.",institutionString:"University of Surrey",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"University of Surrey",institutionURL:null,country:{name:"United Kingdom"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1318",title:"Virtual Learning",slug:"virtual-learning"}],chapters:[{id:"74185",title:"Knotworking as an Analytical Tool for Designing E-Learning While Targeting Industry Competence Needs",doi:"10.5772/intechopen.94998",slug:"knotworking-as-an-analytical-tool-for-designing-e-learning-while-targeting-industry-competence-needs",totalDownloads:337,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This chapter outlines challenges and opportunities for teachers in higher education in their design work of e-learning courses targeting practitioner’s competence development of production technology knowledge. Teachers are challenged to develop up-to-date learning material and digitize learning tasks such as virtual labs and machine-related cases that align to workplace knowledge needs. Design work used for campus education is argued to be insufficient to meet e-learning education while targeting industry competence requirements. Teachers and practitioners are in a transformative process when they engage in mutual design work that both encompass a new e-learning situation, and a new target group of experienced practitioners and workplace demands within smart manufacturing. The theoretical concept knotworking, is applied to shed light on the complexity of designing courses for work-integrated e-learning aiming to enhance professional competences. Knotworking refers to tying, untying, and retying together seemingly separate threads of activity. Based on a longitudinal competence development project, this chapter analyzes considerations of an e-learning design practice through the knotworking concept for understanding learning and practices across professional boundaries.",signatures:"Monika Hattinger and Maria Spante",downloadPdfUrl:"/chapter/pdf-download/74185",previewPdfUrl:"/chapter/pdf-preview/74185",authors:[{id:"325287",title:"Ph.D.",name:"Monika",surname:"Hattinger",slug:"monika-hattinger",fullName:"Monika Hattinger"},{id:"325288",title:"Associate Prof.",name:"Maria",surname:"Spante",slug:"maria-spante",fullName:"Maria Spante"}],corrections:null},{id:"73809",title:"Using E-Learning Platform for Enhancing Teaching and Learning in the Field of Social Work at Sultan Qaboos University, Oman",doi:"10.5772/intechopen.94301",slug:"using-e-learning-platform-for-enhancing-teaching-and-learning-in-the-field-of-social-work-at-sultan-",totalDownloads:544,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"This chapter explores the issue of e-learning as a helpful method in higher education institutes and universities in general, and specifically, in the field of social work education. It is based on a study carried out at Sultan Qaboos University, Oman and presents knowledge and attitudes of students towards reliance on the e-learning platforms, such as Moodle, as a helpful educational tool. It highlights that Moodle as an e-learning platform enhances communication between teachers and students, and among students themselves. The chapter presents the findings about the usefulness of Moodle, as an e-learning platform as well as challenges of social work students face during using e-learning platform in their learning. Finally, it offers recommendations to deal with the challenges and highlights implication of the study beyond social work education.",signatures:"Emad Saleh",downloadPdfUrl:"/chapter/pdf-download/73809",previewPdfUrl:"/chapter/pdf-preview/73809",authors:[{id:"224586",title:"Prof.",name:"Emad",surname:"Saleh",slug:"emad-saleh",fullName:"Emad Saleh"}],corrections:null},{id:"74314",title:"The Impact of Online Learning Strategies on Students’ Academic Performance",doi:"10.5772/intechopen.94425",slug:"the-impact-of-online-learning-strategies-on-students-academic-performance",totalDownloads:84,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Higher education institutions have shifted from traditional face to face to online teaching due to Corona virus pandemic which has forced both teachers and students to be put in a compulsory lockdown. However the online teaching/learning constitutes a serious challenge that both university teachers and students have to face, as it necessarily requires the adoption of different new teaching/learning strategies to attain effective academic outcomes, imposing a virtual learning world which involves from the students’ part an online access to lectures and information, and on the teacher’s side the adoption of a new teaching approach to deliver the curriculum content, new means of evaluation of students’ personal skills and learning experience. This chapter explores and assesses the online teaching and learning impact on students’ academic achievement, encompassing the passing in review the adoption of students’ research strategies, the focus of the students’ main source of information viz. library online consultation and the collaboration with their peers. To reach this end, descriptive and parametric analyses are conducted in order to identify the impact of these new factors on students’ academic performance. The findings of the study shows that to what extent the students’ online learning has or has not led to any remarkable improvements in the students’ academic achievements and, whether or not, to any substantial changes in their e-learning competence. This study was carried out on a sample of University College (UAEU) students selected in Spring 2019 and Fall 2020.",signatures:"Khaled Hamdan and Abid Amorri",downloadPdfUrl:"/chapter/pdf-download/74314",previewPdfUrl:"/chapter/pdf-preview/74314",authors:[{id:"327122",title:"Ph.D.",name:"Khaled",surname:"Hamdan",slug:"khaled-hamdan",fullName:"Khaled Hamdan"},{id:"327125",title:"Dr.",name:"Abid",surname:"Amorri",slug:"abid-amorri",fullName:"Abid Amorri"}],corrections:null},{id:"74424",title:"A Model of the Continual Adaptive Online Knowledge Assessment System",doi:"10.5772/intechopen.95295",slug:"a-model-of-the-continual-adaptive-online-knowledge-assessment-system",totalDownloads:216,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"This chapter presents a model of a novel adaptive online knowledge assessment system and tests the efficiency of its implementation. System enables continual and cumulative knowledge assessment, comprised of sequence of at least two interconnected assessments, carried-out throughout a reasonably long period of time. Important characteristics of the system are: (a) introduction of new course topics in every subsequent assessment, (b) re-assessment of earlier course topics in every subsequent assessment iteration, (c) in an adaptive manner, based on student’s achievements during previous assessments. Personalized post-assessment feedback guides each student in preparations for upcoming assessments. The efficiency has been tested on a sample of 78 students. Results indicate that the proposed adaptive system is efficient on an individual learning goal level.",signatures:"Miran Zlatović, Igor Balaban and Željko Hutinski",downloadPdfUrl:"/chapter/pdf-download/74424",previewPdfUrl:"/chapter/pdf-preview/74424",authors:[{id:"324880",title:"Associate Prof.",name:"Igor",surname:"Balaban",slug:"igor-balaban",fullName:"Igor Balaban"},{id:"324883",title:"Dr.",name:"Miran",surname:"Zlatović",slug:"miran-zlatovic",fullName:"Miran Zlatović"},{id:"326259",title:"Prof.",name:"Željko",surname:"Hutinski",slug:"zeljko-hutinski",fullName:"Željko Hutinski"}],corrections:null},{id:"74519",title:"Blended Learning in Higher Education: Faculty Perspective through the Lens of the Planned Behaviour Theory",doi:"10.5772/intechopen.95375",slug:"blended-learning-in-higher-education-faculty-perspective-through-the-lens-of-the-planned-behaviour-t",totalDownloads:597,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:1,abstract:"Before the COVID-19 pandemic, the Teaching and Learning Centre of the University of Liège (Belgium) administered a questionnaire to disclose the main predictors of faculty’s intention to resort, within a timespan of two years, to blended learning in at least one of their courses. The instrument was constructed according to the Theory of Planned Behaviour, a sound conceptual framework for probing intentions and their antecedents. In the responses of 114 faculty members, multiple regression analyses detected that attitude towards blended learning, subjective norm and perceived control explained 73% of the intention to use blended designs for teaching purposes in a not too distant future. Data treatment also singled out beliefs working indirectly in favour of the intention to use hybrid approaches: the inclination to think of blended learning altogether in a student-centred, conformist and pragmatic way. Moreover, respondents who declared having already used blended learning in the past expressed stronger opinions congruent with the constructs of attitude, norm and perceived control. The results also establish that pre-lockdown e-learning practices remained rather basic. A better knowledge of what can facilitate or impair the diffusion of blended learning is of importance for higher education institutions and their staff training efforts.",signatures:"Dominique Verpoorten, Johanne Huart, Pascal Detroz and Françoise Jérôme",downloadPdfUrl:"/chapter/pdf-download/74519",previewPdfUrl:"/chapter/pdf-preview/74519",authors:[{id:"324893",title:"Prof.",name:"Dominique",surname:"Verpoorten",slug:"dominique-verpoorten",fullName:"Dominique Verpoorten"},{id:"334504",title:"Prof.",name:"Pascal",surname:"Detroz",slug:"pascal-detroz",fullName:"Pascal Detroz"},{id:"334506",title:"Dr.",name:"Françoise",surname:"Jérôme",slug:"francoise-jerome",fullName:"Françoise Jérôme"},{id:"334508",title:"Dr.",name:"Johanne",surname:"Huart",slug:"johanne-huart",fullName:"Johanne Huart"}],corrections:null},{id:"75120",title:"Mainstreaming Blended Learning in a Low-Income University",doi:"10.5772/intechopen.96143",slug:"mainstreaming-blended-learning-in-a-low-income-university",totalDownloads:60,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Due to the COVID-19 pandemic, Maseno University (MU) began to consider institutional shift from traditional face-to-face (F2F) instructions to online and blended modes of teaching and learning. The university was able to draw from its experience with adapted flexible and blended learning (FBL) approaches for high enrollment common courses already offered to students on the Learning Management System (LMS). Several questions have been raised: How to preserve what most lecturers consider as most essential — the regular student interaction, the freewheeling give-and-take discussion sessions — if the class cannot be together in the same physical space at the same time? How to make a synchronous activity dependent course and make it work in a completely asynchronous environment? How to handle the practical based subjects on the online platform? And even if the university is able to find acceptable answers to these questions, where would it begin? However, MU did not try to reinvent the wheel. There were already examples of good practice in a number of common courses had been running on the LMS. The available courses already had a blend of both theory and practical base. The university sought assistance from schools and departments that already had parts of their programmes running on the LMS. They were able to tap into their expertise and get introduced to a valuable collection of resources about online distance teaching and learning (ODTL). That, in turn, assisted the university to develop online or blended versions of its regular F2F courses that far surpassed expectations, judging from how well their courses performed, and get ready for any other unexpected circumstance equal or similar to which the world has had to live through the COVID-19 pandemic.",signatures:"Mildred Atieno Ayere",downloadPdfUrl:"/chapter/pdf-download/75120",previewPdfUrl:"/chapter/pdf-preview/75120",authors:[{id:"326206",title:"Dr.",name:"Mildred",surname:"Atieno Ayere",slug:"mildred-atieno-ayere",fullName:"Mildred Atieno Ayere"}],corrections:null},{id:"78804",title:"Using Synchronous vs. Asynchronous Methods during the COVID-19 Pandemic in Malaysia: Preservice and In-Service Teachers’ Perspectives",doi:"10.5772/intechopen.100219",slug:"using-synchronous-vs-asynchronous-methods-during-the-covid-19-pandemic-in-malaysia-preservice-and-in",totalDownloads:178,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The world witnessed the outbreak of the Coronavirus (2019-nCoV) with lockdowns that forced most schools and other educational institutions to close down. Alternative approaches in the form of synchronous and asynchronous methods were adopted to ensure continuity in teaching and learning in this new norm of providing emergency remote education. This chapter aims at presenting preservice and in-service teachers’ views on using synchronous versus asynchronous teaching and learning methods during the COVID-19 pandemic in Malaysia. Data were elicited from three groups of preservice teachers and one group of in-service teachers from three different courses in one teacher education university in Malaysia. Implementation of the e-learning approaches including synchronous and asynchronous sessions was planned carefully based on the course learning outcomes. Important elements such as identification of the learning platform, delivering and conveying information to preservice teachers about the e-learning activities, assessment strategies, attendance, and students’ reflection were taken into consideration.",signatures:"Charanjit Kaur Swaran Singh, Noor Alhusna Madzlan, Eng Tek Ong, Revathi Gopal, Mazura Mastura Muhammad, Siti Shuhaida Shukor, Nor Azmi Mostafa, Tarsame Singh Masa Singh and Mahendran Maniam",downloadPdfUrl:"/chapter/pdf-download/78804",previewPdfUrl:"/chapter/pdf-preview/78804",authors:[{id:"296199",title:"Prof.",name:"Eng Tek",surname:"Ong",slug:"eng-tek-ong",fullName:"Eng Tek Ong"},{id:"325049",title:"Associate Prof.",name:"Charanjit Kaur",surname:"Swaran Singh",slug:"charanjit-kaur-swaran-singh",fullName:"Charanjit Kaur Swaran Singh"},{id:"326098",title:"Dr.",name:"Noor Alhusna",surname:"Madzlan",slug:"noor-alhusna-madzlan",fullName:"Noor Alhusna Madzlan"},{id:"330210",title:"Dr.",name:"Tarsame Singh",surname:"Masa Singh",slug:"tarsame-singh-masa-singh",fullName:"Tarsame Singh Masa Singh"},{id:"330211",title:"Dr.",name:"Mazura Mastura",surname:"Muhammad",slug:"mazura-mastura-muhammad",fullName:"Mazura Mastura Muhammad"},{id:"435927",title:"Dr.",name:"Revathi",surname:"Gopal",slug:"revathi-gopal",fullName:"Revathi Gopal"},{id:"435928",title:"Dr.",name:"Siti Shuhaida",surname:"Shukor",slug:"siti-shuhaida-shukor",fullName:"Siti Shuhaida Shukor"},{id:"435929",title:"Dr.",name:"Nor Azmi",surname:"Mostafa",slug:"nor-azmi-mostafa",fullName:"Nor Azmi Mostafa"},{id:"435930",title:"Dr.",name:"Mahendran",surname:"Maniam",slug:"mahendran-maniam",fullName:"Mahendran Maniam"}],corrections:null},{id:"76147",title:"STEAME Model in Action: Challenges and Solutions in Mastering the Digital Culture",doi:"10.5772/intechopen.97239",slug:"steame-model-in-action-challenges-and-solutions-in-mastering-the-digital-culture",totalDownloads:232,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Due to the digital transformation of everyday practice the process of education has become more complicated than ever before. The role of teachers is more complex as they are not the only source of information and knowledge for their students anymore. Formally or informally, they need to help students develop new competencies and prepare them for the unknown future in the fast-growing and changing labor market. Essential part of these new competencies lies in the interconnected fields of Science, Technology, Engineering and Mathematics. In order for students to obtain them a variety of learning approaches have to be applied in an interdisciplinary educational environment and digital culture. The new generations of digital natives grow up with a set of skills about engaging in the digital world as a basic knowledge. Furthermore, to provide students with more holistic understanding the concepts of Arts are integrated with STEM to become STEAM education. This chapter presents extended education model taking STEM and STEAM to the next level and bringing the Entrepreneurship discipline to create an integrated STEAME curriculum. This chapter presents an integrated STEAME curriculum model, methodology for its implementation and STEAME classroom and environment design as a new education approach to tackle the challenges of the development of skills for the 21st century.",signatures:"Eugenia Kovatcheva and Milena Koleva",downloadPdfUrl:"/chapter/pdf-download/76147",previewPdfUrl:"/chapter/pdf-preview/76147",authors:[{id:"174963",title:"Associate Prof.",name:"Eugenia",surname:"Kovatcheva",slug:"eugenia-kovatcheva",fullName:"Eugenia Kovatcheva"},{id:"327179",title:"MSc.",name:"Milena",surname:"Koleva",slug:"milena-koleva",fullName:"Milena Koleva"}],corrections:null},{id:"76482",title:"Education in Emergencies, Mental Wellbeing and E-Learning",doi:"10.5772/intechopen.97425",slug:"education-in-emergencies-mental-wellbeing-and-e-learning",totalDownloads:240,totalCrossrefCites:3,totalDimensionsCites:3,hasAltmetrics:0,abstract:"The world has been going through an unprecedented situation due to the world-wide health crisis created by the COVID-19 pandemic. It affected all sectors across the globe, including education. This chapter highlights the importance of education in emergencies and how a situation like the COVID-19 pandemic creates challenges alongside opportunities to learn for personal and professional development as well as to ensure mental wellbeing of individuals through e-learning. The chapter explores literature to draw on different perspectives regarding the issues related to effectiveness in handling education and learning in an emergency in addition to preparedness for post and future emergencies. However, it focuses mainly on the role of the education sector in supporting individuals, especially learners and educators during and after emergencies. It also reflects on educational professionals’ work with students during this pandemic i.e. how educational professionals report on their adaptation journey and how the pandemic impacted the ability to serve and engage learners. From the professionals’ best practices to assist students in being successful through online education or hybrid teaching and learning formats, many opportunities arose to shape and reform education for a better future and transform the process of lifelong learning. This chapter outlines strategies, in general, for the education sector, and in particular, institutions and individuals to be better prepared for future emergencies through the opportunities e-learning offers.",signatures:"M. Mahruf C. Shohel, Arif Mahmud, Munira Azhar Urmee, Muhammad Naveed Anwar, Mohammad Mojibur Rahman, Dev Raj Acharya and Md. Ashrafuzzaman",downloadPdfUrl:"/chapter/pdf-download/76482",previewPdfUrl:"/chapter/pdf-preview/76482",authors:[{id:"94099",title:"Dr.",name:"M. Mahruf C.",surname:"Shohel",slug:"m.-mahruf-c.-shohel",fullName:"M. Mahruf C. Shohel"},{id:"329334",title:"Mr.",name:"Mohammad Mojibur",surname:"Rahman",slug:"mohammad-mojibur-rahman",fullName:"Mohammad Mojibur Rahman"},{id:"329631",title:"Dr.",name:"Dev",surname:"Raj Acharya",slug:"dev-raj-acharya",fullName:"Dev Raj Acharya"},{id:"329632",title:"Dr.",name:"Muhammad Naveed",surname:"Anwar",slug:"muhammad-naveed-anwar",fullName:"Muhammad Naveed Anwar"},{id:"335791",title:"Dr.",name:"Arif",surname:"Mahmud",slug:"arif-mahmud",fullName:"Arif Mahmud"},{id:"471612",title:"Dr.",name:"Munira",surname:"Azhar Urmee",slug:"munira-azhar-urmee",fullName:"Munira Azhar Urmee"},{id:"471613",title:"Dr.",name:"Md.",surname:"Ashrafuzzaman",slug:"md.-ashrafuzzaman",fullName:"Md. Ashrafuzzaman"}],corrections:null},{id:"74468",title:"Emergency Remote Teaching during COVID-19 Pandemic: Roles of Educators in Malaysia",doi:"10.5772/intechopen.95071",slug:"emergency-remote-teaching-during-covid-19-pandemic-roles-of-educators-in-malaysia",totalDownloads:503,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"This chapter responds to the needs of educators in preparing to teach online fully due to the pandemic, COVID-19. This scenario becomes the new normal in the teaching and learning process during the COVID-19 pandemic. The main objective of this chapter is to investigate the roles of educators in one public higher learning institution in Malaysia during emergency remote teaching due to the COVID-19 outbreak. Emergency remote teaching is argued to be the answer to the sudden change from face-to-face teaching to a fully online teaching environment. Data for this chapter were collected through an online survey distributed to potential respondents. Adopting a case study and quantitative approach to research, descriptive and inferential statistical analysis were conducted and presented. Preliminary findings suggest two key challenges. Firstly, educators were ready to embark on transformative emergency remote teaching. Nonetheless, they were not sure of the differences between emergency remote teaching and online teaching; these two have different pedagogical approaches. Secondly, and perhaps most importantly, educators were able to use appropriate platforms and applications during the pandemic; however, they did not have ample time to study other platforms and applications. By this, the author argues that some educators have various options to choose from but may lack the knowledge and understanding on how these options work best. In accepting the new normal in teaching and learning, educators must be open to new and creative strategies to engage students during 100 percent online learning.",signatures:"Jowati Juhary",downloadPdfUrl:"/chapter/pdf-download/74468",previewPdfUrl:"/chapter/pdf-preview/74468",authors:[{id:"297346",title:"Dr.",name:"Jowati",surname:"Juhary",slug:"jowati-juhary",fullName:"Jowati Juhary"}],corrections:null},{id:"78446",title:"Developing Professionals: Experience from a Distance Learning Short Course during the COVID-19 Pandemic",doi:"10.5772/intechopen.99923",slug:"developing-professionals-experience-from-a-distance-learning-short-course-during-the-covid-19-pandem",totalDownloads:103,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The developing and delivering of distance education (DE) courses in the stricto sensu reality in nursing arises in order to strengthen training processes in this area to sensitize critical and reflective professional performance. Thus, this book chapter seeks to report the experience of master’s students of the Academic Master’s Course in Nursing at the Regional University of Cariri, Ceará, Brazil, in the construction and tutoring of a course in the DE modality. Descriptive study, of the experience-report type, resulting from the elaboration and development of a short course on COVID-19, offered in the modality of distance learning, by stricto sensu postgraduate students, destined to graduate nursing students. The experience of developing the short course was positive in the sense of teaching practices, and occurred collectively, through discussions and exchange of knowledge between professors and students, in a planned and organized way. Even before operational limitations, the total process of planning, designing, developing and delivering the short course was considered a successful experience. The recognition of the potentialities and difficulties of the process helped formulating and applying the short course, always based on objectives centered on the perspectives of the students and tutors.",signatures:"Beatriz De Castro Magalhães, Adriana Vieira Nobre, Rachel Cardoso De Almeida, Laís Barreto De Brito Gonçalves, Liz Marjorie Batista De Freitas Leite, Maria Do Socorro Vieira Lopes, Jucier Gonçalves Júnior, Evanira Rodrigues Maia and Grayce Alencar Albuquerque",downloadPdfUrl:"/chapter/pdf-download/78446",previewPdfUrl:"/chapter/pdf-preview/78446",authors:[{id:"325872",title:"Dr.",name:"Jucier Gonçalves",surname:"Junior",slug:"jucier-goncalves-junior",fullName:"Jucier Gonçalves Junior"},{id:"347819",title:"MSc.",name:"Beatriz De Castro",surname:"Magalhães",slug:"beatriz-de-castro-magalhaes",fullName:"Beatriz De Castro Magalhães"},{id:"347820",title:"MSc.",name:"Adriana Vieira",surname:"Nobre",slug:"adriana-vieira-nobre",fullName:"Adriana Vieira Nobre"},{id:"347821",title:"MSc.",name:"Rachel Cardoso De",surname:"Almeida",slug:"rachel-cardoso-de-almeida",fullName:"Rachel Cardoso De Almeida"},{id:"347822",title:"MSc.",name:"Laís Barreto De Brito",surname:"Gonçalves",slug:"lais-barreto-de-brito-goncalves",fullName:"Laís Barreto De Brito Gonçalves"},{id:"347824",title:"MSc.",name:"Liz Marjorie Batista De Freitas",surname:"Leite",slug:"liz-marjorie-batista-de-freitas-leite",fullName:"Liz Marjorie Batista De Freitas Leite"},{id:"347825",title:"Dr.",name:"Evanira Rodrigues",surname:"Maia",slug:"evanira-rodrigues-maia",fullName:"Evanira Rodrigues Maia"},{id:"347826",title:"Dr.",name:"Maria Do Socorro Vieira",surname:"Lopes",slug:"maria-do-socorro-vieira-lopes",fullName:"Maria Do Socorro Vieira Lopes"},{id:"347827",title:"Dr.",name:"Grayce Alencar",surname:"Albuquerque",slug:"grayce-alencar-albuquerque",fullName:"Grayce Alencar Albuquerque"}],corrections:null},{id:"77837",title:"Impact of COVID-19 on Dental Education",doi:"10.5772/intechopen.99504",slug:"impact-of-covid-19-on-dental-education",totalDownloads:99,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The COVID-19 pandemic has brought impacts and changes on dental education around the world. People who are in close contact with the COVID-19 patients, including students and teaching staff, are at increased risk of contamination, as they work close to the oral cavity of patients in direct contact with salivary fluids and in closed environment. In addition, social isolation and distancing measures have been adopted by governments, with severe restrictions on dental education. At this moment, students should have the teaching and experience for adequate dental practice, dental educators should provide solutions to resume dental education remotely to ensure the well-being of students, employees and teaching staff. This chapter discusses the impact of the COVID-19 on dental education and the role of emergency remote education in the continuity of face-to-face classes and preclinical and clinical education, in addition to addressing the challenges and the Brazilian reality of teaching-service-community activities.",signatures:"Isla Camilla Carvalho Laureano, Alidianne Fábia Cabral Cavalcanti and Alessandro Leite Cavalcanti",downloadPdfUrl:"/chapter/pdf-download/77837",previewPdfUrl:"/chapter/pdf-preview/77837",authors:[{id:"347672",title:"Associate Prof.",name:"Alessandro",surname:"Leite Cavalcanti",slug:"alessandro-leite-cavalcanti",fullName:"Alessandro Leite Cavalcanti"},{id:"349298",title:"MSc.",name:"Isla Camilla",surname:"Carvalho Laureano",slug:"isla-camilla-carvalho-laureano",fullName:"Isla Camilla Carvalho Laureano"},{id:"349299",title:"Prof.",name:"Alidianne Fábia",surname:"Cabral Cavalcanti",slug:"alidianne-fabia-cabral-cavalcanti",fullName:"Alidianne Fábia Cabral Cavalcanti"}],corrections:null},{id:"74328",title:"Together Apart during the COVID-19 Pandemic: Assessing Students’ Readiness for Online Assessments Using an E-Learning System",doi:"10.5772/intechopen.95097",slug:"together-apart-during-the-covid-19-pandemic-assessing-students-readiness-for-online-assessments-usin",totalDownloads:403,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Electronic learning (e-learning) is an indispensable management system that supports face-to-face, blended, or fully online courses. In January 2020, 258 students in a second-year management course at a regional university were evaluated on their preparedness for online lectures via e-learning. However, by mid-semester, the COVID-19 pandemic halted face-to-face teaching, pushed final assessments to an online modality, and forced some governments to quickly repatriate their students. This chapter evaluates students’ level of e-learning readiness (e-readiness) and whether it had any effect on their performance in the final assessment. The results show that six percent of the cohort had returned to their home country, six percent had no privacy to take their final online assessments, while 31% depended on Wi-Fi. However, although two-thirds of the cohort preferred the online modality, only a third had acceptable levels of e-readiness. E-ready students felt the disruption in their study routine most, while those who were not e-ready found more time to study after the curfew restrictions were in place. E-ready students attempted their final online assessment earlier than those who were not yet e-ready, but the two groups had similar assessment grades. Evaluating students’ level of e-readiness is vital in providing support for those who have challenges with online learning.",signatures:"Glenda H.E. Gay",downloadPdfUrl:"/chapter/pdf-download/74328",previewPdfUrl:"/chapter/pdf-preview/74328",authors:[{id:"225677",title:"Dr.",name:"Glenda",surname:"H.E. Gay",slug:"glenda-h.e.-gay",fullName:"Glenda H.E. Gay"}],corrections:null},{id:"79929",title:"Transnational Education and E-Learning during a Pandemic: Challenges, Opportunities, and Future",doi:"10.5772/intechopen.101089",slug:"transnational-education-and-e-learning-during-a-pandemic-challenges-opportunities-and-future",totalDownloads:179,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Higher education institutions are globally facing unprecedented disruptive trends, which have rapidly changed the landscape of global higher education due to the COVID-19 pandemic. While transnational education (TNE) is increasingly becoming popular as a provision for internationally recognised education at the doorstep of students, the temporary shift from traditional classroom teaching and learning (T&L) to remote online T&L caused by the COVID-19 pandemic has been challenging for all stakeholders to provide the similar student experience as previously. Regarding TNE programmes, the emergency replacement of traditional classrooms with virtual ones has also raised significant challenges of both equity and pedagogy. However, given the current crisis in higher education, TNE can be a cornerstone in rebuilding the post-COVID-19 international education system. This chapter explores the challenges faced by the TNE programmes based on a systematic literature review and information gathered informally from various stakeholders and discusses the opportunities and future impacts in teaching, learning, and student support as the post-COVID-19 educational landscape emerges. It also provides an insight into how a sustainable transnational learning community can be developed for the quality and sustainability of international higher education in this new decade.",signatures:"Atm S. Alam, Ling Ma, Andy Watson, Vindya Wijeratne and Michael Chai",downloadPdfUrl:"/chapter/pdf-download/79929",previewPdfUrl:"/chapter/pdf-preview/79929",authors:[{id:"346849",title:"Dr.",name:"Atm",surname:"Alam",slug:"atm-alam",fullName:"Atm Alam"},{id:"436414",title:"Dr.",name:"Ling",surname:"Ma",slug:"ling-ma",fullName:"Ling Ma"},{id:"436415",title:"Mr.",name:"Andy",surname:"Watson",slug:"andy-watson",fullName:"Andy Watson"},{id:"436416",title:"Dr.",name:"Michael",surname:"Chai",slug:"michael-chai",fullName:"Michael Chai"},{id:"471615",title:"Dr.",name:"Vindya",surname:"Wijeratne",slug:"vindya-wijeratne",fullName:"Vindya Wijeratne"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. 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Nanomaterials",doi:null,correctionPDFUrl:"https://cdn.intechopen.com/pdfs/80612.pdf",downloadPdfUrl:"/chapter/pdf-download/80612",previewPdfUrl:"/chapter/pdf-preview/80612",totalDownloads:null,totalCrossrefCites:null,bibtexUrl:"/chapter/bibtex/80612",risUrl:"/chapter/ris/80612",chapter:{id:"66689",slug:"risk-assessment-and-health-safety-and-environmental-management-of-carbon-nanomaterials",signatures:"Guilherme Lenz e Silva, Camila Viana, Danieli Domingues and Fernanda Vieira",dateSubmitted:null,dateReviewed:"February 26th 2019",datePrePublished:"April 11th 2019",datePublished:"February 19th 2020",book:{id:"8137",title:"Nanomaterials",subtitle:"Toxicity, Human Health and Environment",fullTitle:"Nanomaterials - Toxicity, Human Health and Environment",slug:"nanomaterials-toxicity-human-health-and-environment",publishedDate:"February 19th 2020",bookSignature:"Simona Clichici, Adriana Filip and Gustavo M. do 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Vieira",slug:"fernanda-vieira",email:"fevieira2001@gmail.com",position:null,institution:null},{id:"286151",title:"M.Sc.",name:"Danieli",middleName:"Silva",surname:"Domingues",fullName:"Danieli Domingues",slug:"danieli-domingues",email:"danielisilva@ymail.com",position:null,institution:null}]}},chapter:{id:"66689",slug:"risk-assessment-and-health-safety-and-environmental-management-of-carbon-nanomaterials",signatures:"Guilherme Lenz e Silva, Camila Viana, Danieli Domingues and Fernanda Vieira",dateSubmitted:null,dateReviewed:"February 26th 2019",datePrePublished:"April 11th 2019",datePublished:"February 19th 2020",book:{id:"8137",title:"Nanomaterials",subtitle:"Toxicity, Human Health and Environment",fullTitle:"Nanomaterials - Toxicity, Human Health and Environment",slug:"nanomaterials-toxicity-human-health-and-environment",publishedDate:"February 19th 2020",bookSignature:"Simona Clichici, Adriana Filip and Gustavo M. do 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Vieira",slug:"fernanda-vieira",email:"fevieira2001@gmail.com",position:null,institution:null},{id:"286151",title:"M.Sc.",name:"Danieli",middleName:"Silva",surname:"Domingues",fullName:"Danieli Domingues",slug:"danieli-domingues",email:"danielisilva@ymail.com",position:null,institution:null}]},book:{id:"8137",title:"Nanomaterials",subtitle:"Toxicity, Human Health and Environment",fullTitle:"Nanomaterials - Toxicity, Human Health and Environment",slug:"nanomaterials-toxicity-human-health-and-environment",publishedDate:"February 19th 2020",bookSignature:"Simona Clichici, Adriana Filip and Gustavo M. do Nascimento",coverURL:"https://cdn.intechopen.com/books/images_new/8137.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"64160",title:"Prof.",name:"Simona",middleName:null,surname:"Clichici",slug:"simona-clichici",fullName:"Simona Clichici"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"11492",leadTitle:null,title:"Space Exploration - Advances in Research",subtitle:null,reviewType:"peer-reviewed",abstract:"
\r\n\tThe purpose of the book is to provide information on new scientific findings in space exploration and their application to other fields. Space exploration provides a fundamental source of knowledge that will improve our understanding of nature and its influence on our views. Its achievements will be directed to phenomena that require a proper explanation involving the analysis of data in studies of the solar system together with views on the origin of the universe and its evolution. The book should also contain aspects involved in the physical description of new phenomena and determine the manner in which they modify our present views and the techniques that we employ. Such contributions should also be accompanied by studies of their effects on human activity including the development of devices that will improve global communication. The importance of the book will be properly assessed by the value of its contributions.
\r\n\t
Mathematical statistics has long been widely practiced in many fields of science [1]. Nevertheless, statistical methods have remained remarkably intact ever since the pioneering work [2] of R.A. Fisher and his contemporary scientists early in the twentieth century. Recently however, it has been claimed that most scientific results are wrong [3], due to malpractice of statistical methods. Errors of that kind are not caused by imperfect methodology but rather, reflect lack of understanding and proper interpretation.
\nIn this introductory chapter, a different cause of errors is addressed—the ubiquitous practice of willful ignorance (WI) [4]. Usually it is applied with intent to remedy lack of knowledge and simplify or merely enable application of established statistical methods. Virtually all statistical approaches require complete statistical knowledge at some stage. In practice though, that can hardly ever be established. For instance, Bayes estimation relies upon prior knowledge. Any equal a priori probability assumption (“uninformed prior”) does hardly disguise some facts are not known, which may be grossly deceiving. Uniform distribution is a specific assumption like any other. Willful ignorance of that kind must not be confused with knowledge to which we associate some degree of confidence. It may be better to explore rather than ignore consequences of what is not known at all. That will require novel perspectives on how mathematical statistics is practiced, which is the scope of this book.
\nIncomplete knowledge implies that obtained results may not be unique. That is, results may be ambiguous. Ambiguity de facto means the uncertainty associated with any estimated quantity itself is uncertain. We may adopt a probabilistic view and classify ambiguity as epistemic uncertainty. Ambiguity will here refer to lack of knowledge typically substituted with willful ignorance. Alternatives propelled by different types of willful ignorance can thus be explored to assess ambiguity.
\nA most powerful source of ambiguity is dependencies. Independence is perhaps the most claimed but often the least discussed presumption. Throwing dices or growing crops, as typically studied by the founders of statistics, independence indeed seems plausible. In all the complexity of modern technology of today however, it is anything but evident observations are independent. For instance, meteorological radar observations may share sources of errors, meaning recorded data will be statistically dependent. A problem may then arise if our analysis makes use of, e.g., the maximum likelihood method which utilizes the entire covariance matrix. Most of its entries, all covariances between pairs of observations, are usually not known but bluntly set to zero to enable evaluation. This willful ignorance has the drastic consequence of extinguishing ambiguity and, as will be shown, minimizing the resulting uncertainty. Elementary considerations should provide the valuable insight that even exceedingly small covariances may substantially influence the result: the number of covariance elements is \n
Various attempts have been made to avoid willful ignorance. The method of maximum entropy [5] focuses on the consequences of improper assignments of unknown statistical information. Covariance intersection [6] fuses observations conservatively to a pair of uncorrelated observations with variance \n
Repeating any statistical analysis with various kinds of willful ignorance [on its input], the ambiguity (A) [of its output] can be assessed. Some WI will give large, while others will yield small resulting uncertainty, not necessarily the maximum and minimum, as it is difficult to imagine all possible kinds of WI. Any specific WI will more or less reduce or quench the uncertainty from its maximum. Identifying a model from calibration data \n
Assume we would like to study the evolution of a field over two spatial coordinates, using a model composed of a set of differential equations. The field could refer to meteorology and describe current observations of air pressure or humidity. The initial state may be expanded in the set of basis functions of the appropriate operator, similar to forecasting in numerical weather prediction (NWP) [7]. The basis functions could be thought of as the eigensolutions of a linear operator, which propagates one meteorological state, from one day to another. Neither the interpretation of the field nor the field itself matters for the discussion here. Rather, it is how the uncertainty of the initial state is represented as uncertainty of the distributed eigensolutions of the NWP propagator. This representation will determine the uncertainty of any subsequent forecast, reflecting the past experience in future confidence of predicting the weather. If the forecast uncertainty is lower than our current knowledge reflects, we may falsely reject, e.g., the possibility of experiencing major thunderstorms. In the eye of sailors planning their journey, the forecast uncertainty is the indisputable decision-maker. Studying the uncertainty quenching \n
To enable illustrations, let the eigenstates of the NWP operator of order \n
where the NWP operator propagates the coefficients \n
Without any supplementary information, the variance of the initial measurement should be completely represented by the variance of the initial model state, i.e., \n
Assuming normal distributed measurement noise, the maximum likelihood method [8] yields the parameter covariance given by Eq. (3), which is propagated to uncertainty of the best predictions according to Eq. (4):
\nCombining these relations, the degree of completeness of the representation of uncertainty by the model can be studied:
\nwhere \n
Uncertainty quenching or excessive reduction of uncertainty due to willful ignorance. Dependence on resolution
It should be emphasized that stating independence is fundamentally different than stating the degree of dependence which is unknown. These statements in fact oppose each other, since independence maximizes the available amount of information. Indeed, the Fisher information matrix [9]
\nis additive as \n
Uncertainty is lost for obvious reasons. The question is how much and for what reason. Since the model cannot represent an arbitrary response, it can neither represent an arbitrary variability. This restriction constitutes the very meaning of a “model.” This makes it important to describe the covariance of observations accurately—inappropriate WI may quench uncertainty dramatically.
\nThe additional information represented by the structure of the model could be denoted by the model innovation. It is strongly affected by WI attributed to observations. With increasing resolution \n
If WI of observation covariance instead resembles what the model is able to represent, the model innovation will be the least. Instead of assuming independent observations, introduce a finite long correlation length\\ksi:
\nIncreasing the correlation length\\ksi from zero as in Figure 1 (bottom), the model innovation decreases, and the variance of the prediction \n
It is a different matter if the model is consistent with the observations it was identified from. Model consistency is usually assessed with a statistical residual analysis. In conventional system identification (CSI) [10], the hypothesis is that the [deterministic] model fully explains the observations. Due to sampling variance of the finite uncertain calibration data though, the best estimate of its parameters will be uncertain. The residual analysis explores if the residual is consistent with the sampling uncertainty of the calibration data but without uncertainty associated with the model.
\nThis conjecture of a model without error whatsoever in CSI is questionable. In practice, no model is completely without error. Rather, a finite uncertainty of the model could be regarded as inherited from mismatch to calibration data. If so, the model merely provides a convenient but to a quantifiable degree imperfect basis for expressing uncertain calibration data. The model is utilized to “passively transform” rather than “actively explain” observations to another unknown situation of interest. That intent is typical in, e.g., weather forecasting and product development. Furthermore, the uncertainty of calibration data can often be assessed from the setup of the calibration experiment. In CSI correlation functions are evaluated from a single residual vector, enforcing homoscedasticity and independence of observations. WI of this kind enables the statistical analysis of the residual but often find little support.
\nThe alternative view on model calibration proposed here is that the identified model, composed of its form or structure, parameters, and uncertainty, represents the uncertain calibration data. Model results can thus substitute our observations, to the degree various aspects of the model and observations are consistent. Any given residual is one realization and should relate to its expected variability, with respect to the uncertainties of both the model and the observations it was identified from.
\nThe Mahalanobis distance [6] can be utilized to measure the relative distance between observations and model output, which constitutes the residual \n
The residual covariance matrix defines its principal variations with typical magnitudes \n
The evaluation of \n
Extracting matrices \n
where \n
To maximize the consistency, in the sense of minimizing the Mahalanobis distance, the variance \n
Minimizing the Fisher information matrix under assumption of normality addresses the covariance \n
In practice, no residual projection \n
A potential conflict is inevitable for exceedingly high ratios \n
Current practice of willful ignorance sometimes makes statistics an art of self-delusion [3]. Consequences of applied WI are rarely explored, as only one proposition normally is made without further ado.
\nDistinguishing what is not known from what is assumed is of paramount importance. Not known to any degree should mean that all possibilities that can be imagined also ought to be considered. Otherwise obtained results only exemplify what the most appropriate answer may be, without any indication of the largest possible deviation.
\nOur knowledge is almost never complete. Virtually all existing statistical methods nevertheless require precisely that. Until alternative methodologies exist, WI must fill the gap between what is actually known and what must be known. As illustrated, the consequences of different WI may vary dramatically. Therefore we should select and tweak WI carefully. WI should not relate to our unconfirmed belief, but rather address its consequences.
\nThe proposal of a quantifiable ambiguity proposed here suggests how ramifications of incomplete knowledge might be mitigated with carefully chosen WI: explore all kinds of ignorance that can be imagined. Analyze and collect obtained results in ambiguity intervals, similar to confidence intervals. Another option is to focus on the worst case in a conservative manner. The method of covariance intersection is one example of how that can be exercised. The principle of maximum entropy provides means to maximize the residual uncertainty, to add the least possible amount of information. Minimizing the Fisher information for observations and the Mahalanobis distance for model identification as proposed here is still another kind of conservatism. These methods tackle unknown information with WI and explore its consequences. Finding the most proper WI is indeed nontrivial and calls for genuinely novel approaches.
\nCurrent practice of statistics utilizes WI in many ways, but the specific choice is rarely discussed in depth. One reason could be that statistics was developed in an entirely different context than practiced today, which is rarely acknowledged and probably not fully comprehended. To exemplify, recall that Fisher’s [2] original interpretation of “never” as a finite probability of 5% was just a humble proposal. He urged his readers to adjust “never” to the current context, a piece of advice almost never followed today.
\nPerhaps the reported breakdown of statistics methodologies [3, 4] is due to neglect of ambiguity, driven by a strong tradition of uncritical application of WI. Could this be caused by lack of awareness of its potentially dramatic consequences? Ignorance of limitations of contemporary state-of-the-art methods is hardly new [12]. Ambiguity indeed sets a meta-perspective on statistical analysis that cannot be avoided and thus needs further exploration.
\nAbout 7% of the population >65 years suffer from a painful heel, even though younger people are often affected, too [1]. The most common cause of this symptom is the so‐called “plantar fasciitis” [2]. This term is widely used, although “plantar fasciopathy” or “plantar fasciosis” would be a better description to point out the degenerative nature of the disease. However, as more than 1100 citations in Pubmed quote “plantar fasciitis” (in comparison with only 50), we will use the traditional term in the following.
Plantar fasciitis has been associated with obesity, with acute or chronic work overload, or with work on hard surfaces [2, 3]. It seems that physiological degeneration of the fascia at the calcaneal insertion exacerbates due to repetitive microtraumas caused by vertical compression [4]. This causes inflammatory tissue reactions. As a result, the fascia is thickened with an associated fluid collection to 4.0 mm and more in ultrasonography [5]. Furthermore, this inflammation may trigger bone formation, the so‐called “plantar heel spur.” This process has been studied intensively by Kumai and Benjamin [6]. They proposed three stages of spur growth: “(a) an initial formation of cartilage cell clusters and fissures at the plantar fascia enthesis; (b) thickening of the subchondral bone plate at the enthesis as small spurs form; and (c) development of vertically oriented trabeculae buttressing the proximal end of larger spurs” [6]. The first description of this spur formation and correlation with the clinical symptoms was carried out by Plettner in 1900 [7]. However, not every heel spur is associated with heel pain, as these spurs are found in 11–16% of the normal asymptomatic population [4]. On the other hand, some patients with painful plantar fasciitis do not have a radiographic confirmation of a spur formation.
A similar mechanism (although caused by longitudinal traction and not by vertical compression) of bone formation has been described at the insertion of the Achilles tendon [8].
According to the American clinical practice guidelines from 2010, diagnosis is established by the typical anamnesis and the characteristic localizations of tenderness. Still, weight‐bearing radiographs are also recommended [9].
Single doses of external beam radiotherapy (EBRT) in the range of 0.3–1 Gy are called “low dose EBRT” (LD‐EBRT). These single fractions are applied two or three times a week until a total dose of about 3–6 Gy is reached. Such radiotherapeutic concepts are used for diverse nonmalignant conditions, e.g., osteoarthrosis, tendinopathy, epicondylitis, or bursitis. A comprehensive review of the historical developments in LD‐EBRT for benign diseases is given by Trott [10].
In contrast, EBRT in oncology is characterized by much higher single and total doses. “Normofractionation” describes single doses of 1.8–2 Gy, applied about five times a week. To treat breast cancer, the total doses of about 62 Gy are necessary, in prostate cancer even more than 72 Gy. From a radiobiological point of view, these high cumulative doses are used to induce DNA double strand breaks. Due to errors in a repair mechanism (nonhomologous end joining), dicentric chromosomes can occur. These can result in unfinished mitoses, the so‐called “mitotic catastrophe,” the main mechanism to reduce clonogenic survival in tumor cells [11]. High doses of EBRT induce local inflammation and tissue reactions.
The much lower doses of LD‐EBRT act via different mechanisms. In the last two decades, several anti‐inflammatory effects have been discovered, contrary to the effects of the above‐mentioned high EBRT doses.
Furthermore, doses between 0.1 and 0.5 Gy reduced the adhesion of PBMC significantly to endothelial cells (ECs)
A third mechanism was the suppression of nitric oxide (NO) production in activated macrophages by LD‐EBRT between 0.3 and 1.25 Gy [18]. As the expression of inducible nitric oxide synthases (iNOS) proteins was not altered, the LD‐EBRT seemed to act at the translational or posttranslational level. Furthermore, a dose of 0.5 Gy significantly reduced oxidative burst and superoxide production of stimulated macrophages [19]. A diminished release of reactive oxygen species (ROS) can also contribute to the anti‐inflammatory effects of LD‐EBRT.
Taken together, all of these pathways and mechanisms showed a similar dose dependence with a maximum effect between 0.3 and 0.7 Gy regarding a discontinuous dose‐effect relation [20].
There are several
Since 1937 [21] for decades, large retrospective studies on the efficacy of LD‐EBRT in calcaneodynia have been published (overview in 22). In 1970, one negative randomized trial was reported and heavily criticized but had not been repeated [23]. Starting in the 1980s, patients were systematically clinically examined and interrogated in a structured manner to try to control for diverse risk factors and to compare the efficacy of different fractionation schemes and total doses [24].
It took until the past decade to perform and report prospectively randomized trials to proof the efficacy of LD‐EBRT and to identify the optimal dose fractionation schedule. In the following, we report the design and the results of these trials. Table 1 gives a short overview of the studied dose concepts and the results. Due to methodological reasons, we will describe the studies not following their publications dates, but according to a systematic order.
Since the publication of the first randomized trial on LD-EBRT in 1970, the efficacy of LD‐EBRT was questioned [23]. Goldie et al. randomized 399 patients, however, only nine patients suffered from calcaneodynia. This is why these results cannot be extrapolated to LD‐EBRT of a painful heel spur. Furthermore, endpoints were not clearly defined, and therapy was started in an acute stage of the disease [25].
The landmark study to prove the efficacy of LD‐EBRT was performed by the German cooperative group on the radiotherapy for benign diseases (GCGBD) under the responsibility of Niewald et al. [26]. A very low dose EBRT (6 × 0.1 Gy applied twice a week up to a total dose of 0.6 Gy) was randomized to a standard dose LD‐EBRT (6 × 1 Gy twice a week up to a total dose of 6 Gy). In the case of an unfavorable response after 3 months, the patient was offered a second treatment series (“reirradiation”) applying a standard dose. The dosage of the experimental arm was chosen to examine if very low doses are effective at all. Second, it acted as a placebo irradiation, as a sham irradiation was regarded unethical. LD‐EBRT was applied using a linear accelerator (4‐ to 6‐MV photons) using lateral parallel opposing fields.
Inclusion criteria were tenderness of the calcaneus with a limitation of the painless walking distance and duration of the symptoms for more than 6 months. Furthermore, a radiological proof of a heel spur was required, and the patients had to be least 40 years of age. Patients with previous traumata to the foot, rheumatic or vascular diseases, lymphatic edema, pregnancy, or breastfeeding were excluded. Concomitant therapy with oral analgesics was not limited. However, local injections with steroids during the study period were not permitted.
Initially, 200 patients were planned [27] to detect a difference of 10% in the quality of life (QOL) sum score (SF‐12) [28] and calcaneodynia sum score (CS) [29] (Table 2) with a power of 80% and an error probability of 5%. Furthermore, the visual analogue scale (VAS) to evaluate pain intensity was used. However, after randomization of 66 patients and interim analysis of 62 patients (4 had to be excluded due to a withdrawal of informed consent or violation of the inclusion criteria), the differences in efficacy between the two treatment arms were so pronounced, that the trial was closed early.
Author | Year | N | Standard arm | Experimental arm | Results | Conclusions |
---|---|---|---|---|---|---|
2012 | 66 | 6 × 1 Gy twice a week | 6 × 0.1 Gy | 3 months: VAS/CS/SF12 sig. better with standard | 1. Dose‐response relationship | |
1 year: less second treatment series with standard | 2. Proof of therapeutic effect of LD‐EBRT | |||||
2007 | 130 | 6 × 1 Gy twice a week | 6 × 0.5 Gy | 6 months: CS no sig. differences | 6 × 0.5 Gy as standard fractionation | |
2014 | 457 | 6 × 1 Gy twice a week | 6 × 0.5 Gy | 6 weeks, 2.5 years: VAS/CS no sig. differences | 6 × 0.5 Gy as standard confirmed | |
2015 | 127 | 6 × 1 Gy twice a week | 12 × 0.5 Gy thrice a week | 3 months: VAS/CS/SF12 no sig. differences | Efficacy not increased with 12 × 0.5 Gy standard still 6 × 0.5 Gy |
Summary of contemporary randomized trials on LD‐EBRT of painful heel spurs: tested schedules, results, and conclusions.
Criteria | Extent of symptoms/alteration | Points |
---|---|---|
S = Pain at | 6 / 4 / 2 / 0 | |
(total: 30%) | N = Pain during D = Pain during R = Pain at I = Pain at none = 6 ; slight = 4 ; moderate = 2 ; severe = 0 points ⇨ | 6 / 4 / 2 / 0 6 / 4 / 2 / 0 6 / 4 / 2 / 0 6 / 4 / 2 / 0 |
per single criterion | ||
(total: 15%) | None Orthopedic shoe, insoles, heel cushion One cane or crutch Two canes or crutches ⇨ | 15 10 5 0 |
(total: 20%) | No limitation, maximum professional strain possible Slight limitation, normal professional work possible Moderate limitation, reduced professional activity Severe limitation, daily professional work impossible ⇨ | 20 10 5 0 |
(total: 15%) | No limitation of daily and leisure activities and sports Slightly limitation/reduced leisure activities and sports Moderate limitation/no leisure activities and sports Complete limitation of any daily and leisure activities ⇨ | 15 10 5 0 |
(total: 20%) | No limp, normal walking is possible without a limitation Slightly altered, limp after walking Moderately altered, limp after walking Severely altered, normal walking is impossible ⇨ | 20 10 5 0 |
The mean age of patients was 54 years in the standard dose group and 58 years in the 6 × 0.1 Gy group. Sixty‐one patients had a plantar, one patient a dorsal heel spur. In mean, patients in the standard dose group suffered for 15.3 months before the start of LD‐EBRT, in the 6 × 0.1 Gy group for 18.8 months. Twenty‐one patients had symptoms on both sides. In 28 patients the pain irradiated into the calf, only in 18 patients it was localized to the sole of the foot. Two patients had received surgery for LD‐EBRT.
Three months after therapy VAS values, CS‐ and QOL‐scores were significantly better after the standard dose in comparison with the very low dose treatment arm. The higher pain relief resulted in a better QOL. Twelve months after therapy about 64% of the patients after 6 × 0.1 Gy had to receive a second treatment series due to insufficient treatment results, in comparison with only 17% of the patients in the standard dose treatment group. As the second series was applied with a standard dose (6 × 1 Gy), patients in the 6 × 0.1 Gy group who were reirradiated showed equally favorable results compared with those in the standard‐dose group who did not receive a second course [26]. This is why the second treatment series in this clinical setting acted as a “salvage therapy.” Another interesting finding was that patients with a good response already at 3 months remained stable or even improved at 12 months. Furthermore, this underlines the long‐lasting efficacy of LD‐EBRT.
Acute side effects or long‐term toxicity did not occur.
In conclusion, this randomized trial established a dose‐response‐relationship of the analgesic effect of LD‐EBRT, thus providing a clinical and methodological proof of the efficacy of 6 × 1 Gy LD‐EBRT on the clinical course of painful heel spurs. The early termination of the study was justified due the interim analysis showing significant differences in the clinical outcome between both treatment arms. Still, the trial was not blinded, so both the patients and the staff were aware of the received dose. With modern linear accelerators, a complete blinding of the staff is nearly impossible. The only option would be a shame irradiation with closed collimator jaws, reducing the dose to the unavoidable “leakage” radiation. A much easier and straight forward way was used in the above‐mentioned study by application of a minimal physical dose with 0.1 Gy. Another critical point might be that only half of the patients were examined 12 months after therapy (
Another potential confounder not only in this study but also in all other published prospective and retrospective case series might be that a lot of the patients had received diverse and other conservative therapies before being referred to LD‐EBRT. An interaction between one of these other treatments and LD‐EBRT cannot be ruled out due to methodological reasons. This reflects clinical reality. Still, an interaction between one of these therapies and LD‐EBRT is rather unlikely and counter‐intuitive, as patients were referred to LD‐EBRT after the clinical failure of all the other conservative treatments.
Two randomized studies investigated the efficacy of 0.5 Gy single dose in comparison to 1 Gy.
The first trial was conducted by Heyd et al. [30]. They randomized 130 patients between 6 × 0.5 Gy twice weekly (low dose) and 6 × 1 Gy (standard dose). A linear accelerator was used, applying a single field technique.
Inclusion criteria were clinical signs of a painful heel spur, radiological evidence of spur formation, patient age ≥30 years and a relapse after previous conservative treatments, in patients >45 years LD‐EBRT could be used as the primary treatment. Endpoints of the study were changes in the “original” calcaneodynia score [31], that was documented before LD‐EBRT, at the end of the course, and 6 weeks and 6 months afterward.
One hundred and thirty patients were randomized. Mean age was 58.4 years. A 102 patients suffered from a plantar, one patient from a dorsal, and 27 patients from combined spurs. In mean, patients had been suffering from symptoms for 9.8 months. The symptoms had been present in 58 patients for less than 6 months, in 72 patients for a longer time. In 7 heels LD‐EBRT was the first therapeutic approach.
At the end of LD‐EBRT, 66% in the low dose group vs. 59% in the standard dose experienced an improvement in symptoms, 6 weeks later 80 vs. 85%. At this time point, 1.5% in each group reported an increase in symptoms, 19 vs. 14% no change. No statistically significant differences were noted. In case of insufficient treatment results patients were offered a second EBRT series. Thus 26 vs. 37% were treated a second time. Six weeks after that, 71 vs. 79% of these patients reported a further improvement. Six months after LD‐EBRT 88% of the patients in both groups had an amelioration of their symptoms, the remaining patients reported no change. During the EBRT series a slight increase in pain was reported by 26 vs. 29% of the patients. No other acute or late toxicity occurred.
In conclusion, 6 × 0.5 Gy twice weekly was as effective as 6 × 1 Gy.
These results were confirmed by a second randomized trial [32, 33]. Ott et al. randomized 457 patients between 6 × 0.5 Gy (low dose) and 6 × 1 Gy (standard dose). In contrast to the above‐cited “Heyd‐study” [30] an X‐ray unit (orthovoltage) and not linear accelerators was used. Patients received a single field (6 × 8 cm on the plantar calcaneus) with 150 kV, 15 mA, 1 mm Cu‐filter, with source‐to‐skin distance (SSD) of 40 cm. Six weeks after the LD‐EBRT a second series was offered to patients with an insufficient response. The endpoint was pain reduction. CS score and VAS values were measured before and at the end of LD‐EBRT (early response), 6 weeks (delayed), and 2.5 years (long‐term) afterward.
With a median follow‐up of 32 months the mean VAS values before treatment, for early, delayed, and long‐term response for the 0.5 and 1.0 Gy groups were 65.5 ± 22.1 and 64.0 ± 20.5 (
Taken together, the above‐mentioned studies proofed an equivalent clinical efficacy of 6 × 0.5 Gy in comparison to 6 × 1 Gy, thus defining a new clinical treatment standard with six times 0.5 Gy twice weekly as the minimum effective dose.
Before proofing 0.5 Gy as the new standard single dose, another randomized study tried to increase efficacy in reaching the “old” cumulative dose of 6 Gy with a single dose of 0.5 Gy. Niewald et al. randomized between 6 × 1 Gy twice a week (old “standard dose”) and 12 × 0.5 Gy three times a week (“experimental dose”) [25]. The aim was not just to get comparable results, but to further improve the analgesic effects. Linear accelerators (6 MV photons) applying a lateral opposing field technique were used.
Inclusion and exclusion criteria were quite similar to the ones used in the landmark study [26]: Clinical evidence of a painful heel spur, and duration of the symptoms for more than 6 months; radiological proof of a spur formation; age at least 40 years; Karnofsky‐Index at least 70%. Patients with previous radiotherapy or previous trauma to the foot, rheumatic or vascular diseases, lymphatic edema, pregnancy, breastfeeding, or severe psychiatric disorders were excluded. Concomitant therapy with analgesics was allowed. However, patients receiving surgery or shock wave therapy after randomization were excluded.
Endpoints were the SF‐12 sum score, the CS sum score (Table 2), and VAS. Follow‐up was scheduled every 6 weeks for 1 year.
Two‐hundred and forty patients were calculated to detect a difference of 15% in the VAS and CS score, with a power of 80%, and an error probability of 5%. After randomization of 127 patients and an interim analysis of 107 patients, the study was closed early, as the intended increase in analgesic efficacy by the experimental treatment was very unlikely to be achieved.
The mean age of the patients in the standard group was 56.1 Gy in comparison with 58.1 Gy in the experimental group. The mean duration of symptoms before initiation of LD‐EBRT was 17 vs. 16 months. In 98% of the standard group and 93% of the experimental group a plantar spur was treated, in 2 and 7% a combined (plantar and dorsal) spur.
Results after 3 months have been issued so far [25], longer follow‐up has yet to be published. After 3 months, there were no significant differences neither in the VAS (standard 42.3 vs. experimental 44.4) nor the CS sum score (28 vs. 28.4) nor in the QOL (SF‐12) scores. Although longer follow‐up has to be awaited, a further increase in the analgesic effect by applying 12 × 0.5 Gy three times a week is unlikely. This is why this fractionation schedule is currently not recommended, as it does not follow the “as low as reasonable achievable” principle of radiation protection.
Further reduced single doses in LD‐EBRT (with the exception of 0.1 Gy [26]) have never been tested in a prospectively randomized clinical trial. In radiotherapy of degenerative joint disorders, single doses of about 0.3–0.4 Gy were established by von Pannewitz in the late 1920s and published in 1933 and 1970 [34, 35]. However, two studies on calcaneodynia have raised serious concerns on single doses as low as 0.3 Gy.
Seegenschmiedt et al. analyzed treatment efficacy in 141 patients (170 irradiated heels), who were treated from 1984–1994 with X‐ray units (250 kV/200 kV, 20 mA, 40 cm SSD), applying a single field of 6 × 8 cm [24]. Seventy‐two heels received 12 Gy with 6 × 1 Gy (three times a week) –6 weeks break – 6 × 1 Gy (group A), 50 heels were treated with 10 × 0.3 Gy every day (group B1), and 38 heels 10 × 0.5 Gy every day (group B2). The endpoint was the value of a semiquantitative pain score 3 months and in mean 4 years after LD‐EBRT.
The median age of patients was 55 years in group A and 59 years in group B1/B2. The mean duration of symptoms before LD‐EBRT was 8 months, in one‐third, the symptoms persisted for more than 6 months.
Complete pain remission was achieved in 68–71% of the patients without significant differences between the treatment groups. However, there were differences in the clinical course of patients with partial remission of the symptoms: The best results in these patients were achieved during longer follow‐up in group B1 (10 × 0.5 Gy), followed by group A (6 × 1–6 × 1 Gy), followed by group B2 (10 × 0.3 Gy). The latter group showed a significantly worse amelioration of symptoms than the other groups.
A reduced efficacy was also reported in another retrospective case series, comprising 673 heels treated with a single dose of 0.3 Gy three times weekly up to 1.5 Gy (X‐ray) [36]. In case of insufficient treatment results the patients were offered a second course. After the first treatment, only 13% reported CR, nearly all patients had undergone a second LD‐EBRT.
Taken together, to the best of our current knowledge a single dose of 0.5 Gy is standard of care and should only be modified in controlled clinical trials.
In Table 3 selected contemporary randomized trials and patient series are shown broken down into several factors that might be correlated with treatment efficacy. For a better overview, we did not differentiate between univariate and multivariate analyses. We did not try to collect all ever published data.
Duration of symptoms before start of LD‐EBRT has been shown to be correlated with treatment efficacy in numerous studies.
Muecke et al. analyzed in a retrospective multicenter study 502 patients [22]. Duration of symptoms ≤6 months was associated with 76% treatment success vs. 44% after a history >6 months. Also Seegenschmiedt et al. found in their large collectives a correlation between the duration of heel pain and treatment outcome [24]. A significant influence of duration of symptoms before LD‐EBRT was also reported in 73 heels by Schneider et al. [37]. With a history of 3–6 months, the VAS value was reduced by 85%, 28 months after LD‐EBRT in comparison with a reduction of 58% with a history > 6 months. Similar results were obtained by Hermann et al. in 285 heels comparing <12 month history of pain vs. >12 months [38].
In contrary, another study could not confirm these results [30].
To the best of our knowledge, in no study, an influence of gender on treatment outcome has been confirmed [22, 24, 30, 38, 39]. In contrast to radiotherapy for oncological indications with high doses, efficacy and tolerability of LD‐EBRT seems to be the same concerning gender.
Several studies described a correlation between older age and better treatment results, at least 6 weeks after LD‐EBRT [37]. Age somewhat over 50 years seems to be important: >50 years [40], > 53 [38], or > 58 [22]. For a possible explanation see Section 2.3.7.
However, other studies found no influence of this patient characteristic on treatment outcome [24, 30, 39].
A very precise registration of changes in pain intensity (VAS) was done by Schneider at al. [37]. Sixty‐two patients (73 treated heels) were prospectively scored every week during LD‐EBRT, at the end of therapy, 6 weeks, 28 months, and 40 months later. Additionally, subjective mechanical heel stress during LD‐EBRT was estimated. A linear accelerator (10 MV) was used, applying one single field with a size of 12 × 17 cm. Patients were treated twice a week to a total dose of 5 Gy, with increasing single fraction doses (0.25 – 0.25 – 0.5 – 1 – 1 – 1 – 1 Gy). Mean patient age was 54 years, and all had a radiologically proven plantar spurn, mean symptom duration before LD‐EBRT was 6.5 months. Nearly all patients had received other conservative therapies before LD‐EBRT with insufficient results.
Interestingly, VAS scores decreased continuously during LD‐EBRT: before treatment the mean value was 6.3 ± 1.5, after the first week of LD‐EBRT 6.2 ± 1.8, after the second week 5.5 ± 2 (
In standard schedules with fixed single doses a slight increase in pain during the treatment series was reported by 26% (during 6 × 0.5 Gy) vs. 29% (6 × 1 Gy) of the patients [30]. Unfortunately, a possible correlation of this phenomenon with definite treatment results was not investigated.
Without further quantification, another study (6 × 1 vs. 6 × 0.1 Gy) stated, that this initial increase in symptoms “had no influence on the final pain relief 3 and 12 months after treatment” [26]. Older studies postulated a temporary reduction of the pH value in the irradiated tissues at the beginning of the treatment series, without consequences for the long‐term efficacy of LD‐EBRT [41].
This is contrasted by observations of LD‐EBRT in peritendinitis humeroscapularis [42]. In 73 patients (86 shoulders) initial increase of pain during the treatment course was significantly associated with a good response.
Muecke et al. analyzed in a retrospective multicenter study the influence of different treatment techniques in 502 patients [22]. Treatment failure was defined as pain persistence after LD‐EBRT and recurrence of pain during follow‐up. Treatment with MV (6–10 MV) was a significant prognostic factor for pain relief in multivariate analysis, as MV was associated with an eight‐year event‐free probability of 68 vs. 61% after X‐ray beams (175 kV). There are two possible explanations for this finding: besides the possibility of a random result, the authors postulate a more homogenous dose distribution with MV treatment in comparison with KV [22].
Schneider et al. reported an efficacy of just one‐third after a second LD‐EBRT course (so‐called “re‐irradiation”) in comparison with the effects of the first course [37]. Out of 73 heels treated with 5 Gy LD‐EBRT 18 heels received reirradiation due to insufficient treatment response. However, pain reduction measured by means of changes in VAS shortly after the second course and during long‐term follow‐up was significantly diminished in comparison with the efficacy of the first course (about 30% reduction in pain at the last evaluation vs. 86%).
Similar results were obtained in the large retrospective series (502 patients) by Muecke et al. [22]. Treatment failure was significantly associated with the number of treatment series: eight‐year event‐free probability was about 70% after the first course in comparison with just about 30% after reirradiation.
A systematic study on the efficacy of a reirradiation has been published by Hautmann et al. [43]. Eighty‐three patients (101 heels) with insufficient response to the first course or recurrent pain afterward due to plantar fasciitis (83 heels), or achillodynia (28 heels) received a second LD‐EBRT course in median 10 weeks (range 4 weeks to 63 months) after the first LD‐EBRT. About 75% of the patients were treated with 6 × 1 Gy, the others 6 × 0.5 Gy. The pain was assessed using the numeric rating scale (NRS) before and at the end of LD‐EBRT, 6, and 12 weeks, and 6, 12, and 24 months thereafter.
Before reirradiation NRS values were 6 (interquartile range 5–8), at the end of LD‐EBRT 5 (2–6), 6 weeks later 2 (1–4), at 12 weeks 1 (0–3), at 6 months 0 (0–2), at 12 and 24 months 0 (0–1). Interestingly, not only the patients with recurrent pain after the first course but also patients with insufficient responses to the first course experienced a profound and long‐lasting amelioration of their symptoms after the second course.
This is why a second treatment course should be recommended in case of insufficient efficacy of the first course.
A significant correlation between avoidance of heel stress during LD‐EBRT and efficacy of LD‐EBRT 6 weeks after therapy was reported by Schneider et al. in 73 heels [37]. With a Pearson\'s correlation coefficient of -0.467 (
An intuitive explanation is given by the authors [37]: As patient age was associated with positive treatment results, too, they proposed that older patients are often retired, thus being able to take more care of their heels.
Interestingly, all randomized trials required the radiological proof of a heel spur before including patients into the studies. Furthermore, most of the prospective and retrospective series warranted such an objective sign. However, as a substantial part of the patients suffers from plantar heel pain without having developed a heel spur, LD‐EBRT should be effective in these patients, too.
Hermann et al. analyzed treatment efficacy in 250 patients (285 heels), who received LD‐EBRT predominantly with 6 × 1 Gy [38]. In this series, 33% of the treated heels were without radiological evidence of a spur. In 185 patients a spur was confirmed with a mean length of 6.5 mm (range 0.6–25 mm). Patients without evidence of a plantar heel spur had a significantly higher chance of CR after LD‐EBRT (43 vs. 35%). Furthermore, the length of the spurs correlated directly with treatment outcome. Spurs >6.5 mm had just a 30% chance of experiencing CR in comparison with shorter ones. No statistical differences were found between treatment results of heels without spurs and those with spurs ≤6.5 mm.
Miszczyk et al. reported on 327 patients (623 LD‐EBRT series) mostly treated with X‐ray (180 kV, usually 1mm Cu filters) with single doses of 1.5 Gy (range 1–3 Gy) up to a total dose between 9 and 12 Gy (range 1–45 Gy) [39]. Mean spur size was 9 mm (range 1–30 mm). With a mean follow‐up of 74 months, no correlation between spur size and duration of pain relief was found. Analysis concerning spur length and treatment outcome in itself were unfortunately not reported.
Multivariate logistic regression enables the identification of factors independently predicting treatment outcome. By combining these factors, models can be calculated, that predict treatment outcome with a high probability. An example from the study of Hermann et al. is given in Table 4: in 285 heels treated with 6 × 1 Gy/6 × 0.5 Gy the influences of the patient characteristics age, spur length, and duration of symptoms before LD-EBRT alone and in combination were calculated [38]. The best results were obtained for patients > 53 years, spur length <6 mm, and a duration of symptoms <12 months with a probability for CR of 55% (CI 36–73%) and PR of 38% (CI 22–58%). Without these characteristics, the chance for CR was just 18% (CI 9–33%), for PR 31% (17–48%).
Study (citation) | [30] | [26] | [24] | [37] | [39] | [22] | [38] | [40] | [83] |
---|---|---|---|---|---|---|---|---|---|
Rand | Rand | Prospect | Prospect | Retrospect | Retrospect | Retrospect | Retrospect | Retrospect | |
130 | 66 | 170 | 73 | 623 | 502 | 285 | 161 | 7947 | |
MV | MV | KV | MV | KV | MV, KV | MV | KV | MV, KV | |
calcaneus | calcaneus | calcaneus | entire dorsal and middle foot | insertion of plantar fascia | calcaneus | calcaneus vs. insertion of calcaneus | calcaneus | entire dorsal foot vs. calcaneus vs. insertion of plantar fascia | |
6 × 1 vs. 6 × 0.5 Gy | 6 × 1 Gy vs. 6 × 0.1 Gy | 12, 3, 5 Gy | 5 Gy (increasing single dose) | 1.5 (1–3) up to 9–12 Gy (1–45) | 5–10 × 0.5–1 Gy | 6 × 1 Gy6 × 0.5 Gy | 6 × 1 Gy | 0.3–1.5 Gy; 2–3x weekly 2.5–18.76 Gy | |
History of symptoms | 0 | n.i. | + | + | 0 | + | + | + | + |
Gender | 0 | n.i. | 0 | n.i. | 0 | 0 | 0 | n.i. | n.i. |
Patient\'s age | 0 | n.i. | 0 | + | 0 | + | + | + | n.i. |
Initial worsening of pain during LD‐EBRT | n.i. | n.i. | n.i. | n.i. | n.i. | n.i. | n.i. | n.i. | n.i. |
MV vs. KV | n.i. | n.i. | n.i. | n.i. | n.i. | + | n.i. | n.i. | 0 |
Number of therapy series | n.i. | n.i. | n.i. | + | n.i. | + | n.i. | n.i. | + |
Heel stress during LD‐EBRT | n.i. | 0 | n.i. | + | n.i. | n.i. | n.i. | n.i. | n.i. |
Factors associated with treatment efficacy in contemporary studies.
Patient\'s age >53 | No spur or spur ≤6.5 mm | Duration of symptoms <12 months | Probability of | ||
---|---|---|---|---|---|
No change | Partial remission | Complete remission | |||
1 | 1 | 1 | 0.07 (0.03–0.14) | 0.38 (0.22–0.58) | 0.55 (0.36–0.73) |
1 | 1 | 0 | 0.13 (0.07–0.28) | 0.37 (0.21–0.57) | 0.50 (0.30–0.70) |
1 | 0 | 1 | 0.15 (0.06–0.24) | 0.53 (0.33–0.72) | 0.32 (0.17–0.53) |
1 | 0 | 0 | 0.25 (0.13–0.45) | 0.48 (0.27–0.69) | 0.27 (0.13–0.48) |
0 | 1 | 1 | 0.17 (0.10–0.31) | 0.33 (0.19–0.50) | 0.50 (0.33–0.66) |
0 | 1 | 0 | 0.34 (0.20–0.53) | 0.40 (0.24–0.59) | 0.26 (0.13–0.45) |
0 | 0 | 1 | 0.30 (0.20–0.46) | 0.29 (0.18–0.43) | 0.41 (0.27–0.56) |
0 | 0 | 0 | 0.51 (0.35–0.69) | 0.31 (0.17–0.48) | 0.18 (0.09–0.33) |
Probabilities (95%‐CI) for NC, PR and CR calculated by polytomous logistic regression in dependence of the risk factors age, spur length, and duration of symptoms before LD‐EBRT according to Hermann et al. in a collective of 285 heels treated with 6 × 1/6 × 0.5 Gy (taken from [38]).
In modern radiotherapeutic departments, X‐ray sources are less and less available. This is why nowadays most patients are treated with linear accelerators, which were initially developed for the treatment of oncological diseases. However, these machines can be used in the treatment of benign diseases without any modifications or problems. Due to the high efforts in physical, technical, and organizational quality assurances for the operation of an accelerator or an X-ray source, the concentration on accelerators and their use for all indications is recommended.
For irradiation of the heel, the patient has to be placed on the treatment couch with the feet toward the gantry of the accelerator (so‐called “feet first”). Two different patient positions are widely used. He can be placed in supine position, with the irradiated leg is stretched out, while the other leg is angled. Another option is to place the patient in a lateral decubitus position on the side of the involved heel. Again, the symptomatic leg is stretched, while the contralateral leg is bent, with a cushion placed beneath the knee. Using X‐rays, the ipsilateral knee is bent by 90% and the foot is positioned on the treatment table. One anterior‐posterior (AP) beam is usually applied in this technique.
For the treatment itself, there are also two different options. Irradiation may be given as a single stationary field (SSD 100cm by convention). Alternatively, parallel opposing fields from 0° and 180° gantry position (in decubitus position) or lateral opposing fields (90° and 270° in supine position) are also applicable but take a little bit longer in daily clinical practice. The hypothetical advantage of using two opposing fields is a uniform dose distribution in the entire beam path in the calcaneus (Figure 1). However, there has never been a clinical proof, whether this theoretical assumption translates into any clinical advantage for the patient. When applying opposing fields, the dose is specified according to the ICRU 50 report, normally in the center of the calcaneus.
Dose distribution of two different treatment techniques generated in a treatment planning system (XIO®). In A and B just one single 6 MV photon field (8 × 8 cm) is applied, while C and D shows the dose distribution with two opposing fields from 0 and 180°. In the upper row, the so‐called “beams eye views” are given, while in the lower row the respective dose distributions on an axial CT scan directly at the calcaneal insertion are shown. Note the more uniform dose distribution with opposing fields. The 95% isodose is given as a green line (2.85 Gy). This dose encompasses larger parts of the calcaneal bone in D (opposing fields) than in B (single field). More information is given in Section 2.4.
A third option is the so‐called “plantar field” with the patient lying in prone position. A single field is positioned directly over the plantar insertion/calcaneus, potentially with rotations of the patient table and the gantry to compensate for inclinations of the patients surface in the irradiated field. However, this technique is regarded problematic when using linear accelerators due to the dose build‐up effect in the critical tissue depth. This problem is illustrated in Figure 2: photons with 6 MV reach just the half of the prescribed dose at the skin level, 100% is reached at 1.5 cm tissue depth. This would result in an insufficient dose in the critical structures (plantar fascia and heel spur). To overcome this problem, a silicone flap of about 1 cm diameter must be positioned on the skin before radiation.
Depth curves of different megavoltage energies. Blue 6 MV photons, red 15 MV photons. At the surface of the body/skin (depth 0 mm), only half (or even less with 15 MV) of the prescribed dose is applied. By physical interactions between photons and the tissue/water, there is a steep increase in dose. A 100% is reached at 1.5 cm depth with 6 MV and at about 3 cm depth with 15 MV. KV‐radiation reaches the maximum dose directly under the surface/skin (not shown). More information is given in Section 2.4.
Patients are often sent to the radiotherapist after a long unsuccessful history of diverse conservative treatments. The reason for this is a widespread fear among general practitioners that LD‐EBRT might be associated with severe side effects and risks. These fears are not substantiated, as reactions of the nerves or vessels require much higher doses than used for LD‐EBRT. For example, a dose of 45 Gy in normofractionated oncological therapy is considered to be safe for the spinal cord and therefore daily clinical practice [44]. Peripheral nerves are even more radioresistant. Acute or chronic side‐effects have never been reported in all contemporary studies on LD‐EBRT.
Acute side effects are negligible, as very low doses of ionizing radiation (in comparison with oncological treatments) are applied to a distal extremity. The total dose of LD‐EBRT with 3 or 6 Gy is far too low to cause any acute or late reactions on the skin overlaying the calcaneus. During normofractionated EBRT (single doses of 1.8–2 Gy, treatment on 5 days a week) erythema and mild edema develop at about 30 Gy [45]. Hyperpigmentation occurs at about 45 Gy, moist epitheliolyses at about 50 Gy. A 50–60 Gy might cause telangiectasias years after the therapy. This is why there is no report on acute treatment side effects in LD‐EBRT until now to the best of our knowledge.
About one‐third of the patients might experience a slight increase in pain during LD‐EBRT. In the randomized trial by Heydt et al. this phenomenon was seen in 26% (during 6 × 0.5 Gy) vs. 29% (6 × 1 Gy) [30]. It does not seem to be correlated with treatment outcome; further detailed information is given in Section 2.3.4.
The dose scattered to the male gonads is somewhat higher than to the ovaries. Jansen et al. calculated for 6 × 0.5 Gy about 1.5 mSv received by the testes and 0.75 mSv to the ovaries [46]. Comparable results have repeatedly been measured in the past [47, 48].
Taken together, the dose received by the gonads is insignificant. As the distal extremity is irradiated, scattered dose to the gonads is comparable to normal diagnostic radiological imaging [49]. The hereditary effects of these doses are very small and very likely negligible [46].
Although spermatogonial cells are very radiosensitive, a single dose of at least 100 mSv is needed to induce a temporary failure of spermatogenesis [50]. A single dose of 1000 mSv (equivalent to 1 Gy photon irradiation) results in an azoospermia for 9–18 months [51]. Interestingly, fractionated doses harm these cells even more. A temporary oligospermia is reported after receiving several fractions up to a cumulative dose of 160 mSv [52]. An azoospermia lasting for 14–22 months has been reported for fractionated doses of 620–860 mSv [53]. The actually during LD‐EBRT received testicular dose is about 100 times smaller than the lowest dose causing temporary changes in testicular tissues.
The dose to the testicles can be further reduced by utilizing a special testicular shielding. However, clinically meaningful dose reductions have been only measured in MV treatment of subdiaphragmatic/pelvine lymphatic regions or tumors [54, 55].
The mean lethal dose for human oocytes has been estimated at 2 Gy (2000 mSv) [56]. Permanent ovarian failure after radiotherapy is age dependent: in perimenopausal women, a dose of 6 Gy is sufficient [57], while in younger women up to 20 Gy are tolerated. The dose scattered to the ovaries during LD‐EBRT for calcaneodynia cannot cause such sequelae (0.75 mSv).
Naturally, pregnancy has to be excluded in all premenopausal women before beginning with LD‐EBRT, to avoid any risk to the fetus.
So far, no studies with long‐term observation periods have been published, describing a case of malignancy induced by LD‐EBRT for calcaneodynia. However, induction of malignancies is a stochastic effect of ionizing radiation. This means that there is no threshold dose—in contrast for example to the above‐mentioned reactions of the skin. A photon can accidentally trigger a mutation, which in turn leads to tumor formation many years later. The higher the radiation dose, the higher the probability of such an event occurring.
The best available data on tumor induction of full dose EBRT in oncology has been collected in patients treated with breast cancer. Almost 11,000 patients have been followed for over 20 years. The risk of a radiation‐induced tumor was approx. 1% per decade after radiotherapy [58].
To estimate the risk associated with much lower doses of LD‐EBRT, mathematical models on the basis of epidemiological long‐term observations of atomic bomb victims have been developed by the ICRP [59].
Jansen et al. applied the ICRP model on LD‐EBRT of a painful heel spur [46]. Assumed was a single field entering at the foot sole with a size of 8 × 10 cm, 200 kV photons, SSD 40 cm. For an LD‐EBRT series with 6 × 1 Gy the average attributable lifetime risk for induction of a fatal tumor was calculated to be about 0.5 in a thousand patients. An important risk factor for radiogenic‐induced cancer is the patient\'s age by the time the radiation exposure occurs. The risk is already reduced in the 3rd decade of the patient\'s life, it starts to decrease steadily from the age of 40 [60]. Applying these calculations, the estimated lifetime risk per one thousand patients for a fatal tumor accounts for the age of 25 0.6 (male)/0.8 (female), for the age of 50 0.2/0.3, for the age of 75 0.07/0.1 [46].
However, it must be critically noted that this mathematical model was developed for radiation protection and relates to the exposure of complete organ systems with approx. 1 Gy. Therefore, other groups argue that a significantly lower risk of radiogenic cancer induction— approx. ten times less—should be adopted [49, 61]. Furthermore, taken the new standard scheme with 6 × 0.5 Gy into account, these risks are additionally halved.
This risk (max. 1/1000, very likely much lower) must be seen in relation to the tumor risk of the not additionally radiotherapeutical‐treated population. In 2008, the lifetime risk of a man in Germany to suffer from cancer was 50.7% (25.9% to die from malignancy), in women 42.8% and 20.2% respectively [62].
By limiting the application of LD‐EBRT treatment to patients > 30 years of age, an exposure of the juvenile “relatively higher risk” patient population is avoided.
Traditionally target volume definition has been quite large. Field sizes of 12 × 17cm were treated, including the entire dorsal and middle foot, and not just the calcaneus [37, 82] (Figure 3A).
Field definitions in LD‐EBRT of a painful plantar heel spur/fasciitis. (A) traditional field definition including the entire dorsal and middle foot. (B) In randomized trials and large prospective series commonly used field definition encompassing the entire calcaneus, including insertion of the plantar fascia and the Achilles tendon. (C) Proposed small field definition for localized painful plantar fasciitis/plantar spur, encompassing only the painful area with 2 cm margins extending into the neighboring areas (calcaneus, fascia, fat pad).
In the recent randomized trials and prospective observational studies target volume definition was more restricted and confined to the calcaneus (Figure 3B). “The target volume consisted of the calcaneus and the region of the plantar aponeurosis” [26]. “The ventral margin is corresponding to the ventral surface of the calcaneus, the plantar and dorsal margins are surrounding the soft‐tissue border, and the cranial margin is below the ankle” [30]. “Target volume is the calcaneus, normally with a field size of 6 cm × 8 cm” [32]. “The calcaneus and the plantar aponeurosis were included in the target volume” [25].
In a German national survey 2001 on LD‐EBRT of painful heel spurs the target volume definition “large” (dorsal and middle foot) vs. “small” (entire calcaneus) was not correlated with treatment outcome [83]. Consequently, very large field definitions should be regarded as obsolete.
However, as the pathophysiological cause of calcaneodynia is thought to be a localized inflammatory process (see Section 1), it is questionable, whether the entire calcaneus has to be irradiated (as long as there are not a plantar as well as a painful dorsal spurs). There are some clinical data that support a further restriction of target volume definition.
Field sizes have been given in the study by Miszczyk et al. on 327 patients treated with X‐ray beams [39]. Target volume was “… the insertion of the plantar fascia with a calcaneal spur and a reasonable margin. The field size varied from 27 to 150 cm2 (mean 47 cm2).” However, although not explicitly stated, no correlation was found between field size and duration of pain relief after LD‐EBRT. Treatment efficacy in itself was apparently not investigated.
In the above‐mentioned series of 285 heels Hermann et al. analyzed treatment efficacy in dependence of field sizes, too [38]. The mean field size was 74 cm2. No correlation between field size (smaller vs. larger than 74 cm2) with treatment efficacy was found. Further analyses of small fields (< 6 × 6 cm), medium‐sized fields (36–64 cm2) and larger fields revealed no significant differences.
This is why it seems to suffice to encompass the painful region with 2 cm margins extending into the neighboring areas (calcaneus, fascia, fat pad; Figure 3C). However, this recommendation is deducted from pathophysiological considerations and the above‐mentioned case series. A randomized trial is necessary to proof clinical equivalence of a field definition “entire calcaneus” (Figure 3B) vs. “insertion of the plantar fascia” (Figure 3C).
The optimal fractionation schedule has not been elucidated yet. All randomized trial used twice weekly treatments. Only one experimental arm was scheduled three times a week [25]. In a National Survey in Germany with 146 answering institutions, about 45% applied two fractions and 37.5% three fractions weekly [83].
Interestingly, in the landmark study by von Pannewitz a fractionation schedule of only once per week was established [34]. Until now, there is no proof of a higher efficacy applying LD‐EBRT twice or three times per week.
In radiotherapy of another benign disease (endocrine orbitopathy) a 1 Gy per week over 20 weeks schedule was more effective than the standard schedules (10 × 2 Gy or 10 × 1 Gy every working day) [84]. Although other immunological mechanisms cause endocrine orbitopathy in comparison with plantar fasciitis, there is sufficient clinical evidence to test in a randomized trial different fractionation schedules (twice a week vs. once a week, possibly thrice a week).
Other therapies than LD‐EBRT have been applied in painful heel spur. In the following, just a rough overview can be given.
Different kinds of insoles and foot orthoses have been developed. The goal was to reduce plantar contact pressure and to distribute the pressure uniformly over the whole rearfoot [63]. Magnetic insoles do not seem to provide additional benefit [64]. As a short‐term treatment, low‐Dye taping techniques are often used. However, in a randomized trial only a modest improvement in ‘first‐step’ pain was seen in comparison with sham‐intervention [65].
Manual stretching is often recommended. A systematic review of six studies found only statistically significant differences in comparison with the control in one study combining calf muscle and plantar fascia stretches [66].
Several trials have investigated acupuncture. A systematic review from 2010 showed (limited) evidence for the effectiveness [67]. A randomized trial published in 2014 recruited 84 patients [68]. The authors concluded, that “dry needling provided statistically significant reductions in plantar heel pain, but the magnitude of this effect should be considered against the frequency of minor transitory adverse events.”
Ultrasound therapy has led to questionable results [69], but a randomized trial on cryo‐ultrasound with about 100 patients published in 2014 showed good effectiveness [70].
Low‐level laser light (635 nm), given twice a week for a total of six applications, reduced in a randomized trial VAS scores significantly after 8 weeks in comparison with placebo [71]. However, the study comprised of just 69 patients; other similar studies have not been reported so far.
Extracorporeal shock waves are widely applied. Three metaanalyses comprising at least five randomized trials found significant short‐term pain relief and improved functional outcomes for this therapeutic option [72–74]. Another study compared the analgesic efficacy of ultrasound and shock wave therapy in 47 patients [75]. The results suggested that the shock wave therapy had greater analgesic efficacy.
Another basic approach is the oral administration of nonsteroidal anti‐inflammatory drugs (NSAID) to achieve a symptomatic relief. Injections into the painful area are also recommended. A recent review summarized ten randomized trials on corticosteroid injections into the plantar fascia [76]. A significant effect of the steroids on the pain has been shown. However, it was usually short‐term, lasting 4–12 weeks in duration. No advantage of ultrasound‐guided injection techniques in comparison with palpation guidance was found, and no superiority of one type of corticosteroid over another was seen. A longer lasting pain relief has been suggested by a small randomized trial of botulinum toxin injections [77]. Another option is the injection of autologous platelet‐rich plasma. A recent review identified three randomized trials, all showing promising results [78]. However, a very small trial challenged this method of plasma preparation, as the same clinical effectivity was observed after the injection of whole blood [79].
Different surgical approaches have been developed. Releases of the plantar fascia are done, in some studies combined with a spur resection [80]. Due to a probably faster recovery after surgery with comparable functional results endoscopic procedures are recommended nowadays [81]. Surgery is usually indicated after failure of conservative therapies as the ultimate “salvage‐therapy.”
There is only a limited amount of studies randomizing patients between LD‐EBRT and the above‐mentioned alternative therapies.
Canyilmaz et al. randomized 123 patients between LD‐EBRT (6 × 1 Gy, three times a week) and 1 ml injection of 40 mg methylprednisolone and 0.5 ml 60 mg 1% lidocaine under the guidance of palpation [85]. After 3 and 6 months, VAS values and CS‐scores were compared between both groups. After 3 months, the results in the radiotherapy arm were significantly superior compared with those after injections.
To corroborate these findings, similar studies should be conducted. Furthermore, more studies randomizing LD‐EBRT against other therapies (e.g. extracorporeal shock waves) are needed. A minimum size of 50 patients per treatment arm should be assured to gain more statistically relevant results. Recruiting patients without prior excessive other therapies for these studies would be optimal.
The goal must be an evidence‐based algorithm defining the therapeutic sequence of the different conservative treatment modalities for plantar fasciitis.
LD‐EBRT for painful plantar fasciitis/heel spur is an effective and safe treatment option for patients over 30 years of age and after exclusion of pregnancy. A fractionation of 6 × 0.5 Gy twice weekly up to a total dose of 3 Gy is currently recommended. In the case of an insufficient response a second course can be offered to the patient.
Randomized trials on target volume definition and further optimization of LD‐EBRT fractionation are currently in the process of planning. Further trials to compare the different conservative therapies for plantar fasciitis with each other are necessary to allow the development of an evidence‐based treatment algorithm.
This chapter is dedicated to Professor Gisela Hermann‐Brennecke on the occasion of her 70th birthday.
AP | anterior‐posterior |
CI | confidence interval |
CR | complete remission |
CS | Calcaneodynia score |
Cu | chemical element symbol for copper |
EC | endothelial cells |
GCG‐BD | German Cooperative Group on Radiotherapy for Benign Diseases |
Gy | Gray |
ICRP | International Commission on Radiological Protection |
IL | interleukin |
iNOS | inducible nitric oxide synthases |
KV | kilovoltage |
LD‐EBRT | low dose external beam radiotherapy |
mA | milliampere |
mRNA | messenger ribonuclein acid |
mSv | milliSievert |
MV | megavoltage |
NC | no change |
NF‐κB | nuclear factor kappa B |
NO | nitric oxide |
NSAID | non‐steroidal anti‐inflammatory drug |
PBMC | peripheral blood mononuclear cells |
PR | partial remission |
QOL | quality of life |
ROS | reactive oxygen species |
SSD | skin‐to‐source distance |
TGF‐β1 | transforming growth factor β1 |
VAS | visual analogue scale |
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He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. 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He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. Dr Ventura also holds the positions of Affiliated Professor at Virginia Commonwealth University (Richmond, USA) and Distinguished Adjunct Professor at King Abdulaziz University (Jeddah, Saudi Arabia). Additionally, he is deputy director of the Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI) and heads the Knowledge Discovery and Intelligent Systems Research Laboratory. He has published more than ten books and over 300 articles in journals and scientific conferences. Currently, his work has received over 18,000 citations according to Google Scholar, including more than 2200 citations in 2020. In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. 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He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. 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