IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
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By listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
All three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
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"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
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"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
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In conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
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“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\n
We invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
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Feel free to share this news on social media and help us mark this memorable moment!
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\n
By listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
All three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n
"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n
"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\n
In conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n
“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\n
We invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\n
Feel free to share this news on social media and help us mark this memorable moment!
\n\n
\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"8135",leadTitle:null,fullTitle:"Agricultural Development in Asia - Potential Use of Nano-Materials and Nano-Technology",title:"Agricultural Development in Asia",subtitle:"Potential Use of Nano-Materials and Nano-Technology",reviewType:"peer-reviewed",abstract:"Agricultural Development in Asia - Potential Use of Nano-Materials and Nano-Technology provides interesting research and information on the use of nanomaterials and nanotechnology for sustainable agriculture in Asia. Chapters discuss the potential use of nanomaterials, nanofertilizers, and nanopesticides for sustainable agricultural development; development of a new generation of nanopesticides for crop protection and plant growth-promoting rhizobacteria; the role of allelopathy for sustainable crop production; and the use of plant materials in livestock farming.",isbn:"978-1-83968-137-0",printIsbn:"978-1-83968-136-3",pdfIsbn:"978-1-83968-138-7",doi:"10.5772/intechopen.78083",price:119,priceEur:129,priceUsd:155,slug:"agricultural-development-in-asia-potential-use-of-nano-materials-and-nano-technology",numberOfPages:144,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"a3b5f35c39fb76b1853e4d480457462d",bookSignature:"Md. Asaduzzaman and Mafruha Afroz",publishedDate:"February 2nd 2022",coverURL:"https://cdn.intechopen.com/books/images_new/8135.jpg",numberOfDownloads:1358,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:0,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"August 31st 2020",dateEndSecondStepPublish:"September 28th 2020",dateEndThirdStepPublish:"November 27th 2020",dateEndFourthStepPublish:"February 15th 2021",dateEndFifthStepPublish:"April 16th 2021",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"171564",title:"Dr.",name:"Md",middleName:null,surname:"Asaduzzaman",slug:"md-asaduzzaman",fullName:"Md Asaduzzaman",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9McQAK/Profile_Picture_1630649832129",biography:"Dr. Asaduzzaman is a native of Bangladesh and received a Ph.D. in Bioproduction Science from Tottori University, Japan. He has expertise in hydroponic crop production and is currently working as a senior researcher at the Horticulture Research Centre, Bangladesh Agricultural Research Institute. His main research focuses on the development of hydroponic techniques for horticultural crops in a greenhouse, production of specialty crops under Controlled Environment Agriculture (CEA), and development of specialty dietary components through hydroponic production of vegetables providing human health benefits beyond basic nutrition. His other research project includes studying autotoxicity, a phenomenon of intraspecific allelopathy in vegetables and ornamentals through hydroponics, and developing suitable control measures to overcome it. He has published thirty-one original research articles, five review articles, twenty-two conference proceedings, eight book chapters, and nine edited books. He was awarded the Gold Medal from Bangladesh Agricultural University in 2011 and the 2016 BAS-TWAS Prize for Young Scientists from Bangladesh.",institutionString:"Bangladesh Agricultural Research Institute",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"5",totalChapterViews:"0",totalEditedBooks:"4",institution:{name:"Bangladesh Agricultural Research Institute",institutionURL:null,country:{name:"Bangladesh"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"435587",title:"Dr.",name:"Mafruha",middleName:null,surname:"Afroz",slug:"mafruha-afroz",fullName:"Mafruha Afroz",profilePictureURL:"https://mts.intechopen.com/storage/users/435587/images/system/435587.png",biography:"Dr. Mafruha Afroz is a plant pathologist at the Bangladesh Agricultural Research Institute, Bangladesh, where she has worked for more than 15 years. Dr. Afroz received a Ph.D. in Bacteriology from Ohio State University, USA. Her main research interests are diagnosis and molecular characterization of plant pathogens and their appropriate management, and management of diseases using varietal resistance as well as cultural, chemical, and biological tools. She has published several original research articles in reputed national and international journals.",institutionString:"Bangladesh Agricultural Research Institute",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Bangladesh Agricultural Research Institute",institutionURL:null,country:{name:"Bangladesh"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"27",title:"Agricultural Science",slug:"agricultural-science"}],chapters:[{id:"79171",title:"Potential Applications of Nanotechnology in Agriculture: A Smart Tool for Sustainable Agriculture",doi:"10.5772/intechopen.101142",slug:"potential-applications-of-nanotechnology-in-agriculture-a-smart-tool-for-sustainable-agriculture",totalDownloads:217,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Most of the early uses of nanotechnology have come from material sciences, although applications in agriculture are still expanding. Due to a few comprehensive reviews, we described application of nanomaterials along with their fate in soil and interaction with soil and plant system. From synthesis to metabolism, nano-fertilizers like zinc, silver, selenium, titanium oxide have enhanced the physio-chemical characteristics of crop plants in every manner conceivable. On the other hand, it has the potential to minimize pesticide use by boosting reactivity and surface area of nanoparticles. Nanotechnology in pesticides will, without a doubt, replace the current way of pesticide application because of its efficacy. Nano-based approaches can readily overcome the constraints of conventional soil remediation technologies. While soil nanomaterials mobility has been investigated in a limited number of research studies, it’s likely the most critical gap in knowing the real risk of their transport. As well as enhancing plant nutrient absorption, nanomaterials may also be used to regulate soil microbial activity and stimulate plant defenses. When it comes to shipping food, nanotechnology has made things easier by extending the shelf life of most foods. While it offers tremendous potential for agricultural applications, the health effects of nanoparticles on plants, animals, and humans must be thoroughly investigated.",signatures:"Mohammad Monirul Hasan Tipu, Artho Baroi, Juwel Rana, Shariful Islam, Raunak Jahan, Md. Shipon Miah and Md. Asaduzzaman",downloadPdfUrl:"/chapter/pdf-download/79171",previewPdfUrl:"/chapter/pdf-preview/79171",authors:[{id:"171564",title:"Dr.",name:"Md",surname:"Asaduzzaman",slug:"md-asaduzzaman",fullName:"Md Asaduzzaman"},{id:"441365",title:"Dr.",name:"Mohammad Monirul Hasan",surname:"Tipu",slug:"mohammad-monirul-hasan-tipu",fullName:"Mohammad Monirul Hasan Tipu"},{id:"441366",title:"Dr.",name:"Artho",surname:"Baroi",slug:"artho-baroi",fullName:"Artho Baroi"},{id:"441367",title:"Dr.",name:"Juwel",surname:"Rana",slug:"juwel-rana",fullName:"Juwel Rana"},{id:"441368",title:"Dr.",name:"Shariful",surname:"Islam",slug:"shariful-islam",fullName:"Shariful Islam"},{id:"441369",title:"Dr.",name:"Raunak",surname:"Jahan",slug:"raunak-jahan",fullName:"Raunak Jahan"},{id:"441370",title:"Dr.",name:"Md. Shipon",surname:"Miah",slug:"md.-shipon-miah",fullName:"Md. Shipon Miah"}],corrections:null},{id:"79465",title:"Enhancing the Productivity of Field Crops through Nano-Fertilizer",doi:"10.5772/intechopen.101146",slug:"enhancing-the-productivity-of-field-crops-through-nano-fertilizer",totalDownloads:276,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The growth of agricultural sectors can be maintained by increasing crop productivity through soil, water, and nutrient management. The most important management practice is nutrient management, which is supported by the effective use of nano-technology, especially nano-fertilizers. It is well known that nano-fertilizers are nutrient carriers of nano dimensions ranging from 30 to 40 nm (10−9 m or one-billionth of a meter). Due to their high surface area, they can hold abundant nutrients ions and release them slowly and steadily, commensurate with crop demand. Nano-fertilizers are easily uptaken and assimilated by the plants because of their ease of solubility, stability, controlled release in time, and easy mode of delivery and disposal. Due to nano fertilizers characteristics, different commercial products are available in the market, namely Nanogro, Geohumus, NanoGreen, and Lithovit High Yield fertilizer, which can be demonstrated among the farmers for increasing agricultural performance through soil and nutrient management. Besides, nano-fertilizer has good criteria like disease resistance properties. Nanoparticles of ZnO, CuO, and MgO can kill different fungal infections of crop plants. Though nano-fertilizers can be beneficial for improving agricultural performance, it has a detrimental effect on soil microflora, fauna, animals, and humans. It is associated with several diseases or hazards like high blood pressure, blood clots, stroke, arrhythmia, heart disease, etc. Nano-fertilizer also improves the yield of several field crops like pearl millet, wheat, pomegranate, onion, tomato, soybean, and vegetable crops like spinach and cucumber. Nano fertilizers also have sound capabilities to find the solution against the issues arising in modern agriculture due to conventional fertilizer application. Thus, nano-fertilizer has the potential to improve the yield of several field crops.",signatures:"Rahul Sadhukhan, L. Devarishi Sharma, Suman Sen, Snehashis Karmakar, Koushik Banerjee and Kirtiranjan Baral",downloadPdfUrl:"/chapter/pdf-download/79465",previewPdfUrl:"/chapter/pdf-preview/79465",authors:[{id:"330135",title:"Assistant Prof.",name:"Rahul",surname:"Sadhukhan",slug:"rahul-sadhukhan",fullName:"Rahul Sadhukhan"},{id:"330139",title:"Dr.",name:"L. Devarishi",surname:"Sharma",slug:"l.-devarishi-sharma",fullName:"L. Devarishi Sharma"},{id:"330140",title:"Mr.",name:"Suman",surname:"Sen",slug:"suman-sen",fullName:"Suman Sen"},{id:"330141",title:"Ph.D. Student",name:"Snehashis",surname:"Karmakar",slug:"snehashis-karmakar",fullName:"Snehashis Karmakar"},{id:"330142",title:"Mr.",name:"Koushik",surname:"Banerjee",slug:"koushik-banerjee",fullName:"Koushik Banerjee"},{id:"330145",title:"Mr.",name:"Krittiranjan",surname:"Baral",slug:"krittiranjan-baral",fullName:"Krittiranjan Baral"}],corrections:null},{id:"79600",title:"Nano Pesticides Application in Agriculture and Their Impact on Environment",doi:"10.5772/intechopen.100690",slug:"nano-pesticides-application-in-agriculture-and-their-impact-on-environment",totalDownloads:154,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Environmental contamination and the tolerance developed by the pests, pathogens are some of the environmental issues related to the aimless utilization of chemical pesticides. It has became matter of serious concern for environment, food quality and soil health. Nanotechnology, envisaged as a swiftly emerging field has capability to reform food systems in agriculture. Nanotechnology provides an imperishable solution to these problems by the establishment of nano-pesticides. The functional components or the conveyor molecules used are of nano size. The performance of these nano sized particles is much better the traditional pesticides, as the smaller size aids in proper spreading on the pest surface. Amelioration in solubility of operational components, betterment in stability of formulation, gradual liberation of operational components and enhancement in mobility are some of the paramount advantages of nano particles attributed to the minute size of particles and greater surface area. Thus, nano particles have strengthened activity against target pests in comparison to bulk materials. Furthermore, nano-formulations sustain productive use in agriculture by offering systemic properties, uniform leaf coverage and enhanced soil properties. Despite all the positive aspects, it might have certain negative effects as well, like exposure of humans through distinct routes Viz, exposure to nano pesticides either directly or indirectly like adsorption through skin, or inhalation while breathing air or transfer from one energy level to another by taking contaminated food and water.",signatures:"Malik Asif, Shayesta Islam, Mushtaq A. Malik, Zaffar Mahdi Dar, Amjad Masood, Saima Shafi, Bisma Rashid and Showkat Sidique",downloadPdfUrl:"/chapter/pdf-download/79600",previewPdfUrl:"/chapter/pdf-preview/79600",authors:[{id:"333063",title:"Dr.",name:"Malik",surname:"Aziz",slug:"malik-aziz",fullName:"Malik Aziz"},{id:"333098",title:"Dr.",name:"Zaffar",surname:"Mahdi Dar",slug:"zaffar-mahdi-dar",fullName:"Zaffar Mahdi Dar"},{id:"342728",title:"Prof.",name:"Mushtaq A.",surname:"Malik",slug:"mushtaq-a.-malik",fullName:"Mushtaq A. Malik"},{id:"342729",title:"Ms.",name:"Saima",surname:"Shafi",slug:"saima-shafi",fullName:"Saima Shafi"},{id:"342731",title:"Ms.",name:"Bisma",surname:"Rashid",slug:"bisma-rashid",fullName:"Bisma Rashid"},{id:"342732",title:"Ms.",name:"Shayesta",surname:"Islam",slug:"shayesta-islam",fullName:"Shayesta Islam"},{id:"342733",title:"Mr.",name:"Showkat",surname:"Sidique",slug:"showkat-sidique",fullName:"Showkat Sidique"},{id:"440120",title:"Dr.",name:"Amjad",surname:"Masood",slug:"amjad-masood",fullName:"Amjad Masood"}],corrections:null},{id:"79863",title:"Vital Role of IPFT in Development of New-Generation Pesticide Formulation for Crop Protection: Advancement Overview in Asian Countries",doi:"10.5772/intechopen.101134",slug:"vital-role-of-ipft-in-development-of-new-generation-pesticide-formulation-for-crop-protection-advanc",totalDownloads:171,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"The agricultural sector of Asian countries supports 60% of the global population, accounting one-fifth of the world’s agricultural land. Despite the gap between demand and supply of food is gradually increasing due to the damages caused by insect and other pest attacks on the limited agricultural land, the pest attack has influenced the entire agriculture sector either directly or indirectly, causing socioeconomic losses. To combat, farmers have been using conventional agrochemicals nonjudiciously that lead to adverse effects such as pesticide resistance, environmental contamination, and non-target toxicity. In this regard, new-generation agrochemical formulation techniques are advantageous over conventional pesticides and play a vital role in sustainable agriculture by fulfilling the demand of over-rising food supply to feed the increasing population. These formulations exhibit desired bio-efficacy at lower doses and have minimum possibility to leave pesticide residues in crop products and the environment. Institute of Pesticide Formulation Technology (IPFT), Gurugram, is one of the leading institutes in Asia, which is actively engaged in developing new-generation formulations to deliver safer, efficient, and environment-friendly pesticide formulations. So far, IPFT has developed 60 pesticide formulations and transferred technologies to different agrochemical industries globally. The new-generation formulations developed by IPFT mainly include microemulsion, nanoemulsion, capsulated suspension, nano-encapsulation, an emulsion in water, mixed formulations including several botanical pesticide formulations. The new advancement in pesticide delivery systems is very supportive in combating the crisis faced by the agricultural sector. In this chapter, formulation of different new-generation pesticides and their advancement are summarized.",signatures:"Nusrat Iqbal, Amrish Agrawal, Md. Imteyaz Alam and Jitendra Kumar",downloadPdfUrl:"/chapter/pdf-download/79863",previewPdfUrl:"/chapter/pdf-preview/79863",authors:[{id:"276457",title:"Dr.",name:"Imteyaz",surname:"Alam",slug:"imteyaz-alam",fullName:"Imteyaz Alam"},{id:"317856",title:"Ms.",name:"Nusrat",surname:"Iqbal",slug:"nusrat-iqbal",fullName:"Nusrat Iqbal"},{id:"332608",title:"Dr.",name:"Amrish",surname:"Agrawal",slug:"amrish-agrawal",fullName:"Amrish Agrawal"},{id:"441373",title:"Dr.",name:"Jitendra",surname:"Kumar",slug:"jitendra-kumar",fullName:"Jitendra Kumar"}],corrections:null},{id:"79756",title:"Characterization of Rhizobium and Plant Growth Promoting Rhizobacteria from French Bean Rhizosphere and Their Effect on French Bean Productivity",doi:"10.5772/intechopen.100592",slug:"characterization-of-em-rhizobium-em-and-plant-growth-promoting-rhizobacteria-from-french-bean-rhizos",totalDownloads:208,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"French bean (Phaseolus vulgaris L.) is used profusely by the common people as an alternative diet of protein. The sparse nodulation in French bean mainly may be due to lack of threshold level of specific rhizobial cells in soil at the time of sowing. The isolates streaked on YEMA with BTB changed to yellow color showing the production of acid which is the characteristic of Rhizobium. Utilization of different carbon sources is an efficient tool to characterize the isolates. Plant growth promoting rhizobacteria is the beneficial rhizobacteria inoculation of which increases growth and yield of French bean through different direct and indirect mechanisms. Inoculation of French beans with rhizobial and rhizobacterial isolates found to be improved growth, physiological, quality parameters and grain yield through symbiotic N2-fixation capacity and plant growth promoting abilities. Co-inoculation of rhizobial and rhizobacterial isolates enhanced the growth and grain yield of French bean. These isolates may be used as consortium to improve the growth of French bean, which may reduce the dependency of farmer on chemical fertilizer as well as risk of pollution. In this chapter characterization of Rhizobium and plant growth promoting rhizobacteria and their effect on plant growth has been reviewed.",signatures:"Saroj Kumar Yadav and Kiran P. Raverkar",downloadPdfUrl:"/chapter/pdf-download/79756",previewPdfUrl:"/chapter/pdf-preview/79756",authors:[{id:"332882",title:"Dr.",name:"Saroj Kumar",surname:"Yadav",slug:"saroj-kumar-yadav",fullName:"Saroj Kumar Yadav"},{id:"439497",title:"Dr.",name:"Kiran P.",surname:"Raverkar",slug:"kiran-p.-raverkar",fullName:"Kiran P. Raverkar"}],corrections:null},{id:"79586",title:"Application of Allelopathy in Crop Production",doi:"10.5772/intechopen.101436",slug:"application-of-allelopathy-in-crop-production",totalDownloads:152,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Need for food production has been increasing greatly in recent years throughout the world. The interest on the supply of quality of food has also increased, but a significant loss of crop production was observed annually, especially the main cereal crops, including rice, wheat and maize, due to the presence of weeds accompanying them in the growing season. Allelopathy has emerged as an alternative approach to solve problem agriculture that including: crop rotations, intercropping, crop residue incorporation and aqueous extracts all that used to explore allelopathy for pest management, enhancement of growth and crop production. As will allelopathic consider as weeds, insect and diseases natural control. Secondary metabolites biosynthesis of at high rates have a great role in provides defense against abiotic stresses. In plant rhizosphere allelochemicals exuded improve nutrient acquisition through the processes of solublization; biological nitrification; chelation and selected retention. In this chapter, application of the allelopathic phenomenon in crop production is discussed and his roller in managing agricultural pests and improving the productivity of agricultural systems. It was found that allelochemicals promote plant growth and production at low concentration; however it can suppress the growth if applied at high concentrations, for that can be used allelopathic compounds for weed control by used high concentrations of plant residues or aqueous extracts of plant.",signatures:"Wasan S. Hussain and Mahmoud M. Abbas",downloadPdfUrl:"/chapter/pdf-download/79586",previewPdfUrl:"/chapter/pdf-preview/79586",authors:[{id:"331198",title:"Ph.D.",name:"Wasan S.",surname:"Hussain",slug:"wasan-s.-hussain",fullName:"Wasan S. Hussain"},{id:"331923",title:"MSc.",name:"Mahmoud Magdy",surname:"Abbas",slug:"mahmoud-magdy-abbas",fullName:"Mahmoud Magdy Abbas"}],corrections:null},{id:"76840",title:"The Role of the Livestock Farming Industry in Supporting the Global Agricultural Industry",doi:"10.5772/intechopen.97868",slug:"the-role-of-the-livestock-farming-industry-in-supporting-the-global-agricultural-industry",totalDownloads:180,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The livestock farming industry is a strategic industry and has a very important potential for the advancement of the agricultural industry. The livestock farming industry is an industry that plays a role in providing protein food for most of the world’s population. Not only as a food provider, but also having a very large contribution to the progress of agricultural cultivation in the world. The livestock industry contributes part of the needs of the agricultural industry through the provision of environmentally friendly organic fertilizers. The integration of the livestock farming industry and the agricultural industry is a mutually supportive system. The integration of plants with livestock is basically an agricultural system characterized by a close relationship between plant and livestock components in a farm in a certain area. The bio-mass waste products from the agricultural industry can be used as a source of animal feed or as raw material for compost. The combination of the livestock industry with the agricultural industry provides enormous economic value for the development of the livestock and agricultural sectors. In Indonesia, the concept of integration between the livestock industry and the agricultural industry has been proven to improve the standard of living and economic status of the community. Some important materials will be discussed in more depth in this paper, including: (1) integration between livestock and rice, (2) integration between goats and cacao plants, (3) integration of livestock with oil palm, (4) integration of ruminants with cassava plants, and (5) integration of cattle with horticultural crops. Utilization of livestock and agricultural waste can reduce environmental burdens. Livestock farming industrial waste in the form of manure can be combined with agricultural wastes. This waste can be used as raw material for organic fertilizers which can be used as a fertilizer provider to support the cultivation of food crops, horticulture and plantations. The development of livestock in an area can encourage farmers to fill their vacant land to be planted with forage. Guidance efforts that will be carried out will be oriented towards land conservation. This is done through the arrangement of forage planting. Therefore, this will have a positive impact on increasing forage production. This effort will ultimately support the improvement of feeding patterns, proper land arrangement and being able to reduce the rate of erosion. The existence of livestock will add a source of manure. This is certainly synonymous with increasing land fertility which can provide business opportunities in optimizing land use diversification. The role of livestock in the livestock industry is the main support and complement in the system of integration in the livestock industry-agricultural industry.",signatures:"Muhammad Irfan Said",downloadPdfUrl:"/chapter/pdf-download/76840",previewPdfUrl:"/chapter/pdf-preview/76840",authors:[{id:"331117",title:"Prof.",name:"Muhammad Irfan",surname:"Said",slug:"muhammad-irfan-said",fullName:"Muhammad Irfan Said"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"4552",title:"Soilless Culture",subtitle:"Use of Substrates for the Production of Quality Horticultural Crops",isOpenForSubmission:!1,hash:"0db90197795ffda070bec7ed97064c74",slug:"soilless-culture-use-of-substrates-for-the-production-of-quality-horticultural-crops",bookSignature:"Md. 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\n\t\t\t
1. Introduction
\n\t\t\t
This chapter quantitatively analyzed the biokinetic models of iodine thyroid and the gastrointestinal tract (GI tract) using MATLAB software. Biokinetic models are widely used to analyze the internally absorbed dose of radiation in patients who have undergone a nuclear medical examination, or to estimate the dose of I-131 radionuclide that is absorbed by a critical organ in patients who have undergone radiotherapy (ICRP-30, 1978). In the specific biokinetic model, human organs or tissues are grouped into many compartments to perform calculations. The defined compartments vary considerably among models, because each model is developed to elucidate a unique function of the human metabolic system.
\n\t\t\t
The solutions to the time-dependent simultaneous differential equations that are associated with both the iodine and the GI tract model, obtained using the MATLAB default programming feature, yield much medical information, because the calculations that are made using these equations provide not only the precise time-dependent quantities of the radionuclides in each compartment in the biokinetic model but also a theoretical basis for estimating the dose absorbed by each compartment. The results obtained using both biokinetic models can help a medical physicist adjust the settings of the measuring instrumentation in the radioactive therapy protocol or the radio-sensitivity of the dose monitoring to increase the accuracy of detection and reduce the uncertainty in practical measurement.
\n\t\t\t
In this chapter, MATLAB algorithms are utilized to solve the time-dependent simultaneous differential equations that are associated with two biokinetic models and to define the correlated uncertainties that are related to the calculation. MATLAB is seldom used in the medical field, because the engineering-based definition of the MATLAB parameters reduces its ease of use by unfamiliar researchers. Nevertheless, using MATLAB can greatly accelerate analysis in a practical study. Some firm recommendations concerning future studies on similar topics are presented and a brief conclusion is drawn.
\n\t\t
\n\t\t
\n\t\t\t
2. Iodine thyroid model
\n\t\t\t
\n\t\t\t\t
2.1. Biokinetic model
\n\t\t\t\t
The iodine model simulates the effectiveness of healing by patients following the post-surgical administering of 131\n\t\t\t\t\tI for the ablation of residual thyroid. Following initial treatment (a near-total or total thyroidectomy), most patients are treated with 131\n\t\t\t\t\tI for ablation of the residual thyroid gland (De Klerk et al., 2000; Schlumberger 1998). However, estimates of cumulative absorbed doses in patients and people close to them remains controversial, despite the establishment of the criteria for applying the iodine biokinetic model to a healthy person from the ICRP-30 report. Conversely, the biokinetic model of iodine that is applied following the remnant ablation of the thyroid must be reconsidered from various perspectives, because the gland that is designated as dominant, the thyroid, in (near-) total thyroidectomy patients is the remnant gland of interest (Kramer et al., 2002; North et al., 2001).
\n\t\t\t\t
According to the ICRP-30 report in the biokinetic model of iodine, a typical human body can be divided into five major compartments. They are
The terms qi andλi are the time-dependent quantity of 131I in all compartments and the decay constants between pairs of compartment, respectively (R: physical half life, ST: stomach, BF: body fluid, Th: thyroid, WB: whole body). Accordingly, the quantity of iodine nuclide in the stomach decreases regularly, whereas the quantity change inside the body fluid is complicated because the iodine can be transported from either stomach or whole body into the body fluid and then removed outwardly also from two channels (to thyroid or to excretion directly). The quantity change of iodine nuclides in either thyroid or whole body is comparatively direct since only one channel is defined for inside or outside [Fig. 1]. Since the biological half-lives of iodine, as recommended by ICRP-30 for the stomach, body fluid, thyroid and whole body, are 0.029d, 0.25d, 80d and 12d, respectively, the corresponding decay constants for each variable can be calculated [Tab. 1]. Additionally, the time-dependent quantity of iodine in each compartment is depicted in Fig. 2, and the initial time is the time when the 131I is administered to the patient.
\n\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
λ
\n\t\t\t\t\t\t\t
coeff.
\n\t\t\t\t\t\t\t
Derivation
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
λR\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
0.0862 d\n\t\t\t\t\t\t\t\t-1\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
ln2 / 8.0
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
λST\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
24 d\n\t\t\t\t\t\t\t\t-1\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
ln2 / 0.029
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
λBF1\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
0.832 d\n\t\t\t\t\t\t\t\t-1\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
0.3xln2 / 0.25
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
λBF2\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
1.940 d\n\t\t\t\t\t\t\t\t-1\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
0.7xln2 / 0.25
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
λTh\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
0.0058 d\n\t\t\t\t\t\t\t\t-1\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
ln2 / 120
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
λWB2\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
0.052 d\n\t\t\t\t\t\t\t\t-1\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
0.9xln2 / 12
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
λWB1\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
0.0052 d\n\t\t\t\t\t\t\t\t-1\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
0.1xln2 / 12
\n\t\t\t\t\t\t
\n\t\t\t\t\t
Table 1.
The coefficients of variables for simultaneous differential equations as adopted in this work. The calculation results are theoretical estimations of the time-dependent quantity of iodine in various compartments for a typical body. Additionally, the decay constant for physical half-life of 131\n\t\t\t\t\t\t\tI is indicated as λR and the physical half-life is 8.0 d.
\n\t\t\t
\n\t\t\t
\n\t\t\t\t
2.2. MATLAB algorithms
\n\t\t\t\t
\n\t\t\t\t\tEqs 1-4 can be reorganized as below and solved by the MATLAB program.
\n\t\t\t\t\tFigure 2 plots the derived time-dependent quantities of iodine in various compartments in the biokinetic model. The solid dots represent either the sum of quantities in the body fluid and the whole body, or the thyroid gland. The practical measurement made regarding body fluid and whole body cannot be separated out, whereas the data concerning the thyroid gland are easily identified data collection.
\n\t\t\t
\n\t\t\t
\n\t\t\t\t
2.3. Experiment
\n\t\t\t\t
\n\t\t\t\t\t
2.3.1. Characteristics of patients
\n\t\t\t\t\t
Five patients (4F/1M) aged 37~46 years underwent one to four consecutive weeks of whole body scanning using a gamma camera following the post-surgical administration of 131I for ablation of the residual thyroid. An iodine clearance measurement was made on all five patients before scanning to suppress interference with the data.
\n\t\t\t\t\t
Figure 2.
The theoretical estimation for time-dependent quantities of iodine in various compartments of the biokinetic model.
\n\t\t\t\t
\n\t\t\t\t
\n\t\t\t\t\t
2.3.2. Gamma camera
\n\t\t\t\t\t
The gamma camera (SIEMENS E-CAM) was located at Chung-Shan Medical University Hospital (CSMUH). The gamma camera\'s two NaI 48×33×0.5 cm3 plate detectors were positioned 5 cm above and 6 cm below the patient\'s body during scanning. Each plate was connected to a 2"-diameter 59 Photo Multiplier Tube (PMT) to record the data. Ideally, the two detectors captured ~70% of the emitted gamma ray. Each patient scanned was given a 1.11GBq (30 mCi) 131I capsule for thyroid gland remnant ablation. The 131I capsule was carrier-free with a radionuclide purity that exceeded 99.9% and radiochemical purity that exceeded 95.0%. All radio pharmaceutical capsules were fabricated by Syncor Int., Corp. The coefficient of variance (%CV) of the activity of all capsules from a single batch was less than 1.0%, as verified by spot checks (Chen et al., 2003). Therefore, the position-sensitive gamma ray emitted from the 131I that was administered to patient could be analyzed and plotted.
\n\t\t\t\t
\n\t\t\t\t
\n\t\t\t\t\t
2.3.3. Whole body scanning of patients
\n\t\t\t\t\t
Each patient was treated with 1.11 GBq 131I once weekly for four consecutive weeks, to ensure ablation of the residual thyroid gland. This treatment suppressed the rapid absorption of ultra high doses by normal organs. Post treatment 131I was typically administered six weeks after the thyroidectomy operation. However, thyroid medication was discontinued during the sixth week to reduce the complexity of any side effects. Care was taken to ensure that drugs that were administrated one week before scanning contained no iodine or radiographic contrast agent. Table 2 presents the measured data and the scanning schedule for the first subject for the first week. The schedules for other patients were similar, with only minor modifications. The final column in Tab. 2 presents data obtained from the thigh as ROI. This area was used to determine the pure background for the NaI counting system. Additionally, the body fluid and whole body compartments were treated as a single compartment and re-defined as "remainder" in the empirical evaluation since in-vivo measurements of these compartments were not separable. Therefore, the net counts for the ROI (either the remainder or the thyroid) were simply determined by subtracting either the count in the thigh region plus that in the thyroid areas or that in the thigh area only from the total counts from the entire whole body.
\n\t\t\t\t
\n\t\t\t
\n\t\t\t
\n\t\t\t\t
2.4. Data analysis
\n\t\t\t\t
Data for each patient are analyzed and normalized to provide initial array in MATLAB output format to fit the optimal data for Eqs. 1-4. Additionally, to distinguish between the results fitted in MATLAB and the practical data from each subject, a value, Agreement (AT), is defined as
where Yn(nor. iten.) and Yn(MATLAB) are the normalized intensity that were practically obtained from each subject in the nth acquisition, and that data computed using MATLAB, respectively. N is defined to be between 11 and 17, corresponding to the different counting schedules of the subjects herein.
\n\t\t\t\t
An AT value of zero indicates perfect agreement between analytical and empirical results. Generally, an AT value of less than 5.00 can be regarded as indicating excellent consistency between computational and practical data, whereas an AT within the range 10.00-15.00 may still offer reliable confidence in the consistency between analytical and empirical results (Pan et al., 2000; 2001). Table 3 shows the calculated data for five subjects over four weeks of whole body scanning. As shown in Tab. 3, the T1/2(thy.) and T1/2(BF) are changed from 80d and 0.25d to 0.66±0.50d and 0.52±0.23d, respectively. Yet, the branching ratio from the body fluid compartment to either the thyroid compartment (Ithy.) or the excretion compartment (Iexc.) is changed from 30% or; 70%, respectively to 11.4±14.6% or; 88.4±14.6%, respectively. A shorter biological half-life (80d→0.66d) and a smaller branching ratio from body fluid to remnant thyroid gland (30%→11.4%) also reveal the rapid excretion of the iodine nuclides by the metabolic mechanism in thyroidectomy patients.
\n\t\t\t\t
\n\t\t\t\t\tFigure 3 presents the results computed using MATLAB along with practical measurement for various subjects, to clarify the evaluation of the 131I nuclides of either the thyroid compartment or the remainder. As clearly shown in Fig. 3, the consistency between each calculated curve and practical data for various subjects reveals not only the accuracy of calculation but also the different characteristics of patients’ biokinetic mechanism, reflecting the real status of remnant thyroid glands.
\n\t\t\t
\n\t\t\t
\n\t\t\t\t
2.5. Discussion
\n\t\t\t\t
Defining the biological half-life of iodine in the thyroid compartment without considering the effects of other compartments in the biokinetic model remains controversial. For healthy people, the thyroid compartment dominates the biokinetic model of iodine. In contrast, based on the analytical results, for (near) total thyroidectomy patients, both the body fluid and the thyroid dominate the revised biokinetic model. Additionally, the biological half-life of iodine in the thyroid of a healthy person can be evaluated directly using the time-dependent curve. The time-dependent curve for thyroidectomy patients degrades rapidly because of iodine has a short biological half-life in the remnant thyroid gland. Withholding iodine from the body fluid compartment of thyroidectomy patients rapidly increases the percentage of iodine nuclides detected in subsequent in-vivo scanning.
\n\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
counting No.
\n\t\t\t\t\t\t\t
elapsed time(hrs)
\n\t\t\t\t\t\t\t
whole body
\n\t\t\t\t\t\t\t
thyroid
\n\t\t\t\t\t\t\t
thigh
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
1
\n\t\t\t\t\t\t\t
0.05
\n\t\t\t\t\t\t\t
21504618
\n\t\t\t\t\t\t\t
355224
\n\t\t\t\t\t\t\t
101133
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
2
\n\t\t\t\t\t\t\t
0.25
\n\t\t\t\t\t\t\t
19894586
\n\t\t\t\t\t\t\t
434947
\n\t\t\t\t\t\t\t
219306
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
3
\n\t\t\t\t\t\t\t
0.5
\n\t\t\t\t\t\t\t
22896468
\n\t\t\t\t\t\t\t
754599
\n\t\t\t\t\t\t\t
308951
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
4
\n\t\t\t\t\t\t\t
0.75
\n\t\t\t\t\t\t\t
23417836
\n\t\t\t\t\t\t\t
834463
\n\t\t\t\t\t\t\t
298034
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
5
\n\t\t\t\t\t\t\t
1.00
\n\t\t\t\t\t\t\t
23645836
\n\t\t\t\t\t\t\t
944563
\n\t\t\t\t\t\t\t
316862
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
6
\n\t\t\t\t\t\t\t
2.00
\n\t\t\t\t\t\t\t
21987448
\n\t\t\t\t\t\t\t
1014885
\n\t\t\t\t\t\t\t
311113
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
7
\n\t\t\t\t\t\t\t
3.00
\n\t\t\t\t\t\t\t
18901178
\n\t\t\t\t\t\t\t
1124704
\n\t\t\t\t\t\t\t
260065
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
8
\n\t\t\t\t\t\t\t
4.00
\n\t\t\t\t\t\t\t
18997956
\n\t\t\t\t\t\t\t
1329043
\n\t\t\t\t\t\t\t
245960
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
9
\n\t\t\t\t\t\t\t
5.00
\n\t\t\t\t\t\t\t
19006712
\n\t\t\t\t\t\t\t
1297005
\n\t\t\t\t\t\t\t
242498
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
10
\n\t\t\t\t\t\t\t
6.00
\n\t\t\t\t\t\t\t
16861720
\n\t\t\t\t\t\t\t
1247396
\n\t\t\t\t\t\t\t
204844
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
11
\n\t\t\t\t\t\t\t
7.00
\n\t\t\t\t\t\t\t
16178016
\n\t\t\t\t\t\t\t
1334864
\n\t\t\t\t\t\t\t
191212
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
12
\n\t\t\t\t\t\t\t
8.00
\n\t\t\t\t\t\t\t
14884935
\n\t\t\t\t\t\t\t
1222750
\n\t\t\t\t\t\t\t
175766
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
13
\n\t\t\t\t\t\t\t
32.00
\n\t\t\t\t\t\t\t
7810032
\n\t\t\t\t\t\t\t
1080369
\n\t\t\t\t\t\t\t
70999
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
14
\n\t\t\t\t\t\t\t
56.00
\n\t\t\t\t\t\t\t
3709699
\n\t\t\t\t\t\t\t
949135
\n\t\t\t\t\t\t\t
17926
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
15
\n\t\t\t\t\t\t\t
80.00
\n\t\t\t\t\t\t\t
2100217
\n\t\t\t\t\t\t\t
673606
\n\t\t\t\t\t\t\t
7377
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
16
\n\t\t\t\t\t\t\t
104.00
\n\t\t\t\t\t\t\t
1639266
\n\t\t\t\t\t\t\t
540182
\n\t\t\t\t\t\t\t
4627
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
17
\n\t\t\t\t\t\t\t
128.00
\n\t\t\t\t\t\t\t
1477639
\n\t\t\t\t\t\t\t
429230
\n\t\t\t\t\t\t\t
5457
\n\t\t\t\t\t\t
\n\t\t\t\t\t
Table 2.
The time schedule for, and measured data from, whole body scanning of patient case 5. The last column presents data for the thigh area. This specific area simulated the pure background for the NaI counting system.
\n\t\t\t\t
In a further examination of the theoretical biokinetic model, since 90% of the administered 131I to the whole body (compartment 4) feeds back to the body fluid (compartment 2) and only 30% of the administered 131I in the body fluid flows directly into the thyroid (compartment 3) [Fig. 1], the cross-links between compartments make obtaining solutions to Eqs. 1-4 extremely difficult. Just a small change in the biological half-life of iodine in the thyroid compartment significantly affects the outcomes for all compartments in the biokinetic model. Moreover, the effect of the stomach (compartment 1) on all compartments is negligible in this calculation because the biological half-life of iodine in the stomach is a mere 0.029 day (~40min). The scanned gamma camera counts from the stomach yield no useful data two hours after I-131 is administered, since almost 90% of all of the iodine nuclides are transferred to other compartments. Therefore, analysis of the calculated 131I nuclides in the biokinetic model remains in either the remainder or the thyroid compartment only (Chen et al., 2007).
\n\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
Case No.
\n\t\t\t\t\t\t\t
week
\n\t\t\t\t\t\t\t
T1/2(thy.) (d)
\n\t\t\t\t\t\t\t
T1/2(BF)(d)
\n\t\t\t\t\t\t\t
Ithy (%)
\n\t\t\t\t\t\t\t
Iexc (%)
\n\t\t\t\t\t\t\t
ATthy\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
ATBF\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
ICRP-30
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
80
\n\t\t\t\t\t\t\t
0.25
\n\t\t\t\t\t\t\t
30
\n\t\t\t\t\t\t\t
70
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
1
\n\t\t\t\t\t\t\t
1
\n\t\t\t\t\t\t\t
1.10
\n\t\t\t\t\t\t\t
0.65
\n\t\t\t\t\t\t\t
12.5
\n\t\t\t\t\t\t\t
87.5
\n\t\t\t\t\t\t\t
1.74
\n\t\t\t\t\t\t\t
31.22.
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
2
\n\t\t\t\t\t\t\t
0.50
\n\t\t\t\t\t\t\t
0.50
\n\t\t\t\t\t\t\t
5.0
\n\t\t\t\t\t\t\t
95.0
\n\t\t\t\t\t\t\t
0.60
\n\t\t\t\t\t\t\t
12.58
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
3
\n\t\t\t\t\t\t\t
0.50
\n\t\t\t\t\t\t\t
0.50
\n\t\t\t\t\t\t\t
5.0
\n\t\t\t\t\t\t\t
95.0
\n\t\t\t\t\t\t\t
0.60
\n\t\t\t\t\t\t\t
12.10
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
4
\n\t\t\t\t\t\t\t
0.50
\n\t\t\t\t\t\t\t
0.50
\n\t\t\t\t\t\t\t
5.0
\n\t\t\t\t\t\t\t
95.0
\n\t\t\t\t\t\t\t
0.55
\n\t\t\t\t\t\t\t
6.23
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
2
\n\t\t\t\t\t\t\t
1
\n\t\t\t\t\t\t\t
1.70
\n\t\t\t\t\t\t\t
1.20
\n\t\t\t\t\t\t\t
55.0
\n\t\t\t\t\t\t\t
45.0
\n\t\t\t\t\t\t\t
4.34
\n\t\t\t\t\t\t\t
7.56
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
2
\n\t\t\t\t\t\t\t
1.25
\n\t\t\t\t\t\t\t
0.80
\n\t\t\t\t\t\t\t
32.5
\n\t\t\t\t\t\t\t
67.5
\n\t\t\t\t\t\t\t
5.24
\n\t\t\t\t\t\t\t
25.38
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
3
\n\t\t\t\t\t\t\t
1.10
\n\t\t\t\t\t\t\t
0.55
\n\t\t\t\t\t\t\t
12.5
\n\t\t\t\t\t\t\t
87.5
\n\t\t\t\t\t\t\t
3.21
\n\t\t\t\t\t\t\t
30.13
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
4
\n\t\t\t\t\t\t\t
0.50
\n\t\t\t\t\t\t\t
0.30
\n\t\t\t\t\t\t\t
5.0
\n\t\t\t\t\t\t\t
95.0
\n\t\t\t\t\t\t\t
1.20
\n\t\t\t\t\t\t\t
35.90
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
3
\n\t\t\t\t\t\t\t
1
\n\t\t\t\t\t\t\t
0.15
\n\t\t\t\t\t\t\t
0.40
\n\t\t\t\t\t\t\t
5.0
\n\t\t\t\t\t\t\t
95.0
\n\t\t\t\t\t\t\t
0.53
\n\t\t\t\t\t\t\t
8.93
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
2
\n\t\t\t\t\t\t\t
0.15
\n\t\t\t\t\t\t\t
0.40
\n\t\t\t\t\t\t\t
5.0
\n\t\t\t\t\t\t\t
95.0
\n\t\t\t\t\t\t\t
0.22
\n\t\t\t\t\t\t\t
2.07
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
3
\n\t\t\t\t\t\t\t
0.15
\n\t\t\t\t\t\t\t
0.40
\n\t\t\t\t\t\t\t
5.0
\n\t\t\t\t\t\t\t
95.0
\n\t\t\t\t\t\t\t
0.10
\n\t\t\t\t\t\t\t
3.64
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
4
\n\t\t\t\t\t\t\t
0.15
\n\t\t\t\t\t\t\t
0.40
\n\t\t\t\t\t\t\t
5.0
\n\t\t\t\t\t\t\t
95.0
\n\t\t\t\t\t\t\t
0.70
\n\t\t\t\t\t\t\t
7.56
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
4
\n\t\t\t\t\t\t\t
1
\n\t\t\t\t\t\t\t
0.25
\n\t\t\t\t\t\t\t
0.25
\n\t\t\t\t\t\t\t
5.0
\n\t\t\t\t\t\t\t
95.0
\n\t\t\t\t\t\t\t
0.62
\n\t\t\t\t\t\t\t
27.65
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
5
\n\t\t\t\t\t\t\t
1
\n\t\t\t\t\t\t\t
1.25
\n\t\t\t\t\t\t\t
0.50
\n\t\t\t\t\t\t\t
5.0
\n\t\t\t\t\t\t\t
95.0
\n\t\t\t\t\t\t\t
1.74
\n\t\t\t\t\t\t\t
5.79
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
Average
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
0.66±0.50
\n\t\t\t\t\t\t\t
0.52±0.23
\n\t\t\t\t\t\t\t
11.4±14.6
\n\t\t\t\t\t\t\t
88.4±14.6
\n\t\t\t\t\t\t\t
1.52±1.54
\n\t\t\t\t\t\t\t
14.05±11.01
\n\t\t\t\t\t\t
\n\t\t\t\t\t
Table 3.
The reevaluated results for five patients in this work. The theoretical data quoted from ICRP-30 report is also listed in the first row for comparing.
\n\t\t\t
\n\t\t
\n\t\t
\n\t\t\t
3. Gastrointestinal tract model
\n\t\t\t
The gastric emptying half time (GET) of solid food in 24 healthy volunteers is evaluated using the gamma camera method. The GET of solids is used to screen for gastric motor disorders and can be determined using many approaches, among which the gamma camera survey is simple and reliable. Additionally, scintigraphic gastric emptying tests are used extensively in both academic research and clinical practice, and are regarded as the gold-standard for evaluating gastric emptying (Minderhoud et al., 2004; Kim et al., 2000). The GET can also be estimated by monitoring the change in the concentration of an ingested tracer in the blood, urine, or breath, since the tracer is rapidly absorbed only after it leaves the stomach. The tracer, the paracetamol absorption approach and the 13C-octanoate breath test (OBT), all support convenient means of evaluating GET. However, the breath test yields only a convolution index of GE, although it requires no gamma camera and can be performed at the bedside (Sanaka et al., 1998; 2006).
\n\t\t\t
Figure 3.
The time-dependent intensity of either whole body plus body fluid compartments or thyroid compartment from the optimized results of revised biokinetic model of iodine. The various data from in-vivo scanning of 5 patients are also included.
\n\t\t\t
The use of a gamma camera to survey the absorption by subjects of Tc-99m radionuclide-labeled products satisfies the criteria for the application of the GI tract biokinetic model, because the short physical half life of Tc-99m is such that a limited dose is delivered. In this study, the revised GET of solids is determined from several in-vivo measurements made of healthy volunteers. Twenty-four healthy volunteers underwent a 5 min. scan from neck to knee once every 30 min. for six hours using a gamma camera. Measured data were analyzed and normalized as input data to a program in MATLAB. The revised GET of solids for volunteers differed significantly from those obtained using a theoretical simulation that was based on the ICRP-30 recommendation.
\n\t\t\t
\n\t\t\t\t
3.1. Biokinetic model
\n\t\t\t\t
According to the ICRP-30 report, the biokinetic model of the GI tract divides a typical human body into five major compartments, which are
\n\t\t\t\t\tEquations 6-9 are the simultaneous differential equations that specify the time-dependent correlation among the quantities of the radio-activated Tc-99m nuclides in the compartments.
\n\t\t\t\t
Figure 4.
Biokinetic model of Gastric Intestine Tract for a standard healthy man. The model is recommended by the ICRP-30 report.
The terms qi and λi are defined as the time-dependent quantities of radionuclide, Tc-99m, and the biological half-emptying constants, respectively, for the compartments. λR is the physical decay constant of the Tc-99m radionuclide.
\n\t\t\t\t
Since the biological half lives of Tc-99m, given by ICRP-30, in the stomach, small intestine, upper large intestine and lower large intestine are 0.029d, 0.116d, 0.385d and 0.693d, respectively, the corresponding half-emptying constants can be calculated, and are presented in Fig. 4. Additionally, λb is the metabolic removal rate and equals [f1×λSI/(1-f1)]. This term varies with the chemical compound and is 0.143 for Tc-99m nuclides.
\n\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
λ
\n\t\t\t\t\t\t\t
Half-emptying constant
\n\t\t\t\t\t\t\t
Derivation
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
λR\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
2.77 d-1\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
(ln2 / 6.0058) × 24
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
λST\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
24 d-1\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
ln 2 / 0.029
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
λSI\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
6 d-1\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
ln 2 / 0.116
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
λULI\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
1.8 d-1\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
ln 2 / 0.385
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
λLLI\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
1 d-1\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
ln 2 / 0.693
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
λb\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
1 d-1\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
0.143×6 / (1-0.143)
\n\t\t\t\t\t\t
\n\t\t\t\t\t
Table 4.
The coefficients of variables for simultaneous differential equations as adopted in this work. The calculation results are theoretical estimations of the time-dependent quantity of Tc-99m in various compartments for a typical body. Additionally, the decay constant for physical half life of Tc-99m is indicated as λR and the physical half-life is 6.0058 h.
\n\t\t\t
\n\t\t\t
\n\t\t\t\t
3.2. MATLAB algorithms
\n\t\t\t\t
\n\t\t\t\t\tEqs 6-9 can be reorganized again as below and solved by the MATLAB program.
\n\t\t\t\t\tFigure 5 shows the time-dependent amount of Tc-99m in each compartment, and the initial time is defined as the time when a Tc-99m dose is administered to the volunteer. The results can be calculated and plotted using a program in MATLAB.
\n\t\t\t
\n\t\t\t
\n\t\t\t\t
3.3. Experiment
\n\t\t\t\t
\n\t\t\t\t\t
3.3.1. Characteristics of volunteers
\n\t\t\t\t\t
Twenty-four healthy volunteers (13F/11M) aged 19~75 years underwent six continuous hours of whole body scanning using a gamma camera after they had ingested Tc-99m- labeled phytate with solid food.
\n\t\t\t\t
\n\t\t\t\t
\n\t\t\t\t\t
3.3.2. Tc-99m-labeled phytate solid food
\n\t\t\t\t\t
The test meal comprised solid food and a cup of 150 ml water that contained 5% dextrose. The solid food was two pieces of toast and a two-egg-omelet. The two eggs were broken, stirred and mixed with 18.5 MBq (0.5 mCi) Tc-99m-labeled phytate. Each omelet was baked in an oven for 20 min at 250 0C, and then served to a volunteer. Each volunteer had fasted for at least eight hours before eating the meal and finished it in 20 minutes, to avoid interference with the data.
\n\t\t\t\t\t
Figure 5.
The theoretical estimation for time-dependent amounts of Tc-99m in various compartments of the biokinetic model.
\n\t\t\t\t
\n\t\t\t\t
\n\t\t\t\t\t
3.3.3. Gamma camera
\n\t\t\t\t\t
The gamma camera (SIEMENS E-CAM) was located at the Department of Nuclear Medicine, TaiChung Veterans General Hospital (TVGH). The camera\'s two NaI (48×33×0.5 cm3) plate detectors were positioned 5 cm above and 6 cm below the volunteer\'s body during scanning. Each plate was connected to a 2"-diameter 59 Photo Multiplier Tube (PMT) to record data. The two detectors captured ~70% of the emitted gamma rays.
\n\t\t\t\t
\n\t\t\t\t
\n\t\t\t\t\t
3.3.4. Whole body scanning of volunteers
\n\t\t\t\t\t
Each volunteer underwent his/her first gamma camera scan immediately after finishing the meal. The scan protocol was as follows; supine position, energy peak of 140 keV (window: 20%), LEHS collimator, 128×128 matrix, and scan speed of 30 cm/min. over a distance of 150 cm (~5 min. scan from neck to knee) for 5 min. every half hour. The complete scan took six hours. Thirteen sets of data were recorded for every volunteer for analysis. The regions of interest (ROIs) of the images in the subsequent analysis were
\n\t\t\t\t\t
whole body, WB,
stomach, ST, and
small intestine, upper large intestine and lower large intestine, SI+ULI+LLI.
\n\t\t\t\t\t
The data that were obtained from SI could not be separated from those obtained from ULI or LLI, whereas the data for ST were easily distinguished during the collection of data. Therefore, the SI, ULI, and LLI data were summed in the data analysis.
\n\t\t\t\t\t
Figure 6.
The time dependent curve of ST and SI+ULI+LLI for males and females, respectively. The inconsistence in comparing the theoretical calculation and practical evaluation is significant.
\n\t\t\t\t
\n\t\t\t
\n\t\t\t
\n\t\t\t\t
3.4. Data analysis
\n\t\t\t\t
\n\t\t\t\t\tTable 5 shows the results that were obtained for 24 healthy volunteers. The first row includes theoretical recommendations in the ICRP-30 report for comparison. The results are grouped into male and female, and each volunteer is indicated. The GET is the effective half life of Tc-99m in the stomach. It equals the reciprocal of the sum of the reciprocal of the biological half life and that of the radiological half life (GET-1= T1/2eff(ST)-1= [T1/2(Tc-99m)-1 + T1/2(ST)-1]). The biological half lives in the stomach T1/2(ST) and small intestine T1/2(SI) in
\n\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
Case No.
\n\t\t\t\t\t\t\t
Sex
\n\t\t\t\t\t\t\t
T1/2(ST) Min.
\n\t\t\t\t\t\t\t
T1/2(SI) Min.
\n\t\t\t\t\t\t\t
T1/2(ULI) Min.
\n\t\t\t\t\t\t\t
T1/2(LLI) Min.
\n\t\t\t\t\t\t\t
T1/2(b) Min.
\n\t\t\t\t\t\t\t
ATST %
\n\t\t\t\t\t\t\t
ATLSI %
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
ICRP-30
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
41.8
\n\t\t\t\t\t\t\t
167.0
\n\t\t\t\t\t\t\t
554.5
\n\t\t\t\t\t\t\t
998.0
\n\t\t\t\t\t\t\t
998.0
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
1
\n\t\t\t\t\t\t\t
F
\n\t\t\t\t\t\t\t
166.4
\n\t\t\t\t\t\t\t
199.6
\n\t\t\t\t\t\t\t
554.5
\n\t\t\t\t\t\t\t
998.0
\n\t\t\t\t\t\t\t
1.0E+05
\n\t\t\t\t\t\t\t
8.4
\n\t\t\t\t\t\t\t
7.5
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
2
\n\t\t\t\t\t\t\t
F
\n\t\t\t\t\t\t\t
142.6
\n\t\t\t\t\t\t\t
199.6
\n\t\t\t\t\t\t\t
554.5
\n\t\t\t\t\t\t\t
998.0
\n\t\t\t\t\t\t\t
1.0E+05
\n\t\t\t\t\t\t\t
10.5
\n\t\t\t\t\t\t\t
7.3
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
3
\n\t\t\t\t\t\t\t
F
\n\t\t\t\t\t\t\t
110.9
\n\t\t\t\t\t\t\t
166.4
\n\t\t\t\t\t\t\t
554.5
\n\t\t\t\t\t\t\t
998.0
\n\t\t\t\t\t\t\t
1.0E+05
\n\t\t\t\t\t\t\t
5.9
\n\t\t\t\t\t\t\t
7.6
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
4
\n\t\t\t\t\t\t\t
F
\n\t\t\t\t\t\t\t
142.6
\n\t\t\t\t\t\t\t
199.6
\n\t\t\t\t\t\t\t
554.5
\n\t\t\t\t\t\t\t
998.0
\n\t\t\t\t\t\t\t
1.0E+05
\n\t\t\t\t\t\t\t
5.9
\n\t\t\t\t\t\t\t
3.6
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
5
\n\t\t\t\t\t\t\t
F
\n\t\t\t\t\t\t\t
124.8
\n\t\t\t\t\t\t\t
199.6
\n\t\t\t\t\t\t\t
554.5
\n\t\t\t\t\t\t\t
998.0
\n\t\t\t\t\t\t\t
1.2E+04
\n\t\t\t\t\t\t\t
11.3
\n\t\t\t\t\t\t\t
6.9
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
6
\n\t\t\t\t\t\t\t
F
\n\t\t\t\t\t\t\t
166.4
\n\t\t\t\t\t\t\t
199.6
\n\t\t\t\t\t\t\t
554.5
\n\t\t\t\t\t\t\t
998.0
\n\t\t\t\t\t\t\t
1.0E+05
\n\t\t\t\t\t\t\t
9.8
\n\t\t\t\t\t\t\t
8.5
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
7
\n\t\t\t\t\t\t\t
F
\n\t\t\t\t\t\t\t
99.8
\n\t\t\t\t\t\t\t
332.7
\n\t\t\t\t\t\t\t
554.5
\n\t\t\t\t\t\t\t
998.0
\n\t\t\t\t\t\t\t
1.0E+05
\n\t\t\t\t\t\t\t
12.7
\n\t\t\t\t\t\t\t
17.0
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
8
\n\t\t\t\t\t\t\t
F
\n\t\t\t\t\t\t\t
142.6
\n\t\t\t\t\t\t\t
249.5
\n\t\t\t\t\t\t\t
554.5
\n\t\t\t\t\t\t\t
998.0
\n\t\t\t\t\t\t\t
1.0E+05
\n\t\t\t\t\t\t\t
14.5
\n\t\t\t\t\t\t\t
10.6
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
9
\n\t\t\t\t\t\t\t
F
\n\t\t\t\t\t\t\t
99.8
\n\t\t\t\t\t\t\t
249.5
\n\t\t\t\t\t\t\t
554.5
\n\t\t\t\t\t\t\t
998.0
\n\t\t\t\t\t\t\t
1.0E+05
\n\t\t\t\t\t\t\t
10.9
\n\t\t\t\t\t\t\t
14.9
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
10
\n\t\t\t\t\t\t\t
F
\n\t\t\t\t\t\t\t
199.6
\n\t\t\t\t\t\t\t
166.4
\n\t\t\t\t\t\t\t
554.5
\n\t\t\t\t\t\t\t
998.0
\n\t\t\t\t\t\t\t
1.0E+05
\n\t\t\t\t\t\t\t
11.9
\n\t\t\t\t\t\t\t
10.1
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
11
\n\t\t\t\t\t\t\t
F
\n\t\t\t\t\t\t\t
99.8
\n\t\t\t\t\t\t\t
166.4
\n\t\t\t\t\t\t\t
554.5
\n\t\t\t\t\t\t\t
998.0
\n\t\t\t\t\t\t\t
1.0E+05
\n\t\t\t\t\t\t\t
8.2
\n\t\t\t\t\t\t\t
7.6
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
12
\n\t\t\t\t\t\t\t
F
\n\t\t\t\t\t\t\t
124.8
\n\t\t\t\t\t\t\t
166.4
\n\t\t\t\t\t\t\t
554.5
\n\t\t\t\t\t\t\t
998.0
\n\t\t\t\t\t\t\t
1.0E+05
\n\t\t\t\t\t\t\t
14.2
\n\t\t\t\t\t\t\t
9.6
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
13
\n\t\t\t\t\t\t\t
F
\n\t\t\t\t\t\t\t
166.4
\n\t\t\t\t\t\t\t
199.6
\n\t\t\t\t\t\t\t
554.5
\n\t\t\t\t\t\t\t
998.0
\n\t\t\t\t\t\t\t
1.0E+05
\n\t\t\t\t\t\t\t
15.8
\n\t\t\t\t\t\t\t
8.6
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
Average (1~13)
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
137.4 ±31.3
\n\t\t\t\t\t\t\t
207.3 ±46.9
\n\t\t\t\t\t\t\t
554.5
\n\t\t\t\t\t\t\t
998.0
\n\t\t\t\t\t\t\t
9.3E+04± 2.4E+04
\n\t\t\t\t\t\t\t
10.8± 3.1
\n\t\t\t\t\t\t\t
9.2 ±3.5
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
14
\n\t\t\t\t\t\t\t
M
\n\t\t\t\t\t\t\t
83.2
\n\t\t\t\t\t\t\t
199.6
\n\t\t\t\t\t\t\t
554.5
\n\t\t\t\t\t\t\t
998.0
\n\t\t\t\t\t\t\t
1.0E+05
\n\t\t\t\t\t\t\t
12.1
\n\t\t\t\t\t\t\t
13.3
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
15
\n\t\t\t\t\t\t\t
M
\n\t\t\t\t\t\t\t
99.8
\n\t\t\t\t\t\t\t
249.5
\n\t\t\t\t\t\t\t
554.5
\n\t\t\t\t\t\t\t
998.0
\n\t\t\t\t\t\t\t
1.0E+05
\n\t\t\t\t\t\t\t
11.4
\n\t\t\t\t\t\t\t
16.3
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
16
\n\t\t\t\t\t\t\t
M
\n\t\t\t\t\t\t\t
99.8
\n\t\t\t\t\t\t\t
166.4
\n\t\t\t\t\t\t\t
554.5
\n\t\t\t\t\t\t\t
998.0
\n\t\t\t\t\t\t\t
1.0E+05
\n\t\t\t\t\t\t\t
7.6
\n\t\t\t\t\t\t\t
8.6
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
17
\n\t\t\t\t\t\t\t
M
\n\t\t\t\t\t\t\t
99.8
\n\t\t\t\t\t\t\t
249.5
\n\t\t\t\t\t\t\t
554.5
\n\t\t\t\t\t\t\t
998.0
\n\t\t\t\t\t\t\t
1.0E+05
\n\t\t\t\t\t\t\t
8.1
\n\t\t\t\t\t\t\t
15.7
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
18
\n\t\t\t\t\t\t\t
M
\n\t\t\t\t\t\t\t
62.4
\n\t\t\t\t\t\t\t
166.4
\n\t\t\t\t\t\t\t
554.5
\n\t\t\t\t\t\t\t
998.0
\n\t\t\t\t\t\t\t
3.3E+04
\n\t\t\t\t\t\t\t
3.3
\n\t\t\t\t\t\t\t
6.5
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
19
\n\t\t\t\t\t\t\t
M
\n\t\t\t\t\t\t\t
142.6
\n\t\t\t\t\t\t\t
124.8
\n\t\t\t\t\t\t\t
554.5
\n\t\t\t\t\t\t\t
998.0
\n\t\t\t\t\t\t\t
1.0E+05
\n\t\t\t\t\t\t\t
11.5
\n\t\t\t\t\t\t\t
6.9
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
20
\n\t\t\t\t\t\t\t
M
\n\t\t\t\t\t\t\t
76.8
\n\t\t\t\t\t\t\t
166.4
\n\t\t\t\t\t\t\t
554.5
\n\t\t\t\t\t\t\t
998.0
\n\t\t\t\t\t\t\t
1.0E+05
\n\t\t\t\t\t\t\t
3.7
\n\t\t\t\t\t\t\t
5.1
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
21
\n\t\t\t\t\t\t\t
M
\n\t\t\t\t\t\t\t
45.4
\n\t\t\t\t\t\t\t
166.4
\n\t\t\t\t\t\t\t
554.5
\n\t\t\t\t\t\t\t
998.0
\n\t\t\t\t\t\t\t
5.0E+04
\n\t\t\t\t\t\t\t
10.9
\n\t\t\t\t\t\t\t
9.6
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
22
\n\t\t\t\t\t\t\t
M
\n\t\t\t\t\t\t\t
62.4
\n\t\t\t\t\t\t\t
166.4
\n\t\t\t\t\t\t\t
554.5
\n\t\t\t\t\t\t\t
998.0
\n\t\t\t\t\t\t\t
1.0E+05
\n\t\t\t\t\t\t\t
10.3
\n\t\t\t\t\t\t\t
9.7
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
23
\n\t\t\t\t\t\t\t
M
\n\t\t\t\t\t\t\t
90.7
\n\t\t\t\t\t\t\t
166.4
\n\t\t\t\t\t\t\t
554.5
\n\t\t\t\t\t\t\t
998.0
\n\t\t\t\t\t\t\t
1.0E+05
\n\t\t\t\t\t\t\t
13.8
\n\t\t\t\t\t\t\t
13.9
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
24
\n\t\t\t\t\t\t\t
M
\n\t\t\t\t\t\t\t
52.5
\n\t\t\t\t\t\t\t
998.1
\n\t\t\t\t\t\t\t
554.5
\n\t\t\t\t\t\t\t
998.0
\n\t\t\t\t\t\t\t
1.0E+05
\n\t\t\t\t\t\t\t
10.9
\n\t\t\t\t\t\t\t
14.4
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
Average (14~24)
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
76.7 ±23.0
\n\t\t\t\t\t\t\t
256.3 ±248.9
\n\t\t\t\t\t\t\t
554.5
\n\t\t\t\t\t\t\t
998.0
\n\t\t\t\t\t\t\t
8.9E+04± 2.4E+04
\n\t\t\t\t\t\t\t
9.3 ±3.4
\n\t\t\t\t\t\t\t
10.5 ±4.0
\n\t\t\t\t\t\t
\n\t\t\t\t\t
Table 5.
The evaluated results for 24 healthy volunteers in this work. The Theoretical recommendation from ICRP-30 report is also listed in the first row for comparing. Either ATST or ATLSI indicates the curve fitting agreement between theoretical estimation and practical measurement for stomach (ST) or small intestine (SI) + upper large intestine (ULI) + lower large intestine (LLI).
\n\t\t\t\t
males are 76.7± 23.0 min. and 256.3± 248.9 min. respectively, and in females are 137.4± 31.3 min., 207.3± 46.9 min, respectively. Therefore, the GET and T1/2eff(SI) for males are 63.2±18.9 min. and 149.8±145.1 min. and those for females are 99.5±22.6 min. and 131.6±29.8 min., respectively. The values of both T1/2(ULI) and T1/2(LLI) that were used in the program calculation were those suggested in the ICRP-30 report. The calculated T1/2(b) 10,000, is greatly higher that that, 998, recommended by the original ICRP-30 report. The increased half life, associated with metabolic removal (around an order of magnitude greater than its suggested value), indicates that only a negligible amount of Tc-99m phytate is transported to the body fluid (BF).
\n\t\t\t\t
Both ATST and ATLSI reveal consistency between the measured and estimated fitted curves for ST and SI+ULI+LLI [Eq. 5]. The ATs are around 3.6~16.3; the average ATs for males are 9.3± 3.4 and 10.5± 4.0 and those for females are 10.8± 3.1 and 9.2± 3.5 [Tab. 5, last two columns]. Twenty-six correlated data are used in the program in MATLAB to find an optimal value of Tc-99m quantities for each volunteer (13×2=26, ST and SI+ULI+LLI). Equations 6-9 must be solved simultaneously and include all four compartments of the GI tract biokinetic model [cf. Fig. 4]. Figure 6 plots the time-dependent curves of ST and SI+ULI+LLI for males and females. The inconsistency between the theoretical and empirical values is significant.
\n\t\t\t
\n\t\t\t
\n\t\t\t\t
3.5. Discussion
\n\t\t\t\t
Unlike the thyroid biokinetic model, which includes a feedback loop between the body fluid compartment and the whole body compartment, the GI Tract biokinetic model applies exactly the direct chain emptying principle, and assumes that no equilibrium exists between the parent and daughter compartments, because the parent’s (ST) biological half emptying time is shorter than the daughter’s (SI+ULI+LLI) biological half emptying time. The unique integration of parent’s and daughter’s biological half emptying times also reflects the unpredictability of the real GET of the gastrointestinal system. Therefore, a total of 13 groups of data were obtained for each volunteer over six continuous hours of scanning and input to the program in MATLAB to determine the complete correlation between ST and SI+ULI+LLI. Simplifying either the biokinetic model or the calculation may generate errors in the output and conclusion. Very few studies have addressed the time-dependent curve for SI+ULI+LLI, because this curve is not a straight line that is associated with a particular emptying constant (slope) [Fig. 6]. Any two or three sets of discrete measurements cannot provide enough data to yield a conclusive result. The optimal fitted time-dependent SI+ULI+LLI curve is a polynomial function of fourth or fifth order. Therefore, the data must be measured discretely in five or six trials to draw conclusions with a satisfactory confidence level.
\n\t\t\t\t
The biological half emptying time of SI dominates the time-dependent curve of SI+ULI+LLI, since the SI biological half emptying time, T1/2(SI), fluctuates markedly, whereas the values of both T1/2(ULI) and T1/2(LLI) contribute inconsiderably to solve the simultaneous differential equations in the program in MATLAB [cf. Tab. 5]. Additionally, a close examination of the time-dependent SI+ULI+LLI curve of either males or females reveals that quantities of Tc-99m radionuclides in the SI compartment for males more rapidly approaches saturation than does that for the females, and so the biological half emptying time is shorter in males [cf. Fig. 6]. However, the analyzed results concerning GETs herein do not support this claim (female: 207.3±46.9 min.; male: 256.3±248.9 min.) because the extent of changes of the SI (daughter compartment) is governed by the chain emptying rate from the ST (parent compartment), and the T1/2(ST) for males (76.7±23.0 min.) is shorter than that for females (137.4±31.3 min.). Restated, the correct interpretation of the results must be based on the GI Tract biokinetic model and satisfy the simultaneous differential equations, Eqs. 6-9.
\n\t\t\t
\n\t\t
\n\t\t
\n\t\t\t
4. Recommendation and conclusion
\n\t\t\t
Both the effective half-life of iodine in either the thyroid or the body fluid compartment of (near) total thyroidectomy patients and the gastric emptying half time of solid food in 24 healthy volunteers (11M/13F) were determined using the in-vivo gamma camera method. The real images that were captured using the gamma camera provide reliable information for biokinetic model-based analysis, since the easy and accurate positioning feature enables the time-dependent quantities of cumulated gamma rays in various biokinetic compartments to be determined.
\n\t\t\t
MATLAB is rarely used in the medical field because of its complicated demanding programming. However, its powerful ability to define time-dependent simultaneous differential equations and to derive optimal numerical solutions can accelerate correlative analyses in most practical studies. Notably, only an appropriate definition at the beginning of study can ensure a reliable outcome that is consistent with practical measurements. The application of a simplistic or excessively direct hypothesis about any radiological topic can yield very erroneous results.
\n\t\t\t
\n\t\t\t\t
4.1. Iodine thyroid model
\n\t\t\t\t
The revised values of Teff of iodine in the thyroid compartment were initially obtained from computations made for each subject using the iodine biokinetic model and averaged over all five subjects. The Teff of iodine in the thyroid compartment was revised from the original 7.3d to 0.61d, while that of iodine in the body fluid compartment was increased from 0.24d to 0.49d. The Ithy. and Iexc. were revised from the original 30% and 70% to 11.4% and 88.4%, respectively following in-vivo measurement. The differences between the results of the original and the revised iodine biokinetic models were used AT to determine the biological half-life of iodine in the thyroid and the remainder. The Teff of the integrated remainder (both body fluid and whole body compartments) remained around 5.8d, since the body fluid and whole body compartment were inseparable in practical scanning of the whole body. The different effective half lies of radioiodine nuclides in thyroidectomy patients had to be considered in evaluating effective dose.
\n\t\t\t
\n\t\t\t
\n\t\t\t\t
4.2. Gastrointestinal tract model
\n\t\t\t\t
The results obtained using the program in MATLAB were based on four time-dependent simultaneous differential equations that were derived to be consistent with the measured gamma ray counts in different compartments in the GI Tract biokinetic model. The GET and T1/2eff(SI) for males thus obtained were 63.2±18.9 min. and 149.8±145.1 min. and those for females were 99.5±22.6 min. and 131.6±29.8 min. The calculated T1/2(b), 10,000 was greatly higher that that, 998, recommended by the original ICRP-30 report. The fact that the half life associated with metabolic removal, T1/2(b), was around ten times the original value implied that a negligible amount of Tc-99m phytate was transported to the body fluid.
\n\t\t\t
\n\t\t
\n\t
Acknowledgments
\n\t\t\t
The authors would like to thank the National Science Council of the Republic of China for financially supporting this research under Contract No. NSC~93-2213-E-166-004. Ted Knoy is appreciated for his editorial assistance.
\n\t\t
\n',keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/18577.pdf",chapterXML:"https://mts.intechopen.com/source/xml/18577.xml",downloadPdfUrl:"/chapter/pdf-download/18577",previewPdfUrl:"/chapter/pdf-preview/18577",totalDownloads:3960,totalViews:227,totalCrossrefCites:1,totalDimensionsCites:4,totalAltmetricsMentions:0,introChapter:null,impactScore:1,impactScorePercentile:53,impactScoreQuartile:3,hasAltmetrics:0,dateSubmitted:"November 11th 2010",dateReviewed:"April 28th 2011",datePrePublished:null,datePublished:"September 9th 2011",dateFinished:null,readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/18577",risUrl:"/chapter/ris/18577",book:{id:"1027",slug:"applications-of-matlab-in-science-and-engineering"},signatures:"Chia Chun Hsu, Chien Yi Chen and Lung Kwang Pan",authors:[{id:"41319",title:"Prof.",name:"Lung-Kwang",middleName:null,surname:"Pan",fullName:"Lung-Kwang Pan",slug:"lung-kwang-pan",email:"lkpan@ctust.edu.tw",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41319/images/84_n.jpg",institution:null},{id:"48731",title:"Dr.",name:"Chia Chun",middleName:null,surname:"Hsu",fullName:"Chia Chun Hsu",slug:"chia-chun-hsu",email:"jiajium@hotmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"52711",title:"Prof.",name:"Chien Yi",middleName:null,surname:"Chen",fullName:"Chien Yi Chen",slug:"chien-yi-chen",email:"ccy@csmu.edu.tw",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction ",level:"1"},{id:"sec_2",title:"2. Iodine thyroid model",level:"1"},{id:"sec_2_2",title:"2.1. Biokinetic model",level:"2"},{id:"sec_3_2",title:"2.2. MATLAB algorithms",level:"2"},{id:"sec_4_2",title:"2.3. Experiment",level:"2"},{id:"sec_4_3",title:"2.3.1. Characteristics of patients",level:"3"},{id:"sec_5_3",title:"2.3.2. Gamma camera",level:"3"},{id:"sec_6_3",title:"2.3.3. Whole body scanning of patients",level:"3"},{id:"sec_8_2",title:"2.4. Data analysis ",level:"2"},{id:"sec_9_2",title:"2.5. Discussion",level:"2"},{id:"sec_11",title:"3. Gastrointestinal tract model",level:"1"},{id:"sec_11_2",title:"3.1. Biokinetic model",level:"2"},{id:"sec_12_2",title:"3.2. MATLAB algorithms",level:"2"},{id:"sec_13_2",title:"3.3. Experiment",level:"2"},{id:"sec_13_3",title:"3.3.1. Characteristics of volunteers",level:"3"},{id:"sec_14_3",title:"3.3.2. Tc-99m-labeled phytate solid food",level:"3"},{id:"sec_15_3",title:"3.3.3. Gamma camera",level:"3"},{id:"sec_16_3",title:"3.3.4. Whole body scanning of volunteers",level:"3"},{id:"sec_18_2",title:"3.4. Data analysis",level:"2"},{id:"sec_19_2",title:"3.5. Discussion",level:"2"},{id:"sec_21",title:"4. Recommendation and conclusion",level:"1"},{id:"sec_21_2",title:"4.1. Iodine thyroid model",level:"2"},{id:"sec_22_2",title:"4.2. Gastrointestinal tract model",level:"2"},{id:"sec_24",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChen\n\t\t\t\t\t\t\tC. Y.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChang\n\t\t\t\t\t\t\tP. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPan\n\t\t\t\t\t\t\tL. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChang\n\t\t\t\t\t\t\tLai. S. P.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChan\n\t\t\t\t\t\t\tC. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2003Effective half life of I-131 of whole body and individual organs for thyroidectomy patient using scintigraphic images of gamma-camera. 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Central Taiwan University of Science and Technology, Taiwan
Buddhist Tzu Chi General Hospital, Taichung Branch, Taiwan
'},{corresp:null,contributorFullName:"Chien Yi Chen",address:null,affiliation:'
Central Taiwan University of Science and Technology, Taiwan
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1. Introduction
Acute exacerbations of Idiopathic Pulmonary fibrosis (AE-IPF) represent important milestone in the disease course of IPF, which is the most common disease among the group of Idiopathic interstitial pneumonia (IIP). The IPF is more common among males and in the elderly age group [1]. Although the exact etiology of AE-IPF is unknown, there are many important risk factors as well as triggers that have been identified. There is associated accelerated decline in lung function which leads to poor prognosis [1]. It is estimated that about 35 to 46% of deaths in IPF are caused by AE-IPF [2]. In hospital mortality is more than 50% and follow up after hospitalization shows a mortality up to 73% at the end of 90 days [2, 3]. Although treatment with high dose Gluco corticoids have been used extensively, there is lack of controlled well designed trials to support its use and in fact survival has been shown to be decreased with steroids and or other immune suppressants [4, 5]. Some newer anti-fibrotic agents like Pirfenidone and Nintedanib may improve survival, the latter may be helpful in preventing AE-IPF [1, 6, 7].
2. Criteria for diagnosis of AE-IPF
Acute exacerbation of IPF is recognized with the help of a set of criteria laid out by the International IPF Working group network which is as follows [2, 4, 8, 9, 10, 11, 12].
“An acute, clinically significant respiratory deterioration characterized by evidence of new widespread alveolar abnormality”.
The following four diagnostic criteria have to be met as shown in Table 1.
A known or concurrent diagnosis of IPF
Clinical respiratory deterioration noted “typically” in the preceding 30 days.
Presence of typical UIP pattern on CT chest including bilateral basilar reticular changes with honeycombing and traction bronchiectasis. Superimposed ground glass attenuation and /or consolidation is necessary in exacerbation. When possible specific UIP pattern may be combined with histopathological information to make a more robust diagnosis.
Absence of heart failure, Pulmonary embolism, fluid overload or any other differential pathology.
Note that endotracheal aspirate is not necessary as per new diagnostic criteria.
The 30-day time limit of clinical deterioration is not strictly enforced.
Exclude other causes of Interstitial Lung disease such as drug toxicity, connective tissue disease, hypersensitivity pneumonitis, etc.
Table 1.
Criteria for diagnosing IPF exacerbation as per working group idiopathic pulmonary fibrosis network (IPF net).
The guidelines also provided certain clarifications that help in making a diagnosis [11].
Events that are clinically considered to meet the definition of acute exacerbation of IPF but fail to meet all four diagnostic criteria owing to missing computed tomography data are to be termed “suspected acute exacerbations.” For example, if CT scan shows unilateral ground glass attenuation or data available is incomplete [2].
If the diagnosis of IPF is not previously established, this criterion can be met by the presence of radiologic and/or histopathologic changes consistent with usual interstitial pneumonia pattern on the current evaluation [11].
It is to be noted that the term “idiopathic” was removed from the older definition, as it was seen to be restrictive [11]. Making a distinction between idiopathic and non-idiopathic respiratory events is not easy as there are not well defined clinical or biological criteria [11]. So, although the acute deterioration could be due to an infectious etiology and it is not necessary to rule this out for the purpose of definition, at a practical level infection needs to be diagnosed and treated empirically or definitely as it does have a definite therapeutic recourse [11, 13]. It also follows from this that Broncho alveolar lavage (BAL) is not needed for diagnosis and hence it will help capture more of such events, but at the expense of specificity [11, 13]. BAL may not be needed when HRCT pattern is consistent with UIP, but when the Usual interstitial pneumonia (UIP) pattern is indeterminate or suspect then BAL can be useful [12]. Similarly, surgical lung biopsy (SLB) is recommended only when UIP is indeterminate or suspect [12]. However there is considerable morbidity and mortality associated with BAL or surgical biopsy in the context of AE and hence such procedures are to be generally avoided [11].
Similar to Acute lung injury in non-IPF lungs precipitated by triggers such as aspiration, post-operative, medication etc., exacerbation in IPF can be sub-categorized as either “triggered” when a known precipitating etiology is documented or “Idiopathic” when no such etiology is apparent [11].
The new definition also replaced the 30-day time restriction for the acute deterioration to “typically or generally of less than one-month duration” [11]. The phrase “typically less than 1 month” was included to provide precision but allow for the inclusion of exceptions that clinicians believe represent acute exacerbations [11]. A more flexible time interval may lead to “heterogeneity” among clinicians and clinical trial endpoint definitions for acute exacerbation [11].
3. Epidemiology
The incidence of acute exacerbations is variably reported in literature. This is because exacerbations could be more common in certain populations like more elderly people who are also likely to have severe disease, inconsistent definitions and its use, statistical design, follow up time and other factors [2, 9]. Exacerbations are less common in mild to moderate disease compared to severe disease [3, 14]. Reporting can vary depending on the type of study as well. Prospective trials may lack sufficient data to report all exacerbations [2, 4, 8],typically include younger patients with less comorbidities, with mild to moderate disease and therefore may under report incidence [15]. Retrospective studies may over report depending on the criteria used, by including events with pulmonary embolism, heart failure etc. [2, 13, 16].
Suspected exacerbations, which may not satisfy the definition of definitive AE-IPF are also important as they are associated with poor outcomes [4].
A meta-analysis analyzed six trials and reported acute exacerbation rate of 41 acute exacerbations per 1000 patient/years [14]. Rate of acute exacerbations were much lower in trials that included only mild to moderate disease [14].
In a retrospective study from Korea, which included 461 patients with IPF of which 269 cases were biopsy-proven and the median follows up period was 22.9 months, acute exacerbation occurred in 96 (20.8%) patients, and 17 (17.7%) of those acute exacerbation patients experienced multiple episodes of acute exacerbations (range 2–3 episodes). The incidence of acute exacerbation was noted to be 14.2, 18.8 and 20.7 percent at the end of 1, 2 and 3 years respectively [17].
It is to be noted that exacerbation of IPF may even occur in individuals with limited fibrosis and well-preserved lung function [2]. In the STEP-IPF trail, definite AE-IPF was reported as 40 per 1000 patient-years. However, the combined definite and suspected AE-IPF increased the exacerbation rate to 200 per 1000 patient-year [2, 4, 8, 13].
There have been reports of increased rate of AE-IPF in people of Asian descent in the far east such as Japan and Korea, however this has not been proven by randomized control trials [7, 8, 18].
4. Risk factors and pathophysiology
There are many risk factors for acute exacerbation. However, the most important risk factor is advanced disease [2, 14]. Other factors described in literature include low Forced vital capacity [8, 17], recent decline in FVC [19, 20], Low diffusion capacity for carbon monoxide [4], low 6 min walk test [4], pulmonary hypertension [21], poor baseline oxygenation [4, 22], increased dyspnea score [4], younger age group [2], presence of concurrent coronary artery disease [4], higher body mass index [22], previous history of acute exacerbation of IPF [19, 23].
Some important triggers for acute exacerbation have been described.
4.1 Infection
Infections are very common causes of respiratory deterioration. Exacerbations are more common in winter and spring season [24] and in those who are immunosuppressed [2, 25]. Postmortem analysis, multiplex polymerase chain reaction (PCR), pan viral micro array, high output cDNA sequencing and other techniques have demonstrated that infectious etiology is incriminated in many but not all acute exacerbations [23]. Based on the cumulative evidence which demonstrates infection to be causing some but not all acute exacerbations, it is thought to be an important but not exclusive trigger for precipitating acute exacerbations.
4.2 Silent aspiration of gastric contents
Aspiration of gastric contents has been postulated to be a causative factor for IPF and exacerbations in IPF.
In a case control study involving 24 acute exacerbations and 30 controls, Pepsin level in Broncho alveolar lavage (BAL) was found to be fairly commonly present, suggestive of gastric aspiration being fairly common in IPF.8 of the 24 acute exacerbation IPF patients had very high levels of Pepsin suggesting that aspiration of gastric contents could be a contributor for acute exacerbation [26].
In a study involving 32 patients with asymmetric idiopathic pulmonary fibrosis (AIPF) compared with 64 matched controls with symmetrical IPF, Gastro esophageal reflux disease (GERD) and AE-IPF was significantly higher in patients with AIPF with the left side being less commonly involved [27].
On the contrary, in a post hoc analysis of the two Phase III randomized placebo-controlled INPULSIS trials of Nintedanib in patients with IPF, the rate of decline of FVC in the placebo group was much higher in patients who were taking an antacid (Proton pump inhibitor or H2-receptor antagonists) at baseline when compared to those who were not [difference of − 47.5 mL/year (95% CI: −105.1, 10.1); p = 0.1057] [28].
The data as it is apparent, that although gastro esophageal reflex has been widely debated to be causative, is not very definitive. Therefore, it can be likely that the aspiration of gastro esophageal contents can trigger acute exacerbations like infections but is not the sole causative factor.
4.3 Surgery and other interventions
Many surgical procedures like bronchoscopy and BAL, lung biopsy, lung resection, non-thoracic surgery and others can precipitate acute exacerbation [24, 29, 30, 31, 32]. The mechanism of action is unclear but could be related to stress like volutrauma, barotrauma, free oxygen radicals, or intra operative fluid balance.
4.4 Air pollution
Air pollution can be a cause for interstitial lung disease. In a retrospective south Korean longitudinal cohort, out of 505 IPF patients 436 patients were included in the final analysis.75 patients experienced at least one exacerbation. There were 89 acute exacerbation events occurring over 1699 patient-years, for an incidence rate of 5.2 exacerbations per 100 patient-years. [23].
Air pollution data for each of the five pollutants Ozone (O3),Nitrogen di oxide (NO2), particles with a 50% cut-off aerodynamic diameter of <10 μm (PM10), sulfur dioxide (SO2) and carbon monoxide (CO) were measured prospectively at Tele-Monitoring-Systems (TMS) situated throughout Korea. Each TMS recorded hourly measurements of each pollutant during the study period. Mean and maximum exposures of all these 5 pollutants were recorded over the 42-day period prior to the exacerbation period. Acute exacerbation of IPF was significantly associated with important measurement metrics of O3 and NO2 during the exposure period. Mean Ozone and Nitrogen dioxide levels were weakly correlated; however, both were statistically significant independent predictors of AE-IPF [23].
4.5 Medications
Medications can provoke respiratory deterioration in interstitial pneumonia which closely resembles acute exacerbation. Such drugs include everolimus, interferon-gamma and others [33, 34]. Drugs and surgery used to treat Lung cancer patients with interstitial pneumonia did not appear to cause more exacerbations compared to best supportive care and hence should not be withheld when treating Lung cancer with interstitial pneumonia patients [35].
As noted, there have been many triggers associated with acute exacerbation of IPF. However currently the most accepted theory is that exacerbation is thought to be “an acceleration of the underlying inflammatory fibro proliferative disease process”.
This theory is supported by markers of cell injury as well as genetic expressions.
In one study by Collard et al., 47 patients with acute exacerbation of IPF, 20 patients with stable IPF and 20 patients with acute lung injury were studied. Plasma from these patients were collected and measured for biomarkers of cell activity/injury-receptor for advanced glycation end (RAGE) products, surfactant protein D, KL-6, von Willebrand factor; systemic inflammation-Interleukin-6; and biomarkers of coagulation/fibrinolysis-protein C, thrombomodulin, plasminogen activator inhibitor-1. Plasma from patients with AE-IPF showed higher levels of markers of type II alveolar epithelial cell injury/proliferation, endothelial cell injury, and coagulation/fibrinolysis very much like stable IPF but the response was much more exaggerated. This biomarker profile was different from patients with acute lung injury which was consistent with type I alveolar epithelial injury [36].
In another study, RNA was extracted from 23 stable IPF lungs, 8 IPF lungs with acute exacerbation of IPF and 15 control lungs. The gene expressions were studied. Results indicated that 579 genes were differentially expressed between stable IPF and acute exacerbation of IPF. Functional analysis of these genes was not suggestive of infectious or inflammatory etiology. Gene expression patterns in acute exacerbations of IPF and IPF samples were quite similar and different from the control lung arm [37].
Other immunological theories have also been proposed. Annexin 1 is an antigen found in human body which is increased in patients who have AE of IPF [38]. This antigen can induce both humoral and cell mediated immune responses and certain parts of this antigen have been implicated in the pathogenesis of AE of IPF [38]. Certain molecular studies have also been performed. Heat shock protein 47 (HSP47), has been studied and found to be a good bio marker for collagen production and secretion [39]. In studies comparing stable and AE-IPF patients, serum HSP47 were significantly elevated in AE-IPF patients in comparison to stable IPF patients [39]. Ironically patients who have anti-HSP70 autoantibodies in smaller studies have much poor prognosis due to AE of IPF when compared to controls or even those patients who have IPF but negative anti-HSP70 autoantibodies [40, 41].
Epithelial damage and impaired healing by abundance fibrosis has been an important theory that tries to explain the pathologic damage in IPF patients. When compared to IPF patients, patients with AE of IPF have higher bio markers of neutrophilic damage such as Alpha-defensins which are produced by activated neutrophils [37, 42] and also increased levels of Fibrocytes have been noted which have been found to be associated with worser outcomes in patients with AE of IPF [42, 43].
5. Clinical features
Patients present with worsening respiratory symptoms generally which are less than 30 days in duration. It consists of cough, worsening dyspnea especially on exertion, fever, malaise, and other flu like symptoms. Criteria for diagnosis include PaO2/FiO2 ratio < 225 or a decrease in PaO2 of ≥10 mmHg over time [8, 16].
Physical examination is consistent with IPF including bibasilar crackles on auscultation, but with increased respiratory rate [37].
Laboratory testing and imaging are directed to rule out other differentials like congestive heart failure, Myocardial infarction, pulmonary embolism, pulmonary hypertension, pulmonary infections etc. [2, 8]. Accordingly, complete blood count, B-type natriuretic peptide, C-reactive protein, chemistry profile including Blood urea nitrogen and serum creatinine can be performed along with highly sensitive troponins. Laboratory values are consistent with an infectious or inflammatory process but there is no evidence of infection on Blood culture, Urine antigen tests or Broncho alveolar lavage (BAL) if these tests are undertaken [8]. BAL if performed typically shows neutrophilic predominance [8]. BNP is typically elevated in heart failure and pulmonary hypertension [44]. Echo may be beneficial in heart failure and pulmonary hypertension [44]. CRP is typically elevated in infections and inflammation [44]. Pro calcitonin can guide when infection is suspected and even helping with limiting duration of antibiotic use [45]. D-dimer and CT pulmonary angiogram can help with ruling in or ruling out Pulmonary embolism [44].
High resolution computed tomography (HRCT) reveals bilateral ground glass or consolidative opacities superimposed on a background of typical HRCT features of IPF which includes bibasilar reticular opacities, honeycomb changes, and traction bronchiectasis [2].
Acute exacerbation of IPF is essentially a clinical diagnosis aided by predominantly noninvasive test. Although surgical biopsy can be performed for diagnosis which may show diffuse alveolar damage, the mortality and morbidity in the acute situation appear to be prohibitively high and not recommended [46].
6. Treatment and prognosis
Treatment is primarily supportive in nature.
Supplemental oxygen consisting of low flow and high flow oxygen can be used to keep Oxygen saturation (Spo2) more than 92%. Noninvasive ventilation mechanical ventilation (NIMV) and Mechanical ventilation (MV) is used as needed.
In a retrospective review of 19 hospitalized patients with IPF and AE, 1/3rd of patients had an infectious etiology, the percentage of patients who were discharged alive was 37% and only 14.8% of patients were alive at 1 year [47]. Patients with IPF experience AE very commonly. In IPF, about 40% of patients may die due to AE [48, 49]. In another observational study of 112 patients, 56 patients (42.9%) died due to AE [48]. The five-year survival rate of all patients with IPF was 38.3% and the Median survival time was 3.1 years post diagnosis. However, in patients who had an AE, the five-year survival rate was 10.7% and median survival time was 0.6 years [48].
In a pooled data consisting of nine studies, including 135 patients who were intubated for AE of IPF the cumulative mortality was 118 (87%) and short-term mortality (within 3 months of discharge) was 127 (94%) [50]. Therefore AE of IPF is not only common, but also a very poor predictor of survival. Based on these observations, the 2011 IPF guidelines discouraged MV in the vast majority and recommended its use in a selective minority of patients after careful weighing of risks and benefits [11]. However, this data pertains to a time period before 2007. In a study that reported US national data of 1703 patients who received Mechanical ventilation (MV)and 778 patients who received Noninvasive mechanical ventilation (NIMV),mortality was about 50% in those who received MV compared to 30% for those who received NIMV. The mortality of IPF patients treated with MV improved from 58.4% in 2006 to 49.3% in 2012 which was significant [51]. Overall this is suggestive that survival of patients treated with MV has seen a marginal improvement which could be due to various factors such as relative changes in diagnostic criteria and their use, difference in variables used and study design, differences in the severity of disease (patients with decreased FVC have poorer prognosis), judicious selection of patients who were placed on MV and widespread adoption and use of lung protective ventilation strategies [52]. Hence it is imperative that well informed discussions relating to advance care directives are made at the time of diagnosis and re visited when hospitalized [50]. In patients who are candidates for Lung transplant, the use of mechanical ventilation and extra corporeal membrane oxygenation, can be effective and lifesaving [11, 52, 53, 54, 55].
Ventilator induced lung injury (VILI) secondary to use of MV results in lung damage and poor prognosis [52]. In IPF, the lungs are fibrotic and non-compliant. Lower PEEP may be more beneficial and protective along with low tidal volume ventilation, hence minimizing both volutrauma and barotrauma [52, 56]. NIMV and high flow oxygen are being increasingly used and may be beneficial [56, 57]. Both NIMV and High flow Oxygen could be beneficial in patients who are not appropriate or choose to forego intubation, the survival may be the same with both modalities [57, 58],with high flow nasal oxygen being better tolerated, allowing patients to even eat and drink [57, 58, 59]. Hence they could be very effective means for palliative care [57, 58].
In patients who undergo thoracic surgery, VILI may be a potential etiological mechanism and can be minimized by the aforementioned lung protective ventilation including reducing lung volume, low PEEP, low partial pressure of inspired oxygen (Fio2), and less invasive surgical techniques [52, 56, 60, 61].
Symptoms such as dyspnea are treated with a palliative intent [8, 11]. Oxygen and opioids can also be given for symptom control [8, 11].
In IPF, a combination of inflammation, epithelial cell injury, fibro proliferative repair, and tissue remodeling which interact with the coagulation system help characterize IPF as a procoagulant state [62]. The use of therapeutic anticoagulation such as Warfarin or Alfa-Thrombomodulin has proven to be either harmful or non-beneficial in well conducted studies [63, 64, 65]. There is no evidence supporting therapeutic anticoagulation in patients experiencing acute exacerbation [63]. Nevertheless, patients with IPF have almost twice the risk of venous thromboembolism compared to general population and hence pharmacological venous thromboprophylaxis should be routinely used in hospitalized patients [66, 67].
There is not enough evidence of protective role from the use of antacids, but patients who are already using them can continue with their use [68, 69]. Evidence is often contradictory if antacids protect or may potentiate or worsen AE of IPF [70, 71].
Corticosteroids have been used extensively but the practice is driven by expert opinion and anecdotal reports and not driven by good data. Expert guidelines give a weak recommendation to the use of steroids [2, 6]. Acute IPF is characterized by high degree of inflammation with areas of diffuse alveolar damage secondary to Acute Lung injury and organizing pneumonia [9]. Therefore, the use of high dose steroids is intuitively thought to be beneficial [9, 72, 73, 74], in spite of absence of good data from randomized control trials [9]. Dosage and duration are also not well defined in literature, although it is typical to use initially high dose corticosteroids followed by a rapid tapering course, as longer duration of steroids may be harmful in IPF [9, 62]. In EXAFIP, a randomized control trial comparing Cyclophosphamide with corticosteroids against placebo with corticosteroids in AE of IPF, the steroid regimen used in all patients was Methylprednisolone 10 mg/kg per day for 3 days followed by a progressive taper to 10 mg per day for patients above 65 kg and 7·5 mg per day for patients below 65 kg at the end of 6 months [75]. Similarly in a RCT involving 77 patients in Japan, Alpha-Thrombomodulin (ART-123) was compared against placebo. All patients received glucocorticoids in two courses of pulse Methylprednisolone (500–1000 mg/day) for 3 days followed by Prednisolone 0.5–1.0 mg/kg/day for 4 days followed by gradual taper [64]. Smaller retrospective studies have shown that using high dose of glucocorticoids used in first 30 days prevent recurrence of exacerbation when compared to lower doses in the same duration or after 30 days but this has not been substantiated by other studies [76, 77]. The use of high dose steroids has been noted to increase survival in non-IPF exacerbation of Interstitial lung disease [76]. It is noteworthy that some studies and even guidelines recommend using no immunosuppressives in select patients, as mortality was no better in the immunosuppressed group when compared to the non-immunosuppressed, with higher incidence of infection in the immune suppressed group, especially in severe disease [11, 14].
Concomitant Immunosuppressive therapy with steroids have also been used and the evidence base for this practice is also not very sound [2, 48]. While treatments such as Alfa-Thrombomodulin and Cyclophosphamide along with concomitant glucocorticoids have been subjected to randomized control trials and have not been shown to improve outcomes [64, 75], others do not have much evidence as they were too small, were uncontrolled, used historical data as control or had no control arm [2]. The latter studies have used medications like Tacrolimus, Cyclosporin-A, Rituximab combined with plasma exchange, Intravenous Immunoglobulin, and polymyxin B-immobilized fiber column (PMX) [6]. Other medications that have been used include Acetylcysteine as standalone therapy, sildenafil, bosentan, interferon-gamma 1b, warfarin, ambrisentan, and imatinib [8].
In a small retrospective study consisting of 11 patients in each group, Corticosteroids alone were compared with Cyclosporin-A and Corticosteroids. The mortality was similar in each group but the Cyclosporin-A group appeared to have longer survival [78]. However in a larger retrospective review with 384 patients in Cyclosporin-A and high dose Corticosteroids and 7605 patients treated with high dose Corticosteroids alone in Japan, no change in survival was noted [79].
Other considerations include empiric treatment of a course of antibiotics since infectious etiology can be treated but cannot be ruled out conclusively in the vast majority of cases [2]. Procalcitonin has been used in clinical trials and can reduce the duration of antibiotics (8.7 ± 6.6 compared to 14.2 ± 5.2 days in the routine treatment group), without any effect on treatment success, mortality rate, days of hospitalization and ventilation therapy [45]. Tacrolimus, an immunosuppressive drug used widely in solid organ transplant patients including Lung transplant was found to have beneficial survival effects and protection against future exacerbations in small retrospective studies, with lack of data from better designed controlled studies [80]. Direct hemoperfusion with Polymyxin B immobilized fiber column (PMX-DHP) has been used in AE of IPF to absorb endotoxins and reactive oxygen species, among other toxic substances, as well as selectively remove activated neutrophils and preventing activation of monocytes with a goal to limit endothelial damage [81, 82]. PMX-DHP may act by adsorbing harmful cytokines such as vascular endothelial growth factor and may have anti-fibrotic effect [83, 84]. The adsorption of proinflammatory, profibrotic and proangiogenic cytokines is postulated to be an important mechanistic action of PMX-DHP [83]. The use of PMX-DHP along with Corticosteroids has demonstrated improvement in oxygenation, with possible improvement in survival in a multicentric Japanese retrospective study with 73 patient who had AE of IPF [82]. There is a prevailing hypothesis that auto antibodies may have a role in IPF progression. Removal of these auto antibodies by plasma exchange and Rituximab followed by IVIG subsequently may be beneficial in AE-IPF [62, 85]. A small pilot study involving 11 patients has shown the safety and possible efficacy, paving way for a Phase 3 randomized control trial [85].
Interestingly in a retrospective study, patients who were not on any immunosuppression had better survival than those who were on immunosuppression [5].
7. Prognostic score
There has been considerable interest in developing prognostication scores for AE of IPF. A number of markers have been used in different studies and Forced vital capacity %, Diffusion capacity for Carbon monoxide, Pao2/Fio2 (P/F) ratio, HRCT patterns, Acute Physiology and Chronic Health Evaluation II score (APACHE II), Glasgow prognostic score and serum biomarkers like C-reactive protein (CRP), Krebs von den Lungen-6 (KL-6) have all been considered [86]. In a retrospective study of 108 patients, a lower FVC % at baseline (1 year before AE) and P/F ratio on AE presentation were predictive of mortality [86]. In another study of 103 AE-IPF cases, a combination of P/F ratio less than 250 (P), CRP ≥ 5.5 (C), and diffuse HRCT pattern (radiological) (R), together called as PCR index was used to stratify and predict mortality at the end of 3 months [87]. In a systematic review and meta-analysis, 37 studies and 31 prognostic factors were analyzed [88]. Five independent variables after multivariate analysis were found to be helpful with prognostication namely APACHE II score, P/F ratio, LDH level, white blood cell (WBC) count, and oxygen therapy before AE [88]. Interestingly the latter did not find use of FVC or imaging scores to be helpful in terms of prognostication [88]. Prognostication scores and models are certainly good research tools but not commonly used in clinical practise as no intervention other than good supportive care has been found to be useful.
8. Prevention
Prevention of exacerbation in IPF is the most effective strategy as we do not seem to have very effective therapies once the exacerbation gets underway. Avoidance of air pollutants [23], preventing infections like Streptococcal pneumonia and Influenza by vaccination [26, 61], general hygiene measures like handwashing again to prevent infections [52], and judicious use of antacids may be helpful strategies [68, 69].
Many medications have been tested, using prevention of acute exacerbation as an end point. Acetylcysteine monotherapy, bosentan, interferon-gamma,sildenafil, showed no effect [8]. Others like imatinib, ambrisentan, triple therapy (prednisone, azathioprine, acetylcysteine combination) and warfarin showed increased risk of exacerbation [8].
Azuma et al. studied 107 IPF patients in a phase 2 Randomized placebo-controlled trial comparing Pirfenidone and placebo. Although there were no acute exacerbations noted in the Pirfenidone arm compared to placebo [89], the same results could not be reproduced in a phase 3 RCT with 275 patients, showing no difference between the intervention and control arm [18]. In the large phase 3 RCT’s, CAPACITY and ASCEND which compared Pirfenidone with placebo yet again, unfortunately AE of IPF as an end point was not studied [90, 91]. Nevertheless, a pooled analysis of the CAPACITY and ASCEND trial did reveal a reduction in non-elective respiratory related hospitalization favoring Pirfenidone [92]. Interestingly Pirfenidone in small studies has proven to be safe and effective in preventing exacerbations in peri operative period in patients who were given 2–4 weeks of medication prior to surgery and continued post operatively when compared against historical controls [93, 94]. Larger RCTs need to be performed for this promising intervention [94].
Another antifibrotic agent Nintedanib was studied after Pirfenidone, which showed a favorable effect against placebo for preventing AE of IPF in the phase 2 TOMORROW trial and phase 3 INPULSIS-2 trial, but no such effect was seen in the phase 3 INPULSIS-1 trial [95, 96]. However the pooled analysis of patients from TOMORROW and INPULSIS trials [6],consisting of 1231 patients (Nintedanib n = 723, placebo n = 508), the hazard ratio for time to first acute exacerbation was 0.53 (95% CI: 0.34, 0.83; p = 0.0047) favoring Nintedanib. The proportion of patients with ≥1 acute exacerbation was 4.6% in the Nintedanib group and 8.7% in the placebo group [6]. Nintedanib can be added after recovering from an exacerbation or continued if it was previously being used.
In a systematic review and meta-analysis, 12,956 patients were included comparing the use of anti fibrotics (Pirfenidone or Nintedanib) vs. nonuse of antifibrotics, which showed that the use of antifibrotics decreased all-cause mortality, RR 0.55 (95% CI, 0.45–0.66). The same review included seven studies involving 2002 treated and 1323 non-treated patients, and showed a decrease in AE, which was statistically significant for Nintedanib (RR 0.62 [95% CI, 0.43–0.89) but only non-significant decrease for Pirfenidone, RR of 0.57 (95% CI, 0.29–1.12) [1].
Overall, the evidence favors Nintedanib over Pirfenidone in terms of preventing AE of IPF. However, there are no head to head comparisons between these two approved medications and real world data could produce results to the contrary [97]. Hence it would be prudent to plan design and conduct appropriate RCT that would give an unambiguous answer to this very important question.
9. Conclusion
Episodes of Acute exacerbation are important events in the disease course of IPF. Up to 40% of deaths in IPF are caused by acute exacerbations. After the initial diagnosis, the median survival of patients with acute exacerbation was much shorter (15.5 months) than that of patients without respiratory deterioration (60.6 months). The 5 year rate of survival of patients with acute exacerbation was 18.4%, whereas 50.0% of patients without respiratory deterioration survived.
While medications like Nintedanib can slow down progression of disease and prevent exacerbations, once diagnosed it has no known effective treatment. Hence more research is needed to alter the disease course of IPF as well as prevent the occurrence of these exacerbations which invariably is an indicator of poor prognosis.
\n',keywords:"acute exacerbation of IPF, idiopathic pulmonary fibrosis, acute exacerbation, drug therapy, treatment, clinical trials, nintedanib, pirfenidone, respiratory failure",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/81614.pdf",chapterXML:"https://mts.intechopen.com/source/xml/81614.xml",downloadPdfUrl:"/chapter/pdf-download/81614",previewPdfUrl:"/chapter/pdf-preview/81614",totalDownloads:33,totalViews:0,totalCrossrefCites:0,dateSubmitted:"July 24th 2021",dateReviewed:"March 22nd 2022",datePrePublished:"May 11th 2022",datePublished:null,dateFinished:"May 2nd 2022",readingETA:"0",abstract:"Episodes of Acute exacerbation (AE) of Idiopathic Pulmonary fibrosis (IPF) are important events in the disease trajectory of IPF, associated with punctuated decline in lung function with significant mortality and morbidity associated with it. These episodes are idiosyncratic, and often unpredictable and may have triggers. Our diagnostic criteria for these events, etiology, pathogenesis, risk factors and management continue to evolve over the years, with limited availability of qualitative research data to help guide management. Outcome in general is poor with no well-defined therapy but prevention may be possible with use of Nintedanib. Our chapter aims to explore the contemporary knowledge of the key aspects of this disease entity.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/81614",risUrl:"/chapter/ris/81614",signatures:"Nitesh Kumar Jain, Shikha Jain, Hisham Ahmed Mushtaq, Anwar Khedr, Thoyaja Koritala, Aysun Tekin, Ramesh Adhikari, Anupam Sule, Samir Gautam, Vishwanath Pattan, Vikas Bansal, Ali Rabaan, Kovid Trivedi, Amos Lal, Brian Bartlett, Abbas Jama, Aishwarya Reddy Korsapati, Mohamed Hassan, Simon Zec, Adham Mohsen, Amit Munshi Sharma, Ibtisam Rauf, Mikael Mir, Lia Nandi, Mool Chand, Hariprasad Reddy Korsapati, Rahul Kashyap, Salim Surani and Syed Anjum Khan",book:{id:"9816",type:"book",title:"Idiopathic Pulmonary Fibrosis",subtitle:null,fullTitle:"Idiopathic Pulmonary Fibrosis",slug:null,publishedDate:null,bookSignature:" Salim Surani and Dr. Venkat Rajasurya",coverURL:"https://cdn.intechopen.com/books/images_new/9816.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-83969-240-6",printIsbn:"978-1-83969-239-0",pdfIsbn:"978-1-83969-241-3",isAvailableForWebshopOrdering:!0,editors:[{id:"15654",title:null,name:"Salim",middleName:null,surname:"Surani",slug:"salim-surani",fullName:"Salim Surani"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Criteria for diagnosis of AE-IPF",level:"1"},{id:"sec_3",title:"3. Epidemiology",level:"1"},{id:"sec_4",title:"4. Risk factors and pathophysiology",level:"1"},{id:"sec_4_2",title:"4.1 Infection",level:"2"},{id:"sec_5_2",title:"4.2 Silent aspiration of gastric contents",level:"2"},{id:"sec_6_2",title:"4.3 Surgery and other interventions",level:"2"},{id:"sec_7_2",title:"4.4 Air pollution",level:"2"},{id:"sec_8_2",title:"4.5 Medications",level:"2"},{id:"sec_10",title:"5. Clinical features",level:"1"},{id:"sec_11",title:"6. Treatment and prognosis",level:"1"},{id:"sec_12",title:"7. Prognostic score",level:"1"},{id:"sec_13",title:"8. Prevention",level:"1"},{id:"sec_14",title:"9. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'Petnak T, Lertjitbanjong P, Thongprayoon C, Moua T. Impact of Antifibrotic therapy on mortality and acute exacerbation in idiopathic pulmonary fibrosis: A systematic review and Meta-analysis. 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Idiopathic pulmonary fibrosis clinical research N: A placebo-controlled randomized trial of warfarin in idiopathic pulmonary fibrosis. American Journal of Respiratory and Critical Care Medicine. 2012;186:88-95. DOI: 10.1164/rccm.201202-0314OC'},{id:"B64",body:'Kondoh Y, Azuma A, Inoue Y, Ogura T, Sakamoto S, Tsushima K, et al. Thrombomodulin alfa for acute exacerbation of idiopathic pulmonary fibrosis. A randomized, double-blind placebo-controlled trial. American Journal of Respiratory and Critical Care Medicine. 2020;201:1110-1119. DOI: 10.1164/rccm.201909-1818OC'},{id:"B65",body:'Tomassetti S, Ruy JH, Gurioli C, Ravaglia C, Buccioli M, Tantalocco P, et al. The effect of anticoagulant therapy for idiopathic pulmonary fibrosis in real life practice. Sarcoidosis, Vasculitis, and Diffuse Lung Diseases. 2013;30:121-127'},{id:"B66",body:'Sprunger DB, Olson AL, Huie TJ, Fernandez-Perez ER, Fischer A, Solomon JJ, et al. Pulmonary fibrosis is associated with an elevated risk of thromboembolic disease. The European Respiratory Journal. 2012;39:125-132. DOI: 10.1183/09031936.00041411'},{id:"B67",body:'Boonpheng B, Ungprasert P. Risk of venous thromboembolism in patients with idiopathic pulmonary fibrosis: A systematic review and meta-analysis. Sarcoidosis, Vasculitis, and Diffuse Lung Diseases. 2018;35:109-114. DOI: 10.36141/svdld.v35i2.6213'},{id:"B68",body:'Jain NK, Khedr A, Mushtaq HA, Bartlett B, Lanz A, Zoesch G, et al. Gastroesophageal Reflux and Idiopathic Pulmonary Fibrosis. In: Idiopathic Pulmonary Fibrosis. London: IntechOpen; 2022. DOI: 10.5772/intechopen.102464'},{id:"B69",body:'Kreuter M, Spagnolo P, Wuyts W, Renzoni E, Koschel D, Bonella F, et al. Antacid therapy and disease progression in patients with idiopathic pulmonary fibrosis who received pirfenidone. Respiration. 2017;93:415-423'},{id:"B70",body:'Lee JS, Collard HR, Anstrom KJ, Martinez FJ, Noth I, Roberts RS, et al. 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DOI: 10.1001/jama.280.2.159'},{id:"B74",body:'Steinberg KP, Hudson LD, Goodman RB, Hough CL, Lanken PN, Hyzy R, et al. Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. The New England Journal of Medicine. 2006;354:1671-1684. DOI: 10.1056/NEJMoa051693'},{id:"B75",body:'Naccache JM, Jouneau S, Didier M, Borie R, Cachanado M, Bourdin A, et al. Investigators E, the OrphaLung n: Cyclophosphamide added to glucocorticoids in acute exacerbation of idiopathic pulmonary fibrosis (EXAFIP): A randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet Respiratory Medicine. 2022;10:26-34. DOI: 10.1016/S2213-2600 (21)00354-4'},{id:"B76",body:'Jang HJ, Yong SH, Leem AY, Lee SH, Kim SY, Lee SH, et al. Corticosteroid responsiveness in patients with acute exacerbation of interstitial lung disease admitted to the emergency department. Scientific Reports. 2021;11:5762. DOI: 10.1038/s41598-021-85539-1'},{id:"B77",body:'Yamazaki R, Nishiyama O, Saeki S, Sano H, Iwanaga T, Tohda Y. Initial therapeutic dose of corticosteroid for an acute exacerbation of IPF is associated with subsequent early recurrence of another exacerbation. Scientific Reports. 2021;11:5782. DOI: 10.1038/s41598-021-85234-1'},{id:"B78",body:'Sakamoto S, Homma S, Miyamoto A, Kurosaki A, Fujii T, Yoshimura K. Cyclosporin a in the treatment of acute exacerbation of idiopathic pulmonary fibrosis. Internal Medicine. 2010;49:109-115. DOI: 10.2169/internalmedicine.49.2359'},{id:"B79",body:'Aso S, Matsui H, Fushimi K, Yasunaga H. Effect of cyclosporine a on mortality after acute exacerbation of idiopathic pulmonary fibrosis. Journal of Thoracic Disease. 2018;10:5275-5282. DOI: 10.21037/jtd.2018.08.08'},{id:"B80",body:'Horita N, Akahane M, Okada Y, Kobayashi Y, Arai T, Amano I, et al. Tacrolimus and steroid treatment for acute exacerbation of idiopathic pulmonary fibrosis. Internal Medicine. 2011;50:189-195. DOI: 10.2169/internalmedicine.50.4327'},{id:"B81",body:'Cruz DN, Antonelli M, Fumagalli R, Foltran F, Brienza N, Donati A, et al. Early use of polymyxin B hemoperfusion in abdominal septic shock: The EUPHAS randomized controlled trial. Journal of the American Medical Association. 2009;301:2445-2452. DOI: 10.1001/jama.2009.856'},{id:"B82",body:'Abe S, Azuma A, Mukae H, Ogura T, Taniguchi H, Bando M, et al. Polymyxin B-immobilized fiber column (PMX) treatment for idiopathic pulmonary fibrosis with acute exacerbation: A multicenter retrospective analysis. Internal Medicine. 2012;51:1487-1491. DOI: 10.2169/internalmedicine.51.6965'},{id:"B83",body:'Oishi K, Mimura-Kimura Y, Miyasho T, Aoe K, Ogata Y, Katayama H, et al. Association between cytokine removal by polymyxin B hemoperfusion and improved pulmonary oxygenation in patients with acute exacerbation of idiopathic pulmonary fibrosis. Cytokine. 2013;61:84-89. DOI: 10.1016/j.cyto.2012.08.032'},{id:"B84",body:'Tachibana K, Inoue Y, Nishiyama A, Sugimoto C, Matsumuro A, Hirose M, et al. Polymyxin-B hemoperfusion for acute exacerbation of idiopathic pulmonary fibrosis: Serum IL-7 as a prognostic marker. Sarcoidosis, Vasculitis, and Diffuse Lung Diseases. 2011;28:113-122'},{id:"B85",body:'Donahoe M, Valentine VG, Chien N, Gibson KF, Raval JS, Saul M, et al. Autoantibody-targeted treatments for acute exacerbations of idiopathic pulmonary fibrosis. PLoS One. 2015;10:e0127771. DOI: 10.1371/journal.pone.0127771'},{id:"B86",body:'Suzuki T, Hozumi H, Miyashita K, Kono M, Suzuki Y, Karayama M, et al. Prognostic classification in acute exacerbation of idiopathic pulmonary fibrosis: A multicentre retrospective cohort study. Scientific Reports. 2021;11:9120. DOI: 10.1038/s41598-021-88718-2'},{id:"B87",body:'Sakamoto S, Shimizu H, Isshiki T, Nakamura Y, Usui Y, Kurosaki A. Isobe K, Takai Y, Homma S: New risk scoring system for predicting 3-month mortality after acute exacerbation of idiopathic pulmonary fibrosis. Scientific Reports. 2022;12:1134. DOI: 10.1038/s41598-022-05138-6'},{id:"B88",body:'Kamiya H, Panlaqui OM. Systematic review and meta-analysis of prognostic factors of acute exacerbation of idiopathic pulmonary fibrosis. BMJ Open. 2020;10:e035420. DOI: 10.1136/bmjopen-2019-035420'},{id:"B89",body:'Azuma A, Nukiwa T, Tsuboi E, Suga M, Abe S, Nakata K, et al. Double-blind, placebo-controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis. American Journal of Respiratory and Critical Care Medicine. 2005;171:1040-1047. DOI: 10.1164/rccm.200404-571OC'},{id:"B90",body:'King TE Jr, Bradford WZ, Castro-Bernardini S, et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. The New England Journal of Medicine. 2014;370:2083-2092. DOI: 10.1056/NEJMoa1402582'},{id:"B91",body:'Noble PW, Albera C, Bradford WZ, Costabel U, Glassberg MK, Kardatzke D, et al. Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): Two randomised trials. Lancet. 2011;377:1760-1769. DOI: 10.1016/s0140-6736 (11)60405-4'},{id:"B92",body:'Ley B, Swigris J, Day BM, Stauffer JL, Raimundo K, Chou W, et al. Pirfenidone reduces respiratory-related hospitalizations in idiopathic pulmonary fibrosis. American Journal of Respiratory and Critical Care Medicine. 2017;196:756-761. DOI: 10.1164/rccm.201701-0091OC'},{id:"B93",body:'Iwata T, Yoshino I, Yoshida S, Ikeda N, Tsuboi M, Asato Y, et al. West Japan oncology G: A phase II trial evaluating the efficacy and safety of perioperative pirfenidone for prevention of acute exacerbation of idiopathic pulmonary fibrosis in lung cancer patients undergoing pulmonary resection: West Japan oncology group 6711 L (PEOPLE study). Respiratory Research. 2016;17:90-90. DOI: 10.1186/s12931-016-0398-4'},{id:"B94",body:'Iwata T, Yoshida S, Fujiwara T, Wada H, Nakajima T, Suzuki H, et al. Effect of perioperative Pirfenidone treatment in lung cancer patients with idiopathic pulmonary fibrosis. The Annals of Thoracic Surgery. 2016;102:1905-1910. DOI: 10.1016/j.athoracsur.2016.05.094'},{id:"B95",body:'Richeldi L, Costabel U, Selman M, Kim DS, Hansell DM, Nicholson AG, et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. The New England Journal of Medicine. 2011;365:1079-1087. DOI: 10.1056/NEJMoa1103690'},{id:"B96",body:'Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U, et al. Efficacy and safety of Nintedanib in idiopathic pulmonary fibrosis. New England Journal of Medicine. 2014;370:2071-2082. DOI: 10.1056/NEJMoa1402584'},{id:"B97",body:'Isshiki T, Sakamoto S, Yamasaki A, Shimizu H, Miyoshi S, Nakamura Y, et al. 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Physical Sciences, Technology and Engineering Board
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Chemistry
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Ayben Kilislioglu - Department of Chemical Engineering Istanbul University, İstanbul, Turkey
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Goran Nikolic - Faculty of Technology, University of Nis, Leskovac, Serbia
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Mark T. Stauffer - Associate Professor of Chemistry, The University of Pittsburgh, USA
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Margarita Stoytcheva - Autonomous University of Baja California Engineering Institute Mexicali, Baja California, Mexico
Joao Luis Garcia Rosa - Associate Professor Bio-inspired Computing Laboratory (BioCom) Department of Computer Science University of Sao Paulo (USP) at Sao Carlos, Brazil
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Jan Valdman - Institute of Mathematics and Biomathematics, University of South Bohemia, České Budějovice, Czech Republic Institute of Information Theory and Automation of the ASCR, Prague, Czech Republic
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Earth and Planetary Science
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Jill S. M. Coleman - Department of Geography, Ball State University, Muncie, IN, USA
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İbrahim Küçük Erciyes - Üniversitesi Department of Astronomy and Space Sciences Melikgazi, Kayseri, Turkey
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Pasquale Imperatore - Electromagnetic Environmental Sensing (IREA), Italian National Council of Research (CNR), Naples, Italy
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Mohammad Mokhtari - Director of National Center for Earthquake Prediction International Institute of Earthquake Engineering and Seismology (IIEES), Tehran, Iran
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Engineering
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Narottam Das - University of Southern Queensland, Australia
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Jose Ignacio Huertas - Energy and Climate Change Research Group; Instituto Tecnológico y Estudios Superiores de Monterrey, Mexico
Likun Pan - Engineering Research Center for Nanophotonics and Advanced Instrument, Ministry of Education, Department of Physics, East China Normal University, China
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Mukul Chandra Paul - Central Glass & Ceramic Research Institute Jadavpur, Kolkata, India
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Stephen E. Saddow - Electrical Engineering Department, University of South Florida, USA
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Ali Demir Sezer - Marmara University, Faculty of Pharmacy, Department of Pharmaceutical Biotechnology, İstanbul, Turkey
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Krzysztof Zboinski - Warsaw University of Technology, Faculty of Transport, Warsaw, Poland
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Materials Science
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Vadim Glebovsky - Senior Researcher, Institute of Solid State Physics, Chernogolovka, Russia Expert of the Russian Fund for Basic Research, Moscow, Russia
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Jianjun Liu - State Key Laboratory of High Performance Ceramics and Superfine Microstructure of Shanghai Institute of Ceramics, Chinese Academy of Sciences, China
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Pietro Mandracci - Department of Applied Science and Technology, Politecnico di Torino, Italy
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Waldemar Alfredo Monteiro - Instituto de Pesquisas Energéticas e Nucleares Materials Science and Technology Center (MSTC) São Paulo, SP, Brazil
Toshio Ogawa - Department of Electrical and Electronic Engineering, Shizuoka Institute of Science and Technology, Toyosawa, Fukuroi, Shizuoka, Japan
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Mathematics
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Paul Bracken - Department of Mathematics University of Texas, Edinburg, TX, USA
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Nanotechnology and Nanomaterials
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Muhammad Akhyar - Farrukh Nano-Chemistry Lab. Registrar, GC University Lahore, Pakistan
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Khan Maaz - Chinese Academy of Sciences, China & The Pakistan Institute of Nuclear Science and Technology, Pakistan
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Physics
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Izabela Naydenova - Lecturer, School of Physics Principal Investigator, IEO Centre College of Sciences and Health Dublin Institute of Technology Dublin, Ireland
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Mitsuru Nenoi - National Institute of Radiological Sciences, Japan
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Christos Volos - Physics Department, Aristotle University of Thessaloniki, Greece
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Robotics
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Alejandra Barrera - Instituto Tecnológico Autónomo de México, México
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Dusan M. Stipanovic - Department of Industrial and Enterprise Systems Engineering, University of Illinois at Urbana-Champaign
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Andrzej Zak - Polish Naval Academy Faculty of Navigation and Naval Weapons Institute of Naval Weapons and Computer Science, Gdynia, Poland
Petr Konvalina - Faculty of Agriculture, University of South Bohemia in České Budějovice, Czech Republic
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Biochemistry, Genetics and Molecular Biology
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Chunfa Huang - Saint Louis University, Saint Louis, USA
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Michael Kormann - University Children's Clinic Department of Pediatrics I, Pediatric Infectiology & Immunology, Translational Genomics and Gene Therapy in Pediatrics, University of Tübingen, Tübingen, Germany
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Bin WU - Ph.D. HCLD Scientific Laboratory Director, Assisted Reproductive Technology Arizona Center for Reproductive Endocrinology and Infertility Tucson, Arizona , USA
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Environmental Sciences
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Juan A. Blanco - Senior Researcher & Marie Curie Research Fellow Dep. Ciencias del Medio Natural, Universidad Publica de Navarra Campus de Arrosadia, Pamplona, Navarra, Spain
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Mikkola Heimo - University of Eastern Finland, Kuopio, Finland
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Bernardo Llamas Moya - Politechnical University of Madrid, Spain
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Toonika Rinken - Department of Environmental Chemistry, University of Tartu, Estonia
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Immunology and Microbiology
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Dharumadurai Dhanasekaran - Department of Microbiology, School of Life Sciences, Bharathidasan University, India
Isabel Gigli - Facultad de Agronomia-UNLPam, Argentina
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Milad Manafi - Department of Animal Science, Faculty of Agricultural Sciences, Malayer University, Malayer, Iran
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Rita Payan-Carreira - Universidade de Trás-os-Montes e Alto Douro, Departamento de Zootecnia, Portugal
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Medicine
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Mazen Almasri - King Abdulaziz University, Faculty of Dentistry Jeddah, Saudi Arabia Dentistry
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Craig Atwood - University of Wisconsin-Madison, USA Stem Cell Research, Tissue Engineering and Regenerative Medicine
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Oreste Capelli - Clinical Governance, Local Health Authority, Modena, Italy Public Health
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Michael Firstenberg - Assistant Professor of Surgery and Integrative Medicine NorthEast Ohio Medical University, USA & Akron City Hospital - Summa Health System, USA Surgery
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Parul Ichhpujani - MD Government Medical College & Hospital, Department of Ophthalmology, India
Amidou Samie - University of Venda, SA Infectious Diseases
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Shailendra K. Saxena - CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India Infectious Diseases
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Dan T. Simionescu - Department of Bioengineering, Clemson University, Clemson SC, USA Stem Cell Research, Tissue Engineering and Regenerative Medicine
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Ke Xu - Tianjin Lung Cancer Institute Tianjin Medical University General Hospital Tianjin, China Oncology
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Ophthalmology
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Hojjat Ahmadzadehfar - University Hospital Bonn Department of Nuclear Medicine Bonn, Germany Medical Diagnostics, Engineering Technology and Telemedicine
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Miroslav Blumenberg - Department of Ronald O. Perelman Department of Dermatology; Department of Biochemistry and Molecular Pharmacology, Dermatology, NYU School of Medicine, NY, USA Dermatology
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Wilfred Bonney - University of Dundee, Scotland, UK Medical Diagnostics, Engineering Technology and Telemedicine
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Christakis Constantinides - Department of Cardiovascular Medicine University of Oxford, Oxford, UK Medical Diagnostics, Engineering Technology and Telemedicine
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Atef Mohamed Mostafa Darwish - Department of Obstetrics and Gynecology , Faculty of Medicine, Assiut University, Egypt Gynecology
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Ana Polona Mivšek - University of Ljubljana, Ljubljana, Slovenia Midwifery
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Gyula Mozsik - First Department of Medicine, Medical and Health Centre, University of Pécs, Hungary
\\n\\t
Shimon Rumelt - Western Galilee-Nahariya Medical Center, Nahariya, Israel Ophthalmology
\\n\\t
Marcelo Saad - S. Paulo Medical College of Acupuncture, SP, Brazil Complementary and Alternative Medicine
\\n\\t
Minoru Tomizawa - National Hospital Organization Shimoshizu Hospital, Japan Gastroenterology
\\n\\t
Pierre Vereecken - Centre Hospitalier Valida and Cliniques Universitaires Saint-Luc, Belgium Dermatology
\\n
\\n\\n
Gastroenterology
\\n\\n
\\n\\t
Hany Aly - Director, Division of Newborn Services The George Washington University Hospital Washington, USA Pediatrics
\\n\\t
Yannis Dionyssiotis - National and Kapodistrian University of Athens, Greece Orthopedics, Rehabilitation and Physical Medicine
\\n\\t
Alina Gonzales- Quevedo Instituto de Neurología y Neurocirugía Havana, Cuba Mental and Behavioural Disorders and Diseases of the Nervous System
\\n\\t
Margarita Guenova - National Specialized Hospital for Active Treatment of Haematological Diseases, Bulgaria
\\n\\t
Eliska Potlukova - Clinic of Medicine, University Hospital Basel, Switzerland Edocrinology
\\n\\t
Raymond L. Rosales -The Royal and Pontifical University of Santo Tomas, Manila, Philippines & Metropolitan Medical Center, Manila, Philippines & St. Luke's Medical Center International Institute in Neuroscience, Quezon City, Philippines Mental and Behavioural Disorders and Diseases of the Nervous System
\\n\\t
Alessandro Rozim - Zorzi University of Campinas, Departamento de Ortopedia e Traumatologia, Campinas, SP, Brazil Orthopedics, Rehabilitation and Physical Medicine
\\n\\t
Dieter Schoepf - University of Bonn, Germany Mental and Behavioural Disorders and Diseases of the Nervous System
\\n
\\n\\n
Hematology
\\n\\n
\\n\\t
Hesham Abd El-Dayem - National Liver Institute, Menoufeyia University, Egypt Hepatology
\\n\\t
Fayez Bahmad - Health Science Faculty of the University of Brasilia Instructor of Otology at Brasilia University Hospital Brasilia, Brazil Otorhinolaryngology
\\n\\t
Peter A. Clark - Saint Joseph's University Philadelphia, Pennsylvania, USA Bioethics
\\n\\t
Celso Pereira - Coimbra University, Coimbra, Portugal Immunology, Allergology and Rheumatology
\\n\\t
Luis Rodrigo - Asturias Central University Hospital (HUCA) School of Medicine, University of Oviedo, Oviedo, Spain Hepatology & Gastroenterology
\\n\\t
Dennis Wat - Liverpool Heart and Chest Hospital NHS Foundation Trust, UK Pulmonology
\\n
\\n\\n
Social Sciences and Humanities Board
\\n\\n
Business, Management and Economics
\\n\\n
\\n\\t
Vito Bobek - University of Applied Sciences, FH Joanneum, Graz, Austria
Joao Luis Garcia Rosa - Associate Professor Bio-inspired Computing Laboratory (BioCom) Department of Computer Science University of Sao Paulo (USP) at Sao Carlos, Brazil
\n\t
Jan Valdman - Institute of Mathematics and Biomathematics, University of South Bohemia, České Budějovice, Czech Republic Institute of Information Theory and Automation of the ASCR, Prague, Czech Republic
\n
\n\n
Earth and Planetary Science
\n\n
\n\t
Jill S. M. Coleman - Department of Geography, Ball State University, Muncie, IN, USA
\n\t
İbrahim Küçük Erciyes - Üniversitesi Department of Astronomy and Space Sciences Melikgazi, Kayseri, Turkey
\n\t
Pasquale Imperatore - Electromagnetic Environmental Sensing (IREA), Italian National Council of Research (CNR), Naples, Italy
\n\t
Mohammad Mokhtari - Director of National Center for Earthquake Prediction International Institute of Earthquake Engineering and Seismology (IIEES), Tehran, Iran
\n
\n\n
Engineering
\n\n
\n\t
Narottam Das - University of Southern Queensland, Australia
\n\t
Jose Ignacio Huertas - Energy and Climate Change Research Group; Instituto Tecnológico y Estudios Superiores de Monterrey, Mexico
Likun Pan - Engineering Research Center for Nanophotonics and Advanced Instrument, Ministry of Education, Department of Physics, East China Normal University, China
\n\t
Mukul Chandra Paul - Central Glass & Ceramic Research Institute Jadavpur, Kolkata, India
\n\t
Stephen E. Saddow - Electrical Engineering Department, University of South Florida, USA
\n\t
Ali Demir Sezer - Marmara University, Faculty of Pharmacy, Department of Pharmaceutical Biotechnology, İstanbul, Turkey
\n\t
Krzysztof Zboinski - Warsaw University of Technology, Faculty of Transport, Warsaw, Poland
\n
\n\n
Materials Science
\n\n
\n\t
Vadim Glebovsky - Senior Researcher, Institute of Solid State Physics, Chernogolovka, Russia Expert of the Russian Fund for Basic Research, Moscow, Russia
\n\t
Jianjun Liu - State Key Laboratory of High Performance Ceramics and Superfine Microstructure of Shanghai Institute of Ceramics, Chinese Academy of Sciences, China
\n\t
Pietro Mandracci - Department of Applied Science and Technology, Politecnico di Torino, Italy
\n\t
Waldemar Alfredo Monteiro - Instituto de Pesquisas Energéticas e Nucleares Materials Science and Technology Center (MSTC) São Paulo, SP, Brazil
Toshio Ogawa - Department of Electrical and Electronic Engineering, Shizuoka Institute of Science and Technology, Toyosawa, Fukuroi, Shizuoka, Japan
\n
\n\n
Mathematics
\n\n
\n\t
Paul Bracken - Department of Mathematics University of Texas, Edinburg, TX, USA
\n
\n\n
Nanotechnology and Nanomaterials
\n\n
\n\t
Muhammad Akhyar - Farrukh Nano-Chemistry Lab. Registrar, GC University Lahore, Pakistan
\n\t
Khan Maaz - Chinese Academy of Sciences, China & The Pakistan Institute of Nuclear Science and Technology, Pakistan
\n
\n\n
Physics
\n\n
\n\t
Izabela Naydenova - Lecturer, School of Physics Principal Investigator, IEO Centre College of Sciences and Health Dublin Institute of Technology Dublin, Ireland
\n\t
Mitsuru Nenoi - National Institute of Radiological Sciences, Japan
\n\t
Christos Volos - Physics Department, Aristotle University of Thessaloniki, Greece
\n
\n\n
Robotics
\n\n
\n\t
Alejandra Barrera - Instituto Tecnológico Autónomo de México, México
\n\t
Dusan M. Stipanovic - Department of Industrial and Enterprise Systems Engineering, University of Illinois at Urbana-Champaign
\n\t
Andrzej Zak - Polish Naval Academy Faculty of Navigation and Naval Weapons Institute of Naval Weapons and Computer Science, Gdynia, Poland
Petr Konvalina - Faculty of Agriculture, University of South Bohemia in České Budějovice, Czech Republic
\n
\n\n
Biochemistry, Genetics and Molecular Biology
\n\n
\n\t
Chunfa Huang - Saint Louis University, Saint Louis, USA
\n\t
Michael Kormann - University Children's Clinic Department of Pediatrics I, Pediatric Infectiology & Immunology, Translational Genomics and Gene Therapy in Pediatrics, University of Tübingen, Tübingen, Germany
\n\t
Bin WU - Ph.D. HCLD Scientific Laboratory Director, Assisted Reproductive Technology Arizona Center for Reproductive Endocrinology and Infertility Tucson, Arizona , USA
\n
\n\n
Environmental Sciences
\n\n
\n\t
Juan A. Blanco - Senior Researcher & Marie Curie Research Fellow Dep. Ciencias del Medio Natural, Universidad Publica de Navarra Campus de Arrosadia, Pamplona, Navarra, Spain
\n\t
Mikkola Heimo - University of Eastern Finland, Kuopio, Finland
\n\t
Bernardo Llamas Moya - Politechnical University of Madrid, Spain
\n\t
Toonika Rinken - Department of Environmental Chemistry, University of Tartu, Estonia
\n
\n\n
Immunology and Microbiology
\n\n
\n\t
Dharumadurai Dhanasekaran - Department of Microbiology, School of Life Sciences, Bharathidasan University, India
Isabel Gigli - Facultad de Agronomia-UNLPam, Argentina
\n\t
Milad Manafi - Department of Animal Science, Faculty of Agricultural Sciences, Malayer University, Malayer, Iran
\n\t
Rita Payan-Carreira - Universidade de Trás-os-Montes e Alto Douro, Departamento de Zootecnia, Portugal
\n
\n\n
Medicine
\n\n
\n\t
Mazen Almasri - King Abdulaziz University, Faculty of Dentistry Jeddah, Saudi Arabia Dentistry
\n\t
Craig Atwood - University of Wisconsin-Madison, USA Stem Cell Research, Tissue Engineering and Regenerative Medicine
\n\t
Oreste Capelli - Clinical Governance, Local Health Authority, Modena, Italy Public Health
\n\t
Michael Firstenberg - Assistant Professor of Surgery and Integrative Medicine NorthEast Ohio Medical University, USA & Akron City Hospital - Summa Health System, USA Surgery
\n\t
Parul Ichhpujani - MD Government Medical College & Hospital, Department of Ophthalmology, India
Amidou Samie - University of Venda, SA Infectious Diseases
\n\t
Shailendra K. Saxena - CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India Infectious Diseases
\n\t
Dan T. Simionescu - Department of Bioengineering, Clemson University, Clemson SC, USA Stem Cell Research, Tissue Engineering and Regenerative Medicine
\n\t
Ke Xu - Tianjin Lung Cancer Institute Tianjin Medical University General Hospital Tianjin, China Oncology
\n
\n\n
Ophthalmology
\n\n
\n\t
Hojjat Ahmadzadehfar - University Hospital Bonn Department of Nuclear Medicine Bonn, Germany Medical Diagnostics, Engineering Technology and Telemedicine
\n\t
Miroslav Blumenberg - Department of Ronald O. Perelman Department of Dermatology; Department of Biochemistry and Molecular Pharmacology, Dermatology, NYU School of Medicine, NY, USA Dermatology
\n\t
Wilfred Bonney - University of Dundee, Scotland, UK Medical Diagnostics, Engineering Technology and Telemedicine
\n\t
Christakis Constantinides - Department of Cardiovascular Medicine University of Oxford, Oxford, UK Medical Diagnostics, Engineering Technology and Telemedicine
\n\t
Atef Mohamed Mostafa Darwish - Department of Obstetrics and Gynecology , Faculty of Medicine, Assiut University, Egypt Gynecology
\n\t
Ana Polona Mivšek - University of Ljubljana, Ljubljana, Slovenia Midwifery
\n\t
Gyula Mozsik - First Department of Medicine, Medical and Health Centre, University of Pécs, Hungary
\n\t
Shimon Rumelt - Western Galilee-Nahariya Medical Center, Nahariya, Israel Ophthalmology
\n\t
Marcelo Saad - S. Paulo Medical College of Acupuncture, SP, Brazil Complementary and Alternative Medicine
\n\t
Minoru Tomizawa - National Hospital Organization Shimoshizu Hospital, Japan Gastroenterology
\n\t
Pierre Vereecken - Centre Hospitalier Valida and Cliniques Universitaires Saint-Luc, Belgium Dermatology
\n
\n\n
Gastroenterology
\n\n
\n\t
Hany Aly - Director, Division of Newborn Services The George Washington University Hospital Washington, USA Pediatrics
\n\t
Yannis Dionyssiotis - National and Kapodistrian University of Athens, Greece Orthopedics, Rehabilitation and Physical Medicine
\n\t
Alina Gonzales- Quevedo Instituto de Neurología y Neurocirugía Havana, Cuba Mental and Behavioural Disorders and Diseases of the Nervous System
\n\t
Margarita Guenova - National Specialized Hospital for Active Treatment of Haematological Diseases, Bulgaria
\n\t
Eliska Potlukova - Clinic of Medicine, University Hospital Basel, Switzerland Edocrinology
\n\t
Raymond L. Rosales -The Royal and Pontifical University of Santo Tomas, Manila, Philippines & Metropolitan Medical Center, Manila, Philippines & St. Luke's Medical Center International Institute in Neuroscience, Quezon City, Philippines Mental and Behavioural Disorders and Diseases of the Nervous System
\n\t
Alessandro Rozim - Zorzi University of Campinas, Departamento de Ortopedia e Traumatologia, Campinas, SP, Brazil Orthopedics, Rehabilitation and Physical Medicine
\n\t
Dieter Schoepf - University of Bonn, Germany Mental and Behavioural Disorders and Diseases of the Nervous System
\n
\n\n
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\n\n
\n\t
Hesham Abd El-Dayem - National Liver Institute, Menoufeyia University, Egypt Hepatology
\n\t
Fayez Bahmad - Health Science Faculty of the University of Brasilia Instructor of Otology at Brasilia University Hospital Brasilia, Brazil Otorhinolaryngology
\n\t
Peter A. Clark - Saint Joseph's University Philadelphia, Pennsylvania, USA Bioethics
\n\t
Celso Pereira - Coimbra University, Coimbra, Portugal Immunology, Allergology and Rheumatology
\n\t
Luis Rodrigo - Asturias Central University Hospital (HUCA) School of Medicine, University of Oviedo, Oviedo, Spain Hepatology & Gastroenterology
\n\t
Dennis Wat - Liverpool Heart and Chest Hospital NHS Foundation Trust, UK Pulmonology
\n
\n\n
Social Sciences and Humanities Board
\n\n
Business, Management and Economics
\n\n
\n\t
Vito Bobek - University of Applied Sciences, FH Joanneum, Graz, Austria
Denis Erasga - De La Salle University, Phillippines
\n\t
Rosario Laratta - Associate Professor of Social Policy and Development Graduate School of Governance Studies, Meiji University, Japan
\n
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Currently, he is a professor of Orthodontics. He holds a Certificate of Advanced Study type A in Technology of Biomaterials used in Dentistry (1995); Certificate of Advanced Study type B in Dento-Facial Orthopaedics (1997) from the Faculty of Dental Surgery, University Denis Diderot-Paris VII, France; Diploma of Advanced Study (DESA) in Biocompatibility of Biomaterials from the Faculty of Medicine and Pharmacy of Casablanca (2002); Certificate of Clinical Occlusodontics from the Faculty of Dentistry of Casablanca (2004); University Diploma of Biostatistics and Perceptual Health Measurement from the Faculty of Medicine and Pharmacy of Casablanca (2011); and a University Diploma of Pedagogy of Odontological Sciences from the Faculty of Dentistry of Casablanca (2013). 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He is an academic staff member of the Department of Reproduction and Artificial Insemination, Selçuk University, Turkey. He manages several studies on sperms and embryos and is an editorial board member for several international journals. His studies include sperm cryobiology, in vitro fertilization, and embryo production in animals.",institutionString:"Selçuk University, Faculty of Veterinary Medicine",institution:null},{id:"90846",title:"Prof.",name:"Yusuf",middleName:null,surname:"Bozkurt",slug:"yusuf-bozkurt",fullName:"Yusuf Bozkurt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/90846/images/system/90846.jpg",biography:"Yusuf Bozkurt has a BSc, MSc, and Ph.D. from Ankara University, Turkey. He is currently a Professor of Biotechnology of Reproduction in the field of Aquaculture, İskenderun Technical University, Turkey. His research interests include reproductive biology and biotechnology with an emphasis on cryo-conservation. He is on the editorial board of several international peer-reviewed journals and has published many papers. Additionally, he has participated in many international and national congresses, seminars, and workshops with oral and poster presentations. He is an active member of many local and international organizations.",institutionString:"İskenderun Technical University",institution:{name:"İskenderun Technical University",country:{name:"Turkey"}}},{id:"61139",title:"Dr.",name:"Sergey",middleName:null,surname:"Tkachev",slug:"sergey-tkachev",fullName:"Sergey Tkachev",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/61139/images/system/61139.png",biography:"Dr. Sergey Tkachev is a senior research scientist at the Institute of Fundamental Medicine and Biology, Kazan Federal University, Russia, and at the Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia. He received his Ph.D. in Molecular Biology with his thesis “Genetic variability of the tick-borne encephalitis virus in natural foci of Novosibirsk city and its suburbs.” His primary field is molecular virology with research emphasis on vector-borne viruses, especially tick-borne encephalitis virus, Kemerovo virus and Omsk hemorrhagic fever virus, rabies virus, molecular genetics, biology, and epidemiology of virus pathogens.",institutionString:"Russian Academy of Sciences",institution:{name:"Russian Academy of Sciences",country:{name:"Russia"}}},{id:"310962",title:"Dr.",name:"Amlan",middleName:"Kumar",surname:"Patra",slug:"amlan-patra",fullName:"Amlan Patra",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/310962/images/system/310962.jpg",biography:"Amlan K. Patra, FRSB, obtained a Ph.D. in Animal Nutrition from Indian Veterinary Research Institute, India, in 2002. He is currently an associate professor at West Bengal University of Animal and Fishery Sciences. He has more than twenty years of research and teaching experience. He held previous positions at the American Institute for Goat Research, The Ohio State University, Columbus, USA, and Free University of Berlin, Germany. His research focuses on animal nutrition, particularly ruminants and poultry nutrition, gastrointestinal electrophysiology, meta-analysis and modeling in nutrition, and livestock–environment interaction. He has authored around 175 articles in journals, book chapters, and proceedings. Dr. Patra serves on the editorial boards of several reputed journals.",institutionString:null,institution:{name:"West Bengal University of Animal and Fishery Sciences",country:{name:"India"}}},{id:"53998",title:"Prof.",name:"László",middleName:null,surname:"Babinszky",slug:"laszlo-babinszky",fullName:"László Babinszky",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/53998/images/system/53998.png",biography:"László Babinszky is Professor Emeritus, Department of Animal Nutrition Physiology, University of Debrecen, Hungary. He has also worked in the Department of Animal Nutrition, University of Wageningen, Netherlands; the Institute for Livestock Feeding and Nutrition (IVVO), Lelystad, Netherlands; the Agricultural University of Vienna (BOKU); the Institute for Animal Breeding and Nutrition, Austria; and the Oscar Kellner Research Institute for Animal Nutrition, Rostock, Germany. In 1992, Dr. Babinszky obtained a Ph.D. in Animal Nutrition from the University of Wageningen. His main research areas are swine and poultry nutrition. He has authored more than 300 publications (papers, book chapters) and edited four books and fourteen international conference proceedings.",institutionString:"University of Debrecen",institution:{name:"University of Debrecen",country:{name:"Hungary"}}},{id:"201830",title:"Dr.",name:"Fernando",middleName:"Sanchez",surname:"Davila",slug:"fernando-davila",fullName:"Fernando Davila",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/201830/images/5017_n.jpg",biography:"I am a professor at UANL since 1988. My research lines are the development of reproductive techniques in small ruminants. We also conducted research on sexual and social behavior in males.\nI am Mexican and study my professional career as an engineer in agriculture and animal science at UANL. Then take a masters degree in science in Germany (Animal breeding). Take a doctorate in animal science at the UANL.",institutionString:null,institution:{name:"Universidad Autónoma de Nuevo León",country:{name:"Mexico"}}},{id:"309250",title:"Dr.",name:"Miguel",middleName:null,surname:"Quaresma",slug:"miguel-quaresma",fullName:"Miguel Quaresma",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/309250/images/9059_n.jpg",biography:"Miguel Nuno Pinheiro Quaresma was born on May 26, 1974 in Dili, Timor Island. He is married with two children: a boy and a girl, and he is a resident in Vila Real, Portugal. He graduated in Veterinary Medicine in August 1998 and obtained his Ph.D. degree in Veterinary Sciences -Clinical Area in February 2015, both from the University of Trás-os-Montes e Alto Douro. He is currently enrolled in the Alternative Residency of the European College of Animal Reproduction. He works as a Senior Clinician at the Veterinary Teaching Hospital of UTAD (HVUTAD) with a role in clinical activity in the area of livestock and equine species as well as to support teaching and research in related areas. He teaches as an Invited Professor in Reproduction Medicine I and II of the Master\\'s in Veterinary Medicine degree at UTAD. Currently, he holds the position of Chairman of the Portuguese Buiatrics Association. He is a member of the Consultive Group on Production Animals of the OMV. He has 19 publications in indexed international journals (ISIS), as well as over 60 publications and oral presentations in both Portuguese and international journals and congresses.",institutionString:"University of Trás-os-Montes and Alto Douro",institution:{name:"University of Trás-os-Montes and Alto Douro",country:{name:"Portugal"}}},{id:"38652",title:"Prof.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",country:{name:"Portugal"}}},{id:"283019",title:"Dr.",name:"Oudessa",middleName:null,surname:"Kerro Dego",slug:"oudessa-kerro-dego",fullName:"Oudessa Kerro Dego",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/283019/images/system/283019.png",biography:"Dr. Kerro Dego is a veterinary microbiologist with training in veterinary medicine, microbiology, and anatomic pathology. Dr. Kerro Dego is an assistant professor of dairy health in the department of animal science, the University of Tennessee, Institute of Agriculture, Knoxville, Tennessee. He received his D.V.M. (1997), M.S. (2002), and Ph.D. (2008) degrees in Veterinary Medicine, Animal Pathology and Veterinary Microbiology from College of Veterinary Medicine, Addis Ababa University, Ethiopia; College of Veterinary Medicine, Utrecht University, the Netherlands and Western College of Veterinary Medicine, University of Saskatchewan, Canada respectively. He did his Postdoctoral training in microbial pathogenesis (2009 - 2015) in the Department of Animal Science, the University of Tennessee, Institute of Agriculture, Knoxville, Tennessee. Dr. Kerro Dego’s research focuses on the prevention and control of infectious diseases of farm animals, particularly mastitis, improving dairy food safety, and mitigation of antimicrobial resistance. Dr. Kerro Dego has extensive experience in studying the pathogenesis of bacterial infections, identification of virulence factors, and vaccine development and efficacy testing against major bacterial mastitis pathogens. Dr. Kerro Dego conducted numerous controlled experimental and field vaccine efficacy studies, vaccination, and evaluation of immunological responses in several species of animals, including rodents (mice) and large animals (bovine and ovine).",institutionString:"University of Tennessee at Knoxville",institution:{name:"University of Tennessee at Knoxville",country:{name:"United States of America"}}},{id:"251314",title:"Dr.",name:"Juan Carlos",middleName:null,surname:"Gardón Poggi",slug:"juan-carlos-gardon-poggi",fullName:"Juan Carlos Gardón Poggi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/251314/images/system/251314.jpeg",biography:"Juan Carlos Gardón Poggi received University degree from the Faculty of Agrarian Science in Argentina, in 1983. Also he received Masters Degree and PhD from Córdoba University, Spain. He is currently a Professor at the Catholic University of Valencia San Vicente Mártir, at the Department of Medicine and Animal Surgery. He teaches diverse courses in the field of Animal Reproduction and he is the Director of the Veterinary Farm. He also participates in academic postgraduate activities at the Veterinary Faculty of Murcia University, Spain. His research areas include animal physiology, physiology and biotechnology of reproduction either in males or females, the study of gametes under in vitro conditions and the use of ultrasound as a complement to physiological studies and development of applied biotechnologies. Routinely, he supervises students preparing their doctoral, master thesis or final degree projects.",institutionString:null,institution:{name:"Valencia Catholic University Saint Vincent Martyr",country:{name:"Spain"}}},{id:"309529",title:"Dr.",name:"Albert",middleName:null,surname:"Rizvanov",slug:"albert-rizvanov",fullName:"Albert Rizvanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/309529/images/9189_n.jpg",biography:'Albert A. Rizvanov is a Professor and Director of the Center for Precision and Regenerative Medicine at the Institute of Fundamental Medicine and Biology, Kazan Federal University (KFU), Russia. He is the Head of the Center of Excellence “Regenerative Medicine” and Vice-Director of Strategic Academic Unit \\"Translational 7P Medicine\\". Albert completed his Ph.D. at the University of Nevada, Reno, USA and Dr.Sci. at KFU. He is a corresponding member of the Tatarstan Academy of Sciences, Russian Federation. Albert is an author of more than 300 peer-reviewed journal articles and 22 patents. He has supervised 11 Ph.D. and 2 Dr.Sci. dissertations. Albert is the Head of the Dissertation Committee on Biochemistry, Microbiology, and Genetics at KFU.\nORCID https://orcid.org/0000-0002-9427-5739\nWebsite https://kpfu.ru/Albert.Rizvanov?p_lang=2',institutionString:"Kazan Federal University",institution:{name:"Kazan Federal University",country:{name:"Russia"}}},{id:"210551",title:"Dr.",name:"Arbab",middleName:null,surname:"Sikandar",slug:"arbab-sikandar",fullName:"Arbab Sikandar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210551/images/system/210551.jpg",biography:"Dr. Arbab Sikandar, PhD, M. Phil, DVM was born on April 05, 1981. He is currently working at the College of Veterinary & Animal Sciences as an Assistant Professor. He previously worked as a lecturer at the same University. \nHe is a Member/Secretory of Ethics committee (No. CVAS-9377 dated 18-04-18), Member of the QEC committee CVAS, Jhang (Regr/Gen/69/873, dated 26-10-2017), Member, Board of studies of Department of Basic Sciences (No. CVAS. 2851 Dated. 12-04-13, and No. CVAS, 9024 dated 20/11/17), Member of Academic Committee, CVAS, Jhang (No. CVAS/2004, Dated, 25-08-12), Member of the technical committee (No. CVAS/ 4085, dated 20,03, 2010 till 2016).\n\nDr. Arbab Sikandar contributed in five days hands-on-training on Histopathology at the Department of Pathology, UVAS from 12-16 June 2017. He received a Certificate of appreciation for contributions for Popularization of Science and Technology in the Society on 17-11-15. He was the resource person in the lecture series- ‘scientific writing’ at the Department of Anatomy and Histology, UVAS, Lahore on 29th October 2015. He won a full fellowship as a principal candidate for the year 2015 in the field of Agriculture, EICA, Egypt with ref. to the Notification No. 12(11) ACS/Egypt/2014 from 10 July 2015 to 25th September 2015.; he received a grant of Rs. 55000/- as research incentives from Director, Advanced Studies and Research, UVAS, Lahore upon publications of research papers in IF Journals (DR/215, dated 19-5-2014.. He obtained his PhD by winning a HEC Pakistan indigenous Scholarship, ‘Ph.D. fellowship for 5000 scholars – Phase II’ (2av1-147), 17-6/HEC/HRD/IS-II/12, November 15, 2012. \n\nDr. Sikandar is a member of numerous societies: Registered Veterinary Medical Practitioner (life member) and Registered Veterinary Medical Faculty of Pakistan Veterinary Medical Council. The Registration code of PVMC is RVMP/4298 and RVMF/ 0102.; Life member of the University of Veterinary and Animal Sciences, Lahore, Alumni Association with S# 664, dated: 6-4-12. ; Member 'Vets Care Organization Pakistan” with Reference No. VCO-605-149, dated 05-04-06. :Member 'Vet Crescent” (Society of Animal Health and Production), UVAS, Lahore.",institutionString:"University of Veterinary & Animal Science",institution:{name:"University of Veterinary and Animal Sciences",country:{name:"Pakistan"}}},{id:"311663",title:"Dr.",name:"Prasanna",middleName:null,surname:"Pal",slug:"prasanna-pal",fullName:"Prasanna Pal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311663/images/13261_n.jpg",biography:null,institutionString:null,institution:{name:"National Dairy Research Institute",country:{name:"India"}}},{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. Dr. Rutland has also written popular science books for the public. https://orcid.org/0000-0002-2009-4898. www.nottingham.ac.uk/vet/people/catrin.rutland",institutionString:null,institution:{name:"University of Nottingham",country:{name:"United Kingdom"}}},{id:"283315",title:"Prof.",name:"Samir",middleName:null,surname:"El-Gendy",slug:"samir-el-gendy",fullName:"Samir El-Gendy",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRduYQAS/Profile_Picture_1606215849748",biography:"Samir El-Gendy is a Professor of anatomy and embryology at the faculty of veterinary medicine, Alexandria University, Egypt. Samir obtained his PhD in veterinary science in 2007 from the faculty of veterinary medicine, Alexandria University and has been a professor since 2017. Samir is an author on 24 articles at Scopus and 12 articles within local journals and 2 books/book chapters. His research focuses on applied anatomy, imaging techniques and computed tomography. Samir worked as a member of different local projects on E-learning and he is a board member of the African Association of Veterinary Anatomists and of anatomy societies and as an associated author at local and international journals. Orcid: https://orcid.org/0000-0002-6180-389X",institutionString:null,institution:{name:"Alexandria University",country:{name:"Egypt"}}},{id:"246149",title:"Dr.",name:"Valentina",middleName:null,surname:"Kubale",slug:"valentina-kubale",fullName:"Valentina Kubale",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246149/images/system/246149.jpg",biography:"Valentina Kubale is Associate Professor of Veterinary Medicine at the Veterinary Faculty, University of Ljubljana, Slovenia. Since graduating from the Veterinary faculty she obtained her PhD in 2007, performed collaboration with the Department of Pharmacology, University of Copenhagen, Denmark. She continued as a post-doctoral fellow at the University of Copenhagen with a Lundbeck foundation fellowship. She is the editor of three books and author/coauthor of 23 articles in peer-reviewed scientific journals, 16 book chapters, and 68 communications at scientific congresses. Since 2008 she has been the Editor Assistant for the Slovenian Veterinary Research journal. 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To date, Katy has taught 22 years in the Department of Animal Medicine and Surgery at the CEU-Cardenal Herrera University in undergraduate courses in Veterinary Medicine (General Pathology, integrated into the Applied Basis of Veterinary Medicine module of the 2nd year, Clinical Equine I of 3rd year, and Equine Clinic II of 4th year). Dr. Satué research activity is in the field of Endocrinology, Hematology, Biochemistry, and Immunology in the Spanish Purebred mare. She has directed 5 Doctoral Theses and 5 Diplomas of Advanced Studies, and participated in 11 research projects as a collaborating researcher. She has written 2 books and 14 book chapters in international publishers related to the area, and 68 scientific publications in international journals. Dr. Satué has attended 63 congresses, participating with 132 communications in international congresses and 19 in national congresses related to the area. Dr. Satué is a scientific reviewer for various prestigious international journals such as Animals, American Journal of Obstetrics and Gynecology, Veterinary Clinical Pathology, Journal of Equine Veterinary Science, Reproduction in Domestic Animals, Research Veterinary Science, Brazilian Journal of Medical and Biological Research, Livestock Production Science and Theriogenology, among others. 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PhD\\\'s degree in Science (Cell and Tissue Biology Area) \n at University of Sao Paulo with scholarship granted by FAPESP; Project \\"Development of morphofunctional changes in ovary of Astyanax altiparanae Garutti & Britski, 2000 (Teleostei, Characidae)\\". She has experience in Reproduction of vertebrates and Morphology, with emphasis in Cellular Biology and Histology. 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Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. 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