More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
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Our breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
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“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
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Additionally, each book published by IntechOpen contains original content and research findings.
\\n\\n
We are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
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Simba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
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IntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\n
Since the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\n
More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\n
Our breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n
“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\n
Additionally, each book published by IntechOpen contains original content and research findings.
\n\n
We are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n
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\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"8983",leadTitle:null,fullTitle:"Sustainability Concept In Developing Countries",title:"Sustainability Concept In Developing Countries",subtitle:null,reviewType:"peer-reviewed",abstract:"Sustainability Concept in Developing Countries is a collection of seven studies addressing the issue of sustainability from the perspective of developing countries. Although it is not a comprehensive review of all developing countries, these contributions do portray some of the major issues in achieving sustainability in many developing countries. The book is divided into two parts: Part 1 includes chapters related to concepts and methodology relevant to sustainability in the context of developing countries. Part 2 presents some actual case studies including descriptions of the situations and advice on how to address sustainability in such economies. This book is a useful reference for professionals in developing countries as well as other jurisdictions.",isbn:"978-1-83880-473-2",printIsbn:"978-1-83880-472-5",pdfIsbn:"978-1-78985-855-6",doi:"10.5772/intechopen.82946",price:119,priceEur:129,priceUsd:155,slug:"sustainability-concept-in-developing-countries",numberOfPages:122,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"2b7e452ede9e56b4a3b7e35c835f8446",bookSignature:"Surendra N. Kulshreshtha",publishedDate:"May 27th 2020",coverURL:"https://cdn.intechopen.com/books/images_new/8983.jpg",numberOfDownloads:4498,numberOfWosCitations:6,numberOfCrossrefCitations:5,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:9,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:20,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 24th 2019",dateEndSecondStepPublish:"September 23rd 2019",dateEndThirdStepPublish:"November 22nd 2019",dateEndFourthStepPublish:"February 10th 2020",dateEndFifthStepPublish:"April 10th 2020",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"37057",title:"Dr.",name:"Surendra N.",middleName:null,surname:"Kulshreshtha",slug:"surendra-n.-kulshreshtha",fullName:"Surendra N. Kulshreshtha",profilePictureURL:"https://mts.intechopen.com/storage/users/37057/images/system/37057.jpeg",biography:"Suren(dra) N. Kulshreshtha is currently a professor of agricultural economics at the University of Saskatchewan, Saskatoon, a position he has held for the past 50 years. He joined the University of Saskatchewan in 1969. He has been a Visiting Scientist at the International Institute for Applied Systems Analysis, at Laxenburg, Austria. He has also served various professional societies in capacities such as Editor of the Canadian Journal of Agricultural Economics, and Associate Editor of the Canadian Water Resources Journal. He has also participated in several oversees projects in Indonesia, Zambia and India through the Canadian International Development Agency. On the basis of his contributions to the profession of agricultural economics, the Canadian Society of Agricultural Economics selected him a Fellow of the Canadian Agricultural Economics Society in 2004.",institutionString:"University of Saskatchewan",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"5",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:"University of Saskatchewan",institutionURL:null,country:{name:"Canada"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"136",title:"Environmental Sustainability",slug:"environmental-sciences-environmental-sustainability"}],chapters:[{id:"71138",title:"A People-Centred Social Totality Approach to Low-Income Housing in the Developing World",doi:"10.5772/intechopen.89258",slug:"a-people-centred-social-totality-approach-to-low-income-housing-in-the-developing-world",totalDownloads:823,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In a significant part of the developing world, especially sub-Saharan Africa, public housing policies and implementation have depended on a top-to-bottom approach in an attempt to ensure housing supply. However, public authorities sometimes backed by international agencies preferring to operate through the housing market have failed to meet the housing need, especially for low-income people. Even when the users are involved like in the slum dwellers association, the organisation of the process is majorly controlled by the public authorities. While government and public institutions attained minimal success in housing provision for the lowest classes in the society, the people have been more successful in housing production. This chapter situates the housing problem and policy responses in the context of the developing world characterised by limited capacity to control and manage the largely more successful informal people-controlled housing production structure. A cyclic people-centred strategy framework for low-income housing is proposed based on town-gown collaboration in studying low-income people, their activated housing process and the houses produced to guide present strategies and synthesise future strategies and policy. This framework emanates from Henri Lefebvre’s social totality explanation to understand how low-income people negotiate housing from the social context.",signatures:"E. Babatunde Jaiyeoba and Abimbola O. Asojo",downloadPdfUrl:"/chapter/pdf-download/71138",previewPdfUrl:"/chapter/pdf-preview/71138",authors:[{id:"284052",title:"Prof.",name:"Abimbola O.",surname:"Asojo",slug:"abimbola-o.-asojo",fullName:"Abimbola O. Asojo"},{id:"284053",title:"Dr.",name:"Babatunde",surname:"Jaiyeoba",slug:"babatunde-jaiyeoba",fullName:"Babatunde Jaiyeoba"}],corrections:null},{id:"71095",title:"Temporal MCDA Methods for Decision-Making in Sustainable Development Context",doi:"10.5772/intechopen.90698",slug:"temporal-mcda-methods-for-decision-making-in-sustainable-development-context",totalDownloads:556,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Public decision-making problems are more and more complex in a context where decisions have to be made based concurrently on economic, social, and environmental considerations. In this context, decisions need to be evaluated in the short, medium, and long term because their planning horizons are usually of several years or even decades. A literature review on MCDA methods used in the sustainable development (SD) context shows that most MCDA methods used are static and existing research does not propose any aggregation framework for temporal assessment of actions. In the last 5 years, development of temporal MCDA has witnessed the interest of some researchers. However, the latest developments remain limited, and only a few research studies offer aggregation frameworks for multi-period settings. This paper presents two recent temporal MCDA methods that were applied in SD context. The first is MUPOM method which demonstrates how outranking methods, based on concordance-discordance principles, can be generalized to processing temporal impacts of decisions. The second, named PROMETHEE-MP, consists of a multi-period generalization of PROMETHEE under random uncertainty.",signatures:"Anissa Frini, Sarah Benamor and Bruno Urli",downloadPdfUrl:"/chapter/pdf-download/71095",previewPdfUrl:"/chapter/pdf-preview/71095",authors:[{id:"304105",title:"Prof.",name:"Anissa",surname:"Frini",slug:"anissa-frini",fullName:"Anissa Frini"},{id:"311926",title:"Prof.",name:"Sarah",surname:"Benamor",slug:"sarah-benamor",fullName:"Sarah Benamor"},{id:"311927",title:"Prof.",name:"Bruno",surname:"Urli",slug:"bruno-urli",fullName:"Bruno Urli"}],corrections:null},{id:"70971",title:"Integrating Water-Food-Energy Nexus with Climate Services: Modelling and Assessment for a Case Study in Africa",doi:"10.5772/intechopen.90914",slug:"integrating-water-food-energy-nexus-with-climate-services-modelling-and-assessment-for-a-case-study-",totalDownloads:513,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This chapter is based on the work of DAFNE project, a decision analytic framework to explore the water-energy-food (WEF) nexus in complex transboundary water resources of fast developing countries. In particular, we developed three geo- and temporally referenced scenarios under economic growth and climate change in the Zambezi river basin (ZRB), which is the fourth largest river basin in Africa and located in eight different countries.1 The future scenarios are conceptually driven by the selected combination of the shared socio-economic pathways (SSPs) and the Representative Concentration Pathway (RCP) 4.5. The time horizon of the explored case study in the ZRB shared by eight countries is the period from 2018 to 2060. The aim of this work is to develop a better understanding of the WEF nexus by providing the input to a cost-benefit optimization model aiming to optimally allocate over time and space water-energy-food. The findings show that the water, energy and food requirements are expected to double during the period of interest considering only demographic development, while economic development and international trade will put an additional burden to the supply chain in meeting those goals.",signatures:"Phoebe Koundouri and Lydia Papadaki",downloadPdfUrl:"/chapter/pdf-download/70971",previewPdfUrl:"/chapter/pdf-preview/70971",authors:[{id:"26338",title:"Dr.",name:"Phoebe",surname:"Koundouri",slug:"phoebe-koundouri",fullName:"Phoebe Koundouri"},{id:"304979",title:"Dr.",name:"Lydia",surname:"Papadaki",slug:"lydia-papadaki",fullName:"Lydia Papadaki"}],corrections:null},{id:"70451",title:"Consequences of Herbicide Use in Rural Environments and Their Effect on Agricultural Workers",doi:"10.5772/intechopen.90546",slug:"consequences-of-herbicide-use-in-rural-environments-and-their-effect-on-agricultural-workers",totalDownloads:662,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The herbicides are used frequently to fight the proliferation of weeds. The use of herbicides correlates with an improvement in agricultural yield, but the harm to the health of human populations is well established and has been demonstrated in numerous scientific studies. In many developing countries, farmers build their own homes, and this, along with the application of herbicides in their fields, increases their exposure, through both contact with skin and respiration. It is scientifically proven that herbicides cause infertility, kidney problems, endocrine disruption, apoptosis, cytotoxicity, and neurotoxic effects. Such diseases impact the quality of those affected, and naturally the contaminated environment negatively affects human health. This chapter focuses on revising the most relevant studies regarding the health effects on agricultural workers living in rural environments due to herbicide contamination and how to sustain the herbicide use.",signatures:"Ana Paola Balderrama-Carmona, Norma Patricia Silva-Beltrán, Luis Alberto Zamora Alvarez, Norma Patricia Adan Bante and Edgar Felipe Moran Palacio",downloadPdfUrl:"/chapter/pdf-download/70451",previewPdfUrl:"/chapter/pdf-preview/70451",authors:[{id:"309100",title:"Dr.",name:"Ana Paola",surname:"Balderrama Carmona",slug:"ana-paola-balderrama-carmona",fullName:"Ana Paola Balderrama Carmona"},{id:"309572",title:"Dr.",name:"Norma Patricia",surname:"Silva Beltran",slug:"norma-patricia-silva-beltran",fullName:"Norma Patricia Silva Beltran"},{id:"309573",title:"Dr.",name:"Edgar Felipe",surname:"Moran Palacio",slug:"edgar-felipe-moran-palacio",fullName:"Edgar Felipe Moran Palacio"},{id:"309574",title:"Dr.",name:"Norma Patricia",surname:"Adan Bante",slug:"norma-patricia-adan-bante",fullName:"Norma Patricia Adan Bante"},{id:"309575",title:"MSc.",name:"Luis Alberto",surname:"Zamora Alvarez",slug:"luis-alberto-zamora-alvarez",fullName:"Luis Alberto Zamora Alvarez"}],corrections:null},{id:"70719",title:"Governance for Sustainable Remediation of Polluted Soil in Developing Countries",doi:"10.5772/intechopen.90744",slug:"governance-for-sustainable-remediation-of-polluted-soil-in-developing-countries",totalDownloads:740,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Environmental governance is a challenge for many developing countries, and soil pollution is typically overlooked by authorities in the Global South. Soil governance should protect people and environment from the hazards of pollution and promote sustainable remediation of polluted sites through legislation and soil policies that facilitate the use of appropriate technology. Today, however, the soil governance landscape is highly fragmented and often fails to adequately address these concerns. Combining soil remediation with profitable activities (alone or in combination) such as food and fiber production, biomass energy production, erosion control, carbon sequestration, favoring biodiversity, etc. is potentially an appropriate strategy to promote the decontamination of polluted agriculture soil in low-income countries. Many potential pitfalls follow such a strategy but decision support tools may provide insights from the latest scientific remediation findings to stakeholders in their exploration of policy options. This chapter explores challenges and opportunities for sustainable soil governance in developing countries.",signatures:"Henrik Haller, Ginnette Flores-Carmenate and Anders Jonsson",downloadPdfUrl:"/chapter/pdf-download/70719",previewPdfUrl:"/chapter/pdf-preview/70719",authors:[{id:"169739",title:"Dr.",name:"Anders",surname:"Jonsson",slug:"anders-jonsson",fullName:"Anders Jonsson"},{id:"169945",title:"Dr.",name:"Henrik",surname:"Haller",slug:"henrik-haller",fullName:"Henrik Haller"},{id:"315854",title:"M.Sc.",name:"Ginnette",surname:"Flores-Carmenate",slug:"ginnette-flores-carmenate",fullName:"Ginnette Flores-Carmenate"}],corrections:null},{id:"71566",title:"Studies, Efforts and Investigations on Various Aspects of Solid Waste Management with Emphasis on Developing Countries",doi:"10.5772/intechopen.91942",slug:"studies-efforts-and-investigations-on-various-aspects-of-solid-waste-management-with-emphasis-on-dev",totalDownloads:793,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Solid waste can be broadly classified as putrescible and non-putrescible based on its biodegradability. Municipal solid waste contains food waste, papers, plastic, paints, heavy metals and rubber. Industrial solid waste may contain waste adsorbent, waste catalyst sludge, solid residue of by-product, residue of reactions and hazardous materials also. Dewatering, centrifugal filtration, drying and incineration are usual steps used for solid waste treatment in industries. Biodegradable solid waste, being rich in organic content, can be used to synthesize various useful organic compounds. Vermicomposting is an effective method for converting organic waste into nutrient-rich fertilizer. Food and vegetable waste can be processed to obtain useful products. Inorganic domestic waste and electronic waste may contain valuable heavy metals like gold and platinum. E-waste and industrial waste containing hazardous waste need to be classified and treated carefully. Non-biodegradable waste like plastic and rubber can be reused or recycled. Non-government organizations in developing countries are playing key role in creating awareness among people about solid waste. Recycling in industries is promoted by government through various schemes and initiatives. This chapter briefly explains initiatives and investigations aimed at increasing adoptability and efficiency of various solid minimizations, reuse, recycle methods and technologies used for synthesis of value-added products.",signatures:"Sunil Jayant Kulkarni",downloadPdfUrl:"/chapter/pdf-download/71566",previewPdfUrl:"/chapter/pdf-preview/71566",authors:[{id:"315479",title:"Dr.",name:"Sunil",surname:"Kulkarni",slug:"sunil-kulkarni",fullName:"Sunil Kulkarni"}],corrections:null},{id:"71940",title:"An Empirical Study on Environmental Sustainability in Melaka City",doi:"10.5772/intechopen.92157",slug:"an-empirical-study-on-environmental-sustainability-in-melaka-city",totalDownloads:411,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Melaka is one of the most historic cities in Malaysia. It has been listed as a UNESCO Heritage Site since July 7, 2008. Once upon a time, it was also known as a trading center of Malaysia particularly in the Southeast Asian countries. But presently, her heritage has been facing numerous problems such as air pollution, water pollution, noise pollution, river pollution, unplanned urbanization, etc., based on several grounds including noncompliance with the existing sustainability laws, and therefore, some impacts such as ecological disruption, water-borne diseases, resource depletion, emission of greenhouse gases, etc. are observed in this city. This study, however, examines the environmental sustainability issues such as water pollution, climate change, food security, natural resource and heritage, bio-diversity, etc. in Melaka City based on the primary and secondary sources consisting of 50 respondents in the different criteria such as lecturers, foreigners, workers, employees, common people, students, security personnel, etc. and finds that on an average the people in this city find around 60–70% sound environment and its sustainability prevailing in this city.",signatures:"Noor Mohammad",downloadPdfUrl:"/chapter/pdf-download/71940",previewPdfUrl:"/chapter/pdf-preview/71940",authors:[{id:"142423",title:"Dr.",name:null,surname:"Mohammad",slug:"mohammad",fullName:"Mohammad"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"5502",title:"Current Perspective on Irrigation and Drainage",subtitle:null,isOpenForSubmission:!1,hash:"f84b58948ba0347cba6ad7d2f1e65fe2",slug:"current-perspective-on-irrigation-and-drainage",bookSignature:"Suren Kulshreshtha and Amin Elshorbagy",coverURL:"https://cdn.intechopen.com/books/images_new/5502.jpg",editedByType:"Edited by",editors:[{id:"37057",title:"Dr.",name:"Surendra N.",surname:"Kulshreshtha",slug:"surendra-n.-kulshreshtha",fullName:"Surendra N. 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1. Introduction
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As complex and expensive mechanical systems, gas turbine engines benefit a lot from the application of advanced diagnostic technologies, and the use of monitoring systems has become a standard practice. To perform effective analysis, there are different diagnostic approaches that cover all gas turbine subsystems. The diagnostic algorithms based on measured gas path variables are considered as principal and pretty complex. These variables (air and gas pressures and temperatures, rotation speeds, fuel consumption, etc.) carry valuable information about an engine’s health condition and allow to detect and identify different engine abrupt faults and deterioration mechanisms (for instance, foreign object damage, fouling, erosion, tip ribs, and seal wear). Malfunctions of measurement and control systems can be diagnosed as well. Thousands of technical publications devoting to the gas path diagnosis can be found. They can be arranged according to input information and mathematical models applied.
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Although advancement of instrumentation and computer science has enabled extensive field data collection, the data with gas turbine faults are still infrequent because real faults rarely appear. Some intensive and practically permanent deterioration mechanisms, for example, compressor fouling, allow their describing on the basis of real data. However, to describe the variety of all possible faults, mathematical models are widely used. These models and the diagnostic methods that use them fall into two main categories: physics-based and data-driven.
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A thermodynamic engine model is a representative physics-based model. This nonlinear model is based on thermodynamic relations between gas path variables. It also employs mass, energy, and momentum conservation laws. Such a sophisticated model has been used in gas turbine diagnostics since the work of Saravanamuttoo H.I.H. (see, e.g., [1]). The model allows to simulate the gas path variables for an engine baseline (healthy engine performance) and for different faults embedded into the model through special internal coefficients called fault parameters. Applying system identification methods to the thermodynamic model, an inverse problem is solved: Unknown fault parameters are estimated using measured gas path variables. During the identification, such parameters are found that minimize the difference between the model variables and the measured ones. Besides the better model accuracy, the simplification of the diagnosing process is reached because the fault parameter estimates contain information of current engine health. The diagnostic algorithms based on the model identification constitute one of two main approaches in gas turbine diagnostics (see, for instance, [1–4]).
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The second approach uses a pattern recognition theory. Since model inaccuracy and measurement errors impede a correct diagnosis, gas path fault localization can be characterized as a challenging recognition issue. Numerous applications of recognition tools in gas path diagnostics are known, for instance, genetic algorithms [5], correspondence and discrimination analysis [6], k-nearest neighbor [7], and Bayesian approach [8]. However, the most widespread techniques are artificial neural networks (ANNs). The ANNs applications are not limited by the fault recognition, they are also applied or can be applied at other diagnostic stages: feature extraction, fault detection, and fault prediction.
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At the feature extraction stage, differences (a.k.a. deviations) between actual gas path measurements and an engine baseline are determined because they are by far better indicators of engine health than the measurements themselves are. To build the necessary baseline model, the multilayer perceptron (MLP), also called a back-propagation network, is usually employed [9, 10]. To filter noise, an auto-associative configuration of the perceptron is sometimes applied to the measurements [11].
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At the fault localization stage, fault classes can be presented by sets of the deviations (patterns) induced by the corresponding faults. Such a pattern-based classification allows to apply the ANNs as recognition techniques, and multiple applications of the MLP (see, e.g., [4, 5]) as well as the radial basis network (RBN) [5], the probabilistic neural network (PNN) [12, 13], and support vector machines (SVM) a.k.a. Support vector network (SVN) [7, 12] were reported. In spite of many publications on gas turbine fault recognition, comparative studies, which allow to choose the best technique [4, 5, 7, 12], are still insufficient. They do not cover all of the used techniques and often provide differing recommendations.
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The fault detection stage can also be presented as a pattern recognition problem with two classes to recognize: a class of healthy engines and a class of faulty engines. If the classification for the fault localization stage is available, it does not seem a challenge to use the patterns of this classification for building the fault detection classification. However, the studies applying recognition techniques, in particular the ANNs, for gas turbine fault detection are absent so far. Instead, the detection problem is solved by tolerance monitoring [14, 15].
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The fault prediction stage is less investigated than the previous stages, and only few ANNs applications are known. Among them, it is worth to mention book [16] analyzing the ways to predict gas turbine faults and study [17], comparing a recurrent neural network and a nonlinear auto-regressive neural network. We can see that in total for all stages, the perceptron is by far the highest demand network. It is used for filtering the measurements, approximating the engine baseline, and recognizing the faults.
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Thus, a brief observation of the neural networks applied for gas turbine diagnosis has revealed that the multiple known cases of their use need better generalization and recommendations to choose the best network. The areas of promising ANNs application were also found. In the present chapter, we generalize our investigations aimed at the optimization of a total diagnostic process through the enhancement of each of its elements. On the one hand, the neural networks help with process realization being its critical elements. On the other hand, the networks themselves are objects of analysis: For known applications, they are compared to choose the best network, and one new application is proposed. During the investigations, the rules of proper network usage have also been established.
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The rest of the chapter describes these investigations and is structured as follows: description of the networks used (Section 2), network-based diagnostic approach (Section 3), diagnostic process optimization (Section 4), feature extraction stage optimization (Section 5), fault detection stage optimization (Section 6), and fault localization stage optimization (Section 7).
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2. Artificial neural networks
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The four networks mentioned in the introduction have been chosen for investigations: MLP, RBN, PNN, and SVN. The PNN is a realization of the Parzon Windows and has the important property of probabilistic outputs, that is, the gas turbine faults are recognized on the basis of their confidence probabilities. These probabilities are computed through numerical estimates of probability density of fault patterns. For the purpose of comparison, a similar recognition tool, the K-nearest neighbor (K-NN) method has been involved into the investigations. Foundations of the chosen techniques can be found in many books on classification theory, for example, in [18, 19, 20]. The next subsections include only a brief description of techniques required to better understand the present chapter.
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2.1. Multilayer perceptron
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The perceptron can solve either approximation or classification issues. The scheme shown in Figure 1 illustrates structure and operation of the MLP [18, 19]. We can see that the perceptron presents a feed-forward neural network in which no feedback is observed, and all signals go only from the input to the output.
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Figure 1.
Multilayer perceptron.
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To determine a hidden layer input vector, the product of a weight matrix W1 and a network input vector (pattern) p→ is summed with a bias vector b1→. A hidden layer transfer function f1 transforms this vector in an output vector a1→. A network output a2→ is computed similarly considering the vector a→1 as an input. In this way, perceptron operation can be expressed by y→=a2→=f2{W2f1(W1p→+b1→)+b2→}. When we apply the MLP to classify patterns, elements of the vector a2→ show how close the pattern p→ is to the corresponding classes. The nearest class is chosen as a class to which the pattern belongs, and such classifying can be considered as deterministic.
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To find unknown matrixes W1 and W2 and vectors b1→ and b2→, a back-propagation learning algorithm distributes a network output error on these unknown quantities. In every learning iteration (epoch), they vary in the direction of error reduction. The iterations continue unless the minimum error has been reached. This algorithm requires differentiable transfer functions, and a sigmoid type is commonly used.
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2.2. Radial basis network
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Figure 2 illustrates operation of an RBN. It includes two layers: a hidden radial basis layer and an output linear layer. Operation of radial basis neurons is different from the perceptron neurons operation [18, 19, 20]. The neuron\'s input n is formed as the Euclidean norm ‖‖ of a difference between a pattern vector p→ and a weight vector w→, multiplied by a scalar b (bias). In this way, n=‖w→−p→‖b. Using this input, a radial basis transfer function determines an output a=exp(−n2). Where there is no distance between the vectors, the function has the maximum value a=1, and the function decreases when the distance increases. The bias b allows changing the neuron sensitivity. The output layer transforms the radial basis output a→1 to a network output a→2. Operation of this layer does not differ from the operation of a perceptron layer with a linear transfer function. The radial basis layer usually needs more neurons than a comparable perceptron hidden layer because the radial basis neuron covers a smaller region compared with the sigmoid neuron.
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Figure 2.
Radial basis network.
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2.3. Probabilistic neural networks
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The PNN is a specific variation of radial basis network [18]. It is used to solve classification problems. Figure 3 presents the scheme of this network and helps to understand its operation. Like the RBN, the probabilistic neural network has two layers.
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Figure 3.
Probabilistic neural network.
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The hidden layer is formed and operates just like the same layer of the RBN. It is built from learning patterns united in a matrix W1. Elements of an output vector a→1 indicate how close the input pattern is to the learning patterns.
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The output or classification layer differs from the RBN output layer. Each class has its output neuron that sums the radial basis outputs aj corresponding to the class patterns. To this end, a weight matrix W2 formed by 0- and 1-elements is employed. A vector W2a→1 contains probabilities of all classes. A transfer function f2 finally chooses the class with the largest probability. In this way, the probabilistic network classifies input patterns using a probabilistic measure that is more realistic than the perceptron classifying. The PNN is the most used realization of a Parzen Windows (PW) [18], a nonparametric method that estimates probability density in a given point (pattern) Z→ using the nearby learning patterns.
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2.4. k-Nearest neighbors
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Like the Parzen Windows (PNNs), the k-nearest neighbors is a nonparametric technique [18]. For a given class and point (pattern) p→, it counts the number k of class patterns in a nearby region of volume V and estimates the necessary probability density in accordance with a simple formula
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ρ=k/nVE1
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where n stands for a total number of class patterns.
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To ensure the convergence of the estimate ρ, we need to satisfy the following requirements
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limV=0n→∞;limk=∞n→∞;limk/n=0.n→∞E2
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To this end, we increase n and can let V be proportional to 1n.
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In contrast to the Parzen Window method that fixes the volume V and looks for the number k, the K-nearest neighbor method specifies k and seeks for the sphere of volume V. Since the PW uses constant window size, it may not capture patterns when the actual density is low. The density estimate will be equal to zero, and the classification decision confidence will be underestimated. A solution to this problem is to use the window that depends on learning data. Using this principle, the K-NN increases a spherical window individually for each class until k patterns (nearest neighbors) fall into the window. A sphere radius will change class by class. The greater the radius is, the lower probability density estimate will be according to Eq. (1).
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2.5. Support vector network
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Any hyperplane can be written in the space RP as the set of points p→ satisfying:
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p→Tw→+b=0E3
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where w→ is a vector perpendicular to the hyperplane and b is the bias. Let us present learning data of two classes as pattern vectors p→i∈RP,i=1,N and their corresponding labels yi∈(−1,1), indicating the class to which the pattern p→ belongs.
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If the learning data are linearly separable, two parallel hyperplanes without points between them can be built to divide the data. The hyperplanes can be given by w→Tp→i+b=1 and w→Tp→i+b=−1. The margin is defined to be the distance between them and is equal to 2/‖w→‖ (Figure 4). Intuitively, it measures how good the separation between the two classes is. The points divided in this manner satisfy the following constraint:\n
yi(w→Tp→i+b)≥1E4
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Figure 4.
SVN: hyperplanes and separation margin.
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The objective of the SVN is to find the hyperplanes that produce the maximal margin or minimum vector w→ [19, 20]. In this way, SVN needs to solve the following primal optimization problem:
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min12w→Tw→E5
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subject to yi(w→Tp→i+b)≥1, for i=1,…,N
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Introducing the Karush-Kuhn-Tucker (KKT) multipliers αi≥0, objective function (5) can be transformed to:
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minw,bmaxα12w→Tw→−∑i−1Nαi(yi(w→Tp→i+b)−1)E6
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As can be seen, expression (6) is a function of w→, b, and α. This function can be transformed into the dual form:
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L=minα12∑i=1N∑j=1Nyiyjαiαjp→Tip→j−∑i=1NαiE7
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subject to αi≥0 and ∑i=1Nαiyi=0 for i=1,…,N
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It can be also expressed as:
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L=minα12α→TQα→−1Tα→E8
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where Q is the matrix of quadratic coefficients. This expression is minimized now only as a function of α→, and the solution is found by Quadratic Programming.
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In SVM classification problems, a complete separation is not always possible, and a flexible margin is suggested in reference [21] that allows misclassification errors while tries to maximize the distance between the nearest fully separable points. The other way to split not separable classes is to use nonlinear functions as proposed in reference [22]. Among them, radial basis functions are recommended [23].
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SVMs were originally intended for binary models; however, they can now address multi-class problems using the One-Versus-All and One-Versus-One strategies.
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A gas turbine diagnostic process using the techniques above described is simulated according to the following approach.
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3. Neural networks-based diagnostic approach
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The approach described corresponds to the diagnostic stages of feature extraction and fault localization and embraces the steps of fault simulation, feature extraction, fault classification formation, making a recognition decision, and recognition accuracy estimation.
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3.1. Fault simulation
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Within the scope of this chapter, faults of engine components (compressor, turbine, combustor, etc.) are simulated by means of a nonlinear gas turbine thermodynamic model
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Y→(U→,Θ→)E9
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The model determines monitored variables Y→ as a function of steady-state operating conditions U→ and engine health parameters Θ→=Θ→0+ΔΘ→. Each component is presented in the model by its performance map. Nominal values Θ→0 correspond to a healthy engine, whereas fault parameters ΔΘ→ imitate fault influence by shifting the component maps.
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3.2. Feature extraction
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Although gas turbine monitored variables are affected by engine deterioration, the influence of the operating conditions is much more significant. To extract diagnostic information from raw measured data, a deviation (fault feature) is computed for each monitored variable as a difference between the actual and baseline values. With the thermodynamic model, the deviations Zi i=1,m induced by the fault parameters are calculated for all m monitored variables according to the following expression
A random error εi makes the deviation more realistic. A parameter ai normalizes the deviation errors, resulting that they will be localized within the interval [−1, 1] for all monitored variables. Such normalization simplifies fault class description.
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Deviations of the monitored variables united in an (m×1) deviation vector Z→\n (feature vector) form a diagnostic space. Every vector \nZ→ presents a point in this space and is a pattern to be recognized.
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3.3. Fault classification formation
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Numerous gas turbine faults are divided into a limited number q of classes D1,D2,...,Dq. In the present chapter, each class corresponds to varying severity faults of one engine component. The class is described by component’s fault parameters ΔΘj. Two types of fault classes are considered. The variation of one fault parameter results in a single fault class, while independent variation of two parameters of one gas turbine component allows to form a class of multiple faults.
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To form one class, many patterns are computed by expression (10). The required parameters ΔΘj and εi are randomly generated using the uniform and Gaussian distributions correspondingly. To ensure high computational precision, each class is typically composed from 1000 patterns. A learning set Z1 uniting patterns of all classes presents a whole pattern-based fault classification. Figure 5 illustrates such a classification by presenting four single fault classes in the diagnostic space of three deviations.
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Figure 5.
Pattern-based fault classification.
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3.4. Making a fault recognition decision
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In addition to the given (observed) pattern Z→ and the constructed fault classification Z1, a classification technique (one of the chosen networks) is an integral part of a whole diagnostic process. To apply and test the classification techniques, a validation set Z2 is also created in the same way as set Z1. The difference between the sets consists in other random numbers that are generated within the same distributions.
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3.5. Recognition accuracy estimation
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It is of practical interest to know recognition accuracy averaged for each fault class and a whole engine. To this end, the classification technique is consequently applied to the patterns of set Z2 producing diagnoses dl. Since true fault classes Dj are also known, probabilities of correct diagnosis (true positive rates) P(d/jDj) can be calculated for all classes resulting in a probability vector P→. A mean number P__ of these probabilities characterizes accuracy of engine diagnosis by the applied technique. In this chapter, the probability P__ is employed as a criterion to compare the techniques described in Section 2.
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4. Optimization of the neural networks-based diagnostic process
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The structure and efficiency of a diagnostic algorithm depend on many factors and the options that can be chosen for each factor. The classification of these factors and options is given in Figure 6 , where the factors are shown in the first line. On the basis of accumulated knowledge and experience, every research center (even a single researcher) chooses an appropriate option for each factor and develops its own diagnostic algorithm. To be optimal, this algorithm should take into account all peculiarities of a given engine, its application, and other diagnostic conditions. Thus, it is not likely that the algorithm be optimal for other engines and applications. As a result, every monitoring system needs an appropriate diagnostic algorithm.
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Figure 6.
Factors that influence structure and efficiency of gas path diagnostic algorithms.
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Thus, comparing complete diagnostic algorithms does not seem to be useful. Instead, comparing options for each above factor and choosing the best option are proposed. When options of one factor are compared, the other factors (comparison conditions) are fixed forming a comparison case. To draw sound conclusions about the best option, the comparison should be repeated for many comparison cases. To form these cases, each comparison condition varies independently according to the theory of the design of experiments. Since every new condition drastically increases the volume of comparative calculations, the most significant conditions are considered first.
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To perform the comparative calculations, a test procedure based on the above-described approach has been developed in Matlab (MathWorks, Inc.). For each compared option, the procedure executes numerous cycles of gas turbine fault diagnosis by the chosen technique and finally computes a diagnosis reliability indicator, which is used as a comparison criterion.
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Three gas turbine engines (Engine 1, Engine 2, and Engine 3) of different construction and application have been chosen as test cases. Engine 1 and Engine 2 are free turbine power plants. Engine 1 is a natural gas compressor driver; it is presented in the investigations by its thermodynamic model and field data recorded. Engine 2 is intended for electricity production and is given by field data. Engine 3 is a three-spool turbofan for a transport aircraft; its thermodynamic model is used. The field data called hourly snapshots present filtered and averaged steady-state values recorded every hour during about one year of operation of Engine 1 and Engine 2. Since the data include periods of compressor fouling and points of washing, they are very suitable for testing diagnostic techniques.
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Using the network-based approach described in Section 3 and the information about the test case engines, many investigations have been conducted to improve the diagnostic process at the stages of feature extraction, fault detection, and fault localization. The results achieved for the feature extraction stage are described in the next section.
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5. Feature extraction stage optimization
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As stated in Section 3, the deviations are useful diagnostic features. Although the thermodynamic model can be used as a baseline model for computing the deviations, it is too complex for real monitoring systems and has intrinsic inaccuracy. As mentioned in the introduction, to build a simple and fast data-driven baseline model, only neural networks, in particular the MLP, are applied. On the other hand, in the previous studies we successfully used a polynomial type baseline model. It was therefore decided [24] to verify whether the application of such a powerful approximator as the MLP instead of polynomials yields higher adequacy of the baseline model and better quality of the corresponding deviations.
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Given a measured value Yi* and data-driven baseline model Y→0(U→), the deviation is written as
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δYi*=Yi*−Y0i(U→)Y0i(U→)E11
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For one monitored variable, a complete second-order polynomial function of four arguments (operating conditions) is written as
For all m monitored variables and measurements at n operating points, equation (12) is transformed to a linear system Y=VA with matrixes Y (n×m) and V (n×k) formed from these data, where k=15 is number of coefficients. To enhance coefficient estimates (matrix A), great volume of input data (n>>k) is involved and the least-squares method is applied.
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As to the perceptron, its typical input is formed by four operating conditions, and the output consists of seven monitored variables. Hidden layer size determines a network’s capability to approximate complex functions and varies in calculations. As a result of MLP tuning, we chose 12 nodes at this layer. Thus, the perceptron structure is written as 4×12×7. Since the MLP has tan-sigmoid transfer functions, and the output varies within the interval (−1, 1), all monitored quantities are normalized.
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Many cases of comparison on the simulated and real data of Engines 1 and 2 were analyzed. The MLP was sometimes more accurate at the learning step. At the validation step, the deviations computed with the MLP had a little worse accuracy for Engine 1. For Engine 2, the best MLP validation results are illustrated in Figure 7 . As can be seen here, both polynomial deviations dTtp and network deviations dTtn reflect the fouling and washing effects equally well. However, in many other cases the polynomials outperformed. Why does the network approximate well a learning set and frequently fail on a validation set? The answer seems to be evident because of an overlearning (overfitting) effect. Due to a greater flexibility, the network begins to follow data peculiarities induced by measurement errors in the learning set and describes worse a gas turbine baseline performance for the validation set.
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Figure 7.
EGT deviations computed on the Engine 2 real data validation set (dTtn—network-based deviation; dTtp—polynomial-based deviation).
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Although the MLP as a powerful approximation technique promised better gas turbine performance description, the results of the comparison have been somewhat surprising. No manifestations of network superiority were detected. When comparing these techniques, it is also necessary to take into consideration that an MLP learning procedure is more complex because it is numerical in contrast to an analytical solution for polynomials. Thus, a polynomial baseline model can be successfully used in real monitoring systems along with neural networks. At least, it seems to be true for simple cycle gas turbines with gradually changed performance, like the turbines considered in this chapter.
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6. Fault detection stage optimization
\n
As mentioned in the Introduction, the fault detection is actually based on tolerances (thresholds). However, it seems reasonable to present it as a pattern recognition problem like we do at the fault recognition stage. Classification D1,D2,...,Dq created for the purpose of fault localization and presented in Figure 5 corresponds to a hypothetical fleet of engines with different faults of variable severity. To form the classification for fault detection, we can reasonably accept that the engine fleet and the distributions of faults are the same. Paper [25] explains how to use patterns of the existing classification D1,D2,...,Dq for two new classes of healthy and faulty engines. The boundary between these classes corresponds to maximal error of the normalized deviations and is determined as a sphere of radius R = 1. The patterns, for which a vector of true deviations (without errors) is situated inside the sphere, form the healthy engine class; the others create the faulty engine class. It is clear that the patterns (deviation vectors with noise) of these two classes are partly intersected, resulting in α- and β-errors during the detection. Figure 8 illustrates the new classification; the intersection is clearly seen. Two variations of the new classification based on single and multiple original classes have been prepared.
\n
Figure 8.
Patterns-based classification for monitoring.
\n
Since new patterns-based classification (learning and testing sets) is ready, we can use any recognition technique to perform fault detection, and the MLP has been selected once more. It conserved sigmoid transfer functions and the hidden layer size of 12. Given that a threshold-based approach, which classifies pattern vectors according to their length, is traditionally used in fault detection, the algorithm with a distance measure (r-criterion) was also developed and compared with the MLP. Since the consequences of α- and β-errors are quite different (α-error is always considered as more dangerous), reduced losses c¯=Pβ+cαcβPα were introduced to quantify monitoring effectiveness, where Pα and Pβ are probabilities of α- and β-errors, cα and cβ denote the corresponding losses, and cαcβare equal to 10.
\n
Figure 9 shows the plots of the reduced losses versus the radius r. For the MLP the change of r was simulated by the corresponding change of the boundary radius R during pattern separation in the learning set. It can be seen that the introduction of an additional threshold r, which is different from the boundary, reduces monitoring errors for both techniques. The best results correspond to the minimums of the curves. By comparing them, we can conclude that the network (MLP) provides better results for single classes, and the techniques are equal for multiple classes. In general for all comparison cases, the MLP slightly outperforms the r-criterion-based technique. Thus, the perceptron can be successfully applied for real gas turbine fault detection.
\n
Figure 9.
Reduced losses due to monitoring errors versus the threshold radius r.
\n
\n
7. Fault localization stage optimization
\n
To draw sound conclusions about the ANN applicability for gas turbine fault localization, the comparison of the chosen networks was repeated for many comparison cases formed by independent variation of the main influencing factors: engines, operating modes, simulated or real information, and class types. In this way not only the best network is chosen but also the influence of these factors on diagnosis results is determined helping with the optimization of a total diagnostic process. For the purpose of correct comparison, the networks were tailored to a concrete task to solve.
\n
7.1. Neural network tuning
\n
We started to use ANNs applications and their tuning with the MLP [26]. The numbers of monitored variables and fault classes unambiguously determine the size of input and output layers of this network. As to the hidden layer, the number of 12 nodes was estimated as optimal using the probability P__ as a criterion. To choose a proper back-propagation algorithm, 12 variations were compared by accuracy and execution time. The resilient back-propagation (“rp”-algorithm) provided the best results and has been chosen. It was also found that 200 batch mode training epochs are sufficient for good learning; however, a learning stop by an Early Stopping Option may be useful as well.
\n
Figure 10 illustrates other example of the tuning. Averaged probabilities computed for the PNN are plotted here against spread b, unique PNN tuning parameter. To determine this probability that has high precision of about ±0.001, calculations of P__ were repeated 100 times for each spread value, each time with a different seed (quantity that determines a consequence of random numbers), and an average value was computed. Such computations to find the best value b were repeated for two operating modes of Engine 1 and for two fault class types. It can be seen in the figure that the highest values of probability P¯av does not depend on operating mode. These values are b=0.35 for the single fault type and b=0.40 for the multiple one.
\n
Figure 10.
Probabilities versus spread parameter.
\n
For all networks, the value 1000 simulated patterns per fault class has been selected as tradeoff between the required computer resources and the accuracy of the probabilities P__ and P¯av.
\n
It is worth mentioning that the networks tuning is very time consuming. A tuning time can occupy up to 80% of a total investigation time, leaving 20% for the calculations related to final learning and validation of the networks.
\n
\n
7.2. Neural network comparison
\n
The comparison of three tuned networks: MLP, RBN, and PNN, was firstly performed in reference [27], then the SVN was also evaluated. The variations of comparison conditions embraced independent changes of two engines, two operating modes, and two classification variations. The resulting probabilities P¯av are given in Table 1. We can see that all networks are practically equal in accuracy for all comparison cases.
\n
Paper [28] provides some additional results extending the comparison on the K-NN technique. The data given in Table 2 confirm the conclusion about equal performances, now for five different techniques.
\n
\n
\n
\n
\n
\n
\n
\n\n
\n
Class type
\n
ANN
\n
Engine 1
\n
Engine 3
\n
\n
\n
Mode 1
\n
Mode 2
\n
Mode 1
\n
Mode 2
\n
\n\n\n
\n
Single
\n
MLP RBN PNN SVN
\n
0.8184 0.8186 0.8134 0.8190
\n
0.8059 0.8058 0.8004 0.8064
\n
0.7338 0.7349 0.7287 -
\n
0.7470 0.7485 0.7456 -
\n
\n
\n
Multiple
\n
MLP RBN PNN SVN
\n
0.8765 0.8783 0.8739 0.8770
\n
0.8686 0.8701 0.8653 0.8698
\n
0.7749 0.7787 0.7730 -
\n
0.7596 0.7643 0.7617 -
\n
\n\n
Table 1.
Results of the network comparison (probabilities computed for Engine 1 and Engine 3).
\n
\n
\n
\n
\n\n
\n
Technique
\n
Class type
\n
\n
\n
Single
\n
Multiple
\n
\n\n\n
\n
PNN K-NN MLP
\n
0.8134 0.8154 0.8193
\n
0.8739 0.8735 0.8765
\n
\n\n
Table 2.
Additional results of the technique comparison (probabilities for Engine 1).
\n
The PNN and K-NN have probabilistic output, and every pattern recognition decision is accompanied with a confidence probability. This is an important advantage for gas turbine diagnosticians and maintenance staff. It can be taken into account for choosing the best technique when mean diagnosis reliability P__ is equal for all techniques considered. The PNN and K-NN are nonparametric techniques that estimate a probability density for each fault class by counting the patterns that fall into a given volume (window). To accurately estimate the probability density in a multidimensional diagnostic space, the number 1000 of available patterns can be insufficient. To assess possible imprecision of the density and confidence probability estimation by the PNN and K-NN techniques, a more precise analytical density estimation (ADE) technique has been proposed and developed [28]. It analytically determines the density and is employed as a reference to assess imprecision of the PNN and K-NN. To verify the newly developed technique, it was firstly compared with the others by the criterion P¯av. The results were reasonably good: the performances of all the techniques remained very close, but the ADE had the highest probability with the increment of 0.366–0.771 relatively the others.
\n
The results of comparison by the estimated confidence probability are illustrated in Figure 11 , when the PNN, K-NN, and MLP errors are plotted for 100 patterns. One can see that the bias and scatter for the K-NN estimates are by far greater. As to the MLP outputs, these non-probabilistic quantities look by far more precise than the K-NN probability estimates and seem to have the same precision level as the PW-PNN estimates.
\n
Figure 11.
Errors of probability estimation by PW-PNN, K-NN, and MPL techniques (Engine 1, first 100 patterns of the first single fault class).
\n
Table 3 presents the mean estimations errors for the case of the single fault classification. The table data confirm the above conclusion on the compared techniques: The bias and standard deviation of the K-NN errors are by far greater. The table also shows that on average the MLP outputs are even more exact than the PNN probabilities. It is one more argument to apply the perceptron in real gas turbine monitoring systems.
\n
\n
\n
\n
\n
\n
\n
\n\n
\n
Bias
\n
σ
\n
\n\n\n
\n
PNN
\n
K-NN
\n
MLP
\n
PW-PNN
\n
K-NN
\n
MLP
\n
\n
\n
-0.0444
\n
-0.3293
\n
-0.0419
\n
0.0845
\n
0.2020
\n
0.0791
\n
\n\n
Table 3.
Mean errors of confidence probability estimation (Engine 1, single fault classification).
\n
\n
7.3. Fault classification extension
\n
In the investigations previously described, only two rigid classifications were maintained: one formed by single fault classes and the other constituted from multiple fault classes created by two fault parameters. However, the classification can vary a lot in practice even for the same engine, and it is difficult to predict what classification variation will be finally used in a real monitoring system. To verify and additionally compare the networks for different classification variations, the test procedure was modified for easily creating any new fault classification, more complex and more realistic than the classifications previously analyzed.
\n
Twelve classification variations have been prepared and three networks: MLP, RBN, and PNN, were examined in reference [29]. These classifications have from 4 to 18 gas path and sensor fault classes, 1 to 4 fault parameters to form each class, positive and negative fault parameter changes. All the networks operated successfully for all fault classifications. Table 4 shows the resulting averaged probabilities of correct diagnosis. Analyzing them, one can state that the differences between the networks within the same classification remain not great (except variation 6), about 0.015 (1.5%), while the difference between the variations can reach the value 0.10. Thus, these results reaffirm once more the conclusion drawn before that many recognition techniques may yield the same gas turbine diagnosis accuracy.
\n
\n
\n
\n
\n
\n\n
\n
Variation
\n
MLP
\n
RBN
\n
PNN
\n
\n\n\n
\n
1
\n
0.8172
\n
0.8169
\n
0.8099
\n
\n
\n
2
\n
0.8732
\n
0.8759
\n
0.8720
\n
\n
\n
3
\n
0.8091
\n
0.8072
\n
0.8037
\n
\n
\n
4
\n
0.8490
\n
0.8524
\n
0.8474
\n
\n
\n
5
\n
0.8033
\n
0.8080
\n
0.8036
\n
\n
\n
6
\n
0.6805
\n
0.7319
\n
0.7316
\n
\n
\n
7
\n
0.7362
\n
0.7616
\n
0.7567
\n
\n
\n
8
\n
0.7828
\n
0.7965
\n
0.7910
\n
\n
\n
9
\n
0.9279
\n
0.9280
\n
0.9260
\n
\n
\n
10
\n
0.7909
\n
0.8017
\n
0.7930
\n
\n
\n
11
\n
0.8075
\n
0.7867
\n
0.7775
\n
\n
\n
12
\n
0.8209
\n
0.8184
\n
0.8076
\n
\n\n
Table 4.
Technique comparison for new classification variations (probabilities P¯av, for Engine 1).
\n
\n
7.4. Real data-based classification
\n
Gas path mathematical models are widely used in building fault classification required for diagnostics because faults rarely occur during field operation. In that case, model errors are transmitted to the model-based classification. Paper [30] looks at the possibility of creating a mixed fault classification that incorporates both model-based and data-driven fault classes. Such a classification will combine a profound common diagnosis with a higher diagnostic accuracy for the data-driven classes. Engine 1 has been chosen as a test case. Its real data with two periods of compressor fouling were used to form a data-driven class of the fouling. Figure 12 illustrates simulated (without errors) and real data.
\n
Figure 12.
Simulated and real compressor fouling deviations (Engine 1: M—simulated deviations, F1 and F2—real deviations for the first and second fouling periods).
\n
Different variations of the classification were considered and compared using the MLP. In spite of irregular distribution of real patterns, the MLP normally operated at the learning and validation steps. We also found that the perceptron trained on simulated data has 30% recognition errors when applied to real compressor fouling data. However, the use of mixed learning data allows to reduce these errors up to 3%. It was shown as well how to form a representative real fault class, which ensures minimal recognition errors.
\n
Paper [31] presents another way to enhance gas turbine fault classification using real information. Diagnostic algorithms widely use theoretical random number distributions to simulate measurement errors. Such simulation differs from real diagnosis because the diagnostic algorithms work with the deviations, which have other error components that differ from simulated errors by amplitude and distribution. As a result, simulation-based investigations might result in too optimistic conclusions on gas turbine diagnosis reliability. To make error presentation more realistic, it was proposed in reference [31] to extract an error component from real deviations and to integrate it in fault description.
\n
Using simulated and real data of Engine 1, six alternative variations of deviation error were integrated in the fault classification. Diagnosis was performed by the MLP, and the diagnosis reliability was estimated for each variation. Despite irregular real error distribution, the MLP successfully operated for all the variations. Experiments with error representation variations have shown what can happen when the classification formed with accurate simulated deviations is applied to classify less accurate real deviations. In that case, the diagnosis accuracy can fall from P¯ ≈ 92% to P¯ ≈ 54%, but this low diagnostic accuracy can be considerably elevated by including real errors into the description of fault classes.
\n
The fault classifications with integrated real errors were used in reference [32] to compare three networks: MLP, RBN, and PNN, one more time. All networks operated well and they differed in accuracy indicators P¯av by less than 1%, thus confirming again the conclusion about equality of recognition techniques.
\n
\n
7.5. Different operating conditions
\n
Many known studies show that grouping the data collected at different engine operating modes for making a single diagnosis (multipoint diagnosis) yields higher diagnostic accuracy than the accuracy provided by traditional one-point methods. But it is of a practical interest to know how significant the accuracy increment is and how it can be explained. The diagnosis of engines at dynamic modes poses the similar questions. To make one diagnosis, this technique combines data from successive measurement sections of a transient operation mode and in this regard looks like multipoint diagnosis.
\n
Paper [33] analyzes the influence of the operating conditions on the diagnostic accuracy by comparing the one-point, multipoint, and transient options. The MLP is used as a pattern recognition technique. In spite of significant increase of the input dimensionality, the perceptron operated well for all options.
\n
The calculations have revealed that the process of network training has peculiarities for multipoint diagnosis. They are illustrated in Figure 13 , which shows the plots of the perceptron error versus training epochs for the cases of one-point and multipoint diagnosis. As can be seen, the curves of the error function for the training and validation processes almost coincide for the one-point option, they slow down along with training epochs, and a total epoch number 300 is relatively large. These are indications of no over-training effect. The behavior of the perceptron applied for the multipoint diagnosis is quite different. We can see that the validation curve falls behind the training curve after the 30th epoch, this gap rapidly increases, and the training process stops earlier (108 epochs) because of the over-training phenomenon. We can conclude that the Early Stopping Option is more required here. The differences indicated above can be explained by the ratio of input data volume to the unknown perceptron parameter number. For both cases, the volume of the training set is equal to 7000 patterns, but the numbers of unknown quantities significantly differ: 144 for the first case and 1540 for the second. Consequently, in the case of multipoint diagnosis, the trained network is much more flexible and the over-training becomes possible. An increase of the reference set volume can improve the training process; however, this increase is presently limited by the computation time.
\n
Figure 13.
Training process (Engine 1, left plot—one-point diagnosis, right plot—multipoint diagnosis).
\n
The results of the option comparison (probabilities P¯) are grouped in Table 5. One can see that a total growth of diagnosis accuracy due to switching to the multipoint diagnosis and data joining from different steady states is significant: The diagnosis errors decrease by two to five times. The diagnosis at transients causes further accuracy growth, but it is not great. It has been found that this positive effect of the data joining is mainly explained by averaging the input data and smoothing the random measurement errors.
\n
\n
\n
\n
\n\n
\n
Option
\n
Single fault classification
\n
Multiple fault classification
\n
\n\n\n
\n
One-point
\n
0.7316
\n
0.7351
\n
\n
\n
Multipoint
\n
0.8915
\n
0.9444
\n
\n
\n
Transient
\n
0.9032
\n
0.9561
\n
\n\n
Table 5.
Comparison of the one-point, multipoint, and transient options (Engine 1).
\n
\n
\n
8. Conclusions
\n
A monitoring system comprises many elements, and many factors influence the final diagnostic accuracy. The present chapter has generalized our investigations aimed to enhance this system by choosing the best option for each element. In every investigation, a diagnostic process was simulated mainly on the basis of neural networks, and we focused on reaching the highest accuracy by choosing the best network and its optimal tuning to the issue to solve. As can be seen, all the examined techniques (MLP, RBN, PNN, SVN, and K-NN) use a pattern-based classification. Such a classification can be formed from complex classes in which faults are simulated by the nonlinear thermodynamic model. Moreover, this classification allows its description by real fault displays that completely exclude a negative effect of model inaccuracy. Thus, being objects of investigation and optimization, neural networks help with enhancement of a whole monitoring system. As a result of the conducted investigations, some methods to elevate diagnostic accuracy were proposed and proven. The chapter also provides the recommendations on choosing and tailoring the networks for different diagnostic tasks. For solving many tasks, the utility of the multilayer perceptron has been proven on simulated and real data.
\n
\n
Acknowledgments
\n
The work has been carried out with the support of the National Polytechnic Institute of Mexico (research project 20150961).
\n
\n',keywords:"gas turbines, gas path diagnosis, fault classification, pattern recognition, artificial neural networks",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/50519.pdf",chapterXML:"https://mts.intechopen.com/source/xml/50519.xml",downloadPdfUrl:"/chapter/pdf-download/50519",previewPdfUrl:"/chapter/pdf-preview/50519",totalDownloads:2262,totalViews:502,totalCrossrefCites:5,totalDimensionsCites:4,totalAltmetricsMentions:6,impactScore:2,impactScorePercentile:75,impactScoreQuartile:3,hasAltmetrics:1,dateSubmitted:"October 17th 2015",dateReviewed:"March 16th 2016",datePrePublished:null,datePublished:"October 19th 2016",dateFinished:"April 30th 2016",readingETA:"0",abstract:"The present chapter addresses the problems of gas turbine gas path diagnostics solved using artificial neural networks. As a very complex and expensive mechanical system, a gas turbine should be effectively monitored and diagnosed. Being universal and powerful approximation and classification techniques, neural networks have become widespread in gas turbine health monitoring over the past few years. Applications of such networks as a multilayer perceptron, radial basis network, probabilistic neural network, and support vector network were reported. However, there is a lack of manuals that summarize neural network applications for gas turbine diagnosis.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/50519",risUrl:"/chapter/ris/50519",book:{id:"5191",slug:"artificial-neural-networks-models-and-applications"},signatures:"Igor Loboda",authors:[{id:"179551",title:"Dr.",name:"Igor",middleName:null,surname:"Loboda",fullName:"Igor Loboda",slug:"igor-loboda",email:"igloboda@gmail.com",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/179551/images/system/179551.jpeg",institution:{name:"Instituto Politécnico Nacional",institutionURL:null,country:{name:"Mexico"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Artificial neural networks",level:"1"},{id:"sec_2_2",title:"2.1. Multilayer perceptron",level:"2"},{id:"sec_3_2",title:"2.2. Radial basis network",level:"2"},{id:"sec_4_2",title:"2.3. Probabilistic neural networks",level:"2"},{id:"sec_5_2",title:"2.4. k-Nearest neighbors",level:"2"},{id:"sec_6_2",title:"2.5. Support vector network",level:"2"},{id:"sec_8",title:"3. Neural networks-based diagnostic approach",level:"1"},{id:"sec_8_2",title:"3.1. Fault simulation",level:"2"},{id:"sec_9_2",title:"3.2. Feature extraction",level:"2"},{id:"sec_10_2",title:"3.3. Fault classification formation",level:"2"},{id:"sec_11_2",title:"3.4. Making a fault recognition decision",level:"2"},{id:"sec_12_2",title:"3.5. Recognition accuracy estimation",level:"2"},{id:"sec_14",title:"4. Optimization of the neural networks-based diagnostic process",level:"1"},{id:"sec_15",title:"5. Feature extraction stage optimization",level:"1"},{id:"sec_16",title:"6. Fault detection stage optimization",level:"1"},{id:"sec_17",title:"7. Fault localization stage optimization",level:"1"},{id:"sec_17_2",title:"7.1. Neural network tuning",level:"2"},{id:"sec_18_2",title:"7.2. Neural network comparison",level:"2"},{id:"sec_19_2",title:"7.3. Fault classification extension",level:"2"},{id:"sec_20_2",title:"7.4. Real data-based classification",level:"2"},{id:"sec_21_2",title:"7.5. Different operating conditions",level:"2"},{id:"sec_23",title:"8. Conclusions",level:"1"},{id:"sec_24",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'Saravanamuttoo, H.I.H., MacIsaac, B.D., 1983, Thermodynamic models for pipeline gas turbine diagnostics, ASME Journal of Engineering for Power, Vol. 105, pp. 875–884.'},{id:"B2",body:'Doel, D.L., 2003, Interpretation of weighted-least-squares gas path analysis results, Journal of Engineering for Gas Turbines and Power, Vol. 125, Issue 3, pp. 624–633.'},{id:"B3",body:'Aretakis, N., Mathioudakis, K., Stamatis, A., 2003, Nonlinear engine component fault diagnosis from a limited number of measurements using a combinatorial approach, Journal of Engineering for Gas Turbines and Power, Vol. 125, Issue 3, pp. 642–650.'},{id:"B4",body:'Volponi, A.J., DePold, H., Ganguli, R., 2003, The use of Kalman filter and neural network methodologies in gas turbine performance diagnostics: a comparative study, Journal of Engineering for Gas Turbines and Power, Vol. 125, Issue 4, pp. 917–924.'},{id:"B5",body:'Sampath, S., Singh, R., 2006, An integrated fault diagnostics model using genetic algorithm and neural networks, ASME Journal of Engineering for Gas Turbines and Power, Vol. 128, Issue 1, pp. 49–56.'},{id:"B6",body:'Pipe K., 1987, Application of advanced pattern recognition techniques in machinery failure prognosis for turbomachinery, Condition Monitoring 1987 International Conference, British Hydraulic Research Association, UK, pp. 73–89.'},{id:"B7",body:'Lokesh Kumar S., et al., 2007, Comparison of a few fault diagnosis methods on sparse variable length time series sequences, IGTI/ASME Turbo Expo 2007, Montreal, Canada, 8 p., ASME Paper GT2007-27843.'},{id:"B8",body:'Romessis, C., Mathioudakis, K., 2006, Bayesian network approach for gas path fault diagnosis, ASME Journal of Engineering for Gas Turbines and Power, Vol. 128, Issue 1, pp. 64–72.'},{id:"B9",body:'Fast, M., Assadi, M., De, S., 2008, Condition based maintenance of gas turbines using simulation data and artificial neural network: a demonstration of feasibility, IGTI/ASME Turbo Expo 2008, Berlin, Germany, 9 p., ASME Paper GT2008-50768.'},{id:"B10",body:'Palme, T., Fast, M., Assadi, M., Pike, A., Breuhaus, P., 2009, Different condition monitoring models for gas turbines by means of artificial neural networks, IGTI/ASME Turbo Expo 2009, Orlando, Florida, USA, 11 p., ASME Paper GT2009-59364.'},{id:"B11",body:'Palme, T., Breuhaus, P., Assadi, M., Klein, A., Kim, M., 2011, Early warning of gas turbine failure by nonlinear feature extraction using an auto-associative neural network approach, IGTI/ASME Turbo Expo 2011, Vancouver, British Columbia, Canada, 12 p., ASME Paper GT2011-45991.'},{id:"B12",body:'Butler, S.W., Pattipati, K.R., Volponi, A., et al., 2006, An assessment methodology for data-driven and model based techniques for engine health monitoring, ASME Paper No. GT2006-91096.'},{id:"B13",body:'Romessis, C., Mathioudakis, K., 2003, Setting up of a probabilistic neural network for sensor fault detection including operation with component fault, Journal of Engineering for Gas Turbines and Power, Vol. 125, pp. 634–641.'},{id:"B14",body:'Jaw, L. C., Wang, W., 2006, Mathematical formulation of model-based methods for diagnostics and prognostics, IGTI/ASME Turbo Expo 2006, Barcelona, Spain, 7 p., ASME Paper GT2006-90655.'},{id:"B15",body:'Borguet, S., Leonard, O., Dewallet, P., 2015, Regression-based modelling of a fleet of gas turbine engines for performance trading, IGTI/ASME Turbo Expo 2015, Montreal, Canada, 12 p., ASME Paper GT2015-42330.'},{id:"B16",body:'Vachtsevanos, G., Lewis, F.L., Roemer, M., Hess, A., Wu, B., 2006, Intelligent Fault Diagnosis and Prognosis for Engineering Systems, John Wiley & Sons, Inc., New Jersey, 434 p.'},{id:"B17",body:'Vatani, A., Korasani, K., Meskin, N., 2015, Degradation prognostics in gas turbine engines using neural networks, IGTI/ASME Turbo Expo 2015, Montreal, Canada, 13 p., ASME Paper GT2015-44101.'},{id:"B18",body:'Duda, R.O., 2001, Pattern Classification, Wiley-Interscience, New York, 654 p.'},{id:"B19",body:'Haykin, S., 1994, Neural Networks, Macmillan College Publishing Company, New York.'},{id:"B20",body:'Bishop, C.M., 2006, Pattern Recognition and Machine Learning, Springer Science, New York.'},{id:"B21",body:'Cortes, C., Vapnik, V., 1995, Support-vector networks, Machine Learning, Vol. 20, pp. 273–297.'},{id:"B22",body:'Boser, B.E., Guyon, I.M., Vapnik, V.N., 1992, A training algorithm for optimal margin classifiers, Fifth Annual Workshop on Computational Learning Theory—COLT ’92, ACM Press, New York, USA, pp. 144–152.'},{id:"B23",body:'Hsu, C.W., Chang, C.C., Lin, C.J., 2010, A practical guide to support vector classification, National Taiwan University. http://www.csie.ntu.edu.tw/~cjlin/papers/guide/guide.pdf'},{id:"B24",body:'Loboda, I., Feldshteyn, Y., 2011, Polynomials and neural networks for gas turbine monitoring: a comparative study, International Journal of Turbo & Jet Engines, Vol. 28, Issue 3, pp. 227–236 (also see ASME paper GT2010-23749).'},{id:"B25",body:'Loboda, I., Yepifanov, S., Feldshteyn, Y., 2009, An integrated approach to gas turbine monitoring and diagnostics, International Journal of Turbo & Jet Engines, Vol. 26, Issue 2, pp. 111–126 (also see ASME paper GT2008-51449).'},{id:"B26",body:'Loboda, I., Yepifanov, S., Feldshteyn, Y., 2007, A generalized fault classification for gas turbine diagnostics on steady states and transients, Journal of Engineering for Gas Turbines and Power, Vol. 129, Issue 4, pp. 977–985.'},{id:"B27",body:'Loboda, I., Yepifanov, S., 2013, On the selection of an optimal pattern recognition technique for gas turbine diagnosis, IGTI/ASME Turbo Expo 2013, San Antonio, Texas, USA, 11 p., ASME Paper GT2013-95198.'},{id:"B28",body:'Loboda, I., 2014, Gas turbine fault recognition using probability density estimation, ASME Turbo Expo 2014, Dusseldorf, Germany, 13 p., ASME Paper GT2014-27265.'},{id:"B29",body:'Perez Ruiz, J.L., Loboda, I., 2014, A flexible fault classification for gas turbine diagnosis, Aerospace Techniques and Technology, Vol. 113, Issue 6, pp. 94–102.'},{id:"B30",body:'Loboda, I., Yepifanov, S., 2010, A mixed data-driven and model based fault classification for gas turbine diagnosis, International Journal of Turbo & Jet Engines, Vol. 27, Issue 3–4, pp. 251–264 (also see ASME Paper GT2010-23075).'},{id:"B31",body:'Loboda, I., Yepifanov, S., Feldshteyn, Y., 2013, A more realistic scheme of deviation error representation for gas turbine diagnostics, International Journal of Turbo & Jet Engines, Vol. 30, Issue 2, pp. 179–189 (also see ASME Paper GT2012-69368).'},{id:"B32",body:'Loboda, I., Olivares Robles, M.A., 2015, Gas turbine fault diagnosis using probabilistic neural networks, International Journal of Turbo & Jet Engines, Vol. 32, Issue 2, pp.175–192.'},{id:"B33",body:'Loboda, I., Feldshteyn, Y., Yepifanov, S., 2007, Gas turbine diagnostics under variable operating conditions, International Journal of Turbo & Jet Engines, Vol. 24, Issues 3–4, pp. 231–244 (also see ASME Paper GT2007-28085).'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Igor Loboda",address:"igloboda@gmail.com",affiliation:'
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1. Introduction
Visceral abdominal pain of the horse, defined as equine colic, is one of the most acute life-threatening problems facing equine practitioners [1]. The incidence of equine colic has been reported as between 4 and 10 cases/100 horses/year [2]. Colic in horses can be caused by more than 70 pathological processes in the gastrointestinal tract and manifests itself in many forms [3]. The diseases that accompany colic in horse are often characterized by ileus. The Greek physician Soranus defined an ileus as “a severe and dangerous twisting of the intestines.” Currently, an ileus can be referred to as a symptom characterized by a complete or partial disturbance passage of contents through the intestinal canal, due to obturation, strangulation, spasm, ischemia, adhesions and impaired motor function (paralytic ileus) [4].
The definition of paralytic ileus is somewhat controversial. Paralytic ileus is mostly defined as a temporary or permanent cessation of propulsive contractions of the gastrointestinal tract, irrespective of pathogenetic mechanisms, with subsequent gut dilation and accumulation of secretions and gas within its lumen [5]. Paralytic ileus in the horse is not a primary disorder but rather an underlying cause and can be classified on the basis of its etiology. More than 95% of all paralytic ileus cases in horses, seen after abdominal surgery, are primarily in the small intestine [6, 7]. Precisely for this reason, the paralytic ileus is often signified as postoperative ileus (POI). Once in a while, equine POI can be classified more precisely according to anatomical localization, for instance POI of the small intestine or POI of the cecum and colon. POI of the small intestine is easy to diagnose, through the presence of gastric reflux (i.a.), and impaired motor function seldom occurs in other parts of the gastrointestinal tract in horses too [8]. In the latter rarer cases, diagnosis is more of a challenge, because the presence of gastric reflux in the postoperative period is relatively uncommon after surgery on the large intestine in horses [9]. However, it must be considered also that the dysmotility in equine POI of small intestine may mask large intestine involvement.
In people following surgery, the return of the small intestine’s action generally begins around 4–8 h postoperatively and generally completes in around 24 h [10]. The colon resumes its function between 48 and 72 h postoperatively [11, 12]. In humans, based on this observation, various additional qualifying terms have been applied to POI, such as physiological POI, prolonged POI and recurrent POI [13]. This classification system can also be applied to horses, but it must be emphasized that the recurrent form of POI is very rare [14].
Regardless of determination or classification, equine paralytic ileus is a common and serious complication of surgery associated with highly increased odds of death. Reported fatality rate in horses with POI also varies widely, from 13 to 86% [15, 16, 17, 18]. In one study, horses that developed postoperative ileus were nearly 30 times less likely to survive than horses that did not develop ileus [19]. Additionally, equine POI leads to increased hospitalization time and treatment costs. It is for these reasons that since the first modern attempts to undertake abdominal surgery 50 years ago through to today, prevention and treatment of POI are widely discussed topics in equine medicine [20, 21]. In human medicine, enhanced recovery after surgery (ERAS) programs exist, which include multiple pre-, intra- and postoperative interventions, aiming to reduce the occurrence of POI [22]. Currently, in equine medicine, no universally-accepted approach exists for the management of equine POI.
Over the past 22 years, we have diagnosed and treated more than 180 horses with POI, using, in two veterinary clinics “Hochmoor” (Germany, 1997–2007) and “New Century” in Moskow (Russia, 2007–2019). In the latter times, with multiple pre-, intra- and postoperative procedures, not only was POI prevalence reduced significantly, but also following occurrences of equine POI successful treatment and survival were possible in more than 94% of cases. The purpose of this chapter review is to clarify some of the proposed key mechanisms in the pathophysiology of POI, share our experiences and make proposals for the prevention and treatment of equine POI.
2. Normal physiology of equine gastrointestinal motility
An appreciation of the basic mechanisms that regulate gastrointestinal motility is a key component to understanding paralytic ileus. The musculature of the gastrointestinal tract in horses is made up of smooth muscle cells that are intimately associated, thus allowing them to conduct electrophysiological functions. There are three distinctive electrical potentials in the equine intestine: resting potential, slow-wave and spike potential that trigger contractions. Slow waves are rhythmic pacemaker currents initiated by the interstitial cells of Cajal (ICC). Normal gastrointestinal motility in horses results from very complex interactions among the enteric nervous system (ENS), autonomic and central nervous systems, ICC, gastrointestinal hormones, immune cells, glial cells and local factors that affect smooth-muscle activity [21, 23, 24, 25]. Extrinsically, the sympathetic nervous input through noradrenaline has an inhibitory effect on gastrointestinal motility, whereas parasympathetic input increases motility. The ENS is involved in all aspects of gastrointestinal function, not only motility, as well as by enteric processes such as immune responses, detecting nutrients, microvascular circulation, intestinal barrier function, and epithelial secretion of fluids and ions [10]. The neurons of the ENS are collected into two types of ganglia: myenteric (Auerbach’s) and submucosal (Meissner’s) plexuses. The enteric nervous system influences the gastrointestinal tract either directly through neurotransmitters or indirectly through intermediate cells, such as the ICC, cells of the immune system or endocrine cells [10]. These intestinal neurons communicate through more than 25 different neurotransmitters, including stimulatory neurotransmitters (acetylcholine, neurokinin A, adenosine, substance P, motilin, serotonin and cholecystokinin) and inhibitory neurotransmitters, for instance, vasoactive intestinal peptide (VIP), nitrous oxide (NO), neuropeptide Y, calcitonin gene-related peptide, GABA and neurotensin [26, 27, 28, 29]. The endocrine system also indirectly affects regulation of the gastrointestinal tract motility. The hormones related to stress activity (glucocorticoids, cortico-realizing peptide, thyroid hormones and somatotropic hormone) have the most pronounced inhibitory effect on gastrointestinal tract activity. Additionally, the intestinal cells produce a range of hormones and hormone-like substances, some of which are also neurotransmitters. These substances regulate the motility of the gastrointestinal tract (motilin, enteroglucagon, cholecystokinin, pancreatic polypeptide and peptide YY) and secretory activity (gastrin, secretin, cholecystokinin, pancreatic polypeptide, gastric inhibitory peptide and neurotensin) and also regulate the production of other hormonal substances (somatostatin and gastrin-releasing peptide) [30].
3. Prevalence and risk factors for equine postoperative ileus
The etiology of paralytic ileus in the horse is multifactorial, and various factors contribute either simultaneously or at various times during the development of this entity. In the current literature, the incidence of POI in horses undergoing surgical treatment of all types of colic has been reported to range from 10 to 21% [31, 32, 33]. The incidence of POI in horses undergoing surgical treatment for small intestine lesions varies widely from 10 to 73% [1, 15, 16, 18, 19, 20, 31, 34, 35, 36, 37, 38]. The large variation in the reported rates can be at least partly explained by the criteria used to define postoperative ileus. Other forms of paralytic ileus, those that do not present due to equine surgery, are much less common than in humans. These include forms that result from metabolic derangements, acid-base abnormalities, electrolyte imbalances (hypokalemia and hypocalcemia), severity stress syndrome, peritonitis, bacterial infection, uremia, hypoalbuminemia, abdominal trauma, burns, botulism, grass sickness, atrophic visceral myopathy and application of drugs and anesthetic agents [6, 7, 26, 32].
According to our investigation, there was no significant age or breed dependence associated with the incidence of postoperative ileus in horses, but stallions more often had POI than geldings [39]. Our observations showed that the horses with a so-called hot temperament (i.e., horses with more excitable demeanors) had increased risks of developing POI than warm- or cold-blooded horses. The preliminary results (unpublished data) also showed that horses with behavioral symptoms of stress and high concentrations of cortisol in their blood in the pre- and postoperative time more often had POI than horses with normal concentrations of cortisol.
According to our observations, if pre- and during surgical intervention the equine jejunum had a high degree of intraluminal distension (more than 8 cm), postoperative ileus was more likely to occur and did so in more than 70% of the cases observed [32]. This is partly confirmed by other authors [15, 18]. A possible reason for this finding is the long onset of colic disease and high degree of endotoxic shock, which leads to enteric nervous system damage and a high degree of intraluminal jejunum distension. It has been demonstrated that decreases in intestinal motility through the distension of equine jejunum are partly due to decreases in motilin receptor synthesis [21].
Horses with small intestinal strangulating obstruction (for instance, by hernia inguinalis, entrapment in foramen omentalis) are at increased risk of developing POI, compared with obstructive ileus (for instance, by ileum or jejunum obstipation) [40, 41]. A basis for higher concentration endotoxins is that horses with entrapment in the foramen omentalis have lower blood pressures during abdominal surgery than horses with ileum obstipation [42]. It has also been shown that horses suffering from pedunculated lipoma obstruction are three times more likely to suffer from POI when compared with horses suffering from other intestinal pathologies [3]. This fact was confirmed in our own observations [4]. Many factors are associated with increased risk of POI in horses with pedunculated lipoma obstruction, for instance age-related decreases in intestinal density of the enteric neurons and glial cells, rapidly developing endotoxic shock and perhaps also high colic pain, which lead to enormous activation of the sympathetic nervous system.
Numerous studies have shown that long duration of colic disease, with evidence of endotoxin shock (high pulse rate and hemoconcentration), the presence of >8 l of reflux at admission, anesthesia for longer than 2.5 h, and the performance of a small intestinal resections pose enormous risks for POI development [15, 31, 43, 44]. Based on our results, the risk of developing POI and other fatal complications were associated with increased duration of surgery [14]. Surgical techniques also affect the incidence of POI in horses. The ability to perform a safe bowel resection and anastomosis techniques also affects the incidence of POI in horses; for instance, the use of jejunocecostomy has been associated more often with the development of POI when compared to horses in which end-to-end jejunostomy is performed [45]. One possible reason for this fact is possibly that the end-end jejunostomy is done more rapidly, and therefore duration of surgery and anesthesia is shorter than by the jejunocecostomy.
Other postoperative complications such as primarily postanesthetic myopathy and peritonitis increased the rapid risk of POI development in horses [46]. Other postoperative complications after colic surgery for example incisional infection, herniation and dehiscence, jugular vein thrombophlebitis, laminitis, adhesions and diarrhea had no important influence on the development of POI; however, these complications tend to develop later during the postoperative period in horses [39].
4. Pathophysiology of equine postoperative ileus
The pathogenesis of postoperative ileus is complex, with multiple factors contributing either simultaneously or at various times during the development of this entity. The classical view in the pathogenesis of POI involves two phases: an initial neurogenic phase resulting in immediate postoperative impairment of intestinal motility and a subsequent inflammatory phase lasting for several days [24, 30, 37, 47]. On the basis of our observations, we expanded this view into three (or five) main mechanisms, which either independently or in combination are involved in the causation of equine postoperative ileus, namely inflammatory-endotoxic mechanism, neurogen-endocrinic mechanism and pharmacological-anesthetic mechanisms. However, the importance of each contributing mechanism may vary over time, with considerable overlap and possible interactions; therefore, this division is conditional.
4.1 The role of inflammation and endotoxemia
Postoperative inflammation of the small intestine (and nearly imperceptibly of equine large intestine) is an important factor in the pathophysiology of equine POI [9, 48]. It is well known that inflammation is a biological response of the immune system, blood vessels and molecular mediators to a broad range of different stimuli such as pathogens, endotoxins, and physical and chemical irritants. There are a lot of inflammatory agents to take into consideration in POI, for instance, specific intestinal pathology and tissue injury (including obturation, strangulation and adhesion), bacteria, endotoxins, surgical trauma and manipulation [49, 50, 51, 52, 53]. The classical intestinal inflammation following paralytic ileus occurs by the duodenitis-proximal jejunitis (DPJ). This syndrome is caused primarily by toxic and infectious agents (e.g., Salmonella and Clostridium perfringens) [4, 44].
Horses with strangulating lesions of the small intestine have been shown to have various degrees of serosal and neuromuscular inflammation and high numbers of apoptotic cells (including smooth muscle, enteric neurons and glia), possibly due to intestinal ischemia and reperfusion injury [23, 54, 55, 56, 57]. According to different studies, equine POI might actually be triggered by a primary disturbance of the smooth muscles’ ability to contract, and how the number of smooth muscles or neural receptors has changed through a leukocytic and macrophage inflammatory response, primarily within the intestinal muscularis externa (Figure 1) [58, 59, 60]. Potentially due to different inhibitory mediators (NO, SP, VIP and NPY), cytokines (TNF, IL-1b, IL-6 and IL-10), monocyte chemotactic protein-1, prostaglandins, histamine, mast cell proteinase-1, tryptase, reactive oxygen intermediates, defensins and adenosine secreted from the muscularis externa during intestinal inflammation and abdominal surgery [49, 61, 62, 63, 64]. This local molecular inflammatory response increases prostaglandin E2 levels in the peritoneal cavity that correlates temporally with the development of postoperative ileus [13, 65, 66]. According to our former investigations, in most cases of equine abdominal surgery, during three postoperative days, the concentration of leukocytes is markedly increased (sometimes up to 100 × 109/l) as are total plasma proteins in the peritoneal cavity [39]. In the horse, postoperative neutrophilic and eosinophilic inflammation of the jejunum has been identified up to 18 h postoperatively [55, 67].
Figure 1.
Histological appearance of the jejunum in a horse affected by postoperative ileus. Note the mucous membrane maintaining its correct structure. In the submucosal layer and on the border with the inner muscle, extensive delaminating hemorrhage and leukocyte reaction were determined. Muscle fibers of the inner muscle layer with pronounced dystrophic changes in the cytoplasm were present. Ganglion cells in the intramuscular layer were not detected; in their place, a loose, weakly basophilic fibrous connective tissue with single mononuclear cells was present. The serosa was moderately edematous. H&E stained, ×10 magnification.
In intestinal inflammation, pathogen-associated molecular patterns or PAMPs have important roles. These molecules can be referred to as small molecular motifs conserved within a class of microbes. Bacterial lipopolysaccharides or endotoxins found on the cell membranes of Gram-negative bacteria are considered to be the prototypical class of PAMPs. The endotoxins are very potent and are widely spread inflammation-inducing substances. One of the basic characteristics of almost all gastrointestinal disorders in horses (primarily by different forms of strangulation ileus) is the development of the endotoxic shock [68]. The mucosal barrier of the equine intestine normally efficiently restricts the transmural movement of endotoxins and bacteria. However, whenever the integrity of the mucosal barrier is lost, as occurs with inflammation or ischemia of the intestinal wall, endotoxins cross into the portal blood and peritoneal cavity [69]. The generally accepted scheme for endotoxin binding is to CD14-bearing receptor cells (monocytes, macrophages, dendritic cells, and possibly vascular endothelial cells), which then associates with the TLR4-MD-2 complex to initiate a downstream signal, causing a proinflammatory response, such as leukocyte recruitment [53]. Macrophage-derived cytokines (such as IL-1b and TNF), as well as arachidonic acid metabolites (i.e., prostacyclin and thromboxane), are responsible for many of the pathophysiologic consequences of endotoxemia and tissue injury in equine colic cases. Endotoxins among other things activate inducible nitric oxide synthase (iNOS) in intestinal macrophages [66]. The resultant increase in NO release stimulates decreased smooth muscle contractility. In healthy ponies, IV infusion of endotoxin also resulted in inhibition of motility in the stomach, cecum, left dorsal colon, and small colon [70]. However, no nasogastric reflux was observed. Although motility in the small intestine was increased, its myoelectric pattern was abnormal. The effects of endotoxins on motility were partially mediated by PGE2 possibly stimulating alpha-2 adrenergic receptors [28, 51, 71]. A platelet-activating factor (PAF) antagonist suppressed some of the endotoxin-induced inhibition of motility in horses. These findings led to the conclusion that the PAF may also play a role in the development of POI [68].
The degree of endotoxic shock in horses is directly dependent on the forms and time span of gastrointestinal disease [72]. As the concentration of Gram-negative bacteria is highest in the large intestine of horses, the release of endotoxin and development of endotoxic shock are logically expected in pathologies of this part of the gastrointestinal tract, for instance by volvulus or colitis [43]. In the small intestine of horses, different population of Gram-negative bacteria exist, but in lower concentrations than observed in the large intestine. It would therefore be expected that in this case the endotoxins would not play a decisive role in development of POI. In contrast to this theory in one study of colic cases, the highest endotoxin concentrations were found in horses with entrapment in the foramen omentalis, pedunculated lipoma obstruction and volvulus (torsion) of the large colon [72]. A significant impairment of small intestine transit has been shown in a rat model of colonic manipulation, which occurred even when the small intestine was surgically isolated [73]. These findings led to the conclusion that colonic manipulation induces an inflammatory response in the muscularis of the small intestine that is initiated and maintained by the release of endotoxins from the colon.
One potential trigger for intestinal inflammation not only endotoxins, as well the damage-associated molecular patterns (DAMPs) which realase by extensive surgical intestinal manipulation, luminale distension and resection [6, 7, 48, 52]. DAMPs are host biomolecules that can initiate a noninfectious inflammatory response. DAMPs are mostly cytosolic proteins and materials derived from the extracellular matrix (including hyaluronan fragments, ATP and heparin sulfate) and are generated following tissue injury [6, 7]. An activation of resident muscularis macrophages in the small intestine through DAMPs results in recruitment of intracellular signaling pathways (p38, JNK/SAP) and the release of pro-inflammatory cytokines [6, 7, 37]. Inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) upregulation then facilitates the production of NO and prostaglandins, both of which impair the contractile activity of the small intestine [52, 74, 75]. It additionally reduces lymphatic drainage with the occurrence of intestinal edema, which further impairs intestinal motility [76].
4.2 The role of the neurogen-endocrinic factors
The sympathetic division of the autonomic nervous system maintains internal organ homeostasis and initiates the stress response. In addition, sympathetic (adrenergic) hyperactivity results in the reduction of propulsive intestinal motility [8, 77, 78]. In the early component of ileus, the sympathetic neural pathways are activated already in the preoperative period, primarily through intestinal distension or strangulation (i.e., through initial colic pain), but inflammation and surgical manipulation and incision of the intestines and abdomen wall additionally stimulate afferent nerve fibers that subsequently activate peripheral, spinal and/or supraspinal reflex pathways [8, 15, 24, 27]. The sympathetic hyperactivity is amplified through various preoperative stressors (i.e., transport to clinic, unfamiliar surroundings with unknown caretakers, restraint of the horse for examination and rectal investigation) and also in the postoperative period of horse, initially by the recovery from anesthesia, but also in many postoperative diagnostic and management procedures (such as tying in stall, fasting, gastric decompression and blood collection) [24, 79]. There is overwhelming experimental and clinical evidence that different stress paradigms influence gastrointestinal motility [47, 80, 81, 82].
Sympathetic hyperactivity in horse primarily depends on the intensity of the nociceptive (pain) receptor stimulus [83]. Numerous nociceptors of sensory intestinal neurons by tissue damage or surgical manipulation send signals to the spinal cord and further to specific hypothalamic and pontine-medullary neurons. Within this pathway, corticotropin-releasing factor (CRF) plays a central role in inhibiting gastric and small intestinal motor function (but not of the colon) via interaction with the CRF-R2 receptors [82, 84, 85, 86, 87, 88]. The CRF stimulates neurons in the supra-optic nucleus of the hypothalamus, which send projections to the spinal cord, including the intermediolateral column of the thoracic cord, where sympathetic preganglionic neurons are located [88, 89]. At this point, inhibitory sympathetic efferent neurons are activated. Norepinephrine is released by sympathetic neurons at the enteric ganglia, which inhibit the release of the excitatory neurotransmitter acetylcholine by stimulating α2-receptors located presynaptically on cholinergic neurons [21]. This causes a depression of smooth muscle contractions in the gastrointestinal tract.
Activation of CRF receptors in the hypothalamus of horses mediates almost the entire repertoire of behavioral, neuroendocrine, autonomic, immunologic and visceral responses characteristic of stress syndrome [77, 90]. CRF release is the first step in activation of the hypothalamic-pituitary-adrenal axis (HPA axis) involved in stress response. The magnitude and duration of the activation in the HPA axis are proportional to the initial tissue damage and surgical injury, but also in other perioperative stress conditions. The pituitary gland responds to CRF by synthesizing a larger precursor molecule, proopiomelanocortin, which is metabolized within the pituitary into ACTH, β-endorphin and N-terminal precursor. Growth hormones and prolactin are also secreted in increased amounts from the pituitary in response to a surgical stimulus. Surgery is one of the most potent activators of ACTH and cortisol secretion; therefore, increased plasma concentrations of both hormones in human can be measured within minutes of the start of surgery [91]. Usually, a feedback mechanism operates so that increased concentrations of circulating cortisol inhibit further secretion of ACTH. This control mechanism appears to be ineffective after surgery resulting in elevated concentrations of both hormones [80]. Cortisol has known complex metabolic effects on the metabolism of carbohydrate, fat and protein. Cortisol impairs inflammation, which is helpful in the short term during conditions such as ‘fight-or-flight,’ also referred to as hyperarousal, or the acute stress response. In response to surgical trauma, massive levels of catecholamine (adrenaline, noradrenaline and dopamine) and glucagons are also released, while serum insulin concentrations decrease relatively [91]. The overall metabolic effect of the hormonal changes is increased catabolism, which mobilizes substrates to provide energy sources, and a mechanism to retain salt and water and maintain fluid volume and cardiovascular homeostasis [86]. According to our own preliminary research results (unpublished data), the cortisol levels increased from a baseline in the postoperative days after colic surgery, but more remarkably in POI group horses.
It seems that upon inflammation, there are numerous neurotransmitters that are mediated through surgical and postoperative stress, which caused disturbances in the motility of the gastrointestinal tract [92]. In an experimental model in ponies, using jejunal trauma through sympathetic reflexes and inflammation, electrical activity was decreased and the normal synchrony of gastric and duodenal MMCs was disrupted [8]. Intestinal manipulation of the small intestine in rodents impairs intestinal transit, through an inhibitory adrenergic pathway, because its sympathetic blockade is not always successful in reversing the inhibition of gastrointestinal motility induced by abdominal surgical procedures [93, 94]. In addition to sympathetic reflexes, surgical manipulation of the intestines activates inhibitory non-adrenergic, non-cholinergic (NANC) neurons in the gastrointestinal tract, resulting in the release primarily of NO and VIP, the consequences of which result in decreased gastrointestinal motility [93, 95, 96]. Substance P, which is a neurotransmitter involved in pain, has also been hypothesized to have a role in postoperative ileus [85]. In a model of POI in rats, where mechanical trauma to the small intestine and cecum was used, reserpine (which depletes catecholamine stores) and L-nitroarginine (a nitric-oxide synthase inhibitor) completely reversed the inhibition of ingesta transit. This finding supported the involvement of adrenergic and nitrergic neurons in the pathogenesis of POI [93]. As blockade of the calcitonin-gene-related peptide resulted in a similar effect, this peptide may be one of the neurotransmitters released by these afferent fibers and partly mediate postoperative ileus [97]. Additionally, endogenous opioids are also released after surgery and contribute toward postoperative ileus [92].
Other changes also occur following surgery stress, notably an increase in cytokine production. In human patients after surgery, cytokines IL-1, TNF-α and IL-6 may augment pituitary ACTH secretion and subsequently increase the release of cortisol. A negative feedback system partially exists; therefore, glucocorticoids inhibit cytokine production and inflammation [98].
Most studies concentrate on central mechanisms whereby a stressful event perceived by the brain triggers neuronal and hormonal reflexes that influence the gastrointestinal motility. According to one study, the intestine produces the same stress peptides that are present in the central nervous system [99]. A local stressor, in this case endotoxins, results in the local generation and action of stress peptides that mediate inflammation without involving the central nervous system. In other words, the peripheral stressors induce local release of CRF possibly from enteric neurons and immune cells [88]. Peripherally derived CRF may act on the enteric nervous system and mast cells to induce inflammation and control motility and secretion [89].
4.3 The role of drugs and anesthetic agents
The pharmacological mechanisms of postoperative ileus are well described in the literature. Xylazine and detomidine are α2-adrenergic agonists and are commonly used in horses for sedation and pain control. Activation of presynaptic α2-adrenergic receptors within the enteric nervous system inhibits ACh release from cholinergic neurons, thereby suppressing intestinal contractions in normal ponies, primarily of the distal jejunum, pelvic flexure, cecum, and right ventral colon [100, 101, 102]. Although the use of α2-agonists has been reported to suppress intestinal motility, no direct significant associations have been made between POI and sedation or type of sedative used.
Anesthesia gases do have an effect on intestinal motility, and the longer anesthesia lasts, the greater the actions [85]. Based on our observations during 1997–2000, the incidence of POI was greater than after the year 2000. One of the reasons for this was that the active use of halothane was stopped, and we began to use isoflurane as an anesthetic gas. Other studies have also shown that anesthetic drugs such as halothane and atropine tend to decrease gastric emptying and inhibit intestinal motility, with the greatest effect on the colon and cecum and they can initiate cecal impaction in horses [103, 104, 105]. Interestingly, the cecal impaction occurs more commonly after orthopedic procedures [106]. Therefore, general anesthesia herein appears to be a less likely primary cause of cecal and small intestine motility dysfunction [104, 107]. Possibly, persistent pain after orthopedic procedures, resulting in sympathetic overstimulation, is a significant contributing factor.
5. Diagnosis of equine postoperative ileus
Large intestinal dysmotility is commonly recognized following a delay in defecation and also by rectal and/or ultrasonographic examination. There are different criteria for the diagnosis of equine small intestine POI in the literature [15, 16, 17, 108, 109]. Based on our previous experience and regardless of the rare cases of exclusion, the main criteria for diagnosis of POI of small intestine are as follows:
Postoperative period during 1–7 days after abdominal surgery. Most cases of POI occur within 12–48 h after recovery from anesthesia.
Postoperative reflux of ≥2 l upon any given intubation, or > 2 l/h on repeated intubation, of gastric contents with pH ≥ 6.0. Another study defined cases of postoperative ileus as horses with >20 l during a 24-h period, or >8 l during any single refluxing event [110]. Merrit and Blikslager [111] suggested the adoption of a consensus on the classification of clinical criteria for POI, which included ≥4 l on any given intubation or > 2 l/h on repeated intubation. In most of our cases of POI, an average of 8–12 l, if intubation is performed every 4–5 h (i.e., approximately 2 l/h of fluid accumulate in the stomach). If more reflux is noticed, other pathologies are possible (e.g., mechanical obstructions and anastomotic leaks).
Moderate abdominal discomfort, which intensifies every 4–5 h after the last intubation. The response to nasogastric decompression provides an important clue that the problem is functional (i.e., POI). If a high degree of pain is noticed and continues, other gastrointestinal pathologies are possible.
Heart frequency 40–65 beats/min, if intubation is performed every 4–5 h.
Hematocrit 0.40–0.50 l/l, if standard infusion therapy is performed. If a high hematocrit is noticed, other gastrointestinal pathologies are possible.
Evidence of multiple fluid-distended small intestinal loops on rectal examination.
Ultrasonographic evidence of multiple fluid-distended small intestinal bowel loops (≥3 cm), edema and lack of motility in different parts of the equine abdomen (Figure 2) [112, 113, 114].
Borborygmi are usually decreased, especially the absence the ileocecal noise dorsally behind the right costal arch [48, 115].
Figure 2.
(A) Transcutaneous ultrasonogram in a horse with POI before surgery in region 3 l with evidence of multiple fluid-distended small intestinal bowel loops [113]. (B) Jejunojejunal distension identified during repeat celiotomy in the same horse.
6. Prevention and treatment of equine postoperative ileus
Since the treatment of this condition is very complex, and the complications are often fatal, the prevention strategy of POI is a very important way to improve the survival rate of horses that have undergone abdominal surgery [34, 109]. There are many methods and procedures and prophylactic and therapeutic choices for equine POI, depending on each individual case. The preventive strategies come from better understanding the pathogenesis of this condition and treatment of POI must first address the underlying cause(s). The prophylactic and treatment strategies of the equine POI we are currently proposing are a multimodal regimen, which can be divided into three phases pre-, intra- and postoperative. The proposed multimodal treatment approach should include limiting factors, which are known to contribute to postoperative ileus. Each phase has the same significance in survival rate of equine POI.
6.1 Preoperative strategies in the prevention of equine POI
The long onset of colic disease producing high degree of endotoxic shock, in accordance with our earlier findings [32], are strongly associated with an increased risk for POI development. In this regard, it is appropriate to again highlight the importance of timely referral and prompt surgical intervention in surgical (strangulation) colic cases for the prevention of POI. Additionally, time from onset of colic to surgery has a decisive role not only in prophylactic but also in terms of a successful treatment by occurrence of equine POI. Failure to refer promptly leads to not only POI but also the occurrence of other perioperative complications by abdominal surgery in the horse. Approximately, every hour of tardiness with surgical interventions in a horse with strangulation ileus (for instance, by small intestine or large colon volvulus) reduces the survival rate from 5 to 10%, due to the rapid development of endotoxic shock [4, 116]. We found a significant correlation between the occurrence and survival of POI with colic duration in horses with inguinal hernia (r = 0.72) and epiploic foramen entrapment (r = 0.78), and partially (not significant) due to ileum obstipation (r = 0.41) [40, 41, 45]. According to our recent study in 33 horses with entrapment in the epiploic foramen, surgery performed within 6 h from onset of colic had a survival rate of 87%, compared with 25% survival with surgery 10 h or more after onset [40].
It is important even before the onset of surgery to prepare, applying medicaments that reduce endotoxin release and alleviate inflammation effect, for instance, the application of NSAIDs (flunixin meglumine), corticosteroids (prednisolone) and antibiotics. Administration of corticosteroid drugs to critically ill surgical colic horses results in a significant reduction of shock symptoms. The use of these drugs should certainly continue in the postoperative period [26]. Antimicrobials should be administered intravenously, ideally within 30–60 min before the first surgical incision. For horses undergoing abdominal surgery in the perioperative period, we introduced the following antibiotics: cobactan® 2.5% (cefquinome) (IM 3 mg/kg BW) for 5 d; gentamicin (6.6 mg/kg BW, IV, q24h) and metronidazole (20 mg/kg BW IV, four times daily) for 3 days. Additionally, if time permits, during urgent transport to the equine clinic, horses should have a balanced polyionic intravenous fluid applied in order to reduce hemoconcentration. It is advisable that before abdominal surgery horses should have a hematocrit level of below 0.45 l/l. In cases of metabolic acidosis, 5% sodium bicarbonate solution should also be administered. We used pre- and intraoperative the hypertonic saline (NaCl 8.0%) only in horses with severe endotoxic shock and if in doubt on the presence of intestinal edema [40].
6.2 Intraoperative strategies in the prevention of equine POI
Surgical procedures and anesthesia affect the development of POI in horses (as discussed above). Operative management should be aimed at reducing duration of surgery and anesthesia in addition to other preventative strategies. In this aspect, an important role is played by a high-performing multidisciplinary surgical team with experience and knowledge as this optimizes surgical procedures. During the abdominal surgery, the least traumatic surgical methods should be selected and performed and these should be carried out as efficiently and therefore quickly as possible. The degree of inhibition of circular muscle contractility is related directly to the magnitude of leukocyte and macrophage infiltration, which in turn depends on the intensity of intestinal manipulation; therefore, every effort should be made to reduce intestinal trauma. One surgical method able to reduce surgery time is the use of the stapled technique for jejunal resections [117]. As already described above, other postoperative complications in horses undergoing abdominal surgeries have an impact in developing POI, notably by postanesthetic myopathy [118, 119]. Therefore, special attention must be paid to optimizing blood pressure during abdominal surgery. For these purposes, anesthesia monitoring should be carried out at all the time, and if a decrease in blood pressure (defined as mean arterial pressure <70 mmHg) is observed, a dobutamine injection should be administered [42, 46]. In cases of severe anesthetic hypoxia (PO2 < 70 mmHg), one ought to have the issue resolved in a timely manner with intermittent positive pressure ventilation (IPPV) with constant positive end-expiratory pressure.
Several methods have recently been developed to decrease the rate of other surgical complications [35, 117]. The methods of minimizing postoperative adhesions are the application of meticulous atraumatic surgical technique, use of a bioresorbable hyaluronate-carboxymethylcellulose membrane [118, 120], administration of heparin [40], omentectomy [121] and performing intraoperative peritoneal lavage [39]. In the case of strangulating obstruction of the small intestine, the bowel to be resected and discarded should be placed over the edge of the surgical field while removing the contents of the small intestine. Performing a pelvic flexure enterotomy may also reduce POI risk [110], which has also been confirmed during our observations [45]. The protective influence of these procedures may be attributable to a reduction in the intraluminal source of endotoxin, but the potential value of evacuating the colon should be weighed against the increased anesthesia time required to perform the surgery, as both factors have been associated with an increased risk of POI [106].
6.3 Postoperative strategies in the prevention and therapy of equine POI
Postoperative strategies in the prevention and treatment of equine POI are numerous and dependent on each individual case [26]. This can be divided into standard supportive postoperative procedures and procedure by risk for the patient. Under standard management, the following should be considered: regular basic clinical measurements (every 4–5 h) including heart and respiration frequency, temperature, auscultation of bowel sound, and of laboratory parameters including hematocrit, total plasma protein and acid-base state of the blood. In the standard postoperative procedures, several checks should be undertaken. We used at least 3 days administration of balanced polyionic intravenous fluid. The amount and length of time of the infusion solution are dependent on blood parameters; on average, we applied 2.5–3 l/h/500 kg BW. Dehydration and electrolyte imbalances are commonly encountered as a result of abdominal disorders and surgery. Even though a horse is stabilized in the perioperative period and the primary problem is corrected, continued replacement of previous and ongoing fluid losses is critical for a successful outcome. If a horse has gastric reflux, the use of the infusion solution should be continued throughout this condition. Given that the introduction of a large number of solutions provokes the development of thrombophlebitis of the jugular veins, it is recommended that a central catheter is installed through the abdominal vein.
In all horses without and with POI after abdominal surgery, NSAIDs should be administered such as flunixin meglumine (1.1 mg/kg BW, IV, q12h initially for 2 days, then 0.55 mg/kg BW, IV, q12h for at least 2 days). Flunixin meglumine controls postoperative pain and improves the cardiovascular manifestations of endotoxemia. Additionally, flunixin meglumine has been shown to significantly attenuate the disruption of gastric, small intestine, and large colon motility elicited by endotoxin infusion [49]. Additional treatments include anti-oxidant medications, which prevent the generation of chemoattractants: DMSO (20 mg/kg BW in 1 l saline IV bolus, q12h) and sodium heparin (20,000 IU, SQ , q12h). In all postoperative horses without gastric reflux, we applied obligatory laxatives (2 l liquid paraffin, p.o.) after abdominal surgery. For the prevention of incisional infection, horses received abdominal bandages during hospitalization. The bandages consisted of sterile absorbent cotton padding next to the incision secured by elastic adhesive tape.
6.4 Postoperative peritoneal lavage
Postoperative peritoneal lavage has been used in an attempt to reduce the rate of postoperative adhesions [119], but this procedure decreases occurrence and increases survival rates of equine POI [39]. Thus, in horses with a high risk of POI and who additionally showed symptoms of peritonitis, we performed retrograde peritoneal lavage through a Foley catheter, which was installed into the abdominal cavity prior to closure of the abdominal incision. For abdomen lavage, we used sterile physiologic saline or Ringer’s lactate solution (10–15 l) containing amoxicillin (5 g) and 20,000 units of sodium heparin.
6.5 Prokinetic drugs for the treatment of equine postoperative ileus
The use of prokinetics in horses with POI is only part of the treatment and is not defined as a unique technique toward the survival rate of this disease, only working in combination with other methods [5]. The effectiveness of some prokinetic drugs in horses is associated with the difficulties of conducting a well-designed, randomized clinical trial with homogenous groups of animals [38]. None of the intestinal prokinetic agents have been subject to rigorous clinical efficacy trials [122]. This statement is supported by the fact that the contractile response of intestinal smooth muscle to prokinetic drugs is significantly impaired in many horses with POI. Prokinetic motility drugs are also commonly used following abdominal surgery in humans to prevent ileus, although a Cochrane review examined 39 randomized controlled trials and found most medications to be of little or no benefit [6, 7]. There are numerous prokinetics drugs that can be used by POI in the horse, which have differing mechanisms of action and different efficiency rates [26].
Parasympathomimetic agents (cholinomimetics) are drugs that mimic the effects of the parasympathetic nervous system activity. Directly acting parasympathomimetic agents, bethanechol chloride, improve myoelectric activity in the stomach, jejunum, ileum, and large and small colons of horses, but produce significant cholinergic side effects (increased salivation), and therefore are not used as a standard in equine praxis [71, 101]. In horses with POI, applications are mostly indirectly acting parasympathomimetic agents such as neostigmine methylsulfate. Neostigmine is a cholinesterase inhibitor that prolongs the activity of acetylcholine by retarding its breakdown at the synaptic junction [102, 123]. Neostigmine has been shown to delay gastric emptying and decrease jejunal myoelectric activity, but enhances myoelectric activity in the ileum, cecum, right ventral colon and pelvic flexure activity in healthy ponies [71, 122]. These results suggest that the drug would not be appropriate for gastric and small intestinal problems but may be beneficial for large intestinal motility dysfunction. However, neostigmine increased the amplitude of rhythmic contractions in both the resting and distended jejunum in anesthetized ponies, and it induced contractile activity in the ileum, supporting its use for motility dysfunction in both the small and large intestine [26, 29, 124]. Based on our clinical impressions, neostigmine if used as monotherapy repeated at 60 min intervals (during 24–48 h) has significant beneficial effects in the treatment of colitis cases, but not in POI of the small intestine [43].
6.5.2 Sodium channel blockers
Sodium channel blockers—lidocaine is currently a prokinetic agent, which is most frequently used for the treatment of POI in equine practice, although scientific evidence on its prokinetic and analgesic effectiveness is limited [33, 124, 125, 126, 127, 128]. Lidocaine has antinociceptive, antihyperalgesic, and anti-inflammatory effects [6, 7]. In an investigation within a UK hospital population, lidocaine therapy had no effect on the prevalence of postoperative reflux, total reflux volume or duration of reflux and as well as no effect on postoperative survival in horses undergoing abdominal surgery [129]. According to our observations, lidocaine if used as monotherapy has little positive effect on the treatment of equine POI and is significantly inferior to a combination of prokinetic drugs [32].
6.5.3 Drugs acting as 5-hydroxytryptamine receptors
Drugs acting as 5-hydroxytryptamine receptors include metoclopramide, cisapride, mosapride citrate and tegaserod [36, 130, 131, 132]. Metoclopramide hydrochloride (MCP) is a first-generation substituted benzamide whose prokinetic activity is both through dopamine 1 (DA1) and 2 (DA2) receptor antagonism and through 5-HT 4-receptor (5-HT4) agonism and 5-HT3 receptor antagonism [11]. Stimulation of DA2 receptors inhibits the release of acetylcholine, and stimulation of 5-HT4 receptors enhances the release of acetylcholine from the myenteric ganglia. MCP is a drug, which for a long time has often been used in the prevention and treatment of equine POI, but results in published studies have been variable [5, 8, 21, 130]. The prokinetic capacity of metoclopramide appears substantial in the equine stomach, duodenum and jejunum, but not in the large intestine [128, 133].
6.5.4 Motilin agonists
Motilin agonists include erythromycin lactobionate, and a macrolide antibiotic has been shown to significantly increase solid phase gastric and dose-dependent cacal emptying and is thought to exert prokinetic effects via activation of motilin receptors [20, 21, 36]. The prokinetic effects of erythromycin reported in healthy horses were not the same in horses with gastrointestinal disease [110, 122, 128].
6.5.5 Adrenergic antagonists
Adrenergic antagonists include acepromazine maleate, a nonselective α-adrenergic antagonist, and yohimbine, tolazamide, and atipamezole, which are selective α2-adrenergic antagonists. Their use as prokinetics is based on the assumption that sympathetic hyperactivity contributes to POI, but their beneficial effects are not well understood [6, 7].
6.5.6 Dopamine antagonist
Dopamine antagonist—domperidone is a selective peripheral DA2 receptor antagonist [26]. In a preliminary experimental model of POI in ponies, domperidone was effective in restoring transit time, electromechanical activity, and coordination of gastric and intestinal cycles [134].
6.5.7 Combination of prokinetic drugs
Combination of prokinetic drugs—based on our research, the best medicinal method for prevention and treatment of equine POI is a combination of three drugs, according to the needs of the individual scheme of each case [5, 14, 32]:
Neostigmine methylsulfate (in a dose of 0.004 mg/kg per 2 h, i.e., 2 mg per 500 kg BW, subcutaneously)
Metoclopramide (in a dose of 0.01–0.02 mg/kg per 2 h, i.e., 5–10 mg per 500 kg BW, subcutaneously or intravenously)
Domperidone (in a dose of 0.16 mg/kg orally, every 8 h)
We found that the prophylactic perioperative use of these drugs in risk horses to reduce the incidence of POI, and by occurrence of ileus significantly improved survival rate [5, 14, 32]. These prokinetic drugs should not be applied at the same time (little benefit), but strictly in turn. Why these drugs benefit only in turn in combination and not at the same time is unknown. Neostigmine methylsulfate and metoclopramide were applied alternatively between each other in 60 min intervals, so that every horse received each of the drugs every second hour (i.e., 1 h neostigmine methylsulfate was administered and in the second hour metoclopramide was given). We used this therapeutic regimen for POI horses continuously for several days until a result was obtained (complete absence of gastric reflux), and usually, this happened within 24–90 h. The withdrawal of these drugs should take place gradually throughout a few days. On average, this occurred 5–6 days after the onset of equine POI. If sharp withdrawal of these prokinetics is undertaken, a relapse of gastric reflux is possible.
6.6 Nasogastric decompression
Nasogastric decompression is a classic supportive treatment that prevents gastric dilation in horses with POI. We performed this procedure in horses that showed gastric reflux, it was applied regularly every 4–6 h, and most horses begin to show clinical signs (colic) associated with excessive fluid accumulation in the stomach. Retaining an indwelling tube for 12–15 h in horses with POI was performed only in cases where animals showed extensive stress syndrome by intubation.
6.7 Judicious timing of feeding
Horses without gastric reflux were allowed access to water within 12–18 h after abdominal surgery and were provided with small amounts of feed at 18–30 h after surgery. Initially, small amounts of grass hay or small amounts of bran mash with 100 ml laxatives were fed every 3–4 h. The quantities were gradually increased daily until the horses were allowed to freely eat hay by choice (usually by 21 days after surgery).
Freeman and coworkers were able to show that of the horses taken to surgery for small intestinal disease, only 10% developed postoperative ileus [17]. According to the authors, one key management factor in prophylactic procedures of POI was early re-feeding, where horses were offered water and small amounts of hay within 18–24 h of the completion of surgery for small intestinal disease. Early feeding following abdominal surgery is a commonly applied prophylactic approach in human medicine, as well. It is hypothesized to promote restoration of gastrointestinal motility via the release of neuropeptides in response to solid feed ingestion. In humans, it is known that chewing gum is a type of sham feeding that promotes intestinal motility through cephalic-vagal stimulation [6, 7, 135].
According to our opinion, the judicious timing of feeding in horses with POI is when no signs of reflux are apparent or when motility is regained. Horses with evidence of gastric reflux are unlikely to tolerate enteral feeding and should receive intravenous nutritional support (i.e., glucose solutions and amino acids). In addition to the intravenous administration of glucose solutions, it is necessary to use insulin subcutaneously at a dose of 0.08 U/kg every 12 h in order to block the lipase enzyme responsible for releasing triglycerides from fat depots. As is well known, if the fasting regime lasts more than 3 days, this may provoke development of a severe form of equine hyperlipidemia, notable in obese horses. Hyperlipidemia is associated with periods of negative energy balance and physiologic stress [136]. For this reason, in horses with POI at 48 h after abdominal surgery, regardless of the presence of gastric reflux, we allowed the horses, after nasogastric decompression, to be fed with a small amount of bran mash with ranitidine oral tables (H2-antihistamine). Additionally, for horses with gastric reflux for which the provision of enteral nutrition is not possible, the provision of a lick (e.g., mineral block) has been suggested as a form of sham feeding, equivalent to gum chewing in humans.
6.8 Stress reduction strategies
Suppression of parasympathetic activity and hyperactivity of the sympathetic nervous system with activation of the hypothalamic-pituitary-adrenal axis (stress syndrome) has a very important role in the development of equine POI (as discussed above). Causes of equine stress syndrome in perioperative period can be varied, primarily pain and inflammation, but also recovery from anesthesia, postoperative diagnostic and management procedures and fasting, as well as different psychological (fear) factors. It is generally considered or hypothesized that a more invasive surgery, with extensive tissue trauma and noxious stimuli, triggers a more significant stress response. After surgery, the horse is placed in an unfamiliar environment with unknown caretakers and probably starved while having additional pain to deal with. Postoperative pain can originate from peritoneal inflammation and abdominal incision. Consequently, it is important on all occasions to consider minimizing sympathetic activity, primarily pain and inflammation control of the horses after abdominal surgery. As is well known, anti-inflammatory drugs lead to lower pain scores and lower plasma cortisol levels [82, 91]. This amount of stress modulates the pain perception and adds further to the perceived pain. This in turn increases appetite, so the horse does not enter a catabolic state in order to produce substrates for healing.
Given all of the stress, it is therefore also extremely important to take care of the horse psychologically. All therapeutic procedures in postoperative period should be performed with minimal stress. Stress-enhancing procedures may include introduction of a nasogastric tube into the stomach, which causes discomfort and the release of catecholamine, and this process is necessarily carried out with the imposition of a twitch and without sedation. It is believed that a twitch calms the horse by releasing endorphins as pressure is applied, thus reducing stress and pain. Administration of corticosteroid drugs results in the reduction of stress syndrome, but non-pharmacologic mechanisms for reducing the stress response are quite successful, for instance, regular visits from the owner or a familiar caretaker, frequent contact and grooming preferably by the same handler or veterinarian, short periods of hand-walking, treats given from time to time, short periods of grazing (1–2 min around 24–48 h after abdominal surgery) and minimal enteral nutrition. As described above, early re-feeding has been attributed to possible downregulation of the metabolic stress response [35]. Additionally, all other external stress factors for horses (including transport, loud noises, bright light and rudeness of medical staff), as far as possible, should be abolished during the postoperative period in an equine clinic, both in horses with a risk of development and also in horses that already have a POI.
6.9 Repeat celiotomy and postoperative ileus
Relaparotomy (repeat celiotomy) is widely accepted as a treatment option in the management of postoperative colic and ileus [6, 7]. A repeated surgical intervention in the abdominal cavity may correct technical errors that occurred during the first surgery and solve conservatively unsolvable motility disorders as well as pathological conditions that occur in the post-surgical period without a clear relation to the first intervention [1]. Previously, authors considered that intestinal manipulation (massage) and repeated enterotomy likely have beneficial effects to equine POI [103]. However, the potential benefit of limiting the degree of intestinal manipulation in equine surgery must be weighed against the increased risk of other postoperative complications (postanesthetic myopathy, wound infection and hernia). According to our observation, repeat celiotomy did not increase survival rate in horses with POI; for example, surgical cases had a lower survival rate than medically managed cases of POI [32].
Acknowledgments
Albert A. Rizvanov was supported by the Russian Government Program of Competitive Growth of Kazan Federal University and funded by state assignments 20.5175.2017/6.7 and 17.9783.2017/8.9 of the Ministry of Science and Higher Education of Russian Federation.
Conflicts of interest
The authors declare no conflicts of interest.
Dedication
This chapter is dedicated to Prof. Dr. Dr. H.C. Bernhard Huskamp (1932–2018) the founder of the Veterinary clinic Hochmoor in recognition of his extensive contributions to equine colic surgery.
\n',keywords:"postoperative ileus, paralytic ileus, horse, prevention, treatment",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/71238.pdf",chapterXML:"https://mts.intechopen.com/source/xml/71238.xml",downloadPdfUrl:"/chapter/pdf-download/71238",previewPdfUrl:"/chapter/pdf-preview/71238",totalDownloads:943,totalViews:0,totalCrossrefCites:1,dateSubmitted:"January 8th 2020",dateReviewed:"January 21st 2020",datePrePublished:"March 2nd 2020",datePublished:"September 23rd 2020",dateFinished:"February 25th 2020",readingETA:"0",abstract:"Equine paralytic (postoperative) ileus generally refers to an acute condition of impaired gastrointestinal motility. Paralytic ileus is most frequently seen following abdominal surgery on the small intestine in horses. Three main mechanisms are involved separately or simultaneously in its causation, namely neurogenic-endocrinic, inflammatory-endotoxic and pharmacological mechanisms. Regardless of the cause, equine paralytic ileus can be fatal, if not properly diagnosed and treated. Over the past 22 years (1997–2019), we have diagnosed and treated more than 180 horses with postoperative ileus using differing methods. Based on our results and experience, and that of others, we have developed a multimodal strategy to reduce the incidence of postoperative ileus. This has resulted in effective treatment of ileus-diagnosed patients in 94% of cases, a significant improvement in survival rates over the last 20 years. In this review, we described pre-, intra-, and postoperative multiple supplementary preventative and treatment procedures that cure this condition. These methods are dependent on individual cases but include the control of endotoxemia and inflammation, as well as using the least traumatic surgical techniques, carrying out the pelvic flexure colotomy, improved anesthesia techniques, treating with continuous postoperative peritoneal lavage, the use of fluid, antibiotic and NSAIDs therapy, according to a scheme the use of different prokinetic agents (including metoclopramide, neostigmine methylsulfate and domperidone), nasogastric decompression, management to minimize the surgical and postoperative stress reaction and judicious timing of postoperative feeding of horses.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/71238",risUrl:"/chapter/ris/71238",signatures:"Milomir Kovac, Ruslan Aliev, Sergey Pozyabin, Nevena Drakul and Albert Rizvanov",book:{id:"9081",type:"book",title:"Equine Science",subtitle:null,fullTitle:"Equine Science",slug:"equine-science",publishedDate:"September 23rd 2020",bookSignature:"Catrin Rutland and Albert Rizvanov",coverURL:"https://cdn.intechopen.com/books/images_new/9081.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83962-317-2",printIsbn:"978-1-83962-316-5",pdfIsbn:"978-1-83962-318-9",isAvailableForWebshopOrdering:!0,editors:[{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"284212",title:"Prof.",name:"Kovac",middleName:null,surname:"Milomir",fullName:"Kovac Milomir",slug:"kovac-milomir",email:"kovacmilomir@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"312551",title:"Prof.",name:"Albert",middleName:null,surname:"Rizvanov",fullName:"Albert Rizvanov",slug:"albert-rizvanov",email:"rizvanov@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Kazan Federal University",institutionURL:null,country:{name:"Russia"}}},{id:"317685",title:"Dr.",name:"Ruslan",middleName:null,surname:"Aliev",fullName:"Ruslan Aliev",slug:"ruslan-aliev",email:"Aliev.ru@yandex.ru",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"317686",title:"Dr.",name:"Sergey",middleName:null,surname:"Pozyabin",fullName:"Sergey Pozyabin",slug:"sergey-pozyabin",email:"jippo77@mail.ru",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"317687",title:"Dr.",name:"Nevena",middleName:null,surname:"Drakul",fullName:"Nevena Drakul",slug:"nevena-drakul",email:"nevenadrakul2@gmail.com",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. Normal physiology of equine gastrointestinal motility",level:"1"},{id:"sec_3",title:"3. Prevalence and risk factors for equine postoperative ileus",level:"1"},{id:"sec_4",title:"4. Pathophysiology of equine postoperative ileus",level:"1"},{id:"sec_4_2",title:"4.1 The role of inflammation and endotoxemia",level:"2"},{id:"sec_5_2",title:"4.2 The role of the neurogen-endocrinic factors",level:"2"},{id:"sec_6_2",title:"4.3 The role of drugs and anesthetic agents",level:"2"},{id:"sec_8",title:"5. Diagnosis of equine postoperative ileus",level:"1"},{id:"sec_9",title:"6. Prevention and treatment of equine postoperative ileus",level:"1"},{id:"sec_9_2",title:"6.1 Preoperative strategies in the prevention of equine POI",level:"2"},{id:"sec_10_2",title:"6.2 Intraoperative strategies in the prevention of equine POI",level:"2"},{id:"sec_11_2",title:"6.3 Postoperative strategies in the prevention and therapy of equine POI",level:"2"},{id:"sec_12_2",title:"6.4 Postoperative peritoneal lavage",level:"2"},{id:"sec_13_2",title:"6.5 Prokinetic drugs for the treatment of equine postoperative ileus",level:"2"},{id:"sec_13_3",title:"6.5.1 Parasympathomimetic agents (cholinomimetics)",level:"3"},{id:"sec_14_3",title:"6.5.2 Sodium channel blockers",level:"3"},{id:"sec_15_3",title:"6.5.3 Drugs acting as 5-hydroxytryptamine receptors",level:"3"},{id:"sec_16_3",title:"6.5.4 Motilin agonists",level:"3"},{id:"sec_17_3",title:"6.5.5 Adrenergic antagonists",level:"3"},{id:"sec_18_3",title:"6.5.6 Dopamine antagonist",level:"3"},{id:"sec_19_3",title:"6.5.7 Combination of prokinetic drugs",level:"3"},{id:"sec_21_2",title:"6.6 Nasogastric decompression",level:"2"},{id:"sec_22_2",title:"6.7 Judicious timing of feeding",level:"2"},{id:"sec_23_2",title:"6.8 Stress reduction strategies",level:"2"},{id:"sec_24_2",title:"6.9 Repeat celiotomy and postoperative ileus",level:"2"},{id:"sec_26",title:"Acknowledgments",level:"1"},{id:"sec_29",title:"Conflicts of interest",level:"1"},{id:"sec_26",title:"Dedication",level:"1"}],chapterReferences:[{id:"B1",body:'Mair TS, Smith LJ, Sherlock CE. 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Effects of psychological stress on small intestinal motility and expression of cholecystokinin and vasoactive intestinal polypeptide in plasma and small intestine in mice. 2005;11(5):737-World J Gastroentero, 740. DOI: 10.3748/wjg.v11.i5.737'},{id:"B82",body:'Tache Y, Martinez V, Million M, Wang L. Stress and the gastrointestinal tract III. Stress-related alterations of gut motor function: Role of brain corticotropin-releasing factor receptors. American Journal of Physiology. Gastrointestinal and Liver Physiology. 2001;280(2):G173-G177. DOI: 10.1152/ajpgi.2001.280.2.G173'},{id:"B83",body:'Adams SB. Recognition and management of ileus. The Veterinary Clinics of North America. Equine Practice. 1988;4(1):91-104. DOI: 10.1016/s0749-0739(17)30652-1'},{id:"B84",body:'Bonaz B, Tache Y. Corticotropin-releasing factor and systemic capsaicin-sensitive afferents are involved in abdominal surgery-induced Fos expression in the paraventricular nucleus of the hypothalamus. 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DOI: 10.1111/j.1471-4159.2004.02490.x'},{id:"B89",body:'Chen CY, Million M, Adelson DW, Martinez V, Rivier J, Tache Y. Intracisternal urocortin inhibits vagally stimulated gastric motility in rats: Role of CRF(2). British Journal of Pharmacology. 2002;136(2):237-247. DOI: 10.1038/sj.bjp.0704713'},{id:"B90",body:'Le Blanc-Louvry I, Coquerel A, Koning E, Maillot C, Ducrotte P. Operative stress response is reduced after laparoscopic compared to open cholecystectomy—The relationship with postoperative pain and ileus. Digestive Diseases and Sciences. 2000;45(9):1703-1713. DOI: 10.1023/A:1005598615307'},{id:"B91",body:'Dubois M, Pickar D, Cohen MR, Roth YF, Macnamara T, Bunney WE Jr. Surgical stress in humans is accompanied by an increase in plasma beta-endorphin immunoreactivity. Life Sciences. 1981;29(12):1249-1254. DOI: 10.1016/0024-3205(81)90230-7'},{id:"B92",body:'De Winter BY, Boeckxstaens GE, De Man JG, Moreels TG, Herman AG, Pelckmans PA. 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American Journal of Veterinary Research. 1996;57(6):884-890'},{id:"B96",body:'Boeckxstaens GE, Hirsch DP, Kodde A, Moojen TM, Blackshaw A, Tytgat GN, et al. Activation of an adrenergic and vagally-mediated NANC pathway in surgery-induced fundic relaxation in the rat. Neurogastroenterology and Motility. 1999;11(6):467-474. DOI: 10.1046/j.1365-2982.1999.00172.x'},{id:"B97",body:'Zittel TT, Lloyd KC, Rothenhofer I, Wong H, Walsh JH, Raybould HE. Calcitonin gene-related peptide and spinal afferents partly mediate postoperative colonic ileus in the rat. Surgery. 1998;123(5):518-527. DOI: 10.1067/msy.1998.88090'},{id:"B98",body:'Jameson P, Desborough JP, Bryant AE, Hall GM. The effect of cortisol suppression on interleukin-6 and white blood cell responses to surgery. Acta Anaesthesiologica Scandinavica. 1997;41(2):304-308. DOI: 10.1111/j.1399-6576.1997.tb04683.x'},{id:"B99",body:'la Fleur SE, Wick EC, Idumalla PS, Grady EF, Bhargava A. Role of peripheral corticotropin-releasing factor and urocortin II in intestinal inflammation and motility in terminal ileum. Proceedings of the National Academy of Sciences of the United States of America. 2005;102(21):7647-7652. DOI: 10.1073/pnas.0408531102'},{id:"B100",body:'Merritt AM, Burrow JA, Hartless CS. Effect of xylazine, detomidine, and a combination of xylazine and butorphanol on equine duodenal motility. American Journal of Veterinary Research. 1998;59(5):619-623'},{id:"B101",body:'Lester GD, Merritt AM, Neuwirth L, Vetro-Widenhouse T, Steible C, Rice B. Effect of alpha(2)-adrenergic, cholinergic, and nonsteroidal anti-inflammatory drugs on myoelectric activity of ileum, cecum, and right ventral colon and on cecal emptying of radiolabeled markers in clinically normal ponies. American Journal of Veterinary Research. 1998;59(3):320-327'},{id:"B102",body:'Adams SB, Lamar CH, Masty J. Motility of the distal portion of the jejunum and pelvic flexure in ponies: Effects of six drugs. American Journal of Veterinary Research. 1984;45(4):795-799'},{id:"B103",body:'Lester G. Gastrointestinal ileus. In: Smith B, editor. Large Animal Internal Medicine. St. Louis, USA: Mosby; 2002. p. 674-679'},{id:"B104",body:'Lester GD, Bolton JR, Cullen LK, Thurgate SM. Effects of general-anesthesia on myoelectric activity of the intestine in horses. American Journal of Veterinary Research. 1992;53(9):1553-1557'},{id:"B105",body:'Schurizek BA, Willacy LH, Kraglund K, Andreasen F, Juhl B. Effects of general anaesthesia with halothane on antroduodenal motility, pH and gastric emptying rate in man. British Journal of Anaesthesia. 1989;62(2):129-137. DOI: 10.1093/bja/62.2.129'},{id:"B106",body:'Little D, Redding WR, Blikslager AT. Risk factors for reduced postoperative fecal output in horses: 37 cases (1997-1998). Journal of the American Veterinary Medical Association. 2001;218(3):414-420. DOI: 10.2460/javma.2001.218.414'},{id:"B107",body:'Salciccia A, Gougnard A, Grulke S, de Pouyade GD, Libertiaux V, Busoni V, et al. Gastrointestinal effects of general anaesthesia in horses undergoing non abdominal surgery: Focus on the clinical parameters and ultrasonographic images. Research in Veterinary Science. 2019;124:123-128. DOI: 10.1016/j.rvsc.2019.03.011'},{id:"B108",body:'Lefebvre D, Hudson NPH, Elce YA, Blikslager A, Divers TJ, Handel IG, et al. Clinical features and management of equine post operative ileus (POI): Survey of Diplomates of the American Colleges of Veterinary Internal Medicine (ACVIM), Veterinary Surgeons (ACVS) and Veterinary Emergency and Critical Care (ACVECC). Equine Veterinary Journal. 2016;48(6):714-719. DOI: 10.1111/evj.12520'},{id:"B109",body:'Lefebvre D, Pirie RS, Handel IG, Tremaine WH, Hudson NPH. Clinical features and management of equine post operative ileus: Survey of diplomates of the European Colleges of Equine Internal Medicine (ECEIM) and Veterinary Surgeons (ECVS). Equine Veterinary Journal. 2016;48(2):182-187. DOI: 10.1111/evj.12355'},{id:"B110",body:'Roussel AJ, Cohen ND, Hooper RN, Rakestraw PC. Risk factors associated with development of postoperative ileus in horses. Journal of the American Veterinary Medical Association. 2001;219(1):72-78. DOI: 10.2460/javma.2001.219.72'},{id:"B111",body:'Merritt AM, Blikslager AT. Post operative ileus: To be or not to be? Equine Veterinary Journal. 2008;40(4):295-296. DOI: 10.2746/042516408X302537'},{id:"B112",body:'Mitchell CF, Malone ED, Sage AM, Niksich K. Evaluation of gastrointestinal activity patterns in healthy horses using B mode and Doppler ultrasonography. The Canadian Veterinary Journal. 2005;46(2):134-140'},{id:"B113",body:'Kovac M, Aliev R, Tkacenko A. Improved methodology of abdominal ultrasonography in horses with gastrointestinal disease. Veterinár̆ství. 2018;5:31-37. Availabel from: http://vetpharma.org/articles/140/7827/'},{id:"B114",body:'Freeman SL, England GC. Effect of romifidine on gastrointestinal motility, assessed by transrectal ultrasonography. Equine Veterinary Journal. 2001;33(6):570-6.10.2746/042516401776563436'},{id:"B115",body:'Durongphongtorn S, McDonell WN, Kerr CL, Neto FJT, Mirakhur KK. Comparison of hemodynamic, clinicopathologic, and gastrointestinal motility effects and recovery characteristics of anesthesia with isoflurane and halothane in horses undergoing arthroscopic surgery. American Journal of Veterinary Research. 2006;67(1):32-42. DOI: 10.2460/ajvr.67.1.32'},{id:"B116",body:'Phillips TJ, Walmsley JP. Retrospective analysis of the results of 151 exploratory laparotomies in horses with gastrointestinal-disease. Equine Veterinary Journal. 1993;25(5):427-431. DOI: 10.1111/j.2042-3306.1993.tb02985.x'},{id:"B117",body:'Bracamonte JL, Devick I, Thomas KL, Hendrick S. Comparison of hand-sewn and oversewn stapled jejunojejunal anastomoses in horses. The Canadian Veterinary Journal. 2018;59(1):67-73'},{id:"B118",body:'Klohnen A. New perspectives in postoperative complications after abdominal surgery. Veterinary Clinics of North America: Equine Practice. 2009;25(2):341. DOI: 10.1016/j.cveq.2009.05.003'},{id:"B119",body:'Alonso Jde M, Alves AL, Watanabe MJ, Rodrigues CA, Hussni CA. Peritoneal response to abdominal surgery: The role of equine abdominal adhesions and current prophylactic strategies. Vet Med Int. 2014;2014:279730. DOI: 10.1155/2014/279730'},{id:"B120",body:'Lim R, Morrill JM, Lynch RC, Reed KL, Gower AC, Leeman SE, et al. Practical limitations of bioresorbable membranes in the prevention of intra-abdominal adhesions. Journal of Gastrointestinal Surgery. 2009;13(1):35-42. DOI: 10.1007/s11605-008-0724-3'},{id:"B121",body:'Kuebelbeck KL, Slone DE, May KA. Effect of omentectomy on adhesion formation in horses. Veterinary Surgery. 1998;27(2):132-137. DOI: 10.1111/j.1532-950X.1998.tb00109.x'},{id:"B122",body:'Smith MA, Edwards GB, Dallap BL, Cripps PJ, Proudman CJ. Evaluation of the clinical efficacy of prokinetic drugs in the management of post-operative ileus: Can retrospective data help us? Veterinary Journal. 2005;170(2):230-236. DOI: 10.1016/j.tvjl.2004.06.006'},{id:"B123",body:'van der Spoel JI, Oudemans-van Straaten HM, Stoutenbeek CP, Bosman RJ, Zandstra DF. Neostigmine resolves critical illness-related colonic ileus in intensive care patients with multiple organ failure—a prospective, double-blind, placebo-controlled trial. Intensive Care Medicine. 2001;27(5):822-827. DOI: 10.1007/s001340100926'},{id:"B124",body:'Van Hoogmoed LM, Nieto JE, Snyder JR, Harmon FA. Survey of prokinetic use in horses with gastrointestinal injury. Veterinary Surgery. 2004;33(3):279-285. DOI: 10.1111/j.1532-950X.2004.04041.x'},{id:"B125",body:'Milligan M, Beard W, Kukanich B, Sobering T, Waxman S. The effect of lidocaine on postoperative jejunal motility in normal horses. Veterinary Surgery. 2007;36(3):214-220. DOI: 10.1111/j.1532-950X.2007.00255.x'},{id:"B126",body:'Brianceau P, Chevalier H, Karas A, Court MH, Bassage L, Kirker-Head C, et al. Intravenous lidocaine and small-intestinal size, abdominal fluid, and outcome after colic surgery in horses. Journal of Veterinary Internal Medicine. 2002;16(6):736-741. DOI: 10.1892/0891-6640(2002)016<0736:ilassa>2.3.co;2'},{id:"B127",body:'Freeman DE. Is there still a place for lidocaine in the (postoperative) management of colics? Veterinary Clinics of North America: Equine Practice. 2019;35(2):275. DOI: 10.1016/j.cveq.2019.03.003'},{id:"B128",body:'Nieto JE, Rakestraw PC, Snyder JR, Vatistas NJ. In vitro effects of erythromycin, lidocaine, and metoclopramide on smooth muscle from the pyloric antrum, proximal portion of the duodenum, and middle portion of the jejunum of horses. American Journal of Veterinary Research. 2000;61(4):413-419. DOI: 10.2460/ajvr.2000.61.413'},{id:"B129",body:'Salem SE, Proudman CJ, Archer DC. Has intravenous lidocaine improved the outcome in horses following surgical management of small intestinal lesions in a UK hospital population? BMC Veterinary Research. 2016;12:1-11. DOI: 10.1186/s12917-016-0784-7'},{id:"B130",body:'Dart AJ, Hodgson DR. Role of prokinetic drugs for treatment of postoperative ileus in the horse. Australian Veterinary Journal. 1998;76(1):25-31'},{id:"B131",body:'Gerring EL, King JN. Cisapride in the prophylaxis of equine post operative ileus. Equine Veterinary Journal. Supplement. 1989;21(S7):52-55. DOI: 10.1111/j.2042-3306.1989.tb05656.x'},{id:"B132",body:'Sojka JE, Adams SB, Lamar CH, Eller LL. Effect of butorphanol, pentazocine, meperidine, or metoclopramide on intestinal motility in female ponies. American Journal of Veterinary Research. 1988;49(4):527-529'},{id:"B133",body:'Doherty TJ, Andrews FM, Abraha TW, Osborne D, Frazier DL. Metoclopramide ameliorates the effects of endotoxin on gastric emptying of acetaminophen in horses. Canadian Journal of Veterinary Research. 1999;63(1):37-40'},{id:"B134",body:'Nieto JE, Maher O, Stanley SD, Larson R, Snyder JR. In vivo and in vitro evaluation of the effects of domperidone on the gastrointestinal tract of healthy horses. American Journal of Veterinary Research. 2013;74(8):1103-1110'},{id:"B135",body:'Holte K, Kehlet H. Postoperative ileus: a preventable event. British Journal of Surgery. 2000;87(11):1480-1493. DOI: 10.1046/j.1365-2168.2000.01595.x'},{id:"B136",body:'McKenzie HC. Equine hyperlipidemias. Veterinary Clinics of North America: Equine Practice. 2011;27(1):59. DOI: 10.1016/j.cveq.2010.12.008'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Milomir Kovac",address:"kovacmilomir@gmail.com",affiliation:'
Veterinary Clinic “New Century”, Moscow State Academy of Veterinary Medicine and Biotechnology, Russia
Institute of Fundamental Medicine and Biology, Kazan Federal University, Russia
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She organised the international scientific conference “Mediterranean Malvasias” in Poreč, Croatia, in 2005, and the International Scientific Congress GESCO (Groupe d’Etude des Systemes de Conduite de la Vigne) in Poreč (Croatia) in 2007. She acted as a collaborator or leader on many national and international scientific projects covering the grape and olive field. 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In the present paper, the available records on the influence of non-native invasive species and the relationship between services lost and new services acquired due to their presence will be discussed.",signatures:"Barbara Sladonja, Danijela Poljuha and Mirela Uzelac",authors:[{id:"88464",title:"Dr.",name:"Barbara",surname:"Sladonja",fullName:"Barbara Sladonja",slug:"barbara-sladonja",email:"barbara@iptpo.hr"},{id:"227713",title:"Dr.",name:"Danijela",surname:"Poljuha",fullName:"Danijela Poljuha",slug:"danijela-poljuha",email:"danijela@iptpo.hr"},{id:"243906",title:"MSc.",name:"Mirela",surname:"Uzelac",fullName:"Mirela Uzelac",slug:"mirela-uzelac",email:"mirela.uzelac0708@gmail.com"}],book:{id:"6570",title:"Ecosystem Services and Global Ecology",slug:"ecosystem-services-and-global-ecology",productType:{id:"1",title:"Edited Volume"}}}],collaborators:[{id:"60732",title:"Dr.",name:"Alfredo",surname:"Ortega-Rubio",slug:"alfredo-ortega-rubio",fullName:"Alfredo Ortega-Rubio",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"73153",title:"Dr.",name:"Maricar",surname:"Samson",slug:"maricar-samson",fullName:"Maricar Samson",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"De La Salle University",institutionURL:null,country:{name:"Philippines"}}},{id:"73155",title:"Prof.",name:"Rene",surname:"Rollon",slug:"rene-rollon",fullName:"Rene Rollon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Philippines Diliman",institutionURL:null,country:{name:"Philippines"}}},{id:"85097",title:"Dr.",name:"Magdalena",surname:"Lagunas",slug:"magdalena-lagunas",fullName:"Magdalena Lagunas",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"85123",title:"Dr.",name:"César Alejandro",surname:"Berlanga-Robles",slug:"cesar-alejandro-berlanga-robles",fullName:"César Alejandro Berlanga-Robles",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"85187",title:"Dr.",name:"Arturo",surname:"Ruiz-Luna",slug:"arturo-ruiz-luna",fullName:"Arturo Ruiz-Luna",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"85189",title:"MSc.",name:"Rafael",surname:"Hernández-Guzmán",slug:"rafael-hernandez-guzman",fullName:"Rafael Hernández-Guzmán",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Autonomous University of Mexico",institutionURL:null,country:{name:"Mexico"}}},{id:"89213",title:"Dr",name:"Francesco",surname:"Tamberlich",slug:"francesco-tamberlich",fullName:"Francesco Tamberlich",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"89214",title:"BSc",name:"Nicola",surname:"Bettoso",slug:"nicola-bettoso",fullName:"Nicola Bettoso",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"93843",title:"BSc.",name:"Aurelio",surname:"Zentilin",slug:"aurelio-zentilin",fullName:"Aurelio Zentilin",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null}]},generic:{page:{slug:"WIS-cost",title:"What Does It Cost?",intro:"
Open Access publishing helps remove barriers and allows everyone to access valuable information, but article and book processing charges also exclude talented authors and editors who can’t afford to pay. The goal of our Women in Science program is to charge zero APCs, so none of our authors or editors have to pay for publication.
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All of our IntechOpen sponsors are in good company! The research in past IntechOpen books and chapters have been funded by:
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. 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From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. 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The application of this test has significantly changed the practice of medical laboratories in which it is used for detection and quantification of molecules such as hormones, peptides, antibodies, and proteins. Various technical variants of this test can detect antigen (native or foreign) or antibody, determine the intensity of the immune response whether pathological or not; the type of induced immune response as well as the innate immunity potential; and much more. These capabilities, as well as the high sensitivity and robustness of the test and a small price, make it possible to quickly and reliably diagnose diseases in most laboratories. Besides, ELISA is a test that is also used in veterinary medicine, toxicology, allergology, food industry, etc. Despite the fact that it has existed for almost 50 years, different ELISA tests with different technical solutions are still being developed, which improves and expands the application of the this exceptional test. The aim of this chapter is to empower the rider to optimize, standardize and validate an enzyme linked immunosorbent assay.",book:{id:"9850",slug:"norovirus",title:"Norovirus",fullTitle:"Norovirus"},signatures:"Rajna Minic and Irena Zivkovic",authors:[{id:"325806",title:"Ph.D.",name:"Irena",middleName:null,surname:"Zivkovic",slug:"irena-zivkovic",fullName:"Irena Zivkovic"},{id:"325839",title:"Dr.",name:"Rajna",middleName:null,surname:"Minic",slug:"rajna-minic",fullName:"Rajna Minic"}]},{id:"56750",title:"Laboratory Approach to Anemia",slug:"laboratory-approach-to-anemia",totalDownloads:6181,totalCrossrefCites:2,totalDimensionsCites:4,abstract:"Anemia is a major cause of morbidity and mortality worldwide and can be defined as a decreased quantity of circulating red blood cells (RBCs). The epidemiological studies suggested that one-third of the world’s population is affected with anemia. Anemia is not a disease, but it is instead the sign of an underlying basic pathological process. However, the sign may function as a compass in the search for the cause. Therefore, the prediagnosis revealed by thorough investigation of this sign should be supported by laboratory parameters according to the underlying pathological process. We expect that this review will provide guidance to clinicians with findings and laboratory tests that can be followed from the initial stage in the anemia search.",book:{id:"5942",slug:"current-topics-in-anemia",title:"Current Topics in Anemia",fullTitle:"Current Topics in Anemia"},signatures:"Ebru Dündar Yenilmez and Abdullah Tuli",authors:[{id:"183998",title:"Ph.D.",name:"Ebru",middleName:null,surname:"Dündar Yenilmez",slug:"ebru-dundar-yenilmez",fullName:"Ebru Dündar Yenilmez"},{id:"209103",title:"Prof.",name:"Abdullah",middleName:null,surname:"Tuli",slug:"abdullah-tuli",fullName:"Abdullah Tuli"}]},{id:"33133",title:"Waist Circumference in Children and Adolescents from Different Ethnicities",slug:"waist-circumference-in-children-and-adolescents-from-different-ethnicities",totalDownloads:8e3,totalCrossrefCites:4,totalDimensionsCites:7,abstract:null,book:{id:"642",slug:"childhood-obesity",title:"Childhood Obesity",fullTitle:"Childhood Obesity"},signatures:"Peter Schwandt and Gerda-Maria Haas",authors:[{id:"29867",title:"Prof.",name:"Peter",middleName:null,surname:"Schwandt",slug:"peter-schwandt",fullName:"Peter Schwandt"}]}],onlineFirstChaptersFilter:{topicId:"185",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81939",title:"Translational Research on Chagas Disease: Focusing on Drug Combination and Repositioning",slug:"translational-research-on-chagas-disease-focusing-on-drug-combination-and-repositioning",totalDownloads:19,totalDimensionsCites:0,doi:"10.5772/intechopen.104231",abstract:"Chagas disease, caused by the protozoan Trypanosoma cruzi, is a major neglected disease endemic to Latin America, associated to significant morbimortality comprising a remarkable socioeconomic problem mainly for low-income tropical populations. The present chapter focuses translational research on Chagas disease, approaching drug combinations and repositioning, particularly exploiting the parasite oxidative stress by prospecting prooxidant compounds combined with antagonists of antioxidant systems, for developing low-cost and safe therapies for this infection. The pertinent literature on protozoal parasitic diseases is reviewed as well as on repurposing disulfiram aiming the combination with the Chagas disease drug of choice benznidazole. Both disulfiram and its first derivative sodium diethyldithiocarbamate (DETC) are able not only to inhibit p-glycoprotein, possibly reverting resistance phenotypes, but also to reduce toxicity of numerous other drugs, heavy metals, etc. Therefore, this innovation, presently in clinical research, may furnish a novel therapeutic for T. cruzi infections overcoming the adverse effects and refractory cases that impair the effectiveness of Chagas disease treatment.",book:{id:"11377",title:"Chagas Disease - From Cellular and Molecular Aspects of Trypanosoma cruzi-Host Interactions to the Clinical Intervention",coverURL:"https://cdn.intechopen.com/books/images_new/11377.jpg"},signatures:"Marcos André Vannier-Santos, Ana Márcia Suarez-Fontes, Juliana Almeida-Silva, Alessandra Lifsitch Viçosa, Sandra Aurora Chavez Perez, Alejandro Marcel Hasslocher-Moreno, Gabriel Parreiras Estolano da Silveira, Luciana Fernandes Portela and Roberto Magalhães Saraiva"},{id:"81702",title:"The Saga of Selenium Treatment Investigation in Chagas Disease Cardiopathy: Translational Research in a Neglected Tropical Disease in Brazil",slug:"the-saga-of-selenium-treatment-investigation-in-chagas-disease-cardiopathy-translational-research-in",totalDownloads:8,totalDimensionsCites:0,doi:"10.5772/intechopen.103772",abstract:"This chapter describes the steps from basic research to the definition of a putative public health recommendation in the clinical protocols and therapeutic guidelines for selenium (Se) supplementation for patients with Chagas disease. From 1998 to 2018, we conducted a translational research project to test the concept that chronic Chagas disease cardiopathy (CCC) severity could be associated with low levels of blood selenium (Se), and if oral Se supplementation could help to sustain the asymptomatic cardiac stage and reduce disease severity. Pre-clinical studies in mice and a clinical trial conducted in the early asymptomatic cardiac stage of CCC patients (B stage) were performed, identified as “Selenium Treatment of Chagasic Cardiopathy (STCC)” trial. The roadmap of the selenium project was/is a real saga, with important obstacles that tested team resilience and revealed Brazilian conditions of science development. We discuss the main possible mechanisms involved in the physiopathology of CCC and the lessons learned in this process. In this chapter, we also organized the timeline of the translational project and described the crucial moments of the journey, as well as the next steps driving the research teams and their international and health industry connections.",book:{id:"11377",title:"Chagas Disease - From Cellular and Molecular Aspects of Trypanosoma cruzi-Host Interactions to the Clinical Intervention",coverURL:"https://cdn.intechopen.com/books/images_new/11377.jpg"},signatures:"Tania C. de Araujo-Jorge, Anna Cristina C. Carvalho, Roberto R. Ferreira, Luciana R. Garzoni, Beatriz M.S. Gonzaga, Marcelo T. Holanda, Gilberto M. Sperandio da Silva, Maria da Gloria Bonecini-Almeida, Mauro F.F. Mediano, Roberto M. Saraiva and Alejandro M. Hasslocher-Moreno"},{id:"81938",title:"How Do Mouse Strains and Inoculation Routes Influence the Course of Experimental Trypanosoma cruzi Infection?",slug:"how-do-mouse-strains-and-inoculation-routes-influence-the-course-of-experimental-trypanosoma-cruzi-i",totalDownloads:13,totalDimensionsCites:0,doi:"10.5772/intechopen.104461",abstract:"Chagas’ disease outcomes depend on several factors including parasite and host genetics, immune response, and route of infection. In this study, we investigate the influence of inoculation route and host genetic background on the establishment and development of Chagas disease in mice, using an isolate of Trypanosoma cruzi SC2005 strain (TcII), which was obtained from an oral Chagas’ disease outbreak in Santa Catarina, Brazil. Comparative analysis of the immunopathological, histopathological, and hematological profiles of mice was performed demonstrating the influence of the route of infection in disease severity. In outbred mice, intraperitoneal (IP) infection led to higher infection and mortality rates and more severe parasitaemia, when compared with intragastric (IG) infection. Nevertheless, tissue colonization was similar, showing severe damage in the heart, with intense lymphocytic inflammatory infiltrates, regardless of the route of infection. On the other hand, in mice IG-infected, the host genetic background influences the start timing of immune response against Trypanosoma cruzi. The susceptible BALB/c inbred mouse strain presented an earlier development of a cytotoxic cellular profile, when compared with A mice. We hypothesize that the cytotoxic response mounted before the parasitaemia increase allowed for a milder manifestation of Chagas’ disease in intragastrically infected mice.",book:{id:"11377",title:"Chagas Disease - From Cellular and Molecular Aspects of Trypanosoma cruzi-Host Interactions to the Clinical Intervention",coverURL:"https://cdn.intechopen.com/books/images_new/11377.jpg"},signatures:"Flávia de Oliveira Cardoso, Carolina Salles Domingues, Tânia Zaverucha do Valle and Kátia da Silva Calabrese"},{id:"81814",title:"Evaluation of Molecular Variability of Isolates of Trypanosoma cruzi in the State of Rio de Janeiro-Brazil",slug:"evaluation-of-molecular-variability-of-isolates-of-trypanosoma-cruzi-in-the-state-of-rio-de-janeiro-",totalDownloads:11,totalDimensionsCites:0,doi:"10.5772/intechopen.104498",abstract:"Trypanosoma cruzi, the etiological agent of Chagas disease, presents considerable heterogeneity among populations of isolates within the sylvatic and domestic cycle. This study aims to evaluate the genetic diversity of 14 isolates collected from specimens of Triatoma vitticeps from Triunfo, Conceição de Macabu, and Santa Maria Madalena cities (Rio de Janeiro—Brazil). By using PCR based on the mini-exon gene, all isolates showed a profile characteristic of bands zymodeme III and with a lower intensity characteristic of TcII. To verify possible hybrids among the strains analyzed, the polymorphisms analysis of the MSH2 gene was performed. HhaI restriction enzyme digestion products resulted in characteristic TcII fragments only, demonstrating the absence of hybrids strains. In our attempt to characterize isolation in accordance with the reclassification of T. cruzi into six new groups called DTUs (“discrete typing unit”), we genotyped the mitochondrial cytochrome oxidase subunit two gene, ribosomal RNA gen (24Sα rDNA), and the spliced leader intergenic region (SL-IR). This procedure showed that TcII, TcIII, and TcIV are circulating in this area. This highlights the diversity of parasites infecting specimens of T. vitticeps, emphasizing the habit of wild type and complexity of the region epidemiological study that presents potential mixed populations.",book:{id:"11377",title:"Chagas Disease - From Cellular and Molecular Aspects of Trypanosoma cruzi-Host Interactions to the Clinical Intervention",coverURL:"https://cdn.intechopen.com/books/images_new/11377.jpg"},signatures:"Helena Keiko Toma, Luciana Reboredo de Oliveira da Silva, Teresa Cristina Monte Gonçalves, Renato da Silva Junior and Jacenir R. Santos-Mallet"},{id:"81252",title:"Modulation of Host Cell Apoptosis by Trypanosoma cruzi: Repercussions in the Development of Chronic Chagasic Cardiomyopathy",slug:"modulation-of-host-cell-apoptosis-by-trypanosoma-cruzi-repercussions-in-the-development-of-chronic-c",totalDownloads:33,totalDimensionsCites:0,doi:"10.5772/intechopen.103740",abstract:"Trypanosoma cruzi is an intracellular parasite, which causes Chagas disease, affecting millions of people throughout the world. T. cruzi can invade several cell types, among which macrophages and cardiomyocytes stand out. Chagas disease goes through two stages: acute and chronic. If it becomes chronic, its most severe form is the chagasic chronic cardiomyopathy, which accounts for most of the fatalities due to this disease. For parasites to persist for long enough in cells, they should evade several host immune responses, one of these being apoptosis. Apoptosis is a type of programmed cell death described as a well-ordered and silent collection of steps that inevitably lead cells to a noninflammatory death. Cells respond to infection by initiating their own death to combat the infection. As a result, several intracellular microorganisms have developed different strategies to overcome host cell apoptosis and persist inside cells. It has been shown that T. cruzi has the ability to inhibit host cells apoptosis and can also induce apoptosis of cells that combat the parasite such as cytotoxic T cells. The aim of this chapter is to present up-to-date information about the molecules and mechanisms engaged by T. cruzi to achieve this goal and how the modulation of apoptosis by T. cruzi reflects in the development of chronic chagasic cardiomyopathy.",book:{id:"11377",title:"Chagas Disease - From Cellular and Molecular Aspects of Trypanosoma cruzi-Host Interactions to the Clinical Intervention",coverURL:"https://cdn.intechopen.com/books/images_new/11377.jpg"},signatures:"Fiordaliso Carolina Román-Carraro, Diego Maurizio Coria-Paredes, Arturo A. Wilkins-Rodríguez and Laila Gutiérrez-Kobeh"},{id:"80917",title:"Digestive Disorders in Chagas Disease: Megaesophagus and Chagasic Megacolon",slug:"digestive-disorders-in-chagas-disease-megaesophagus-and-chagasic-megacolon",totalDownloads:25,totalDimensionsCites:0,doi:"10.5772/intechopen.102871",abstract:"Chagas disease, also known as American trypanosomiasis, caused by Trypanosoma cruzi and transmitted by hematophagous vectors, is a parasitic disease, which according to the WHO ranks fourth as a cause of loss of potential years of life due to complications that can occur in multiple body systems. According to the reports presented by the World Health Organization, there are between 16 and 18 million infected people in the world, predominantly in endemic areas of Latin America, of which only 1% receives an adequate diagnosis and full treatment, thereby that the chronic phase comes to present digestive disorders that are one of the main causes of loss in the quality of life of patients, as well as complications that can lead to life-threatening surgical emergencies.",book:{id:"11377",title:"Chagas Disease - From Cellular and Molecular Aspects of Trypanosoma cruzi-Host Interactions to the Clinical Intervention",coverURL:"https://cdn.intechopen.com/books/images_new/11377.jpg"},signatures:"Víctor Hugo García Orozco, Juan Enrique Villalvazo Navarro, Carlos Solar Aguirre, Carlos Manuel Ibarra Ocampo, César Iván Díaz Sandoval, Carlos Alejandro Ortíz Gallegos, Diego Javier Oregel Camacho and Araceli Noriega Bucio"}],onlineFirstChaptersTotal:6},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:106,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"June 29th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:32,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. Dr. Ekinci serves as the Editor in Chief of four international books and is involved in the Editorial Board of several international journals.",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null},{id:"17",title:"Metabolism",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",isOpenForSubmission:!0,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. 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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. 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She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. 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Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. 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