Basic statistics and the estimated heritability of wellness traits [Dianelys Gonzalez, personal communication, 2021].
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\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:"6230",leadTitle:null,fullTitle:"Topics in Splines and Applications",title:"Topics in Splines and Applications",subtitle:null,reviewType:"peer-reviewed",abstract:"Splines provide a significant tool for the design of computationally economical curves and surfaces for the construction of various objects like automobiles, ship hulls, airplane fuselages and wings, propeller blades, shoe insoles, bottles, etc. It also contributes in the description of geological, physical, statistical, and even medical phenomena. Spline methods have proven to be indispensable in a variety of modern industries, including computer vision, robotics, signal and image processing, visualization, textile, graphic designs, and even media. This book aims to provide a valuable source on splines and their applications. It focuses on collecting and disseminating information in various disciplines including computer-aided geometric design, computer graphics, data visualization, data fitting, power systems, clinical and epidemiologic studies, disease detection, regression curves, social media, and biological studies. The book is useful for researchers, scientists, practitioners, and many others who seek state-of-the-art techniques and applications using splines. It is also useful for undergraduate senior students as well as graduate students in the areas of computer science, engineering, health science, statistics, and mathematics. Each chapter also provides useful information on software developments and their extensions.",isbn:"978-1-78923-251-6",printIsbn:"978-1-78923-250-9",pdfIsbn:"978-1-83881-350-5",doi:"10.5772/intechopen.68737",price:119,priceEur:129,priceUsd:155,slug:"topics-in-splines-and-applications",numberOfPages:160,isOpenForSubmission:!1,isInWos:1,isInBkci:!1,hash:"93059c7907be129c419e4f9960b4e9c3",bookSignature:"Young Kinh-Nhue Truong and Muhammad Sarfraz",publishedDate:"June 6th 2018",coverURL:"https://cdn.intechopen.com/books/images_new/6230.jpg",numberOfDownloads:7233,numberOfWosCitations:4,numberOfCrossrefCitations:4,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:8,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:16,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 13th 2017",dateEndSecondStepPublish:"May 4th 2017",dateEndThirdStepPublish:"December 3rd 2017",dateEndFourthStepPublish:"January 3rd 2018",dateEndFifthStepPublish:"March 3rd 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"207517",title:"Dr.",name:"Young Kinh-Nhue",middleName:null,surname:"Truong",slug:"young-kinh-nhue-truong",fullName:"Young Kinh-Nhue Truong",profilePictureURL:"https://mts.intechopen.com/storage/users/207517/images/system/207517.jpg",biography:"Young Kinh-Nhue Truong, Ph.D., is a professor of Biostatistics at the University of North Carolina at Chapel Hill. His research expertise includes statistical learning, functional modeling, time series, Spatio-temporal data analysis, and event history analysis. He has contributed significantly in the areas of statistical time series/longitudinal modeling using splines, window or kernel-based smoothing methods, and wavelets. His current research focuses mainly on Spatio-temporal data analysis with the aim to spatially localize dynamic processes in the functional magnetic resonance imaging (fMRI) or electroencephalography (EEG) human brain data. He is also interested in developing statistical inference for group comparison based on human brain imaging data and methods for analyzing neuro-spike train data. His teaching and research experience in linear mixed modeling has provided new insights and approaches to many statistical analyses for handling between- and within-subject variability.",institutionString:"University of North Carolina at Chapel Hill",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"University of North Carolina at Chapel Hill",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University, Kuwait. His research interests include optimization, computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, and intelligent systems. Prof. Sarfraz has been a keynote/invited speaker at various platforms around the globe. He has advised/supervised more than 110 students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He has authored and/or edited around seventy books. Prof. Sarfraz is a member of various professional societies. He is a chair and member of international advisory committees and organizing committees of numerous international conferences. He is also an editor and editor in chief for various international journals.",institutionString:"Kuwait University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"4",institution:{name:"Kuwait University",institutionURL:null,country:{name:"Kuwait"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1407",title:"Applied Mathematics",slug:"numerical-analysis-and-scientific-computing-applied-mathematics"}],chapters:[{id:"60363",title:"Scalar and Parametric Spline Curves and Surfaces",doi:"10.5772/intechopen.74929",slug:"scalar-and-parametric-spline-curves-and-surfaces",totalDownloads:1040,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"A common engineering task consists of interpolating a set of discrete points that arise from measurements and experiments. Another traditional requirement implies creating a curve that mimics a given array of points, namely, a polyline. Any of these problems require building an analytical representation of the given discrete set of points. If the geometrical shape represented by the input polyline is complicated, then we may expect that a global interpolant or polynomial will be of a high degree, to honor all imposed constraints, which makes its use prohibited. Indeed, a global interpolant often experiences inflection points and sudden changes in curvature. To avoid these drawbacks, we often seek solving the interpolation/approximation problem using piecewise polynomial functions called “splines.”",signatures:"Horacio Florez and Belsay Borges",downloadPdfUrl:"/chapter/pdf-download/60363",previewPdfUrl:"/chapter/pdf-preview/60363",authors:[{id:"209163",title:"Ph.D.",name:"Horacio",surname:"Florez",slug:"horacio-florez",fullName:"Horacio Florez"},{id:"244249",title:"Dr.",name:"Belsay",surname:"Borges",slug:"belsay-borges",fullName:"Belsay Borges"}],corrections:null},{id:"60099",title:"An Algorithm Based on the Continuous Wavelet Transform with Splines for the Automatic Measurement of QT Dispersion: Validation and Application in Chronic Kidney Disease",doi:"10.5772/intechopen.74864",slug:"an-algorithm-based-on-the-continuous-wavelet-transform-with-splines-for-the-automatic-measurement-of",totalDownloads:955,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Chronic kidney disease (CKD) is considered a risk factor for the development of cardiovascular disease. QT interval is an electrocardiographic parameter that quantifies the duration of ventricular repolarization. An increase of its spatial variability measured from the selected leads of a standard electrocardiogram (ECG), named QT dispersion (QTd), is considered a risk factor for malign ventricular arrhythmias and sudden death in the CKD. An algorithm for automatic measurement of QTd in the ECG leads DI, aVF and V2 using the continuous wavelet transform with splines is presented. Validation of QRS complex detection has been done on records from MIT-BIH database, and the accuracy is 99.5%. Validation of detection of QRS wave onset and T wave end has been done on records from CSE and QT databases, and the measurements were within the tolerance limits for deviations with respect to the manual measurements defined by the experts. The algorithm was applied in two studies. In the first study, QTd was evaluated in normal subjects and patients with CKD. In the second study, QTd was analyzed in patients with CKD before, during and after the hemodialysis treatment. In both studies, the algorithm had a good performance for the QTd analysis.",signatures:"María de Lourdes Corzo-Cuesta and Carlos Alvarado-Serrano",downloadPdfUrl:"/chapter/pdf-download/60099",previewPdfUrl:"/chapter/pdf-preview/60099",authors:[{id:"41163",title:"Dr.",name:"Carlos",surname:"Alvarado-Serrano",slug:"carlos-alvarado-serrano",fullName:"Carlos Alvarado-Serrano"},{id:"210387",title:"MSc.",name:"María De Lourdes",surname:"Corzo-Cuesta",slug:"maria-de-lourdes-corzo-cuesta",fullName:"María De Lourdes Corzo-Cuesta"}],corrections:null},{id:"60170",title:"Multivariate Adaptive Regression Splines in Standard Cell Characterization for Nanometer Technology in Semiconductor",doi:"10.5772/intechopen.74854",slug:"multivariate-adaptive-regression-splines-in-standard-cell-characterization-for-nanometer-technology-",totalDownloads:953,totalCrossrefCites:1,totalDimensionsCites:4,hasAltmetrics:0,abstract:"Multivariate adaptive regression splines (MARSP) is a nonparametric regression method. It is an adaptive procedure which does not have any predetermined regression model. With that said, the model structure of MARSP is constructed dynamically and adaptively according to the information derived from the data. Because of its ability to capture essential nonlinearities and interactions, MARSP is considered as a great fit for high-dimension problems. This chapter gives an application of MARSP in semiconductor field, more specifically, in standard cell characterization. The objective of standard cell characterization is to create a set of high-quality models of a standard cell library that accurately and efficiently capture cell behaviors. In this chapter, the MARSP method is employed to characterize the gate delay as a function of many parameters including process-voltage-temperature parameters. Due to its ability of capturing essential nonlinearities and interactions, MARSP method helps to achieve significant accuracy improvement.",signatures:"Taizhi Liu",downloadPdfUrl:"/chapter/pdf-download/60170",previewPdfUrl:"/chapter/pdf-preview/60170",authors:[{id:"209988",title:"Dr.",name:"Taizhi",surname:"Liu",slug:"taizhi-liu",fullName:"Taizhi Liu"}],corrections:null},{id:"61455",title:"Smoothing Spline ANOVA Models and their Applications in Complex and Massive Datasets",doi:"10.5772/intechopen.75861",slug:"smoothing-spline-anova-models-and-their-applications-in-complex-and-massive-datasets",totalDownloads:1117,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Complex and massive datasets can be easily accessed using the newly developed data acquisition technology. In spite of the fact that the smoothing spline ANOVA models have proven to be useful in a variety of fields, these datasets impose the challenges on the applications of the models. In this chapter, we present a selected review of the smoothing spline ANOVA models and highlight some challenges and opportunities in massive datasets. We review two approaches to significantly reduce the computational costs of fitting the model. One real case study is used to illustrate the performance of the reviewed methods.",signatures:"Jingyi Zhang, Honghe Jin, Ye Wang, Xiaoxiao Sun, Ping Ma and\nWenxuan Zhong",downloadPdfUrl:"/chapter/pdf-download/61455",previewPdfUrl:"/chapter/pdf-preview/61455",authors:[{id:"210386",title:"Prof.",name:"Ping",surname:"Ma",slug:"ping-ma",fullName:"Ping Ma"},{id:"210393",title:"Ph.D. Student",name:"Jingyi",surname:"Zhang",slug:"jingyi-zhang",fullName:"Jingyi Zhang"},{id:"210394",title:"Mr.",name:"Ye",surname:"Wang",slug:"ye-wang",fullName:"Ye Wang"},{id:"210395",title:"Mr.",name:"Honghe",surname:"Jin",slug:"honghe-jin",fullName:"Honghe Jin"},{id:"210396",title:"Mr.",name:"Xiaoxiao",surname:"Sun",slug:"xiaoxiao-sun",fullName:"Xiaoxiao Sun"},{id:"210397",title:"Dr.",name:"Wenxuan",surname:"Zhong",slug:"wenxuan-zhong",fullName:"Wenxuan Zhong"}],corrections:null},{id:"60692",title:"Model Testing Based on Regression Spline",doi:"10.5772/intechopen.74858",slug:"model-testing-based-on-regression-spline",totalDownloads:906,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Tests based on regression spline are developed in this chapter for testing nonparametric functions in nonparametric, partial linear and varying-coefficient models, respectively. These models are more flexible than linear regression model. However, one important problem is if it is really necessary to use such complex models which contain nonparametric functions. For this purpose, p-values for testing the linearity and constancy of the nonparametric functions are established based on regression spline and fiducial method. In the application of spline-based method, the determination of knots is difficult but plays an important role in inferring regression curve. In order to infer the nonparametric regression at different smoothing levels (scales) and locations, multi-scale smoothing methods based on regression spline are developed to test the structures of the regression curve and compare multiple regression curves. It could sidestep the determination of knots; meanwhile, it could give a more reliable result in using the spline-based method.",signatures:"Na Li",downloadPdfUrl:"/chapter/pdf-download/60692",previewPdfUrl:"/chapter/pdf-preview/60692",authors:[{id:"210317",title:"Dr.",name:"Na",surname:"Li",slug:"na-li",fullName:"Na Li"}],corrections:null},{id:"60798",title:"Penalized Spline Joint Models for Longitudinal and Time-To-Event Data",doi:"10.5772/intechopen.75975",slug:"penalized-spline-joint-models-for-longitudinal-and-time-to-event-data",totalDownloads:889,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The joint models for longitudinal data and time-to-event data have recently received numerous attention in clinical and epidemiologic studies. Our interest is in modeling the relationship between event time outcomes and internal time-dependent covariates. In practice, the longitudinal responses often show non-linear and fluctuated curves. Therefore, the main aim of this chapter is to use penalized splines with a truncated polynomial basis to parameterize the non-linear longitudinal process. Then, the linear mixed effects model is applied to subject-specific curves and to control the smoothing. The association between the dropout process and longitudinal outcomes is modeled through a proportional hazard model. Two types of baseline risk functions are considered, namely a Gompertz distribution and a piecewise constant model. 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Taylor",authors:[{id:"19818",title:"Prof.",name:"Aarne",middleName:null,surname:"Mämmelä",fullName:"Aarne Mämmelä",slug:"aarne-mammela"},{id:"19824",title:"MSc.",name:"Adrian",middleName:null,surname:"Kotelba",fullName:"Adrian Kotelba",slug:"adrian-kotelba"},{id:"19825",title:"MSc.",name:"Marko",middleName:null,surname:"Höyhtyä",fullName:"Marko Höyhtyä",slug:"marko-hoyhtya"},{id:"24334",title:"Prof.",name:"Desmond P.",middleName:null,surname:"Taylor",fullName:"Desmond P. 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In many developed countries, the milk production per cow has more than doubled. About half of that progress can be contributed to genetics [1]. Along with increase in production, dairy farming has become more intensive. While the number of dairy farms is decreasing globally, the average herd size is increasing [2]. Selection pressure for higher yields and intensive farming have been linked to reduced welfare and an increased incidence of many common diseases in dairy cows, mostly due to genetic antagonisms between production and health traits [3, 4, 5]. Consequently, dairy cows are becoming less “robust,” which have negative consequences for the health and fertility of the modern day dairy cow [6, 7].
Profitable dairy cows are productive, fertile, and mostly “invisible”—they do not require extra attention or intervention to maintain their health through all phases of production. Having a larger proportion of mature cows that are productive and healthy during multiple lactations can enhance profitability of dairy operations. To reach their full potential and longevity, animals need to remain healthy from birth until calving, and then stay healthy and structurally sound, in addition to regularly calving and producing milk. Dairy animals that experience adverse health events negatively affect herd profitability through increased culling, veterinary expenses, and labor, as well as monetary losses through reduced milk sales [8]. The costs per case of the common dairy cow diseases were estimated to range from $181 for ketosis to $391 for displaced abomasum [9].
Dairy researchers and producers have made progress on providing the best environment for animals to reduce health events through nutrition, management, and housing. Additionally, genetic improvement of health and wellness traits in dairy cows is an attractive option for dairy producers because genetic gains are permanent and cumulative from one generation to another [10].
Genetic evaluation and selection for improved health traits has been lagging compared with selection for production and reproduction in dairy cows due to low heritability of health traits and the lack of centralized recording. Most health events in dairy herds have not been recorded by trained veterinarians, but rather by producers themselves using herd management software. However, research has shown that, given the large amount of data, availability of genomic information, and advanced statistical methodology, it is possible to provide accurate genetic and genomic predictions that producers can use as a tool to improve health and wellness of their herds.
In many countries, including the United States, the most frequently cited reason for not using health data in genetic evaluation of dairy cattle is the lack of a centralized national system to collect health record data. Although most dairy producers record health information of their animals using herd management software, the subjectivity of diagnosis and the user-defined terminology of health events contribute to increased difficulty in using health data in a genetic evaluation due to insufficient accuracy and inconsistency of recording [11]. However, several studies based on large amounts of producer-recorded data have shown that genetic selection for wellness traits can be effective in improving herd health in dairy cattle as long as the recording protocols within a herd are fairly consistent [8, 12, 13].
Genetic evaluation of health traits has a long tradition in countries with routine health data recording. In Scandinavian countries, health traits have been included in breeding programs since the mid-1970s [14]. Currently, over 97% of Norwegian dairy cows are included in the recording system [15, 16]. In other countries, the use of direct health data in genetic evaluation is progressing rapidly. Routine data collection and genetic evaluation for health traits in Germany and Austria started in 2006 [17]. In France, clinical mastitis has been included in routine genetic evaluation since 2010 [18]. In 2014, genetic evaluation for mastitis resistance was introduced for Canadian dairy cows; the evaluation is based on clinical mastitis incidence recorded in the first and second lactation and SCS [19, 20]. In Canada, genetic evaluation for ketosis and displaced abomasum was implemented in December 2016, followed by metritis and retained placenta, hoof health and lameness, and other functional traits in the following years [21].
The advances in molecular genetics and genome sequences have created unprecedented opportunities to select for genetically superior animals and increase the speed of genetic improvement of production, reproduction, and, especially, health traits in farm animals. In March 2016, Zoetis Genetics launched CLARIFIDE Plus, the first commercially available genomic test for wellness traits of dairy cattle. Today, CLARIFIDE Plus provides genomic predictions for 14 health and wellness traits in cows and calves of Holstein and Jersey breeds.
The goals of this chapter are (1) to describe the research leading to the development of genomic predictions for wellness traits mastitis (MAST), metritis (METR), retained placenta (RETP), displaced abomasum (DA), ketosis (KETO), and lameness (LAME) based on large producer-recorded data, genomic information, and sophisticated statistical methodology and (2) to present examples of studies focused on assessing efficacy of genomic predictions for wellness traits in independent commercial dairy herds in the United States and other countries.
Phenotypic data have mostly been collected directly from producers upon obtaining their signed permissions. The main source of data was backup files from herd management software DairyComp 305 (Valley Agricultural Software, Tulare, CA), PC Dart (Dairy Records Management Systems, Raleigh, NC), and DHI Plus (DHI Computing Services Inc., Provo, UT). Backup files are processed using internally written scripts, and information on pedigree, production, reproduction, and health events is extracted. Terminology used to record the health events varies across different herds, which was standardized as described [12, 34]. About 300 herds from around the United States have been participating in providing data.
The majority of genotypes used in genomic evaluation have been obtained in the Zoetis genotyping lab. Samples from animals from commercial herds (hair, blood, ear tissue, or semen for males) submitted to Zoetis for genomic testing were analyzed. Upon DNA extraction, genotyping was performed using Illumina BeadArray SNP chips with a number of SNP markers ranging from about 3000 to over 80,000. Raw genotypes were edited following the criteria as described previously [22, 23]. All animals genotyped with lower-density chips (<40,000 markers) were imputed using the program FImpute [24] to a set of 45,245 markers selected based on their call rates and minor allele frequencies that are used in genomic evaluation.
Health events of interest were extracted from the herd management software backup files. Wellness traits mastitis (MAST), metritis (METR), retained placenta (RETP), displaced abomasum (DA), ketosis (KETO), and lameness (LAME) were considered.
Each wellness trait was defined as a binary event, having a value of one if a respective health event has been recorded at least once during the lactation and zero otherwise. Animal were required to have a lactation record with a valid calving date and lactation number, with a calving interval ranging from 250 to 999 days [23]. Lactations of the same cow without recorded disorders, as well as lactations of all herdmates of an animal without recorded health events, were added as “healthy” records. Phenotype records were checked against the pedigree, and all animals recorded as male as well as those having incompatible birth and calving dates were removed. Records were also removed if an animal in her most recent lactation did not reach an opportunity period, which was defined as a number of days in milk (DIM) by which 90% of all cases of a particular disorder have been recorded, or if the health event was recorded after the highest number of DIM when the occurrence of a disorder was biologically plausible. Animals not reaching the opportunity period were removed from the analysis regardless of whether they were healthy or sick.
Contemporary groups were created by combining the herd, year, and season of calving. Each group was required to have a minimum of 20 lactation records and at least one “sick” and one “healthy” record; otherwise, the entire group was discarded.
Single-step genomic BLUP (ssGBLUP) was the method of choice for creating genomic predictions for wellness traits. ssGBLUP combines all available sources of information–pedigree, phenotypes, and genotypes–into one single evaluation, without the need of post-analysis processing, and incorporating information on genotyped and non-genotyped animals in this method in a straightforward manner [25].
The data were analyzed for each trait separately, using the following threshold model [23]:
where
In ssGBLUP, the inverse of the traditional pedigree relationship matrix, A−1 is replaced by the inverse of H matrix, which is the pedigree relationship matrix augmented using genotypes [26, 27].
where
Prior to genetic evaluation, variance components for each trait were estimated using the same data and model, but without including genotype information. Heritability of each trait was expressed as the ratio of genetic variance (
All analyses were performed using the BLUPF90 suite of programs created by Prof. Ignacy Misztal and his team at the University of Georgia in Athens (UGA) [29]. First, the data were formatted and renumbered using the program RENUMF90 v. 1.14. The variance components were estimated using the program THRGIBBS1F90 ver. 2.116. The genetic evaluation was performed with a program CBLUP90IOD2 version 3.21, which is appropriate for massive datasets as it uses iteration on data. To accommodate the large number of genotypes, the algorithm for proven and young animals (APY) was applied [30]. The APY algorithm generates the inverse of the genomic relationship matrix (
The solutions for the random animal effect obtained by the cblup90iod program represent raw estimated breeding values (EBV) on the liability scale. To make them easier to interpret, raw EBV for each trait were transformed into probabilities of exceeding the value of the threshold. The threshold value represents the estimated point of transition between the two categories of a binary trait (in the case of wellness traits, the transition from healthy to sick). Threshold values for all traits were estimated from the data. For each animal solution, the probability that a standard normal variable with a mean equal to that solution and a variance of 1 exceeds the threshold was calculated [23]. These probabilities were then transformed into percentages by multiplying by 100, divided by 2 to obtain predicted transmitting abilities (PTA), which are defined as a half of EBV, and expressed as the differences from the average of the reference population, that is, a group of animals selected to represent relevant individuals from current commercial herds. Higher values of PTA (or genomically enhanced PTA—gPTA—if the animal was genotyped) represent higher risk of having a disorder. For example, in a reference population with an average incidence of mastitis of 20%, an animal with a PTA for mastitis of 2.5 will have offspring with an estimated 22.5% chance of getting mastitis during lactation. Animals’ genetic merit for wellness traits is reported as standardized transmitting abilities (STA) [34] where;
where μ and σ represent the mean and the standard deviation of gPTA, respectively. Therefore, a value of 100 represents the average expected disease risk, with animals at 95 or 105 being one standard deviation away from the mean. For wellness traits, larger STA are more desirable for all traits, because they represent lower expected average disease risk. Selecting for a higher STA is expected to result in reduced incidence of the respective disease.
Table 1 shows the number of phenotypic records, the number of animals with phenotypic records, mean and standard deviation of the incidence, and the estimated heritability of wellness traits. The number of records for cow wellness traits ranged from about 3.2 million for KETO to almost 5.8 million for MAST. Large differences in the number of records available for individual traits were caused by variations in recording among the farms. The mean incidence of the disorders in our analysis varied from 2.6% for DA to 16.7% and 29.1% for LAME and MAST, respectively, indicating that MAST and LAME are the most common health problems in dairy herds.
Distribution of STA for MAST for all animals in the analysis. Animals with extremely low STAs are more likely to develop MAST. Animals with extremely high STAs are considered more resistant to MAST [Dianelys Gonzalez, personal communication, 2021].
Trait | No records | No animals | Mean | SD | Heritability |
---|---|---|---|---|---|
MAST | 5,768,760 | 2,770,872 | 0.291 | 0.454 | 0.097 |
METR | 4,865,943 | 2,435,542 | 0.100 | 0.300 | 0.090 |
RETP | 5,505,269 | 2,714,416 | 0.050 | 0.218 | 0.112 |
DA | 4,489,831 | 2,262,183 | 0.026 | 0.158 | 0.089 |
KETO | 3,221,467 | 1,735,818 | 0.057 | 0.232 | 0.081 |
LAME | 4,336,602 | 2,247,900 | 0.167 | 0.373 | 0.079 |
Basic statistics and the estimated heritability of wellness traits [Dianelys Gonzalez, personal communication, 2021].
The estimated heritabilities for wellness traits were in the narrow range from 0.079 (LAME) to 0.112 (RETP) and were comparable to those reported previously based on studies using similar data and methodology [8, 12]. Heritabilities under 10% are generally considered low, due to proportionally large effects of the environment and not to the lack of genetic variability within the population. Traits with low heritabilities require more data to produce accurate estimates of animals’ breeding values.
Table 2 shows descriptive statistics for gPTA, STA, and reliabilities for all genotyped animals (n = 1,512,546) in the current genetic evaluation. The average values of gPTA and STA were close to zero and 100, respectively, as expected. The variation of gPTA, expressed by their standard deviation and range, reflects the heritability of the trait and the incidence of the disorder. Traits with higher heritabilities and incidence (MAST, LAME) show higher amount of variation in gPTAs. Broader range of gPTA is preferable because it enables better segregation of animals of different genetic merit for wellness traits. Reliabilities for all traits averaged around 50%, but ranging from 0 to over 99%. The reliabilities reflect both the amount of data and the heritabilities of the traits. Very high reliabilities were obtained for bulls with large numbers of phenotyped daughters. A small number of genotyped animals had reliabilities equal to 0. Zero reliabilities for genotyped animals are not expected unless an animal belongs to a different breed or is poorly connected to the population and has an extreme value of the diagonal of the genomic relationship matrix. Animals with zero reliabilities were either crossbreds registered as Holsteins or Holstein animals from unrelated populations from other countries or their offspring without genotyped ancestors or relatives in our data.
Trait | gPTA | STA | Reliability | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Mean | SD | Min | Max | Mean | SD | Min | Max | Mean | SD | Min | Max | |
MAST | −0.543 | 4.49 | −14.10 | 22.61 | 99.5 | 5.1 | 73 | 115 | 50.8 | 5.44 | 0 | 99.8 |
METR | −0.903 | 3.02 | −9.31 | 20.75 | 101.4 | 5.0 | 66 | 115 | 50.0 | 5.53 | 0 | 99.7 |
RETP | 0.111 | 2.71 | −7.80 | 18.70 | 99.8 | 4.9 | 66 | 114 | 51.4 | 5.44 | 0 | 99.7 |
DA | −0.249 | 2.85 | −6.77 | 24.03 | 100.0 | 4.5 | 62 | 110 | 46.1 | 5.52 | 0 | 99.7 |
KETO | −0.964 | 2.55 | −7.05 | 18.83 | 101.7 | 4.8 | 65 | 113 | 46.5 | 5.64 | 0 | 99.6 |
LAME | 0.395 | 3.73 | −10.80 | 22.19 | 99.3 | 5.1 | 70 | 115 | 47.8 | 5.66 | 0 | 99.7 |
Statistics of gPTA, STA, and reliabilities for wellness traits for genotyped animals (n = 1,512,546) [Dianelys Gonzalez, personal communication, 2021].
Genomic prediction for wellness trait obtained at young age is considered a useful tool for selection and management for genetic progress and to assist with culling and breeding decisions in the existing herd. Genetically better heifers and cows can be bred with sexed semen, whereas genetically inferior animals can be sold for beef early on or bred with beef semen [35]. It is best practice for any genetic evaluation to assess the effectiveness of the genetic estimates to predict performance of the evaluated animals. For that matter, we conducted a validation study to determine the effectiveness of the wellness trait genomic predictions in US Holstein cows in an independent population of animals [34].
The study involved 11 large dairy herds distributed across the major dairy-producing regions of the United States. One of the criteria for including herds in the study was that they did not provide phenotypic data for the development of genomic predictions for wellness traits. This was important in order to mimic the experience of new customers who decide to genomically test their animals.
Tissue samples from 2875 animals from the 11 herds were genotyped (Zoetis Genetics, Kalamazoo, MI) after which their genotypes and pedigree information were included in the genetic evaluation for wellness traits. gPTA and STA were obtained for six wellness traits—MAST, METR, RETP, DA, KETO, and LAME. Wellness trait predictions (STA) were used to rank and assign animals to 4 quartiles—genetic groups, for each trait (bottom 25, 26–50, 51–75, and top 25%). Animals were ranked within herd to account for the lack of independence between animal and herd.
Statistical analysis was performed using a GLIMMIX model with a binomial distribution in SAS (version 9.3, SAS Institute Inc., Cary, NC; SAS, 2011). The statistical model included the fixed effects of genetic group, lactation, and age group at the beginning of the study. Herd and animal nested within herd were included as the random effects. The marginal means (incidence) and odds ratios were obtained. The average cost per animal associated with each case of an adverse health event was calculated as a product of the estimated marginal mean and the previously published cost estimate per case of a health event [34].
Table 3 shows the average incidence (marginal means) for the four genetic groups—quartiles—based on gSTAs, the estimated average costs of disease per animal, and the odds ratio compared to the best quartile. The differences in disease incidence between the top and bottom quartiles were 2.9% for retained placenta, 10.8% for metritis, 1.1% for displaced abomasum, 1.7% for ketosis, 7.4% for mastitis, and 3.9% for lameness. The differences in marginal means by genetic groups (disease incidence) translate into appreciable differences in expected economic costs.
To date, demonstration studies for the wellness traits have been conducted in multiple countries using similar methodology as described in [34] (Anthony McNeel and Fernando Di Croce, Zoetis Genetics Technical Services, personal communication, 2021). In 2020, a demonstration study was conducted using 1053 animals across four farms in the United Kingdom [36]. Table 4 shows disease incidence (marginal means) of the best and worst third (33%) of the animals when animals are ranked by genomic standardized transmitting abilities (STA) and the estimated disease cost per 100 cows. In this study, a 43% relative reduction in the incidence of mastitis was observed between the bottom and top third of cows ranked on the MAST STA. Translated into economic terms, this equates to £38 a cow per lactation. Similarly, a 42% reduction in the incidence of lameness was observed between the bottom and top third of animals ranked on the LAME STA, equating to £13 a cow per lactation.
Trait | Genetic group | Incidence (marginal mean, %) | Disease cost per animal ($) | Odds ratio |
---|---|---|---|---|
MAST | Bottom 25 | 15.9 | 33.63 | 2.03 |
26–50 | 11.2 | 23.65 | 1.35 | |
51–76 | 11.1 | 23.32 | 1.33 | |
Top 25 | 8.5 | 18.00 | — | |
METR | Bottom 25 | 23.6 | 70.92 | 2.10 |
26–50 | 18.5 | 55.47 | 1.54 | |
51–76 | 19.1 | 57.42 | 1.61 | |
Top 25 | 12.9 | 38.58 | — | |
RETP | Bottom 25 | 4.5 | 9.30 | 2.94 |
26–50 | 3.3 | 6.88 | 2.15 | |
51–76 | 2.5 | 5.10 | 1.58 | |
Top | 1.6 | 3.26 | — | |
DA | Bottom 25 | 1.1 | 5.58 | 17.05 |
26–50 | 0.5 | 2.32 | 7.13 | |
51–76 | 0.1 | 0.64 | 1.95 | |
Top 25 | 0.1 | 0.35 | — | |
KETO | Bottom 25 | 3.2 | 3.75 | 2.20 |
26–50 | 2.5 | 2.87 | 1.67 | |
51–76 | 1.7 | 1.97 | 1.14 | |
Top 25 | 1.5 | 1.73 | — | |
LAME | Bottom 25 | 11.4 | 20.23 | 1.58 |
26–50 | 8.7 | 15.40 | 1.17 | |
51–76 | 8.6 | 15.28 | 1.16 | |
Top 25 | 7.6 | 13.37 | — |
Results of the analysis of genetic groups for wellness traits in the validation animals [34].
Trait | Incidence (%) | Economic losses per 100 animals (£) | ||
---|---|---|---|---|
Best third | Worst third | Best third | Worst third | |
MAST | 11.3 | 22.3 | 2083 | 4025 |
METR | 1.2 | 5.1 | 307 | 1293 |
RETP | 3.0 | 4.8 | 699 | 1137 |
LAME | 23.0 | 38.2 | 3586 | 5949 |
Results of the independent demonstration study conducted in the United Kingdom in 2020 [36].
These observations have important implications for the sustainability of animal agriculture as fewer health events translate into less antibiotic usage. Table 5 shows the results for antibiotic use for mastitis treatment in the genomic groups (quartiles) when animals are ranked by standardized transmitting abilities (STA) for MAST. The animals in the best genetic group required almost three times fewer the intramammary antibiotic tubes compared with worst genetic group ranking animals.
Genomic Groups | Mastitis STA Average | No. of tubes per group | No. of tubes per cow | Antibiotic use reduction compared to worst 25% |
---|---|---|---|---|
76–100% (Best) | 105 | 178 | 0.68 | −65% |
51–75% | 101 | 250 | 0.95 | −52% |
26–50% | 98 | 480 | 1.83 | −7% |
0–25% (Worst) | 93 | 518 | 1.96 | 0% |
Antibiotic use for mastitis treatment in the genomic groups for MAST [36].
Another demonstration study using similar methodology as in [34] was conducted in 2019 across multiple European countries (Anthony McNeel and Fernando Di Croce, Zoetis Genetics Technical Services, personal communication, 2021). Over 4000 animals from 29 dairy herds in 7 different countries (France, Germany, Russia, Poland, Spain, Ukraine, and the Netherlands) were sampled for the study. First and second lactation animals that produced a usable genotype, passed breed check and calved within the desired time frame (April 1st to September 30th, 2018) were included in the analysis. The incidence of the respective health events and the costs associated with disease were calculated. Table 6 contains average STA, disease incidence (marginal means), and the estimated disease cost per 100 cows of the genetic groups (quartiles) when animals are ranked by standardized transmitting abilities (STA).
Trait | STA quartile group | STA means | Disease prevalence (%) (Marginal mean) | Estimated disease cost (€*) per 100 cows |
---|---|---|---|---|
Worst 25% | 91 | 42.2 | 7870 | |
26–50% | 98 | 36.0 | 6720 | |
51–75% | 102 | 36.3 | 6771 | |
Best 25% | 107 | 32.7 | 6098 | |
METR | Worst 25% | 95 | 10.8 | 2854 |
26–50% | 100 | 11.4 | 3037 | |
51–75% | 103 | 10.0 | 2663 | |
Best 25% | 107 | 7.8 | 2073 | |
Worst 25% | 93 | 12.1 | 2202 | |
26–50% | 99 | 10.1 | 1832 | |
51–75% | 103 | 8.4 | 1533 | |
Best 25% | 107 | 6.7 | 1212 | |
Worst 25% | 93 | 4.5 | 1963 | |
26–50% | 98 | 2.6 | 1113 | |
51–75% | 102 | 2.0 | 873 | |
Best 25% | 105 | 1.7 | 739 | |
Worst 25% | 92 | 17.7 | 2772 | |
26–50% | 98 | 17.0 | 2668 | |
51–75% | 101 | 15.8 | 2473 | |
Best 25% | 105 | 15.0 | 2351 |
Summary of results obtained in the validation study conducted in 7 European countries in 2019 (McNeel and Di Croce, personal communication, 2021).
The validation studies performed in the US commercial herds as well as in the UK and European herds showed consistent results, regardless of differences in location, herd size, and farm management. Genomic predictions for wellness traits in Holstein have been created using data from US commercial herds and they have been shown to accurately predict performance of the animals in Holstein herds not only in the USA, but also in other countries, in herds that did not contribute phenotypic data for development of genomic predictions. How is that possible?
The Holstein population in the United States is genetically fairly homogeneous. A study of genetic variation on the Y chromosome has revealed that more than 99% of all known Holstein artificial insemination (AI) bulls in the United States can be traced through their male lineage to just two bulls born in the 1950s, Round Oak Rag Apple Elevation (Elevation) and Pawnee Farm Arlinda Chief (Chief) [37]. Therefore, the genomic relationships among all Holstein animals are strong in the United States, as well as in other countries that have imported Holstein genetics (mostly
A small number of animals registered as Holstein may not be well connected to the rest of the population. Crossbred animals or Holstein animals from other countries from populations that did not use Holstein bulls imported from the United States may show loose relationships to the rest of the population, which results in poor predictions and low reliabilities of wellness traits gPTAs, even if the animal has a high-quality genotype in the evaluation. Figure 2(a) shows the population structure characterized by principal component analysis (PCA) of purebred animals distributed across the first two principal components, obtained using about 40,000 SNP markers. Breeds included in the analysis were Holstein, Jersey, Brown Swiss, Ayrshire, Guernsey, and the beef breed Angus. It is clearly visible that the individual breeds form distinct clusters, with the Holstein cluster being the largest (due to the largest number of Holstein genotypes in the analysis). However, when magnified (Figure 2(b)), the Holstein cluster shows several outliers, that is, animals that fall outside the main cluster, likely due to mild crossbreeding with Jersey. The genomic predictions for wellness traits for those animals may be less accurate than the predictions for animals within the main cluster, due to their poor connection to the rest of the Holstein population.
(
This chapter describes the development of genomic predictions for wellness traits in US Holstein cattle using large producer-recorded data, genomic information, and sophisticated statistical methodology designed to handle large amounts of phenotypic, pedigree, and genomic data. Genomic predictions for wellness traits have been successfully validated in commercial herds in the United States, UK, and several European countries. These results indicate that genomic data of young calves and heifers can be used to effectively predict future health performance as long as the target population is genetically connected to the population used for developing those predictions. Improving health traits, commonly referred to as functional or wellness traits, through direct genetic selection presents a compelling opportunity for dairy producers to help manage disease incidence and improve profitability when coupled with sound management practices. Genetic selection for improved wellness traits will result in a permanent and cumulative improvement of herd health, as opposed to temporary relief achieved using antibiotics, vaccinations, and other management interventions. Including genomic predictions for wellness traits in an index, along with existing predictions for other economically relevant traits, could provide dairy producers with a more complete tool for selecting potentially most profitable animals.
IntechOpen aims to ensure that original material is published while at the same time giving significant freedom to our Authors. To that end we maintain a flexible Copyright Policy guaranteeing that there is no transfer of copyright to the publisher and Authors retain exclusive copyright to their Work.
',metaTitle:"Publication Agreement - Journals",metaDescription:"IntechOpen aims to ensure that original material is published while at the same time giving significant freedom to our Authors",metaKeywords:null,canonicalURL:"/page/publication-agreement-journals",contentRaw:'[{"type":"htmlEditorComponent","content":"The Corresponding Author (acting on behalf of all Authors) and INTECHOPEN LIMITED, incorporated and registered in England and Wales with company number 11086078 and a registered office at 5 Princes Gate Court, London, United Kingdom, SW7 2QJ conclude the following Agreement regarding the publication of a Journal Article:
\\n\\n1. DEFINITIONS
\\n\\nCorresponding Author: The Author of the Article who serves as a Signatory to this Agreement. The Corresponding Author acts on behalf of any other Co-Author. Co-Author: All other Authors of the Article besides the Corresponding Author. IntechOpen: IntechOpen Ltd., the Publisher of the Journal.
\\n\\nJournal: The publication as a collection of Articles compiled by IntechOpen .
\\n\\nArticle: The original literary work created by Corresponding Author and any Co Author that is the subject of this Agreement.
\\n\\n2. CORRESPONDING AUTHOR'S GRANT OF RIGHTS
\\n\\n2.1 Subject to the following Article, the Corresponding Author grants and shall ensure that each Co-Author grants, to IntechOpen, during the full term of copyright and any extensions or renewals of that term the following:
\\n\\n• An irrevocable, worldwide, royalty-free, perpetual, transferable, sublicensable, non-exclusive right to publish, communicate to the public, reproduce, republish, transmit, sell, distribute and otherwise use and make available the Article in whole, partial or adapted from and/or incorporated in or in conjunction with other works, in electronic and print editions of the Publication and in derivative works and on any platform owned and/or operated by IntechOpen, throughout the world, in all languages, and in all media and formats now known or later developed.
\\n\\n• An irrevocable, worldwide, royalty-free, perpetual, transferable, sublicensable, non-exclusive right to create and store electronic archival copies of the Article, including the right to deposit the Article in open access digital repositories.
\\n\\n• An irrevocable, worldwide, royalty-free, perpetual, transferable, sublicensable, non-exclusive right to license others to reproduce, translate, republish, transmit and distribute the Article in whole, partial or adapted from and/or incorporated in or in conjunction with other works under the condition that the Corresponding Author and each Co-Author is attributed (currently this is carried out by publishing the Article under a Creative Commons 4.0 International Licence).
\\n\\nThe aforementioned licenses shall survive the expiry or termination of this Agreement for any reason.
\\n\\n2.2 The Corresponding Author (on their own behalf and on behalf of any Co-Author) reserves the following rights to the Article but agrees not to exercise them in such a way as to adversely affect IntechOpen's ability to utilize the full benefit of this Publication Agreement: (i) reprographic rights worldwide, other than those which subsist in the typographical arrangement of the Article as published by IntechOpen; and (ii) public lending rights arising under the Public Lending Right Act 1979, as amended from time to time, and any similar rights arising in any part of the world. The Corresponding Author confirms that they (and any Co-Author) are and will remain a member of any applicable licensing and collecting society and any successor to that body responsible for administering royalties for the reprographic reproduction of copyright works.
\\n\\nSubject to the license granted above, copyright in the Article and all versions of it created during IntechOpen's editing process (including the published version) is retained by the Corresponding Author and any Co-Author.
\\n\\nSubject to the license granted above, the Corresponding Author and any Co-Author retains patent, trademark and other intellectual property rights to the Article.
\\n\\n2.3 All rights granted to IntechOpen in this Article are assignable, sublicensable or otherwise transferrable to third parties without the Corresponding Author's or any Co-Author’s specific approval.
\\n\\n2.4 The Corresponding Author (on their own behalf and on behalf of each Co Author) will not assert any rights under the Copyright, Designs and Patents Act 1988 to object to derogatory treatment of the Article as a consequence of IntechOpen's changes to the Article arising from translation of it, corrections and edits for house style, removal of problematic material and other reasonable edits.
\\n\\n3. CORRESPONDING AUTHOR'S DUTIES
\\n\\n3.1 When distributing or re-publishing the Article, the Corresponding Author agrees to credit the Journal in which the Article has been published as the source of first publication, as well as IntechOpen. The Corresponding Author warrants that each Co-Author will also credit the Journal in which the Article has been published as the source of first publication, as well as IntechOpen, when they are distributing or re publishing the Article.
\\n\\n3.2 When submitting the Article, the Corresponding Author agrees to:
\\n\\n• Comply with all instructions and guidelines provided by IntechOpen;
\\n\\n• Produce the Article with all due skill, care and diligence, and in accordance with good scientific practice;
\\n\\n• Submit all the corrections in due time as defined during the publishing process schedule.
\\n\\nThe Corresponding Author will be held responsible for the payment of the Article Processing Charge.
\\n\\nAll payments shall be due 30 days from the date of the issued invoice. The Corresponding Author or the payer on the Corresponding Author's and Co-Authors' behalf will bear all banking and similar charges incurred.
\\n\\n3.3 The Corresponding Author shall obtain in writing all consents necessary for the reproduction of any material in which a third-party right exists, including quotations, photographs and illustrations, in all editions of the Article worldwide for the full term of the above licenses, and shall provide to IntechOpen upon request the original copies of such consents for inspection (at IntechOpen's option) or photocopies of such consents.
\\n\\nThe Corresponding Author shall obtain written informed consent for publication from people who might recognize themselves or be identified by others (e.g. from case reports or photographs).
\\n\\n3.4 The Corresponding Author and any Co-Author shall respect confidentiality rights during and after the termination of this Agreement. The information contained in all correspondence and documents as part of the publishing activity between IntechOpen and the Corresponding Author and any Co-Author are confidential and are intended only for the recipient. The contents may not be disclosed publicly and are not intended for unauthorized use or distribution. Any use, disclosure, copying, or distribution is prohibited and may be unlawful.
\\n\\n4. CORRESPONDING AUTHOR'S WARRANTY
\\n\\n4.1 The Corresponding Author represents and warrants that the Article does not and will not breach any applicable law or the rights of any third party and, specifically, that the Article contains no matter that is defamatory or that infringes any literary or proprietary rights, intellectual property rights, or any rights of privacy. The Corresponding Author warrants and represents that: (i) the Article is the original work of themselves and any Co-Author and is not copied wholly or substantially from any other work or material or any other source; (ii) the Article has not been formally published in any other peer-reviewed journal or in a Journal or edited collection, and is not under consideration for any such publication; (iii) they themselves and any Co-Author are qualifying persons under section 154 of the Copyright, Designs and Patents Act 1988; (iv) they themselves and any Co-Author have not assigned and will not during the term of this Publication Agreement purport to assign any of the rights granted to IntechOpen under this Publication
\\n\\nAgreement; and (v) the rights granted by this Publication Agreement are free from any security interest, option, mortgage, charge or lien.
\\n\\nThe Corresponding Author also warrants and represents that: (i) they have the full power to enter into this Publication Agreement on their own behalf and on behalf of each Co-Author; and (ii) they have the necessary rights and/or title in and to the Article to grant IntechOpen, on behalf of themselves and any Co-Author, the rights and licenses expressed to be granted in this Publication Agreement. If the Article was prepared jointly by the Corresponding Author and any Co-Author, the Corresponding Author warrants and represents that: (i) each Co-Author agrees to the submission, license and publication of the Article on the terms of this Publication Agreement; and (ii) they have the authority to enter into this Publication Agreement on behalf of and bind each Co-Author. The Corresponding Author shall: (i) ensure each Co-Author complies with all relevant provisions of this Publication Agreement, including those relating to confidentiality, performance and standards, as if a party to this Publication Agreement; and (ii) remain primarily liable for all acts and/or omissions of each such Co-Author.
\\n\\nThe Corresponding Author agrees to indemnify and hold IntechOpen harmless against all liabilities, costs, expenses, damages and losses and all reasonable legal costs and expenses suffered or incurred by IntechOpen arising out of or in connection with any breach of the aforementioned representations and warranties. This indemnity shall not cover IntechOpen to the extent that a claim under it results from IntechOpen's negligence or willful misconduct.
\\n\\n4.2 Nothing in this Publication Agreement shall have the effect of excluding or limiting any liability for death or personal injury caused by negligence or any other liability that cannot be excluded or limited by applicable law.
\\n\\n5. TERMINATION
\\n\\n5.1 IntechOpen has a right to terminate this Publication Agreement for quality, program, technical or other reasons with immediate effect, including without limitation (i) if the Corresponding Author or any Co-Author commits a material breach of this Publication Agreement; (ii) if the Corresponding Author or any Co Author (being an individual) is the subject of a bankruptcy petition, application or order; or (iii) if the Corresponding Author or any Co-Author (being a company) commences negotiations with all or any class of its creditors with a view to rescheduling any of its debts, or makes a proposal for or enters into any compromise or arrangement with any of its creditors.
\\n\\nIn case of termination, IntechOpen will notify the Corresponding Author, in writing, of the decision.
\\n\\n6. INTECHOPEN’S DUTIES AND RIGHTS
\\n\\n6.1 Unless prevented from doing so by events outside its reasonable control, IntechOpen, in its discretion, agrees to publish the Article attributing it to the Corresponding Author and any Co-Author.
\\n\\n6.2 IntechOpen has the right to use the Corresponding Author’s and any Co-Author’s names and likeness in connection with scientific dissemination, retrieval, archiving, web hosting and promotion and marketing of the Article and has the right to contact the Corresponding Author and any Co-Author until the Article is publicly available on any platform owned and/or operated by IntechOpen.
\\n\\n6.3 IntechOpen is granted the authority to enforce the rights from this Publication Agreement, on behalf of the Corresponding Author and any Co-Author, against third parties (for example in cases of plagiarism or copyright infringements). In respect of any such infringement or suspected infringement of the copyright in the Article,
\\n\\nIntechOpen shall have absolute discretion in addressing any such infringement which is likely to affect IntechOpen's rights under this Publication Agreement, including issuing and conducting proceedings against the suspected infringer.
\\n\\n7. MISCELLANEOUS
\\n\\n7.1 Further Assurance: The Corresponding Author shall and will ensure that any relevant third party (including any Co-Author) shall, execute and deliver whatever further documents or deeds and perform such acts as IntechOpen reasonably requires from time to time for the purpose of giving IntechOpen the full benefit of the provisions of this Publication Agreement.
\\n\\n7.2 Third Party Rights: A person who is not a party to this Publication Agreement may not enforce any of its provisions under the Contracts (Rights of Third Parties) Act 1999.
\\n\\n7.3 Entire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces and extinguishes all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by or on behalf of the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (together "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of its pre-contract fraudulent misrepresentation or fraudulent concealment.
\\n\\n7.4 Waiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
\\n\\n7.5 Variation: No variation of this Publication Agreement shall be effective unless it is in writing and signed by the parties (or their duly authorized representatives).
\\n\\n7.6 Severance: If any provision or part-provision of this Publication Agreement is or becomes invalid, illegal or unenforceable, it shall be deemed modified to the minimum extent necessary to make it valid, legal and enforceable. If such modification is not possible, the relevant provision or part-provision shall be deemed deleted.
\\n\\nAny modification to or deletion of a provision or part-provision under this clause shall not affect the validity and enforceability of the rest of this Publication Agreement.
\\n\\n7.7 No partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Corresponding Author or any Co-Author, nor authorize any party to make or enter into any commitments for or on behalf of any other party.
\\n\\n7.8 Governing law: This Publication Agreement and any dispute or claim (including non-contractual disputes or claims) arising out of or in connection with it or its subject matter or formation shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of or in connection with this Publication Agreement (including any non-contractual disputes or claims).
\\n"}]'},components:[{type:"htmlEditorComponent",content:"The Corresponding Author (acting on behalf of all Authors) and INTECHOPEN LIMITED, incorporated and registered in England and Wales with company number 11086078 and a registered office at 5 Princes Gate Court, London, United Kingdom, SW7 2QJ conclude the following Agreement regarding the publication of a Journal Article:
\n\n1. DEFINITIONS
\n\nCorresponding Author: The Author of the Article who serves as a Signatory to this Agreement. The Corresponding Author acts on behalf of any other Co-Author. Co-Author: All other Authors of the Article besides the Corresponding Author. IntechOpen: IntechOpen Ltd., the Publisher of the Journal.
\n\nJournal: The publication as a collection of Articles compiled by IntechOpen .
\n\nArticle: The original literary work created by Corresponding Author and any Co Author that is the subject of this Agreement.
\n\n2. CORRESPONDING AUTHOR'S GRANT OF RIGHTS
\n\n2.1 Subject to the following Article, the Corresponding Author grants and shall ensure that each Co-Author grants, to IntechOpen, during the full term of copyright and any extensions or renewals of that term the following:
\n\n• An irrevocable, worldwide, royalty-free, perpetual, transferable, sublicensable, non-exclusive right to publish, communicate to the public, reproduce, republish, transmit, sell, distribute and otherwise use and make available the Article in whole, partial or adapted from and/or incorporated in or in conjunction with other works, in electronic and print editions of the Publication and in derivative works and on any platform owned and/or operated by IntechOpen, throughout the world, in all languages, and in all media and formats now known or later developed.
\n\n• An irrevocable, worldwide, royalty-free, perpetual, transferable, sublicensable, non-exclusive right to create and store electronic archival copies of the Article, including the right to deposit the Article in open access digital repositories.
\n\n• An irrevocable, worldwide, royalty-free, perpetual, transferable, sublicensable, non-exclusive right to license others to reproduce, translate, republish, transmit and distribute the Article in whole, partial or adapted from and/or incorporated in or in conjunction with other works under the condition that the Corresponding Author and each Co-Author is attributed (currently this is carried out by publishing the Article under a Creative Commons 4.0 International Licence).
\n\nThe aforementioned licenses shall survive the expiry or termination of this Agreement for any reason.
\n\n2.2 The Corresponding Author (on their own behalf and on behalf of any Co-Author) reserves the following rights to the Article but agrees not to exercise them in such a way as to adversely affect IntechOpen's ability to utilize the full benefit of this Publication Agreement: (i) reprographic rights worldwide, other than those which subsist in the typographical arrangement of the Article as published by IntechOpen; and (ii) public lending rights arising under the Public Lending Right Act 1979, as amended from time to time, and any similar rights arising in any part of the world. The Corresponding Author confirms that they (and any Co-Author) are and will remain a member of any applicable licensing and collecting society and any successor to that body responsible for administering royalties for the reprographic reproduction of copyright works.
\n\nSubject to the license granted above, copyright in the Article and all versions of it created during IntechOpen's editing process (including the published version) is retained by the Corresponding Author and any Co-Author.
\n\nSubject to the license granted above, the Corresponding Author and any Co-Author retains patent, trademark and other intellectual property rights to the Article.
\n\n2.3 All rights granted to IntechOpen in this Article are assignable, sublicensable or otherwise transferrable to third parties without the Corresponding Author's or any Co-Author’s specific approval.
\n\n2.4 The Corresponding Author (on their own behalf and on behalf of each Co Author) will not assert any rights under the Copyright, Designs and Patents Act 1988 to object to derogatory treatment of the Article as a consequence of IntechOpen's changes to the Article arising from translation of it, corrections and edits for house style, removal of problematic material and other reasonable edits.
\n\n3. CORRESPONDING AUTHOR'S DUTIES
\n\n3.1 When distributing or re-publishing the Article, the Corresponding Author agrees to credit the Journal in which the Article has been published as the source of first publication, as well as IntechOpen. The Corresponding Author warrants that each Co-Author will also credit the Journal in which the Article has been published as the source of first publication, as well as IntechOpen, when they are distributing or re publishing the Article.
\n\n3.2 When submitting the Article, the Corresponding Author agrees to:
\n\n• Comply with all instructions and guidelines provided by IntechOpen;
\n\n• Produce the Article with all due skill, care and diligence, and in accordance with good scientific practice;
\n\n• Submit all the corrections in due time as defined during the publishing process schedule.
\n\nThe Corresponding Author will be held responsible for the payment of the Article Processing Charge.
\n\nAll payments shall be due 30 days from the date of the issued invoice. The Corresponding Author or the payer on the Corresponding Author's and Co-Authors' behalf will bear all banking and similar charges incurred.
\n\n3.3 The Corresponding Author shall obtain in writing all consents necessary for the reproduction of any material in which a third-party right exists, including quotations, photographs and illustrations, in all editions of the Article worldwide for the full term of the above licenses, and shall provide to IntechOpen upon request the original copies of such consents for inspection (at IntechOpen's option) or photocopies of such consents.
\n\nThe Corresponding Author shall obtain written informed consent for publication from people who might recognize themselves or be identified by others (e.g. from case reports or photographs).
\n\n3.4 The Corresponding Author and any Co-Author shall respect confidentiality rights during and after the termination of this Agreement. The information contained in all correspondence and documents as part of the publishing activity between IntechOpen and the Corresponding Author and any Co-Author are confidential and are intended only for the recipient. The contents may not be disclosed publicly and are not intended for unauthorized use or distribution. Any use, disclosure, copying, or distribution is prohibited and may be unlawful.
\n\n4. CORRESPONDING AUTHOR'S WARRANTY
\n\n4.1 The Corresponding Author represents and warrants that the Article does not and will not breach any applicable law or the rights of any third party and, specifically, that the Article contains no matter that is defamatory or that infringes any literary or proprietary rights, intellectual property rights, or any rights of privacy. The Corresponding Author warrants and represents that: (i) the Article is the original work of themselves and any Co-Author and is not copied wholly or substantially from any other work or material or any other source; (ii) the Article has not been formally published in any other peer-reviewed journal or in a Journal or edited collection, and is not under consideration for any such publication; (iii) they themselves and any Co-Author are qualifying persons under section 154 of the Copyright, Designs and Patents Act 1988; (iv) they themselves and any Co-Author have not assigned and will not during the term of this Publication Agreement purport to assign any of the rights granted to IntechOpen under this Publication
\n\nAgreement; and (v) the rights granted by this Publication Agreement are free from any security interest, option, mortgage, charge or lien.
\n\nThe Corresponding Author also warrants and represents that: (i) they have the full power to enter into this Publication Agreement on their own behalf and on behalf of each Co-Author; and (ii) they have the necessary rights and/or title in and to the Article to grant IntechOpen, on behalf of themselves and any Co-Author, the rights and licenses expressed to be granted in this Publication Agreement. If the Article was prepared jointly by the Corresponding Author and any Co-Author, the Corresponding Author warrants and represents that: (i) each Co-Author agrees to the submission, license and publication of the Article on the terms of this Publication Agreement; and (ii) they have the authority to enter into this Publication Agreement on behalf of and bind each Co-Author. The Corresponding Author shall: (i) ensure each Co-Author complies with all relevant provisions of this Publication Agreement, including those relating to confidentiality, performance and standards, as if a party to this Publication Agreement; and (ii) remain primarily liable for all acts and/or omissions of each such Co-Author.
\n\nThe Corresponding Author agrees to indemnify and hold IntechOpen harmless against all liabilities, costs, expenses, damages and losses and all reasonable legal costs and expenses suffered or incurred by IntechOpen arising out of or in connection with any breach of the aforementioned representations and warranties. This indemnity shall not cover IntechOpen to the extent that a claim under it results from IntechOpen's negligence or willful misconduct.
\n\n4.2 Nothing in this Publication Agreement shall have the effect of excluding or limiting any liability for death or personal injury caused by negligence or any other liability that cannot be excluded or limited by applicable law.
\n\n5. TERMINATION
\n\n5.1 IntechOpen has a right to terminate this Publication Agreement for quality, program, technical or other reasons with immediate effect, including without limitation (i) if the Corresponding Author or any Co-Author commits a material breach of this Publication Agreement; (ii) if the Corresponding Author or any Co Author (being an individual) is the subject of a bankruptcy petition, application or order; or (iii) if the Corresponding Author or any Co-Author (being a company) commences negotiations with all or any class of its creditors with a view to rescheduling any of its debts, or makes a proposal for or enters into any compromise or arrangement with any of its creditors.
\n\nIn case of termination, IntechOpen will notify the Corresponding Author, in writing, of the decision.
\n\n6. INTECHOPEN’S DUTIES AND RIGHTS
\n\n6.1 Unless prevented from doing so by events outside its reasonable control, IntechOpen, in its discretion, agrees to publish the Article attributing it to the Corresponding Author and any Co-Author.
\n\n6.2 IntechOpen has the right to use the Corresponding Author’s and any Co-Author’s names and likeness in connection with scientific dissemination, retrieval, archiving, web hosting and promotion and marketing of the Article and has the right to contact the Corresponding Author and any Co-Author until the Article is publicly available on any platform owned and/or operated by IntechOpen.
\n\n6.3 IntechOpen is granted the authority to enforce the rights from this Publication Agreement, on behalf of the Corresponding Author and any Co-Author, against third parties (for example in cases of plagiarism or copyright infringements). In respect of any such infringement or suspected infringement of the copyright in the Article,
\n\nIntechOpen shall have absolute discretion in addressing any such infringement which is likely to affect IntechOpen's rights under this Publication Agreement, including issuing and conducting proceedings against the suspected infringer.
\n\n7. MISCELLANEOUS
\n\n7.1 Further Assurance: The Corresponding Author shall and will ensure that any relevant third party (including any Co-Author) shall, execute and deliver whatever further documents or deeds and perform such acts as IntechOpen reasonably requires from time to time for the purpose of giving IntechOpen the full benefit of the provisions of this Publication Agreement.
\n\n7.2 Third Party Rights: A person who is not a party to this Publication Agreement may not enforce any of its provisions under the Contracts (Rights of Third Parties) Act 1999.
\n\n7.3 Entire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces and extinguishes all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by or on behalf of the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (together "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of its pre-contract fraudulent misrepresentation or fraudulent concealment.
\n\n7.4 Waiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
\n\n7.5 Variation: No variation of this Publication Agreement shall be effective unless it is in writing and signed by the parties (or their duly authorized representatives).
\n\n7.6 Severance: If any provision or part-provision of this Publication Agreement is or becomes invalid, illegal or unenforceable, it shall be deemed modified to the minimum extent necessary to make it valid, legal and enforceable. If such modification is not possible, the relevant provision or part-provision shall be deemed deleted.
\n\nAny modification to or deletion of a provision or part-provision under this clause shall not affect the validity and enforceability of the rest of this Publication Agreement.
\n\n7.7 No partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Corresponding Author or any Co-Author, nor authorize any party to make or enter into any commitments for or on behalf of any other party.
\n\n7.8 Governing law: This Publication Agreement and any dispute or claim (including non-contractual disputes or claims) arising out of or in connection with it or its subject matter or formation shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of or in connection with this Publication Agreement (including any non-contractual disputes or claims).
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He serves as a reviewer for more than eighty international journals, books, and research proposals as well as an editor for special issues of renowned scientific journals.",institutionString:"Centro de Investigación en Materiales Avanzados",institution:{name:"Centro de Investigación en Materiales Avanzados",country:{name:"Mexico"}}},{id:"76477",title:"Prof.",name:"Mirza",middleName:null,surname:"Hasanuzzaman",slug:"mirza-hasanuzzaman",fullName:"Mirza Hasanuzzaman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/76477/images/system/76477.png",biography:"Dr. Mirza Hasanuzzaman is a Professor of Agronomy at Sher-e-Bangla Agricultural University, Bangladesh. He received his Ph.D. in Plant Stress Physiology and Antioxidant Metabolism from Ehime University, Japan, with a scholarship from the Japanese Government (MEXT). Later, he completed his postdoctoral research at the Center of Molecular Biosciences, University of the Ryukyus, Japan, as a recipient of the Japan Society for the Promotion of Science (JSPS) postdoctoral fellowship. He was also the recipient of the Australian Government Endeavour Research Fellowship for postdoctoral research as an adjunct senior researcher at the University of Tasmania, Australia. Dr. Hasanuzzaman’s current work is focused on the physiological and molecular mechanisms of environmental stress tolerance. Dr. Hasanuzzaman has published more than 150 articles in peer-reviewed journals. He has edited ten books and written more than forty book chapters on important aspects of plant physiology, plant stress tolerance, and crop production. According to Scopus, Dr. Hasanuzzaman’s publications have received more than 10,500 citations with an h-index of 53. He has been named a Highly Cited Researcher by Clarivate. He is an editor and reviewer for more than fifty peer-reviewed international journals and was a recipient of the “Publons Peer Review Award” in 2017, 2018, and 2019. He has been honored by different authorities for his outstanding performance in various fields like research and education, and he has received the World Academy of Science Young Scientist Award (2014) and the University Grants Commission (UGC) Award 2018. He is a fellow of the Bangladesh Academy of Sciences (BAS) and the Royal Society of Biology.",institutionString:"Sher-e-Bangla Agricultural University",institution:{name:"Sher-e-Bangla Agricultural University",country:{name:"Bangladesh"}}},{id:"187859",title:"Prof.",name:"Kusal",middleName:"K.",surname:"Das",slug:"kusal-das",fullName:"Kusal Das",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBDeQAO/Profile_Picture_1623411145568",biography:"Kusal K. Das is a Distinguished Chair Professor of Physiology, Shri B. M. Patil Medical College and Director, Centre for Advanced Medical Research (CAMR), BLDE (Deemed to be University), Vijayapur, Karnataka, India. Dr. Das did his M.S. and Ph.D. in Human Physiology from the University of Calcutta, Kolkata. His area of research is focused on understanding of molecular mechanisms of heavy metal activated low oxygen sensing pathways in vascular pathophysiology. He has invented a new method of estimation of serum vitamin E. His expertise in critical experimental protocols on vascular functions in experimental animals was well documented by his quality of publications. He was a Visiting Professor of Medicine at University of Leeds, United Kingdom (2014-2016) and Tulane University, New Orleans, USA (2017). For his immense contribution in medical research Ministry of Science and Technology, Government of India conferred him 'G.P. Chatterjee Memorial Research Prize-2019” and he is also the recipient of 'Dr.Raja Ramanna State Scientist Award 2015” by Government of Karnataka. He is a Fellow of the Royal Society of Biology (FRSB), London and Honorary Fellow of Karnataka Science and Technology Academy, Department of Science and Technology, Government of Karnataka.",institutionString:"BLDE (Deemed to be University), India",institution:null},{id:"243660",title:"Dr.",name:"Mallanagouda Shivanagouda",middleName:null,surname:"Biradar",slug:"mallanagouda-shivanagouda-biradar",fullName:"Mallanagouda Shivanagouda Biradar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243660/images/system/243660.jpeg",biography:"M. S. Biradar is Vice Chancellor and Professor of Medicine of\nBLDE (Deemed to be University), Vijayapura, Karnataka, India.\nHe obtained his MD with a gold medal in General Medicine and\nhas devoted himself to medical teaching, research, and administrations. He has also immensely contributed to medical research\non vascular medicine, which is reflected by his numerous publications including books and book chapters. Professor Biradar was\nalso Visiting Professor at Tulane University School of Medicine, New Orleans, USA.",institutionString:"BLDE (Deemed to be University)",institution:{name:"BLDE University",country:{name:"India"}}},{id:"289796",title:"Dr.",name:"Swastika",middleName:null,surname:"Das",slug:"swastika-das",fullName:"Swastika Das",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/289796/images/system/289796.jpeg",biography:"Swastika N. Das is Professor of Chemistry at the V. P. Dr. P. G.\nHalakatti College of Engineering and Technology, BLDE (Deemed\nto be University), Vijayapura, Karnataka, India. She obtained an\nMSc, MPhil, and PhD in Chemistry from Sambalpur University,\nOdisha, India. Her areas of research interest are medicinal chemistry, chemical kinetics, and free radical chemistry. She is a member\nof the investigators who invented a new modified method of estimation of serum vitamin E. She has authored numerous publications including book\nchapters and is a mentor of doctoral curriculum at her university.",institutionString:"BLDEA’s V.P.Dr.P.G.Halakatti College of Engineering & Technology",institution:{name:"BLDE University",country:{name:"India"}}},{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248459/images/system/248459.png",biography:"Akikazu Takada was born in Japan, 1935. After graduation from\nKeio University School of Medicine and finishing his post-graduate studies, he worked at Roswell Park Memorial Institute NY,\nUSA. He then took a professorship at Hamamatsu University\nSchool of Medicine. In thrombosis studies, he found the SK\npotentiator that enhances plasminogen activation by streptokinase. He is very much interested in simultaneous measurements\nof fatty acids, amino acids, and tryptophan degradation products. By using fatty\nacid analyses, he indicated that plasma levels of trans-fatty acids of old men were\nfar higher in the US than Japanese men. . He also showed that eicosapentaenoic acid\n(EPA) and docosahexaenoic acid (DHA) levels are higher, and arachidonic acid\nlevels are lower in Japanese than US people. By using simultaneous LC/MS analyses\nof plasma levels of tryptophan metabolites, he recently found that plasma levels of\nserotonin, kynurenine, or 5-HIAA were higher in patients of mono- and bipolar\ndepression, which are significantly different from observations reported before. In\nview of recent reports that plasma tryptophan metabolites are mainly produced by\nmicrobiota. He is now working on the relationships between microbiota and depression or autism.",institutionString:"Hamamatsu University School of Medicine",institution:{name:"Hamamatsu University School of Medicine",country:{name:"Japan"}}},{id:"137240",title:"Prof.",name:"Mohammed",middleName:null,surname:"Khalid",slug:"mohammed-khalid",fullName:"Mohammed Khalid",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/137240/images/system/137240.png",biography:"Mohammed Khalid received his B.S. degree in chemistry in 2000 and Ph.D. degree in physical chemistry in 2007 from the University of Khartoum, Sudan. He moved to School of Chemistry, Faculty of Science, University of Sydney, Australia in 2009 and joined Dr. Ron Clarke as a postdoctoral fellow where he worked on the interaction of ATP with the phosphoenzyme of the Na+/K+-ATPase and dual mechanisms of allosteric acceleration of the Na+/K+-ATPase by ATP; then he went back to Department of Chemistry, University of Khartoum as an assistant professor, and in 2014 he was promoted as an associate professor. In 2011, he joined the staff of Department of Chemistry at Taif University, Saudi Arabia, where he is currently an assistant professor. His research interests include the following: P-Type ATPase enzyme kinetics and mechanisms, kinetics and mechanisms of redox reactions, autocatalytic reactions, computational enzyme kinetics, allosteric acceleration of P-type ATPases by ATP, exploring of allosteric sites of ATPases, and interaction of ATP with ATPases located in cell membranes.",institutionString:"Taif University",institution:{name:"Taif University",country:{name:"Saudi Arabia"}}},{id:"63810",title:"Prof.",name:"Jorge",middleName:null,surname:"Morales-Montor",slug:"jorge-morales-montor",fullName:"Jorge Morales-Montor",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/63810/images/system/63810.png",biography:"Dr. Jorge Morales-Montor was recognized with the Lola and Igo Flisser PUIS Award for best graduate thesis at the national level in the field of parasitology. He received a fellowship from the Fogarty Foundation to perform postdoctoral research stay at the University of Georgia. He has 153 journal articles to his credit. He has also edited several books and published more than fifty-five book chapters. He is a member of the Mexican Academy of Sciences, Latin American Academy of Sciences, and the National Academy of Medicine. He has received more than thirty-five awards and has supervised numerous bachelor’s, master’s, and Ph.D. students. Dr. Morales-Montor is the past president of the Mexican Society of Parasitology.",institutionString:"National Autonomous University of Mexico",institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"217215",title:"Dr.",name:"Palash",middleName:null,surname:"Mandal",slug:"palash-mandal",fullName:"Palash Mandal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217215/images/system/217215.jpeg",biography:null,institutionString:"Charusat University",institution:null},{id:"49739",title:"Dr.",name:"Leszek",middleName:null,surname:"Szablewski",slug:"leszek-szablewski",fullName:"Leszek Szablewski",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49739/images/system/49739.jpg",biography:"Leszek Szablewski is a professor of medical sciences. He received his M.S. in the Faculty of Biology from the University of Warsaw and his PhD degree from the Institute of Experimental Biology Polish Academy of Sciences. He habilitated in the Medical University of Warsaw, and he obtained his degree of Professor from the President of Poland. Professor Szablewski is the Head of Chair and Department of General Biology and Parasitology, Medical University of Warsaw. Professor Szablewski has published over 80 peer-reviewed papers in journals such as Journal of Alzheimer’s Disease, Biochim. Biophys. Acta Reviews of Cancer, Biol. Chem., J. Biomed. Sci., and Diabetes/Metabol. Res. Rev, Endocrine. He is the author of two books and four book chapters. He has edited four books, written 15 scripts for students, is the ad hoc reviewer of over 30 peer-reviewed journals, and editorial member of peer-reviewed journals. Prof. Szablewski’s research focuses on cell physiology, genetics, and pathophysiology. He works on the damage caused by lack of glucose homeostasis and changes in the expression and/or function of glucose transporters due to various diseases. He has given lectures, seminars, and exercises for students at the Medical University.",institutionString:"Medical University of Warsaw",institution:{name:"Medical University of Warsaw",country:{name:"Poland"}}},{id:"173123",title:"Dr.",name:"Maitham",middleName:null,surname:"Khajah",slug:"maitham-khajah",fullName:"Maitham Khajah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/173123/images/system/173123.jpeg",biography:"Dr. Maitham A. Khajah received his degree in Pharmacy from Faculty of Pharmacy, Kuwait University, in 2003 and obtained his PhD degree in December 2009 from the University of Calgary, Canada (Gastrointestinal Science and Immunology). Since January 2010 he has been assistant professor in Kuwait University, Faculty of Pharmacy, Department of Pharmacology and Therapeutics. His research interest are molecular targets for the treatment of inflammatory bowel disease (IBD) and the mechanisms responsible for immune cell chemotaxis. He cosupervised many students for the MSc Molecular Biology Program, College of Graduate Studies, Kuwait University. Ever since joining Kuwait University in 2010, he got various grants as PI and Co-I. He was awarded the Best Young Researcher Award by Kuwait University, Research Sector, for the Year 2013–2014. He was a member in the organizing committee for three conferences organized by Kuwait University, Faculty of Pharmacy, as cochair and a member in the scientific committee (the 3rd, 4th, and 5th Kuwait International Pharmacy Conference).",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"195136",title:"Dr.",name:"Aya",middleName:null,surname:"Adel",slug:"aya-adel",fullName:"Aya Adel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/195136/images/system/195136.jpg",biography:"Dr. Adel works as an Assistant Lecturer in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. Dr. Adel is especially interested in joint attention and its impairment in autism spectrum disorder",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"94911",title:"Dr.",name:"Boulenouar",middleName:null,surname:"Mesraoua",slug:"boulenouar-mesraoua",fullName:"Boulenouar Mesraoua",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94911/images/system/94911.png",biography:"Dr Boulenouar Mesraoua is the Associate Professor of Clinical Neurology at Weill Cornell Medical College-Qatar and a Consultant Neurologist at Hamad Medical Corporation at the Neuroscience Department; He graduated as a Medical Doctor from the University of Oran, Algeria; he then moved to Belgium, the City of Liege, for a Residency in Internal Medicine and Neurology at Liege University; after getting the Belgian Board of Neurology (with high marks), he went to the National Hospital for Nervous Diseases, Queen Square, London, United Kingdom for a fellowship in Clinical Neurophysiology, under Pr Willison ; Dr Mesraoua had also further training in Epilepsy and Continuous EEG Monitoring for two years (from 2001-2003) in the Neurophysiology department of Zurich University, Switzerland, under late Pr Hans Gregor Wieser ,an internationally known epileptologist expert. \n\nDr B. Mesraoua is the Director of the Neurology Fellowship Program at the Neurology Section and an active member of the newly created Comprehensive Epilepsy Program at Hamad General Hospital, Doha, Qatar; he is also Assistant Director of the Residency Program at the Qatar Medical School. \nDr B. Mesraoua's main interests are Epilepsy, Multiple Sclerosis, and Clinical Neurology; He is the Chairman and the Organizer of the well known Qatar Epilepsy Symposium, he is running yearly for the past 14 years and which is considered a landmark in the Gulf region; He has also started last year , together with other epileptologists from Qatar, the region and elsewhere, a yearly International Epilepsy School Course, which was attended by many neurologists from the Area.\n\nInternationally, Dr Mesraoua is an active and elected member of the Commission on Eastern Mediterranean Region (EMR ) , a regional branch of the International League Against Epilepsy (ILAE), where he represents the Middle East and North Africa(MENA ) and where he holds the position of chief of the Epilepsy Epidemiology Section; Dr Mesraoua is a member of the American Academy of Neurology, the Europeen Academy of Neurology and the American Epilepsy Society.\n\nDr Mesraoua's main objectives are to encourage frequent gathering of the epileptologists/neurologists from the MENA region and the rest of the world, promote Epilepsy Teaching in the MENA Region, and encourage multicenter studies involving neurologists and epileptologists in the MENA region, particularly epilepsy epidemiological studies. \n\nDr. Mesraoua is the recipient of two research Grants, as the Lead Principal Investigator (750.000 USD and 250.000 USD) from the Qatar National Research Fund (QNRF) and the Hamad Hospital Internal Research Grant (IRGC), on the following topics : “Continuous EEG Monitoring in the ICU “ and on “Alpha-lactoalbumin , proof of concept in the treatment of epilepsy” .Dr Mesraoua is a reviewer for the journal \"seizures\" (Europeen Epilepsy Journal ) as well as dove journals ; Dr Mesraoua is the author and co-author of many peer reviewed publications and four book chapters in the field of Epilepsy and Clinical Neurology",institutionString:"Weill Cornell Medical College in Qatar",institution:{name:"Weill Cornell Medical College in Qatar",country:{name:"Qatar"}}},{id:"282429",title:"Prof.",name:"Covanis",middleName:null,surname:"Athanasios",slug:"covanis-athanasios",fullName:"Covanis Athanasios",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/282429/images/system/282429.jpg",biography:null,institutionString:"Neurology-Neurophysiology Department of the Children Hospital Agia Sophia",institution:null},{id:"190980",title:"Prof.",name:"Marwa",middleName:null,surname:"Mahmoud Saleh",slug:"marwa-mahmoud-saleh",fullName:"Marwa Mahmoud Saleh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/190980/images/system/190980.jpg",biography:"Professor Marwa Mahmoud Saleh is a doctor of medicine and currently works in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. She got her doctoral degree in 1991 and her doctoral thesis was accomplished in the University of Iowa, United States. Her publications covered a multitude of topics as videokymography, cochlear implants, stuttering, and dysphagia. She has lectured Egyptian phonology for many years. Her recent research interest is joint attention in autism.",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259190/images/system/259190.png",biography:"Dr. Naqvi is a radioanalytical chemist and is working as an associate professor of analytical chemistry in the Department of Chemistry, Government College University, Faisalabad, Pakistan. Advance separation techniques, nuclear analytical techniques and radiopharmaceutical analysis are the main courses that he is teaching to graduate and post-graduate students. In the research area, he is focusing on the development of organic- and biomolecule-based radiopharmaceuticals for diagnosis and therapy of infectious and cancerous diseases. Under the supervision of Dr. Naqvi, three students have completed their Ph.D. degrees and 41 students have completed their MS degrees. He has completed three research projects and is currently working on 2 projects entitled “Radiolabeling of fluoroquinolone derivatives for the diagnosis of deep-seated bacterial infections” and “Radiolabeled minigastrin peptides for diagnosis and therapy of NETs”. He has published about 100 research articles in international reputed journals and 7 book chapters. Pakistan Institute of Nuclear Science & Technology (PINSTECH) Islamabad, Punjab Institute of Nuclear Medicine (PINM), Faisalabad and Institute of Nuclear Medicine and Radiology (INOR) Abbottabad are the main collaborating institutes.",institutionString:"Government College University",institution:{name:"Government College University, Faisalabad",country:{name:"Pakistan"}}},{id:"58390",title:"Dr.",name:"Gyula",middleName:null,surname:"Mozsik",slug:"gyula-mozsik",fullName:"Gyula Mozsik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/58390/images/system/58390.png",biography:"Gyula Mózsik MD, Ph.D., ScD (med), is an emeritus professor of Medicine at the First Department of Medicine, Univesity of Pécs, Hungary. He was head of this department from 1993 to 2003. His specializations are medicine, gastroenterology, clinical pharmacology, clinical nutrition, and dietetics. His research fields are biochemical pharmacological examinations in the human gastrointestinal (GI) mucosa, mechanisms of retinoids, drugs, capsaicin-sensitive afferent nerves, and innovative pharmacological, pharmaceutical, and nutritional (dietary) research in humans. He has published about 360 peer-reviewed papers, 197 book chapters, 692 abstracts, 19 monographs, and has edited 37 books. He has given about 1120 regular and review lectures. He has organized thirty-eight national and international congresses and symposia. He is the founder of the International Conference on Ulcer Research (ICUR); International Union of Pharmacology, Gastrointestinal Section (IUPHAR-GI); Brain-Gut Society symposiums, and gastrointestinal cytoprotective symposiums. He received the Andre Robert Award from IUPHAR-GI in 2014. Fifteen of his students have been appointed as full professors in Egypt, Cuba, and Hungary.",institutionString:"University of Pécs",institution:{name:"University of Pecs",country:{name:"Hungary"}}},{id:"277367",title:"M.Sc.",name:"Daniel",middleName:"Martin",surname:"Márquez López",slug:"daniel-marquez-lopez",fullName:"Daniel Márquez López",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/277367/images/7909_n.jpg",biography:"Msc Daniel Martin Márquez López has a bachelor degree in Industrial Chemical Engineering, a Master of science degree in the same área and he is a PhD candidate for the Instituto Politécnico Nacional. His Works are realted to the Green chemistry field, biolubricants, biodiesel, transesterification reactions for biodiesel production and the manipulation of oils for therapeutic purposes.",institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/196544/images/system/196544.jpg",biography:"Angel Catalá studied chemistry at Universidad Nacional de La Plata, Argentina, where he received a Ph.D. in Chemistry (Biological Branch) in 1965. From 1964 to 1974, he worked as an Assistant in Biochemistry at the School of Medicine at the same university. From 1974 to 1976, he was a fellow of the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor of Biochemistry at the Universidad Nacional de La Plata. He is a member of the National Research Council (CONICET), Argentina, and the Argentine Society for Biochemistry and Molecular Biology (SAIB). His laboratory has been interested for many years in the lipid peroxidation of biological membranes from various tissues and different species. Dr. Catalá has directed twelve doctoral theses, published more than 100 papers in peer-reviewed journals, several chapters in books, and edited twelve books. He received awards at the 40th International Conference Biochemistry of Lipids 1999 in Dijon, France. He is the winner of the Bimbo Pan-American Nutrition, Food Science and Technology Award 2006 and 2012, South America, Human Nutrition, Professional Category. In 2006, he won the Bernardo Houssay award in pharmacology, in recognition of his meritorious works of research. Dr. Catalá belongs to the editorial board of several journals including Journal of Lipids; International Review of Biophysical Chemistry; Frontiers in Membrane Physiology and Biophysics; World Journal of Experimental Medicine and Biochemistry Research International; World Journal of Biological Chemistry, Diabetes, and the Pancreas; International Journal of Chronic Diseases & Therapy; and International Journal of Nutrition. He is the co-editor of The Open Biology Journal and associate editor for Oxidative Medicine and Cellular Longevity.",institutionString:"Universidad Nacional de La Plata",institution:{name:"National University of La Plata",country:{name:"Argentina"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",slug:"francisco-javier-martin-romero",fullName:"Francisco Javier Martin-Romero",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",biography:"Francisco Javier Martín-Romero (Javier) is a Professor of Biochemistry and Molecular Biology at the University of Extremadura, Spain. He is also a group leader at the Biomarkers Institute of Molecular Pathology. Javier received his Ph.D. in 1998 in Biochemistry and Biophysics. At the National Cancer Institute (National Institute of Health, Bethesda, MD) he worked as a research associate on the molecular biology of selenium and its role in health and disease. After postdoctoral collaborations with Carlos Gutierrez-Merino (University of Extremadura, Spain) and Dario Alessi (University of Dundee, UK), he established his own laboratory in 2008. The interest of Javier's lab is the study of cell signaling with a special focus on Ca2+ signaling, and how Ca2+ transport modulates the cytoskeleton, migration, differentiation, cell death, etc. He is especially interested in the study of Ca2+ channels, and the role of STIM1 in the initiation of pathological events.",institutionString:null,institution:{name:"University of Extremadura",country:{name:"Spain"}}},{id:"217323",title:"Prof.",name:"Guang-Jer",middleName:null,surname:"Wu",slug:"guang-jer-wu",fullName:"Guang-Jer Wu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217323/images/8027_n.jpg",biography:null,institutionString:null,institution:null},{id:"148546",title:"Dr.",name:"Norma Francenia",middleName:null,surname:"Santos-Sánchez",slug:"norma-francenia-santos-sanchez",fullName:"Norma Francenia Santos-Sánchez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/148546/images/4640_n.jpg",biography:null,institutionString:null,institution:null},{id:"272889",title:"Dr.",name:"Narendra",middleName:null,surname:"Maddu",slug:"narendra-maddu",fullName:"Narendra Maddu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272889/images/10758_n.jpg",biography:null,institutionString:null,institution:null},{id:"242491",title:"Prof.",name:"Angelica",middleName:null,surname:"Rueda",slug:"angelica-rueda",fullName:"Angelica Rueda",position:"Investigador Cinvestav 3B",profilePictureURL:"https://mts.intechopen.com/storage/users/242491/images/6765_n.jpg",biography:null,institutionString:null,institution:null},{id:"88631",title:"Dr.",name:"Ivan",middleName:null,surname:"Petyaev",slug:"ivan-petyaev",fullName:"Ivan Petyaev",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Lycotec (United Kingdom)",country:{name:"United Kingdom"}}},{id:"423869",title:"Ms.",name:"Smita",middleName:null,surname:"Rai",slug:"smita-rai",fullName:"Smita Rai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424024",title:"Prof.",name:"Swati",middleName:null,surname:"Sharma",slug:"swati-sharma",fullName:"Swati Sharma",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"439112",title:"MSc.",name:"Touseef",middleName:null,surname:"Fatima",slug:"touseef-fatima",fullName:"Touseef Fatima",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424836",title:"Dr.",name:"Orsolya",middleName:null,surname:"Borsai",slug:"orsolya-borsai",fullName:"Orsolya Borsai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca",country:{name:"Romania"}}},{id:"422262",title:"Ph.D.",name:"Paola Andrea",middleName:null,surname:"Palmeros-Suárez",slug:"paola-andrea-palmeros-suarez",fullName:"Paola Andrea Palmeros-Suárez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Guadalajara",country:{name:"Mexico"}}}]}},subseries:{item:{id:"41",type:"subseries",title:"Water Science",keywords:"Water, Water resources, Freshwater, Hydrological processes, Utilization, Protection",scope:"