These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\n
This collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\n
To celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\n
Initially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\n
These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\n
This collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\n
To celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\n'}],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:"7784",leadTitle:null,fullTitle:"Spina Bifida and Craniosynostosis - New Perspectives and Clinical Applications",title:"Spina Bifida and Craniosynostosis",subtitle:"New Perspectives and Clinical Applications",reviewType:"peer-reviewed",abstract:"This book is a comprehensive overview of spina bifida and craniosynostosis with emphasis on new trends in the management of these diseases. Chapters on spina bifida cover such topics as the etiology and pathophysiology of caudal neural tube defects, the overall management of pediatric patients with spina bifida, surgical treatment, and urological and orthopedic care. The chapters on craniosynostosis present new technologies of surgical treatment, craniomaxillofacial corrective surgery, and telescoping techniques with multiple cranial osteotomies.",isbn:"978-1-83962-951-8",printIsbn:"978-1-83962-950-1",pdfIsbn:"978-1-83962-952-5",doi:"10.5772/intechopen.77598",price:119,priceEur:129,priceUsd:155,slug:"spina-bifida-and-craniosynostosis-new-perspectives-and-clinical-applications",numberOfPages:172,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"a979d42a6e93e686c533420a9a638c07",bookSignature:"Branislav Kolarovszki, Raffaella Messina and Valeria Blè",publishedDate:"June 23rd 2021",coverURL:"https://cdn.intechopen.com/books/images_new/7784.jpg",numberOfDownloads:2845,numberOfWosCitations:0,numberOfCrossrefCitations:1,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:2,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:3,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 30th 2020",dateEndSecondStepPublish:"July 21st 2020",dateEndThirdStepPublish:"September 19th 2020",dateEndFourthStepPublish:"December 8th 2020",dateEndFifthStepPublish:"February 6th 2021",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"92436",title:"Associate Prof.",name:"Branislav",middleName:null,surname:"Kolarovszki",slug:"branislav-kolarovszki",fullName:"Branislav Kolarovszki",profilePictureURL:"https://mts.intechopen.com/storage/users/92436/images/system/92436.png",biography:"Assoc. Prof. Branislav Kolarovszki, MD, Ph.D., is the head of the Clinic of Neurosurgery, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, University Hospital in Martin, Slovakia. For many years he deals with the issues of pediatric neurosurgery, especially hydrocephalus, spina bifida, and craniosynostosis. He published the results of his work in many scientific journals and monographs. He actively participates in congresses, including invited lectures on pediatric neurosurgery. Dr. Kolarovszki is a member of editorial boards and a reviewer of many medical journals. He is currently the first vice-dean of the Jessenius Faculty of Medicine.",institutionString:"Comenius University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Comenius University",institutionURL:null,country:{name:"Slovakia"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"291148",title:"Dr.",name:"Raffaella",middleName:null,surname:"Messina",slug:"raffaella-messina",fullName:"Raffaella Messina",profilePictureURL:"https://mts.intechopen.com/storage/users/291148/images/system/291148.jpg",biography:"Dr. Raffaella Messina is an Italian board-certified neurosurgeon. She was trained in neurosurgery at the University Hospital of Bari, Italy. She has held a fellowship in pediatric neurosurgery at the IRCCS Institute for Treatment and Research - Bambino Gesù Children\\'s Hospital, Rome. She is currently pursuing a Ph.D. in Neurosciences and has been an assistant professor at the\nUniversity of Bari “Aldo Moro,” Italy, since 2010. Her major field of interest is pediatric neurosurgery, in which she has focused her main scientific activity. She had the opportunity to improve her surgical skills and to achieve board certification for the European Society for Pediatric Neurosurgery (ESPN), attending the three-year cycle of ESPN.",institutionString:'University of Bari Medical School "Aldo Moro"',position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Bari Aldo Moro",institutionURL:null,country:{name:"Italy"}}},coeditorTwo:{id:"327232",title:"Dr.",name:"Valeria",middleName:null,surname:"Blè",slug:"valeria-ble",fullName:"Valeria Blè",profilePictureURL:"https://mts.intechopen.com/storage/users/327232/images/system/327232.jpeg",biography:"Dr. Valeria Blé is an Italian board-certified neurosurgeon. She was trained in neurosurgery at the University Hospital of Bari, Italy, and was an observer in pediatric neurosurgery at Hôpital Femme Mère Enfant, Lyon, France, and fellow at the IRCCS Institute for Treatment and Research - Bambino Gesu Children\\'s Hospital, Rome. \n\nShe is a consultant neurosurgeon in the University Hospital in Bari, Italy. Her major field of interest is pediatric neurosurgery, and she is currently taking a post-graduate course in Pediatric Neurosurgery.",institutionString:'University of Bari Medical School "Aldo Moro"',position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Bari Aldo Moro",institutionURL:null,country:{name:"Italy"}}},coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1108",title:"Neonatology",slug:"neonatology"}],chapters:[{id:"76268",title:"Etiology and Pathophysiology of the Spina Bifida",doi:"10.5772/intechopen.97467",slug:"etiology-and-pathophysiology-of-the-spina-bifida",totalDownloads:307,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The spina bifida is a congenital anomaly that results in an abnormal formation of the spine and the spinal cord. The two dominant types of spinal dysraphism are based on appearance - open spina bifida if the lesion is visible and closed spina bifida if the lesion is not visible on the body surface. These conditions lead to a different spectrum of neurological effects according to the degree of neurulation disruption. The prevalence of neural tube defects has different rates among different ethnicity, geography, gender, and countries. Genetic, nutritional and environmental factors play a role in the etiology and pathogenesis of the spina bifida. Congenital anomalies in the vast majority concern children living in the early neonatal period who have important medical, social or educational needs. The lifetime cost of a child born with the spina bifida is estimated at over €500,000.",signatures:"René Opšenák, Romana Richterová and Branislav Kolarovszki",downloadPdfUrl:"/chapter/pdf-download/76268",previewPdfUrl:"/chapter/pdf-preview/76268",authors:[{id:"182753",title:"Dr.",name:"Romana",surname:"Richterová",slug:"romana-richterova",fullName:"Romana Richterová"},{id:"328583",title:"Dr.",name:"René",surname:"Opšenák",slug:"rene-opsenak",fullName:"René Opšenák"},{id:"334527",title:"Dr.",name:"Branislav",surname:"Kolarovszki",slug:"branislav-kolarovszki",fullName:"Branislav Kolarovszki"}],corrections:null},{id:"77003",title:"Management of Pediatric Patients with Spina Bifida",doi:"10.5772/intechopen.97237",slug:"management-of-pediatric-patients-with-spina-bifida",totalDownloads:326,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Spina bifida is a neurodevelopmental disorder and belong to most common congenital malformations. It is a neural tube defect that originates within first 28 days after conception. Although survival rate of these patients had changed rapidly within last decades, neural tube defects are still cause of substantial part of children morbidity. Occult type of spina bifida is a simple nonunion of vertebral arch without causing any symptoms. Open defects according to degree of involvement of neural tissue cause symptoms such as paralysis of lower extremities, bladder and bowel morbidity, delay in development of cognitive functions of various severity and other possible complications affecting morbidity of these patients. Early diagnosis and treatment of open spina bifida and accompaying complications is crucial and largely affects the outome. Succesfull treatment requires lifelong cooperation of a whole range of specialists and guiding of treatment by primary care doctor. Survival and quality of life are associated with acces to proper medical and surgical treatment as well as community support systems. This chapter offers overview of this topic with emphasis on general management of patients suffering from this congenital malformation.",signatures:"Romana Richterová, Branislav Kolarovszki and René Opšenák",downloadPdfUrl:"/chapter/pdf-download/77003",previewPdfUrl:"/chapter/pdf-preview/77003",authors:[{id:"182753",title:"Dr.",name:"Romana",surname:"Richterová",slug:"romana-richterova",fullName:"Romana Richterová"},{id:"328583",title:"Dr.",name:"René",surname:"Opšenák",slug:"rene-opsenak",fullName:"René Opšenák"},{id:"328585",title:"Dr.",name:"Branislav",surname:"Kolarovszki",slug:"branislav-kolarovszki",fullName:"Branislav Kolarovszki"}],corrections:null},{id:"75122",title:"Surgical Treatment of Neural Tube Defects",doi:"10.5772/intechopen.95408",slug:"surgical-treatment-of-neural-tube-defects",totalDownloads:289,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Neural tube defects (NTDs) are developmental pathologies associated with undesirable lifelong consequences. Incidence of these pathologies differs between countries and regions depending on socio-economic and healthcare quality. It is also influenced by folic acid and zinc supplementation. Genetic factors influence probability of NTD, increasing risk of defect in siblings up to 3–8%. Estimated incidence in United States is 3–4/10000 live births, and worldwide incidence increases on about 10/10000 live births. Despite various types and localizations of spina bifida, in all of them neural tissue is in danger. This can lead to various types of neurologic disorders. Not only due to direct damaging of spinal cord and nerve roots but also other parts of central nervous system are also endangered by disturbed prenatal development. Other consequences as orthopedic abnormalities, bladder, and bowel dysfunction influence quality of life. Surgical therapy is often the only possibility to preserve existing function of neural tissue, allows its further development and prevents complications. In this chapter surgical techniques with aim to restore spinal cord and nerve roots anatomy, preservation of its function and defect closures are presented. Also, treatment of possible comorbidities and complications is discussed. Spina bifida management requires multi-speciality cooperation and care to monitor, prevent and treat various potential complication that can negatively influence quality of life and even survival. Prenatal diagnosis is based on maternal screening of serum alpha fetoprotein (AFP) levels and prenatal ultrasonography examination. As the suspicion of neural tube defect arises, an amniocentesis is recommended to complete a genetic analysis and obtain amniotic fluid for more precise AFP and acetylcholinesterase examination. Some types of neural tube defects are diagnosed after delivery, some are symptomatic until adulthood and some are diagnosed incidentally. Each of them requires specific management, based on underlying pathology.",signatures:"Juraj Šutovský",downloadPdfUrl:"/chapter/pdf-download/75122",previewPdfUrl:"/chapter/pdf-preview/75122",authors:[{id:"328591",title:"Dr.",name:"Juraj",surname:"Sutovsky",slug:"juraj-sutovsky",fullName:"Juraj Sutovsky"}],corrections:null},{id:"74187",title:"Urologic Implications and Management in Spina Bifida",doi:"10.5772/intechopen.94938",slug:"urologic-implications-and-management-in-spina-bifida",totalDownloads:354,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Urological disorders, including urinary infections, incontinence, and renal failure, represent a significant source of morbidity and mortality in these patients. Long-term mortality is associated to urological causes in approximately 33%. In order to prevent this complications, urologic evaluation since early childhood must be done. The evaluation of the degree of damage to the urinary tract and the determination of the type of neurogenic bladder involved in the spina bifida spectrum will be the guideline for establishing therapeutic management, which can be from behavioral modifications, medical management, minimally invasive therapy and, as a last resort, surgery. In this chapter, we will discuss the wide spectrum of urologic implications, a brief reminder of urinary tract physiology and the pathological processes involved in spina bífida, as well as long-term complications. The diagnostic evaluation of urinary tract and the different therapeutic modalities according to the type of neurogenic bladder and age will be discussed.",signatures:"Adrián Gutiérrez-González, José Iván Robles-Torres and Daniel García-Sánchez",downloadPdfUrl:"/chapter/pdf-download/74187",previewPdfUrl:"/chapter/pdf-preview/74187",authors:[{id:"326043",title:"Prof.",name:"Adrián",surname:"Gutiérrez-González",slug:"adrian-gutierrez-gonzalez",fullName:"Adrián Gutiérrez-González"},{id:"329735",title:"Dr.",name:"José Iván",surname:"Robles-Torres",slug:"jose-ivan-robles-torres",fullName:"José Iván Robles-Torres"},{id:"329736",title:"Dr.",name:"Daniel",surname:"García-Sánchez",slug:"daniel-garcia-sanchez",fullName:"Daniel García-Sánchez"}],corrections:null},{id:"74241",title:"Orthopedic Approach to Spina Bifida",doi:"10.5772/intechopen.94901",slug:"orthopedic-approach-to-spina-bifida",totalDownloads:453,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Spina bifida is a common nervous system malformation and it encompasses a wide array of presentations with diverse orthopedic challenges. Manifestations of this disease can include dislocates hips, joint contractures, spine deformity such as scoliosis or kyphosis, clubfeet and limb rotational deformities. Additionally, many of these patients are non-ambulatory and prone to osteoporosis induced pathological fractures. The care of spina bifida patients is a challenging one, requiring many health care professionals from different areas to be working in conjunction. Nowadays, spina bifida patients live longer due to advances in health care and improving the quality of life of these patients is paramount.",signatures:"Roselle C. Okubo, Claudio Silveri and Ana C. Belzarena",downloadPdfUrl:"/chapter/pdf-download/74241",previewPdfUrl:"/chapter/pdf-preview/74241",authors:[{id:"326613",title:"Dr.",name:"Ana C.",surname:"Belzarena",slug:"ana-c.-belzarena",fullName:"Ana C. Belzarena"},{id:"331945",title:"Mrs.",name:"Roselle",surname:"Okubo",slug:"roselle-okubo",fullName:"Roselle Okubo"},{id:"331946",title:"Dr.",name:"Claudio",surname:"Silveri",slug:"claudio-silveri",fullName:"Claudio Silveri"}],corrections:null},{id:"73913",title:"New Technologies to Improve Surgical Outcome during Open-Cranial Vault Remodeling",doi:"10.5772/intechopen.94536",slug:"new-technologies-to-improve-surgical-outcome-during-open-cranial-vault-remodeling",totalDownloads:293,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Current approaches for the surgical correction of craniosynostosis are highly dependent on surgeon experience. Therefore, outcomes are often inadequate, causing suboptimal esthetic results. Novel methods for cranial shape analysis based on statistical shape models enable accurate and objective diagnosis from preoperative 3D photographs or computed tomography scans. Moreover, advanced algorithms are now available to calculate a reference cranial shape for each patient from a multi-atlas of healthy cases, and to determine the most optimal approach to restore normal calvarial shape. During surgery, multiple technologies are available to ensure accurate translation of the preoperative virtual plan into the operating room. Patient-specific cutting guides and templates can be designed and manufactured to assist during osteotomy and remodeling. Then, intraoperative navigation and augmented reality visualization can provide real-time guidance during the placement and fixation of the remodeled bone. Finally, 3D photography enables intraoperative surgical outcome evaluation and postoperative patient follow-up. This chapter summarizes recent literature on all these technologies, showing how their integration into the surgical workflow could increase reproducibility and reduce inter-surgeon variability in open cranial vault remodeling procedures.",signatures:"David García-Mato, Javier Pascau and Santiago Ochandiano",downloadPdfUrl:"/chapter/pdf-download/73913",previewPdfUrl:"/chapter/pdf-preview/73913",authors:[{id:"325305",title:"M.Sc.",name:"David",surname:"García-Mato",slug:"david-garcia-mato",fullName:"David García-Mato"},{id:"326845",title:"Prof.",name:"Javier",surname:"Pascau",slug:"javier-pascau",fullName:"Javier Pascau"},{id:"326861",title:"Dr.",name:"Santiago",surname:"Ochandiano",slug:"santiago-ochandiano",fullName:"Santiago Ochandiano"}],corrections:null},{id:"74024",title:"Craniofacial Corrective Surgery in Syndromic Craniosynostosis",doi:"10.5772/intechopen.94584",slug:"craniofacial-corrective-surgery-in-syndromic-craniosynostosis",totalDownloads:398,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This surgical field has now progressed and becoming an established subspecialty involving various surgical disciplines worldwide. Various complex CMF syndromes reported in syndromic craniosynostosis include Crouzon, Apert and Pfeiffer syndromes. These syndromes carry specific functional discrepancies associated with the affected structural anomaly and may therefore have functional issues involving the brain, eye and airway among others. As corrective surgery is often indicated depending on the affected vital functions, other factors that need to be considered are patient’s age, comorbidities, urgency, available expertise and patient’s overall prognosis based on the degree of anomaly. As such, the corrective surgery can be categorized into; (1) intermediate which is performed at an early phase and aimed to improve or salvage important vital functions such as the brain, eye, airway or feeding which are important for the child’s development and, (2) definitive treatment aimed at permanently correct the functional discrepancies. Intermediate corrective surgery may include invasive procedures such as ventriculo-peritoneal (VP) shunts, tarsorrhaphy, adenotonsillectomy and tracheostomy whereas definitive corrective surgery may include surgical procedures such as monobloc, Le Fort III osteotomy, posterior cranial vault expansion and mandibular advancement. This chapter will elaborate on the indications, types, challenges in the management and the proposed prevention measures in corrective surgery for specifically for syndromic craniosynostosis patients.",signatures:"Khairul Bariah Chi Adam, Firdaus Hariri, Wei Lee Chee, Kathiravan Purmal, Mohd Faizal Abdullah and Nazer Berahim",downloadPdfUrl:"/chapter/pdf-download/74024",previewPdfUrl:"/chapter/pdf-preview/74024",authors:[{id:"325940",title:"Assistant Prof.",name:"Khairul Bariah",surname:"Chi Adam",slug:"khairul-bariah-chi-adam",fullName:"Khairul Bariah Chi Adam"},{id:"326066",title:"Prof.",name:"Firdaus",surname:"Hariri",slug:"firdaus-hariri",fullName:"Firdaus Hariri"},{id:"326068",title:"Dr.",name:"Lee",surname:"Chee Wei",slug:"lee-chee-wei",fullName:"Lee Chee Wei"},{id:"326069",title:"Dr.",name:"Nazer",surname:"Berahim",slug:"nazer-berahim",fullName:"Nazer Berahim"},{id:"326070",title:"Dr.",name:"Kathiravan",surname:"Perumal",slug:"kathiravan-perumal",fullName:"Kathiravan Perumal"},{id:"326071",title:"Dr.",name:"Mohd Faizal",surname:"Abdullah",slug:"mohd-faizal-abdullah",fullName:"Mohd Faizal Abdullah"}],corrections:null},{id:"74419",title:"Telescoping with Multiple Revolution Cranial Osteotomies in Patients with Simple Craniosynostosis",doi:"10.5772/intechopen.94926",slug:"telescoping-with-multiple-revolution-cranial-osteotomies-in-patients-with-simple-craniosynostosis",totalDownloads:431,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Simple craniosynostosis is a cranial deformity that occurs secondary to a premature closure of one or more sutures, with a consequent alteration in cranial growth and cerebral expansion. The cranial alteration presents as flattening parallel to the compromised suture, with compensatory bulging in a perpendicular vector. The surgical treatment consists in cranial decompressions with suturectomies and simultaneous cranioplasties. Dynamic multiple revolution osteotomies allow the design of bone flaps that can help with decompression and correct secondary deformities caused by the synostosis. This multicenter descriptive case series study assessed 52 patients (12 plagiocephaly, 29 scaphocephaly, 7 brachycephaly and 4 trigonocephaly) operated in Cali, Colombia. In each case, suturectomy and telescoping with multiple revolution cranial osteotomies were designed to correct each particular deformity. No clinical complications were observed in the postoperative period (1, 90, and 180 days), and excellent outcomes with no re ossification of sutures and maintenance of the cranioplasty, based on clinical observation and findings in the 3D reconstruction scans.",signatures:"Diego José Caycedo, Marcela Cabal Castro and Luís Fernando Santacruz",downloadPdfUrl:"/chapter/pdf-download/74419",previewPdfUrl:"/chapter/pdf-preview/74419",authors:[{id:"326657",title:"Prof.",name:"Diego José",surname:"Caycedo",slug:"diego-jose-caycedo",fullName:"Diego José Caycedo"},{id:"326658",title:"Dr.",name:"Marcela",surname:"Cabal Castro",slug:"marcela-cabal-castro",fullName:"Marcela Cabal Castro"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"6508",title:"The Role of Transcranial Doppler Sonography in the Management of Pediatric Hydrocephalus",subtitle:null,isOpenForSubmission:!1,hash:"4fc5fd6bba9da6cb5271faac79e55df9",slug:"the-role-of-transcranial-doppler-sonography-in-the-management-of-pediatric-hydrocephalus",bookSignature:"Branislav Kolarovszki",coverURL:"https://cdn.intechopen.com/books/images_new/6508.jpg",editedByType:"Authored by",editors:[{id:"92436",title:"Associate Prof.",name:"Branislav",surname:"Kolarovszki",slug:"branislav-kolarovszki",fullName:"Branislav Kolarovszki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"3",chapterContentType:"chapter",authoredCaption:"Authored by"}},{type:"book",id:"2990",title:"Neonatal Bacterial Infection",subtitle:null,isOpenForSubmission:!1,hash:"093e4b7e0964b0fe0229a4b4cafef28c",slug:"neonatal-bacterial-infection",bookSignature:"Bernhard Resch",coverURL:"https://cdn.intechopen.com/books/images_new/2990.jpg",editedByType:"Edited by",editors:[{id:"66173",title:"Prof.",name:"Bernhard",surname:"Resch",slug:"bernhard-resch",fullName:"Bernhard Resch"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"741",title:"Neonatal Care",subtitle:null,isOpenForSubmission:!1,hash:"b0edbdb5d5b8c322337668b98822eb79",slug:"neonatal-care",bookSignature:"Deborah Raines and Zoe Iliodromiti",coverURL:"https://cdn.intechopen.com/books/images_new/741.jpg",editedByType:"Edited by",editors:[{id:"165631",title:"Dr.",name:"Zoe",surname:"Iliodromiti",slug:"zoe-iliodromiti",fullName:"Zoe Iliodromiti"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7527",title:"Neonatal Medicine",subtitle:null,isOpenForSubmission:!1,hash:"777de6ff63e03a7b9c8e443d8f06828c",slug:"neonatal-medicine",bookSignature:"Antonina I. 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\n
1. Introduction
\n
In the Greater Mekong Subregion (GMS)1, malaria is still a substantial public health problem, especially along international borders and forested areas, adversely putting populations such as migrants, refugees, and forest workers most at risk. In 2013, there were 447,800 malaria cases and 342 deaths in the GMS, with close to 700 million people living in risk areas [1]. Between 2012 and 2016, the reported number of malaria cases in the GMS fell by 74% (Figure 1) and malaria deaths by 91% in the same period (Figure 2).
\n
Figure 1.
Declining trends of malaria transmission in the Greater Mekong Subregion (GMS) since 2012 (source: [2]).
\n
Figure 2.
Declining trend of malaria deaths in the Greater Mekong Subregion (GMS) since 2012 (source: [2]).
\n
Mid-year estimates for 2017 point to a further decline in cases [2]. Contributing to these impressive results, all six countries of the Subregion are making significant headway towards a common target: eliminating malaria by the year 2030 at the latest.
\n
These goals will not be easy to achieve. Despite these reductions and the subsequent move towards elimination, malaria remains an important cause of morbidity for an estimated 32 million inhabitants, especially in remote areas with low population densities and limited healthcare services and infrastructure, located in and near forested areas, which often lie close to international borders [3, 4]. In many places, the population groups most affected are ethnic minorities and forest-goers who are rapidly becoming the most important source of transmission in areas where main vectors are present. Within these groups, cultural and linguistic barriers often constrain malaria control efforts due to their high mobility and low access to interventions to prevent, diagnose and treat malaria.
\n
In some areas the malaria situation has deteriorated by armed conflict affecting access to malaria control services. Population movements are a key feature in the GMS and are largely occupationally/economically driven; occur within borders and across borders; involve multiple factors and complex dynamics of movement; and affect different subsets of moving populations [5], thus further complicating the epidemiology and control of the disease [6]. The rapid increase in the number of large infrastructure and agricultural development projects in the region is also having a significant impact on the epidemiology of communicable diseases in general, and malaria in particular [7]. This chapter addresses several key challenges faced by elimination programmes to contain the unacceptably high disease burden against the background of rapidly declining incidence.
\n
\n
\n
2. Resistance to artemisinin and ACT: current and future approaches
\n
Antimalarial drug resistance is not a new biological phenomenon. In the 1970s and 1980s, Plasmodium falciparum—the parasite species responsible for the most common and deadliest form of malaria—developed widespread resistance to previous antimalarial medicines, such as chloroquine and sulfadoxine-pyrimethamine (SP) [8]. Artemisinin based combination therapies (ACTs), introduced in the 1990s, are currently the most effective antimalarial drugs [9] and represent the first line-treatment for uncomplicated falciparum malaria in all endemic countries.
\n
Although artemisinin usually kills all malaria parasites, the use of a combination of drugs—as opposed to monotherapy—helps ensure that any remaining parasites will be killed by the partner drug before the resistant parasites can spread. According to the World Health Organisation (WHO), clinical artemisinin (and its derivatives) resistance is defined as delayed parasite clearance and represents a partial/relative resistance that has thus far only affected ring-stage malaria parasites [10]. In Southeast Asia, however, some malaria parasites have already developed resistance to artemisinin-based drugs; a recent report of a single multidrug resistant malaria parasite lineage (PfPailin) with associated piperaquine resistance in Vietnam and its implications of subsequent transnational spread is of international concern [11]. Artemisinin resistance was first reported along the Thailand-Cambodia border in 2008 [12, 13] and has continued to spread in all Greater Mekong Subregion countries [14, 15, 16, 17, 18]. In addition, artemisinin resistance has been involved in selecting for resistance to ACT partner drugs, resulting in high late treatment failure rates with dihydroartemisinin-piperaquine in Cambodia [14, 19, 20, 21, 22, 23, 24, 25] and with artesunate-mefloquine on the Thai-Myanmar border [26].
\n
There are many factors that are thought to have contributed to the emergence and spread of artemisinin resistance in the GMS. One important factor is thought to be the use of oral artemisinin monotherapy (AMT) in place of WHO-recommended ACTs (as unregulated artemisinin or artesunate monotherapy has been available since mid-1970s in the region). In Myanmar, private healthcare facilities and healthcare providers who prioritize consumers’ demand instead of recommended practices were more likely to stock oral AMT [26, 27]. Malaria elimination strategies should include targeted interventions to effectively reach these outlets. Fortunately, a major achievement during the resistance containment (and more recently elimination) activities has ceased the use of artemisinin monotherapies. ACT watch methods are monitoring displacement of oral AMTs, a major objective of the resistance containment strategy [28], and data will feed into regional score cards such as the Asia Pacific Leaders Malaria Alliance Access to Quality Medicines Task Force and the World Health Organisation (WHO) Emergency Response to Artemisinin Resistance (ERAR), which are vested in supporting national programs in tracking progress towards halting the availability and use of oral AMTs [28]. In Southeast Asia, where malaria transmission is generally low and emergence of resistance has been documented in multiple independent locations [29]; containment programmes have been converted into elimination of P. falciparum strategies to ensure halting the spread of resistance entirely.
\n
Other contributing factors are the use of substandard and counterfeit anti-malarial drugs and the difficulty of controlling malaria within migrant and hard-to-reach populations [30]. Given the transnational nature of this problem, the establishment of effective mechanisms for cross-country surveillance, information exchange and coordinated action is also necessary. This includes reinforcing existing institutional frameworks for regional health cooperation, particularly the Association of Southeast Asian Nations, and their potential to support enhanced capacities and cooperation to address this challenge [31]. Lastly, selection pressure—genetic mutations of wild-type genes in the parasite render them insusceptible to antimalarial drug treatment—is also thought to be important. The use of antimalarial drugs in patients with parasites containing mutations can eliminate susceptible parasites but leave resistant mutants to survive and reproduce [32].
\n
More recently another potential contributing factor has been hypothesized. Given that there are parasite isolates that do not infect some Anopheles species, it is thought that artemisinin-resistant parasites are spreading so fast in Southeast Asia because they infect most or all native Anopheles species (e.g., Anopheles dirus and An. minimus), including African vector counterparts such as An. coluzzii (formerly Anopheles gambiae M form) [33]. The ability of artemisinin-resistant parasite clones to infect three highly genetically diverse vectors suggests that these resistant parasites have enhanced their transmission in the region and could effectively spread in sub-Saharan Africa, where most of the world’s malaria mortality, morbidity, and transmission occurs [33, 34].
\n
Since there are no equally effective alternative drugs to treat malaria, the spread of artemisinin resistance through India (Asia) to Africa and beyond could be a catastrophic setback to global efforts to control and eliminate the disease. Infection and mortality rates could dramatically increase in both regions, reversing the progress made towards malaria control and elimination efforts. The spread of artemisinin resistance would in turn expose the partner drugs in ACTs to greater selection pressure for the development of resistance and increased failure rates for the treatment of uncomplicated malaria. For severe malaria, the recent change in recommended treatment from quinine to artesunate [35] increased survival by 25%, and many endemic countries have adopted (or are adopting) this policy [36, 37]. Reverting back to quinine because of artemisinin resistance would also jeopardise all these gains achieved in the management of severe malaria.
\n
The spread of ACT resistance requires constant and comprehensive monitoring across regions. Continuous monitoring of drug resistance in malaria-endemic countries along with contributing factors is a key and will enable health authorities and practitioners to prevent drug resistance from spreading. WHO issues regular reports about the status of artemisinin resistance in malaria endemic countries [38], provides updates on the status of resistance to artemisinins and ACT, and maintains a network of sentinel sites performing therapeutic efficacy studies of first and second-line antimalarial drugs [38, 39].
\n
\n
\n
3. Targeting interventions in hard-to-reach population groups
\n
Although most of malaria endemic countries in Southeast Asia have incorporated malaria elimination goals in their national strategic plans, yet this region experiences high volume of population movement (both within and between countries) causing a great hindrance in achieving their elimination targets given the increased risk of importation of infection, spread of drug resistance, and challenges in providing healthcare services to mobile populations at higher risk of malaria [40, 41].
\n
It is the movement of populations that results in importation of new infections leading to a source of local transmission [42, 43]. Cross-border movement of populations has contributed to establishment of “hot-spots” of high transmission along international borders [44, 45], and spread of drug resistance [6], because mobile populations often experience delays in receiving diagnosis and treatment, have improper health-seeking behaviour or self-medicate [88], and are subject to lower levels of surveillance [41, 46, 47]. Population mobility in the GMS is strongly associated with shifting land use, including large rural infrastructure projects and agricultural industries that attract migrant labor and influence human-vector contact. With the recent Association of Southeast Asian Nations (ASEAN) Economic Community agreement, allowing free movement of goods, services and labor between ASEAN countries [48]; population movement is expected to rise even more in the coming years [6].
\n
In addition, the epidemiology of malaria in many parts of Southeast Asia is shifting toward migratory labor force that gets exposed to vectors in the forest, construction sites, and has variable access to healthcare services [46, 47, 49, 50, 51, 52, 53]. Since forested regions are concentrated along borders and much of the cross-border movement is from the migrant labor population, malaria prevalence in these pockets was hypothesized to represent foci of hot-spots. Following this rationale, the increased malaria risk in these groups was recently documented in a cross-border malaria project conducted in the Thai-Cambodian, Lao-Cambodia and Vietnam-Cambodian borders. In this study [45], it was observed that the odds of infection in security/armed forces and forest-goers was 8 and 13 times higher compared to low-risk occupations (e.g., teachers, traders, salesmen, etc.). Mechanisms and risk reduction strategies should be in place to appropriately cover these special occupational high-risk groups.
\n
Therefore, although population mobility is a key factor to take into account when addressing drug resistance, it suffers from a range of challenges that limit countries’ capacity to effectively engage and deliver interventions to migrant and mobile populations (MMPs). In addition, outdoor biting mosquitoes represent a major challenge for vector control for MMPs working during the night or sleeping outdoors, as well as forest-fringe communities.
\n
Another challenge is the large proportion of asymptomatic infections within geographical clusters of high malaria transmission (hot-spots), where infections with low and sub-microscopic parasite densities are highly prevalent in MMP and other risk groups [54]. Asymptomatic carriers can repeatedly fuel transmission to surrounding areas as the vector population expands during the wet season [55, 56, 57]. Whilst groups of homesteads consisting of asymptomatic carriers can act as stable clusters over several years [7], it is likely that the flight range of 800 m for An. dirus may account for increased probability of repeated mosquito feeding in the same house and clustering of cases over the dry season in Southeastern Thailand [58]. Recent clusters of malaria infection among the parasite reservoir responsible for preserving malaria over the dry season in Ratanakiri Province (northeastern Cambodia) may also explain recurrent transmission at the onset of the rainy season when the vector populations expand [59]. This reservoir is often not (completely) covered by control strategies [60] and parasite specific approaches are non-existent [61]. Programmatic interventions to interrupt transmission in “hidden” asymptomatic reservoir must focus on individuals with malaria infection at early stage, as asexual parasitemia left untreated will eventually produce gametocytes, and diagnostics for the sexual stage are limited [62].
\n
This represents an important hindrance to malaria elimination as these infections are unlikely to be detected by passive surveillance and conventional diagnostic tools, and therefore require additional approaches to effectively reach all infections [63]. A combination of methods, or new diagnostics, may be required to detect infections in these asymptomatic parasite reservoirs. Also, a cross-sectoral response, involving non-health government agencies and the private sector addressing the links between malaria transmission, mobility and labor, will play an important role in responding to drug resistance and achieving elimination in the Southeast Asia region. Preliminary studies of the use of peer outreach workers to conduct screening of suspected cases, providing health education, and distributing nets in hot-spot areas in or near the forest, suggest that it is feasible to target high-risk populations in a culturally appropriate and evidence-based manner to reach the goal of elimination in Pursat Province, Cambodia [64]. Mobile Malaria Workers or peer outreach activities often face logistic challenges including muddy roads, river crossings, and transportation difficulties that make it hard to quickly respond to all infections. The recent President Malaria Initiative (PMI) studies show this is a potential resource that can be piloted or replicated across GMS countries (John Hustedt, personal communication).
\n
Lastly, persisting low health-care coverage and access in remote locations remains an important challenge for mobile populations and migrant workers in some Southeast Asian countries, limiting the ability of malaria programmes to effectively capture these groups through the routine surveillance system, but most importantly to adequately provide the necessary preventive measures and care needed [65]. It is encouraging, however, to see that malaria infection rates in people who had sought treatment, or blood-smear examined in a previous malaria episode, and/or who knew how to prevent malaria (e.g., sleeping under a mosquito net), tend to be lower than those that did not seek treatment or had inadequate malaria knowledge [45]. This highlights the importance of scaling up and expanding the reach of point of access care and dissemination of information, such as through border posts or at large development or construction areas that are likely to host high-risk malaria occupational groups. These posts can potentially be used as effective channels to target and deliver specific interventions such as Behavioral Change Communication (BCC) materials, insecticide-treated uniforms or hammock nets.
\n
Therefore, there is an urgent need to develop appropriate and sustainable malaria services for MMPs in different settings, in the context of the spread of artemisinin resistance and malaria elimination in the GMS. Different types of mobility require different malaria control interventions and therefore elimination strategies that should be based on an in-depth understanding of malaria risk in each group [66]. A population movement framework can assist in improved targeting of malaria (and other public health interventions) by going beyond a simple labeling of risk groups to develop a better understanding of risk behaviour and vulnerabilities. The implementation of the framework should be carefully evaluated to identify the changes in coverage, access, and effectiveness of the programme efforts to serve MMPs [67].
\n
\n
\n
4. Residual and outdoor transmission: how much and where?
\n
In 2012, global malaria transmission was reported as mainly attributable to 51 Anopheles species, with an average of about 3 major species per country [68]. Biological factors that determine whether a species becomes a major local threat are its competence for transmitting human malaria parasites, its anthropophilic versus zoophilic preference, and its abundance in relation to its ability to multiply, survive, and compete for resources with other Anopheles species. The third of these factors is regulated by the ecosystem’s carrying capacity for potent vectors depending on their ecological niches [69]. Species of several Anopheles complexes are either major or secondary malaria vectors depending on their geographical range of distribution [70]. The peculiarity of these sibling species within a complex is that they cannot be distinguished using morphological criteria. However, several Asian malaria vectors within the Dirus, Leucosphyrus, Minimus, Maculatus, Culicifacies, Sundaicus, Subpictus complexes or groups show similar morphological characteristics, different ecological traits and vector competencies and overlapping geographical distribution with other vectors and non-vectors [70, 85, 92]. As some of these sibling species occur sympatrically and differ in their ability to transmit malaria and in their behaviour, the use of molecular tools to differentiate the vectors from the non-vectors is essential to target the correct species in vector control programs.
\n
Malaria vector control relies largely on Long-Lasting Insecticidal Nets (LLINs) and Indoor Residual Spraying (IRS), along with Larval Source Management (LSM) as a supplementary measure appropriate in certain settings. These core interventions are highly efficacious for control of susceptible malaria vectors when implemented at universal coverage; LLINs and IRS contributed to a 48% reduction in malaria infection prevalence and 47% reduction in mortality worldwide between 2000 and 2013 [71]. However, malaria transmission can persist even when LLINs and/or IRS are effectively implemented and malaria vectors are susceptible to the insecticides used. This may be due to a combination of vector and human behaviour and bionomical characteristics, which compromise inadequate control measures against early and/or outdoor biting mosquitoes, and human activity away from protected houses or places at peak biting times. With current efforts focusing on malaria elimination [72], there is considerable interest in vector behaviour that is not influenced by application of core interventions (i.e., conventional IRS and Insecticide Treated Nets (ITNs)), such as feeding earlier and resting outdoors when humans are not protected. For example, an unprecedented malaria outbreak, related to illegal rosewood logging, occurred in 2014 with a seven-fold increase of cases in 1 year in Ubon Ratchathani Province, Northeastern Thailand [73]. Insecticide-susceptible and exophilic An. dirus s.l. were collected from a forested area in Ban Pakla and Chong Ta Ou Thai border control station, including An. maculatus s.l. collected remote villages with potentially low insecticide pressure [73]. These susceptible vector species are less amenable to control interventions due to their behaviour and their interactions with humans contribute to persistent residual transmission and represent barrier to success [74, 75].
\n
From a geographical perspective, residual malaria parasite transmission has been reported across numerous transmission settings, even with good access and usage of LLINs or well-implemented IRS [76, 77, 78, 79, 80]. From the programmatic perspective, residual malaria transmission (RMT) is defined as the persistent malaria transmission that occurs once universal coverage of LLINs and maximal coverage of IRS have been achieved. Identification and elucidation of RMT requires the following pre-conditions: (a) comprehensive and up-to-date LLIN and IRS coverage data, where coverage is defined as 100% access and usage of ITN/LLIN or IRS [81]; (b) outdoor human activity or behaviour to allow identification of outdoor sites and “gaps” in protection, not only before sleeping time, but also for people that remain outdoors during the night. In many countries of the GMS, LLIN and IRS distribution data are sparse or not readily available. Where these data are available, it is often compiled at a relatively high administrative level, such as district or province. Malaria transmission at the community level can vary considerably within a small area and thus to investigate RMT at this level, LLIN and IRS coverage data by village are necessary. Furthermore, LLIN coverage figures quoted at the province or district level often do not match the actual situation at the community level, perhaps due to inequities in distribution, inaccurate population estimates, and calculation of procurement need, limited replacement of outdated and damaged LLIN; the outcome of which could lead to an underestimation of the magnitude of RMT.
\n
As malaria is becoming more and more restricted to hard-to-reach population groups, alternative or adapted control strategies are required who are somehow marginalised, poor, on the fringes of the public health system, living in dwellings that are either very close to the forest or harbour people who are exposed to the forest through their occupation (e.g., development sites and seasonal labour areas) or mobility behaviour. As shown in Table 1, the risk of RMT in the malaria foci is spread over the entire night, from dusk-to-dawn, requiring a combination of complementary vector control measures, such as long-lasting insecticide hammock nets (LLIHN) that can be used during different periods of the night. However, the use of LLIHN, single LLIN/ITN or topical repellents in the field may not be acceptable due to cultural and linguistic barriers of ethnic minorities and MMPs for which specific acceptability studies should be conducted to guide the feasibility of these vector control tools.
\n
\n
\n
\n
\n
\n
\n
\n\n
\n
District, province, country
\n
Ecotype
\n
% Access to LLIN
\n
% Use of LLIN
\n
Proportion of Anopheles bites or infective bites in relation to sleeping time
Another driver of RMT is mega and micro-development projects impacting the forest or creating new conditions suitable for vector species, and often attracting a substantial workforce from various horizons across borders and cultural boundaries [6]. Their sleeping or residential places can have additional vulnerabilities if they are remote, comprising mainly ethnic minorities, or in conflict areas, all of which can hinder access to the public health system. Another key concern is to restrict or mitigate the widespread dispersal of parasites by these elusive population groups.
\n
Just as forest workers often stay in the forests for several days and sleep exposed to vectors [84], rubber tappers also work in plantations at night with higher likelihoods of being bitten by Anopheles mosquitoes, in particular vector species of the Dirus Complex [3, 85]; they all have poor access to healthcare services [86]. Plantation work is seasonal, and manpower is often composed of highly mobile seasonal migrants, but little is known about their patterns of movement. More malaria infections were observed in people with temporary labour positions and plantation workers at the Thailand-Myanmar border [87], but this was not confirmed due to a very high proportion of the study participants opting to perform forest or field activities, and a very low number opting to work in rubber plantation [59]. Many migrants that arrive for rubber tapping settle beyond the harvest season [87] and go on to work on other cash crops (e.g., rice, cassava, fruit orchards). On return to their usual settlements, they contribute to the spread of malaria within and across international borders [41, 43]. By creating hot-spots of malaria and disproportionately affecting people with certain high-risk occupations [86, 89], residual transmission under these circumstances has so far hindered progress towards elimination.
\n
\n
\n
5. Correct identification of malaria vectors and Plasmodium detection
\n
High levels of malaria transmission occurring in forest-fringe areas of Southeast Asia is explained by movements of people in search of forest products and exposure to many highly efficient vector species that have adapted to forest ecotypes [66, 85, 102, 103]. The wide diversity of both the deep-forest (e.g., Leucosphyrus Group of mosquitoes), forest-fringe and deforested area main vectors (e.g., An. minimus, An. maculatus s.l., An. culicifacies s.l., An. fluviatilis s.l., An. letifer, An. donaldi), as well as their great potential to adapt to habitat changes, means that the consequences of deforestation on malaria transmission in Southeast Asia are difficult to predict and unlikely to be unidirectional [104]. Whilst An. dirus and An. baimaii, main vectors of the Dirus complex, can find tree-crop plantations suitable for breeding, a close association between malaria and rubber plantations has been demonstrated [4, 105, 106, 107, 108], contributing to high larval and pupal density during the rainy season [90, 91] and low numbers during the cool-dry season [92, 109], or provide conditions that are similar to this vector’s natural habitat [110]. This ecological adaptation in human settlements and shaded plantations contributes to outdoor transmission among rubber tappers.
\n
The identification of secondary or incidental vector species poses new challenges as shown by mixed results of sporozoite-positivity using nested Polymerase chain reaction (PCR) and routine circumsporozoite enzyme-linked immunosorbent assay (CSP-ELISA) (Table 2). Confirmation of all positive CSP-ELISA results by a second CSP-ELISA test on the heated ELISA lysate, especially in zoophilic species showed a relatively high proportion of false positives (40%) [93]. On the other hand, PCR analysis of Deoxyribonucleic acid (DNA) extracted from the head and thorax alone, along with sequence data, revealed five Anopheles species (An. hyrcanus, An. barbirostris s.s., An. barbirostris clade III, An. nivipes, and An. peditaeniatus) infected with Plasmodium falciparum, which are not considered major vectors in the GMS [94]. Similarly, out of 11 P. falciparum CSP positive samples from Bangladesh, seven turned out to be positive by PCR suggesting that An. maculatus, An. jeyporiensis and An. nivipes play important roles in malaria transmission in Kuhalong District [95]. In Vietnam, the role of a secondary vector, An. pampanai infected with P. vivax, was also reported in the Binh Phuoc Province [96]. Morphological mis-identification of the closely related sympatric species, such as An. aconitus, An. pampanai and An. varuna are common [99, 100]. Morphological identification of Anopheles specimens prior to PCR assays allows them to be sort out at the group or complex level but does not permit species identification [85]. PCR assays must be applied for a reliable identification to the species level, which ensures that data received by malaria vector control programmes are suitable for targeting the correct vector species [101]. Given the low infection rates among many of these species especially in elimination phase, it is important for field entomologists to assess various species’ role in malaria transmission in the eco-epidemiological context. When changing objectives from control to elimination of malaria in Southeast Asia, the need to focus not only in the so-called main vector species, but also on secondary vectors is increasingly important.
Prior heating of eluate and circumsporozoite ELISA, Bangladesh [98]
\n
PCR confirmation of ELISA-positives Bangladesh [95]
\n
\n
\n
Total collection (%)
\n
Positive/total
\n
Total collection (%)
\n
Positive /total
\n
Total collection (%)
\n
Positive /total
\n
Total collection (%)
\n
Positive /total
\n
\n\n\n
\n
An. maculatus s.l
\n
\n
\n
21.43
\n
4/640
\n
\n
\n
4.3
\n
2/97
\n
\n
\n
An. annularis s.l.
\n
\n
\n
14.43
\n
3/431
\n
0.78
\n
1/19
\n
\n
\n
\n
\n
An. kochi
\n
\n
\n
\n
\n
0.93
\n
1/44
\n
\n
\n
\n
\n
An. barbirostris s.s.
\n
6.6
\n
3/55
\n
3.52
\n
1/105
\n
2.9
\n
1/140
\n
7.4
\n
1/186
\n
\n
\n
An. peditaeniatus
\n
\n
\n
\n
\n
5.08
\n
3/139
\n
\n
\n
\n
\n
An. hyrcanus
\n
0.09
\n
2/2
\n
\n
\n
\n
\n
\n
\n
\n
\n
An. nigerrimus
\n
0.87
\n
1/21
\n
\n
\n
\n
\n
4.1
\n
1/104
\n
\n
\n
An. philippinensis
\n
\n
3/219
\n
\n
\n
24.7
\n
25/1169
\n
\n
\n
\n
\n
An. vagus
\n
\n
\n
\n
\n
41.9
\n
25/1978
\n
\n
\n
\n
\n
An. nivipes
\n
\n
\n
\n
\n
\n
\n
10.8
\n
1/264
\n
\n
\n
An. jeyporiensis
\n
\n
\n
\n
\n
3.1
\n
1/142
\n
18.9
\n
2/479
\n
\n
\n
An. karwari
\n
\n
\n
\n
\n
5.16
\n
11/244
\n
1.7
\n
\n
\n\n
Table 2.
Sporozoite infectivity rates of less known (secondary) vectors along the Bangladesh-Thailand-Cambodia corridor.
Molecular identification was specifically conducted on Anopheles barbirostris s.s. and An. barbirostris clade III; An. hyrcanus and An. hyrcanus s.s; An. peditaeniatus and An. nivipes, and morphological identification for the other Anopheles species.
\n
Deforestation may deplete the populations of deep-forest vectors and so initially reduce malaria transmission; in some localities this depletion may be followed by the invasion of other efficient vector species resulting in increased transmission. With the exception of two longitudinal studies examining the effects of progressive land use changes from pre-development forest to oil palm cultivation on the distribution of disease vectors and malaria incidence [111], there is a striking lack of primary research directly measuring the impact of deforestation on malaria in Southeast Asia [104]. Recent studies showed that An. dirus s.l. was abundant in rubber plantations in Myanmar [109] and An. baimaii (molecularly identified) adults were caught from human landing collections in Wae Kha Mi, Mon State, the site of an acceptability study of permethrin-treated clothing [110]. In Lao PDR, a total of 46 An. dirus s.l. were collected, of which 31 were from immature rubber plantations, nine from mature rubber plantations, five from secondary forests and one from the rural village [105] (Tangena Julie-Ann, personal communication).
\n
\n
\n
6. Plasmodium knowlesi: an additional challenge to malaria elimination
\n
Plasmodium knowlesi, a simian malaria parasite, is now considered the 5th parasite affecting humans [112]. All countries in Southeast Asia have reported cases of P. knowlesi with the exception of Lao PDR and Timor Leste [113]. Since most countries are now working towards malaria elimination, it is pertinent to pay serious attention to malaria cases especially in areas where malaria has been reduced to very low levels. A good example is Sabah, Malaysian Borneo where large numbers of P. knowlesi were diagnosed in areas where P. falciparum and P. vivax were occurring in very low numbers [114]. Malaysia is working towards malaria elimination by 2020 and currently more than 60% of the malaria cases are due to P. knowlesi (MOH personal communication).
\n
Recently, an increasing number of cases of P. knowlesi were reported from Kalimantan and Ache in Indonesia [115, 116] where malaria was in process of being eliminated. In Northern Sumatra, Indonesia where they are working towards malaria elimination, they recorded only 614 (16.5%) positive malaria cases by microscopy out of 3731 people examined [117]. However, PCR detected malaria parasites in 1169 (31.3%) individuals. Of these, 74.9% were mono-infection and 25.1% were multiple infection. P. falciparum constituted 24.8%, P. vivax 33.9%, P. malariae 9.3%, and P. knowlesi 32% [114] of the cases. It was also found that the primers developed from the SICAvar gene were more sensitive than the SSU rRNA gene [117]. It is obvious that parasite species are being mis-identified and many people who are asymptomatic are also missed by conventional microscopy [117, 118]. Thus, it is important to develop Rapid Diagnostic Tests (RDTs) that can be used by field workers to detect accurately malaria parasite species, especially P. knowlesi, and also additional laboratories should be established to conduct molecular assays for malaria diagnosis in the context of malaria elimination.
\n
Deforestation and changes in the environment are the key factors leading to a surge of P. knowlesi malaria [119]. This parasite occurs in Macaca fascicularis (long-tailed) and Macaca nemestrina (pig-tailed) monkeys and its distribution is limited by some species of the Leucosphyrus Group of Anopheles mosquitoes [120]. These species are found biting in greater abundance in forest and farms compared to villages [121, 122]. However, in Sabah, Malaysian Borneo, it was found that An. balabacensis was abundant in villages as well [123], and sporozoite-positive specimens were reported in addition to farms and forest [123], while infective mosquitoes were found only in the forested sites and farms in Sarawak (Borneo) and Pahang (Peninsular), Malaysia [121, 122]. In addition, vector studies have also been conducted in Vietnam [124, 125] where the species An. dirus has been incriminated as the simian malaria vector in Khanh Phu—South Central Vietnam. Studies were conducted in the forest and forest-fringe areas near Nga Hai village where both human malaria parasites, P. falciparum and P. vivax, were found along with P. knowlesi in order to determine the potential role of An. dirus as bridge vectors of Plasmodium parasites from monkeys to humans [126]. Based on these studies, it was possible for An. dirus to pick up infection from humans and macaques during the mosquito’s lifespan. However, since there have been no reports of epidemics of P. knowlesi, it is believed that humans are infected by mosquitoes which acquired infection from the macaques. Perhaps even likely given that confirmed vectors of human plasmodia in Southeast Asia also become naturally infected by the monkey malaria species [127]. A recent case control study conducted in Sabah revealed that the age group >15, predominantly males, working in farms, plantations, forested areas, and with travel history, were independently associated with the risk of acquiring knowlesi malaria [128]. It also highlighted that IRS was associated with decrease of risk [128].
\n
There are only few investigations on record in understanding bionomics of vectors transmitting P. knowlesi malaria. In order to implement vector control activities, the bionomics of the vectors must be understood. Based on few studies, it has been shown that the vectors are biting in the early part of the night from 18:00 h to 21:00 h and mostly outdoors [121, 122, 123, 129]. In these rural areas, people go to bed by 22:00 h and they are up by 05:00 h. The results showed that only 39.79% of An. balabacensis [123], 43.8% of An. latens [121] and 12.8% of An. cracens [122] were found biting during this sleeping time. Thus, current vector control measures like IRS and ITNs are not appropriate for the exophagic and exophilic vectors. The forests in Southeast Asia is providing a favorable environment with high percentage of macaques being positive for P. knowlesi [130, 131, 132], and with the presence of the vectors, it is going to be a daunting task to eliminate malaria. On a global scale, malaria has been reduced to low levels due to the scaling up of ITNs, IRS, ACTs, and intermittent preventive treatment to infants and pregnant women [133]. Thus, it is obvious that new tools are urgently required for successful malaria elimination.
\n
It is known that the two human malaria species (P. falciparum and P. vivax), which infects millions of people actually were of zoonotic origin (from the African apes), which evolved thousands of years ago [134, 135]. Thus, there is always a possibility that in the future P. knowlesi and other simian malarias may become established in humans, especially when human malaria is eliminated. However, currently human-to-human transmission of knowlesi malaria by mosquitoes has not been established. This is crucial in the light of malaria elimination and more focused research is needed on this topic if we are to succeed with malaria elimination.
\n
Changing landscape affects Anopheles distribution, mosquito density and diversity in Malaysia, and more globally Southeast Asia [105, 111, 136, 137, 138]. It has been shown that with loss of forest cover, cases of P. knowlesi have increased in Sabah [119]. Land use change has also led to increase of malaria cases due to various factors such as increase of macaques in small forest patches along with the colonization of the main vectors [119, 136]. It is interesting to note that An. balabacensis, the predominant vector of human and simian malaria, was found in great abundance in logged forest, followed by thinly logged virgin jungle reserve and was lowest in primary forest [136]. This vector was also found to be biting humans more at ground level compared to canopy level [136]. It is therefore important to include both the public health and agro-forestry sectors in controlling malaria vectors in the country. Studies from Thailand also indicate that if landscape management should be used for malaria control in northern Thailand, large-scale reduction and fragmentation of forest cover would be needed [139, 140]. Such drastic actions, however, do not align with current global objectives concerning forest and biodiversity conservation.
\n
The vectors of simian malaria described to date were An. hackeri (Leucosphyrus Group) [141] recorded biting mainly the macaques and large numbers were collected resting on Nipah palm trees in Selangor in 1960s; An. cracens (Dirus Complex) [122] biting both macaques and humans and found mainly in the forest and farms; An. latens (Leucosphyrus Complex) [121] was the predominant mosquito in the forest compared to farm and village, and was biting macaques at ground level and at six meters in the canopy compared to three meters. The biting ratio of monkey versus human for An. latens was 1:1.3 [121]. An. introlatus (Leucosphyrus Complex) [142]was biting in the early part of the night from 19:00 h to 21:00 h and was the predominant mosquito in Hulu Selangor where cases of P. knowlesi were reported. Most recently, An. balabacensis (Leucosphyrus Complex) has been incriminated as vector of P. knowlesi in Sabah [123], as well as human malaria and Bancroftian lymphatic filariasis due to Wuchereria bancrofti [143, 144, 145].
\n
Although an increased number of countries are successfully eliminating human malaria in recent years, no country has yet eliminated non-human malaria, which adds another layer of complexity to be addressed. The complex situation of malaria is Southeast Asia is very unique from the rest of the tropical countries. More effort is needed to study the host switching mechanisms between the parasites in humans, macaques and vectors. A series of review papers have been published over the years and all these have indicated the importance of addressing the problem caused by P. knowlesi, if malaria elimination is to be successful in the region [113, 146, 147, 148, 149, 150, 151].
\n
\n
\n
7. Targeting vivax malaria: a bottleneck to malaria elimination
\n
As opposed to P. falciparum infection, which does not have latency (dormant), P. vivax causes two distinct infection syndromes, one that actively proliferates and the other latent due to hypnozoites. Each of these P. vivax forms requires distinct therapeutic treatments and the latent form cannot be diagnosed [152]. Most acute attacks of P. vivax in endemic areas originate from hypnozoites, and unless that reservoir is aggressively attacked, elimination of transmission may be an unrealistic goal.
\n
Treatment of latent vivax represents an important challenge as the only known therapies are 8-aminoquinoline drugs, which results in acute hemolytic anemia in patients deficient in glucose-6-phosphate dehydrogenase (G6PD)—a highly polymorphic inherited disorder affecting 1–30% of residents of malaria-endemic nations [153]. The single low dose of primaquine against gametocytes of P. falciparum does not threaten the G6PD deficient subjects [154]. Another challenge is that the parasitemia of vivax malaria patients is typically an order of magnitude lower than falciparum malaria, causing larger proportions of parasitemia to fall below diagnostics detection thresholds [152]. In addition, vivax malaria patients may exhibit very low parasitemia, and yet become severely ill. These fundamental distinctions between the two dominant human malarias explain why P. vivax is relatively unaffected by interventions tailored to control P. falciparum calling for new strategies needed for combatting vivax malaria [155].
\n
In addition, P. vivax has the ability to develop at lower temperature than P. falciparum and has a shorter sporogonic cycle in the vector, which results in P. vivax extending beyond tropical climates into temperate regions. This ability, combined with its early-biting, outdoor-feeding and outdoor-resting behavior of vector mosquito species, also makes them less susceptible to vector control measures such as IRS, which have proven effective against transmission of P. falciparum [156]. Also having dormant forms in the liver (hypnozoites) mean that one successful infection will generate a number of parasitological and clinical episodes without reinfection. Therefore, recurrent cases cannot be prevented via vector control, though, paradoxically, successful transmission control of vivax malaria could reduce the disease burden more than that of P. falciparum, because avoiding one infection will result in preventing a number of clinical episodes over several years [155].
\n
Vivax malaria is diagnosed late, because infected people get ill with low parasite densities, which cannot be detected with current diagnostics, such as RDTs and microscopy. Delayed diagnosis means not only delayed treatment (hence prolonged morbidity, especially anemia) but also ability to transmit over an extended period. This is further amplified by the fact that mature gametocytes appear simultaneously with asexual forms—hence transmission occurs before diagnosis and treatment [157, 158].
\n
As recently described [156], an effective P. vivax control and elimination toolbox should include:
Practical point-of-care G6PD deficiency diagnostics allowing wider access to safe primaquine therapy or with tafenoquine—a related single dose hypnozoitocide recently developed by GSK and Medicines for Malaria Venture (MMV); the latter has been submitted to the United States Food and Drug Administration (FDA) seeking approval of single-dose tafenoquine for the radical cure (prevention of relapse) of vivax malaria in patients 16 years of age and older [159];
More sensitive point-of-care diagnostics for detecting intrinsically lower parasitemia, including sub-patent and asymptomatic infections;
Validated strategies for relapse prevention in special population groups, i.e., pregnant women, young infants, G6PD deficient and G6PD unknowns in which 8-aminoquinoline is contraindicated;
Clinical care algorithms acknowledging risk of severe and threatening syndromes despite seemingly non-threatening levels of parasitemia; and
Interventions of proven efficacy to minimize human contact with often zoophilic, exophagic and exophilic Anopheles species of great diversity.
\n
In conclusion, the malaria community needs to address these challenges and create a viable strategy to achieve vivax elimination goals, providing novel solutions for overcoming critical bottlenecks. This process needs to begin now to enhance treatment practice for 8-aminoquinoline drugs based radical cure. Highlighting the benefits of radical cure for the patient and community will improve prescription practice and patient adherence [160]. Coupling this with improved access to adequate G6PD testing will pave the way for the introduction of tafenoquine, with huge potential to accelerate the elimination of P. vivax.
\n
\n
\n
8. Socio-ecological and adaptive management of malaria ecosystem in areas approaching malaria elimination
\n
WHO has recently proposed sustainable prevention and control of diseases emerging within complex, dynamic, adaptive systems, such as malaria, based on interdisciplinary and approaches addressing environmental and social health determinants holistically [161]. More insights into transmission dynamics and the possibility of intersectoral ecosystem management programs for malaria elimination and control are urgently needed. An ecosystem approach to successful reduction of vector-borne disease burden [162, 163] can lead to considerable health gains [Available at: http://www.maweb.org/documents/document.317.aspx.pdf].
\n
Once local entomological inoculation rates (EIRs) have been reduced to a level of unstable transmission the infectious reservoir can be eliminated via several approaches without a threat of malaria re-emergence from reintroduction of parasites. At this point, use of time-limited mass drug administrations (MDA) campaign at high coverage should be sufficient to effectively clear the majority of remaining P. falciparum cases, and may be considered for epidemic control as part of the initial response, along with the urgent introduction of other interventions [164]. This can be supplemented by screening and treatment programmes based on WHO Global Malaria Programme’s T3: Test, Treat, Track initiative supporting malaria-endemic countries in their efforts to achieve universal coverage with diagnostic testing and antimalarial treatment, as well as in strengthening their malaria surveillance system [WHO T3: Test, Treat, Track. Scaling up diagnostic testing, treatment and surveillance for malaria. World Health Organisation; 2012. http://www.who.int/malaria/publications/atoz/t3_brochure/en/]. Healthcare workers or locally trained and supervised community volunteer networks can apply this method to effectively limit reintroduction of parasites from other areas to a minimum, and apply additional active case management, e.g., the systematic detection and treatment of parasitemia using highly sensitive RDTs can reduce the risk attributed to any unscreened or asymptomatic cases.
\n
Depending on the local situations, supplementary measures, in addition to LLINs or IRS, such as repellents or treated clothing for high-risk individuals, offer special precautionary preventive protection [1, 110, 165, 166]. Passive case management should suffice for treating any symptomatic infections as they may occur. This, however, assumes at least a periodic provision of health services at all locations, including remote ones. A transdisciplinary approach integrates different scientific perspectives [167, 168] and provides a formal platform for stakeholder participation in the research and development of new information, ideas and strategies, their testing and eventual application.
\n
Participatory approaches that engage local communities in a complex social-ecological mapping process are a vital starting point for identifying community-applicable solutions and leveraging community capacity for local interventions [169, 170] and promoting integrative and equitable collaboration within partnership of researchers and communities [170, 171]. Ownership of continuous surveillance, monitoring, treatment and preventive efforts should be transferred to members of local communities, assuming collective responsibility for their continuous well-being.
\n
\n
\n
9. Conclusions
\n
This review attempts to consolidate the challenges of operational research for innovations in designing interventions [172], according to the current situation and progress made, for achieving malaria elimination in Southeast Asia. As the entry of artemisinin resistant parasites to India could be the first step in their spread to Africa, the current priority must be to address this problem in Southeast Asia before it can become a threat in Africa. Continuous monitoring of drug resistance in conjunction with analysis and proper interpretation is critical to guide the appropriate action for effective treatment. While P. falciparum elimination in the GMS is realistic, feasible and particularly urgent in the context of drug resistance, the main challenges are to ensure community participation and plan for the preservation of ACT potency so that the dosing regimens and surveillance for resistance are rigorously pursued to sustain their efficacy for as long as possible [172].
\n
We support a priority focus on MMP and other high-risk groups to contain the spread of artemisinin resistance and new hot-spots, however, implementation challenges should be considered when planning future interventions. More efforts are needed in documenting the malaria risk among different types of MMPs, innovative tools and interventions, as well as designing implementation in a way that can be evaluated, lessons learned, and programmes adapted in an on-going process [172]. New ways of evaluating MMP interventions (including highly sensitive RDTs) are needed, as routine health information systems have limitations and might not allow capturing the information and data needed, and existing type of surveys might not be sufficient for monitoring interventions for MMP.
\n
Malaria programmes need to heed the recent revised WHO recommendations for achieving universal coverage with LLINs or IRS for populations at risk [173]. The coverage of key interventions is critically low in some countries and sub-optimal in most others, threatening progress across the region as a whole [174]. Malaria programmes are encouraged to evaluate the magnitude (and drivers) of the residual transmission in their country, regarding both mosquito and human behavior. This information will provide a boost for industry and academic partners to develop new vector control methods and paradigms for outdoor and residual transmission.
\n
The current precarious funding situation could undermine elimination efforts and result in a resurgence of disease. The threat posed to regional and global malaria control and elimination efforts by artemisinin resistant P. falciparum parasites is imminent and potentially severe. In many Asian countries, operational feasibility of P. vivax elimination is lower than that for P. falciparum [27]. Therefore, creating a viable strategy to achieve vivax elimination goals should include improvements in access to safe treatment to 8-aminoquinoline drugs based radical cure together with improved access to adequate G6PD testing in P. vivax endemic countries.
\n
Whilst human P. knowlesi is still largely a zoonosis, all indications suggest that human-to human transmission can take place, and probably is taking place in some situations [175]. More research is required to substantiate the body of evidence for human-to-human transmission, laboratory diagnosis and clinical management, and mapping vectors of P. knowlesi and environmental risk factors.
\n
The challenge for elimination programmes is dealing with dynamic, social-ecological systems for which an entirely different kind of thinking and scientific framework is required. The retooling for this next phase is more challenging this time since it requires malaria experts and managers to understand complex systems, thinking and practices. This thinking and actions are more or less contrary to conventional understandings of disease control, which tend to be top down and not guided by concepts like resilience and adaptive management developed as part of so-called ecosystem approach/management.
\n
\n
Acknowledgments
\n
The authors would like to specifically thank Sergio Lopes and Allan Schapira for their comments and inputs to the manuscript. We thank Irwin Chavez for supporting EndNote citations and references. The authors thank WHO for approval to reproduce Figures 1 and 2 taken from [2]. Data for Thailand and Vietnam in Table 1 was supported by the Special Programme for Research and Training in Tropical Diseases (TDR), in partnership with the Global Malaria Programme of the World Health Organisation (WHO) to develop multi-country, multi-institutional research on Investigation of the magnitude and causes of residual malaria parasite transmission in selected settings.
\n
Conflict of interest
All authors declare no conflict of interest related to the writing of this chapter.
List of acronyms
ACT
Artemisinin-based combination therapy
AMT
Artemisinin monotherapy
ASEAN
Association of Southeast Asian nations
BCC
Behavioral change communication
DNA
Deoxyribonucleic acid
CSP
Circumsporozoite
EIR
Entomological inoculation rate
ELISA
Enzyme-linked immunosorbent assay
ERAR
Emergency response to artemisinin resistance
FDA
Food and drug administration
G6PD
Glucose-6-phosphate dehydrogenase
GMS
Greater Mekong Subregion
IRS
Indoor residual spraying
ITN
Insecticide treated nets
LLIN
Long lasting insecticidal nets
LLIHN
Long lasting insecticidal hammock nets
LSM
Larval source management
MDA
Mass drug administration
MMP
Mobile and migrant populations
MMV
Medicines for malaria venture
MOH
Ministry of Health
PCR
Polymerase chain reaction
PMI
President Malaria Initiative
RDT
Rapid diagnostic test
RMT
Residual malaria transmission
SES
Socio-ecological system
SP
Sulfadoxine-pyrimethamine
WHO
World Health Organisation
\n',keywords:"malaria, elimination, Greater Mekong Subregion, drug-resistance, Plasmodium knowlesi, vivax malaria, residual transmission",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/61329.pdf",chapterXML:"https://mts.intechopen.com/source/xml/61329.xml",downloadPdfUrl:"/chapter/pdf-download/61329",previewPdfUrl:"/chapter/pdf-preview/61329",totalDownloads:1249,totalViews:385,totalCrossrefCites:2,totalDimensionsCites:12,totalAltmetricsMentions:0,impactScore:8,impactScorePercentile:97,impactScoreQuartile:4,hasAltmetrics:0,dateSubmitted:"June 20th 2017",dateReviewed:"March 30th 2018",datePrePublished:null,datePublished:"July 18th 2018",dateFinished:"May 9th 2018",readingETA:"0",abstract:"In recent years malaria initiatives have increasingly shifted from malaria control to a focus on achieving malaria elimination in the Southeast Asia region. However, this region experiences unique challenges in this transition due to its distinctive malaria ecosystem (mainly related to forests) and high volume of population movement (both within and between countries). These bioenvironmental factors increase the exposure of populations at higher risk due to their close association with forest, and contributes to outdoor and residual transmission. Given that this region has also historically been the source of resistance to anti-malarial drugs, the potential spread of artemisinin resistance via global transportation routes would pose a major threat to malaria control and elimination efforts worldwide. In addition, other factors also hinder the malaria elimination goal such as importation of parasite infection, uncontrolled monkey malaria (Plasmodium knowlesi), or the fact that many countries in this region experience mixed infections where P. vivax becomes a more predominant species as overall malaria transmission decreases. This chapter addresses these challenges in detail and provide recommendations and key priorities to overcome these obstacles to accelerate efforts for achieving malaria elimination.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/61329",risUrl:"/chapter/ris/61329",book:{id:"6339",slug:"towards-malaria-elimination-a-leap-forward"},signatures:"Jeffrey Hii, Indra Vythilingam and Arantxa Roca-Feltrer",authors:[{id:"151116",title:"Dr.",name:"Indra",middleName:null,surname:"Vythilingam",fullName:"Indra Vythilingam",slug:"indra-vythilingam",email:"indrav@um.edu.my",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"214902",title:"Dr.",name:"Arantxa",middleName:null,surname:"Roca-Feltrer",fullName:"Arantxa Roca-Feltrer",slug:"arantxa-roca-feltrer",email:"a.roca@malariaconsortium.org",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Malaria Consortium",institutionURL:null,country:{name:"United Kingdom"}}},{id:"215079",title:"Dr.",name:"Jeffrey",middleName:null,surname:"Hii",fullName:"Jeffrey Hii",slug:"jeffrey-hii",email:"j.hii@malariaconsortium.org",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Malaria Consortium",institutionURL:null,country:{name:"Uganda"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Resistance to artemisinin and ACT: current and future approaches",level:"1"},{id:"sec_3",title:"3. Targeting interventions in hard-to-reach population groups",level:"1"},{id:"sec_4",title:"4. Residual and outdoor transmission: how much and where?",level:"1"},{id:"sec_5",title:"5. Correct identification of malaria vectors and Plasmodium detection",level:"1"},{id:"sec_6",title:"6. Plasmodium knowlesi: an additional challenge to malaria elimination",level:"1"},{id:"sec_7",title:"7. Targeting vivax malaria: a bottleneck to malaria elimination",level:"1"},{id:"sec_8",title:"8. Socio-ecological and adaptive management of malaria ecosystem in areas approaching malaria elimination",level:"1"},{id:"sec_9",title:"9. Conclusions",level:"1"},{id:"sec_10",title:"Acknowledgments",level:"1"},{id:"sec_13",title:"Conflict of interest",level:"1"},{id:"sec_12",title:"List of acronyms",level:"1"}],chapterReferences:[{id:"B1",body:'WHO. 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DOI: 10.1186/s12936-017-1787-y\n'},{id:"B152",body:'Baird JK, Valecha N, Duparc S, White NJ, Price RN. Diagnosis and treatment of Plasmodium vivax malaria. American Journal of Tropical Medicine and Hygiene. 2016;95:35-51. DOI: 10.4269/ajtmh.16-0171\n'},{id:"B153",body:'Howes RE, Piel FB, Patil AP, Nyangiri OA, Gething PW, Dewi M, Hogg MM, Battle KE, Padilla CD, Baird JK. G6PD deficiency prevalence and estimates of affected populations in malaria endemic countries: A geostatistical model-based map. PLoS Medicine. 2012;9:e1001339. DOI: 10.1371/journal.pmed.1001339\n'},{id:"B154",body:'WHO. Single dose primaquine as a gametocytocide in Plasmodium falciparum malaria. 2012. Available from: http://www.who.int/malaria/publications/atoz/who_pq_policy_recommendation/en/ [Accessed: 2017-12-5]\n'},{id:"B155",body:'Olliaro PL, Barnwell JW, Barry A, Mendis K, Mueller I, Reeder JC, Shanks GD, Snounou G, Wongsrichanalai C. 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Nature Medicine. 2013;19:150-155. DOI: 10.1038/nm.3077\n'},{id:"B160",body:'Vivax Working Group. Targeting vivax malaria in the Asia Pacific: The Asia Pacific malaria elimination network Vivax working group. Malaria Journal. 2015;14:484. DOI: 10.1186/s12936-015-0958-y\n'},{id:"B161",body:'WHO. Research priorities for the environment, agriculture and infectious diseases of poverty. 2013. Available from: http://apps.who.int/iris/bitstream/10665/78129/1/WHO_TRS_976_eng.pdf [Accessed: 2017-12-5]\n'},{id:"B162",body:'Campbell-Lendrum D, Molyneux D. Ecosystems and vector-borne disease control. In: Epstein P, Githeko A, Rabinovich J, Weinstein P, editors. Ecosystems and Human Well-Being: Policy Responses. Vol. 3. Washington, USA: Island Press; 2005. pp. 353-372\n'},{id:"B163",body:'Stewart-Ibarra M. A social-ecological systems approach to dengue-chikungunya-zika in urban coastal Ecuador. In: A social-ecological Systems Approach to Dengue-chikungunya-zika in Urban Coastal Ecuador. Vol. 2017. 2016\n'},{id:"B164",body:'WHO. Mass drug administration for malaria. A practical field manual. Malaria Policy Advisory Committee. 2017. Available from: http://www.who.int/malaria/mpac/mpac-mar2017-MDA-draft-manual-session7-presentation.pdf [Accessed: 2017-12-6]\n'},{id:"B165",body:'Wilson AL, Chen-Hussey V, Logan JG, Lindsay SW. Are topical insect repellents effective against malaria in endemic populations? A systematic review and meta-analysis. Malaria Journal. 2014;13:446. DOI: 10.1186/1475-2875-13-446\n'},{id:"B166",body:'Banks S, Murray N, WilderSmith A, Logan J. Insecticide-treated clothes for the control of vector-borne diseases: A review on effectiveness and safety. Medical and Veterinary Entomology. 2014;28:14-25. DOI: 10.1111/mve.12068\n'},{id:"B167",body:'Parkes MW, Bienen L, Breilh J, Hsu L-N, McDonald M, Patz JA, Rosenthal JP, Sahani M, Sleigh A, Waltner-Toews D. All hands on deck: Transdisciplinary approaches to emerging infectious disease. EcoHealth. 2005;2:258-272. DOI: 10.1007/s12275-013-2393-5\n'},{id:"B168",body:'Wilcox B, Kueffer C. Transdisciplinarity in EcoHealth: Status and future prospects. EcoHealth. 2008;5:1-3. DOI: 10.1007/s10393-008-0161-5\n'},{id:"B169",body:'Okello-Onen J, Mboera LE, Mugisha S. Malaria research and management need rethinking: Uganda and Tanzania case studies. In: Charron DF, editor. Ecohealth Research in Practice. New York: Springer; 2012. pp. 139-151. DOI: 10.1007/978-1-4614-0517-7\n'},{id:"B170",body:'Richter CH, Xu J, Wilcox BA. Opportunities and challenges of the ecosystem approach. Futures. 2015;67:40-51. DOI: 10.1016/j.futures.2014.12.002\n'},{id:"B171",body:'Minkler M, Wallerstein N. Introduction to community-based participatory research. In: Wallerstein MMN, editor. Community-Based Participatory Research for Health: From Process to Outcomes. 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Expert Consultation on Plasmodium knowlesi malaria to guide malaria elimination strategies. 2017. Available from: ww.wpro.who.int/mvp/meetings/exp_con_pknowlesi_2017/en/ [Accessed: 2018-01-27]\n'}],footnotes:[{id:"fn1",explanation:"Cambodia, The People’s Republic of China (specifically Yunnan Province), the Lao People’s Democratic Republic (Lao PDR), Myanmar, Thailand, and Vietnam."}],contributors:[{corresp:null,contributorFullName:"Jeffrey Hii",address:null,affiliation:'
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1. Introduction
Sample analysis consists of various analytical steps, including sampling, sample preparation, separation, detection and data analysis. One of the most important steps is sample preparation, which involves the extraction, isolation and concentration of target analytes from complex matrices. Sample preparation [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18] is the most labor-intensive and error-prone process in analytical methodology and markedly influences the reliability and accuracy of analyte determination. In addition, sample preparation requires large amounts of sample and organic solvents, and is therefore difficult to automate. An ideal sample preparation technique should be simple and fast; be specific for analytes through the efficient removal of coexisting components; provide high sample throughput; utilize fewer operation steps to minimize analyte losses; and be solvent-free, inexpensive, and compatible with chromatography systems. Online automated sample preparation [19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29], in which sample preparation is directly connected to chromatographic separation systems, eliminates further sample handling between the trace-enrichment and separation steps. Online automated sample preparation methods usually improve data quality, increase sample throughput, reduce costs, and improve the productivity of personnel and instruments.
In-tube solid-phase microextraction (SPME), using a capillary tube as an extraction device, was introduced by Eisert and Pawliszyn [30] to overcome the problems inherent to conventional fiber SPME. These drawbacks included fragility, low sorption capacity, bleeding from thick-film coatings on fibers, limited effectiveness for extraction of weakly volatile or thermally labile compounds not amenable to gas chromatography (GC) or GC-mass spectrometry (MS), and reduced stability in solvents used in high performance liquid chromatography (HPLC). In-tube SPME was also developed to completely automate the sample preparation process and to enable direct online coupling of in-tube SPME with HPLC using capillary column switching systems [31].
This chapter reviews the configurations and characteristics of in-tube SPME technology and discusses current and future directions, including the strategies involved in extraction efficiency and method development. The details of in-tube SPME have been described in well documented reviews [27, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50].
2. Configurations of in-tube SPME
In-tube SPME is an efficient sample preparation technique for extraction in capillary columns using stationary phases coated on the inner wall of the capillary or on the surface of the packing material (Figure 1). Various in-tube SPME capillary devices have been developed, such as inner wall-coated fused-silica open tubular (Figure 1A), fiber-packed (Figure 1B), sorbent-packed (Figure 1C), and rod-type porous monolith (Figure 1D) capillaries [16, 31]. The capillaries are easily fixed with the autosampler injection system, and are generally reusable without plugging or breaking the column and without exfoliation of coating materials.
Figure 1.
Capillary devices for in-tube SPME: (A) polymer coated, (B) sorbent-packed, (C) fiber-packed, and (D) monolith capillary tubes.
2.1 Operating systems of in-tube SPME
Flow-through systems (Figure 2), in which sample solutions are continuously passed in one direction through a capillary column; or as repeated draw/ejection systems (Figure 3), in which sample solutions are repeatedly aspirated and dispensed from a capillary column, are used as an operating system of in-tube SPME [18]. These systems are operated by column switching techniques under computer control.
Figure 2.
Schematic diagrams of a flow-through extraction system used for online in-tube SPME. (A) Load position (extraction), and (B) injection position (desorption).
Figure 3.
Schematic diagrams of a draw/eject extraction system used for online in-tube SPME (reproduced from Ref. [37]). (A) Extraction and concentration step, and (B) desorption and injection step.
In flow-through systems, the complete analytical system consists of an automatic six-port valve, two pumps (a sample pump and a wash pump) and a liquid chromatography (LC) system. A capillary column is installed in the six-port valve or sometimes placed in the loop. Although one or two six-port valves are available, one valve mode is used more frequently than others. The procedure consists of four steps, conditioning, extracting, washing and desorbing. After conditioning of capillary column with water, the aqueous sample is pumped through the column under the load position (Figure 2A). Remaining matrix and residues in capillary are removed by washing with water. After switching the six-port valve to the injection position, the LC mobile phase is passed through the column (dynamic desorption), with the flow-rate of the LC pump (Figure 2B). The desorbed analytes are subsequently transferred to the analytical column for separation and detection. The flow-through extraction system, however, may include systematic troubles, such as contamination of the switching valve by sample matrix [18, 31, 37, 41].
Repeated draw/ejection systems include the placement of a capillary column for extraction between the injection loop and the injection needle of the autosampler. Since the sample solution moves only in the capillary, the metering pump and switching valve are not contaminated by sample matrix [18, 31, 37, 41]. A built-in UV diode array detector (DAD) or fluorescence detector (FLD) between the HPLC and the MS can enhance the multidimensional and simultaneous multi-detections, improving analyte identification. During the extraction and concentration step (Figure 3A), the injection syringe is programmed to repeatedly draw and eject sample solution from the vial until the concentration of the analyte reaches distribution equilibrium between the sample solution and the stationary phase. After switching the six-port valve to the injection position, the extracted analytes can be directly desorbed from the capillary coating by LC mobile phase flow (dynamic desorption) or by an aspirated desorption solvent (static desorption) (Figure 3B) [31]. The desorbed analytes are subsequently transferred to an LC column. The computer controls the drawing and ejection of sample solution; switching of the valves; control of peripheral equipment, such as the HPLC and MS; and analytical data processing, thus reducing labor and enhancing precision. In addition, the autosampler can automatically process a large number of samples without carryover, because the injection needle and capillary column are washed in methanol and the mobile phase before the sample is extracted.
2.2 Extraction sorbent materials
The amount of analyte extracted into the stationary phase of the capillary during in-tube SPME is dependent on the characteristics of the capillary coating and the target analyte. Among the commercially available GC capillary columns, silica modified columns have been found more suitable for the analysis of nonpolar compounds. Porous polymer type capillary columns such as Supel-Q PLOT (divinylbenzene polymer, film thickness 17 μm) have shown better extraction efficiencies due to their large surface area for most organic compounds than other liquid-phase type capillary columns, such as CP-Sil 5CB (100% polydimethylsiloxane, film thickness 5 μm), Quadrex 007–5 (5% phenyl polydimethylsiloxane, film thickness 12 μm), CP-Sil 19CB (14% cyanopropyl phenyl methylsilicone, film thickness 1.0 μm), and CP-Wax 52CB (polyethylene glycol, film thickness 1.2 μm). CP-Sil 19CB was superior for extraction of polyaromatic hydrocarbons, although the film layer was thin. In contrast, some compounds were effectively extracted with other PLOT type coatings, including Carboxen-1006 PLOT (carboxen molecularsives, film thickness 17 μm) and CP-Pora PLOT amine (basic modified styrene divinylbenzene polymer, film thickness 10 μm).
Several unique phases and technical solutions have been developed to improve extraction efficiency and selectivity when extended to microscale applications [44, 51, 52, 53]. These include polypyrrole (PPY) coated capillaries; PEEK tube capillaries packed with molecularly imprinted polymer (MIP) particles [54, 55, 56, 57, 58, 59, 60, 61]; and highly biocompatible SPME capillaries packed with alkyl-diol-silica (ADS) particles as restricted access media (RAM) [62, 63], immunosorbents [64], ionic liquids [65, 66, 67], monolithic materials [68, 69, 70, 71, 72, 73], carbon nanomaterials [74, 75, 76, 77, 78, 79, 80, 81, 82], silica-coated magnetite (SiO2-Fe3O4) [83, 84, 85, 86], and temperature responsive polymers [87, 88]. Novel extraction sorbent materials for in-tube SPME are shown in Figure 4.
Figure 4.
Novel extraction sorbent materials for in-tube SPME (eproduced from Ref. [37, 42, 84]). (A) Molecularly imprinted polymers, (B) restricted access media, (C) immunosorbents, (D) monolithic polymers, (E) carbon nanotubes, (F) silica-coated magnetite, and (G) temperature responsive polymers.
For example, chemically or electrochemically deposited PPY coatings have higher extraction efficiencies than commercial GC coatings due to the various types of interactions (e.g., π–π, polar, hydrogen bonding, and ionic interactions) between these multifunctional PPY coatings and the analytes. Capillary tubes have been coated with MIP, consisting of cross-linked synthetic polymers produced by copolymerizing a monomer with a cross-linker in the presence of a template molecule (Figure 4A), and PEEK tubes have been packed with MIP particles. By removing the template after polymerization, it is possible to leave open sites of a specific size and shape suitable for binding the same or similar chemicals in a sample. MIPs recognize chemicals through combination of shape, hydrogen bonding, and hydrophobic and electrostatic interactions [16, 18, 31]. RAM materials possess defined diffusion barriers with small sized pores and biocompatible outer particle surfaces (Figure 4B). The bifunctionality of ADS particles used as a RAM SPME device can prevent fouling of the capillary by protein adsorption while simultaneously trapping the analytes in the hydrophobic porous interior. Furthermore, a simple SPME device has been fabricated for use in online immunoaffinity capillaries packed with immunosorbent materials, consisting of covalently immobilized antibodies (Figure 4C).
An alternative approach consists of in-tube SPME using monolithic capillary columns comprised of one piece of organic polymer or silica rods with a unique flow-through double-pore structure (Figure 4D). Monoliths are also highly permeable to liquids and biological samples, enabling reduced solvent use, varied support formats, and/or automation. Monolithic capillaries are especially suitable for in-tube SPME media due to the low pressure drop, allowing a high flow-rate to achieve high throughput and a total porosity greater than that of particle-packed capillaries. Hydrophobic main chains and acidic pendant groups of poly (methacrylic acid-ethylene glycol dimethacrylate) enhance the ability to extract basic analytes from aqueous matrices. The physicochemical properties of graphene-based sorbents and carbon nanotubes (Figure 4E) enable their use in extraction, with these combinations showing excellent results when used for in-tube SPME. In addition, various cationic, anionic and zwitterionic liquid-mediated sol–gel coatings have been developed for effective in-tube SPME.
Other innovative extractive phases that enhance the affinity of the analytes include silica magnetite (SiO2-Fe3O4; Figure 4F) and poly (N-isopropylacrylamide; Figure 4G), which have been used in new microextraction processes involving magnetism and thermal energy, respectively. Magnetic and temperature controlled in-tube SPME are performed using flow-through systems, due to the need for additional equipment providing a magnetic or thermal field, which is easier to implement using flow-through devices. Other techniques include wire-in-tube SPME, using modified capillary columns with inserted stainless steel wires, and fiber-in-tube SPME, using PEEK tubes packed with fibrous rigid-rod heterocyclic polymers. These methods increase extraction efficiency by reducing capillary volume or increasing the extracting surface and have shown improved extraction efficiency when extended to microscale applications.
3. Method development and characteristics of in-tube SPME
3.1 Optimization of in-tube SPME
In-tube SPME depends on the distribution coefficient of each analyte. Extraction conditions may be optimized by increasing the distribution factor in the stationary phase. The selectivity and efficiency of extraction depend on the type of stationary phase and on the internal diameter, length, and film thickness of the capillary column. Sorption equilibrium is attained by optimizing various extraction parameters for each type of analyte. These parameters include extraction rate, sample volume, sample pH, flow-rate, number of draw/eject cycles (only draw/eject system), and desorption conditions. As described in the preceding section, the choice of capillary coating is important for optimizing extraction selectivity and efficiency. Generally, low and high polarity columns selectively retain hydrophobic and hydrophilic compounds, respectively. Stationary phase consisting of a thicker film and longer column can extract larger amounts of compound, but quantitative desorption of compounds from capillary columns may be difficult. PLOT-type columns have a larger adsorption surface area and thicker film layer than liquid-phase-type columns, enabling more analytes to be extracted [16, 18].
Generally, the optimal length and internal diameter of a capillary column used in combination with HPLC is 20–80 cm and 0.25 or 0.32 mm, respectively. Although thick-film capillaries often show higher sample capacity and extraction sensitivity, it is extremely difficult to reliably bind thicker chemical coatings to the inner surfaces of fused-silica capillary tubes using conventional approaches. In contrast, thin-film capillaries can minimize the time to reach extraction equilibrium due to their low sample capacity. Capillary columns with chemically bonded or cross-linked liquid phases are very stable in water and organic solvents and can prevent loss of phase by LC mobile phase [18].
The volume of sample passed through a capillary is usually 0.2–2 mL in flow-through extraction systems, and their optimum extraction flow rates are 0.25–4 mL/min depending on the volume of the column. Although increases in the number and volume of draw/eject cycles can enhance extraction efficiency in draw/ejection systems, peak broadening is often observed [16]. Optimal conditions for a capillary column of inner diameter 0.25 mm and length 60 cm include a draw/ejection volume of 30–40 μL, a draw/ejection flow rate of 50–100 μL/min and 10–15 draw/ejection cycles. Below this rate, extractions require an inconveniently long time, and above this rate, bubbles form on the inside of the capillary, reducing extraction efficiency. Furthermore, the extraction efficiency of the analyte to the stationary phase varies with the pH of the sample solution. The presence of hydrophilic solvents such as methanol in the sample reduces the extraction efficiency. The analyte extracted on capillary coatings can be easily desorbed statically or dynamically without carryover [18].
3.2 Characteristics of the in-tube SPME technique
Table 1 summarizes the characteristics of in-tube SPME. The main advantage is that the series of processes can be automated, which enables continuous extraction, desorption and injection with column switching using a standard autosampler, and online coupling with the LC system [16, 18, 31]. In-tube SPME may be suitable for the determination of polar and thermolabile compounds. Compared with manual techniques, automated sample-handling procedures not only shorten the total analysis time but are more accurate and precise. Automated techniques are also suitable for miniaturization, high-throughput performance, and online coupling with analytical instruments, and reduce the consumption of solvent. Online procedures can limit contact with dirty and hazardous samples, reducing sample contamination and loss. Online column-switching systems are highly sensitive due to pre-concentration resulting from the injection of large sample volumes into the extraction support without loss of chromatographic performance. The main disadvantage is that the capillaries tend to clog, which may be avoided by removing interfering phases such as particles or macromolecules by filtration or centrifugation before extraction. Although the absolute recovery rate of the in-tube SPME method is generally low, it can be extracted and concentrated reproducibly using an autosampler, and all extracts can be introduced into the LC column [16, 18, 31].
Advantage
Disadvantage
Minimal sample adjustment
Large injection volume (flow-through system)
Applicable to polar and thermolabile liquid samples
Low solvent consumption
Decreased handling of biohazardous samples
Less sample loss due to online closed system
Lower likelihood of carryover
Higher mechanical stability of capillaries
Reusability of capillaries without plugging or breaking
Commercially available GC capillary columns
Applicability of various unique adsorbents to specific and efficient extraction
Easy on-line coupling with liquid chromatography
Enabling of full automation by column switching
Commercially available autosamplers
Improvements in selectivity and sensitivity
Better precision and accuracy
Tendency of the capillary to clog
Limited to particulate-free samples
Stripping of non-bonding thick-film coatings
Possible peak broadening
Switching of valves, extraction columns, and pumps required
Complicated switching system
Relatively low enrichment factor
Relatively long extraction time
Table 1.
Advantages and disadvantages of in-tube SPME.
The online in-tube SPME method can be applied to polar and nonpolar compounds in liquid samples, and can be coupled with various analytical methods, such as HPLC and LC–MS. Early applications of online in-tube SPME have involved draw/eject extraction systems and commercially available open-tubular GC capillaries such as Supel Q PLOT and Carboxen 1006 PLOT capillaries. The subsequent development of various operating systems and new sorbent materials improved extraction efficiency, such as sorption capacity and selectivity, and extended the range of applications. Last decade, numerous applications of online in-tube SPME methods have been reported to many types of pharmaceutical and biomedical [86, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124], food [125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137], and environmental [138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178] analyses.
4. Conclusions and future directions
The online in-tube SPME techniques described in this chapter have many desirable features for automated separation of analytes, using column-switching techniques. These methods are especially well suited to the analysis of samples requiring significant cleanup and concentration to improve their selectivity and sensitivity, as well as being useful for high-throughput sampling. Since the in-tube SPME method using capillaries as an extraction device is useful for online sample preparation to extract and concentrate polar and non-polar compounds from aqueous solution, it has become an effective technique for convenient analysis of a wide variety of compounds in complex matrices such as biological, pharmaceutical, food and environmental samples [31]. Furthermore, various operating systems and new sorbent materials have been developed to improve extraction efficiency and sorption capacity and selectivity, and to extend the range of applications. These include MIPs, RAM, immunosorbents, monolithic materials, carbon nanoparticles, ionic liquids, temperature responsive polymers and magnetic hybrid adsorbents.
The main future direction in sample preparation is the development of more sensitive and selective extraction sorbents [31]. Chiral active phases, ionic liquids, dendrimers, aptamer modified sorbents, magnetic materials, temperature responsive materials may be available as new polymer devices for effective sample preparation. Furthermore, biomimetic coating materials including ultrasound and light responsive polymers may be available as a selective extraction device in the future. These customized coating materials, differing in type, shape, and size, are expected to result in highly efficient extraction of various samples. Biocompatible RAM and monolithic sorbents are useful for direct analysis, without pre-treatment other than dilution and centrifugation of biological samples. As another future direction, better integration of sampling/sample preparation and instrumental analysis will allow wider use of automated online analysis. Especially, the use of column-switching systems involving microextraction techniques and/or microdevices will offer convenient integration of sample preparation with various analytical instruments such as HPLC as well as other chromatographic systems, electrophoresis, direct MS, etc.
Finally, this chapter provides an overview of the configurations and characteristics of in-tube SPME technology for online automated micro sample preparation for HPLC. We hope that this chapter will serve as a guide to choosing the most effective sample preparation techniques for the analysis of various complex samples.
Acknowledgments
This work was supported by a Grant-in-Aid for Basic Scientific Research (C, No. 17 K08259).
Conflict of interest
The authors declare no conflict of interest.
\n',keywords:"sample preparation, online automated analysis, column switching, in-tube solid-phase microextraction, high-performance liquid chromatography",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/68865.pdf",chapterXML:"https://mts.intechopen.com/source/xml/68865.xml",downloadPdfUrl:"/chapter/pdf-download/68865",previewPdfUrl:"/chapter/pdf-preview/68865",totalDownloads:945,totalViews:0,totalCrossrefCites:0,dateSubmitted:"March 16th 2019",dateReviewed:"August 8th 2019",datePrePublished:"August 29th 2019",datePublished:"June 24th 2020",dateFinished:"August 29th 2019",readingETA:"0",abstract:"Sample preparation is one of the most labor-intensive and time-consuming operations in sample analysis. Sample preparation strategies include the exhaustive or non-exhaustive extraction of analytes from matrices. Online coupling of sample preparation with the separation system is regarded as an important goal. In-tube solid-phase microextraction (SPME) is an effective sample preparation technique that uses an open tubular fused-silica capillary column as an extraction device. In-tube SPME is useful for trace enrichment, automated sample cleanup, and rapid online analysis. Moreover, this method can be used to determine the analytes in complex matrices by direct sample injection or merely by simple sample treatment such as filtration. In-tube SPME is frequently combined with high-performance liquid chromatography (HPLC) using online column-switching techniques. Various operating systems and new sorbent materials have been reported to improve extraction efficiency, such as sorption capacity and selectivity. This chapter discusses efficient micro sample preparation techniques for HPLC, especially online automated in-tube SPME.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/68865",risUrl:"/chapter/ris/68865",signatures:"Hiroyuki Kataoka, Atsushi Ishizaki and Keita Saito",book:{id:"8912",type:"book",title:"Biochemical Analysis Tools",subtitle:"Methods for Bio-Molecules Studies",fullTitle:"Biochemical Analysis Tools - Methods for Bio-Molecules Studies",slug:"biochemical-analysis-tools-methods-for-bio-molecules-studies",publishedDate:"June 24th 2020",bookSignature:"Oana-Maria Boldura, Cornel Baltă and Nasser Sayed Awwad",coverURL:"https://cdn.intechopen.com/books/images_new/8912.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-78984-857-1",printIsbn:"978-1-78984-856-4",pdfIsbn:"978-1-83880-903-4",isAvailableForWebshopOrdering:!0,editors:[{id:"189429",title:"Prof.",name:"Oana-Maria",middleName:null,surname:"Boldura",slug:"oana-maria-boldura",fullName:"Oana-Maria Boldura"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"88155",title:"Prof.",name:"Hiroyuki",middleName:null,surname:"Kataoka",fullName:"Hiroyuki Kataoka",slug:"hiroyuki-kataoka",email:"hkataoka@shujitsu.ac.jp",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Shujitsu University",institutionURL:null,country:{name:"Japan"}}},{id:"308808",title:"MSc.",name:"Atsushi",middleName:null,surname:"Ishuzaki",fullName:"Atsushi Ishuzaki",slug:"atsushi-ishuzaki",email:"ishizaki@shujitsu.ac.jp",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Shujitsu University",institutionURL:null,country:{name:"Japan"}}},{id:"308809",title:"Dr.",name:"Keita",middleName:null,surname:"Saito",fullName:"Keita Saito",slug:"keita-saito",email:"ksaito@shujitsu.ac.jp",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Shujitsu University",institutionURL:null,country:{name:"Japan"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Configurations of in-tube SPME",level:"1"},{id:"sec_2_2",title:"2.1 Operating systems of in-tube SPME",level:"2"},{id:"sec_3_2",title:"2.2 Extraction sorbent materials",level:"2"},{id:"sec_5",title:"3. Method development and characteristics of in-tube SPME",level:"1"},{id:"sec_5_2",title:"3.1 Optimization of in-tube SPME",level:"2"},{id:"sec_6_2",title:"3.2 Characteristics of the in-tube SPME technique",level:"2"},{id:"sec_8",title:"4. Conclusions and future directions",level:"1"},{id:"sec_9",title:"Acknowledgments",level:"1"},{id:"sec_12",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'Pawliszyn J, Lord H. Handbook of Sample Preparation. Hoboken: John Wiley & Sons; 2010'},{id:"B2",body:'Papadoyannis IN, Samanidou VF. Sample preparation for HPLC. In: Cazes J, editor. Encyclopedia of Chromatography. 3rd ed. Vol. III. Broken Sound Parkway: CRC Press; 2010. pp. 2090-2105'},{id:"B3",body:'Ashri NY, Abdel-Rehim M. 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Electroplating of nanostructured polyaniline-polypyrrole composite coating in a stainless-steel tube for on-line in-tube solid phase microextraction. Journal of Chromatography. A. 2015;1397:19-26'},{id:"B131",body:'Ishizaki A, Saito K, Hanioka N, Narimatsu S, Kataoka H. Determination of polycyclic aromatic hydrocarbons in food samples by automated on-line in-tube solid-phase microextraction coupled with high-performance liquid chromatography-fluorescence detection. Journal of Chromatography. A. 2010;1217:5555-5563'},{id:"B132",body:'Ishizaki A, Saito K, Kataoka H. Analysis of polycyclic aromatic hydrocarbons contamination in tea products and crude drugs. Analytical Methods. 2011;3:299-305'},{id:"B133",body:'Ying LL, Wang DY, Yang HP, Deng XY, Peng C, Zheng C, et al. Synthesis of boronate-decorated polyethyleneimine-grafted porous layer open tubular capillaries for enrichment of polyphenols in fruit juices. Journal of Chromatography. A. 2018;1544:23-32'},{id:"B134",body:'Andrade MA, Lanças FM. Determination of ochratoxin A in wine by packed in-tube solid phase microextraction followed by high performance liquid chromatography coupled to tandem mass spectrometry. Journal of Chromatography. A. 2017;1493:41-48'},{id:"B135",body:'Saito K, Ikeuchi R, Kataoka H. Determination of ochratoxins in nuts and grain samples by in-tube solid-phase microextraction coupled with liquid chromatography-mass spectrometry. Journal of Chromatography. A. 2012;1220:1-6'},{id:"B136",body:'Wu F, Xu C, Jiang N, Wang J, Ding CF. Poly (methacrylic acid-co-diethenyl-benzene) monolithic microextraction column and its application to simultaneous enrichment and analysis of mycotoxins. Talanta. 2018;178:1-8'},{id:"B137",body:'Wang X, Ma Q , Li M, Chang C, Bai Y, Feng Y, et al. 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School of Pharmacy, Shujitsu University, Nishigawara, Okayama, Japan
School of Pharmacy, Shujitsu University, Nishigawara, Okayama, Japan
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If your research is financed through any of the below-mentioned funders, please consult their Open Access policies or grant ‘terms and conditions’ to explore ways to cover your publication costs (also accessible by clicking on the link in their title).
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UK Research and Innovation (former Research Councils UK (RCUK) - including AHRC, BBSRC, ESRC, EPSRC, MRC, NERC, STFC.) Processing charges for books/book chapters can be covered through RCUK block grants which are allocated to most universities in the UK, which then handle the OA publication funding requests. It is at the discretion of the university whether it will approve the request.)
Wellcome Trust (Funding available only to Wellcome-funded researchers/grantees)
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Gulrez, Saphwan Al-Assaf and Glyn O Phillips",authors:[{id:"58120",title:"Prof.",name:"Saphwan",middleName:null,surname:"Al-Assaf",slug:"saphwan-al-assaf",fullName:"Saphwan Al-Assaf"}]},{id:"13254",doi:"10.5772/13474",title:"Insight Into Adsorption Thermodynamics",slug:"insight-into-adsorption-thermodynamics",totalDownloads:7141,totalCrossrefCites:87,totalDimensionsCites:258,abstract:null,book:{id:"25",slug:"thermodynamics",title:"Thermodynamics",fullTitle:"Thermodynamics"},signatures:"Papita Saha and Shamik Chowdhury",authors:[{id:"13943",title:"Dr.",name:"Papita",middleName:null,surname:"Saha",slug:"papita-saha",fullName:"Papita Saha"},{id:"24184",title:"Mr.",name:"Shamik",middleName:null,surname:"Chowdhury",slug:"shamik-chowdhury",fullName:"Shamik Chowdhury"}]},{id:"35261",doi:"10.5772/34233",title:"Anisotropic Mechanical Properties of ABS Parts Fabricated by Fused Deposition Modelling",slug:"anisotropic-mechanical-properties-of-abs-parts-fabricated-by-fused-deposition-modeling-",totalDownloads:7248,totalCrossrefCites:113,totalDimensionsCites:239,abstract:null,book:{id:"1982",slug:"mechanical-engineering",title:"Mechanical Engineering",fullTitle:"Mechanical Engineering"},signatures:"Constance Ziemian, Mala Sharma and Sophia Ziemian",authors:[{id:"89554",title:"Dr.",name:"Mala",middleName:null,surname:"Sharma",slug:"mala-sharma",fullName:"Mala Sharma"},{id:"98759",title:"Dr.",name:"Constance",middleName:null,surname:"Ziemian",slug:"constance-ziemian",fullName:"Constance Ziemian"},{id:"137165",title:"Ms.",name:"Sophia",middleName:null,surname:"Ziemian",slug:"sophia-ziemian",fullName:"Sophia Ziemian"}]},{id:"8446",doi:"10.5772/39538",title:"2 µm Laser Sources and Their Possible Applications",slug:"2-m-laser-sources-and-their-possible-applications",totalDownloads:12042,totalCrossrefCites:138,totalDimensionsCites:217,abstract:null,book:{id:"3161",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",title:"Frontiers in Guided Wave Optics and Optoelectronics",fullTitle:"Frontiers in Guided Wave Optics and Optoelectronics"},signatures:"Karsten Scholle, Samir Lamrini, Philipp Koopmann and Peter Fuhrberg",authors:[{id:"4951",title:"Dr.",name:"Karsten",middleName:null,surname:"Scholle",slug:"karsten-scholle",fullName:"Karsten Scholle"},{id:"133366",title:"Prof.",name:"Samir",middleName:null,surname:"Lamrini",slug:"samir-lamrini",fullName:"Samir Lamrini"},{id:"133370",title:"Prof.",name:"Philipp",middleName:null,surname:"Koopmann",slug:"philipp-koopmann",fullName:"Philipp Koopmann"},{id:"133371",title:"Mr.",name:"Peter",middleName:null,surname:"Fuhrberg",slug:"peter-fuhrberg",fullName:"Peter Fuhrberg"}]},{id:"27163",doi:"10.5772/31200",title:"Synergisms between Compost and Biochar for Sustainable Soil Amelioration",slug:"synergism-between-biochar-and-compost-for-sustainable-soil-amelioration",totalDownloads:6040,totalCrossrefCites:68,totalDimensionsCites:170,abstract:null,book:{id:"873",slug:"management-of-organic-waste",title:"Management of Organic Waste",fullTitle:"Management of Organic Waste"},signatures:"Daniel Fischer and Bruno Glaser",authors:[{id:"84418",title:"Prof.",name:"Bruno",middleName:null,surname:"Glaser",slug:"bruno-glaser",fullName:"Bruno Glaser"},{id:"96141",title:"Mr.",name:"Daniel",middleName:null,surname:"Fischer",slug:"daniel-fischer",fullName:"Daniel Fischer"}]}],mostDownloadedChaptersLast30Days:[{id:"35255",title:"Mechanical Transmissions Parameter Modelling",slug:"mechanical-transmissions-parameter-modelling",totalDownloads:7240,totalCrossrefCites:1,totalDimensionsCites:2,abstract:null,book:{id:"1982",slug:"mechanical-engineering",title:"Mechanical Engineering",fullTitle:"Mechanical Engineering"},signatures:"Isad Saric, Nedzad Repcic and Adil Muminovic",authors:[{id:"101313",title:"Prof.",name:"Isad",middleName:null,surname:"Saric",slug:"isad-saric",fullName:"Isad Saric"}]},{id:"67558",title:"Polymerase Chain Reaction (PCR): Principle and Applications",slug:"polymerase-chain-reaction-pcr-principle-and-applications",totalDownloads:10477,totalCrossrefCites:6,totalDimensionsCites:15,abstract:"The characterization of the diversity of species living within ecosystems is of major scientific interest to understand the functioning of these ecosystems. It is also becoming a societal issue since it is necessary to implement the conservation or even the restoration of biodiversity. Historically, species have been described and characterized on the basis of morphological criteria, which are closely linked by environmental conditions or which find their limits especially in groups where they are difficult to access, as is the case for many species of microorganisms. The need to understand the molecular mechanisms in species has made the PCR an indispensable tool for understanding the functioning of these biological systems. A number of markers are now available to detect nuclear DNA polymorphisms. In genetic diversity studies, the most frequently used markers are microsatellites. The study of biological complexity is a new frontier that requires high-throughput molecular technology, high speed computer memory, new approaches to data analysis, and the integration of interdisciplinary skills.",book:{id:"7728",slug:"synthetic-biology-new-interdisciplinary-science",title:"Synthetic Biology",fullTitle:"Synthetic Biology - New Interdisciplinary Science"},signatures:"Karim Kadri",authors:[{id:"290766",title:"Dr.",name:"Kadri",middleName:null,surname:"Karim",slug:"kadri-karim",fullName:"Kadri Karim"}]},{id:"62059",title:"Types of HVAC Systems",slug:"types-of-hvac-systems",totalDownloads:12222,totalCrossrefCites:8,totalDimensionsCites:14,abstract:"HVAC systems are milestones of building mechanical systems that provide thermal comfort for occupants accompanied with indoor air quality. HVAC systems can be classified into central and local systems according to multiple zones, location, and distribution. Primary HVAC equipment includes heating equipment, ventilation equipment, and cooling or air-conditioning equipment. Central HVAC systems locate away from buildings in a central equipment room and deliver the conditioned air by a delivery ductwork system. Central HVAC systems contain all-air, air-water, all-water systems. Two systems should be considered as central such as heating and cooling panels and water-source heat pumps. Local HVAC systems can be located inside a conditioned zone or adjacent to it and no requirement for ductwork. Local systems include local heating, local air-conditioning, local ventilation, and split systems.",book:{id:"6807",slug:"hvac-system",title:"HVAC System",fullTitle:"HVAC System"},signatures:"Shaimaa Seyam",authors:[{id:"247650",title:"M.Sc.",name:"Shaimaa",middleName:null,surname:"Seyam",slug:"shaimaa-seyam",fullName:"Shaimaa Seyam"},{id:"257733",title:"MSc.",name:"Shaimaa",middleName:null,surname:"Seyam",slug:"shaimaa-seyam",fullName:"Shaimaa Seyam"},{id:"395618",title:"Dr.",name:"Shaimaa",middleName:null,surname:"Seyam",slug:"shaimaa-seyam",fullName:"Shaimaa Seyam"}]},{id:"70315",title:"Some Basic and Key Issues of Switched-Reluctance Machine Systems",slug:"some-basic-and-key-issues-of-switched-reluctance-machine-systems",totalDownloads:1235,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Although switched-reluctance machine (SRM) possesses many structural advantages and application potential, it is rather difficult to successfully control with high performance being comparable to other machines. Many critical affairs must be properly treated to obtain the improved operating characteristics. This chapter presents the basic and key technologies of switched-reluctance machine in motor and generator operations. The contents in this chapter include: (1) structures and governing equations of SRM; (2) some commonly used SRM converters; (3) estimation of key parameters and performance evaluation of SRM drive; (4) commutation scheme, current control scheme, and speed control scheme of SRM drive; (5) some commonly used front-end converters and their operation controls for SRM drive; (6) reversible and regenerative braking operation controls for SRM drive; (7) some tuning issues for SRM drive; (8) operation control and some tuning issues of switched-reluctance generators; and (9) experimental application exploration for SRM systems—(a) wind generator and microgrid and (b) EV SRM drive.",book:{id:"8899",slug:"modelling-and-control-of-switched-reluctance-machines",title:"Modelling and Control of Switched Reluctance Machines",fullTitle:"Modelling and Control of Switched Reluctance Machines"},signatures:"Chang-Ming Liaw, Min-Ze Lu, Ping-Hong Jhou and Kuan-Yu Chou",authors:[{id:"37616",title:"Prof.",name:"Chang-Ming",middleName:null,surname:"Liaw",slug:"chang-ming-liaw",fullName:"Chang-Ming Liaw"},{id:"306461",title:"Mr.",name:"Min-Ze",middleName:null,surname:"Lu",slug:"min-ze-lu",fullName:"Min-Ze Lu"},{id:"306463",title:"Mr.",name:"Ping-Hong",middleName:null,surname:"Jhou",slug:"ping-hong-jhou",fullName:"Ping-Hong Jhou"},{id:"306464",title:"Mr.",name:"Kuan-Yu",middleName:null,surname:"Chou",slug:"kuan-yu-chou",fullName:"Kuan-Yu Chou"}]},{id:"70874",title:"Social, Economic, and Environmental Impacts of Renewable Energy Resources",slug:"social-economic-and-environmental-impacts-of-renewable-energy-resources",totalDownloads:4834,totalCrossrefCites:27,totalDimensionsCites:49,abstract:"Conventional energy source based on coal, gas, and oil are very much helpful for the improvement in the economy of a country, but on the other hand, some bad impacts of these resources in the environment have bound us to use these resources within some limit and turned our thinking toward the renewable energy resources. The social, environmental, and economical problems can be omitted by use of renewable energy sources, because these resources are considered as environment-friendly, having no or little emission of exhaust and poisonous gases like carbon dioxide, carbon monooxide, sulfur dioxide, etc. Renewable energy is going to be an important source for power generation in near future, because we can use these resources again and again to produce useful energy. Wind power generation is considered as having lowest water consumption, lowest relative greenhouse gas emission, and most favorable social impacts. It is considered as one of the most sustainable renewable energy sources, followed by hydropower, photovoltaic, and then geothermal. As these resources are considered as clean energy resources, they can be helpful for the mitigation of greenhouse effect and global warming effect. Local employment, better health, job opportunities, job creation, consumer choice, improvement of life standard, social bonds creation, income development, demographic impacts, social bonds creation, and community development can be achieved by the proper usage of renewable energy system. Along with the outstanding advantages of these resources, some shortcomings also exist such as the variation of output due to seasonal change, which is the common thing for wind and hydroelectric power plant; hence, special design and consideration are required, which are fulfilled by the hardware and software due to the improvement in computer technology.",book:{id:"7636",slug:"wind-solar-hybrid-renewable-energy-system",title:"Wind Solar Hybrid Renewable Energy System",fullTitle:"Wind Solar Hybrid Renewable Energy System"},signatures:"Mahesh Kumar",authors:[{id:"309842",title:"Mr.",name:"Kamlesh",middleName:null,surname:"Kumar",slug:"kamlesh-kumar",fullName:"Kamlesh Kumar"}]}],onlineFirstChaptersFilter:{topicId:"11",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82396",title:"Fluid Inventory Models under Markovian Environment",slug:"fluid-inventory-models-under-markovian-environment",totalDownloads:0,totalDimensionsCites:null,doi:"10.5772/intechopen.104183",abstract:"Today’s products are subject to fast changes due to market conditions, short life cycles, and technological advances. Thus, an important problem in inventory planning is how to effectively manage the inventory control in a dynamic and stochastic environment. The traditional Economic Order Quantity (EOQ) and Economic Production Quantity (EPQ) both are widely and successfully used models of inventory management. However, both models assume constant and fixed parameters over time. Unfortunately, most of these assumptions are unrealistic. In this study, we generalize the EOQ and EPQ models and study production-inventory fluid models operating in a stochastic environment. The inventory level increases or decreases according to a fluid-flow rate modulated by an n-state continuous time Markov chain (CTMC). Our main objective is to minimize the expected discounted total cost which includes ordering, purchasing, production, set up, holding, and shortage costs. Applying regenerative theory, optional sampling theorem (OST) to the multi-dimensional martingale and fluid flow techniques, we develop methods to obtain explicit formulas for these cost functionals. As such, we provide managers with a useful framework and an efficient and easy-to-implement tool to coop with different demand–supply patterns.",book:{id:"11169",title:"Logistics Engineering",coverURL:"https://cdn.intechopen.com/books/images_new/11169.jpg"},signatures:"Yonit Barron"},{id:"82326",title:"Probabilistic Risk Assessments for Static Equipment Integrity",slug:"probabilistic-risk-assessments-for-static-equipment-integrity",totalDownloads:1,totalDimensionsCites:0,doi:"10.5772/intechopen.105550",abstract:"The mechanical integrity of batch-produced machinery is successfully safeguarded using online condition monitoring and reliability theory principles. However, the integrity of nonreplaceable static equipment (pressure vessels, cranes, bridges, and other critical infrastructure) is still widely assured and managed using basic equations (e.g., safety factors and design loads), with no or little regard to the probabilistic nature of their operational damage. The gap between the deterministic “remnant life” assumptions and the probabilistic reality restrains the implementation of new asset integrity technologies (advanced condition monitoring and asset management) because these novel tools are not supported by a numeric cost/benefit analysis in many practical cases. The latter is impossible to implement confidently, while the probability of failure (PoF) versus time remains unquantified. The solution to this problem is holistic and logical: individual equipment integrity analysis now needs to be upgraded to the probabilistic terms at all the stages of life. Even well-known asset integrity technologies can help achieve this goal, providing that they are considered and utilized from the standpoint of harmonizing and aligning their outputs with risk owner’s actual decision-making. This chapter shows real-life case studies to briefly illustrate how the existing integrity engineering tools can be advanced via further PoF considerations, in order to provide the outputs needed for a cost/benefit-based confident and compliant risk control.",book:{id:"11528",title:"Maintenance Management - Current Challenges, New Developments, and Future Directions",coverURL:"https://cdn.intechopen.com/books/images_new/11528.jpg"},signatures:"Yury Sokolov"},{id:"1083885",title:"Design and Planning Robust and Competitive Supply Chains",slug:null,totalDownloads:1,totalDimensionsCites:0,doi:"10.5992/intechopen.1000208",abstract:'
In recent years, supply chains in the manufacturing industry have become more and more complicated, and many cases of supply chain disruptions due to natural disasters have been confirmed. It is necessary for manufacturers to build a system that can help them alleviate losses and shorten recovery periods due to supply chain disruptions. Supplier diversification, as well as supplier evaluation and selection, are discussed as risk aversion measures in many papers. However, even if the procurement source has been evaluated enough, there are problems, such as opportunity loss during recovery periods and soaring procurement costs during normal periods. In this chapter, to help Japanese manufacturers to alleviate opportunity loss under component procurement disruption situations and keep cost competitiveness in normal periods, decision-making models of supply chain structure assessment, supplier selection, procurement allocation, and trading contracts are designed and verified.
',book:{id:"11082",title:"Operations Management",coverURL:"https://cdn.intechopen.com/books/images_new/11082.jpg"},signatures:"Kotomichi Matsuno, Jiahua Weng, Noriyuki Hosokawa and Takahiro Ohno"},{id:"1085055",title:"Performance Measurement Using Deterministic and Stochastic Multiplicative Directional Distance Functions",slug:null,totalDownloads:3,totalDimensionsCites:0,doi:"10.5992/intechopen.1000179",abstract:'
Performance measurement is essential for fostering continuous improvement of the production and operation management in a firm or organization. We consider a deterministic scenario based on a flexible structure of production technology and establish a multiplicative relationship between the generalized multiplicative directional distance function (GMDDF) and geometric distance function (GDF). We also introduce a stochastic multiplicative directional distance function (SMDDF). Based on a stochastic scenario, the SMDDF can be estimated by the method of convex nonparametric least squares. As an illustrative application, we investigate the productive performance of Japanese life insurance companies using a panel dataset spanning 2016 to 2020.
',book:{id:"11082",title:"Operations Management",coverURL:"https://cdn.intechopen.com/books/images_new/11082.jpg"},signatures:"Yu Zhao"},{id:"1085559",title:"Assessment of Medical Equipment Maintenance Management",slug:null,totalDownloads:2,totalDimensionsCites:0,doi:"10.5992/intechopen.1000210",abstract:'
Today's modern hospital is highly dependent on different types of medical equipment to help diagnose, monitor, and treat patients. Medical equipment maintenance is important to reduce costs, reduce patient dissatisfaction, treat the patient in a timely manner, and reduce mortality and risks during patient care. Good maintenance management is important to have well-planned and implemented programs through which hospitals can minimize medical device failures or other problems with the operation of medical equipment. Medical equipment plays an important role in the hospital system; therefore, the acquisition, maintenance, and replacement of medical equipment are key factors in hospitals for the implementation of the health service. Thus, in order to ensure the quality of medical devices for the provision of medical care, it is imperative to evaluate the safety of using hospital maintenance management. In order to achieve these goals, hospitals must develop checklists that identify the state of performance of medical equipment maintenance. It is essential for clinical managers and engineers not only to increase the capacity of the hospital but also to predict the risks of sudden failure. Given the lack of unique and comprehensive maintenance management checklists, the current goal is to design and develop medical equipment maintenance management checklists.
',book:{id:"11082",title:"Operations Management",coverURL:"https://cdn.intechopen.com/books/images_new/11082.jpg"},signatures:"Călin Corciovă, Robert Fuior, Doru Andriţoi and Cătălina Luca"},{id:"81687",title:"Managing Foodservice Quality in the Foodservice Industry",slug:"managing-foodservice-quality-in-the-foodservice-industry",totalDownloads:2,totalDimensionsCites:0,doi:"10.5772/intechopen.104800",abstract:"Quality has become a value that enables businesses to survive and continue existing. Henceforth, food industries need to entrench quality into their business performance. Foodservice quality is characterized as a service that bears on its ability to satisfy stated or implied needs and service free of defects. Foodservice businesses are an integral part of social life, both biologically and socially, biologically as satisfying the nutrition requirements of the society and socially in terms of addressing socialization and esthetics-pleasure values. Therefore, by adopting quality approaches, food industry businesses may encourage customers’ preferences for those businesses that diligently offer these services. Managing food service quality is a complex and challenging task requiring commitment, discipline, and emergent effort from everyone involved in food production processes. The task also requires the necessary management and administration techniques to continuously improve all processes (including quality control from raw material to finished product). Food industries need to be organizationally structured, establish policies and quality programs, measure customer satisfaction, use more quality tools and methodologies, embrace knowledge, apply techniques, and food safety programs to manage food quality. This chapter aims to describe the ISO 22000 system—widely used for quality management in the food industry.",book:{id:"11170",title:"Quality Control",coverURL:"https://cdn.intechopen.com/books/images_new/11170.jpg"},signatures:"Lindiwe Julia Ncube"}],onlineFirstChaptersTotal:278},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:31,numberOfPublishedChapters:314,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:11,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:17,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:14,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. 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He has both an MS and Ph.D. in Biomedical Engineering. He was previously a research scientist at the University of California Los Angeles (UCLA) and visiting professor and researcher at the University of North Dakota. He is currently working in artificial intelligence and its applications in medical signal processing. In addition, he is using digital signal processing in medical imaging and speech processing. Dr. Asadpour has developed brain-computer interfacing algorithms and has published books, book chapters, and several journal and conference papers in this field and other areas of intelligent signal processing. He has also designed medical devices, including a laser Doppler monitoring system.",institutionString:"Kaiser Permanente Southern California",institution:null},{id:"169608",title:"Prof.",name:"Marian",middleName:null,surname:"Găiceanu",slug:"marian-gaiceanu",fullName:"Marian Găiceanu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/169608/images/system/169608.png",biography:"Prof. Dr. Marian Gaiceanu graduated from the Naval and Electrical Engineering Faculty, Dunarea de Jos University of Galati, Romania, in 1997. He received a Ph.D. (Magna Cum Laude) in Electrical Engineering in 2002. Since 2017, Dr. Gaiceanu has been a Ph.D. supervisor for students in Electrical Engineering. He has been employed at Dunarea de Jos University of Galati since 1996, where he is currently a professor. Dr. Gaiceanu is a member of the National Council for Attesting Titles, Diplomas and Certificates, an expert of the Executive Agency for Higher Education, Research Funding, and a member of the Senate of the Dunarea de Jos University of Galati. He has been the head of the Integrated Energy Conversion Systems and Advanced Control of Complex Processes Research Center, Romania, since 2016. He has conducted several projects in power converter systems for electrical drives, power quality, PEM and SOFC fuel cell power converters for utilities, electric vehicles, and marine applications with the Department of Regulation and Control, SIEI S.pA. (2002–2004) and the Polytechnic University of Turin, Italy (2002–2004, 2006–2007). He is a member of the Institute of Electrical and Electronics Engineers (IEEE) and cofounder-member of the IEEE Power Electronics Romanian Chapter. He is a guest editor at Energies and an academic book editor for IntechOpen. He is also a member of the editorial boards of the Journal of Electrical Engineering, Electronics, Control and Computer Science and Sustainability. Dr. Gaiceanu has been General Chairman of the IEEE International Symposium on Electrical and Electronics Engineering in the last six editions.",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',country:{name:"Romania"}}},{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:null},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:"Manufacturing and Technology Integrated Campus – SENAI CIMATEC",institution:null},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:"Polytechnic University of Timişoara",institution:{name:"Polytechnic University of Timişoara",country:{name:"Romania"}}},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:null},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"357085",title:"Mr.",name:"P. Mohan",middleName:null,surname:"Anand",slug:"p.-mohan-anand",fullName:"P. Mohan Anand",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356696",title:"Ph.D. Student",name:"P.V.",middleName:null,surname:"Sai Charan",slug:"p.v.-sai-charan",fullName:"P.V. Sai Charan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"357086",title:"Prof.",name:"Sandeep K.",middleName:null,surname:"Shukla",slug:"sandeep-k.-shukla",fullName:"Sandeep K. Shukla",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356823",title:"MSc.",name:"Seonghee",middleName:null,surname:"Min",slug:"seonghee-min",fullName:"Seonghee Min",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Daegu University",country:{name:"Korea, South"}}},{id:"353307",title:"Prof.",name:"Yoosoo",middleName:null,surname:"Oh",slug:"yoosoo-oh",fullName:"Yoosoo Oh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:"Yoosoo Oh received his Bachelor's degree in the Department of Electronics and Engineering from Kyungpook National University in 2002. He obtained his Master’s degree in the Department of Information and Communications from Gwangju Institute of Science and Technology (GIST) in 2003. In 2010, he received his Ph.D. degree in the School of Information and Mechatronics from GIST. In the meantime, he was an executed team leader at Culture Technology Institute, GIST, 2010-2012. In 2011, he worked at Lancaster University, the UK as a visiting scholar. In September 2012, he joined Daegu University, where he is currently an associate professor in the School of ICT Conver, Daegu University. Also, he served as the Board of Directors of KSIIS since 2019, and HCI Korea since 2016. From 2017~2019, he worked as a center director of the Mixed Reality Convergence Research Center at Daegu University. From 2015-2017, He worked as a director in the Enterprise Supporting Office of LINC Project Group, Daegu University. His research interests include Activity Fusion & Reasoning, Machine Learning, Context-aware Middleware, Human-Computer Interaction, etc.",institutionString:null,institution:{name:"Daegu Gyeongbuk Institute of Science and Technology",country:{name:"Korea, South"}}},{id:"262719",title:"Dr.",name:"Esma",middleName:null,surname:"Ergüner Özkoç",slug:"esma-erguner-ozkoc",fullName:"Esma Ergüner Özkoç",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Başkent University",country:{name:"Turkey"}}},{id:"346530",title:"Dr.",name:"Ibrahim",middleName:null,surname:"Kaya",slug:"ibrahim-kaya",fullName:"Ibrahim Kaya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"419199",title:"Dr.",name:"Qun",middleName:null,surname:"Yang",slug:"qun-yang",fullName:"Qun Yang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Auckland",country:{name:"New Zealand"}}}]}},subseries:{item:{id:"20",type:"subseries",title:"Animal Nutrition",keywords:"Sustainable Animal Diets, Carbon Footprint, Meta Analyses",scope:"An essential part of animal production is nutrition. Animals need to receive a properly balanced diet. One of the new challenges we are now faced with is sustainable animal diets (STAND) that involve the 3 P’s (People, Planet, and Profitability). We must develop animal feed that does not compete with human food, use antibiotics, and explore new growth promoters options, such as plant extracts or compounds that promote feed efficiency (e.g., monensin, oils, enzymes, probiotics). These new feed options must also be environmentally friendly, reducing the Carbon footprint, CH4, N, and P emissions to the environment, with an adequate formulation of nutrients.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/20.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11416,editor:{id:"175967",title:"Dr.",name:"Manuel",middleName:null,surname:"Gonzalez Ronquillo",slug:"manuel-gonzalez-ronquillo",fullName:"Manuel Gonzalez Ronquillo",profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",biography:"Dr. Manuel González Ronquillo obtained his doctorate degree from the University of Zaragoza, Spain, in 2001. He is a research professor at the Faculty of Veterinary Medicine and Animal Husbandry, Autonomous University of the State of Mexico. He is also a level-2 researcher. He received a Fulbright-Garcia Robles fellowship for a postdoctoral stay at the US Dairy Forage Research Center, Madison, Wisconsin, USA in 2008–2009. He received grants from Alianza del Pacifico for a stay at the University of Magallanes, Chile, in 2014, and from Consejo Nacional de Ciencia y Tecnología (CONACyT) to work in the Food and Agriculture Organization’s Animal Production and Health Division (AGA), Rome, Italy, in 2014–2015. He has collaborated with researchers from different countries and published ninety-eight journal articles. He teaches various degree courses in zootechnics, sheep production, and agricultural sciences and natural resources.\n\nDr. Ronquillo’s research focuses on the evaluation of sustainable animal diets (StAnD), using native resources of the region, decreasing carbon footprint, and applying meta-analysis and mathematical models for a better understanding of animal production.",institutionString:null,institution:{name:"Universidad Autónoma del Estado de México",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,series:{id:"13",title:"Veterinary Medicine and Science",doi:"10.5772/intechopen.73681",issn:"2632-0517"},editorialBoard:[{id:"175762",title:"Dr.",name:"Alfredo J.",middleName:null,surname:"Escribano",slug:"alfredo-j.-escribano",fullName:"Alfredo J. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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