\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"8163",leadTitle:null,fullTitle:"Translational Studies on Inflammation",title:"Translational Studies on Inflammation",subtitle:null,reviewType:"peer-reviewed",abstract:"Inflammation is known worldwide, from the bench to the bedside, but it is a hard theme to approach with one single point of view.In this sense, a selection of translational studies would support the medical-scientific community to better understand the complex network of the inflammatory process, its maintenance, and potential treatment targets. The eleven chapters that compose this book present interesting insights into inflammation and its mechanisms, merging classic background with innovative approaches. From the molecular basis to experimental models, the chapters selected for this book bring to readers at different academic levels updated and practical data on inflammation. Find out what drives interdisciplinary medical research on inflammation and enjoy this informative collection.",isbn:"978-1-78984-358-3",printIsbn:"978-1-78984-357-6",pdfIsbn:"978-1-83968-001-4",doi:"10.5772/intechopen.78112",price:119,priceEur:129,priceUsd:155,slug:"translational-studies-on-inflammation",numberOfPages:248,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"70da4d81101fe0cdaecad1f0fdaa2cf5",bookSignature:"Ane C.F. Nunes",publishedDate:"January 8th 2020",coverURL:"https://cdn.intechopen.com/books/images_new/8163.jpg",numberOfDownloads:10104,numberOfWosCitations:3,numberOfCrossrefCitations:6,numberOfCrossrefCitationsByBook:1,numberOfDimensionsCitations:18,numberOfDimensionsCitationsByBook:1,hasAltmetrics:1,numberOfTotalCitations:27,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 15th 2018",dateEndSecondStepPublish:"November 26th 2018",dateEndThirdStepPublish:"January 25th 2019",dateEndFourthStepPublish:"April 15th 2019",dateEndFifthStepPublish:"June 14th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"55270",title:"Prof.",name:"Ane",middleName:null,surname:"Claudia Fernandes Nunes",slug:"ane-claudia-fernandes-nunes",fullName:"Ane Claudia Fernandes Nunes",profilePictureURL:"https://mts.intechopen.com/storage/users/55270/images/system/55270.jpg",biography:"Dr. Ane C.F. Nunes is a geneticist with a master’s degree and Ph.D. in Medical Sciences and Nephrology from the Federal University of Rio Grande do Sul (UFRGS), Brazil. She has postdoctoral experience in renal physiology from the Federal University of Rio de Janeiro (UFRJ), Brazil; clinical medicine and nephrology from the University of São Paulo (USP), Brazil; and nephrology and hypertension from the University of California, Irvine (UCI), USA. She is a Professor of Medical Genetics, Human Genetics, and Molecular Biology. Her research interests include human genetic diseases and cellular and molecular biology applied to nephrology, biochemistry, and microbiology with projects in the following subjects: inflammatory markers, molecular diagnosis, DNA polymorphisms, chronic kidney disease (CKD), polycystic kidney disease (PKD), Fabry disease, rare diseases, cellular and murine models for CKD, RNA processing, fluorescent image analysis, nanoparticles development, and nanomedicine.",institutionString:"University of California, Irvine",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"5",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:"University of California, Irvine",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1035",title:"Clinical Immunology",slug:"immunology-allergology-and-rheumatology-clinical-immunology"}],chapters:[{id:"68815",title:"Introductory Chapter: Overview of the Cellular and Molecular Basis of Inflammatory Process",doi:"10.5772/intechopen.88967",slug:"introductory-chapter-overview-of-the-cellular-and-molecular-basis-of-inflammatory-process",totalDownloads:751,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:null,signatures:"Ane C.F. Nunes",downloadPdfUrl:"/chapter/pdf-download/68815",previewPdfUrl:"/chapter/pdf-preview/68815",authors:[{id:"55270",title:"Prof.",name:"Ane",surname:"Claudia Fernandes Nunes",slug:"ane-claudia-fernandes-nunes",fullName:"Ane Claudia Fernandes Nunes"}],corrections:null},{id:"69530",title:"Spontaneous Prematurity, Innate Immune System, and Oxidative Stress at the Maternal-Fetal Interface: An Overview",doi:"10.5772/intechopen.88379",slug:"spontaneous-prematurity-innate-immune-system-and-oxidative-stress-at-the-maternal-fetal-interface-an",totalDownloads:680,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Despite the multifactorial etiology of prematurity, intra-amniotic infection is present in 25–40% of preterm pregnancies. Bacteria in amniotic cavity synthesize phospholipases associated with the production of prostaglandins that leads to rupture of fetal membranes and uterine contractions. Bacterial pathogen-associated molecular patterns (PAMPs) activate pattern recognition receptors (PRRs) such as Toll-like (TLRs) and NOD-like receptors (NLRs), triggering pathways that culminate in the production of cytokines that further increase prostaglandin release. Importantly, endogenous molecules called damage-associated molecular patterns (DAMPs) released under stressful conditions can also activate PRRs. Risk factors for both preterm labor (PTL) and preterm premature rupture of membranes (PPROM), including infection-induced inflammation, may cause an increase of ROS release and depletion of antioxidant defenses. In spite of the similarity between the pathophysiology of PTL and PPROM, there are significant differences regarding molecular mediators, degree of tissue damage, and oxidative stress present in these two conditions. PPROM seems to be a consequence of notable tissue damage resulting from chronic oxidative stress, while PTL is associated with minimal tissue degradation resulting from acute exposure and greater antioxidant status. A better understanding of prematurity pathophysiology and the differences between PTL and PPROM can benefit therapeutic approaches to prevent these important inflammatory syndromes.",signatures:"Natália Prearo Moço, Bruna Ribeiro de Andrade Ramos, Mariana de Castro Silva, Jossimara Polettini, Ramkumar Menon and Márcia Guimarães da Silva",downloadPdfUrl:"/chapter/pdf-download/69530",previewPdfUrl:"/chapter/pdf-preview/69530",authors:[{id:"180264",title:"Dr.",name:"Bruna",surname:"Ribeiro de Andrade Ramos",slug:"bruna-ribeiro-de-andrade-ramos",fullName:"Bruna Ribeiro de Andrade Ramos"},{id:"291199",title:"Dr.",name:"Márcia",surname:"Guimarães Da Silva",slug:"marcia-guimaraes-da-silva",fullName:"Márcia Guimarães Da Silva"},{id:"291223",title:"Dr.",name:"Natália",surname:"Prearo Moço",slug:"natalia-prearo-moco",fullName:"Natália Prearo Moço"},{id:"291326",title:"BSc.",name:"Mariana",surname:"De Castro Silva",slug:"mariana-de-castro-silva",fullName:"Mariana De Castro Silva"},{id:"291327",title:"Dr.",name:"Ramkumar",surname:"Menon",slug:"ramkumar-menon",fullName:"Ramkumar Menon"},{id:"315959",title:"Dr.",name:"Jossimara",surname:"Polettini",slug:"jossimara-polettini",fullName:"Jossimara Polettini"}],corrections:null},{id:"66350",title:"Pharmacological Challenge Models in Clinical Drug Developmental Programs",doi:"10.5772/intechopen.85352",slug:"pharmacological-challenge-models-in-clinical-drug-developmental-programs",totalDownloads:888,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Early phase clinical research for drug development requires the investigation of safety, tolerability and efficacy of novel compounds. The latter is hampered by the absence of the disorder in healthy volunteers, which is why challenge models are often applied in order to demonstrate ‘proof of pharmacology.’ These challenge models can often be translatable from animal work and can inform the drug developer which dose, dosing regimen or application frequency should be selected prior to phase II studies in the target population. Furthermore, these challenge models represent well-controlled settings to perform activity screening of the compound. The following skin challenge models will be reviewed in this chapter: inflammation induced by Toll-like receptor agonists such as imiquimod, KLH challenge, UV-B irradiation and histamine.",signatures:"Salma Assil, Robert Rissmann and Martijn Bastiaan Adriaan van Doorn",downloadPdfUrl:"/chapter/pdf-download/66350",previewPdfUrl:"/chapter/pdf-preview/66350",authors:[{id:"284601",title:"Dr.",name:"Martijn Bastiaan Adriaan",surname:"Van Doorn",slug:"martijn-bastiaan-adriaan-van-doorn",fullName:"Martijn Bastiaan Adriaan Van Doorn"},{id:"287620",title:"Dr.",name:"Robert",surname:"Rissmann",slug:"robert-rissmann",fullName:"Robert Rissmann"},{id:"295605",title:"Ms.",name:"Salma",surname:"Assil",slug:"salma-assil",fullName:"Salma Assil"}],corrections:null},{id:"66216",title:"Sex Differences in Obesity-Induced Inflammation",doi:"10.5772/intechopen.84941",slug:"sex-differences-in-obesity-induced-inflammation",totalDownloads:1441,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Obesity is defined as a BMI greater than 25 kg/m2. Once thought to simply be a nutritional disorder, obesity has become a major health concern characterized by a state of constant low-grade inflammation caused by chronic adiposity. This state of inflammation is characterized by circulating inflammatory mediators, such as IL-6, leptin, and TNF-α, as well as varying levels of glucose-regulating hormones produced by obese adipose tissue. When left untreated, obesity can lead to a number of diseases including, but not limited to, cardiovascular disease, metabolic syndrome, neurodegeneration, type II diabetes mellitus, chronic kidney disease, and infertility. The distribution of adiposity differs in men and women, and these differences, along with the differences in sex hormones and sex hormone levels, can exacerbate or attenuate the course of disease pathology. Obesity can also be exacerbated by stress, which can worsen disease pathogenesis. In this review, we will explore how obesity affects inflammation and disease and how sex can affect the course of these diseases.",signatures:"Sari Terrazas, Lauren Brashear, Anna-Katherine Escoto, Shannon Lynch, Dylan Slaughter, Neena Xavier, Norman Robert Estes II and Samantha Giordano-Mooga",downloadPdfUrl:"/chapter/pdf-download/66216",previewPdfUrl:"/chapter/pdf-preview/66216",authors:[{id:"213186",title:"Dr.",name:"Samantha",surname:"Giordano-Mooga",slug:"samantha-giordano-mooga",fullName:"Samantha Giordano-Mooga"},{id:"294123",title:"Ms.",name:"Sari",surname:"Terrazas",slug:"sari-terrazas",fullName:"Sari Terrazas"},{id:"294124",title:"Ms.",name:"Lauren",surname:"Brashear",slug:"lauren-brashear",fullName:"Lauren Brashear"},{id:"294125",title:"Ms.",name:"Anna-Katherine",surname:"Escoto",slug:"anna-katherine-escoto",fullName:"Anna-Katherine Escoto"},{id:"294126",title:"Ms.",name:"Shannon",surname:"Lynch",slug:"shannon-lynch",fullName:"Shannon Lynch"},{id:"294127",title:"Mr.",name:"Dylan",surname:"Slaughter",slug:"dylan-slaughter",fullName:"Dylan Slaughter"},{id:"294128",title:"Dr.",name:"Neena",surname:"Xavier",slug:"neena-xavier",fullName:"Neena Xavier"},{id:"294129",title:"Dr.",name:"Norman Robert",surname:"Estes II",slug:"norman-robert-estes-ii",fullName:"Norman Robert Estes II"}],corrections:null},{id:"66451",title:"The Wound-Healing Portal Hypertensive Response",doi:"10.5772/intechopen.84689",slug:"the-wound-healing-portal-hypertensive-response",totalDownloads:850,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Portal hypertensive inflammation is associated with chronic liver diseases. The three successive and overlapping systemic inflammatory phenotypes, i.e., neurogenic, immune, and endocrine, which characterize the wound-healing response, are expressed by the portal venous system upon liver injury. The diverse functions of hepatic stellate cells in homeostasis and inflammation indicate the versatile nature of these mesenchymal-derived cells, which could adopt numerous phenotypes according to the interstitial microenvironmental characteristics. Consequently, these inflammatory phenotypes could represent the reexpression of two extra-embryonic functional axis, i.e., coelomic-amniotic and trophoblastic-vitelline, whose coupling in the portal system would induce a gastrulation-related phenotype. Therefore, hepatic stellate cells and liver-specific mesenchymal cells could recapitulate and couple these abovementioned extra-embryonic phenotypes during portal hypertension. These hepatic cellular population, thanks to their potential ability to integrate and reexpress functions showing analogies to extra-embryonic functions, display characteristics of stem/progenitor cells. In this way, during the development of portal hypertension, hepatic stellate cells not only could reexpress extra-embryonic functions, but also could adapt themselves in order to induce a gastrulation-related process in the space of Disse. Hence, by understanding the ontogenic interactions between hepatic stellate cells and the host inflammatory response in portal hypertension, it is possible to design effective therapeutic and prophylactic strategies to avoid or reverse wound-like hypertensive response.",signatures:"Maria Angeles Aller, Javier Blanco-Rivero, Ana Arias and Jaime Arias",downloadPdfUrl:"/chapter/pdf-download/66451",previewPdfUrl:"/chapter/pdf-preview/66451",authors:[{id:"287050",title:"Prof.",name:"Jaime",surname:"Arias",slug:"jaime-arias",fullName:"Jaime Arias"},{id:"287064",title:"Dr.",name:"Ana",surname:"Arias",slug:"ana-arias",fullName:"Ana Arias"},{id:"288136",title:"Prof.",name:"Maria Angeles",surname:"Aller",slug:"maria-angeles-aller",fullName:"Maria Angeles Aller"},{id:"288154",title:"Prof.",name:"Javier",surname:"Blanco-Rivero",slug:"javier-blanco-rivero",fullName:"Javier Blanco-Rivero"}],corrections:null},{id:"70170",title:"Review and Implications of Traditional Indian Medicine for Inflammatory Bowel Disease",doi:"10.5772/intechopen.89465",slug:"review-and-implications-of-traditional-indian-medicine-for-inflammatory-bowel-disease",totalDownloads:694,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Inflammatory bowel disease (IBD) is a group of intestinal disorders that cause prolonged inflammation of digestive tract. Chronic inflammation results in Crohn’s disease (CD) and ulcerative colitis (UC). There is a disruption of homeostasis of various regulatory factors, for example, cohesive functioning of intestinal epithelial barrier, macrophages, and cellular mediators such as cytokines and chemokines. Natural products derived from plants based on traditional system of medicine have exhibited efficacy for UC and CD in experimental models and clinical trials. In the present review, current developments of natural products and herbs for the treatment of IBD in the context of Indian traditional medicine have been highlighted. Two classes of Ayurvedic formulation, fermented preparations (Asava and Arishta) and Ghrita (preparations involving butter), are employed for the maintenance of intestinal disorders. Here, we discuss mainly about the fermented preparations, their main constituents, and correlations with modern findings. The way these fermented formulations are processed also affects the extraction of constituents in them. So, the correlation between the chemistry of the plant material (their constituents as well) with the IBD was done. These correlations may serve as a step forward to reduce the gap between modern system of medicine and traditional system of medicine.",signatures:"Uma Ranjan Lal and Inder Pal Singh",downloadPdfUrl:"/chapter/pdf-download/70170",previewPdfUrl:"/chapter/pdf-preview/70170",authors:[{id:"208194",title:"Dr.",name:"Uma",surname:"Ranjan Lal",slug:"uma-ranjan-lal",fullName:"Uma Ranjan Lal"},{id:"315800",title:"Dr.",name:"Inder Pal",surname:"Singh",slug:"inder-pal-singh",fullName:"Inder Pal Singh"}],corrections:null},{id:"66963",title:"Immuno-Oncology, Imaging Biomarkers and Response to Chemotherapy in Cancer Treatment",doi:"10.5772/intechopen.84690",slug:"immuno-oncology-imaging-biomarkers-and-response-to-chemotherapy-in-cancer-treatment",totalDownloads:837,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Immuno-oncology is a young and growing field in cancer therapy. It stimulates immune system to target and attack the tumor or inhibiting the immune response. Recent findings in cancer immunotherapy has revealed that the immune system can control many cancers across various histologies, producing durable responses in a way which not seen with many small molecule drugs. Advances in understanding the role and molecular mechanisms of immunotherapy are revolutionizing clinical practice in cancer treatment. Immunotherapy is being intensively explored with the aim of improving primary response rates or prolonging overall survival. The purpose of this chapter is to review the different aspect of immunotherapy including blockade of immunological checkpoints, immuno-oncology and imaging biomarkers, immune response, therapeutic resistance and combination therapy, while several additional immuno-therapeutic strategies are also highlighted.",signatures:"Alireza Ziaei and Forough Kheiry",downloadPdfUrl:"/chapter/pdf-download/66963",previewPdfUrl:"/chapter/pdf-preview/66963",authors:[{id:"271630",title:"Dr.",name:"Alireza",surname:"Ziaei",slug:"alireza-ziaei",fullName:"Alireza Ziaei"},{id:"300612",title:"Dr.",name:"Forough",surname:"Kheiry",slug:"forough-kheiry",fullName:"Forough Kheiry"}],corrections:null},{id:"66299",title:"TLR4-Induced Inflammation Is a Key Promoter of Tumor Growth, Vascularization, and Metastasis",doi:"10.5772/intechopen.85195",slug:"tlr4-induced-inflammation-is-a-key-promoter-of-tumor-growth-vascularization-and-metastasis",totalDownloads:1051,totalCrossrefCites:2,totalDimensionsCites:5,hasAltmetrics:0,abstract:"Toll-like receptor-4 (TLR4) is a powerful pathway best known for inducing inflammation in response to bacteria-produced lipopolysaccharide. TLR4 is also activated by endogenous ligands produced by host-damaged cells and a chemo-drug paclitaxel. Under normal conditions, TLR4 is expressed mainly in macrophages and, at a lower level, in epithelial, endothelial, and stromal cells. Activated TLR4 significantly increases inflammatory cytokines and enhances cell proliferation, migration, invasion, and survival. While these functions in normal cells are essential for host defense and tissue repair, TLR4 overexpression in malignant cells promotes tumor growth and metastasis. This is because pro-oncogenic effects of activated TLR4 in tumor cells are amplified by similar event in TLR4-positive tumor-associated cells including endothelial cells and their mobilized progenitors. The collective activation of multiple cell types within the tumor promotes chemoresistance and metastasis. Here, we summarize the current knowledge of the TLR4 pathway and its functional outcomes in normal and tumor cells. We also discuss its underappreciated role in supporting tumor progression through vascular activation and recruitment of endothelial progenitors. The review considers several open questions regarding the impact of TLR4-mediated pro- and antitumor effects, structural requirements for recognition of the TLR4 complex, and a potential contribution of chemotherapy to tumor spread.",signatures:"Sophia Ran, Nihit Bhattarai, Radhika Patel and Lisa Volk-Draper",downloadPdfUrl:"/chapter/pdf-download/66299",previewPdfUrl:"/chapter/pdf-preview/66299",authors:[{id:"79980",title:"Dr.",name:"Sophia",surname:"Ran",slug:"sophia-ran",fullName:"Sophia Ran"},{id:"294697",title:"BSc.",name:"Nihit",surname:"Bhattarai",slug:"nihit-bhattarai",fullName:"Nihit Bhattarai"},{id:"294698",title:"BSc.",name:"Radhika",surname:"Patel",slug:"radhika-patel",fullName:"Radhika Patel"},{id:"294699",title:"MSc.",name:"Lisa",surname:"Volk-Draper",slug:"lisa-volk-draper",fullName:"Lisa Volk-Draper"}],corrections:null},{id:"65944",title:"The Potential Contribution of Nanoparticles in the Treatment of Inflammatory Diseases",doi:"10.5772/intechopen.84776",slug:"the-potential-contribution-of-nanoparticles-in-the-treatment-of-inflammatory-diseases",totalDownloads:946,totalCrossrefCites:1,totalDimensionsCites:4,hasAltmetrics:0,abstract:"The scope of this chapter is to review the significant effect that nanomedicine has had in the treatment of inflammatory diseases. Nanotechnology has been widely studied in the last decade and proved to be an encouraging strategy in the healthcare system and the medical field. This novel technology provides a vast number of nanomaterials and tools that could actually diagnose and treat different inflammatory disorders and conditions. An enormous amount of in vivo and in vitro research was conducted by many groups to validate the positive contribution that nanoparticles have in regard to the treatment of inflammation and its associated illnesses. This contribution is due to the fact that nanoparticles could be modulated to pass through metabolic barriers and specifically targeted to deliver drugs to the required sites without affecting healthy cells and tissues. This makes them a promising therapeutical choice for the treatment of inflammatory diseases in the future.",signatures:"Mona A. Elsayed and Ayman Norredin",downloadPdfUrl:"/chapter/pdf-download/65944",previewPdfUrl:"/chapter/pdf-preview/65944",authors:[{id:"283226",title:"M.Sc.",name:"Mona A.",surname:"Elsayed",slug:"mona-a.-elsayed",fullName:"Mona A. Elsayed"},{id:"290741",title:"Dr.",name:"Ayman",surname:"Noreddin",slug:"ayman-noreddin",fullName:"Ayman Noreddin"}],corrections:null},{id:"66248",title:"Exploring Epigenetic Drugs in the Regulation of Inflammatory Autoimmune Diseases",doi:"10.5772/intechopen.85168",slug:"exploring-epigenetic-drugs-in-the-regulation-of-inflammatory-autoimmune-diseases",totalDownloads:1095,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"During recent years, numerous studies have shown that epigenetics, heritable changes that do not involve alterations in the DNA sequence, play an important role in the development, function, and regulation of the immune system as well as in the onset and progress of autoimmune diseases. For that reason, in the following chapter, we will review some of the most important concepts about epigenetics and how they modulate the development and function of immune cells, specifically macrophages, dendritic cells, and T cells. Moreover, we will review the role of epigenetics on autoimmune diseases, as well as the use of pharmacological modulation of the epigenetic machinery, as an innovative way to approach a potential new treatment or improve the current treatments of autoimmune diseases.",signatures:"Cristian Doñas, Alejandra Loyola and Mario Rosemblatt",downloadPdfUrl:"/chapter/pdf-download/66248",previewPdfUrl:"/chapter/pdf-preview/66248",authors:[{id:"283197",title:"Dr.",name:"Mario",surname:"Rosemblatt",slug:"mario-rosemblatt",fullName:"Mario Rosemblatt"},{id:"283198",title:"Dr.",name:"Cristian",surname:"Doñas",slug:"cristian-donas",fullName:"Cristian Doñas"},{id:"283199",title:"Dr.",name:"Alejandra",surname:"Loyola",slug:"alejandra-loyola",fullName:"Alejandra Loyola"}],corrections:null},{id:"66824",title:"The Experimental Bioengineering of Complete Spinal Cord Injury in Adult Rats",doi:"10.5772/intechopen.85353",slug:"the-experimental-bioengineering-of-complete-spinal-cord-injury-in-adult-rats",totalDownloads:871,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The chapter is devoted to the research of experimental complete mechanical spinal injury in adult rats and attempts at bioengineering restoration of the structure and function of the spinal cord using a protein-polysaccharide construct that includes bovine collagen, highly purified crab chitosan ascorbate, nanostructuring additives in the form of sodium chondroitin sulfate, sodium hyaluronate, heparin sulfate in the presence of complete nutrient medium DMEM, neural supplement N2, conditioned nutrient medium, obtained about brain cell mouse embryos and mouse embryonic stem cells, retinoic acid, and mouse neural progenitor cells derived from embryonic stem cells. After a complete intersection of the spinal cord at the level of the ninth thoracic vertebra, the authors directly implanted a collagen-chitosan construct into the gap between the ends of the spinal cord. Analysis of the recovery of motor and sensory and vegetative functions of the spinal cord for 20 weeks after surgery using the cytological immune-fluorescent method showed a high viability of the transplanted neural cell precursors during the entire observation period and the early emergence of activity of mediators of nerve signal transmission in the implantation zone of the structure with accompaniment active dynamics of reducing neurodeficiency.",signatures:"I.N. Bolshakov, A.V. Svetlakov, A.V. Eremeev and Yu.I. Sheina",downloadPdfUrl:"/chapter/pdf-download/66824",previewPdfUrl:"/chapter/pdf-preview/66824",authors:[{id:"287303",title:"Prof.",name:"Igor",surname:"Bolshakov",slug:"igor-bolshakov",fullName:"Igor Bolshakov"},{id:"290764",title:"M.Sc.",name:"Anatoly V.",surname:"Svetlakov",slug:"anatoly-v.-svetlakov",fullName:"Anatoly V. Svetlakov"},{id:"290854",title:"Dr.",name:"A.V.",surname:"Eremeev",slug:"a.v.-eremeev",fullName:"A.V. Eremeev"},{id:"290855",title:"Dr.",name:"Yu.I.",surname:"Sheina",slug:"yu.i.-sheina",fullName:"Yu.I. 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Malignant mesothelioma (MM) is a rare malignant disease originating from neoplastic mesothelial cells which compose the serous membranes of pleura, peritoneum, pericardium, or testis. Mesothelioma responds little to chemo and radiotherapy and is associated with a poor prognosis. In Western Europe, the incidence is increasing and is expected to peak in the year 2020 (Peto et al., 1999; Pelucchi et al., 2004) while in Japan and Australia, the peak is expected for 2025 and 2015 respectively. Thus in order to improve the clinical outcome in the pharmacological treatment of this refractory tumour, drugs directed against novel and/or characterized tumour-specific cellular targets are needed. Malignant pleural mesothelioma (MPM) originates from the pleural layers. Pleura is not just a limiting protective layer for lung, but a dynamic cellular structure regulating serial responses to injury, infection, and disease. Mesothelial cells are biologically active because they can sense and respond to signals within their microenvironment. The development of MM is associated in most patients with a history of asbestos exposure (Mossman et al., 1996). In addition, some investigations have implicated SV40 virus in the pathogenesis of a subset of mesotheliomas (Carbone et al., 2003). Exposure to asbestos typically occurs during mining and milling of the fibers or during industrial application of asbestos in textiles, insulation, shipbuilding, brake lining mechanics, and other areas. Non occupational exposure is usually related to asbestos fibers inadvertently released into the environment and transported by asbestos-contaminated clothing or other materials. After asbestos inhalation, fibers deposited in the lungs typically remain in close contact with lung epithelial cells. Since this fiber-cell interaction could potentially initiate or inhibit cellular functions, asbestos acts as a carcinogen by initiating the carcinogenic process. Carcinogens are known to modulate the transcription factors, anti-apoptotic proteins, proapoptotic proteins, protein kinases, cell cycle proteins, cell adhesion molecules, cyclooxygenase-2, and growth factor signaling pathways. Research has demonstrated that asbestos exposure generates reactive oxygen species and activates macrophages and other cell types to produce these compounds as well as cytokines and growth factors (Kamp & Weitzman, 1999). Furthermore, the deposition of insoluble amphibole fibers results in a chronic inflammatory state and increased rates of MM in exposed individuals (Mossman & Churg, 1998). This article reviews recent studies regarding some MM molecular targets involved in inflammation for not only prevention but also for therapy of this deadly cancer.
The existence of inflammation has been associated with up-regulation of the inducible cyclooxygenases-2 (COX-2), leading to an increase in its product prostaglandin-E2 (PGE-2) (Vane et al., 1994), and is associated with an increased risk of cancer (Ambs et al., 1999). Considerable evidence indicates that COX-2–derived PGE2 can activate epidermal growth factor receptor (EGFR) signaling and thereby stimulate cell proliferation. The mechanism(s) by which this occurs seem to be complex and context specific. Regardless of the precise mechanism for doing so, exposure to COX-2–derived PGE2 can initiate a positive feedback loop whereby activation of EGFR results in enhanced expression of COX-2 and increased synthesis of prostaglandins (Lippman et al., 2005). Although there is a crosstalk between EGFR and COX-2 in carcinogenesis it is important to stress that EGFR and its downstream effectors can be activated independently of COX-2/PGE2. For example, in MM, asbestos fibers activate the EGFR resulting in activation of extracellular signal regulated kinase downstream (Shukla et al., 2011). Similarly, COX-2/PGE2 and its downstream effectors can be regulated independently of EGFR signaling. For example, PGE2 is able to rapidly stimulate Erk phosphorylation in a subset of non–small cell lung cancer (NSCLC) cell lines via intracellular activation of kinase cascades independently of the proteolytic release of EGFR ligands via Src. (Gutkind, 1998; Krysan et al., 2005). These findings have provided the underpinnings for developing agents targeting EGFR or COX-2. A recent study with COX-2 and EGFR inhibitors in MM has shown that the differences in the susceptibility to drugs could be due to the differences in the signalling pathways affected, in addition to the responses that may depend on cell type. In particular it was demonstrated in the Ist-Mes-2 MM cell line a synergistic effect on the inhibition of cell growth between the active small molecule inhibitor of EGFR, gefitinib and rofecoxib, a drug that specifically targets COX-2. Interestingly, the other two cell lines sensitive to treatment with single drugs Ist-Mes-1 and MPP89, did not display this synergistic effect. Only in Ist-Mes-2, the cell line where p-AKT was not detectable, did the combination of rofecoxib and gefitinib result in a synergistic effect. This study suggests that identifying the mechanisms that underlie these differences in sensitivity of cell lines of MM single agents and their combinations, can help us to explore new proteins involved in drug resistance. (Stoppoloni et al., 2010). Lately a new therapeutic target, the Aromatase (CYP19A1), has been identified in MM. This new discovery has highlighted the possibility that there may be in MM as well as in breast cancer a relationship between inflammation, COX-2, EGFR and Aromatase (Fig.1)(Chumsri et al. 2011. These key molecules and pathways that connect chronic inflammation with inflammation associated oncogenic transformation will be described. We emphasize how the increased understanding of the role of COX-2, EGFR and CYP19A1 in MM may provide novel preventive, diagnostic and therapeutic strategies for MM.
Posible relationship among inflammation, COX-2, EGFR and Aromatase.
Arachidonic acid (AA) metabolic pathway can be activated by inflammation (Stimulus). AA is released from membrane phospholipids by a phospholipase named phospholipase A2 (PLA-2) enzyme and converted to bioactive PGE-2 by COX-2. PGE2 is an important regulator of
COXs, also known as prostaglandin-endoperoxide synthases, are key regulatory enzymes in the biosynthesis of prostanoids, a class of hormones including prostaglandins, prostacyclins, and thromboxanes responsible for multiple inflammatory mitogenic, and angiogenic activities in various tissue and organ systems. Increasing interest on COXs is due to the many evidences showing the involvement of these enzymes not only in physiologic but even in pathophysiologic processes such as development and progression of cancer. Two COX isoforms have been identified as COX-1 and COX-2. COX-1 is expressed constitutively in several cell types of normal mammalian tissues, where it is involved in the maintenance of tissue homeostasis. In contrast, COX-2 is an inducible enzyme responsible for PGE2 production at sites of inflammation (Harris, 2007). The mechanism through which COX-2 exherts its tumorigenic action can be directly mediated by the enzyme or due to effects of its products. COX-2 is an oxygenase and its intermediates are highly reactive. It is possible that these compounds may cause free radical damage, for example, against DNA molecule (Cardillo et al., 2005). There is considerable evidence that prostaglandins, participate both in normal growth responses and in aberrant growth, including carcinogenesis (Greenhough et al., 2009). PGE2 exerts its autocrine/paracrine effects on target cells by binding to four types of membrane-bound, G protein-coupled receptors termed as EP1, EP2, EP3, and EP4 (E-series prostanoid receptors ) (Narumiya et al. 1999). These receptors are often coexpressed in the same cell type and use different, and in some cases, opposing intracellular signalling pathways (Breyer et al. 2001).Following ligand binding, the EP receptors activate different signal transduction pathways. EP1 raises intracellular Ca2_, whereas EP3 reduces or increases cyclic -adenosin monophosphate (cAMP) by activating inhibitory G (Gi) or stimulatory G (Gs) proteins depending on the particular splice variant expressed by the cell (Kotani, M et al. 1995). The EP2 and EP4 receptors increase intracellular cAMP by activating adenylate cyclase via Gs proteins. However, differences in the strength of Gs coupling, activation of other signal transduction pathways, agonist-induced desensitization, and agonist-induced internalization result in a differential response of the target cell to a ligand-induced activation of the EP2 or EP4 receptors (Akaogi et al. 2006).It was shown that PGE2 stimulation of both EP2 and EP4 receptors involves transactivation of the epidermal growth factor receptor (EGFR) signaling pathway to promote tumorigenesis (Buchanan et al.; Pai et al 2003; Sale set al. 2005 ). PGE-2 promotes tumor growth with subsequent enhancement of cellular proliferation, promotion and angiogenesis, stimulation of invasion/mobility, suppression of immune responses and inhibitiuon of programmed cell death by inducing expression of the Bcl-2 protooncogene (which can suppress apoptosis) (Cardillo et al.,2005) (Fig.2).
PGE2 in carcinogenesis
For several types of cancer the real risk factor seems to be chronic inflammation (Prescott & Fitzpatrick, 2000) that maintains high level of COX-2 and increase events that promote tumor formation. A tragic example of this mechanism is MM. Although molecular mechanisms of asbestos tumorigenicity have not been elucidated, research has shown that deposition of insoluble amphibole fibers results in a chronic inflammatory state (Mossman & Churg, 1998) and that this state generates reactive oxygen and nitrogen species, as well as cytokines and growth factors, through the activation of macrophages and other cell types (Kamp & Weitzman, 1999).
As expected, the prolonged inflammation causes the increase of COX-2 level, that is actually recognized as an important MM prognostic factor (Edwards et al., 2002; Mineo et al., 2010). A study clearly demonstrated that COX-2 expression is a strong prognostic factor in human mesothelioma, which contributes independently to the other clinical and histopathologic factors in determining a short survival (Edwards et al., 2002). Although the regulation of mRNA stability appears to be the most important regulatory step for COX-2 expression, several studies have reported that other mechanisms, such as transcriptional control or hypermethylation (Dixon et al., 2000), also are involved in the regulation of COX-2 expression. In cancer cells, it was demonstrated previously that altered post-transcriptional regulation of COX-2 is mediated by increased cytoplasmic mRNA binding of the mRNA stability factor HuR (Dixon et al., 2001). In MM, the cytoplasmic expression of HuR was correlated significantly with high COX-2 expression and with poor survival (Stoppoloni et al.,2008). Finally, COX-2 has been proposed to exert its influence on mesangial cell proliferation
The epidermal growth factor receptor (EGFR) is the cell-surface receptor for members of the epidermal growth factor family (EGF-family) of extracellular protein ligands (Herbst, 2004). Upon activation by its growth factor ligands, EGFR undergoes a transition from an inactive monomeric form to an active homodimer. In addition, EGFR may pair with another member of the ErbB receptor family, such as ErbB2/Her2/neu, to create an activated heterodimer. EGFR dimerization stimulates its intrinsic intracellular protein-tyrosine kinase activity. As a result, autophosphorylation of several tyrosine residues in the C-terminal domain of EGFR occurs (P-EGFR). This autophosphorylation leads to the activation of downstream signalling cascades including the RAS/extracellular signal regulated kinase (ERK) pathway, the phosphatidylinositol 3-kinase/AKT (PI3K/AKT) pathway and the Janus kinase/Signal transducer and activator of transcription (JAK/ STAT) pathway (Fig.3).
Activation of downstream signaling cascade by P-EGFR
These pathways act in a coordinated manner to promote cell survival (Oda et al., 2005). Such proteins modulate phenotypes such as cell migration, adhesion, and proliferation. EGFR is reportedly over-expressed in a wide variety of malignancies. Various studies suggest that receptor tyrosine kinase activation participates in the oncogenic progression of non neoplastic mesothelial progenitor cells to malignant mesothelioma. Asbestos fiber interact with the external domain of the EGFR to cause dimerization, activation and increased EGFR mRNA and protein levels in rat and human SV-40 immortalized mesothelial cells (Shukla et al., 2011). Up-regulated EGFR and resulting tyrosine phosphorylation leads to the Ras activation which phosphorylates directly and activates Raf (Rapidly Accelerated Fibrosarcoma). Raf is responsible for phosphorylation of the mitogen associated / extracellular regulated kinase-1 (MEK) which in turn phosphorylates extracellular regulated kinases (ERK) on specific residues of threonine and tyrosine (Ras-Raf-MEK-ERK mitogen activated protein kinase (MAPK) pathway). ERK activates a variety of substrates involved in cell cycle. The ERK family consists of at least seven isoforms, and little is known about their regulation and function. ERK1/2 phosphorylation by asbestos, is dependent on phosphorylation of the EGFR. Moreover, has been shown that ERK5, a redox-sensitive kinase known to mediate c-
A novel marker of MM recently identified is the CYP19A1 (Stoppoloni et al., 2011). CYP19A1 is the cytochrome P450 enzyme complex that converts C19 androgens to C18 estrogens. The human CYP19A1 gene, located in the 21.2 region on the long arm of chromosome 15 (15q21.2), spans a region that consists of a 30 kb coding region and a 93 kb regulatory region. Its regulatory region contains at least 10 distinct promoters regulated in a tissue- or signalling pathway-specific manner. Each promoter is regulated by a distinct set of regulatory sequences in DNA and transcription factors that bind to these specific sequences. These partially tissue-specific promoters are used in the gonads, bone, brain, vascular tissue, adipose tissue, skin, foetal liver, and placenta for estrogen biosynthesis necessary for human physiology (Bulun et al., 2004). Estrogens contribute to differentiation and maturation in normal lung (Patrone et al., 2003) and also stimulate growth and progression of lung tumors (Stabile et al., 2002; Pietras et al., 2005). Two major pathways, generally termed genomic and non-genomic, are known to mediate estradiol effects on cells. (Fig.4)
Estrogen Receptor fuction: Genomic (Nuclear ER) and Non Genomic (Membrane ER) action
Estradiol has traditionally been described to mediate its effects via intracellular receptors located in the cytoplasm or on the nuclear membrane and thus studies have investigated the effect of estradiol on transcription factors in the regulation of target genes. Estradiol also acts on the plasma membrane to initiate signaling pathways in the cytoplasm and regulate cellular functions, which is called the non-genomic pathway (Simoncini et al., 2004; Simoncini & Genazzani, 2003). PGE2 is thought to be an important regulator of CYP19A1 gene expression (Zhao et al., 1996). PGE2 increased CYP19A1 activity level in MM cell lines (Stoppoloni et al., 2011). Over the last decade many studies have been carried out to identify potential CYP19A1 stimulatory factors: IL-6 was the most potent factor detected that could stimulate CYP19A1 activity (Reed et al., 1992). The MM cell lines were capable of releasing a constitutively high amount of IL-6 (>1,100 pg.mL supernatant-1 of confluent cultures) (Orengo et al., 1999). This could explain the presence of CYP19A1 in MM cells. Furthermore, estrogen receptor (ER) were also detected in MM cell lines by western blot. The classic 67 kDa and a variant 46 kDa of ERα and 59 kDa of ERβ were expressed in MM cell lines. In support of these results there are recent literature data pointing to a role for estrogens in MM pathogenesis. Epidemiologic studies have identified female gender as a positive prognostic factor for MM (Pinton et al., 2009), although no experimental explanation of this finding has been provided thus far. CYP19A1 was expressed in the majority of samples from patients with MM. Cytoplasmic expression of CYP19A1 significantly correlated with poor survival (Stoppoloni et al., 2011). The World Health Organization classifies MM into epithelial, sarcomatoid, and biphasic types, each of which can be subdivided further (Travis et al., 1999). This classification has implications for both diagnosis and prognosis. Prognosis is poor for all MMs, but sarcomatoid MMs have a particularly poor response rate to treatment (Neragi-Miandoab et al., 2008). A significant association between high expression of CYP19A1 and sarcomatoid MMs was found (Stoppoloni et al., 2011). These observations strongly suggest that CYP19A1 plays a role in tumour progression in MM. MM cell proliferation was significantly reduced by exemestane (aromatase inhibitor) treatment. Treatment of MM cells with exemestane led to significant reduction of tumor cell growth, perturbation of cell cycle, caspase activation, PARP cleavage, down-regulation of p-AKT and Bcl-xL.. Since Akt pathway as well as Bcl-xL are implicated in conferring resistance to conventional chemotherapy exemestane could open new treatment strategies to be associated with standard therapy for patients afflicted with MM (Stoppoloni et al., 2011).
COX-2, EGFR and CYP19A1 are investigational at the present time. The cross-talk between markers that have been described and their value as prognostic indicators will need to be validated in prospective studies in larger patient populations. Their role at the present time is to give us direction towards development of newer therapies in this very resistant tumor. The standard of care at the present time for malignant mesothelioma does not involve checking for these markers and making patient care decisions based on them. But we hope that in the near future this would become a reality with a better treatment approach and prognosis for these patients. Furthermore the possibility of using natural anti-inflammatory products in the chemoprevention of people at risk of MM can not exclude.
Venous thromboembolism (VTE) is a set of diseases in which blood clot forms and occludes venous circulation and regard as the third frequent acute cardiovascular disease [1]. Clinically, VTE presents as deep vein thrombosis (DVT) and pulmonary embolism (PE) which account for two-third and one-third of VTE, respectively [2]. The estimated annual rate of incidence of VTE is 80 to 260 per 100000 population [3]. In general, the incidence of VTE increases with age. One epidemiologic study in United States showed that the incidence of VTE was 143 per 100000 in papulation at age 45–49 years and 1134 per 100000 in those at age > 80 years [4]. There is difference of incidence between ethnicities and black and white have higher incidence than other races [2]. Although patients with VTE might be asymptomatic, VTE is a potentially fatal disease. One study reported that the estimated annual VTE-related death was around 300000 in U.S [5] and nearly 30% of VTE patients died within 30 days after diagnosis. Compared to DVT, PE accounts for majority of early-stage mortality of VTE [6, 7]. In addition to VTE-related mortality and cardiovascular sequelae, such as post-thrombotic syndrome, chronic venous insufficiency and chronic thromboembolic pulmonary hypertension, etc., patients with VTE have high risk of other atherosclerotic diseases and acute cardiovascular events, such as acute myocardial infarction and ischemic stroke, in the short-term and long-term follow-up [8, 9, 10]. With a brief review of pathogenesis and risk factors of VTE, the following of this chapter focuses on percutaneous interventions for VTE.
Virchow’s triad composed of stasis, vascular damage and hypercoagulable status describes the essential components contributing to the thrombus formation [11]. In most cases of VTE, stasis plays a major role triggering the formation of venous thrombosis [12]. However, the exact pathogenesis of VTE seems to be more complex and is not fully understood [2, 13]. Only one existing contributing factor is hard to result in the development of clot formation [14]. Nonetheless, the interaction between multiple concurrent contributing factors increases the risk of formation of venous thrombosis which progresses to significant VTE clinically thereafter.
In clinical aspect, many diseases and circumstances regarded as risk factors are identified to predispose to the development of VTE. In general, these risk factors are classified into genetic and acquired risk [15, 16, 17, 18]. Genetic risk factors including protein C and S deficiency, antithrombin deficiency, the factor V Leiden gene mutation, antiphospholipid syndrome, etc. Acquired risk factors are further divided into concurrent diseases (elderly, chronic diseases, active cancer, obesity) and transient states (surgery, trauma, hospitalization, immobility, central venous catheter or device indwelling, oral contraceptives, etc.) [2]. Of note, hospitalization is an important period that multiple risk factors encounter concurrently and increase the risk of VTE greatly [2, 19]. Although predisposing factors are identified in most cases of VTE, there are still almost 20% of case having no obvious etiology. The result suggests the significance of unknown genetic or acquired risk factors to the development of VTE [2, 3].
To date, anticoagulation is still the principal treatment in VTE. In addition to traditional anticoagulation, including heparin, low molecular weight heparin and vitamin K antagonists, as well as direct thrombin inhibitors, non-vitamin K oral anticoagulants (NOACs), known as direct oral-anticoagulant (DOACs) change the strategy in medical treatment of VTE. The update of principles and strategies of medical treatment of VTM will be illustrated in another chapter. On the other hand, endovascular or surgical thrombectomy and embolectomy have role in treatment of VTE. Historically, Läwen conducted the first thrombectomy for venous thrombosis of upper extremity in 1938 [20]. After evolution in nearly 90 years, there are great advances in techniques and modalities in performing thrombectomy and embolectomy. However, thrombectomy or embolectomy is still indicated in limited population in modern treatment of VTE, especially in patients with massive or submassive thrombus burden accompanied by unstable hemodynamic status or critical complications [21, 22, 23]. Theoretically, endovascular or surgical thrombectomy removes majority of thrombus load more completely and recanalization of occluded vessels earlier [24, 25]. Moreover, some previous studies even reported that thrombectomy may have potential benefits comparing to anticoagulation alone in long-term complications and quality of life in certain VTE patients [22, 26]. The aim of this chapter will focus on the advances of modalities of endovascular and surgical thrombectomy.
Percutaneous management, also known as catheter-based therapy (CBT), for VTE can be divided into two mechanisms: thrombolysis-based and mechanical thrombectomy. There are also devices combining these two mechanisms. For certain conditions, percutaneous approaches also include balloon angioplasty and stenting. We describe different types of CBT in the following sections.
Compared to systemic thrombolysis, catheter-based thrombolysis is, by concept, more likely a local therapy. The advantage of this approach is a reduced-dose thrombolysis. Therefore, there is less risk of bleeding [27, 28]. Although with lower dosage needed, absolute contraindications for catheter-directed thrombolysis are the same as for systemic thrombolysis, including history of any intracranial hemorrhage, ischemic stroke within three months, structural intracranial lesion, active bleeding, recent head, eye or spinal surgery, and recent head trauma [29, 30].
This approach is done by placing an infusion catheter with multiple side holes and a tip occluding wire or a dedicated catheter specifically for a certain device, preferentially into the thrombus. It may sometimes require two catheters to be placed in each of the main pulmonary arteries. If there is no specialized catheter, a standard pig-tail or pulmonary artery catheter may also serve to deliver thrombolytic agent locally. When performing intervention for pulmonary embolism (PE), power injection may be necessary to take clear angiography to localizes the emboli. For each main pulmonary artery, perform contrast injection at 15–20 m/s for a total volume of 30 ml [28]. For intervention of deep venous thrombosis (DVT), careful hand injection with low-volume contrast is preferred to avoid disruption of thrombi with progression to PE [30].
Thrombolytic agent is administered via the carefully placed catheter. There is no standard for the agent and dosage used. It varies according to accompanied device, patients’ bleeding tendency, and physicians’ preferences. A commonly used regimen is tissue plasminogen activator (tPA) 0.5–1.0 mg/hr for 6–24 hours, with total dosage usually between 12 and 24 mg. Fibrinogen should be monitored during infusion of fibrinolytic agent. Dose reduction or discontinuation should be considered if level of fibrinogen falls below 150 mg/dL. During t-PA infusion, a low-dose heparin infusion is usually kept, with a partial thromboplastin time (PTT) just around the lower limit of therapeutic range, usually PTT 40–50 seconds [28, 30].
Catheter-directed thrombolysis applies for both DVT and PE. A key factor to success of lytic-based approach is that whether the thrombolytic agent is delivered into the thrombus with good penetration. A resolution to this problem is combining other method to enhance efficacy of drug delivery, such as the EkoSonic system.
EkoSonic™ Endovascular System (EKOS) is a device for ultrasound-assisted catheter-directed thrombolysis. It includes a control unit and a uniquely designed catheter to achieve better penetration of thrombolytics by so-called acoustic pulse thrombolysis. The catheter is composed of an ultrasonic core in central lumen, central coolant lumen, and drug delivery lumen. The ultrasonic core generates an acoustic field to enhance drug delivery into the clot and to unwind the fibrin for better exposure to thrombolytic agents. This system is indicated for both DVT and PE [31].
There were also devices designed for a true localized therapy. Trellis™ Peripheral Infusion System is a specialized device for isolated thrombolysis. It consists of two occlusive balloons to isolate the treatment area, an infusion zone to deliver thrombolytic agents, an oscillation drive unit to better disperse the drug to thrombi, and an aspiration window to remove the dissolved clot. Although with a unique design to ensure localized thrombolysis and thrombi removal, the devices were recalled due to incorrectly labelling of proximal and distal balloons [32].
Of note, catheter-directed thrombolysis alone may not be sufficient to clear all blood clots, although it is true that the goal of catheter-directed thrombolysis for PE is not to remove emboli completely, but to reduce the risk from high to intermediate [29]. Further intervention to remove emboli and thrombi may be needed and there are devices combining local thrombolysis and sequential blood clot removal, which would be described later.
Mechanical thrombectomy is achieved by physical disruption of thrombus via different methods, with various devices designed for this purpose. These devices have different benefits, adverse effects, and special concerns while manipulation. Overall, they are less invasive compared with traditional surgical thrombectomy. Some devices achieve thrombus removal in a single session, sparing the use of thrombolytic agents. The following section describes devices with approval. Devices still under development are not covered.
Mechanical thrombectomy without a device has long been described in both treatment for DVT and PE. It is usually done by a pigtail with manual rotation or by balloon angioplasty [28]. An important issue of fragmentation is that it might create distal emboli, causing worse distal obstruction; and fragmentation alone may not be enough to resolve obstruction. It may be followed by systemic thrombolysis, catheter-directed thrombolysis, or thrombi removal by manual aspiration. Due to lack of clinical evidence, there is no recommendation for how to combine other strategy after manual thrombus fragmentation.
Besides manual thrombus aspiration with a regular guide catheter or specialized catheters with greater power of suction, there are devices designed to remove thrombus by suction via negative pressure. The advantages are the ability to remove large thrombi or even chronic thrombi, avoidance of thrombolytic agents, and possible less risk of bleeding.
The AngioVac® system works in an extracorporeal circuit and needs two large venous access sites for AngioVac inflow cannula (22Fr) and reinfusion outflow cannula (16–20 Fr). The third generation uses funnel-shaped and different-angled tip (20 degree or 180 degree) to facilitate navigation. Besides the need of two large-bore accesses, another disadvantage of this device is that perfusionist is required. It is indicated for removal of fresh, soft thrombi or emboli in right atrium, right ventricle, superior vena cava, inferior vena cava, and iliofemoral veins during extracorporeal bypass. It is not indicated in pulmonary vasculature although there are case series [33].
The FlowTriever® system includes an Triever Aspiration Catheter, a FlowTriever catheter, and a retraction aspiration device. Thrombus removal is done by manual aspiration with a syringe via the large-lumen aspiration catheter. There are nitinol mesh disks on the tip of FlowTriever catheter to disrupt and drag residual clots into the aspiration catheter for extraction. This system is indicated for PE [34]. A similar system dedicated for DVT is the ClotTriever® system. It includes a ClotTriever sheath and a ClotTriever catheter. The procedure steps are somewhat different. The ClotTriever catheter is position beyond the thrombus. A mesh collection bag on the tip of ClotTriever catheter retracts thrombi into the ClotTriever sheath with a self-expanding funnel tip, providing embolic protection. Manual aspiration is applied if there are residual thrombi in the sheath. Since treatment is completed in a single session and there is no need for thrombolysis, care in intensive care unit (ICU) after procedure may not be necessary. However, a large-bore vascular access (20 Fr) is needed [35].
Penumbra’s Indigo® Aspiration System operates in a more “automatic” way, with less need of manual control. The main components of the system are a catheter, a Penumbra ENGINE to generate vacuum for aspiration, and a tubing system. When the catheter is in position, the system performs automatic aspiration. With different catheters, there are corresponding Separator wires to remove clot in the lumen of aspiration catheters. Compared to AngioVac® and FlowTriever®, the Indigo® system does not require large-bore vascular access but may therefore unable to remove larger thrombi. It is indicated for removal of fresh, soft thrombi or emboli in both peripheral arterial and venous system and for treatment of PE [36].
Syringed-based thrombectomy offers limited force and aspirated volume, and operators could not further manipulate. Pump systems with specific devices provide increased force and volume but usually with increased complexity of the procedure and increased cost. Control Mechanical Thrombectomy™ system (Aspire) works in a different way. The system includes a thrombectomy catheter and a control mechanical aspirator which is like a handle. Through the handle, the operator can adjust strength of the aspirated force, and switch between continuous and pulsed force. It is indicated for removal of fresh, soft thrombi in peripheral vasculature, but not PE [37].
The concept of rotational thrombectomy is thrombus disruption by a catheter with rotating head. Most devices also have the ability to remove thrombus via active suction.
Aspirex® mechanical thrombectomy device consists of a catheter with a handle and a drive system. At the tip of the catheter, there is aspiration port to suck in thrombi; and inside the catheter, there is rotational coil to break down thrombi. The fragmented thrombi are then aspirated out. The device is indicated for both arterial and venous thrombi. With limited case studies, it is not approved for treatment of PE [38].
CLEANER™ Rotational Thrombectomy System is a one-piece device. Rotating action of its sinusoidal wire breaks down thrombi. The sinusoidal shape provides atraumatic action on thrombi adhered to vessel wall. The device also enables infusion of thrombolytic agents via a distal side hole. It is indicated for removal of thrombus in peripheral vasculature, but not for PE [39].
Rheolytic thrombectomy is based on Bernoulli effect. A high-velocity saline jet creates a low-pressure, drawing thrombi into the catheter. To eliminate thrombi better, it may be accompanied with thrombolysis or other mechanical method such as aspiration.
Among this category, the mostly studied device is AngioJet™ Rheolytic Thrombectomy System, consisting of a console and a thrombectomy catheter. The system works in both pharmacological and mechanical ways. Operators can deliver thrombolytic agents directly into the clot to facilitate removal of thrombus. The console generates pressurized saline to draw thrombi into the catheter via an inflow window near the tip of the catheter, and then evacuates the thrombi. Notable adverse events include pain, cardiac arrythmia (mainly bradyarrhythmia), hypotension, transient hemolysis, bleeding, and acute kidney injury. Hydration before, during, and after the procedure may be considered. AngioJet™ system is indicated in removal of thrombi in peripheral vasculature. When used in PE, there were severe adverse events, including death; so, there is a “black box” warning for AngioJet™ in treating PE [40].
The concept of combination works in at least two modes. One is to combine multiple mechanisms at the same time, usually by devices, like EKOS or AngioJet™. The other way is to use different methods sequentially. For instance, physicians may perform balloon angioplasty first to disrupt the thrombi; and then leave an infusion catheter for thrombolysis. This concept also works in a reverse way. Physicians may place an infusion catheter for thrombolysis first, usually for 24 hours; and then break the loosen thrombi with balloon angioplasty. Theoretically, combing thrombolysis and mechanical thrombectomy improves efficacy of thrombus removal, but there is no standard for how to combine multiple strategies due to limited studies. This so-called pharmacomechanical approach is therefore, largely based on clinicians’ experience.
Besides thrombolysis and mechanical thrombectomy, some adjuvant procedures may be needed, mainly for DVT. Balloon angioplasty plays a role in chronic thromboembolic pulmonary hypertension, but not for acute PE. For DVT, placement of inferior vena cava filter before procedure may be considered to prevent PE, especially for patients with poor cardiopulmonary function and deemed unable to tolerate PE [30]. The results of studies regarding stenting for DVT were inconsistent, although some showed reduced severity in post-thrombotic syndrome and improved quality of life in some aspects [41, 42, 43]. This approach is therefore largely based on clinicians’ experience.
Stenting is considered if there is residual thrombi or residual venous outflow obstruction. It may also be considered when there is non-thrombotic cause of stenosis, such as in May-Thurner syndrome. Therefore, careful assessment of the lesion is important. It is helpful to combine other image modality such as computed tomography or intravascular ultrasound. Besides anatomical nature, clinicians should put patients’ life expectancy, bleeding risk, and likelihood of symptom improvement into consideration. When a stent is placed, there is always risk of in-stent restenosis or occlusion. Risk factors include poor inflow, external compression, inappropriate stent design, stent misplacement or migration, stent fracture, and bleeding. Patients should be notified about the possibility of reintervention [44].
The purpose of CBT is to relieve obstruction quicker, compared with traditional medical therapy. However, there is no strong evidence that CBT is better than traditional systemic thrombolysis since randomized trial assessing hard outcomes, such as mortality, is lacking. Also, among CBT, there is no trial comparing catheter-directed thrombolysis and mechanical thrombectomy or comparing different devices. It is also important to remember that published studies for CBT with devices are of small patient numbers. There are many trials still going on. Hopefully, these trials will provide evidences for more specific guidance.
For any intervention, there are always complications. Possible complications of CBT include access site bleeding, vascular injury, major bleeding (including intracranial hemorrhage), distal emboli (especially of concern with PE when performing intervention for DVT), cardiac tamponade (intervention for PE), hemodynamic deterioration, and deterioration in renal function. Some studies did not demonstrate the presumed benefit of less major bleedings (including intracranial hemorrhage) in percutaneous methods, compared with systemic thrombolysis [28, 29]. The balance between risk and benefit of these interventions should be personalized.
Generally speaking, CBT may be considered in patients with iliofemoral DVT who have severe symptoms and a low risk of bleeding [45]. For PE, CBT is an alternative to systemic thrombolysis and surgical embolectomy, considered when these approaches are contraindicated or fail [46]. For now, the choice of CBT largely remains on physicians’ experience and local availability.
Surgical intervention is an old skill compared with percutaneous intervention. Surgical embolectomy of PE requires cardiopulmonary bypass. After thoracotomy, emboli are removed manually with forceps. Balloon catheter and suction may be used for residual emboli. Although surgical embolectomy is a class I indication for massive pulmonary embolism, it is usually reserved as a salvage therapy when other therapies fail or are contraindicated, due to its invasive nature. If there is thrombus in right heart or thrombus across patent foramen ovale, surgical embolectomy would be considered the first-line therapy [27].
On the other hand, surgical thrombectomy for DVT is usually done with a special balloon catheter to pull out thrombi in the direction of venous flow, called Fogarty maneuvers [47]. Unlike for PE, surgical thrombectomy for DVT is not recommended by clinical guidelines. Although there are studies showing good patency rates after surgery, it is usually considered only in certain conditions when rapid reduction of venous obstruction is needed, such as in patients with phlegmasia cerulea dolens [48].
Although rapid evolution of modalities and relatively high successful rate in experienced center, routine use of endovascular or surgical thrombectomy and thrombolysis in patient with VTE is not recommended. To date, large-scale clinical trial assessing the efficacy and safety of invasive thrombolysis or thrombectomy is still lack. The application of endovascular or surgical strategies should be considered in selective VTE patients with unstable hemodynamic status or critical VTE-associated complications or having contraindications or high risk of bleeding while receiving systemic thrombolysis. In addition, future studies focusing on cost-effectiveness are needed to integrate these invasive procedures with medical strategies in the protocol of VTE treatment.
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. 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Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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Design/methodology: The paper applied vector error correction model (VECM) Granger casualty test for assessing the direction of causality and variance decomposition to explain the magnitude of the forecast error variance determined by the shocks to each of the explanatory variables over time. LB (Q-stat) test is to determine data properties and WILD test is to assess short run causality from independent variables to dependent variable. Findings: The study results revealed that variables are integrated in the same order. The results of Johansen Juselius cointegration tests indicate that there is a unique long-term or equilibrium relationship among variables. Again, Granger causality test revealed that short run unidirectional causality are running from carbon dioxide emission to exports, GDP to import, and from import to carbon dioxide emissions. Variance decomposition function shows that the positive shocks in error term will produce positive effects on all variables in the long run. Therefore, a concerted effort from all national and international stakeholders, i.e., enterprises, consumers, and governments are expected to take measures to offset carbon emission and pursue environment-friendly trade plan for better managing the cities and regions in order to fight against global warming and climate change risk.",book:{id:"6075",slug:"management-of-cities-and-regions",title:"Management of Cities and Regions",fullTitle:"Management of Cities and Regions"},signatures:"Farhana Ferdousi and Md. Qamruzzaman",authors:[{id:"198685",title:"Dr.",name:"Farhana",middleName:null,surname:"Ferdousi",slug:"farhana-ferdousi",fullName:"Farhana Ferdousi"},{id:"217382",title:"Mr.",name:"Md",middleName:null,surname:"Qamruzzaman",slug:"md-qamruzzaman",fullName:"Md Qamruzzaman"}]},{id:"58316",doi:"10.5772/intechopen.72028",title:"Immigration and Social Inclusion: Possibilities from School and Sports",slug:"immigration-and-social-inclusion-possibilities-from-school-and-sports",totalDownloads:1275,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Immigration is a manifestation of cultural pluralism that crosses a transversal form, an important part of the western societies, generating consequences in political, social and cultural terms. Likewise, the evidence shows that the educational system attached to sport can be a positive context to promote inclusive processes associated to the immigrant population, due to its high social transcendence and its universal character. On the other hand, sports may act as a tool for social and cultural conflict if they focus on the imposition of a dominant culture or exacerbates the competitive sense. The present chapter has by objective to analyze the possibilities of sports as a tool for the social inclusion of the immigrant population, giving special emphasis to the educational options that were offered by the sport practice in the school context. To do this, it presents an important number of theoretical and empirical backgrounds associated with this topic, which will allow the reader to understand the existing relationship between sport, education and immigration, exposing their possible risks and virtues.",book:{id:"6357",slug:"immigration-and-development",title:"Immigration and Development",fullTitle:"Immigration and Development"},signatures:"Bastian Carter-Thuillier, Victor López-Pastor, Francisco Gallardo-\nFuentes and Juan Carter-Beltran",authors:[{id:"212425",title:"Dr.",name:"Bastian",middleName:null,surname:"Carter-Thuillier",slug:"bastian-carter-thuillier",fullName:"Bastian Carter-Thuillier"},{id:"214391",title:"Dr.",name:"Victor",middleName:null,surname:"Lopez-Pastor",slug:"victor-lopez-pastor",fullName:"Victor Lopez-Pastor"},{id:"214392",title:"Dr.",name:"Francisco",middleName:null,surname:"Gallardo",slug:"francisco-gallardo",fullName:"Francisco Gallardo"},{id:"214393",title:"Dr.",name:"Juan",middleName:null,surname:"Carter-Beltran",slug:"juan-carter-beltran",fullName:"Juan Carter-Beltran"}]},{id:"58382",doi:"10.5772/intechopen.72063",title:"Social Capital as Survival Strategy for Immigrants in South Africa: A Conceptual Framework",slug:"social-capital-as-survival-strategy-for-immigrants-in-south-africa-a-conceptual-framework",totalDownloads:1409,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"Social survival strategies are premised on relations anchored around ethnicity, culture, nationality, and language. Out of this strategy is the concept of social capital which is defined as the link that allow people to discover opportunities as well as employment based in social relationships with previous migrants. There is no doubt that foreign nationals utilise different forms of social capital to achieve different means—the reliance on family at the point of entry to access shelter and employment opportunities whereas they access friendships and networks within the employment circles to access other employment opportunities. The aim of this research is to detail how foreign nationals employ social capital networks as a survival strategy in South African urban townships using Diepsloot, found in the northwest of Johannesburg, as a case study. It is an important study because there is a lack of literature linking social capital as a survival strategy. We focus on social capital because it is a propeller—at least at initial and transition stages of migration—to access other forms of survival strategies. This paper, before all else, derives a conceptual framework that should guide the empirical part of such a research.",book:{id:"6357",slug:"immigration-and-development",title:"Immigration and Development",fullTitle:"Immigration and Development"},signatures:"Nosipho Hlatshwayo and Kambidima Wotela",authors:[{id:"212717",title:"Dr.",name:"Kambidima",middleName:null,surname:"Wotela",slug:"kambidima-wotela",fullName:"Kambidima Wotela"},{id:"212719",title:"Ms.",name:"Nosipho",middleName:null,surname:"Hlatshwayo",slug:"nosipho-hlatshwayo",fullName:"Nosipho Hlatshwayo"}]},{id:"56489",doi:"10.5772/intechopen.70158",title:"The Economic Geography of Most North‐Western Region of Spain: Galicia and the Effect of Market Access on Regional Development Levels",slug:"the-economic-geography-of-most-north-western-region-of-spain-galicia-and-the-effect-of-market-access",totalDownloads:1200,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"This chapter estimates the nominal wage equation of the geographical economics literature using data on the Galician regions over the period 2003–2013. The results of the estimations show the existence of a spatial wage structure across the Galician regions with a clear West‐East gradient. Additionally, we have controlled for the inclusion of potential covariates that might be influencing the levels of regional per capita income such as educational attainment levels and technological levels. The results are robust to these alternative estimations",book:{id:"6075",slug:"management-of-cities-and-regions",title:"Management of Cities and Regions",fullTitle:"Management of Cities and Regions"},signatures:"Jesús López‐Rodríguez and Guillermo Manso‐Fernández",authors:[{id:"141386",title:"Prof.",name:"Jesús",middleName:null,surname:"López-Rodríguez",slug:"jesus-lopez-rodriguez",fullName:"Jesús López-Rodríguez"},{id:"207335",title:"Ph.D.",name:"Guillermo",middleName:null,surname:"Manso-Fernandez",slug:"guillermo-manso-fernandez",fullName:"Guillermo Manso-Fernandez"}]},{id:"57815",doi:"10.5772/intechopen.71773",title:"Welfare Dependency Among Immigrants to Norway: A Panel Data Study of Transfer Shares",slug:"welfare-dependency-among-immigrants-to-norway-a-panel-data-study-of-transfer-shares",totalDownloads:973,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Using Norwegian panel data, we specify and estimate transfer share equations for immigrants belonging to different subgroups. The share measures how import transfers are relative to a gross income concept incorporating transfers and gross income coming from labor market participation. For both genders, we consider three types of immigrants: refugees, individuals immigrating for reunification with refugees and individuals immigrating because of work. The transfer share for an individual depends on different characteristics of it. The explanatory variables we consider are related to age, duration of stay in Norway, family composition, educational attainment and area of geographical residence in Norway. Unobserved individual-specific heterogeneity is represented by random effects. Of special concern, not at least from a policy point of view, is the effect of duration of stay on the transfer shares. For refugees and individuals reunifying with refugees we find, at least for a substantial number of years, that the transfer share decreases as the duration of stay becomes longer. An essential part of the analysis is that we compare the effects across gender. Among the refugees we find that the effect of duration of stay is quite similar for men and women.",book:{id:"6357",slug:"immigration-and-development",title:"Immigration and Development",fullTitle:"Immigration and Development"},signatures:"Tom Kornstad and Terje Skjerpen",authors:[{id:"193167",title:"Mr.",name:"Terje",middleName:null,surname:"Skjerpen",slug:"terje-skjerpen",fullName:"Terje Skjerpen"},{id:"213983",title:"Dr.",name:"Tom",middleName:null,surname:"Kornstad",slug:"tom-kornstad",fullName:"Tom Kornstad"}]}],mostDownloadedChaptersLast30Days:[{id:"57322",title:"Export, Import, Economic Growth, and Carbon Emissions in Bangladesh: A Granger Causality Test under VAR (Restricted) Environment",slug:"export-import-economic-growth-and-carbon-emissions-in-bangladesh-a-granger-causality-test-under-var-",totalDownloads:1399,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Purpose: This paper examines the causal and cointegrating relationship between economic growth and CO2 emissions in a multivariate framework by including imports and exports as others control variables for an emerging economy like Bangladesh. Design/methodology: The paper applied vector error correction model (VECM) Granger casualty test for assessing the direction of causality and variance decomposition to explain the magnitude of the forecast error variance determined by the shocks to each of the explanatory variables over time. LB (Q-stat) test is to determine data properties and WILD test is to assess short run causality from independent variables to dependent variable. Findings: The study results revealed that variables are integrated in the same order. The results of Johansen Juselius cointegration tests indicate that there is a unique long-term or equilibrium relationship among variables. Again, Granger causality test revealed that short run unidirectional causality are running from carbon dioxide emission to exports, GDP to import, and from import to carbon dioxide emissions. Variance decomposition function shows that the positive shocks in error term will produce positive effects on all variables in the long run. Therefore, a concerted effort from all national and international stakeholders, i.e., enterprises, consumers, and governments are expected to take measures to offset carbon emission and pursue environment-friendly trade plan for better managing the cities and regions in order to fight against global warming and climate change risk.",book:{id:"6075",slug:"management-of-cities-and-regions",title:"Management of Cities and Regions",fullTitle:"Management of Cities and Regions"},signatures:"Farhana Ferdousi and Md. Qamruzzaman",authors:[{id:"198685",title:"Dr.",name:"Farhana",middleName:null,surname:"Ferdousi",slug:"farhana-ferdousi",fullName:"Farhana Ferdousi"},{id:"217382",title:"Mr.",name:"Md",middleName:null,surname:"Qamruzzaman",slug:"md-qamruzzaman",fullName:"Md Qamruzzaman"}]},{id:"58382",title:"Social Capital as Survival Strategy for Immigrants in South Africa: A Conceptual Framework",slug:"social-capital-as-survival-strategy-for-immigrants-in-south-africa-a-conceptual-framework",totalDownloads:1409,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"Social survival strategies are premised on relations anchored around ethnicity, culture, nationality, and language. Out of this strategy is the concept of social capital which is defined as the link that allow people to discover opportunities as well as employment based in social relationships with previous migrants. There is no doubt that foreign nationals utilise different forms of social capital to achieve different means—the reliance on family at the point of entry to access shelter and employment opportunities whereas they access friendships and networks within the employment circles to access other employment opportunities. The aim of this research is to detail how foreign nationals employ social capital networks as a survival strategy in South African urban townships using Diepsloot, found in the northwest of Johannesburg, as a case study. It is an important study because there is a lack of literature linking social capital as a survival strategy. We focus on social capital because it is a propeller—at least at initial and transition stages of migration—to access other forms of survival strategies. This paper, before all else, derives a conceptual framework that should guide the empirical part of such a research.",book:{id:"6357",slug:"immigration-and-development",title:"Immigration and Development",fullTitle:"Immigration and Development"},signatures:"Nosipho Hlatshwayo and Kambidima Wotela",authors:[{id:"212717",title:"Dr.",name:"Kambidima",middleName:null,surname:"Wotela",slug:"kambidima-wotela",fullName:"Kambidima Wotela"},{id:"212719",title:"Ms.",name:"Nosipho",middleName:null,surname:"Hlatshwayo",slug:"nosipho-hlatshwayo",fullName:"Nosipho Hlatshwayo"}]},{id:"58316",title:"Immigration and Social Inclusion: Possibilities from School and Sports",slug:"immigration-and-social-inclusion-possibilities-from-school-and-sports",totalDownloads:1275,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Immigration is a manifestation of cultural pluralism that crosses a transversal form, an important part of the western societies, generating consequences in political, social and cultural terms. Likewise, the evidence shows that the educational system attached to sport can be a positive context to promote inclusive processes associated to the immigrant population, due to its high social transcendence and its universal character. On the other hand, sports may act as a tool for social and cultural conflict if they focus on the imposition of a dominant culture or exacerbates the competitive sense. The present chapter has by objective to analyze the possibilities of sports as a tool for the social inclusion of the immigrant population, giving special emphasis to the educational options that were offered by the sport practice in the school context. To do this, it presents an important number of theoretical and empirical backgrounds associated with this topic, which will allow the reader to understand the existing relationship between sport, education and immigration, exposing their possible risks and virtues.",book:{id:"6357",slug:"immigration-and-development",title:"Immigration and Development",fullTitle:"Immigration and Development"},signatures:"Bastian Carter-Thuillier, Victor López-Pastor, Francisco Gallardo-\nFuentes and Juan Carter-Beltran",authors:[{id:"212425",title:"Dr.",name:"Bastian",middleName:null,surname:"Carter-Thuillier",slug:"bastian-carter-thuillier",fullName:"Bastian Carter-Thuillier"},{id:"214391",title:"Dr.",name:"Victor",middleName:null,surname:"Lopez-Pastor",slug:"victor-lopez-pastor",fullName:"Victor Lopez-Pastor"},{id:"214392",title:"Dr.",name:"Francisco",middleName:null,surname:"Gallardo",slug:"francisco-gallardo",fullName:"Francisco Gallardo"},{id:"214393",title:"Dr.",name:"Juan",middleName:null,surname:"Carter-Beltran",slug:"juan-carter-beltran",fullName:"Juan Carter-Beltran"}]},{id:"58881",title:"Refugee Learners’ Experiences of Curriculum Transition in South Africa",slug:"refugee-learners-experiences-of-curriculum-transition-in-south-africa",totalDownloads:1038,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"There is a dearth of scholarship on refugee education particularly the way in which learners navigate a new curriculum in the host country. The purpose of this study is to explore Zimbabwean learners’ experiences of curricula transition at a refugee school in South Africa. The study was performed using a qualitative case study, and its paradigmatic position was interpretive. Bronfenbrenner’s Social Ecological Model was used as a theoretical framework. Ten participants were purposively selected to participate in semi-structured interviews. The study found that refugee learners’ experiences of curricula transition manifest in three categories: content, contextual and conceptual experiences. It is concluded that providing education to refugee learners without giving them the necessary support, which is needed for them to adapt to a new curriculum, is tantamount to setting them up for a failure.",book:{id:"6357",slug:"immigration-and-development",title:"Immigration and Development",fullTitle:"Immigration and Development"},signatures:"Lawrence Meda",authors:[{id:"214446",title:"Dr.",name:"Lawrence",middleName:null,surname:"Meda",slug:"lawrence-meda",fullName:"Lawrence Meda"}]},{id:"57051",title:"Urban Planning in Decentralization and Local Autonomy Era: A Case Study on the Relationship Between Local Government and Civic Group in Development and Budget Planning in Malang City (Indonesia)",slug:"urban-planning-in-decentralization-and-local-autonomy-era-a-case-study-on-the-relationship-between-l",totalDownloads:1182,totalCrossrefCites:1,totalDimensionsCites:0,abstract:"This study aims to explore the relationship between local government and civic groups in the budget planning process of the government of Malang during 2015. Using a grounded theory approach, qualitative methods are applied in this study. The unit of the study is Malang, East Java, Indonesia. Malang is selected as the unit of study because of the many civic groups. The findings of this study show that there exists a relationship between local government and civic groups but that the relationship does not represent the principles of democracy (equality, participation, and justice) in the budget planning. Local government has dominated civic groups in budget planning so that the budget policy does not take public interest into consideration. However, civic groups such as Malang Corruption Watch (MCW) and Education Forum of Society (FMPP) have developed different strategies to develop collective lobbying to direct the development of public awareness through education. These findings contribute to developing budget planning in Malang that establishes a democratic budget policy process that is more responsive to public needs. The local government should realize that public participation is a way to achieve democratic budget process. In this context, elected and appointed officials should provide access for civic groups to be involved in all stages of budget planning. 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