Dr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
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Seeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\\n\\n
Over these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\\n\\n
We are excited about the present, and we look forward to sharing many more successes in the future.
\\n\\n
Thank you all for being part of the journey. 5,000 times thank you!
\\n\\n
Now with 5,000 titles available Open Access, which one will you read next?
Preparation of Space Experiments edited by international leading expert Dr. Vladimir Pletser, Director of Space Training Operations at Blue Abyss is the 5,000th Open Access book published by IntechOpen and our milestone publication!
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"This book presents some of the current trends in space microgravity research. The eleven chapters introduce various facets of space research in physical sciences, human physiology and technology developed using the microgravity environment not only to improve our fundamental understanding in these domains but also to adapt this new knowledge for application on earth." says the editor. Listen what else Dr. Pletser has to say...
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Dr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\n\n
Seeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\n\n
Over these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\n\n
We are excited about the present, and we look forward to sharing many more successes in the future.
\n\n
Thank you all for being part of the journey. 5,000 times thank you!
\n\n
Now with 5,000 titles available Open Access, which one will you read next?
\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:"4786",leadTitle:null,fullTitle:"Updates on Brucellosis",title:"Updates on Brucellosis",subtitle:null,reviewType:"peer-reviewed",abstract:"Brucellosis is a major zoonotic disease that may cause a serious illness in humans and animals. Global prevalence of human brucellosis remains significant. More than half a million new brucellosis cases from 100 countries are reported annually to the World Health Organization (WHO). The majority of these cases are reported in developing countries.In humans, brucellosis (undulant fever, Malta fever) is characterized by an acute bacteremic phase followed by a chronic stage that may extend over many years and may involve many tissues. It is a systemic disease, and many organ systems (nervous system, heart, skeletal system, bone marrow, etc.) may become involved following hematogenous dissemination.\nAlthough eradicated in some countries, it remains one of the most economically important zoonosis worldwide as it is responsible for huge economic losses as well as significant human morbidity in endemic areas.\nBecause of the nonspecific clinical manifestations of human brucellosis and the need for prolonged combination therapy with antibiotics that are not routinely prescribed for other infectious diseases, laboratory confirmation of the diagnosis is of paramount importance for adequate patient management. In addition, evidence of brucellosis has serious public health implications because it discloses exposure to a contaminated source (infected animals or their products, unsafe laboratory practices, or a potential biological warfare attack). \nThis book addresses human brucellosis with stress on symptoms including those related to the less recognized disease localizations, risk of exposure, treatment, and prevention. Light is shed on animal brucellosis as it pertains to human exposure. The book also emphasizes on laboratory procedures in culturing and serologic techniques. Epidemiologic surveillance is among this books subjects as well as veterinary control measures.",isbn:null,printIsbn:"978-953-51-2211-1",pdfIsbn:"978-953-51-7267-3",doi:"10.5772/59890",price:119,priceEur:129,priceUsd:155,slug:"updates-on-brucellosis",numberOfPages:256,isOpenForSubmission:!1,isInWos:1,isInBkci:!1,hash:"dc389e7ef54fb572ca89ae1ac6e5f3ec",bookSignature:"Manal Mohammad Baddour",publishedDate:"November 19th 2015",coverURL:"https://cdn.intechopen.com/books/images_new/4786.jpg",numberOfDownloads:23386,numberOfWosCitations:22,numberOfCrossrefCitations:28,numberOfCrossrefCitationsByBook:1,numberOfDimensionsCitations:50,numberOfDimensionsCitationsByBook:1,hasAltmetrics:0,numberOfTotalCitations:100,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 17th 2014",dateEndSecondStepPublish:"December 8th 2014",dateEndThirdStepPublish:"March 21st 2015",dateEndFourthStepPublish:"June 12th 2015",dateEndFifthStepPublish:"July 12th 2015",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"174598",title:"Dr.",name:"Manal Mohammad",middleName:null,surname:"Baddour",slug:"manal-mohammad-baddour",fullName:"Manal Mohammad Baddour",profilePictureURL:"https://mts.intechopen.com/storage/users/174598/images/system/174598.jpeg",biography:"Manal Mohammad Baddour is a Professor of Medical Microbiology and Immunology in the Faculty of Medicine, Alexandria University, Egypt. She obtained a Ph.D. in Microbiology and Immunology from the same university in 1995. \n\nDr. Baddour was ranked first among high school examinees in Saudi Arabia in 1979. She has also been listed in the Marquis Who’s Who in the World 2009 and in the Academic Keys Who’s Who list for Medicine Higher Education. \n\nShe has held several positions including secretary general of the Permanent Scientific Committee for Promotion of Professors and Associate Professors in Medical Microbiology and Immunology, Egypt. She is also an editor and reviewer for numerous scientific journals. She has edited or authored several books and has thirty-six journal publications to her credit. She is an assessor for promotion files of faculty members from Egyptian, Jordanian, and Saudi Arabian universities. \n\nDr. Baddour is a member of several organizations including the Gerson Lehrman Group for Healthcare & Biomedical Council; Society for General Microbiology, England; Egyptian Society for Medical Microbiology; Egyptian Association of Immunologists; Egyptian Society for Infection Control; Egyptian Medical Syndicate; Alexandria Medical Syndicate Council; African Association of Physiological Sciences, South Africa; and African Regional Training Network for Medical and Allied Health Sciences, South Africa.",institutionString:"Alexandria University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"4",institution:{name:"Alexandria University",institutionURL:null,country:{name:"Egypt"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1046",title:"Infectious Diseases",slug:"infectious-diseases"}],chapters:[{id:"49295",title:"Risk Factors for Brucella spp. in Domestic and Wild Animals",doi:"10.5772/61325",slug:"risk-factors-for-brucella-spp-in-domestic-and-wild-animals",totalDownloads:2505,totalCrossrefCites:8,totalDimensionsCites:15,hasAltmetrics:0,abstract:"Brucella spp. is the aetiological agent of brucellosis, a serious contagious disease that results in reproductive failure and that has profound public health significance because of its zoonotic characteristics. This disease also is responsible for a high economic impact associated with the application of prevention, surveillance and test-and-slaughter programmes in animals by national authorities. Brucella spp. infects a large variety of animals and their prevalence is variable worldwide, mainly associated with the presence or absence of control programmes and also with the vaccination of animals against brucellosis. To achieve the control and eradication of brucellosis, the identification of the risk factors of brucellosis that maintain the infection in animals and/or the environment is fundamental. Although several risks have been identified, the most important have been associated with the biology of the bacteria, animal management (age, sex, species or breed), herd management (herd/flock size, number of species, contact with wild animals or type of animal production), farm management (facilities, cleaning and disinfection or veterinary support) and farmers’ knowledge about the disease. Thus, to benefit from proper risk identification of brucellosis, it is essential to put a cost-effective and efficient brucellosis control programme into place.",signatures:"Ana Cláudia Coelho, Juan García Díez and Adosinda Maria Coelho",downloadPdfUrl:"/chapter/pdf-download/49295",previewPdfUrl:"/chapter/pdf-preview/49295",authors:[{id:"79219",title:"Prof.",name:"Ana Cláudia",surname:"Coelho",slug:"ana-claudia-coelho",fullName:"Ana Cláudia Coelho"},{id:"175363",title:"Dr.",name:"Juan",surname:"Garcia-Díez",slug:"juan-garcia-diez",fullName:"Juan Garcia-Díez"},{id:"175364",title:"Dr.",name:"Adosinda",surname:"Coelho",slug:"adosinda-coelho",fullName:"Adosinda Coelho"}],corrections:null},{id:"48984",title:"Brucellosis at the Wildlife/Livestock/Human Interface",doi:"10.5772/61212",slug:"brucellosis-at-the-wildlife-livestock-human-interface",totalDownloads:1718,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"There are a number of bacterial, viral, and parasitic diseases present at the Wildlife/livestock/human interface. Brucellosis is a zoonotic disease of importance and highly prevalent in sub-Saharan Africa. The important Brucella species at the wildlife/livestock/human interface are Brucella arbortus, Brucella suis, and Brucella melitensis. These species have been isolated from humans, livestock (cattle and goats), and wildlife (African buffalo and giraffe). A lot of studies indicated that density, herd size, age of cow, reduced veterinary services like vaccination programs, and geographical area are associated with Brucella prevalence. Studies in developing countries have indicated that the disease is more prominent in the both commercial and communal farming sectors. Access and consumption of contaminated foods and/or occupational exposure remain the significant source of infection to humans. The pathogen transmission of brucellosis is bidirectional in nature; hence, for control efforts to be successful, cooperation is required between livestock owners, animal health officials, and wildlife managers. Globally, trend is moving toward focusing on “one health,” which recognizes that human, animal (both domestic and wild), and ecosystems are tightly linked. The successful management of disease requires an integrated approach where efforts are focused in concert across these domains. Climate change, increased human populations, and increased interaction at wildlife/livestock/human interface have resulted in the change of brucellosis dynamics.",signatures:"Calvin Gomo",downloadPdfUrl:"/chapter/pdf-download/48984",previewPdfUrl:"/chapter/pdf-preview/48984",authors:[{id:"175241",title:"Dr.",name:"Calvin",surname:"Gomo",slug:"calvin-gomo",fullName:"Calvin Gomo"}],corrections:null},{id:"49266",title:"The Interaction Between Brucella and the Host Cell in Phagocytosis",doi:"10.5772/61463",slug:"the-interaction-between-brucella-and-the-host-cell-in-phagocytosis",totalDownloads:1601,totalCrossrefCites:3,totalDimensionsCites:4,hasAltmetrics:0,abstract:"Brucella spp. are facultative intracellular parasitic pathogens that can survive and multiply in professional and nonprofessional phagocytes. These pathogens are responsible for brucellosis, which can cause abortion in domestic animals and undulant fever in humans. Brucella spp. can survive in a variety of cells and their virulence and chronic infections are thought to be due to their ability to evade the killing mechanisms within host cells, one of which is the inhibition of phagosome-lysosome fusion. Lipid raft-associated molecules, such as GPI-anchored proteins, GM1 ganglioside, and cholesterol, are selectively integrated into Brucella-containing macropinosomes following the internalization of Brucella into macrophages, continuously sustaining a dynamic state of the phagosomal membrane. Toll-like receptors (TLRs) are important systems that detect microbial invasion via recognition of microbial components that triggers signaling pathways to promote the expression of genes and regulate innate immune responses. Recent several studies have revealed the importance between TLRs-Brucella interactions to control Brucella infection. Here, we reviewed selected aspects of lipid raft-associated molecules and TLRs-Brucella interaction, which may help to understand the mechanism of Brucella pathogenesis.",signatures:"Suk Kim",downloadPdfUrl:"/chapter/pdf-download/49266",previewPdfUrl:"/chapter/pdf-preview/49266",authors:[{id:"175168",title:"Prof.",name:"Suk",surname:"Kim",slug:"suk-kim",fullName:"Suk Kim"}],corrections:null},{id:"48829",title:"Brucella-induced Thrombocytopenia and Bleeding",doi:"10.5772/61134",slug:"brucella-induced-thrombocytopenia-and-bleeding",totalDownloads:1336,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Mild anemia and leukopenia are the most common hematologic problems of acute brucellosis. Mild thrombocytopenia also occurs, but severe cases are uncommon. Thrombocytopenia occurs because of bone marrow suppression, hypersplenisem, hemophagocytosis, and immunologic destruction of the cells or disseminated intravascular coagulation. In endemic areas, hemorrhagic fevers, hematologic malignancies, as well as idiopathic thrombocytopenic purpura should be considered as differential diagnoses for complicated brucellosis. Thrombocytopenia and bleeding can be improved with antibiotic and hematologic supportive therapy whereas in severe cases corticosteroid therapy or splenectomy might be necessary.",signatures:"Ali Akbar Heydari",downloadPdfUrl:"/chapter/pdf-download/48829",previewPdfUrl:"/chapter/pdf-preview/48829",authors:[{id:"175053",title:"Dr.",name:"Ali Akbar",surname:"Heydari",slug:"ali-akbar-heydari",fullName:"Ali Akbar Heydari"}],corrections:null},{id:"49315",title:"Ocular Manifestations of Brucellosis",doi:"10.5772/61475",slug:"ocular-manifestations-of-brucellosis",totalDownloads:1403,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Brucellosis is considered a zoonotic disease which is still an important health problem in endemic areas such as the Middle East, the Mediterranean, and Asia. Brucellosis is a systemic infection that might affect any organ or system in the body. Ocular involvement has been reported in 21% of brucellosis patients. The most common ocular manifestations of brucellosis were considered as anterior uveitis and choroiditis. The patients with anterior uveitis were reported to be usually in the acute stage and the patients with choroiditis, papilledema, and posterior uveitis were reported to be usually in the chronic stage of the disease. Ocular manifestations of brucellosis might also involve dacryoadenitis, conjunctivitis, episcleritis, scleritis, nummular keratitis, cataract, glaucoma, exudative retinal detachment, maculopathy, and neuro-ophthalmic defects including papilledema, papillitis, and cranial nerve paresis. Optic nerve involvement in brucellosis is considered secondary to meningeal inflammation, and it usually involves both optic nerves. Premacular hemorrhage related to Brucella endocarditis was reported as a rare ocular manifestation. Since ocular brucellosis has a wide spectrum of clinical manifestations, the diagnosis is considered to be mainly dependent on positive bacteriological and serological tests. Agglutinations and/or culture has been widely used for diagnosis of brucellosis. Brucella agglutination test over 1/160 titer and positive blood culture are considered as diagnostic factors for brucellosis. Early diagnosis and prompt treatment are considered to be effective for preventing blindness from severe ocular damage. Systemic antibiotics including streptomycine, rifampicin, doxycycline along with topical or systemic corticosteroid treatment have been recommended for at least 2 months. The purpose of this chapter is to describe the ocular manifestations of brucellosis, early diagnostic procedures, and treatment with reviewing the literature.",signatures:"Ozlem Sahin",downloadPdfUrl:"/chapter/pdf-download/49315",previewPdfUrl:"/chapter/pdf-preview/49315",authors:[{id:"68307",title:"Dr.",name:"Ozlem",surname:"Sahin",slug:"ozlem-sahin",fullName:"Ozlem Sahin"}],corrections:null},{id:"49414",title:"Neurobrucellosis",doi:"10.5772/61655",slug:"neurobrucellosis",totalDownloads:1444,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Brucellosis is a multi-system infectious disease that presents with various clinical manifestations and complications. Neurobrucellosis is an uncommon but serious presentation of brucellosis that can be seen in all stages of the disease. Neurobrucellosis is a focal complication of brucellosis affecting both central and peripheral nervous system presenting varieties of signs and symptoms. The most reported manifestations are meningitis and meningoencephalitis. It is a rare presentation of brucellosis. The estimated mean incidence of neurobrucellosis is 1.7%–10%. The incidence is equal in males and females. Initial clinical manifestations consisted of meningoencephalitis, acute and subacute meningitis, intracranial hypertension, polyradiculoneuritis, cerebral and subarachnoid hemorrhage, transverse myelitis, lumbar epidural abscess with root involvement, and cranial nerve involvement. Other rare manifestation includes pseudotumor cerebri, intracranial granuloma, sagittal sinus thrombosis, spinal arachnoiditis, and intracranial vasculitis. High index of suspicion, especially in endemic areas is essential to prevent morbidity from this disease. Clinical suspicion and accurate evaluation of a patient's history is the most important clue in diagnosis and treatment. Neurobrucellosis can be diagnosed by isolation of microorganism from the CSF or detection of antibodies in the CSF. The CSF pattern in neurobrucellosis can be helpful for diagnosis; lymphocytic pleocytosis, increased protein, and decreased glucose levels in the CSF are in favor of neurobrucellosis. Imaging modalities, including CT scan or magnetic resonance imaging, may reveal information for diagnosis. Many laboratory procedures are usually employed in the diagnosis of neurobrucellosis. Even though the culture method is the gold standard, growth rate is low and time consuming. Coombs' test should be performed in both the CSF and serum. Different regimens are usually used based on ceftriaxone, doxycycline, cotrimoxasole, streptomycin, and rifampicin. Treatment with intravenous ceftriaxone and oral rifampicin, doxycycline, and trimethoprim–sulfamethoxazole resulted in a good clinical response. Patients with severe and persistent headache and other neurologic symptoms and signs should be considered for neurobrucellosis in endemic regions. Early diagnosis and treatment of neurobrucellosis will be helpful in decreasing the sequelae of this complication.",signatures:"Farhad Abbasi and Soolmaz Korooni",downloadPdfUrl:"/chapter/pdf-download/49414",previewPdfUrl:"/chapter/pdf-preview/49414",authors:[{id:"76934",title:"Dr.",name:"Farhad",surname:"Abbasi",slug:"farhad-abbasi",fullName:"Farhad Abbasi"}],corrections:null},{id:"49033",title:"Brucellosis – Granulomatous Spine Infection",doi:"10.5772/61214",slug:"brucellosis-granulomatous-spine-infection",totalDownloads:1608,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Brucellosis mainly affects the musculoskeletal system, with the spine as the most common location. Diagnosis is based on clinical symptoms, but in some cases, they may be lacking. Laboratory diagnosis is mainly made on the combination of high erythrocyte sedimentation rate (ESR) together with high levels of C-reactive protein (CRP) and leukocytosis. Blood culture is a very cost-effective investigation; plain radiographs may be useful, but magnetic resonance images (MRI) with gadolinium enhancement is the choice for diagnosing osteoarticular and spinal complications of human brucellosis. MRI diffusion-weighted imaging fast sequence is the most sensitive for differentiating acute and chronic forms of spondylodiscitis. The basis for treatment is usually the medical management. The indications for surgical treatment (endoscopy or open) are when: no microorganism has been isolated, spinal cord or dural compression is seen in MRI, or there's spinal instability or severe deformity. Open surgery is the standard: the anterior approach allows for anterior disc and bone debridement. If there is an epidural abscess or posterior elements are involved it's indicated as a posterior approach. To prevent relapses and reduce the rate of sequelae, it's necessary to have an appropriate duration of antimicrobial therapy and a timely indication to perform surgery.",signatures:"Ana M. Cerván, Miguel Hirschfeld, Miguel Rodriguez and Enrique\nGuerado",downloadPdfUrl:"/chapter/pdf-download/49033",previewPdfUrl:"/chapter/pdf-preview/49033",authors:[{id:"175401",title:"Dr.",name:"Ana Maria",surname:"Cervan",slug:"ana-maria-cervan",fullName:"Ana Maria Cervan"}],corrections:null},{id:"49044",title:"Blood Cultures for the Diagnosis of Human Brucellosis",doi:"10.5772/61143",slug:"blood-cultures-for-the-diagnosis-of-human-brucellosis",totalDownloads:1978,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Brucellosis represents a serious health threat to human populations living in areas endemic for the disease. The clinical manifestations of brucellosis are protean and non-specific, and laboratory confirmation of the diagnosis is crucial for an adequate management of the patient and implementation of infection control measures aimed to control the disease in affected herds. Although brucellosis can be confirmed by serologic tests and nucleic acid amplification assays, culture detection of circulating Brucella organisms remains a diagnostic cornerstone. Traditionally, prolonged incubation of media and performance of blind subcultures of negative blood culture vials have been recommended to maximize isolation of the organism. In recent years, modern automated blood culture systems have revolutionized the diagnosis of human brucellosis by improving sensitivity and enabling detection of brucellae within the routine one-week incubation protocol followed in most Clinical Microbiology laboratories. Development of molecular techniques and mass-spectrometry technology have also shortened the time needed to identify members of the genus, whereas use of biological safety cabinets considerably reduce the risks of contagion to laboratory personnel.",signatures:"Pablo Yagupsky",downloadPdfUrl:"/chapter/pdf-download/49044",previewPdfUrl:"/chapter/pdf-preview/49044",authors:[{id:"174887",title:"Prof.",name:"Pablo",surname:"Yagupsky",slug:"pablo-yagupsky",fullName:"Pablo Yagupsky"}],corrections:null},{id:"49399",title:"Antibiotic Susceptibility Testing of Brucella Species - Old and New Drugs",doi:"10.5772/61706",slug:"antibiotic-susceptibility-testing-of-brucella-species-old-and-new-drugs",totalDownloads:1301,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Brucella species cause brucellosis in humans and animals, a zoonosis that can manifest not only as acute or chronic diseases but also as silent infections persisting throughout life with recurrences potentially occurring after several decades. In vitro and in vivo methods have been developed to evaluate the bacteriostatic and bactericidal activity of antibiotics against Brucella sp. Especially eukaryotic cells and animal models have been used to evaluate the ability of antibiotics, alone or in combination, to eradicate these bacteria from their intracellular reservoir. Although treatment recommendations have been established for common clinical forms of brucellosis, optimized therapeutic alternatives are still needed for severe forms of the disease, and for infections occurring in young children and pregnant women. Moreover, acquired resistance to first-line treatments of brucellosis is a current concern. This chapter will summarize current knowledge on in vitro and in vivo interactions between Brucella species and antibiotics and new therapeutic strategies that have been evaluated.",signatures:"Max Maurin",downloadPdfUrl:"/chapter/pdf-download/49399",previewPdfUrl:"/chapter/pdf-preview/49399",authors:[{id:"45873",title:"Prof.",name:"Max",surname:"Maurin",slug:"max-maurin",fullName:"Max Maurin"}],corrections:null},{id:"49433",title:"Recombinant Proteins as Antigens in Serological Diagnosis of Brucellosis",doi:"10.5772/61762",slug:"recombinant-proteins-as-antigens-in-serological-diagnosis-of-brucellosis",totalDownloads:1635,totalCrossrefCites:3,totalDimensionsCites:4,hasAltmetrics:0,abstract:"Brucellosis is considered the major zoonosis in developing countries. In susceptible animal species, diagnosis of brucellosis remains a challenge due to the variety of clinical signs that it shares with a wide range of diseases. At present, isolation of Brucella is considered the gold standard for diagnosis of brucellosis; because of its low sensitivity and becoming potentially hazardous to laboratory technicians, serology is used for the detection of specific antibodies induced by infection. However, since traditional methods commonly show drawbacks and do not differentiate between vaccinated and naturally infected animals, it is necessary to search and test immunoreactive molecules for specific diagnosis of Brucella-infected cattle, thus significantly reducing the killing of suspected herds mainly due to vaccination. Advances in biotechnology have allowed exploring the use of recombinant proteins as antigens to avoid the risk involved in the use of viable Brucella strains. The benefit of using recombinant proteins, such as outer membrane proteins (OMP) and other non-lipopolysaccharide (non-LPS) molecules as antigens, for serological diagnosis is promising, but there are still many concerns about their application. The aim of the present work is to show advances in the use of recombinant antigens and discuss their advantages and potential use as markers for the serological diagnosis in brucellosis.",signatures:"Magda Celina Navarro-Soto, Alberto Morales-Loredo, Genoveva\nÁlvarez-Ojeda, Carlos Ramírez-Pfeiffer, Patricia Tamez-Guerra and\nRicardo Gomez-Flores",downloadPdfUrl:"/chapter/pdf-download/49433",previewPdfUrl:"/chapter/pdf-preview/49433",authors:[{id:"175049",title:"Dr.",name:"Ricardo Alberto",surname:"Gomez Flores",slug:"ricardo-alberto-gomez-flores",fullName:"Ricardo Alberto Gomez Flores"}],corrections:null},{id:"48725",title:"Treatment of Brucellosis",doi:"10.5772/61093",slug:"treatment-of-brucellosis",totalDownloads:2562,totalCrossrefCites:3,totalDimensionsCites:4,hasAltmetrics:0,abstract:"The goal of brucellosis therapy is to control the illness and prevent complications, relapses and sequelae. Important principles of brucellosis treatment include the use of antibiotics with activity in the acidic intracellular environment (doxycycline, rifampin), use of combination regimens and prolonged duration of treatment.",signatures:"Mitra Ranjbar",downloadPdfUrl:"/chapter/pdf-download/48725",previewPdfUrl:"/chapter/pdf-preview/48725",authors:[{id:"79344",title:"Dr.",name:"Mitra",surname:"Ranjbar",slug:"mitra-ranjbar",fullName:"Mitra Ranjbar"}],corrections:null},{id:"49074",title:"Treatment of Human Brucellosis — Review of Evidence from Clinical Trials",doi:"10.5772/61223",slug:"treatment-of-human-brucellosis-review-of-evidence-from-clinical-trials",totalDownloads:1580,totalCrossrefCites:3,totalDimensionsCites:5,hasAltmetrics:0,abstract:"Unresolved issues remain surrounding the treatment of human brucellosis. The present work aims to provide useful information to help clinicians make decisions when treating brucellosis patients. Information based on scientific evidence from clinical trials published over the past 30 years has been compiled and presented in an updated form, covering both focal and non-focal, or uncomplicated, human brucellosis. This chapter shows that, despite the studies published in recent years, areas such as the role of monotherapy or treatment in cases of focal disease, have not been adequately addressed in clinical trials, and demonstrates the need for further research.",signatures:"Julián Solís García del Pozo and Javier Solera",downloadPdfUrl:"/chapter/pdf-download/49074",previewPdfUrl:"/chapter/pdf-preview/49074",authors:[{id:"175325",title:"Dr.",name:"Julián",surname:"Solís García Del Pozo",slug:"julian-solis-garcia-del-pozo",fullName:"Julián Solís García Del Pozo"},{id:"175328",title:"Dr.",name:"Javier",surname:"Solera",slug:"javier-solera",fullName:"Javier Solera"}],corrections:null},{id:"49083",title:"Control of Animal Brucellosis — The Most Effective Tool to Prevent Human Brucellosis",doi:"10.5772/61222",slug:"control-of-animal-brucellosis-the-most-effective-tool-to-prevent-human-brucellosis",totalDownloads:2719,totalCrossrefCites:5,totalDimensionsCites:14,hasAltmetrics:0,abstract:"The World Health Organization classifies brucellosis as one of the seven neglected endemic zoonosis which contribute to the perpetuation of poverty in developing countries. Although most of the developed countries are free from this important zoonosis, brucellosis has still a widespread distribution in the Mediterranean region, the Middle East, Central Asia, and parts of Latin America, making it a global problem. Nearly half a million of new cases of human brucellosis are reported each year around the world, in which animals (or products of animal origin) are the most likely source of infection. Brucella melitensis, the main etiologic agent of small ruminant brucellosis, is the most prevalent specie involved in cases of human disease in most parts of the world. Additionally, Brucella abortus (main responsible of bovine brucellosis) and Brucella suis (the most common etiological agent of porcine brucellosis) are often associated with human brucellosis. In animal production, brucellosis has a strong economic impact due not only to its direct consequences (e.g., reproductive failures) but also to indirect loses (e.g., trade restrictions). The problem of brucellosis could be considered a clear example of the need for a “One World, One Health” strategy, given that the only approach to achieve its control and subsequent eradication is the cooperation between public and animal health authorities. The prevention of human brucellosis cannot be achieved without the control of the disease in the animals, as exemplified by the impact that the early measures adopted in the beginning of the 20th century forbidding the consumption of goat milk had on the prevalence of the disease in the British soldiers in Malta. When the prevalence of the disease in the animal population is high or when eradication cannot be achieved due to other factors (e.g., lack of economic resources), its control in livestock must be the first objective. When deciding the optimal approach to tackle the disease, the prevalence of animal brucellosis is not the only parameter to consider by the decision makers since other epidemiological and economic aspects should be considered in order to implement the most adequate control strategy in each region. Cooperation between all stakeholders involved is a cornerstone in the success of any control strategy. Strict biosafety and management measures, vaccination, and test-and-slaughter strategy are recognized as the most effective strategies to control this pathology in livestock. The adequate combination of these measures depends on several factors that will determine the success of the eradication efforts. The present chapter will review the abovementioned measures for the control and eradication of brucellosis in livestock, focusing on the advantages and drawbacks of the diagnosis tools and immunization strategies currently available and evaluating new approaches based on the advance on the knowledge of different aspects of this disease and its etiological agents.",signatures:"Marta Pérez-Sancho, Teresa García-Seco, Lucas Domínguez and\nJulio Álvarez",downloadPdfUrl:"/chapter/pdf-download/49083",previewPdfUrl:"/chapter/pdf-preview/49083",authors:[{id:"83698",title:"Dr.",name:"Lucas",surname:"Dominguez",slug:"lucas-dominguez",fullName:"Lucas Dominguez"},{id:"175392",title:"Dr.",name:"Marta",surname:"Pérez-Sancho",slug:"marta-perez-sancho",fullName:"Marta Pérez-Sancho"},{id:"175402",title:"Ms.",name:"Teresa",surname:"García-Seco",slug:"teresa-garcia-seco",fullName:"Teresa García-Seco"},{id:"175403",title:"Dr.",name:"Julio",surname:"Alvarez",slug:"julio-alvarez",fullName:"Julio Alvarez"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"5294",title:"Steps Forwards in Diagnosing and Controlling Influenza",subtitle:null,isOpenForSubmission:!1,hash:"15d072595f188560cf6edce50307b529",slug:"steps-forwards-in-diagnosing-and-controlling-influenza",bookSignature:"Manal Mohammad Baddour",coverURL:"https://cdn.intechopen.com/books/images_new/5294.jpg",editedByType:"Edited by",editors:[{id:"174598",title:"Dr.",name:"Manal Mohammad",surname:"Baddour",slug:"manal-mohammad-baddour",fullName:"Manal Mohammad Baddour"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7082",title:"Surgical Infections",subtitle:"Some Facts",isOpenForSubmission:!1,hash:"b5cab76ab84efa06f84fce22420ee43d",slug:"surgical-infections-some-facts",bookSignature:"Manal Mohammad Baddour",coverURL:"https://cdn.intechopen.com/books/images_new/7082.jpg",editedByType:"Edited by",editors:[{id:"174598",title:"Dr.",name:"Manal Mohammad",surname:"Baddour",slug:"manal-mohammad-baddour",fullName:"Manal Mohammad Baddour"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10706",title:"Fighting the COVID-19 Pandemic",subtitle:null,isOpenForSubmission:!1,hash:"1a5246f0b6ba4f0e9ad1fbfa4134c598",slug:"fighting-the-covid-19-pandemic",bookSignature:"Manal Mohammad Baddour",coverURL:"https://cdn.intechopen.com/books/images_new/10706.jpg",editedByType:"Edited by",editors:[{id:"174598",title:"Dr.",name:"Manal Mohammad",surname:"Baddour",slug:"manal-mohammad-baddour",fullName:"Manal Mohammad Baddour"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"825",title:"Current Topics in Tropical Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ef65e8eb7a2ada65f2bc939aa73009e3",slug:"current-topics-in-tropical-medicine",bookSignature:"Alfonso J. 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This book presents examples of local installations of AD, or their proposals, located at small factories, workplaces, and in rural areas and housing complexes. The facilities consider the specific nature of the region, site conditions, and specificity of the utilized wastes. They protect the environment and ensure dispersed energy production. The latter is of great economic significance due to its closeness to end customers. Small local installations expand the pool of renewable energy on a global scale.",isbn:"978-1-83969-224-6",printIsbn:"978-1-83969-223-9",pdfIsbn:"978-1-83969-225-3",doi:"10.5772/intechopen.92507",price:119,priceEur:129,priceUsd:155,slug:"anaerobic-digestion-in-built-environments",numberOfPages:130,isOpenForSubmission:!1,isSalesforceBook:!1,hash:"082ec753a05d6c7ed8cc5559e7dac432",bookSignature:"Anna Sikora",publishedDate:"November 3rd 2021",coverURL:"https://cdn.intechopen.com/books/images_new/10491.jpg",keywords:null,numberOfDownloads:1406,numberOfWosCitations:0,numberOfCrossrefCitations:1,numberOfDimensionsCitations:5,numberOfTotalCitations:6,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 28th 2020",dateEndSecondStepPublish:"December 1st 2020",dateEndThirdStepPublish:"January 30th 2021",dateEndFourthStepPublish:"April 20th 2021",dateEndFifthStepPublish:"June 19th 2021",remainingDaysToSecondStep:"a year",secondStepPassed:!0,currentStepOfPublishingProcess:5,editedByType:"Edited by",kuFlag:!1,biosketch:"Principal investigator of grant projects funded by the Polish institutions: The National Centre for Research and Development, The National Science Centre, and Ministry of Science and High Education. Dr. Anna Sikora cooperates with the industry and foreign and domestic research centers.",coeditorOneBiosketch:"A specialist in the Anaerobic Digestion process - molecular and technical aspects of microbiological biofuels production. Dr. Anna Detman connects her engineering, biochemical, and microbiological knowledge with experience in different laboratory scales to create innovative and applicable Science.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"146985",title:"Dr.",name:"Anna",middleName:null,surname:"Sikora",slug:"anna-sikora",fullName:"Anna Sikora",profilePictureURL:"https://mts.intechopen.com/storage/users/146985/images/system/146985.jpg",biography:"Anna Sikora is a microbiologist, professor at the Institute of Biochemistry and Biophysics (IBB) PAS, Warsaw, Poland, and a leader of the Laboratory of White Biotechnology, Warsaw, Poland. She is a graduate of the Faculty of Biology, University of Warsaw. She received her Ph.D. and postdoctoral degrees from IBB PAS. She specializes in research on anaerobic digestion, fermentation processes, biogases (biohydrogen and biomethane) production; microbial communities and nutritional interactions between microorganisms; microbial iron reduction; and mutagenesis and DNA repair in bacteria. She has authored experimental papers, book chapters, and conference reports. She cooperates with the sugar industry in the field of applied research on the development of a method to obtain hydrogen and methane during anaerobic digestion of byproducts and wastes from sugar production.",institutionString:"Polish Academy of Sciences",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Polish Academy of Sciences",institutionURL:null,country:{name:"Poland"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1405",title:"Waste Management",slug:"engineering-environmental-engineering-waste-management"}],chapters:[{id:"77550",title:"Acetogenic Pretreatment as an Energy Efficient Method for Treatment of Textile Processing Wastewater",slug:"acetogenic-pretreatment-as-an-energy-efficient-method-for-treatment-of-textile-processing-wastewater",totalDownloads:136,totalCrossrefCites:0,authors:[{id:"336840",title:"Associate Prof.",name:"nadimkhandaker",surname:"Khandaker",slug:"nadimkhandaker-khandaker",fullName:"nadimkhandaker Khandaker"},{id:"425795",title:"Dr.",name:"Mohammad Moshiur",surname:"Rahman",slug:"mohammad-moshiur-rahman",fullName:"Mohammad Moshiur Rahman"},{id:"425796",title:"Dr.",name:"De Salima",surname:"Diba",slug:"de-salima-diba",fullName:"De Salima Diba"}]},{id:"77247",title:"Evaluation of Physical and Chemical Pretreatment Methods to Improve Efficiency of Anaerobic Digestion of Waste Streams from Grain Processing",slug:"evaluation-of-physical-and-chemical-pretreatment-methods-to-improve-efficiency-of-anaerobic-digestio",totalDownloads:132,totalCrossrefCites:0,authors:[{id:"341131",title:"Dr.",name:"Jagannadh",surname:"Satyavolu",slug:"jagannadh-satyavolu",fullName:"Jagannadh Satyavolu"},{id:"414018",title:"Dr.",name:"Robert",surname:"Lupitskyy",slug:"robert-lupitskyy",fullName:"Robert Lupitskyy"}]},{id:"76068",title:"Employment of Organic Residues for Methane Production: The Use of Wastes of the Pulp and Paper Industry to Produce Biogas - 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From chapter submission and review to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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\n
1. Introduction
\n
Operation management (OM) is vital to achieve success in many disciplines, particularly in a field which requires dealing with large amounts of information such as the construction industry. Most construction projects are a collection of different activities, processes and requirements, involving different factors and aspects to consider. In this way, making decisions in such environments can be a hard task. For these reasons, the need for OM to assist the characterization of such complex scenarios arises. OM could help project managers to improve their decision regarding project time–cost trade-offs (TCTP) [1]. To expedite the execution of a project, project managers need to reduce the scheduled execution time by hiring extra labor or using productive equipment. But this idea will incur additional cost; hence, shortening the completion time of jobs on critical path network is needed. According to several researchers, time–cost trade-off problem (TCTP) is considered as one of the vital decisions in project accomplishment [2]. Usually, there is a trade-off between the duration and the direct cost to do an activity; the cheaper the resources, the larger the time needed to complete an activity. Reducing the time on an activity will usually increase its direct cost. Direct costs for the project contain materials cost, labor cost and equipment cost. Conversely, indirect costs are the necessary costs of doing work which cannot be related to a specific activity and in some cases, cannot be related to a specific project. The total project construction cost can be found by adding direct cost to indirect cost. When the trade-off of all the activities is considered in the project then the relationship between project duration and the total cost is developed as shown in Figure 1. Figure 1 shows that when the duration for the project is reduced, the total cost becomes quite high and as the duration increases, the total cost increases [3]. The literature review of current practices reveals a shortage of existing tools and techniques specifically tailored to solve the time–cost trade-off problem while accounting for uncertainty in project time and cost. The objective of this research is to develop a model to find time–cost trade-off alternatives using TDABC and fuzzy logic. The next sections discuss these analytical methods.
\n
Figure 1.
Project cost and time relationship.
\n
\n
\n
2. Time-driven activity-based costing
\n
The activity-based costing (ABC) concept was first defined in the late 1980s by Robert Kaplan and William Burns [4]. At first, ABC was utilized by the manufacturing industry where technological expansions and productivity developments had reduced the proportion of direct costs but increased the proportion of indirect costs [5].
\n
ABC was developed as a method to address problems associated with traditional cost management systems, which tend to be usable to accurately determine actual production and service costs or provide useful information for operating decisions. ABC is defined as “a method for tracing costs within a process back to individual activities” [6].
\n
ABC has been used in the construction industry for cost estimating [7]. Further, ABC has been used to forecast the optimum duration of a project as well as the optimum resources required to complete a defined quantity of work in a timely and cost-effective manner [8]. Although traditional ABC systems provide construction managers with valuable information, many have been abandoned or never were implemented fully [3]. The traditional ABC system is costly to build, requires time to process, is difficult to maintain and is inflexible when needing modification [3]. These problems are particularly acute for small companies that are not likely to have a sophisticated information processing system. Further, ABC is very expensive for medium-sized-to-large companies.
\n
To overcome the difficulties inherent in traditional ABC, Kaplan and Steven presented a new method called “time-driven activity-based costing (TDABC).” The new TDABC has overcome traditional ABC difficulties, offering a clear, accessible methodology that is easy to implement and update [4]. TDABC relies only on simple time estimates that, for example, can be established based on direct observation of processes [9].
\n
TDABC utilizes time equations that directly allocate resource costs to the activities performed and transactions processed. Only two values need to be estimated: the capacity cost rate for the project (Eq. (1)) and the capacity usage by each activity in the project (Eq. (2)). Both values can be estimated easily and accurately [4]. Kaplan and Steven (2007) further define the capacity cost rate and the capacity usage as follows:
Although TDABC has many advantages over ABC, TDABC is not flawless. There are many difficulties associated with this deterministic TDABC approach. TDABC is unable of accounting for any variation or uncertainty in the project cost and duration (Hoozée and Hansen, 2015). Research carried out in TDABC, so far, has applied deterministic approaches. But, because of uncertainty present in the estimation of project cost and duration, a fuzzy TDABC would lead to more accurate results [10].
\n
\n
\n
3. Fuzzy logic
\n
Fuzzy logic is a technique that provides a definite conclusion from vague and inaccurate information. Fuzzy set theory was first introduced by Zadeh in 1965. He was motivated after witnessing that human reasoning can utilize concepts and knowledge that do not have well-defined boundaries [11].
\n
A useful method for investigating many everyday problems is fuzzy approximate reasoning or fuzzy logic. This technique is founded on the fuzzy set theory that allows the elements of a set to have variable degrees of membership, from a non-membership grade of 0 to a full membership of 1.0 [12]. This smooth gradation of values is what makes fuzzy logic tie well with the ambiguity and uncertainty of many everyday problems.
\n
Fuzzy logic has become an important tool for many different applications ranging from the control of engineering systems to artificial intelligence. Fuzzy logic has been extended to handle the concept of partial truth, where the truth value may range between completely true and false [13]. Fuzzy logic and fuzzy hybrid techniques have been used to capture and model uncertainty in construction, thereby improving workforce and project management. Fuzzy logic can effectively capture expert knowledge and engineering judgment and combine these subjective elements with project data to improve construction decision-making, performance and productivity [14].
\n
Among the various shapes of fuzzy numbers, the triangular fuzzy numbers (TFNs) are the most popular [15]. A triangular fuzzy number μA(x) can be defined as a triplet (a1, aM, a2). Its membership function is defined as follows [16]:
where [a1, a2] is the interval of possible fuzzy numbers and the point (aM, 1) is the peak. This parameter (a1, aM, a2) signifies the smallest possible value, the most promising value and the largest possible value, respectively [17]. Figure 2 illustrates a TFN.
\n
Figure 2.
Triangular fuzzy number.
\n
\n
\n
4. Fuzzy time-driven activity-based costing model
\n
This model utilizes TDABC as a tool for tracing costs and time within a project back to individual activities. TFNs are proposed as a logical approach to manage uncertainty in the deterministic TDABC system. TFNs were used to signify vagueness of TDABC because of their simplification to formulate in a fuzzy environment. Further, they are potentially more intuitive than other complicated types of fuzzy numbers such as trapezoidal or bell-shaped fuzzy numbers [16]. This model has the ability to fuzzify the project cost and duration by transferring these values from crisp numbers to fuzzy sets. A crisp number has a specific value while a fuzzy set has a possible range of values [15]. Then after applying a fuzzy rule, the model will defuzzify the cost and duration of the project to transfer these values back to crisp numbers. Figure 3 shows the fuzzy logic process that has been used in this model, as suggested by [14]. The fuzzy TDABC model consists of three stages as follows:
\n
Figure 3.
Fuzzy logic controller.
\n
\n
4.1. Model stage one
\n
The first step in stage one is to transfer the three-point estimate of project duration from crisp values to the fuzzy set. This can be done by calculating the estimated project duration using one of the traditional scheduling techniques (i.e., CPM) [18]. This value will be called the moderate duration and will use the notation DM. Then the pessimistic duration (the maximum project duration) should be calculated using expert opinion. The pessimistic duration notation is DP. Finally, the optimistic duration (the minimum project duration) should be calculated also using expert opinion. The optimistic duration notation is DO.
\n
The second step is to transfer the three-points estimate of project cost from crisp values to the fuzzy set. This can be done by calculating the estimated project cost using one of the traditional cost estimation techniques (i.e., unit area cost estimate, unit volume cost estimate or parameter cost estimate) [18]. This value will be called the moderate cost and will use the notation CM. Then, the pessimistic cost (the maximum project cost) should be calculated using expert opinion. The pessimistic cost notation is CP. Finally, the optimistic cost (the minimum project cost) should be calculated also using expert opinion. The optimistic cost notation is CO.
\n
During this step, each activity’s moderate duration, optimistic duration and pessimistic duration should be determined. The notations for an activity moderate duration, optimistic duration and pessimistic duration are dm, do and dp, respectively. The third step is to calculate the fuzzy capacity cost rate (CCR) using Eq. (4):
The fourth step is to defuzzify the triangular membership function (TMF) to get crisp CUR values. Available defuzzification techniques include a max-membership principle, a centroid method, a weighted average method, a mean-max membership method, a center of sums, a center of largest area, the first of maxima or last of maxima [19]. Among these, a centroid method (also called Center of Gravity [COG]) is the most prevalent and physically appealing method [20]. The α-cut method is a standard method for performing arithmetic operations on a Triangular Membership Function [21]. The α-cut signifies the degree of risk that the decision-makers are prepared to take (i.e., no risk to full risk). Since the value of α could severely influence the solution, its choice should be carefully considered by decision-makers. Figure 4 shows a TFN with α-cut. The higher the value of α, the greater the confidence (α = 1 means no risk) [21].
\n
Figure 4.
Triangular fuzzy number with α-cut.
\n
By using the center of gravity (COG) defuzzification technique and \n\n∝\n=\n0.1\n\n, crisp CUR values (cost values) can be calculated for each activity using the following formula:
The crisp \n\n\nCUR\nCOST\n∝\n\n\n value that is calculated in this step is the improved cost estimate for an activity at \n\n∝\n=\n0.1\n\n and its notation is \n\n\n\niac\n0.1\n\n\n\n.
\n
The fifth step is to repeat the same process to get the improved cost estimate for all project activities. Finally, add the improved cost estimate for all the activities to get an improved cost estimate for the project at \n\n∝\n=\n0.1\n\n. The project improved cost estimate will be abbreviated as \n\nI\n\nPC\n0.1\n\n\n
where \n\n\niac\n0.1\n\n\n = The improved activity cost at \n\n∝\n=\n0.1\n\n (it is already calculated in stage one).
\n
The third step is to defuzzify the triangular membership function (TMF) using the center of gravity (COG) defuzzification technique. Using COG and \n\n∝\n=\n0.1\n\n, a crisp CUR value (time value) can be calculated for each activity using the following formula:
The crisp \n\n\nCUR\nTIME\n∝\n\n\n\nvalue that is calculated in this step is the improves duration for an activity at\n\n∝\n=\n0.1\n\n and its notation is \n\n\n\niad\n0.1\n\n\n\n.
\n
The fourth step is to repeat the same process to get the improved duration for all project activities. Finally, add the improved duration for all the activities to get an improved duration for the project. The project improved duration will be abbreviated as \n\n\nIPD\n0.1\n\n\n
In stage three, a sensitivity analysis should be performed to investigate the variability of the results obtained with respect to the choice of the α-cut value. Sensitivity analysis is “the study of how the uncertainty in the output of a model can be apportioned to different sources of uncertainty in the model input” [22]. One of the simplest and most common approaches to sensitivity analysis is changing the α-cut value, to see what effect this produces on the project cost and duration. To achieve that, stage one and two should be repeated using α-cut values equal to 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9 and 1.0. The results obtained from the different α-cut values will be saved as shown in Table 1. The sensitivity analysis will help investigate various levels of confidence associated with each time–cost alternative.
\n
\n
\n
\n
\n\n
\n
α-cut
\n
Improved project cost
\n
Improved project duration
\n
\n\n\n
\n
0.1
\n
\n\n\n\nIPC\n0.1\n\n\n\n
\n
\n\n\n\nIPD\n0.1\n\n\n\n
\n
\n
\n
0.2
\n
\n\n\nI\n\nPC\n0.2\n\n\n\n
\n
\n\n\n\nIPD\n0.2\n\n\n\n
\n
\n
\n
0.3
\n
\n\n\nI\n\nPC\n0.3\n\n\n\n
\n
\n\n\nI\n\nPD\n0.3\n\n\n\n
\n
\n
\n
0.4
\n
\n\n\n\nIPC\n0.4\n\n\n\n
\n
\n\n\n\nIPD\n0.4\n\n\n\n
\n
\n
\n
0.5
\n
\n\n\n\nIPC\n0.5\n\n\n\n
\n
\n\n\n\nIPD\n0.5\n\n\n\n
\n
\n
\n
0.6
\n
\n\n\n\nIPC\n0.6\n\n\n\n
\n
\n\n\n\nIPD\n0.6\n\n\n\n
\n
\n
\n
0.7
\n
\n\n\n\nIPC\n0.7\n\n\n\n
\n
\n\n\n\nIPD\n0.7\n\n\n\n
\n
\n
\n
0.8
\n
\n\n\n\nIPC\n0.8\n\n\n\n
\n
\n\n\nI\n\nPD\n0.8\n\n\n\n
\n
\n
\n
0.9
\n
\n\n\n\nIPC\n0.9\n\n\n\n
\n
\n\n\n\nIPD\n0.9\n\n\n\n
\n
\n
\n
1.0
\n
\n\n\n\nIPC\n1.0\n\n\n\n
\n
\n\n\nI\n\nPD\n1.0\n\n\n\n
\n
\n\n
Table 1.
Project time and cost at each α-cut.
\n
\n
\n
\n
5. Fuzzy time-driven model verification and validation
\n
To illustrate an application of the fuzzy TDABC model, a case study of seven activities proposed initially by Zheng et al. (2004) was used [23]. The case study illustrates a construction project that has seven activities as shown in Table 2. The letters O, M and P in Table 2 signify optimistic, moderate and pessimistic time and direct cost. The assumed value for indirect cost per day is $1000, $1150 and $2000 for optimistic, moderate and pessimistic values, respectively. The calculated project duration is (60, 81 and 92) days for optimistic, moderate and pessimistic, respectively.
\n
\n
\n
\n
\n
\n
\n
\n
\n
\n\n
\n
Activity
\n
Predecessor
\n
Time (Days)
\n
Direct cost ($)
\n
\n
\n
O
\n
M
\n
P
\n
O
\n
M
\n
P
\n
\n\n\n
\n
A
\n
—
\n
14
\n
20
\n
24
\n
23,000
\n
18,000
\n
12,000
\n
\n
\n
B
\n
A
\n
15
\n
18
\n
20
\n
3000
\n
2400
\n
1800
\n
\n
\n
C
\n
A
\n
15
\n
22
\n
33
\n
4500
\n
4000
\n
3200
\n
\n
\n
D
\n
A
\n
12
\n
16
\n
20
\n
45,000
\n
35,000
\n
30,000
\n
\n
\n
E
\n
B, C
\n
22
\n
24
\n
28
\n
20,000
\n
17,500
\n
15,000
\n
\n
\n
F
\n
D
\n
14
\n
18
\n
24
\n
40,000
\n
32,000
\n
18,000
\n
\n
\n
G
\n
E, F
\n
9
\n
15
\n
18
\n
30,000
\n
24,000
\n
22,000
\n
\n\n
Table 2.
Activities duration and cost.
\n
The first step is to calculate the total cost of the project by adding the indirect cost to the direct cost. Table 3 shows the optimistic, moderate and pessimistic total cost.
\n
\n
\n
\n
\n\n
\n
Total cost ($)
\n
\n
\n
P
\n
M
\n
O
\n
\n\n\n
\n
296,772
\n
238,169
\n
205,192
\n
\n\n
Table 3.
Project total cost.
\n
Applying stage one of the fuzzy TDABC model begins by using Eq. (4) to calculate the fuzzy CCR as shown in Table 4.
\n
\n
\n
\n
\n\n
\n
CCR ($): Phase I
\n
\n
\n
O
\n
M
\n
P
\n
\n\n\n
\n
2938
\n
1791
\n
1229
\n
\n\n
Table 4.
Fuzzy capacity cost rate (CCR).
\n
Then, the fuzzy capacity usage rate (CUR) is calculated as a cost function using Eq. (5). Table 5 shows the CUR values.
\n
\n
\n
\n
\n
\n\n
\n
Activity
\n
CUR ($): Phase I
\n
\n
\n
O
\n
M
\n
P
\n
\n\n\n
\n
A
\n
41,137
\n
35,815
\n
29,489
\n
\n
\n
B
\n
44,075
\n
32,233
\n
24,574
\n
\n
\n
C
\n
44,075
\n
39,396
\n
40,547
\n
\n
\n
D
\n
35,260
\n
28,652
\n
24,574
\n
\n
\n
E
\n
64,643
\n
42,978
\n
34,403
\n
\n
\n
F
\n
41,137
\n
32,233
\n
29,489
\n
\n
\n
G
\n
26,445
\n
26,861
\n
22,117
\n
\n\n
Table 5.
Fuzzy capacity usage rate (CUR).
\n
Next, α-cut values of 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9 and 1.0 are applied to the CUR values in Table 5. This will generate new CUR values associated with each α-cut. Table 6 shows the CUR values that are associated with each α-cut for each activity in the project.
\n
\n
\n
\n
\n
\n
\n
\n
\n
\n
\n\n
\n
α
\n
Fuzzy CUR ($)
\n
Activities
\n
\n
\n
A
\n
B
\n
C
\n
D
\n
E
\n
F
\n
G
\n
\n\n\n
\n
0.1
\n
CURo
\n
40,604
\n
42,891
\n
43,607
\n
34,599
\n
62,477
\n
40,246
\n
26,487
\n
\n
\n
CURM
\n
35,815
\n
32,233
\n
39,396
\n
28,652
\n
42,978
\n
32,233
\n
26,861
\n
\n
\n
CURP
\n
30,121
\n
25,340
\n
40,432
\n
24,982
\n
35,261
\n
29,763
\n
22,591
\n
\n
\n
0.2
\n
CURo
\n
40,072
\n
41,707
\n
43,139
\n
33,938
\n
60,310
\n
39,356
\n
26,528
\n
\n
\n
CURM
\n
35,815
\n
32,233
\n
39,396
\n
28,652
\n
42,978
\n
32,233
\n
26,861
\n
\n
\n
CURP
\n
30,754
\n
26,106
\n
40,317
\n
25,390
\n
36,118
\n
30,038
\n
23,065
\n
\n
\n
0.3
\n
CURo
\n
39,540
\n
40,523
\n
42,671
\n
33,278
\n
58,144
\n
38,466
\n
26,570
\n
\n
\n
CURM
\n
35,815
\n
32,233
\n
39,396
\n
28,652
\n
42,978
\n
32,233
\n
26,861
\n
\n
\n
CURP
\n
31,387
\n
26,872
\n
40,202
\n
25,797
\n
36,976
\n
30,312
\n
23,540
\n
\n
\n
0.4
\n
CURo
\n
39,008
\n
39,338
\n
42,204
\n
32,617
\n
55,977
\n
37,575
\n
26,611
\n
\n
\n
CURM
\n
35,815
\n
32,233
\n
39,396
\n
28,652
\n
42,978
\n
32,233
\n
26,861
\n
\n
\n
CURP
\n
32,019
\n
27,638
\n
40,087
\n
26,205
\n
37,833
\n
30,587
\n
24,014
\n
\n
\n
0.5
\n
CURo
\n
38,476
\n
38,154
\n
41,736
\n
31,956
\n
53,811
\n
36,685
\n
26,653
\n
\n
\n
CURM
\n
35,815
\n
32,233
\n
39,396
\n
28,652
\n
42,978
\n
32,233
\n
26,861
\n
\n
\n
CURP
\n
32,652
\n
28,404
\n
39,972
\n
26,613
\n
38,691
\n
30,861
\n
24,489
\n
\n
\n
0.6
\n
CURo
\n
37,944
\n
36,970
\n
41,268
\n
31,295
\n
51,644
\n
35,795
\n
26,695
\n
\n
\n
CURM
\n
35,815
\n
32,233
\n
39,396
\n
28,652
\n
42,978
\n
32,233
\n
26,861
\n
\n
\n
CURP
\n
33,284
\n
29,170
\n
39,857
\n
27,021
\n
39,548
\n
31,135
\n
24,963
\n
\n
\n
0.7
\n
CURo
\n
37,411
\n
35,786
\n
40,800
\n
30,634
\n
49,477
\n
34,904
\n
26,736
\n
\n
\n
CURM
\n
35,815
\n
32,233
\n
39,396
\n
28,652
\n
42,978
\n
32,233
\n
26,861
\n
\n
\n
CURP
\n
33,917
\n
29,936
\n
39,741
\n
27,428
\n
40,405
\n
31,410
\n
25,438
\n
\n
\n
0.8
\n
CURo
\n
36,879
\n
34,602
\n
40,332
\n
29,973
\n
47,311
\n
34,014
\n
26,778
\n
\n
\n
CURM
\n
35,815
\n
32,233
\n
39,396
\n
28,652
\n
42,978
\n
32,233
\n
26,861
\n
\n
\n
CURP
\n
34,550
\n
30,701
\n
39,626
\n
27,836
\n
41,263
\n
31,684
\n
25,912
\n
\n
\n
0.9
\n
CURo
\n
36,347
\n
33,418
\n
39,864
\n
29,313
\n
45,144
\n
33,124
\n
26,820
\n
\n
\n
CURM
\n
35,815
\n
32,233
\n
39,396
\n
28,652
\n
42,978
\n
32,233
\n
26,861
\n
\n
\n
CURP
\n
35,182
\n
31,467
\n
39,511
\n
28,244
\n
42,120
\n
31,959
\n
26,387
\n
\n
\n
1.0
\n
CURo
\n
35,815
\n
32,233
\n
39,396
\n
28,652
\n
42,978
\n
32,233
\n
26,861
\n
\n
\n
CURM
\n
35,815
\n
32,233
\n
39,396
\n
28,652
\n
42,978
\n
32,233
\n
26,861
\n
\n
\n
CURP
\n
35,815
\n
32,233
\n
39,396
\n
28,652
\n
42,978
\n
32,233
\n
26,861
\n
\n\n
Table 6.
CUR value at each α-cut ($): Phase I.
\n
Using Eq. (7), crisp CUR values associated with each α-cut are determined for each activity. These CUR values are the improved cost estimate for each activity at the associated α-cut. By adding the improved activities’ costs, the project improved cost estimates are determined as shown in Table 7.
\n
\n
\n
\n
\n
\n
\n
\n
\n
\n
\n\n
\n
Crisp CUR Values ($) - Phase I
\n
\n
\n
α-cut
\n
Activities
\n
Improved project cost ($)
\n
\n
\n
A
\n
B
\n
C
\n
D
\n
E
\n
F
\n
G
\n
\n\n\n
\n
0.1
\n
35,622
\n
34,868
\n
42,040
\n
30,049
\n
50,132
\n
35,266
\n
24,590
\n
252,567
\n
\n
\n
0.2
\n
35,617
\n
34,504
\n
41,744
\n
29,869
\n
49,226
\n
34,905
\n
24,837
\n
250,703
\n
\n
\n
0.3
\n
35,620
\n
34,158
\n
41,449
\n
29,695
\n
48,345
\n
34,550
\n
25,085
\n
248,902
\n
\n
\n
0.4
\n
35,628
\n
33,829
\n
41,154
\n
29,527
\n
47,490
\n
34,200
\n
25,335
\n
247,164
\n
\n
\n
0.5
\n
35,643
\n
33,517
\n
40,860
\n
29,366
\n
46,663
\n
33,857
\n
25,586
\n
245,491
\n
\n
\n
0.6
\n
35,665
\n
33,223
\n
40,566
\n
29,210
\n
45,863
\n
33,519
\n
25,839
\n
243,885
\n
\n
\n
0.7
\n
35,693
\n
32,947
\n
40,273
\n
29,061
\n
45,094
\n
33,188
\n
26,092
\n
242,348
\n
\n
\n
0.8
\n
35,727
\n
32,690
\n
39,980
\n
28,918
\n
44,356
\n
32,863
\n
26,347
\n
240,882
\n
\n
\n
0.9
\n
35,768
\n
32,452
\n
39,688
\n
28,782
\n
43,650
\n
32,545
\n
26,604
\n
239,488
\n
\n
\n
1.0
\n
35,815
\n
32,233
\n
39,396
\n
28,652
\n
42,978
\n
32,233
\n
26,861
\n
238,169
\n
\n\n
Table 7.
Project improved cost estimates.
\n
At this point, stage one of the model is done and stage two begins. By using the improved project costs that have been calculated in Table 7, the fuzzy capacity cost rates (CCR) are calculated using Eq. (9). Table 8 shows the CCR value associated with each α-cut.
\n
\n
\n
\n
\n
\n\n
\n
Activity
\n
CCR - Phase II
\n
\n
\n
O
\n
M
\n
P
\n
\n\n\n
\n
0.1
\n
0.000238
\n
0.000321
\n
0.000364
\n
\n
\n
0.2
\n
0.000239
\n
0.000323
\n
0.000367
\n
\n
\n
0.3
\n
0.000241
\n
0.000325
\n
0.000370
\n
\n
\n
0.4
\n
0.000243
\n
0.000328
\n
0.000372
\n
\n
\n
0.5
\n
0.000244
\n
0.000330
\n
0.000375
\n
\n
\n
0.6
\n
0.000246
\n
0.000332
\n
0.000377
\n
\n
\n
0.7
\n
0.000248
\n
0.000334
\n
0.000380
\n
\n
\n
0.8
\n
0.000249
\n
0.000336
\n
0.000382
\n
\n
\n
0.9
\n
0.000251
\n
0.000338
\n
0.000384
\n
\n
\n
1.0
\n
0.000252
\n
0.000340
\n
0.000386
\n
\n\n
Table 8.
The CCR value associated with each α-cut.
\n
Then, the fuzzy capacity usage rate (CUR) is calculated as a time function using Eq. (10). Table 9 shows the CUR values.
\n
\n
\n
\n
\n
\n
\n
\n
\n
\n
\n\n
\n
α
\n
Fuzzy CUR (Days)
\n
Activities
\n
\n
\n
A
\n
B
\n
C
\n
D
\n
E
\n
F
\n
G
\n
\n\n\n
\n
0.1
\n
CURo
\n
9
\n
9
\n
10
\n
7
\n
12
\n
9
\n
6
\n
\n
\n
CURM
\n
11
\n
11
\n
13
\n
10
\n
16
\n
11
\n
8
\n
\n
\n
CURP
\n
13
\n
13
\n
15
\n
11
\n
18
\n
13
\n
9
\n
\n
\n
0.2
\n
CURo
\n
9
\n
9
\n
11
\n
8
\n
13
\n
9
\n
6
\n
\n
\n
CURM
\n
12
\n
11
\n
13
\n
10
\n
16
\n
11
\n
8
\n
\n
\n
CURP
\n
13
\n
12
\n
15
\n
11
\n
18
\n
13
\n
9
\n
\n
\n
0.3
\n
CURo
\n
9
\n
9
\n
11
\n
8
\n
13
\n
9
\n
6
\n
\n
\n
CURM
\n
12
\n
11
\n
13
\n
10
\n
16
\n
11
\n
8
\n
\n
\n
CURP
\n
13
\n
12
\n
15
\n
11
\n
18
\n
12
\n
9
\n
\n
\n
0.4
\n
CURo
\n
10
\n
9
\n
11
\n
8
\n
14
\n
10
\n
7
\n
\n
\n
CURM
\n
12
\n
11
\n
13
\n
10
\n
16
\n
11
\n
8
\n
\n
\n
CURP
\n
12
\n
12
\n
15
\n
10
\n
17
\n
12
\n
9
\n
\n
\n
0.5
\n
CURo
\n
10
\n
10
\n
12
\n
8
\n
14
\n
10
\n
7
\n
\n
\n
CURM
\n
12
\n
11
\n
13
\n
10
\n
15
\n
11
\n
8
\n
\n
\n
CURP
\n
12
\n
12
\n
14
\n
10
\n
17
\n
12
\n
8
\n
\n
\n
0.6
\n
CURo
\n
10
\n
10
\n
12
\n
9
\n
14
\n
10
\n
7
\n
\n
\n
CURM
\n
12
\n
11
\n
13
\n
10
\n
15
\n
11
\n
9
\n
\n
\n
CURP
\n
12
\n
12
\n
14
\n
10
\n
17
\n
12
\n
8
\n
\n
\n
0.7
\n
CURo
\n
11
\n
10
\n
12
\n
9
\n
15
\n
10
\n
7
\n
\n
\n
CURM
\n
12
\n
11
\n
13
\n
10
\n
15
\n
11
\n
9
\n
\n
\n
CURP
\n
12
\n
12
\n
14
\n
10
\n
17
\n
12
\n
8
\n
\n
\n
0.8
\n
CURo
\n
11
\n
11
\n
13
\n
9
\n
15
\n
11
\n
7
\n
\n
\n
CURM
\n
12
\n
11
\n
13
\n
10
\n
15
\n
11
\n
9
\n
\n
\n
CURP
\n
12
\n
11
\n
14
\n
10
\n
17
\n
12
\n
8
\n
\n
\n
0.9
\n
CURo
\n
11
\n
11
\n
13
\n
9
\n
16
\n
11
\n
8
\n
\n
\n
CURM
\n
12
\n
11
\n
13
\n
10
\n
15
\n
11
\n
9
\n
\n
\n
CURP
\n
12
\n
11
\n
14
\n
10
\n
16
\n
11
\n
8
\n
\n
\n
1.0
\n
CURo
\n
11
\n
11
\n
13
\n
10
\n
16
\n
11
\n
8
\n
\n
\n
CURM
\n
12
\n
11
\n
13
\n
10
\n
15
\n
11
\n
9
\n
\n
\n
CURP
\n
11
\n
11
\n
13
\n
10
\n
16
\n
11
\n
8
\n
\n\n
Table 9.
CUR value at each α-cut (days): Phase II.
\n
Using Eq. (12), new crisp CUR values associated with each α-cut are determined for each activity. These CUR values are the improved duration for each activity at the associated α-cut. By adding the improved activities’ durations, the project improved durations are determined as shown in Table 10.
\n
\n
\n
\n
\n
\n
\n
\n
\n
\n
\n\n
\n
Crisp CUR (Days): Phase II
\n
\n
\n
α-cut
\n
Activities
\n
Improved project duration (Days)
\n
\n
\n
A
\n
B
\n
C
\n
D
\n
E
\n
F
\n
G
\n
\n\n\n
\n
0.1
\n
10.9
\n
10.7
\n
12.9
\n
9.2
\n
15.4
\n
10.8
\n
7.5
\n
77.4
\n
\n
\n
0.2
\n
11.0
\n
10.7
\n
12.9
\n
9.2
\n
15.4
\n
10.9
\n
7.6
\n
77.7
\n
\n
\n
0.3
\n
11.0
\n
10.8
\n
13.0
\n
9.3
\n
15.5
\n
10.9
\n
7.6
\n
78.0
\n
\n
\n
0.4
\n
11.1
\n
10.8
\n
13.0
\n
9.3
\n
15.6
\n
10.9
\n
7.6
\n
78.4
\n
\n
\n
0.5
\n
11.1
\n
10.9
\n
13.1
\n
9.4
\n
15.6
\n
11.0
\n
7.7
\n
78.8
\n
\n
\n
0.6
\n
11.2
\n
10.9
\n
13.2
\n
9.4
\n
15.7
\n
11.1
\n
7.7
\n
79.2
\n
\n
\n
0.7
\n
11.2
\n
11.0
\n
13.2
\n
9.5
\n
15.8
\n
11.1
\n
7.7
\n
79.6
\n
\n
\n
0.8
\n
10.9
\n
10.7
\n
12.9
\n
9.2
\n
15.4
\n
10.8
\n
7.5
\n
77.4
\n
\n
\n
0.9
\n
11.0
\n
10.7
\n
12.9
\n
9.2
\n
15.4
\n
10.9
\n
7.6
\n
77.7
\n
\n
\n
1.0
\n
11.0
\n
10.8
\n
13.0
\n
9.3
\n
15.5
\n
10.9
\n
7.6
\n
78.0
\n
\n\n
Table 10.
Project improved duration.
\n
Using the results in Tables 7 and 10, the improved project cost and the improved project duration associated with each α-cut are summarized in Table 11.
\n
\n
\n
\n
\n\n
\n
α-cut
\n
Improved project cost ($)
\n
Improved project duration (Days)
\n
\n\n\n
\n
0.1
\n
252,567
\n
77.4
\n
\n
\n
0.2
\n
250,703
\n
77.7
\n
\n
\n
0.3
\n
248,902
\n
78.0
\n
\n
\n
0.4
\n
247,164
\n
78.4
\n
\n
\n
0.5
\n
245,491
\n
78.8
\n
\n
\n
0.6
\n
243,885
\n
79.2
\n
\n
\n
0.7
\n
242,348
\n
79.6
\n
\n
\n
0.8
\n
240,882
\n
80.0
\n
\n
\n
0.9
\n
239,488
\n
80.5
\n
\n
\n
1.0
\n
238,169
\n
81.0
\n
\n\n
Table 11.
Improved project cost and duration associated with each α-cut.
\n
Using Table 11, a plot of the improved project costs versus the improved project durations is created as shown in Figure 5. The robustness of the new proposed TDABC model is compared with two previous models:
Gen and Cheng (2000) model.
Zheng et al. (2004) model.
\n
Figure 5.
Improved project cost versus project durations.
\n
Gen and Cheng (2004) used a genetic algorithm (GA) approach to find the best Time–Cost Trade-Offs. GA is a search method used for finding optimized solutions to problems based on the natural selection theory and biological evolution [24]. The Zheng et al. model used the modified adaptive weight approach with GA to solve the time–cost trade-off problem. The modified adaptive weight approach is a method to represent the importance of each function by assigning different weights to different functions [23].
\n
The results of these two models are compared with the fuzzy TDABC model in Table 12.
\n
\n
\n
\n
\n
\n\n
\n
Approaches
\n
Criteria
\n
Target
\n
\n
\n
Time (days)
\n
Cost ($)
\n
\n\n\n
\n
Gen and Cheng (2000)
\n
83
\n
243,500
\n
Least cost
\n
\n
\n
79
\n
256,400
\n
Least time
\n
\n
\n
Zheng et al. (2004)
\n
73
\n
236,500
\n
Least cost
\n
\n
\n
66
\n
251,500
\n
Least time
\n
\n
\n
Fuzzy TDABC (This research)
\n
81
\n
238,169
\n
Least cost
\n
\n
\n
77
\n
252,567
\n
Least time
\n
\n\n
Table 12.
Fuzzy TDABC result vs. previous research results.
\n
Figure 6 compares between the fuzzy TDABC result and the results obtained by Gen and Cheng (2004) and Zheng et al. (2004).
\n
Figure 6.
Fuzzy TDABC result versus previous research results.
\n
Table 12 and Figure 6 show that the fuzzy TDABC obtains better values of time and cost compared to the result obtained by Gen and Cheng (2000). However, the result obtained by Zheng (2004) is better than the fuzzy TDABC result.
\n
To further compare the results of the fuzzy TDABC model with the past published results, a test called Wilcoxon signed-ranks test is performed. The Wilcoxon Signed-Ranks test is a non-parametric analysis that statistically compared the average of two dependent samples and assessed for significant differences. Wilcoxon signed-ranks test does not assume normality of the differences of the compered groups [25]. The Wilcoxon test has been selected because the datasets in this case do not follow normal distribution. The method to perform Wilcoxon test starts with two hypotheses. A null hypothesis (H₀) assumes that the results obtained from the three approaches are the same. An alternative hypothesis (H₁) assumes that the results obtained from the three approaches are not the same. Table 13 shows the Wilcoxon signed-ranks test result.
\n
\n
\n
\n
\n
\n
\n\n
\n
Source
\n
N
\n
Wilcoxon Statistic
\n
P-Value
\n
Estimated median
\n
\n\n\n
\n
Time
\n
6
\n
21.0
\n
0.036
\n
77 Day
\n
\n
\n
Cost
\n
6
\n
21.0
\n
0.036
\n
$246,450
\n
\n\n
Table 13.
Wilcoxon signed-ranks test result.
\n
Table 13 shows that the p-value is 0.036. The p-value, or calculated probability, assesses if the sample data support the argument that the null hypothesis (H₀) is true. A small p-value (less or equal to 0.05) indicates solid evidence against the null hypothesis, so the null hypothesis should be rejected. A large p-value (larger than 0.05) indicates weak evidence against the null hypothesis, so the null hypothesis should not be rejected [25]. The p-value is 0.036, in this case, which is less than the significance level of 0.05. As a result, there is enough evidence to reject the null hypothesis and to conclude that the difference between the results obtained from the three approaches is significant.
\n
\n
\n
6. Conclusion
\n
The objective of this research is to develop a model to find time–cost trade-off alternatives while accounting for uncertainty in project time and cost. The presented fuzzy TDABC model provides an attractive alternative for the traditional solutions of the time–cost trade-offs optimization problem. The presented model is simple and easy to apply compared with other approaches. Further, this model obtained a better solution when compared to the GA model that is presented by Gen and Cheng (2000). The fuzzy TDABC model could improve the reliability of the time–cost trade-off decisions. This could help construction companies mitigate the risk of projects running over budget or behind schedule.
\n
\n\n',keywords:"scheduling, fuzzy logic, time–cost trade-off, cost estimating, risk management",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/59366.pdf",chapterXML:"https://mts.intechopen.com/source/xml/59366.xml",downloadPdfUrl:"/chapter/pdf-download/59366",previewPdfUrl:"/chapter/pdf-preview/59366",totalDownloads:1133,totalViews:250,totalCrossrefCites:2,totalDimensionsCites:4,totalAltmetricsMentions:0,impactScore:4,impactScorePercentile:86,impactScoreQuartile:4,hasAltmetrics:0,dateSubmitted:"October 12th 2017",dateReviewed:"January 15th 2018",datePrePublished:"February 22nd 2018",datePublished:"June 20th 2018",dateFinished:"February 15th 2018",readingETA:"0",abstract:"The time–cost trade-off problem (TCTP) is fundamental to project scheduling. Risks in estimation of project cost and duration are significant due to uncertainty. This uncertainty cannot be eliminated by any scheduling or estimation techniques. Therefore, a model that can represent uncertainty in the real world to solve time–cost trade-off problems is needed. In this chapter, fuzzy logic is utilized to consider affecting uncertainties in project duration and cost. An optimization algorithm based on time-driven activity-based costing (TDABC) is applied to provide a trade-off between project time and cost. The presented model could solve the time–cost trade-off problem while accounting for uncertainty in project cost and duration. This could help generate a more reliable schedule and mitigate the risk of projects running overbudget or behind schedule.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/59366",risUrl:"/chapter/ris/59366",book:{id:"6535",slug:"contemporary-issues-and-research-in-operations-management"},signatures:"Mohammad Ammar Al-Zarrad and Daniel Fonseca",authors:[{id:"16972",title:"Dr.",name:"Daniel",middleName:null,surname:"Fonseca",fullName:"Daniel Fonseca",slug:"daniel-fonseca",email:"dfonseca@eng.ua.edu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"227043",title:"Dr.",name:"Ammar",middleName:null,surname:"Alzarrad",fullName:"Ammar Alzarrad",slug:"ammar-alzarrad",email:"mazarrad@gmail.com",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/227043/images/6220_n.jpg",institution:{name:"Marshall University",institutionURL:null,country:{name:"United States of America"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Time-driven activity-based costing",level:"1"},{id:"sec_3",title:"3. Fuzzy logic",level:"1"},{id:"sec_4",title:"4. Fuzzy time-driven activity-based costing model",level:"1"},{id:"sec_4_2",title:"4.1. Model stage one",level:"2"},{id:"sec_5_2",title:"4.2. Model stage two",level:"2"},{id:"sec_6_2",title:"4.3. Model stage three",level:"2"},{id:"sec_8",title:"5. Fuzzy time-driven model verification and validation",level:"1"},{id:"sec_9",title:"6. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'Eydi A, Farughi H, Abdi F, Hybrid Method A. Based on fuzzy AHP and VIKOR for the discrete time-cost-quality trade-off problem. Journal of Optimization in Industrial Engineering. 2016;19:105-116\n'},{id:"B2",body:'Pour NS, Modarres M, Moghaddam RT. Time-cost-quality trade-off in project scheduling with linguistic variables. World Applied Sciences Journal. 2012;18:404-413\n'},{id:"B3",body:'Trivedi MK, Namdev S. Use of optimization techniques in time-cost trade-off (TCT) in civil construction: An overview. International Journal of Civil Engineering and Mechanics. 2015;2:1-13\n'},{id:"B4",body:'Kaplan R, Steven A. Time-Driven Activity-Based Costing: A Simpler and more Powerful Path to Higher Profits. Boston: Harvard Business School Press; 2007\n'},{id:"B5",body:'Bjornenak T, Falconer M. The development of activity-based costing journal literature, 1987-2000. The European Accounting Review. 2002;11:481-508\n'},{id:"B6",body:'Chartered Institute of Management Accountants. Activity Based Costing: Topic Gateway Series No. 1 for 2008 [Internet]. 2008. Available from http://www.cimaglobal.com/Documents/ImportedDocuments/cid_tg_activity_based_costing_nov08.pdf.pdf, [Accessed: 2017-12-02]\n'},{id:"B7",body:'Back W, Maxwell D, Isidore L. Activity-based costing as a tool for process improvement evaluations. Journal of Engineering Management. 2000;16:48-58\n'},{id:"B8",body:'Maxwell D, Back W, Toon J. Optimization of crew configurations using activity-based costing. Journal of Construction Engineering Management. 1998;124:162-168\n'},{id:"B9",body:'Azhdari M, Lalisarabi A. Implementing the time-driven activity-based costing system (TDABC) in a food production company and comparing it with the traditional system. Technical. Journal of Engineering and Applied Sciences. 2015;5:471-475\n'},{id:"B10",body:'Chansaad A, Rattanamanee W. A Fuzzy Time-Driven Activity-Based Costing Model in an Uncertain Manufacturing Environment. Proceedings of the 13th Asia Pacific Industrial Engineering & Management Systems Conference; 14-17 December 2012; Phuket, Thailand, p. 1949-1959\n'},{id:"B11",body:'Mehrdad M, Abbas NA. Supplier performance evaluation based on fuzzy logic. International Journal of Applied Science and Technology. 2011;1:257-265\n'},{id:"B12",body:'Zadeh LA. Fuzzy set as a basis for theory of possibility. Fuzzy Sets Systems. 1976;1:3-28\n'},{id:"B13",body:'Shruti SJ, Mudholkar RR. Performance evaluation by fuzzy inference technique. International Journal of Soft Computing and Engineering. 2013;3:2231-2307\n'},{id:"B14",body:'Fayek AR, Jose RRF. Application of fuzzy logic to quality assessment of infrastructure projects at conceptual cost estimating stage. Canadian Journal of Civil Engineering. 2010;37:1137-1147\n'},{id:"B15",body:'Chou SY, Chang YH. A decision support system for supplier selection based on a strategy-aligned fuzzy SMART approach. Expert Systems with Applications. 2008;344:2241-2253\n'},{id:"B16",body:'Dutta P, Boruah H, Ali T. Fuzzy arithmetic with and without using α-cut method: A comparative study. International Journal of Latest Trends in Computing. 2011;2:99-107\n'},{id:"B17",body:'Kaufmann A, Gupta MM. Introduction to Fuzzy Arithmetic: Theory and Applications. New York: Van Nostrand Reinhold; 1991\n'},{id:"B18",body:'Sears SK, Sears GA, Clough RH. Construction Project Management: A Practical Guide to Field Construction Management. 6th ed. New York: John Wiley & Sons Inc; 2015\n'},{id:"B19",body:'Sivanandam S N, Deepa S N, Sumathi S. Introduction to Fuzzy Logic using MATLAB. 1st ed. Berlin Heidelberg: Springer; 2010\n'},{id:"B20",body:'Lee C. Fuzzy logic in control systems: Fuzzy logic controller, parts I and II. IEEE Transaction on Systems, Man and Cybernetics. 1990;20:404-435\n'},{id:"B21",body:'Li J, Moselhi O, Alkass S. Forecasting project status by using fuzzy logic. Journal of Construction Engineering and Management. 2006;132:1193-1202\n'},{id:"B22",body:'Saltelli A. Sensitivity analysis for importance assessment. Risk Analysis. 2002;22:579-590\n'},{id:"B23",body:'Zheng DXM, Ng TST, Kumaraswamy MM. Applying a genetic algorithm-based multiobjective approach for time-cost optimization. Journal of Construction Engineering and Management. 2004;130:168-176\n'},{id:"B24",body:'Gen M, Cheng R. Genetic Algorithms and Engineering Optimization. New York: John Wiley & Sons Inc.; 2000\n'},{id:"B25",body:'Devore JL. Probability and statistics for engineering and sciences. Cengage Learning: Boston; 2016\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Mohammad Ammar Al-Zarrad",address:"mazarrad@gmail.com",affiliation:'
Department of Civil, Construction and Environmental Engineering, University of Alabama, USA
Department of Mechanical Engineering, University of Alabama, USA
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1. Introduction
The coronavirus disease 2019 (COVID-19) proclaiming millions of lives, is an infectious respiratory disease affecting the lungs. COVID-19 is devastating mainly in patients of old age and with co-morbidities like obesity, cardiovascular complications etc. COVID-19 is caused by recently recognized coronavirus termed as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1]. COVID-19 outbreak was instigated in December 2019 from the Wuhan city of China, which is rapidly spreading worldwide and badly impacted the entire world [2]. The COVID-19 pandemic is currently the prevalent world health crisis and a daily large number of new cases is reported around the world [3, 4]. By June 24, 2021, the mortality rates raised to 3.9 million among 180 million confirmed cases of COVID-19. Currently, the world healthcare system is in severe crisis due to the constant and varied challenges created by COVID-19. Initially, due to the lack of understanding regarding novel coronavirus and vaccines or any treatment for the COVID-19, governments officials globally implemented various non-pharmaceutical interventions (NPIs), such as the utilization of masks, social distancing, hand-washing, remote working, closures of schools and colleges, restrictions on public gatherings, fourteen days quarantines, for the slow transmission of the disease [5]. These measures are found to be effective in mitigating the number of cases [6, 7], however, they lead to a considerable impact on the social, economic [8] and psychological wellbeing of the society [9].
Government’s professionals, pharmaceutical companies and professionals in the health care system are taking great efforts to manage and combat the disease across the world. To alleviate the burden on society, a massive effort is being made by health care professionals worldwide to develop and get access to different vaccines [10, 11]. Vaccination has been started around the globe after a year of the first reported cases of COVID-19 [12]. Vaccines were developed and have been found successful in decreasing the number of patients affected with COVID-19 as well as the severity of the disease, however, it is not completely avoiding the risk of being affected with COVID-19. Additionally, new strains of coronavirus are also gradually identified. Recently it is found that novel coronavirus is having various mutations. This means that there are slight changes in the genetic composition of the virus. The Delta-plus variant is a mutated version of the Delta variant (the virus that wreaked havoc in the second wave). Delta plus is considered highly infectious. The virus can potentially dodge immune response, vaccines and antibody therapies. However, more research has to be done in this context. Few cases have been recorded in some states of India. The Government official has classified it as a Variant of Concern (VOC). There is no certainty regarding delta plus and the current numbers cannot determine any particular trend. Certain vaccines work against the Delta Plus variant, but they show 3 to 8 times less efficacy as compared to other variants. There are no conclusive reports about these variants but we should not keep our guards down [13, 14]. The United States Food and Drug Administration (U.S. FDA) approved the antiviral drug, remdesivir (Veklury), for treating COVID-19 affected patients requiring hospitalization. Remdesivir approved to be administered in the health care setting or hospital that is efficient enough of affording acute care comparable to inpatient hospital care. This approval of using remdesivir for treating COVID-19 does not include the entire population rather it is only approved for hospitalized patients who are adults and pediatric (≥12 years of age) with a bodyweight of at least 40 kilograms [15]. Moreover, health care systems are facing huge difficulties in combating the enormous demands of medicines and vaccines. Thus, providing additional therapies for preventing and curing the disease is an important step in combating this pandemic. Currently, the worldwide impetus is unabated, and a third wave is also predicted.
India and China are known for their rich history of traditional medicine [16]. Indian households are being considered as a hub of natural products, consisting of a plethora of pharmacologically active ingredients inspired by the traditional medication system (Ayurveda) [16]. Complementary and alternative medicines (CAMs) have emerged as a ray of hope in these times [17]. The following book chapter focuses on ‘the role of CAMs in the prevention, treatment and management of COVID-19’.
2. Pathogenesis of COVID-19
The recently identified SARS-CoV-2 is a new member added into the family of β-coronavirus with earlier known members like Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV), which results in severe pulmonary pneumonia and potentially deadly acute respiratory distress syndrome (ARDS). The large population of COVID-19 patients is asymptomatic. Six prominent symptoms include dry cough, malaise, fatigue, fever, dyspnea, secretion or sputum among various clinical manifestations noticed in patients infected with SARS-CoV-2. The gastrointestinal symptoms consist of vomiting, anorexia, and diarrhea in the patients affected with COVID-19. Pathogenesis of COVID-19 is classified into three discrete clinical phases based on the cells/tissue being infected. These three phases include asymptomatic state, upper and conducting airway response and hypoxia, ground-glass infiltrates and progression to ARDS. In Phase, I of asymptomatic state inhaled SARS-CoV-2, bind to the receptor present on the epithelial cells i.e., angiotensin-converting enzyme-2 (ACE-2) on the nasal cavity and begin reproducing [18]. There is local propagation of the COVID-19 virus and an inadequate innate immunity in the asymptomatic stage. In phase II, there is an occurrence of the upper airway and conducting airway infection. In this phase or stage, there is a robust immune response when the virus migrates and propagates down the conducting duct and along the respiratory tract. Epithelium of the upper and conducting airway infected virally results in the release of cytokines [19]. During this phase, clinical manifestations are observed. Predictions and monitoring of the subsequent course of the disease may be improved by determining the host immune responses. In most of the patients infected with SARS-CoV-2, the infection will be mild and mostly limited to the upper and conducting airways [20]. These patients do not require hospitalization and may be monitoring of patients at home with conventional symptomatic treatment will be adequate [19]. In the third stage or phase III, there will be ground-glass infiltrates, hypoxia and progression to ARDS. Typically, around 20% of the patients infected with SARS-CoV-2 advance to the severe stage and develop pulmonary infiltrates and ARDS. In this stage, the virus reaches and infects the gas exchange unit of the lungs i.e., alveolar type II cells mainly in the subpleural region of lungs [21]. Once the virus reaches the type II alveolar cells self-replicating pulmonary toxins are released and it results in apoptosis and cell death [22]. This in turn causes diffuse alveolar injury, with a few multinucleated large cells and a fibrin membrane rich in hyaline [23, 24]. Extensive scarring, fibrosis, and various kinds of ARDS may occur from aberrant wound healing. Improvement requires epithelial cells regeneration and robust innate and adaptive immune responses. Patients with older age or co-morbidities are at greater risk due to weakened capacity to repair the damaged epithelium and deteriorated immune response against the virus. In the elderly, the mucociliary clearance is also reduced and this allows propagation and rapid spread into the gas exchange unit of the lungs [25].
3. Interaction of virus with the immune system
Manifestations of COVID-19 is extremely heterogeneous, with a wide clinical spectrum varying from asymptomatic infection through mild upper respiratory and conducting airways infection, to severe pneumonia leading to fatality [24, 26]. Recognizing the machinery for the virus invasion into the host body and its interaction with the host immunity will facilitate the prevention and treatment of the COVID-19. Infection with SARS-CoV-2 has two distinct clinical phases: primary and secondary inflammatory phases. The primary phase involves the invasion of viral in the host and its replication and the inflammatory phase involves exaggerated host immune response towards the virus. Augmented host immune response eventually results in fast and uncontrolled deterioration and worsening of respiration and ultimately emerges the need for hospitalization [27, 28]. SARS-CoV-2 is a lower respiratory tract virus and enters the host through a specific receptor i.e., ACE-2, resulting in pneumonia in severe cases. It chiefly consists of four structural proteins including nucleocapsid polymer, small envelope glycoprotein, membrane glycoprotein and spike polymer, as well as numerous accessory proteins. Spike protein projected from the surface of the virus is responsible for the attachment with ACE-2 assists the invasion of viruses into the host cells [29]. ACE2 is mainly expressed on the lung, kidney, intestine and epithelial cells of blood vessels. It is worth mentioning that spike protein is considered as the potential target in the vaccination against COVID-19. The innate and the adaptive immunity pathways are two pieces of machinery of the host immune system against foreign pathogens [30]. To effectively deal with and rapidly control the spread of viral infection, the innate immunity activates and concomitantly stimulates the adaptive immunological reactions. The innate system is the first-line defense against the pathogen which comprises of external defense mechanism (e.g. epithelial cells or the mucous membranes in the nasopharynx, lung, gut, periodontium and skin), nonspecific phagocytic leukocytes (macrophages and neutrophils) as well as serum proteins [30, 31]. Adaptive immune build up in a long time includes a specific response i.e., production of protein molecules known as antibodies that react with the antigens of infectious agents to eradicate the virus and to forbid progression of the disease to severe stages [32]. The host immune system via frequently interacting innate and adaptive mechanisms defends against external pathogens. Better management and prevention of disease requires timely identification of disease as well as its influence on the immune system. The disease complexity is further noticeable when it is reported variability in susceptibility to severe infection and mortality in certain sections of the population. However, earlier literature reported that the viral infection alerts immune system operations and influences immunoglobulin levels, antibody generation, phagocytosis, lymphocyte transformation etc. [33]. Similarly, SARS-CoV-2 also impacted the innate and adaptive immunity of the host.
3.1 Impact of SARS-CoV-2 on innate immunity
It has been reported in numerous studies that interleukin-6 (IL-6) is upregulated in patients affected with SARS-CoV-2 [24]. IL-6 is chiefly produced by monocytes or macrophages. IL-6 employs immune mediators and results in the cytokine storm, which cause tissue damage and uncontrolled systemic inflammation [34]. Moreover, inflammatory cytokines including chemokines, interferon-gamma (IFN-γ), IFN-γ induced protein 10 (IP-10), tumor necrosis factor (TNF-α), interleukin-10 (IL-10) and monocyte chemoattractant protein-1 (MCP-1) are observed to be augmented in patients affected with COVID-19 [24]. Lactate dehydrogenase is a marker of pyroptosis and is also found to be augmented in patients affected with COVID-19, and is considered to be correlated with the severity of the disease as well as the rate of mortality. Innate immune response was observed to be activated in COVID-19 patients, but unsuccessful to commence robust interferon (IFN) responses. The deficient of IFN responses could probably result in insufficiency in confining the viral load and viral infection at the initial stage of disease progression [34]. There is limited literature regarding the mechanisms underlying the SARS-CoV-2 induced mitigation of IFN responses. Macrophages play important role in immune responses against viral infection. ACE2 receptors are found to be expressed on the surface of macrophages [35]. This leads to increased susceptibility of macrophages to SARS-CoV-2 infection. This signifies that macrophages may serve as a possible reservoir of the COVID-19 virus [36].
3.2 Impact of SARS-CoV-2 on adaptive immunity
Stimulation of the innate immunity subsequently activates the adaptive immunity. Thymus cells (T cells) and bone marrow- or bursa-derived cells (B cells) are key players in adaptive immunity. Effector T cells mediate cellular response against the virus by either directly killing the cells infected with the virus or by discharging regulatory and pro-inflammatory mediators. B cells mediate the humoral responses by producing neutralizing antibodies (NAbs). The released NAbs in turn obstruct the interaction between the spike protein of SARS-CoV-2 and ACE2 expressed on the surface of the cell membrane and thus block the invasion of the virus into the host cell. On the contrary, the virus-specific antibodies interact with complementary receptors expressed on the exterior of the host cell and thus assist the entrance of the virus into the host cells. This is termed antibody-dependent enhancement (ADE) [37]. The NAbs titer is reported to be associated with disease severity [38]. However, there is a range of levels of NAbs among various patients, demonstrating the individual variation in immune responses towards viral infection. Cellular immunity is another intend of the adaptive immune system is against viral infections including the cluster of differentiation 4 (CD4) and the cluster of differentiation 8 (CD8) positive T cells. CD4 and CD8 are glycoproteins that serve as a co-receptor for the T-cell receptor (TCR). CD4+ T releases cytokines, which help cytotoxic T cells and B cells. On the other hand, the CD8+ T cells after being activated eradicate the infected cells. Depletion as well as the exhaustion of peripheral CD4+ and CD8+ T cells are reported in COVID-19 patients [39]. This depletion and exhaustion of T cells may be due to the augmented level of IL-6 in COVID-19 patients [40].
4. Management of COVID-19 with the use of complementary and alternative medicines (CAMs) endorsement
Complementary and Alternative Medicine (CAM) is an umbrella term for a broad range of substances and treatments which consist of a cluster of a variety of medic and health care supplies, orders, and actions not characterized under the conceptual framework of medicines. The definition of CAM throughout the literature is not consistent. However, the National Centre for Complementary and Alternative Medicines (NCCAM) of the National Institute of Health (NIH) defines CAM as “a group of diverse medical and health care systems, products, and practices that are not currently fall under the category of conventional medicine”(NCCAM, 2002) [41]. CAM is utilized either as an alternative or adjuvant therapy of conventional treatments.
The inclination towards using CAM in and around the world, both in terms of prophylactic as well as therapeutic strategies against problems related to health, has been augmented recently [42]. CAM is an extremely broad area that consists of all health beliefs, values, practices, as well as methods exterior to the streamlined present health care system [43]. These are further classified into five important categories by National Center for Complementary and Integrative Health (NCCIH). The first category includes alternative medical systems/whole medical systems (homeopathy, traditional Chinese medicine, ayurvedic medicine), the second category includes biologically-based therapies (probiotics, minerals, vitamins, phytochemicals, whole diets and functional foods, animal-derived extracts, amino acids, proteins and fatty acids), the third category includes manipulative and body-based methods (chiropractic, osteopathic manipulation, reflexology and massage), the fourth category includes mind–body therapies; healing techniques based on mind–body therapies (art, praying, meditation, dance, music) and finally the fifth category includes energy-oriented treatments or energy therapies or (therapeutic touch, Qi gong, healing touch) [44].
Greater than 80% of the population around the globe utilizes CAMs. The foundation of the National CAM-Center leads to a significantly augmented number of CAM-related basic research and clinical trials based on CAM therapies. Approximately 30% of the adult population of the U.S. [45] and 10–40% of Europe [46] use CAM. It is predicted that the market per annum for herbal remedies, consisting of raw materials and herbal products will expand by 15% and 5% respectively. The global market for the herbal drug is projected to be $62 billion, which is likely to rise to $5 trillion by 2050 [47]. Herbal remedies for boosting the immune system are consumed in several countries across the globe to uplift health, endorse the body’s defense against various infectious as well as prohibit and cure several infectious diseases [48]. In this section, several examples of CAMs projected for preventing and curing diseases are elaborated.
4.1 Methodology
Databases such as PubMed, Scopus, Embase, Google Scholar, Web of Science, and Cochrane were searched without time limitation to find relevant articles exploring the impact of CAM in COVID-19. The terms and words searched included “COVID-19”, “SARS-CoV-2”, “CAM”, “micronutrients”, “phytochemical”, “Ayurveda”, “extract”, “essential oil”, “herbal medicines”, “In vitro”, “In vivo”, “clinical trial” etc.
4.2 Ayurveda and yoga as the prophylactic and adjuvant therapy of COVID-19
To develop a preventive and curative intervention for COVID-19, the Ministry of Ayurveda, Yoga, and Naturopathy, Unani, Siddha, and Homeopathy (AYUSH), Government of India (GoI), formulated an interdisciplinary AYUSH research and development task force and guidelines for initiating, monitoring, coordinating efforts and conducting clinical studies of diverse traditional medicines against COVID-19 [49].
Visualizing the severity and infectivity of COVID-19, the Ministry of AYUSH, GoI recommended certain immunity boosters like lukewarm water, Kadha, (an ayurvedic preparations containing curcumin, ginger, cumin seeds, fennel seeds, cloves and honey) and homeopathic medicine ‘Arsenic Album 30C’ [50]. Ayurveda defined NPIs in addition to pharmacological as preventive measures in combating COVID-19. NPIs recommended by the Ministry of AYUSH include sadvritta (Sad means ‘good’ and vritta means ‘regimen’), healthy lifestyles, enough sleep, adequate physical activity, avoidance and isolation from infected persons [51]. Certain medicines suggested by Ayurveda include turmeric (Curcuma longa), garlic (Allium sativum), Ajwain or Carom (Trachyspermum Ammi) as a disinfectant for the prevention of COVID-19 [52].
The nose, mouth and eyes, are the main entry portals for the droplets consisting of the virus, SARS-CoV-2. Before reaching and final attack on the lungs, the virus stays in the nose and throat region for hours. The virus is coated with fatty acid which helps in adhering the virus to the moist mucosal layers and thus facilitates its entrance into the host cells by attaching to definite receptors [53]. Ayurveda mentioned various interventions that interfere in these entry portals [54] for virus invasion to the lungs by improving the innate immunologic response of the mucus membranes. These measures work as “physiological masks” or “local prophylaxis” for obstructing the viral invasion. The common recommendation for respiratory diseases written in Ayurvedic texts [55] includes consumption of hot food, hot water, steam inhalation, gargling, local applications and herbal decoctions with medicated water. These may be useful for relief in mild cases [53]. Ayurveda recommended drinking hot and warm water for improving the digestion of Ama. Ama is a pro-inflammatory mediator of weaken metabolic disorders and is associated with augmented susceptibility to infections [56].
Warm oils and liquids are employed as mouth rinses (Kavala) or gargles (gandusha) to thoroughly clean the mouth and throat [57]. The oily decoctions coat the mucosa as biofilm as well as rinse the oral cavity, tonsillar area, and pharynx. These decoctions also have supplementary benefits of antioxidant, immunomodulatory, and antimicrobial [58]. It is well known that host mucosal immunity plays a vital role in controlling infectious agents [59]. Literature regarding Yoga advocates Jala neti which implies rinsing of the nasal passage with saline water [60]. Randomized controlled trials (RCTs) reported the effectiveness of saline water in upper respiratory infections [61].
4.3 Herb/phytochemicals
Herbal products are consumed in various countries across the globe. Literature suggests immune-boosting properties of these herbal materials which endorse the normal resistance ability of the body against infectious pathogens and to raise health, and as well as to cure and to prohibit diverse infectious diseases [48]. Curcumin, a polyphenolic compound isolated from turmeric, which is a commonly used food colorant and spice [62], can augment the antibody reaction even if it is consumed at reduced doses [63]. Additionally, literature shows that curcumin has a promising affinity for protein binding towards SARS-CoV-2 and thus directly inhibit the invasion of SARS-CoV-2 into target cells [64]. The ability of curcumin in improving various disease conditions is attributed partially to its capability to modulate the immune responses [63]. Numerous reports show that curcumin can alter the proliferation as well as the activation of T cells [65, 66]. Additionally, curcumin has the potential of regulating the response and growth of various immune cells like natural killer (NK) cells, B cells, T cells, dendritic cells (DCs), macrophages and neutrophils [63]. Glycyrrhizin, an active phytochemical moiety found in liquorice was observed to be efficient in comparison to commonly used anti-virals in mitigating the replication of SARS-CoV as well as inhibiting its adsorption and penetration [67]. A recent in-vitro study also showed that glycyrrhizin is a potential inhibitor of SARS-CoV-2 replication by hindering the viral main protease (Mpro) [68]. Molecular docking study showed two phytoconstituents Somniferine and Withanoside V from Ashwagandha (Withania somnifera) [69, 70], Tinocordiside [70] and berberine [71] from Giloy (Tinospora cordifolia) and three active ingredients i.e., Vicenin, Ursolic acid and Isorientin 4’-O-glucoside 2″-O-p-hydroxybenzoagte isolated from Tulsi (Ocimum sanctum) [70] may have an antiviral effect against novel coronavirus via potentially inhibiting Mpro of SARS-CoV-2.
4.4 Nutritional supplements
Recently conducted studies show that suboptimal intake of micronutrients and inadequate nutritional status can lead to poor immunity and consequently affect the severity of infections. Nutritional supplements emerge to reinforce the immune system. Micronutrients consisting of a variety of vitamins (A, D, C, E, B6, B12, folate) and minerals (iron, zinc, selenium and copper) are engaged in various stages of the immune responses against foreign pathogens. A study conducted in the United Arab Emirates (UAE) confirmed the association of low levels of vitamin D3 (25(OH)D3) (<12 ng/mL) with severity and death due to COVID-19 [72]. Another study shows that hospitalized COVID-19 patients receiving vitamin D3 (calcifediol) in contrast with those not consuming vitamin D3, was significantly linked with a lesser rate of mortality during the initial thirty days of hospitalization [73]. Supplementation with vitamin D at high-dose may be well-tolerated, effective, and readily accessible for the management of COVID-19 [74]. One report showed that intake of a high dose of vitamin D has significantly reduced the inflammatory markers (neutrophil/lymphocyte ratio, ferritin, C-reactive protein (CRP), lactate dehydrogenase (LDH), IL-6 associated with COVID-19 without any side effects [75]. A study confirmed that deficiency of vitamin D is correlated with severe lung injury, disease prolongation and risk of mortality, in COVID-19 patients [76]. Another study shows that combination therapy of vitamin D with vitamin B12 and magnesium in geriatric patients with COVID-19 was correlated with a considerable decline in the proportion of patients with clinical deterioration and requiring intensive care support and oxygen support [77]. Vitamin D was found to modulate innate and adaptive immune systems [78, 79]. It augments the innate immune responses while attenuates the adaptive immune responses [78]. Vitamin D metabolites directly target the adaptive immune cells [80] and it is an important part of intricate features that control the immune response against infection [81]. These findings necessitate examining the level of vitamin D in pediatric as well as geriatric persons to maintain it at optimum levels for the prevention of SARS-CoV-2 infection.
In addition to the consumption of higher doses of vitamin D3, previously it was also stated that coronavirus pandemic can be considerably controlled by the utilization of high amounts of vitamin C. Significantly low levels of vitamin C in patients affected with COVID-19 were found and daily supplementation of 100 mg/kg is highly recommended [82]. A high dose of intravenous vitamin C might repress cytokine storms associated with COVID-19, and facilitate improving pulmonary function and lessen the risk of ARDS associated with COVID-19 [83]. As SARS-CoV-2 was found to affect the host immune system, it seems crucial to boost the natural immunity and antioxidant capacity to lessen the effect of any virus infection. Vitamin C is known for its ability to activate the immune system. Therefore it seems promising to administered vitamin C concomitantly with other medications to cure the infection in acute conditions. The ingestion of vitamin C orally up to the daily threshold of bowel tolerance seems to be effective for the majority of persons. However, intravenous administration of vitamin C is suggested for serious cases. On the other side, there are certain reports, claiming that the overstimulation of immune cells in COVID-19 leads to cytokine storm which ultimately causes lung injury following pneumonia. Certain clinical investigations also suggested that intravenous administration of vitamin C in high-dose can be a safe and effective choice for the management of COVID-19 infection in its early stages. Even though previous literature recognized and approved the antiviral activity of vitamin C, but its impact has not been studied widely and, limited information is available on its effect on coronavirus. Moreover, some studies show that adjunctive intravenous administration of vitamin C for the treatment of infection in critically ill COVID-19 patients was unable to reduce the rate of mortality, ventilator settings, the requirement of vasopressor, etc. [84]. Therefore although vitamin C is vital for lessening the inflammatory response and assists in boosting the immune system of the host, there is a lack of substance to support that utilization of vitamin C at a high dose can be successful in the prevention or management of COVID-19. Moreover, as Therapeutic Goods Administration (TGA) [85] declared that more studies are required for any recommendation for utilizing intravenous vitamin C in the management of COVID-19. In addition to vitamin C and vitamin D3, it was reported that vitamin K antagonist regular use was correlated with augmented mortality in hospitalized elderly patients affected with COVID-19 [86].
Studies show that treatment with zinc as adjuvant therapy was appeared to be feasible and safe for the management of COVID-19. However, the infusion of zinc causes limited infusion site irritation on the periphery [87]. Zinc supplement was found to be efficiently clear the SARS-CoV-2 from the nasopharynx in a lesser time than other symptomatic therapy [88]. Zinc cation (Zn2+) coupled with zinc ionophores pyrithione and found to inhibit RNA polymerase of coronavirus and thus block the replication of the virus [89]. Additionally, zinc also mitigates the invasion of the virus by escalating the cell membrane stability as well as stimulate interferon-alpha (IFN-α) and IFN-γ formation and attenuate tumor necrosis factor (TNF) and mononuclear cells [90]. Apart from zinc, iron also plays a vital component of enzymes involved in the stimulation of immune cells, lower levels of iron was found to influence severe symptoms associated with COVID-19. Selenium contributes to adaptive immunity by boosting the production and development of antibodies. Lack of selenium can lessen antibody production, compromised cellular immunity, attenuated the cytotoxicity of NK cells, and decreased response to vaccination. Oxidative stresses alter the viral genome from a mildly pathogenic form to a highly virulent form of the virus in the host. Selenium is a known anti-oxidant. Hence selenium with vitamin E and a cluster of certain enzymes scavenges the free radicals and lessens the oxidative stress and thus as a result, the adjuvant therapy of selenium may be considered for the treatment of COVID-19 infection [91].
5. Limitations
Literature shows that people who either have positive attitudes towards CAM or those who consume CAM are unwilling to comply with conventional therapy, most prominently the vaccinations and to follow the official COVID-19 guidelines [92, 93, 94, 95, 96, 97, 98]. It has been reported that the optimistic attitudes towards CAM are correlated with negative attitudes towards vaccination is not evidence-based but because of an underlying outlook on health or perhaps a reluctance to stick to conventional therapy [93, 94, 95]. Those who utilize CAM perceived CAM as a natural, safe approach to improve the host immunity, while vaccines are considered as a risky option [94]. Additionally, both anti-vaccination attitudes and higher utilization of CAM are correlated to the poor trust of individuals towards the healthcare system or medical authorities [92].
6. Summary/conclusion
It is apparent from the above findings, that the understanding of the COVID-19 pathogenesis and its impact on immunity will progress the management of this lethal infectious disease. As per the earlier studies, the host immune response has an elementary function of defense against the majority of infectious diseases including COVID-19. In this chapter specifically attempt has been made on the utilization of various NPIs, herbs, phytochemicals and micronutrients which has the potential to assist in the prevention and/or management of SARS-CoV-2 infection. Thus utilization of CAMs may be an efficient approach in improving immunological reactions against infections. Moreover, the consumption of vitamins and minerals was observed to be favorable in improving the immune system and its function. Although, certain clinical studies reported the success of CAMs in the treatment, prevention and management of COVID-19, additional studies through clinical analysis as well as consumers’ experience on CAMs are essential to draw strong conclusions in the success of utilization of CAMs for treatment, prevention and management of COVID-19.
Conflict of interest
“The authors declare no conflict of interest.”
ACE-2
Angiotensin-converting enzyme-2
ADE
Antibody-dependent enhancement
ARDS
Acute respiratory distress syndrome
AYUSH
Ayurveda, Yoga, and Naturopathy, Unani, Siddha, and Homeopathy
B cells
Bone marrow- or bursa-derived cells
CAM
Complementary and Alternative Medicine
CD4
Cluster of differentiation 4
CD8
Cluster of differentiation 8
COVID-19
Coronavirus Disease 2019
CRP
C - reactive protein
IFN
Interferon
IFN-α
Interferon alpha
IFN-γ
Interferon-gamma
IL-6
Interleukin 6
IL-10
Interleukin-10
IP-10
IFN-γ induced protein 10
LDH
Lactate dehydrogenase
MCP-1
Monocyte chemoattractant protein-1
MERS-CoV
Middle East Respiratory Syndrome Coronaviruses
Nabs
Neutralizing antibodies
NCCAM
National Centre for Complementary and Alternative medicines
NCCIH
National Center for Complementary and Integrative Health
NIH
National Institute of Health
NPIs
Non-pharmaceutical interventions
SARS-CoV
Severe Acute Respiratory Syndrome Coronavirus
SARS-CoV-2
Severe Acute Respiratory Syndrome Coronavirus 2
T cells
Thymus cells
TGA
Therapeutic Goods Administration
TNF
Tumor necrosis factor
TNF-α
Tumor necrosis factor alpha
U.S. FDA
United States Food and Drug Administration
VOC
Variant of Concern
\n',keywords:"COVID-19, SARS-CoV-2, Complementary and Alternative Medicines, Innate immunity, Adaptive immunity, Micronutirents",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/78913.pdf",chapterXML:"https://mts.intechopen.com/source/xml/78913.xml",downloadPdfUrl:"/chapter/pdf-download/78913",previewPdfUrl:"/chapter/pdf-preview/78913",totalDownloads:71,totalViews:0,totalCrossrefCites:0,dateSubmitted:"May 22nd 2021",dateReviewed:"September 12th 2021",datePrePublished:"October 21st 2021",datePublished:null,dateFinished:"October 9th 2021",readingETA:"0",abstract:"Interception of coronavirus disease 2019 (COVID-19) into our life and its rapid global expansion, humanity has succumbed to a vulnerable position. COVID-19 is proclaiming millions of lives, underscores the urgent need for more effective therapeutic interventions. This disease created catastrophe and developments of new drugs and vaccines take a long duration. Hence, scientists and medical society turned their heads towards different approaches of treatment, referred to as complementary and alternative medicine (CAM) for eradicating the deadly virus. Ayurveda, herbal medicines, nutritional supplements, naturopathy, and yoga are some of the CAMs which have emerged as a ray of hope in these times. The understanding of the COVID-19 pathogenesis and its impact on immunity will progress the effective management of this lethal infectious disease. The host immune response has an elementary function of defense against the majority of infectious diseases including COVID-19. This chapter focuses on the utilization of various CAMs (Ayurveda, yoga, herbs, phytochemicals and nutritional supplements) in COVID-19 treatment. An additional attempt has been made in this chapter on the potential of CAMs to assist in improving immunological reactions against infections and thus may be an efficient approach in the prevention and/or management of severe acute respiratory syndrome coronavirus 2 infections.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/78913",risUrl:"/chapter/ris/78913",signatures:"Bhagawati Saxena",book:{id:"11042",type:"book",title:"Complementary Therapies",subtitle:null,fullTitle:"Complementary Therapies",slug:null,publishedDate:null,bookSignature:"Prof. Mario Bernardo-Filho, Prof. Redha Taiar, Danúbia Da Cunha De Sá-Caputo and Dr. Adérito Seixas",coverURL:"https://cdn.intechopen.com/books/images_new/11042.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-83969-012-9",printIsbn:"978-1-83969-011-2",pdfIsbn:"978-1-83969-013-6",isAvailableForWebshopOrdering:!0,editors:[{id:"157376",title:"Prof.",name:"Mario",middleName:null,surname:"Bernardo-Filho",slug:"mario-bernardo-filho",fullName:"Mario Bernardo-Filho"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Pathogenesis of COVID-19",level:"1"},{id:"sec_3",title:"3. Interaction of virus with the immune system",level:"1"},{id:"sec_3_2",title:"3.1 Impact of SARS-CoV-2 on innate immunity",level:"2"},{id:"sec_4_2",title:"3.2 Impact of SARS-CoV-2 on adaptive immunity",level:"2"},{id:"sec_6",title:"4. Management of COVID-19 with the use of complementary and alternative medicines (CAMs) endorsement",level:"1"},{id:"sec_6_2",title:"4.1 Methodology",level:"2"},{id:"sec_7_2",title:"4.2 Ayurveda and yoga as the prophylactic and adjuvant therapy of COVID-19",level:"2"},{id:"sec_8_2",title:"4.3 Herb/phytochemicals",level:"2"},{id:"sec_9_2",title:"4.4 Nutritional supplements",level:"2"},{id:"sec_11",title:"5. Limitations",level:"1"},{id:"sec_12",title:"6. Summary/conclusion",level:"1"},{id:"sec_16",title:"Conflict of interest",level:"1"},{id:"sec_15",title:"",level:"1"}],chapterReferences:[{id:"B1",body:'Singhal T. 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Nutrition. 2020;79-80:111017. doi: 10.1016/j.nut.2020.111017'},{id:"B78",body:'Bikle DD. Vitamin D and the immune system: role in protection against bacterial infection. Curr Opin Nephrol Hypertens. 2008;17(4):348-352. doi: 10.1097/MNH.0b013e3282ff64a3'},{id:"B79",body:'Kempinska-Podhorodecka A, Milkiewicz M, Wasik U, Ligocka J, Zawadzki M, Krawczyk M, Milkiewicz P. Decreased Expression of Vitamin D Receptor Affects an Immune Response in Primary Biliary Cholangitis via the VDR-miRNA155-SOCS1 Pathway. Int J Mol Sci. 2017;18(2):289. doi: 10.3390/ijms18020289'},{id:"B80",body:'Peelen E, Knippenberg S, Muris AH, Thewissen M, Smolders J, Tervaert JW, Hupperts R, Damoiseaux J. Effects of vitamin D on the peripheral adaptive immune system: a review. Autoimmun Rev. 2011;10(12):733-743. doi: 10.1016/j.autrev.2011.05.002'},{id:"B81",body:'Gruber-Bzura BM. Vitamin D and Influenza-Prevention or Therapy? Int J Mol Sci. 2018;19(8):2419. doi: 10.3390/ijms19082419'},{id:"B82",body:'Xing Y, Zhao B, Yin L, Guo M, Shi H, Zhu Z, Zhang L, He J, Ling Y, Gao M, Lu H, Mao E, Zhang L. Vitamin C supplementation is necessary for patients with coronavirus disease: An ultra-high-performance liquid chromatography-tandem mass spectrometry finding. J Pharm Biomed Anal. 2021;196:113927. doi: 10.1016/j.jpba.2021.113927'},{id:"B83",body:'Liu F, Zhu Y, Zhang J, Li Y, Peng Z. Intravenous high-dose vitamin C for the treatment of severe COVID-19: study protocol for a multicentre randomised controlled trial. BMJ Open. 2020 Jul 8;10(7):e039519. doi: 10.1136/bmjopen-2020-039519'},{id:"B84",body:'Li M, Ching TH, Hipple C, Lopez R, Sahibzada A, Rahman H. Use of Intravenous Vitamin C in Critically Ill Patients With COVID-19 Infection. J Pharm Pract. 2021:8971900211015052. doi: 10.1177/08971900211015052'},{id:"B85",body:'Administration, T.G. 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Global temperatures are predicted to rise by 2–4°C due to human activities and increased market globalization, coupled with rising temperatures, leads to a situation favorable to pest movement and establishment. Maize is an important crop after wheat and rice. Changes in rainfall distribution and temperature may result in temporary excessive soil moisture or water logging or drought in some maize producing areas leading to alterations in biotic stress factors. In Indian subcontinent warming trend in climate along the west coast, central, interior peninsula and northeast regions creates favorable conditions for diseases in maize like sorghum downy mildew (SDM) and Turcicum leaf blight (TLB). The decreasing trend of monsoon, seasonal rainfall in North India, Central India, parts of Gujarat and Kerala is suitable for post flowering stalk-rot (PFSR) which is gaining importance in maize. The outcome for any host-pathogen interaction under changing climate is not readily predictable. 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Open Access publishing helps remove barriers and allows everyone to access valuable information, but article and book processing charges also exclude talented authors and editors who can’t afford to pay. The goal of our Women in Science program is to charge zero APCs, so none of our authors or editors have to pay for publication.
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Some systems are highly affected by a small fraction of influential nodes. Number of fast and efficient spreaders in a network is much less compared to the number of ordinary members. Information about the influential spreaders is significant in the planning for the control of propagation of critical pieces of information in a social or information network. Identifying important members who act as the fastest and efficient spreaders is the focal theme of a large number of research papers. Researchers have identified approximately 10 different methods for this purpose. Degree centrality, closeness centrality, betweenness centrality, k‐core decomposition, mixed degree decomposition, improved k‐shell decomposition, etc., are some of these methods. In this expository article, we review all previous works done in the field of identifying potential spreaders in a network.",book:{id:"5842",slug:"graph-theory-advanced-algorithms-and-applications",title:"Graph Theory",fullTitle:"Graph Theory - Advanced Algorithms and Applications"},signatures:"Reji Kumar Karunakaran, Shibu Manuel and Edamana Narayanan\nSatheesh",authors:[{id:"200190",title:"Dr.",name:"Reji Kumar",middleName:null,surname:"Karunakaran",slug:"reji-kumar-karunakaran",fullName:"Reji Kumar Karunakaran"},{id:"200193",title:"Mr.",name:"Manuel",middleName:null,surname:"Shibu",slug:"manuel-shibu",fullName:"Manuel Shibu"},{id:"200194",title:"Dr.",name:"E N",middleName:null,surname:"Satheesh",slug:"e-n-satheesh",fullName:"E N Satheesh"}]},{id:"55541",doi:"10.5772/intechopen.68703",title:"Modeling Rooted in‐Trees by Finite p‐Groups",slug:"modeling-rooted-in-trees-by-finite-p-groups",totalDownloads:1131,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Graph theoretic foundations for a kind of infinite rooted in-trees T(R)=(V,E) with root R, weighted vertices v ∈ V, and weighted directed edges e∈E⊂V×V are described. Vertex degrees deg(v) are always finite but the trees contain infinite paths (vi)i≥0. A concrete group theoretic model of the rooted in-trees T(R) is introduced by representing vertices by isomorphism classes of finite p-groups G, for a fixed prime p, and directed edges by epimorphisms π: G → πG of finite p-groups with characteristic kernels ker(π). The weight of a vertex G is realized by its nuclear rank n(G) and the weight of a directed edge π is realized by its step size s(π)=logp(#ker(π)). These invariants are essential for understanding the phenomenon of multifurcation. Pattern recognition methods are used for finding finite subgraphs which repeat indefinitely. Several periodicities admit the reduction of the complete infinite graph to finite patterns. The proof is based on infinite limit groups and successive group extensions. It is underpinned by several explicit algorithms. As a final application, it is shown that fork topologies, arising from repeated multifurcations, provide a convenient description of complex navigation paths through the trees, which are of the greatest importance for recent progress in determining p-class field towers of algebraic number fields.",book:{id:"5842",slug:"graph-theory-advanced-algorithms-and-applications",title:"Graph Theory",fullTitle:"Graph Theory - Advanced Algorithms and Applications"},signatures:"Daniel C. Mayer",authors:[{id:"198580",title:"Dr.",name:"Daniel C.",middleName:null,surname:"Mayer",slug:"daniel-c.-mayer",fullName:"Daniel C. Mayer"}]},{id:"57771",doi:"10.5772/intechopen.71774",title:"Governance Modeling: Dimensionality and Conjugacy",slug:"governance-modeling-dimensionality-and-conjugacy",totalDownloads:1310,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"The Q-analysis governance approach and the use of simplicial complexes—type of hypergraph—allow to introduce the formal concepts of dimension and conjugacy between the network of entities involved in governance (typically organizations) and the networks of those attributes taken into account (e.g. their competences), which offer a specific angle of analysis. The different sources of existing data (e.g. textual corpora) to feed the analysis of governance—environmental in particular—are mentioned, their reliability is briefly discussed and the required pre-processing steps are identified in the perspective of evidence-based analyses. Various indices are constructed and evaluated to characterize the context of governance as a whole, at mesoscale, or locally, i.e. at the level of each of the entities and each of the attributes considered. The analysis of ideal-type stylizing boundary cases provides useful references to the analysis of concrete systems of governance and to the interpretation of their empirically observed properties. The use of this governance modeling approach is illustrated by the analysis of a health-environment governance system in Southeast Asia, in the context of a One Health approach.",book:{id:"5842",slug:"graph-theory-advanced-algorithms-and-applications",title:"Graph Theory",fullTitle:"Graph Theory - Advanced Algorithms and Applications"},signatures:"Pierre Mazzega, Claire Lajaunie and Etienne Fieux",authors:[{id:"220099",title:"Dr.",name:"Pierre",middleName:null,surname:"Mazzega",slug:"pierre-mazzega",fullName:"Pierre Mazzega"},{id:"220102",title:"Dr.",name:"Claire",middleName:null,surname:"Lajaunie",slug:"claire-lajaunie",fullName:"Claire Lajaunie"},{id:"220103",title:"Prof.",name:"Etienne",middleName:null,surname:"Fieux",slug:"etienne-fieux",fullName:"Etienne Fieux"}]},{id:"57940",doi:"10.5772/intechopen.72145",title:"Graph-Based Decision Making in Industry",slug:"graph-based-decision-making-in-industry",totalDownloads:1660,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Decision-making in industry can be focused on different types of problems. Classification and prediction of decision problems can be solved with the use of a decision tree, which is a graph-based method of machine learning. In the presented approach, attribute-value system and quality function deployment (QFD) were used for decision problem analysis and training dataset preparation. A decision tree was applied for generating decision rules.",book:{id:"5842",slug:"graph-theory-advanced-algorithms-and-applications",title:"Graph Theory",fullTitle:"Graph Theory - Advanced Algorithms and Applications"},signatures:"Izabela Kutschenreiter-Praszkiewicz",authors:[{id:"218951",title:"Associate Prof.",name:"Izabela",middleName:null,surname:"Kutschenreiter-Praszkiewicz",slug:"izabela-kutschenreiter-praszkiewicz",fullName:"Izabela Kutschenreiter-Praszkiewicz"}]},{id:"70434",doi:"10.5772/intechopen.90521",title:"Solution Attractor of Local Search System: A Method to Reduce Computational Complexity of the Traveling Salesman Problem",slug:"solution-attractor-of-local-search-system-a-method-to-reduce-computational-complexity-of-the-traveli",totalDownloads:535,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"The traveling salesman problem (TSP) is presumably difficult to solve exactly using local search algorithms. It can be exactly solved by only one algorithm—the enumerative search algorithm. However, the scanning of all possible solutions requires exponential computing time. Do we need exploring all the possibilities to find the optimal solution? How can we narrow down the search space effectively and efficiently for an exhausted search? This chapter attempts to answer these questions. A local search algorithm is a discrete dynamical system, in which a search trajectory searches a part of the solution space and stops at a locally optimal point. A solution attractor of a local search system for the TSP is defined as a subset of the solution space that contains all locally optimal tours. The solution attractor concept gives us great insight into the computational complexity of the TSP. If we know where the solution attractor is located in the solution space, we simply completely search the solution attractor, rather than the entire solution space, to find the globally optimal tour. This chapter describes the solution attractor of local search system for the TSP and then presents a novel search system—the attractor-based search system—that can solve the TSP much efficiently with global optimality guarantee.",book:{id:"8241",slug:"novel-trends-in-the-traveling-salesman-problem",title:"Novel Trends in the Traveling Salesman Problem",fullTitle:"Novel Trends in the Traveling Salesman Problem"},signatures:"Weiqi Li",authors:[{id:"312758",title:"Dr.",name:"Weiqi",middleName:null,surname:"Li",slug:"weiqi-li",fullName:"Weiqi Li"}]}],mostDownloadedChaptersLast30Days:[{id:"55642",title:"Monophonic Distance in Graphs",slug:"monophonic-distance-in-graphs",totalDownloads:1506,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"For any two vertices u and v in a connected graph G, a u − v path is a monophonic path if it contains no chords, and the monophonic distance dm(u, v) is the length of a longest u − v monophonic path in G. For any vertex v in G, the monophonic eccentricity of v is em(v) = max {dm(u, v) : u ∈ V}. The subgraph induced by the vertices of G having minimum monophonic eccentricity is the monophonic center of G, and it is proved that every graph is the monophonic center of some graph. Also it is proved that the monophonic center of every connected graph G lies in some block of G. With regard to convexity, this monophonic distance is the basis of some detour monophonic parameters such as detour monophonic number, upper detour monophonic number, forcing detour monophonic number, etc. The concept of detour monophonic sets and detour monophonic numbers by fixing a vertex of a graph would be introduced and discussed. Various interesting results based on these parameters are also discussed in this chapter.",book:{id:"5842",slug:"graph-theory-advanced-algorithms-and-applications",title:"Graph Theory",fullTitle:"Graph Theory - Advanced Algorithms and Applications"},signatures:"P. Titus and A.P. Santhakumaran",authors:[{id:"198301",title:"Dr.",name:"P.",middleName:null,surname:"Titus",slug:"p.-titus",fullName:"P. Titus"},{id:"199035",title:"Prof.",name:"A. P.",middleName:null,surname:"Santhakumaran",slug:"a.-p.-santhakumaran",fullName:"A. P. Santhakumaran"}]},{id:"71501",title:"Accelerating DNA Computing via PLP-qPCR Answer Read out to Solve Traveling Salesman Problems",slug:"accelerating-dna-computing-via-plp-qpcr-answer-read-out-to-solve-traveling-salesman-problems",totalDownloads:736,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"An asymmetric, fully-connected 8-city traveling salesman problem (TSP) was solved by DNA computing using the ordered node pair abundance (ONPA) approach through the use of pair ligation probe quantitative real time polymerase chain reaction (PLP-qPCR). The validity of using ONPA to derive the optimal answer was confirmed by in silico computing using a reverse-engineering method to reconstruct the complete tours in the feasible answer set from the measured ONPA. The high specificity of the sequence-tagged hybridization, and ligation that results from the use of PLPs significantly increased the accuracy of answer determination in DNA computing. When combined with the high throughput efficiency of qPCR, the time required to identify the optimal answer to the TSP was reduced from days to 25 min.",book:{id:"8241",slug:"novel-trends-in-the-traveling-salesman-problem",title:"Novel Trends in the Traveling Salesman Problem",fullTitle:"Novel Trends in the Traveling Salesman Problem"},signatures:"Fusheng Xiong, Michael Kuby and Wayne D. 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A decision tree was applied for generating decision rules.",book:{id:"5842",slug:"graph-theory-advanced-algorithms-and-applications",title:"Graph Theory",fullTitle:"Graph Theory - Advanced Algorithms and Applications"},signatures:"Izabela Kutschenreiter-Praszkiewicz",authors:[{id:"218951",title:"Associate Prof.",name:"Izabela",middleName:null,surname:"Kutschenreiter-Praszkiewicz",slug:"izabela-kutschenreiter-praszkiewicz",fullName:"Izabela Kutschenreiter-Praszkiewicz"}]},{id:"55375",title:"An Example Usage of Graph Theory in Other Scientific Fields: On Graph Labeling, Possibilities and Role of Mind/Consciousness",slug:"an-example-usage-of-graph-theory-in-other-scientific-fields-on-graph-labeling-possibilities-and-role",totalDownloads:1795,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"This paper provides insights into some aspects of the possibilities and role of mind, consciousness, and their relation to mathematical logic with the application of problem solving in the fields of psychology and graph theory. This work aims to dispel certain long-held notions of a severe psychological disorder and a well-known graph labeling conjecture. The applications of graph labelings of various types for various kinds of graphs are being discussed. 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Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. 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He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. 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He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. 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Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null}]},overviewPageOFChapters:{paginationCount:49,paginationItems:[{id:"80495",title:"Iron in Cell Metabolism and Disease",doi:"10.5772/intechopen.101908",signatures:"Eeka Prabhakar",slug:"iron-in-cell-metabolism-and-disease",totalDownloads:1,totalCrossrefCites:0,totalDimensionsCites:null,authors:null,book:{title:"Iron Metabolism - Iron a Double‐Edged Sword",coverURL:"https://cdn.intechopen.com/books/images_new/10842.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"81799",title:"Cross Talk of Purinergic and Immune Signaling: Implication in Inflammatory and Pathogenic Diseases",doi:"10.5772/intechopen.104978",signatures:"Richa Rai",slug:"cross-talk-of-purinergic-and-immune-signaling-implication-in-inflammatory-and-pathogenic-diseases",totalDownloads:7,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"81764",title:"Involvement of the Purinergic System in Cell Death in Models of Retinopathies",doi:"10.5772/intechopen.103935",signatures:"Douglas Penaforte Cruz, Marinna Garcia Repossi and Lucianne Fragel Madeira",slug:"involvement-of-the-purinergic-system-in-cell-death-in-models-of-retinopathies",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"81756",title:"Alteration of Cytokines Level and Oxidative Stress Parameters in COVID-19",doi:"10.5772/intechopen.104950",signatures:"Marija Petrusevska, Emilija Atanasovska, Dragica Zendelovska, Aleksandar Eftimov and Katerina Spasovska",slug:"alteration-of-cytokines-level-and-oxidative-stress-parameters-in-covid-19",totalDownloads:8,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Chemokines Updates",coverURL:"https://cdn.intechopen.com/books/images_new/11672.jpg",subseries:{id:"18",title:"Proteomics"}}}]},overviewPagePublishedBooks:{paginationCount:27,paginationItems:[{type:"book",id:"7006",title:"Biochemistry and Health Benefits of Fatty Acids",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7006.jpg",slug:"biochemistry-and-health-benefits-of-fatty-acids",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Viduranga Waisundara",hash:"c93a00abd68b5eba67e5e719f67fd20b",volumeInSeries:1,fullTitle:"Biochemistry and Health Benefits of Fatty Acids",editors:[{id:"194281",title:"Dr.",name:"Viduranga Y.",middleName:null,surname:"Waisundara",slug:"viduranga-y.-waisundara",fullName:"Viduranga Y. Waisundara",profilePictureURL:"https://mts.intechopen.com/storage/users/194281/images/system/194281.jpg",biography:"Dr. Viduranga Waisundara obtained her Ph.D. in Food Science and Technology from the Department of Chemistry, National University of Singapore, in 2010. She was a lecturer at Temasek Polytechnic, Singapore from July 2009 to March 2013. She relocated to her motherland of Sri Lanka and spearheaded the Functional Food Product Development Project at the National Institute of Fundamental Studies from April 2013 to October 2016. She was a senior lecturer on a temporary basis at the Department of Food Technology, Faculty of Technology, Rajarata University of Sri Lanka. She is currently Deputy Principal of the Australian College of Business and Technology – Kandy Campus, Sri Lanka. 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\r\n\tIn general, the harsher the environmental conditions in an ecosystem, the lower the biodiversity. Changes in the environment caused by human activity accelerate the impoverishment of biodiversity.
\r\n
\r\n\tBiodiversity refers to “the variability of living organisms from any source, including terrestrial, marine and other aquatic ecosystems and the ecological complexes of which they are part; it includes diversity within each species, between species, and that of ecosystems”.
\r\n
\r\n\tBiodiversity provides food security and constitutes a gene pool for biotechnology, especially in the field of agriculture and medicine, and promotes the development of ecotourism.
\r\n
\r\n\tCurrently, biologists admit that we are witnessing the first phases of the seventh mass extinction caused by human intervention. It is estimated that the current rate of extinction is between a hundred and a thousand times faster than it was when man first appeared. The disappearance of species is caused not only by an accelerated rate of extinction, but also by a decrease in the rate of emergence of new species as human activities degrade the natural environment. The conservation of biological diversity is "a common concern of humanity" and an integral part of the development process. Its objectives are “the conservation of biological diversity, the sustainable use of its components, and the fair and equitable sharing of the benefits resulting from the use of genetic resources”.
\r\n
\r\n\tThe following are the main causes of biodiversity loss:
\r\n
\r\n\t• The destruction of natural habitats to expand urban and agricultural areas and to obtain timber, minerals and other natural resources.
\r\n
\r\n\t• The introduction of alien species into a habitat, whether intentionally or unintentionally which has an impact on the fauna and flora of the area, and as a result, they are reduced or become extinct.
\r\n
\r\n\t• Pollution from industrial and agricultural products, which devastate the fauna and flora, especially those in fresh water.
\r\n
\r\n\t• Global warming, which is seen as a threat to biological diversity, and will become increasingly important in the future.
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