Proportion of LVV-h7 in total area of peptides after extraction process.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"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"},{slug:"intechopen-identified-as-one-of-the-most-significant-contributor-to-oa-book-growth-in-doab-20210809",title:"IntechOpen Identified as One of the Most Significant Contributors to OA Book Growth in DOAB"}]},book:{item:{type:"book",id:"10411",leadTitle:null,fullTitle:"Materials at the Nanoscale",title:"Materials at the Nanoscale",subtitle:null,reviewType:"peer-reviewed",abstract:"Nanocrystals play very important roles in the interdisciplinary fields of biology, physics and chemistry. They are used for various applications, including to develop and formulate new drugs and vaccines to fight diseases and pandemics. This book contains nine chapters that discuss nanocrystals in electronics, medicine, the food industry, geology, and more.",isbn:"978-1-83968-823-2",printIsbn:"978-1-83968-822-5",pdfIsbn:"978-1-83968-824-9",doi:"10.5772/intechopen.91597",price:119,priceEur:129,priceUsd:155,slug:"materials-at-the-nanoscale",numberOfPages:184,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"be29908600b7067c583ac21da1544a2d",bookSignature:"Awadesh Kumar Mallik",publishedDate:"October 6th 2021",coverURL:"https://cdn.intechopen.com/books/images_new/10411.jpg",numberOfDownloads:2306,numberOfWosCitations:0,numberOfCrossrefCitations:2,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:4,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:6,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 15th 2020",dateEndSecondStepPublish:"December 15th 2020",dateEndThirdStepPublish:"February 13th 2021",dateEndFourthStepPublish:"May 4th 2021",dateEndFifthStepPublish:"July 3rd 2021",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"178218",title:"Dr.",name:"Awadesh",middleName:null,surname:"Mallik",slug:"awadesh-mallik",fullName:"Awadesh Mallik",profilePictureURL:"https://mts.intechopen.com/storage/users/178218/images/system/178218.jpg",biography:"Dr. Awadesh Kumar Mallik is a ceramic engineer from the University of Calcutta, India, who is currently a materials researcher. He started growing CVD diamond at the Indian Institute of Science Bangalore laboratory during his master’s thesis project for the development of vacuum tribology coatings for the Indian Space Research Organisation. He continued his scientific journey of making ceramic components for high-power electron tubes at the Council of Scientific and Industrial Research laboratory CGCRI as part of a national mission for the international fusion energy ITER program. He has executed and delivered several national and international projects. His research interests include diamond materials, thin films and coatings, CVD, PVD, tribology, bioceramics, ceramic membranes, fuel cells and batteries, ceramic powder processing, and materials science in general. He obtained a Ph.D. graduate from Jadavpur University, India, and completed an FWO postdoctoral research fellowship at Hasselt University, Belgium. He has published forty peer-reviewed articles and presented many papers at international conferences.",institutionString:"Hasselt University and IMEC VZW",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"University of Hasselt",institutionURL:null,country:{name:"Belgium"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"208",title:"Material Science",slug:"nanotechnology-and-nanomaterials-material-science"}],chapters:[{id:"76003",title:"Nonthermal Crystalline Forming of Ceramic Nanoparticles by Non-Equilibrium Excitation Reaction Field of Electron",doi:"10.5772/intechopen.97037",slug:"nonthermal-crystalline-forming-of-ceramic-nanoparticles-by-non-equilibrium-excitation-reaction-field",totalDownloads:201,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In this work, we have discovered a method of forming ZnO thin films with high mobility, high carrier density and low resistivity on plastic (PET) films using non-equilibrium reaction fields, even when the films are deposited without heating, and we have also found a thin film formation technique using a wet process that is different from conventional deposition techniques. The field emission electron-beam irradiation treatment energetically activates the surface of ZnO particles and decomposes each ZnO particles. The energy transfer between zinc ions and ZnO surface and the oxygen present in the atmosphere around the ZnO particles induce the oxidation of zinc. In addition, the ZnO thin films obtained in this study successfully possess high functional thin films with high electrical properties, including high hole mobility of 208.6 cm2/Vs, despite being on PET film substrates. These results contribute to the discovery of a mechanism to create highly functional oxide thin films using a simple two-dimensional process without any heat treatment on the substrate or during film deposition. In addition, we have elucidated the interfacial phenomena and crosslinking mechanisms that occur during the bonding of metal oxide particles, and understood the interfacial physical properties and their effects on the electronic structure. and surface/interface control, and control of higher-order functional properties in metal/ceramics/semiconductor composites, and contribute to the provision of next-generation nanodevice components in a broad sense.",signatures:"Norihiro Shimoi",downloadPdfUrl:"/chapter/pdf-download/76003",previewPdfUrl:"/chapter/pdf-preview/76003",authors:[{id:"341836",title:"Prof.",name:"Norihiro",surname:"Shimoi",slug:"norihiro-shimoi",fullName:"Norihiro Shimoi"}],corrections:null},{id:"74283",title:"Biomineralization of Magnetosomes: Billion-Year Evolution Shaping Modern Nanotools",doi:"10.5772/intechopen.94465",slug:"biomineralization-of-magnetosomes-billion-year-evolution-shaping-modern-nanotools",totalDownloads:359,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Biomineralization in the microbial realm usually gives origin to finely structured inorganic nanomaterials. Perhaps, one of the most elegant bioinorganic processes found in nature is the iron biomineralization into magnetosomes, which is performed by magnetotactic bacteria. A magnetosome gene cluster within the bacterial genome precisely regulates the mineral synthesis. The spread and evolution of this ability among bacteria are thought to be a 2,7-billion-year process mediated by horizontal gene transfers. The produced magnetite or greigite nanocrystals coated by a biological membrane have a narrow diameter dispersibility, a highly precise morphology, and a permanent magnetic dipole due to the molecular level control. Approaches inspired by this bacterial biomineralization mechanism can imitate some of the biogenic nanomagnets characteristics in the chemical synthesis of iron oxide nanoparticles. Thus, this chapter will give a concise overview of magnetosome synthesis’s main steps, some hypotheses about the evolution of magnetosomes’ biomineralization, and approaches used to mimic this biological phenomenon in vitro.",signatures:"Tarcisio Nascimento Correa, Igor Nunes Taveira, Rogerio Presciliano de Souza Filho and Fernanda de Avila Abreu",downloadPdfUrl:"/chapter/pdf-download/74283",previewPdfUrl:"/chapter/pdf-preview/74283",authors:[{id:"254251",title:"Dr.",name:"Fernanda",surname:"de Avila Abreu",slug:"fernanda-de-avila-abreu",fullName:"Fernanda de Avila Abreu"}],corrections:null},{id:"77960",title:"Nanostructuring Bi2Te3-Based Thermoelectric Thin-Films Grown Using Pulsed Laser Deposition",doi:"10.5772/intechopen.99469",slug:"nanostructuring-bi2te3-based-thermoelectric-thin-films-grown-using-pulsed-laser-deposition",totalDownloads:365,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This book chapter reports recent advances in nanostructured Bi2Te3-based thermoelectric (TE) thin-films fabricated by pulsed laser deposition (PLD). By controlling the processing conditions in PLD growths, various fascinating Bi2Te3-based nanostructured films with promising or enhanced TE properties have been successfully fabricated, including super-assembling of Bi2Te3 hierarchical nanostructures, self-assembled Bi2Te3 films with well-aligned 0D to 3D nanoblocks, polycrystalline-nanostructured Bi2Se3 and Bi2Te3 thin-films, etc. In addition, a PLD-growth mechanism for fabricating the super-assembling Bi2Te3 thin-films is presented. This book chapter provides fundamental understanding the relationship amongst processing condition, structure-morphology, and TE property of PLD-growths Bi2Te3-based thin-films. It also presents an overview of TE materials and applications with the challenges and perspectives.",signatures:"Le Thi Cam Tuyen, Phuoc Huu Le and Sheng-Rui Jian",downloadPdfUrl:"/chapter/pdf-download/77960",previewPdfUrl:"/chapter/pdf-preview/77960",authors:[{id:"187013",title:"Dr.",name:"Phuoc",surname:"Huu Le",slug:"phuoc-huu-le",fullName:"Phuoc Huu Le"},{id:"348310",title:"Dr.",name:"Le Thi Cam",surname:"Tuyen",slug:"le-thi-cam-tuyen",fullName:"Le Thi Cam Tuyen"},{id:"420973",title:"Prof.",name:"Sheng-Rui",surname:"Jian",slug:"sheng-rui-jian",fullName:"Sheng-Rui Jian"}],corrections:null},{id:"75563",title:"Characterization of Nanocrystalline Cores for EMI Suppression in Cables",doi:"10.5772/intechopen.96694",slug:"characterization-of-nanocrystalline-cores-for-emi-suppression-in-cables",totalDownloads:246,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Electromagnetic interferences (EMI) can cause different kinds of problems in digital and analog systems, leading to malfunctions, system reboots, or even permanent damage to the system if this is not adequately designed or protected. Nowadays, most electronic products are connected to the main power network or are designed to be interconnected with others through cables. These cable interconnections are becoming more difficult due to the rigid restrictions related to the accomplishment of electromagnetic compatibility (EMC) compliance. When the cables of a system represent an EMI source, it cannot pass the conducted or radiated emissions test. A widely used technique to reduce these problems is applying an EMI suppressor such as a sleeve core. This EMI suppressor provides selective attenuation of undesired interference components that the designer may wish to suppress, and it does not significantly affect the intended signal. This contribution focuses on analyzing different nanocrystalline (NC) EMI suppressors’ performance intended for attenuating interferences in cables. Some NC novel samples are characterized and compare to MnZn and NiZn cores to determine this novel material’s effectiveness compared to the conventional ceramic solutions by analyzing samples with different dimensions.",signatures:"Adrian Suarez, Jorge Victoria, Jose Torres, Pedro A. Martinez, Andrea Amaro and Julio Martos",downloadPdfUrl:"/chapter/pdf-download/75563",previewPdfUrl:"/chapter/pdf-preview/75563",authors:[{id:"2803",title:"Dr.",name:"Julio",surname:"Martos",slug:"julio-martos",fullName:"Julio Martos"},{id:"66221",title:"Dr.",name:"Jose",surname:"Torres",slug:"jose-torres",fullName:"Jose Torres"},{id:"193686",title:"MSc.",name:"Pedro A.",surname:"Martinez",slug:"pedro-a.-martinez",fullName:"Pedro A. Martinez"},{id:"193687",title:"Prof.",name:"Adrian",surname:"Suarez",slug:"adrian-suarez",fullName:"Adrian Suarez"},{id:"348209",title:"MSc.",name:"Jorge",surname:"Victoria",slug:"jorge-victoria",fullName:"Jorge Victoria"},{id:"348231",title:"BSc.",name:"Andrea",surname:"Amaro",slug:"andrea-amaro",fullName:"Andrea Amaro"}],corrections:null},{id:"76843",title:"Fullerenes and Nanodiamonds for Medical Drug Delivery",doi:"10.5772/intechopen.97867",slug:"fullerenes-and-nanodiamonds-for-medical-drug-delivery",totalDownloads:242,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Carbon is a chemical element has the ability of forming long carbonic chain. Due to its special electronic structure, each carbon atom can be linked with another carbon atom or with another element via single, double or triple covalent bonds. The special electronic structure of carbon atom affecting on its properties also affecting on its ability of existing in different forms called allotropes. During few last decades, new carbon-based nanomaterials have been described including fullerene, carbon nanotube, graphene and nanodiamond. These new allotropes attracted the interest of science and industry and became as a new and important class of materials due to its outstanding features which candidate for numerous applications. In parallel with new developments in nanomedicine especially in drug delivery field, the targeted delivery systems became an important to overcome the limitations of the old fashion systems. So, it become very important to translate this idea into reality. Fullerene and nanodiamond have a unique combination of structure, morphology and biological properties that make them as a powerful tools for targeted delivery system. So, this chapter will focus on two major aspects: synthesis routes of fullerenes and nanodiamonds, and their role in nanomedicine as drug delivery systems.",signatures:"Basma H. Al-Tamimi and Saad B.H. Farid",downloadPdfUrl:"/chapter/pdf-download/76843",previewPdfUrl:"/chapter/pdf-preview/76843",authors:[{id:"341563",title:"Dr.",name:"Basma H.",surname:"Al-Tamimi",slug:"basma-h.-al-tamimi",fullName:"Basma H. Al-Tamimi"},{id:"350855",title:"Prof.",name:"Saad",surname:"B. H. Farid",slug:"saad-b.-h.-farid",fullName:"Saad B. H. Farid"}],corrections:null},{id:"76027",title:"Nano-Sized Minerals from Lower Cretaceous Sandstones in Israel Observed by Transmission Electron Microscopy (TEM)",doi:"10.5772/intechopen.96948",slug:"nano-sized-minerals-from-lower-cretaceous-sandstones-in-israel-observed-by-transmission-electron-mic",totalDownloads:220,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Fine fraction in quartz arenite sandstones from Lower Cretaceous Hatira formation in Israel was observed by Transmission electron microscope (TEM). Samples were collected from Hatira and Ramon craters located in southern part of Israel and from Manara cliff from the northern part of Israel. The additional phases cause yellow, red, dark red and dark violet colors of the layered sandstones. The motivation was to identify the minerals of the fine factions that cause the variations in the colors. The minerals observed were clay minerals, mainly kaolinite (Al4Si4O20(OH)8), some illite (K0.65Al2.0[Al0.65Si3.35O10](OH)2) and smectite. Iron oxides were goethite (FeOOH) and hematite (Fe2O3), Titanium-iron oxides observed was ilmenite (FeTiO3), and Titanium-oxides were rutile (TiO2), and anatase (TiO2). Sulphates observed were jarosite (KFe3(SO4)2(OH)6) and alunite (KAl3(SO4)2(OH)6). Some of the hematite was formed by recrystallization of goethite. Ilmenite disintegrated into small iron oxides mainly hematite. Euhedral to sub-hedral rutile (TiO2) and anatase (TiO2) were preserved in clay-minerals. Crystals of alunite and jarosite were observed in sandstones in both craters. They probably crystallized due to some transgression of the Thetis Sea.",signatures:"Nurit Taitel-Goldman and Vladimir Ezersky",downloadPdfUrl:"/chapter/pdf-download/76027",previewPdfUrl:"/chapter/pdf-preview/76027",authors:[{id:"161472",title:"Dr.",name:"Nurit",surname:"Taitel-Goldman",slug:"nurit-taitel-goldman",fullName:"Nurit Taitel-Goldman"},{id:"354267",title:"Dr.",name:"Vladimir",surname:"Ezersky",slug:"vladimir-ezersky",fullName:"Vladimir Ezersky"}],corrections:null},{id:"76267",title:"Diluted Magnetic Semiconductors Nanocrystals: Saturation and Modulation",doi:"10.5772/intechopen.96679",slug:"diluted-magnetic-semiconductors-nanocrystals-saturation-and-modulation",totalDownloads:263,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Diluted Magnetic Semiconductor (DMS) nanocrystals are a new class of materials formed by doping the semiconductor with transition metals (TM), which gives interesting magneto-optical properties. These properties are attributed to the exchange interaction between the pure semiconductor’s sp-electrons and the localized TM d-electrons. This book chapter shows exciting results of new DMS developed by the group, both in powder form and embedded in glassy systems. Depending on the concentration of doping ions, saturation of the incorporation of substitutional and interstitial sites in the nanocrystal structure may occur, forming other nanocrystals. In this context, we investigated the doping saturation limit in nanopowders of DMS Zn1-xMnxO NCs and Zn1-xMnxTe, Zn0.99-xMn0.01CoxTe, and Bi2-xCoxS NCs synthesized in glassy matrices. Thus, the sites’ saturation into the crystalline lattice of nanocrystals is a topic little reported in the literature, and we will comment on this work. Therefore, we will show results from the group about the modulation and saturation in diluted magnetic semiconductors nanocrystals in this work.",signatures:"Anielle C.A. Silva, Amanda I.S. Barbosa, Alessandra S. Silva, Elisson A. Batista, Thaís K. de Lima Rezende, Éder V. Guimarães, Ricardo S. Silva and Noelio O. Dantas",downloadPdfUrl:"/chapter/pdf-download/76267",previewPdfUrl:"/chapter/pdf-preview/76267",authors:[{id:"340051",title:"Prof.",name:"Anielle C.A.",surname:"Silva",slug:"anielle-c.a.-silva",fullName:"Anielle C.A. Silva"},{id:"346696",title:"Dr.",name:"Alessandra S.",surname:"Silva",slug:"alessandra-s.-silva",fullName:"Alessandra S. Silva"},{id:"346697",title:"Dr.",name:"Éder V.",surname:"Guimarães",slug:"eder-v.-guimaraes",fullName:"Éder V. Guimarães"},{id:"346698",title:"Prof.",name:"Ricardo S.",surname:"Silva",slug:"ricardo-s.-silva",fullName:"Ricardo S. Silva"},{id:"346701",title:"Prof.",name:"Noelio",surname:"Dantas",slug:"noelio-dantas",fullName:"Noelio Dantas"},{id:"347625",title:"MSc.",name:"Amanda I. S.",surname:"Barbosa",slug:"amanda-i.-s.-barbosa",fullName:"Amanda I. S. Barbosa"},{id:"347626",title:"Dr.",name:"Elisson A.",surname:"Batista",slug:"elisson-a.-batista",fullName:"Elisson A. Batista"},{id:"347627",title:"MSc.",name:"Thaís",surname:"K. de Lima Rezende",slug:"thais-k.-de-lima-rezende",fullName:"Thaís K. de Lima Rezende"}],corrections:null},{id:"75698",title:"Doped Semiconductor Nanocrystals: Development and Applications",doi:"10.5772/intechopen.96753",slug:"doped-semiconductor-nanocrystals-development-and-applications",totalDownloads:263,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This chapter aims to show significant progress that our group has been developing and the applications of several doped semiconductor nanocrystals (NCs), as nanopowders or embedded in glass systems. Depending on the type of dopant incorporated in the nanocrystals, the physical, chemical, and biological properties can be intensified. However, it can also generate undesired toxic effects that can potentially compromise its use. Here we present the potential of zinc oxide NCs doped with silver (Ag), gold (Au), and magnesium (Mg) ions to control bacterial diseases in agriculture. We have also performed biocompatibility analysis of the pure and Ag-doped sodium titanate (Na2Ti3O7) NCs in Drosophila. The doped nanocrystals embedded in glassy systems are chrome (Cr) or copper (Cu) in ZnTe and Bi2Te3 NCs for spintronic development nanodevices. Therefore, we will show several advantages that doped nanocrystals may present in the technological and biotechnological areas.",signatures:"Anielle C.A. Silva, Eliete A. Alvin, Francisco R.A. dos Santos, Samanta L.M. de Matos, Jerusa M. de Oliveira, Alessandra S. Silva, Éder V. Guimarães, Mirella S. Vieira, Eurípedes A. da Silva Filho, Ricardo S. Silva, Lucas Anhezini, Nilvanira D. Tebaldi and Noelio O. Dantas",downloadPdfUrl:"/chapter/pdf-download/75698",previewPdfUrl:"/chapter/pdf-preview/75698",authors:[{id:"340051",title:"Prof.",name:"Anielle C.A.",surname:"Silva",slug:"anielle-c.a.-silva",fullName:"Anielle C.A. Silva"},{id:"346696",title:"Dr.",name:"Alessandra S.",surname:"Silva",slug:"alessandra-s.-silva",fullName:"Alessandra S. Silva"},{id:"346697",title:"Dr.",name:"Éder V.",surname:"Guimarães",slug:"eder-v.-guimaraes",fullName:"Éder V. Guimarães"},{id:"346698",title:"Prof.",name:"Ricardo S.",surname:"Silva",slug:"ricardo-s.-silva",fullName:"Ricardo S. Silva"},{id:"346701",title:"Prof.",name:"Noelio",surname:"Dantas",slug:"noelio-dantas",fullName:"Noelio Dantas"},{id:"221975",title:"Dr.",name:"Jerusa M.",surname:"de Oliveira",slug:"jerusa-m.-de-oliveira",fullName:"Jerusa M. de Oliveira"},{id:"346692",title:"Prof.",name:"Eurípedes A.",surname:"da Silva Filho",slug:"euripedes-a.-da-silva-filho",fullName:"Eurípedes A. da Silva Filho"},{id:"346700",title:"Prof.",name:"Lucas",surname:"Anhezini",slug:"lucas-anhezini",fullName:"Lucas Anhezini"},{id:"346981",title:"MSc.",name:"Eliete A.",surname:"Alvin",slug:"eliete-a.-alvin",fullName:"Eliete A. Alvin"},{id:"347305",title:"Mr.",name:"Francisco",surname:"R.A. dos Santos",slug:"francisco-r.a.-dos-santos",fullName:"Francisco R.A. dos Santos"},{id:"348389",title:"Ms.",name:"Samanta L.M.",surname:"de Matos",slug:"samanta-l.m.-de-matos",fullName:"Samanta L.M. de Matos"},{id:"348390",title:"Ms.",name:"Mirella S.",surname:"Vieira",slug:"mirella-s.-vieira",fullName:"Mirella S. Vieira"},{id:"348391",title:"Prof.",name:"Nilvanira D.",surname:"Tebaldi",slug:"nilvanira-d.-tebaldi",fullName:"Nilvanira D. Tebaldi"}],corrections:null},{id:"77799",title:"Antimicrobial Efficacy of Biogenic Silver and Zinc Nanocrystals/Nanoparticles to Combat the Drug Resistance in Human Pathogens",doi:"10.5772/intechopen.99200",slug:"antimicrobial-efficacy-of-biogenic-silver-and-zinc-nanocrystals-nanoparticles-to-combat-the-drug-res",totalDownloads:153,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The emergence of biogenic nanomaterials as novel antimicrobials introduces a new paradigm in human health care. Based on the recent reports of the World Health Organization, infectious diseases pose one of the greatest health challenges. Increased multi-drug resistance prevalence among human pathogens, due to the inefficiency of commercially available antimicrobial drugs in the market is a great threat to humans. The poor solubility, stability and side effects of the antibacterial therapy prompted the researchers to explore new innovative strategies for developing new antimicrobials. Recently, biogenic nanoparticles have proven their effectiveness against multidrug-resistant (MDR) pathogens as an alternative to conventional antibiotics. Biogenic nanoparticles such as silver nanoparticles (AgNPs) and Zinc Oxide nanoparticles (ZnONPs) are easy to produce, biocompatible, provide enhanced uptake and are eco-friendly. Moreover, the capping of the biogenic nanocrystals provides an active surface for interaction with biological components, facilitated by free active surface functional groups to enhance their efficacy and delivery. Inorganic nanocrystals (AgNPs and ZnONPs) are effective both as nano-bactericides and as nanocarriers against sensitive and MDR) pathogens. The present chapter focuses on the utilization of the recent nanosystems to combat drug resistance in human pathogens. Nanomedicine represents a new generation of potiential antimicrobial candidates capable of combating the drug resistance in various pathogenic organisms.",signatures:"Gulzar Ahmed Rather, Saqib Hassan, Surajit Pal, Mohd Hashim Khan, Heshu Sulaiman Rahman and Johra Khan",downloadPdfUrl:"/chapter/pdf-download/77799",previewPdfUrl:"/chapter/pdf-preview/77799",authors:[{id:"226198",title:"Dr.",name:"Johra",surname:"Khan",slug:"johra-khan",fullName:"Johra Khan"},{id:"253612",title:"Dr.",name:"Heshu Sulaiman",surname:"Rahman",slug:"heshu-sulaiman-rahman",fullName:"Heshu Sulaiman Rahman"},{id:"347400",title:"Mr.",name:"Gulzar Ahmed",surname:"Rather",slug:"gulzar-ahmed-rather",fullName:"Gulzar Ahmed Rather"},{id:"353075",title:"Mr.",name:"Mohd Hashim",surname:"Khan",slug:"mohd-hashim-khan",fullName:"Mohd Hashim Khan"},{id:"418490",title:"Dr.",name:"Saqib",surname:"Hassan",slug:"saqib-hassan",fullName:"Saqib Hassan"},{id:"421881",title:"Mr.",name:"Surajit",surname:"Pal",slug:"surajit-pal",fullName:"Surajit Pal"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"10257",title:"Engineering Applications of Diamond",subtitle:null,isOpenForSubmission:!1,hash:"6062b591f89e8bdbbd8e7f59c0d366a1",slug:"engineering-applications-of-diamond",bookSignature:"Awadesh Mallik",coverURL:"https://cdn.intechopen.com/books/images_new/10257.jpg",editedByType:"Edited by",editors:[{id:"178218",title:"Dr.",name:"Awadesh",surname:"Mallik",slug:"awadesh-mallik",fullName:"Awadesh Mallik"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6408",title:"Novel Nanomaterials",subtitle:"Synthesis and Applications",isOpenForSubmission:!1,hash:"f3585d338d78e4d31c200d9991b03692",slug:"novel-nanomaterials-synthesis-and-applications",bookSignature:"George Z. Kyzas and Athanasios C. 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\r\n\r\n\tThe proposed book should cover the energy conversion mechanisms of triboelectric, piezoelectric, and hybrid generators and their boosting performance strategies. Furthermore, the various strategies adopted so far to improve the performance of various nanogenerators using the theoretical assumptions and experimental analysis can be also described briefly. Ultimately, this book will cover the application of nanogenerators in self-powered sensors & systems and their commercialization.
",isbn:"978-1-80356-255-1",printIsbn:"978-1-80356-254-4",pdfIsbn:"978-1-80356-256-8",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,hash:"d52edc8b54e3451fe151b38cb4c9aee9",bookSignature:"Dr. Bhaskar Dudem and Dr. Vivekananthan Venkateswaran",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11465.jpg",keywords:"Surface Modification, Charge Transfer, Charge Accumulation, High Performance, Hybridization, Composite Films, Self-Powered, Pressure Sensor, Tactile Sensor, Blue Energy, Triboelectric, Piezoelectric",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 10th 2022",dateEndSecondStepPublish:"April 14th 2022",dateEndThirdStepPublish:"June 13th 2022",dateEndFourthStepPublish:"September 1st 2022",dateEndFifthStepPublish:"October 31st 2022",remainingDaysToSecondStep:"a month",secondStepPassed:!0,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"An active researcher in harnessing the ubiquitously available biomechanical energies to power portable electronics, with over 1000 citations, and a high h index(20). Dr. Dudem was awarded an ATI Research Laurette award 2019/20 for his high-impact paper published in Nano Energy, and his research activities have also been featured in most-famous news websites including MSN, Nanowerk, Phys.org, and Medical Design Briefs.",coeditorOneBiosketch:"An active researcher in energy harvesting using triboelectric and piezoelectric effects, graduated from Anna University, member of the Royal Society of Chemistry, and winner of the President Award for Outstanding Achievement in research and academics.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"315573",title:"Dr.",name:"Bhaskar",middleName:null,surname:"Dudem",slug:"bhaskar-dudem",fullName:"Bhaskar Dudem",profilePictureURL:"https://mts.intechopen.com/storage/users/315573/images/system/315573.png",biography:"Bhaskar Dudem is currently working as a Post-Doctoral Research Fellow (from Oct 2019) at the Advanced Technology Institute (ATI), University of Surrey, England, UK. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"63025",title:"From a Sequential to a Continuous Approach for LVV-h7 Preparation during Enzymatic Proteolysis in a Microfluidic- Based Extraction Process",doi:"10.5772/intechopen.80228",slug:"from-a-sequential-to-a-continuous-approach-for-lvv-h7-preparation-during-enzymatic-proteolysis-in-a-",body:'\nIntensification of process is considered as an indispensable part in the development of approach for obtaining product with high added value. The improvement of a process could concern the technology used, the safety or also the source of raw material employed. Among these sources, wastes of agricultural and food processing are considered as a cheap source of valuable components since the existent technologies allow the recovery of target compounds and their recycling [1]. The process was developed at industrial scale to valorise these kinds of products [2]. In this work, animal blood was studied as a source of bioactive peptides [3, 4, 5, 6]. Some of these peptides revealed their potential as antimicrobial [7], opioid [8], antihypertensive [8] or antioxidative activities [9]. These peptides are generally obtained by enzymatic degradation of haemoglobin alpha and beta chains [3]. Among these peptides, one opioid peptide was studied, known as LVV-haemorphin-7. LVV-h7 corresponds to the amino acid sequence LVVYPWTQRF (Leu-Val-Val-Tyr-Pro-Trp-Thr-Gln-Arg-Phe), obtained from β chain of haemoglobin (β 31–40) by pepsin hydrolysis and well known as bioactive peptides involved in the treatment of humans diseases [8, 10, 11, 12].
\nLVV-h7 presents also interesting physical properties, especially hydrophobic character which makes it able to transfer from aqueous to organic media in liquid/liquid extraction process [13]. Previous studies were interested to extract this peptide during haemoglobin hydrolysis using water/butan-2-ol-octan-1-ol liquid/liquid biphasic system [14, 15, 16]. Even if this process has shown the ability to extract selectively LVV-h7, its implementation was very complex and laborious, due to the long time of the process carried out (more than 10 h) to obtain low extraction yield of peptide (about 5%), the control of the immobilised enzyme stability during the process to avoid its inhibition by solvents and a high quantity of solvent.
\nKeeping in mind the economic and environmental impacts of a process development which requires the use of organic solvent, the microfluidic domain could bring solutions to reduce these disadvantages. First, reduction of scale allows to improve the surface/volume ratio and thus the molecular transfer capacity while reducing the volume of solvent used and energy [17, 18]. Second, the implementation for continuous flow platforms brings advantages of liquid-liquid transfer favoured by laminar flow [19, 20, 21], in the case of non-miscible liquids, for molecular transfer. Several studies revealed the real advantage of using LLE in microfluidic system [19, 22, 23].
\nPrevious study realised on the enzymatic hydrolysis of haemoglobin by pepsin in a microfluidic reactor has shown the influence of the microfluidic scale to the kinetics acceleration of bioactive peptides appearance, such as LVV-h7, comparing to bench scale [24]. This study shows also the potential of combining enzymatic microreactor with liquid/liquid biphasic system for LVV-h7 extraction. Therefore, the approach that we propose is based on continuous aqueous haemoglobin hydrolysis by pepsin, LVV-h7 extraction towards an intermediate organic phase and LVV-h7 DES extraction in a receiving aqueous phase, allowing the solvent recycling. This integrated process with solvent recycling is presented in Figure 1. Before fully designing the entire microfluidic process, where all the reactions are carried out simultaneously, we separately investigated each reaction to notably determine their respective optimal ranges of conditions before combination as follows: (1) haemoglobin hydrolysis by pepsin occurs in a primary aqueous feed phase, generating the LVV-h7 in a very complex peptide mixture with more than one hundreds of peptides with different primary sequences; (2) the as-formed LVV-h7 is then selectively extracted into an organic solvent (octan-1-ol); (3) eventually, the LVV-h7 is des extracted in a second aqueous phase (called receiving aqueous phase), which also allows the octan-1-ol recycling in the extraction step. Our approach is not only focused on the compatibility issues of enzymatic catalysis and opioid peptide extraction, but also pays particular attention to integrating all the steps to minimise separation and recycling burdens, which can be detrimental for the overall economics and efficiency of the process. The methodology envisioned to move from a sequential approach towards an integrated continuous process is schematised in Figure 2. Each step was optimised to obtain the best conditions concerning LVV-h7 concentration and purity, through residence time (i.e. flow rate) of both aqueous and organic phases inside the system. After optimisation, enzymatic hydrolysis and extractions steps were combined for a continuous approach to obtain final aqueous phase containing the bioactive peptide. Quantification and purity of LVV-h7 were determined to evaluate the efficiency of integrated process.
\nSimultaneous process applied to the haemoglobin hydrolysis by pepsin, the liquid/liquid extraction of LVV-h7 and the solvent recycling, to produce pure opioid peptide.
Methodology from a sequential approach towards an integrated continuous process.
Bovine haemoglobin (64.5 kDa, Sigma Chemicals Co.) was hydrolysed by porcine pepsin (E.C. 3.4.23.1, 3.440 U mg−1, 35 kDa, Sigma Chemicals Co.), protease from the family of aspartic acid proteases which preferentially catalyses the cleavage of peptide bonds at the carboxyl side of aromatic and hydrophobic amino acids. This proteolytic reaction leads to the appearance of product molecules called peptides. Haemoglobin was prepared under denaturing conditions at pH 3.0 by adding 2 M HCl for a 20 mg mL−1 final concentration. All aqueous solutions were prepared in 18.2 MΩ Milli-Q water (Millipore).
\nIn order to obtain a maximum concentration of LVV-h7 peptides for the extraction step studies, kinetic of reaction was implemented in microfluidic system (75 μm inner diameter, 2 m length). Denatured bovine haemoglobin (1% w/v) was hydrolysed by porcine pepsin at different flow rates (9, 4.5, 1, 0.4 and 0.2 μL min−1), which corresponded to a residence time of 15 s, 30 s, 2 min, 5 min and 10 min, respectively. Samples of peptidic solution were collected during the reaction and mixed with sodium hydroxide 1 M in order to inhibit the pepsin. Samples were conserved at 4°C for RP-HPLC analysis to determine the progress of the reaction.
\nPrevious studies have shown the choice of octan-1-ol as the better extraction solvent for hydrophobic peptides and particularly in the case of LVV-h7 [16, 25]. The haemoglobin hydrolysate was pumped using peristaltic pump (Minipulls 3, Gilson Inc., Middleton, WI, USA) and sent in co-flow with octan-1-ol solution in the same capillary (75 μm inner diameter, 10 cm length) for liquid-liquid extraction (LLE) of peptides from haemoglobin phase to the organic phase. The liquid-liquid extraction was performed with different flow rates to appreciate the impact of contact time on the opioid peptide extraction. The two phases were collected out of the capillary in a 2 mL Eppendorf, immediately separated and analysed by RP-HPLC.
\nOctan-1-ol phase obtained after the extraction procedure was pumped with peristaltic pump and fed in another capillary where acidic water (pH 3 obtained with acetic acid adjustment) was injected at different flow rates to perform a second liquid-liquid extraction from the octan-1-ol to the aqueous phase, called “DES extraction step”. In these conditions, the acidic water extracts peptides and favours the extraction without mixing of the two phases [26]. Phases were collected out of the capillary in a 2 mL Eppendorf, immediately separated and analysed by RP-HPLC.
\nA coupling between both extractions optimised method was implemented, and its efficiency on LVV-h7 peptide extraction selectivity was measured. The entire system was represented on scheme Figure 3 where the volume containing the peptidic hydrolysate and the octan-1-ol was pumped in the same capillary for extraction, followed by a pumping of octan-1-ol phase recovered in a second capillary, connected with acidic water for DES extraction of LVV-h7. For each part of the process, samples were collected for identification and quantification of species.
\nImplementation of microfluidic extraction and DES extraction steps of LVV-h7 from hydrolysate and recycling phases (black: employed method for extraction; green: recycling possibilities of solution).
The liquid chromatographic system is consisted of a Waters 600E automated gradient controller pump module, a Waters Wisp 717 automatic sampling device and a Waters 996 photodiode array detector. Spectral and chromatographic data were stored in a NECImage 466 computer. Detection of the produced peptides was carried out at 215 nm by reverse phase HPLC (RP-HPLC) on a C4-column (Vydak 0.46 × 25 cm, 3 mm I.D.). The mobile phase was water/trifluoroacetic acid (100, 0.1, v/v) and acetonitrile/water/trifluoroacetic acid (60, 40, 0.1, by vol.) at 0.4 mL min−1 flow rate. All common chemicals and reagents were of analytical grade and were purchased from Sigma Chemicals Co. and Flandres Chimie. Identification and quantification of LVV-h7 were performed using peptide standard (purity: 91.63% M.W. 1308.56 Da) purchased from GeneCust Society (Luxembourg).
\nThe sample was loaded on a ground steel MALDI target (Bruker Daltonics, Bremen, Germany) following the dried droplet method. The MS (positive reflectron mode) and MS/MS (lift mode) measurements were performed in an automatic mode on an AUTOFLEXTM Speed TOF/TOF mass spectrometer (Bruker Daltonics) running FlexControlTM3.0 software (Bruker Daltonics). Peptide fragmentation was performed by automatic method of the manufacturer. MS and MS/MS spectra were processed using FlexanalysisTM3.3 and BioTools 3.4 software packages (Bruker Daltonics). Fragmentation pattern of peptides was deduced from matching of amino acid sequences (Uniprot accession numbers: P02070 & P01966) of each chain of bovine haemoglobin to the MS/MS spectra using BioTools 3.4.
\nHaemoglobin 1% (w/v) was hydrolysed by porcine pepsin at room temperature, at pH 3 and at different residence time of substrate and enzyme in the microchannel. At the outlet of the capillary, samples were sent to an Eppendorf containing a disodium tetraborate buffer solution (0.32 M, pH 9.0), that caused enzyme denaturation and thus reaction stopping, and analysed by RP-HPLC.
\nFigure 4 shows the progressive decrease of alpha and beta chains of haemoglobin (between 40 and 60 min) to generate intermediate peptides (between 25 and 40 min) after 15 s of reaction. Next, after 30 s of reaction, there is an increase of peptide population between 25 and 30 min and an emergence of peptides between 15 and 25 min. For the last samples (5 and 10 min), there is a disappearance of peptides between 30 and 40 min to the profit of peptides between 5 and 25 min. This phenomenon was already described in the literature and was explained by an enzymatic hydrolysis of alpha and beta chains to produce a population of hydrophobic peptides with high molecular weight, observed between 30 and 35 min in Figure 3 [3, 5]. Next, this population is hydrolysed to produce other peptides with intermediate molecular weight, observed between 20 and 30 min. Finally, these intermediate peptides are hydrolysed to generate small peptides with hydrophilic character (retention time between 5 and 20 min). This mechanism is called “zipper” mechanism, which is characterised by a denatured state of the initial haemoglobin structure. Moreover, this mechanism is more suitable for obtaining intermediate bioactive peptides, such as LVV-h7 (retention time of about 29 min in Figure 4), compared to a “one by one” mechanism where initial haemoglobin structure is in a native state [3, 5]. LVV-h7 was used as a standard to evaluate the efficiency of extraction process by octan-1-ol. Thus, for studying of the extraction step in microfluidic system, we decided to stop the reaction after 30 s of hydrolysis by sodium hydroxide 1 M in order to obtain the maximum quantity of LVV-h7 (Figure 3c).
\nRP-HPLC chromatograms of haemoglobin 1% hydrolysed by porcine pepsin for different residence times of both haemoglobin and pepsin solutions. (a) Denatured haemoglobin without enzyme, (b) 15 s, (c) 30 s, (d) 2 min, (e) 5 min and (f) 10 min. Samples were analysed on C4 column.
Haemoglobin hydrolysate whose concentration of LVV-h7 was the more important (1%, 30 s of hydrolysis with pepsin) was injected in co-flow (using a T connector) with octan-1-ol at different flow rates (5, 10, 20 and 50 μL min−1). Samples were collected in Eppendorf, and octan-1-ol phase was analysed by RP-HPLC to highlight the extracted peptides. Results are shown in Figure 5.
\nHPLC chromatograms of octan-1-ol phase after extraction applied on haemoglobin hydrolysate in microfluidic system at different flow rates ((a) 10 μL min−1, (b) 20 μL min−1, (c) 40 μL min−1 and (d) 100 μL min−1).
The flow rates used for our analysis correspond to the additive flow rates of both solutions during the extraction step (i.e. initial flow rate multiplied by 2). Chromatograms show a good selectivity of the LLE method and octan-1-ol using microfluidic system. Indeed, we observe only three major peaks from the initial complex peptidic hydrolysate. Moreover, a predominance of LVV-h7 peptide is observed (RT of 29 min), which represents more than 55% of the peptides extracted by octan-1-ol. The selectivity of octan-1-ol for hydrophobic peptides such as LVV-h7 was previously confirmed by our team in batch and continuous reactors from enzymatic haemoglobin hydrolysates, but not in microfluidic system [14, 15, 16]. Two other peaks (RT of 27 and 31 min) are observed and supposed having a hydrophobic character.
\nThe three peaks identified in the octan-1-ol phase were analysed by MALDI mass spectroscopy to appreciate their composition (Figure 6).
\nMALDI-TOF spectra obtained for each peak (elution time (a) 27 min, (b) 29 min and (c) 31 min) collected after octan-1-ol extraction and separated by RP-HPLC.
Concerning the fraction eluted at a 29 min (Figure 6b), result from mass spectroscopy shows unique peak at m/z = 1308.930 Da corresponding to molecular weight for LVV-h7 (with one hydrogen more from mass analysis). No other components were observed, which shows that LVV-h7 peptide is pure. The other fractions collected were also identified. At retention time of 27 min, another pure peptide with 1195.933 Da for molecular weight was identified. It corresponds to the VV-h7 peptide, also obtained by haemoglobin hydrolysis with pepsin and characterised as a hydrophobic bioactive peptide [7]. The fraction eluted at 31 min was composed of two major compounds (1422.138 and 1733.23 Da). These peptides correspond to other peptides without known biological activity.
\nFinally, using standard concentration curve (R2 = 0.98) prepared with a pure standard of LVV-h7 (GeneCust, 91%), the quantity of pure LVV-h7 extracted from bovine haemoglobin hydrolysate was 6.12 ± 0.34 μg mL−1. With an initial concentration of LVV-h7 calculated at 16.12 ± 0.85 μg mL−1 in the hydrolysate, performance of our system is around 38% of peptide extracted with only one cycle of extraction.
\nTable 1 resumes the total area of peptides extracted and particularly for LVV-h7 depending on the flow rate and thus on the residence time of hydrolysate in the microsystem. The area of peptides extracted from peptidic hydrolysate increases with the decreasing of flow rate used, confirming the influence of the time of contact between both phases in the capillary. A relative high time of contact between peptidic hydrolysate and octan-1-ol favours the diffusion of peptides to the solvent phase. However, even if the quantity of LVV-h7 obtained between 10 and 20 μL min−1 was relatively proportional (×1.5), this difference was less marked for flow rates used up to 20 μL min−1.
\nFlow rate (μL min−1) | \nTime of contact (s) | \nTotal area of peptides (μV/*s) | \nLVV-h7 area (μV/*s) | \nTotal % of LVV-h71 | \n
---|---|---|---|---|
10 | \n2.65 | \n10,793,556 | \n6,292,478 | \n58 | \n
20 | \n1.32 | \n6,976,911 | \n4,064,156 | \n58 | \n
40 | \n0.66 | \n6,316,966 | \n3,599,507 | \n57 | \n
100 | \n0.26 | \n5,921,488 | \n3,181,856 | \n54 | \n
Proportion of LVV-h7 in total area of peptides after extraction process.
Total % LVV-h7 = (area of LVV-h7/total area) × 100)
Using the same process than in the first extraction (from peptidic hydrolysate to octan-1-ol), the octan-1-ol phase containing peptides was injected in co-flow with acidic aqueous phase in order to transfer these peptides from organic to receiving aqueous phase. Different flow rates were used to evaluate the impact of contact time between the two phases during the DES extraction process.
\nChromatograms (Figure 7) show clearly a transfer of peptides from the organic phase to the aqueous phase by liquid-liquid DES extraction in the microfluidic conditions. The three major fractions corresponding to the peptides previously described and mainly present in the initial octan-1-ol phase were found in the receiving aqueous phase. Moreover, a small proportion of these peptides were still present in octan-1-ol after the DES extraction step. Figure 8 illustrates the concentration of LVV-h7 in octan-1-ol and the receiving aqueous phase after the DES extraction for different flow rates.
\nRP-HPLC chromatograms of octan-1-ol phase before DES extraction of peptides (a) water phase, (b) and octan-1-ol phase (c) obtained after DES extraction in microfluidic system for a flow rate of 20 μL min−1.
Proportion of LVV-h7 (μg mL−1) in each phase after the DES extraction step in the microfluidic system for different flow rates.
The LVV-h7 concentration in the aqueous phase increases with the decrease of flow rate, indicating the influence of contact time between the two phases on the peptide diffusion. For 10 μL min−1, more than 82% of the initial concentration of LVV-h7 phase was transferred in the aqueous phase. The calculation of LVV-h7 proportion in the aqueous phase compared to the total quantity of peptides extracted was 50 ± 1%. LVV-h7 fraction was analysed by MALDI mass spectroscopy to verify its purity (result not shown). Mass analysis reveals the purity of the LVV-h7 fraction to recover from organic phase to the receiving aqueous phase using microfluidic system. Both fractions (27 and 31 min) were also analysed by mass spectroscopy. It confirmed the same composition than obtained during the extraction step that is, a pure VV-h7 peptide for 27 min of elution time and other peptides for 31 min. Thus, the DES extraction step of peptides from octan-1-ol phase to an acidic aqueous phase using microfluidic system was validated with a good efficiency (more than 82% of transfer yield).
\nIn the optimal conditions previously determined, a continuous integrated process was tested. The microfluidic system, phases and matter flows are presented in Figure 1. The experiment was conducted following the same approach than those in Figure 3 but with a feed aqueous phase formed by a haemoglobin solution, previously prepared under denaturing conditions at pH 3.0 (see part 3.1, haemoglobin final concentration of 1%, p/v), and a solution of pepsin with a E/S ratio of 1/11 (mol/mol). The introduction of these solutions in the microreactor (75 μm I.D. × 150 μm O.D.) was achieved by a syringe pump with a flow rate for both pepsin and haemoglobin solutions at about 4.5 μL min−1 for a capillary length of 2 m. The flow rates used correspond to the additive flow rates of both solutions, that is, initial flow rate multiplied by 2. The outlet fused silica capillary was in contact with a disodium tetraborate buffer solution (0.32 M, pH 9.0), thanks to a T-connection and a capillary (75 μm inner diameter, 10 cm length, flow rate of 5 μL min−1), that caused enzyme denaturation and thus reaction stopping. Consequently to the enzymatic reaction, the resulting peptidic hydrolysate was sent in co-flow in a T-connector with octan-1-ol solution in a new capillary (75 μm inner diameter, 10 cm length) for LVV-h7 extraction at 10 μL min−1. The two phases were collected out of the capillary in an Eppendorf. Octan-1-ol was pumped at 10 μL min−1 in a third capillary connected with acidic water for DES extraction of LVV-h7 thanks to a T-connector. Finally, the octan-1-ol phase remaining was pumped (10 μL min−1) and re-injected in the initial octan-1-ol phase for a new cycle of extraction-DES extraction. To avoid the pumping of the bad phase, an offset of 10 min was done between each extraction step to have sufficient volume of phases. For each step of the continuous process, samples were collected for identification and quantification of species (Figure 9 and Table 2).
\nRP-HPLC chromatograms obtained from each step of the continuous process in the microfluidic system. (a) Peptidic hydrolysate after 30 s of haemoglobin hydrolysis by pepsin, (b) octan-1-ol phase after the extraction, (c) water phase after the DES extraction and (d) octan-1-ol phase after the DES extraction.
Phases collected | \nLVV-h7 area (μV/*s) | \nLVV-h7 concentration (μg mL−1) | \n
---|---|---|
Octan-1-ol (extraction step) | \n6,354,896 | \n6.18 | \n
Octan-1-ol (DES extraction step) | \n1,687,646 | \n1.64 | \n
Water (DES extraction step) | \n4,982,647 | \n4.85 | \n
Concentrations of LVV-h7 in each phase during the complete process.
First, the peptidic profile obtained during the enzymatic hydrolysis step confirms the results previously obtained by Elagli et al. [24] and the presence of LVV-h7 in the reaction medium (Figure 9a). Then, extraction of the opioid peptide to octan-1-ol phase is also observed in Figure 9b, showing the good selectivity of the organic phase for the same hydrophobic peptides detected before, whose LVV-h7 (Figure 7). Finally, we observe the haemorphin in the acidic receiving aqueous phase, confirming the DES extraction step efficiency. A proportion of the peptidic fractions is also found in the octan-1-ol phase after the DES extraction, translating an incomplete transfer in the receiving aqueous phase. However, results validate the process of simultaneous enzymatic hydrolysis of haemoglobin with LVV-h7 extraction and DES extraction at the microscale level.
\nThe calculation of the different concentrations of LVV-h7 in each phase (Table 2) shows the transfer of 78% of the initial concentration of LVV-h7 from octan-1-ol to water. This result confirms the efficiency of the coupling approach of the extraction-DES extraction steps in microfluidic system after the enzymatic reaction. Moreover, after the DES extraction step, a low concentration of LVV-h7 remained in octan-1-ol phase (1.64 μg mL−1). Thus, the reuse of octan-1-ol for a new cycle of extraction allows to obtain an efficient method of peptide recovery with a minimal of organic solvent quantity. An optimisation of the process, particularly the time of contact between feed aqueous/organic phases during the extraction and receiving aqueous/organic phases during the DES extraction could certainly improve the final concentration of LVV-h7 recovered and consequently decrease peptide concentration remained in the organic phase.
\nIn this work, we have first provided the conditions of the key parameters in microfluidic systems (residence times, flow rates, and concentrations) applied for a sequential process from liquid/liquid extraction of LVV-h7, present in a very complex peptidic hydrolysate, in octan-1-ol to its DES extraction in a second acidic aqueous phase. The optimised conditions have been then applied to an unprecedented integrated process in a specifically microfluidic approach. Therein, enzymatic hydrolysis of denatured haemoglobin by pepsin in a first microfluidic system was coupled with LVV-h7 extraction in octan-1-ol. This organic phase was then put in contact with a second aqueous phase for LVV-h7 DES extraction. The microfluidic scale allowed to increase the ratio surface/volume in order to favour the transfer of hydrophobic peptide to the organic solvent. A very good selectivity of extraction of the opioid peptide is obtained, from a very complex peptidic population generated during the enzymatic hydrolysis of haemoglobin by pepsin, with more than 38% of LVV-h7 initial concentration transferred to the organic phase. The DES extraction reveals also a very good transfer of LVV-h7 from octan-1-ol to the acidic aqueous phase, with more than 80%. Thus, the simultaneous process allowed to recover until more than 6 μg mL−1 of LVV-h7 with an excellent purity measured by mass spectroscopy with only one cycle of process (2.65 s of contact for each LLE).
\nThe coupling of both extractions confirmed the feasibility of this process with a recycling of each phase to obtain a continuous process of extraction at microfluidic scale. An optimisation of the time of contact during the extraction is the key of peptide transfer between each phase and particularly for the recycling step. Currently, a study of a complete continuous process is in progress, where pepsin is immobilised in the microchannel and the outlet microcapillary is directly in contact with a solution of octan-1-ol, to avoid stopping the enzymatic reaction before extraction.
\nThis work was supported by the CPER Alibiotech project, which is financed by European Union, French State and the French Region of Hauts-de-France.
\nThe biopharma industry is facing significant challenges reflected by unsustainable research and development (R&D) costs. This challenge is seen in several ways. First, aggressive pricing pressure has led to an increase in the cost needed to bring products to market—from $1.188 billion in 2010 to a record level of $2.168 billion in 2018. A second major reason is the threat of patent expirations on numerous blockbuster drugs. As a result, biopharma companies experienced record low R&D returns in 2018—10.1% in 2010 to 1.9% in 2018, the lowest levels the industry has seen in 9 years [1].
\nIn parallel to biopharma challenges, the healthcare system is having a crisis due to the prevalence of chronic diseases and increased life expectancy, the main causes for skyrocketing healthcare costs (in US, the health share of GDP is 18% and expected to reach 19.6% by 2014) [2]. Today, 50% of the entire US population is considered chronic patients, which accounts for 85% of the overall cost of healthcare [3]. Fortunately, the majority of chronic diseases can be prevented or delayed until significantly later stages in life due to successful medical interventions.
\nToday, the healthcare industry is seeing an integration of novel genetic and digital technologies that help identify and cope with the complexity of chronic diseases and their often “silent” transition from healthy status to an active disease with a late onset of symptoms. The challenge is to move medical interventions upstream to the pre-disease state, during which symptoms are cheaper and easier to treat. Significant change must be made to the current pharma R&D model, if productivity and profitability are ever to be restored and maximized. The view today is that a complete digital transformation is what is needed to achieve these goals and deliver the next generation of scientific breakthroughs.
\nBig Data analysis based on artificial intelligence (AI) and machine learning (ML) offer opportunities to address some of these challenges expected to drive greater efficiency across the entire R&D value chain, and eventually improve the quality of the assets produced, as well as the time and cost it takes to bring them to the market. The change is already beginning to take place. In fact, most of the big pharma companies (such as Novartis, Roche, Pfizer, Merck, AstraZeneca, GlaxoSmithKline, Sanofi, Abbvie, Bristol-Myers Squibb, Johnson & Johnson, etc.) are already on the road to taking advantage of AI innovation (healthcareweekly.com, online) as it becomes a driving force in the innovation of medicine and healthcare.
\nAI is a growing industry of personalized health technology, or personalized medicine, which will have tremendous effect on healthcare management. The key idea behind the technological personalization of medicine and healthcare is to capture, analyze, and utilize individual patient characteristics, such as biomarkers, then to base medical decisions on these individual characteristics rather than on population averages. Another direct application is the technological development of assisted devices that augment traditional medical practice and healthcare, such as the broad use of robotics as well as patient-worn devices (“wearables”) that optimize care. This chapter reviews leading publications in these areas and outlines major advantages and also methodological and clinical weak points that need to be addressed in order for personalized medicine to realize its potential.
\nAdvances in technology are shifting the practice of medicine from anecdotal to data-driven. Due to this shift, improvement in screening, prediction, diagnosis, and the treatment of disease has increased the quality of medical care worldwide and cost effectively ([4]: p. 139). Personalized medicine is generally recognized as promising and advantageous in several important ways. It can improve the efficacy of medication as treatments become better matched to patients; when patients are better matched to treatments, ineffective treatments and their accompanying harmful side effects are avoided; healthcare costs are driven down as a result of better use of therapies; diseases are detected sooner or even anticipated so care is shifted from detection to prevention, thereby avoiding late-care, less effective, and more costly treatment; disease management is more effective through wearable patient technology; and clinical trials can be more accurate as patient selection becomes more precise ([5]: pp. 1-2).
\nDespite these apparent advantages, the technological personalization of medicine brings numerous challenges that must be addressed in order to harness its full potential. When healthcare and medical technologies first enter the marketplace, for example, they are often initially more expensive, as the companies that develop these products need to recoup high expenses from R&D. As a result, personalized health technologies are utilized first by the more affluent, driving an even larger wedge between affluent populations and marginalized ones. This serves to broaden the already wide socioeconomic gap in health inequalities in the short term ([5]: p. 2).
\nSolutions must be found to provide for diverse socioeconomic patient access to personalized medicine, so that its benefits reach all populations. This is especially important as marginalized and disadvantaged populations are precisely the ones least likely to access and utilize these products, but typically the very populations that would disproportionally benefit from them. Early disease diagnosis and management provided by advances in personalized medicine are especially needed in these populations and innovating for these populations is crucial in order for personalized health technology to reach its public health potential. For this, creative, strategic health initiatives must be developed that aim to lower costs while expanding access ([6]: pp. 2–4).
\nThe challenge in personalized medicine is methodological and inherent in cross-industry innovation itself—the ways in which different technologies are utilized for healthcare and medicine. While machine learning techniques can process complex and large data and provide accurate predictions based on this analysis, they are unable to provide a deeper understanding of phenomena ([6]: p. 5). In this way, Data Science and AI do not replace classical research. As a result, there remains a gap between the potential of personalized medicine and its realized application borne out as solutions that impact clinical practice.
\nOne foreseeable way to bridge this gap is to push for a better coordinated interdisciplinary effort. Scientists, physicians, patients and their advocates, regulatory agencies, and health insurance providers need to create a healthcare system that can learn and adapt as it develops ([6]: p. 12). In short, technology is not meant to replace physicians. Rather, the idea is to provide physicians with a tool that supports their decisions based on the accurate processing, understanding, and analysis of large amounts of already available biomedical data ([6]: p. 13).
\nAnother way to understand this difficulty is that personalized medicine is “underpinned” by convergent, cross-industry innovation. This naturally results in complexity, and uncertainty in terms of organization ([7]: p. 44). The question becomes how best to innovate given this challenge of cross-industry integration.
\nThe two dominant forms of organizational learning aim for simplification and specialization. This is especially so in the context of uncertainty and complex integration issues that arise from innovation in an emerging cross-industry ecosystem. However, new research suggests a need to face this complexity via an adaption of a multitude of approaches, recognizing that uncertainty and risk are part and parcel of the very nature of innovation.
\nIn this context, the management of risk might best be replaced with addressing uncertainty, understanding that in an emerging ecosystem of convergent innovation, comprehensive understanding is lacking. Approaches that embrace complexity rather than just managing it might prove more effective, specifically by adopting numerous measures to address the divergent factors in cross-industry innovation ([7]: pp. 51–52).
\nAs a case in point, consider the impact of AI in cardiology and cardiac imaging. Machine learning and the “deep” neural networks used for this purpose hold great promise when applied to medical imaging. Improving the identification accuracy in patients at risk for cardiovascular events is critical, as well as patients who are not at risk but suffer from misdiagnosis and are given unnecessary and sometimes harmful treatments with negative side effects. The importance of improving the accuracy in detection and diagnosis is thus monumental given that cardiovascular disease is leading cause of death worldwide ([4]: p. 139).
\nThe use of AI in cardiology has increased dramatically in the past 5 years. Machine learning algorithms now outperform many traditional algorithms, including the established risk prediction algorithm used by the American College of Cardiology (ACC)/American Heart Association (AHA), performing with a 3.6% predictive accuracy improvement over the ACC/AHA algorithm ([4]: p. 139).
\nStill major challenges lie ahead. Before AI can reliably be utilized by any field of medicine let alone realize its potential for cardiac patients, the neural networks necessary for its application require constant and extremely time-consuming expansion and revision. Key difficulties are (i) the extremely large amount of training data required by neural networks; (ii) the need to annotate (label) any dataset used for the training of a neural network; (iii) creating an understating of what computers learn given that the patterns and knowledge gained by a network are contained in the weights of the nodes of the network; and (iv) the risk of “overfitting” the training data when designing and training a neural network.
\nIn other words, better efficiency of machine learning, together with improved accuracy with less training and data necessary, are all needed in order to approximate the efficiency of human learning and bring its relevance to a clinical setting.
\nGiven these challenges, AI in cardiac CT angiography has made tremendous gains in the past 10 years, and over the next 10 years, the expectation is that we will see more AI software development and use in cardiac imaging than in the past 50 years ([4]: p. 139).
\nA recent study revealed that one in every 71 cases from 6000 tissue samples of cancer patients across the US was misdiagnosed and up to one in five were misclassified. This same study reviewed 25 years of US malpractice claims and concluded that diagnostic errors were the cause of the most severe patient harm. According to the National Academies’ Institute of Medicine, 10% of patient deaths and as much as 17% of hospital complications are a result of diagnostic errors ([8]: p. 1).
\nWhat is more, it was not primarily the physicians who were the cause of most diagnostic errors. Instead, the study found, the fault lies primarily in substandard collaboration and synthesis of information in the healthcare system as well as communication gaps, and that the healthcare system as a whole failed to effectively support the diagnostic process ([8]: p. 1).
\nNow let us consider the application of AI to address the need for collaboration and integration in healthcare to improve the diagnostic process. Optum, a leading company providing these solutions for the healthcare industry, developed a program called Care Coordination Platform. It processes vast amounts of data and provides a comprehensive overview of every patient’s full medical history, allowing healthcare providers an immediate, complete picture of each patient. The platform suggests the most appropriate and cost-effective treatment options; identifies high-risk patients before symptoms occur; and has adaptive algorithms that incorporate clinical data, claims, and socioeconomic figures ([8]: p. 2).
\nA recent study examined the effects of clinical decision-support systems (CDSSs) on practitioner performance and patient outcomes. Clinical decision-support tools made available to practitioners and patients, such as computer-generated clinical knowledge and patient-related information, were studied. When such data are filtered and made available at appropriate times, it was shown to enhance patient care. CDSS can also send reminders, warnings, test results, check for drug interactions, dosage errors, contraindications, and list patients eligible for specific interventions such as immunizations and follow-ups [9].
\nThe study found that CDSSs that require large amounts of data entry adversely affect physician satisfaction and use of the system. When large amounts of data required for the CDSS to be effective are incomplete, diagnoses will be less accurate, or it will take longer to complete the data, resulting in delays in the CDSS to accurately deliver advice. Anticoagulant-prescribing CDSSs are a case in point; the data required are more complex and have a higher patient variance.
\nCDSSs requiring limited number of patient data items for input were the most used and clinically successful. Examples include preventative care reminder systems for routine tasks such as blood pressure tests, pap smears, vaccinations, etc.
\nThe study concluded that CDSSs become more effective as they become more specified and sensitive in their levels of advice but at the same time the manual input of data needs to be minimized, and the CDSS advice needs to be available in a timely manner to be of relevance for physician use.
\nPersonalized medicine is making an impact in advanced genetic technologies as well. Genome modulation (modifications), in particular, has an array of applications, from energy, food, and industrial to medical. Researchers are turning to genome modulation with the hope that it will provide the key to understanding and answering some of life’s most difficult and challenging questions.
\nGenome modulation applied medically has been known as gene therapy, but with new technologies, has evolved into the science of gene editing. At the forefront of this technology is what is now known as Clustered Regularly Interspaced Short Palindromic Repeats, or CRISPR. Experts claim CRISPR has brought with it new streams of business based on its cutting-edge technologies [10].
\nOne recent example of CRISPR technology application is the correction of blood clotting problems in newborn and adult mice, with marked success. The aim is to cure the majority of patients with hemophilia B with CRISPR-based gene targeting [10].
\nGrowing interest in CRISPR technology is speeding its transition to research, clinical trials, and applications in humans, and it was recently tested on a human being for the first time. In China, a patient diagnosed with terminal lung cancer was treated with CRISPR gene editing therapy as part of a clinical trial. Meanwhile, clinical trials in the United States using CRISPR technology are underway.
\nCRISPR technology has opened channels for business, but there are still many daunting challenges before its application can be realized clinically. One such hurdle, if not the most significant one, is regulation. Personalized medicine, including gene editing technologies, is involved in a regulatory business, involving peer-reviewed, published papers and clinical trials. Even in cooperation with the FDA, for example, it could still take a new technology 20 years to be approved.
\nAnother way in which personalized medicine is driven by advancements in technology is in healthcare robotics. The introduction of robotics in healthcare is driven by the desire to improve quality, safety, and control expenditure. Surgical robots, service robots, companion robots, cognitive therapy robots, robotic limbs and exoskeletons, humanoids, and rehabilitation robots are just a few applied areas already making use of this technology.
\nDespite clear advantages and a promising, growing future of robotics in healthcare and in medical devices, there is a need for a robotics strategy that addresses concerns and challenges. Patient and cultural perceptions, liability rules, and ethical debates present challenges to the integration and development of robotics in healthcare.
\nA recent study suggested that a deliberative approach is needed to find a balance between developing overarching rules in this industry and allowing innovation to flourish, and that robots and robotic devices should be viewed as “augmenting human capabilities and empowering professionals in their role” so that patients would have a more positive perception of robotics in their healthcare settings [11].
\nAnother recent study suggests that robotics lags behind its healthcare potential primarily because the industry has yet to live up to a primary principle of Cybernetics. According to this theory, robots and robotic devices should have a high level of adaptation and reaction to environments, resulting in complete interaction between humans and robots [12]. In this study, robotics-assisted surgery, rehabilitation, prosthetics, and companion systems were analyzed.
\nIn all areas, the study concluded, for one, that the real potential of robotics in these fields requires a much greater degree of customization. Customization is defined as the robotic technology’s adaptation to clinicians and patients, and the authors argue that existing robotic systems are limited in their ability for customization, which greatly limits its practical use in healthcare. The idea is that technology should adapt to users, rather than forcing users to adapt to technology.
\nDespite implicit or even explicit claims of the superiority of robotic systems for healthcare, when compared to more traditional methods, the clear advantage of these systems is currently unproven and highly dependent on the skills of the users. Therefore, the success of such technologies is still heavily dependent on adequate training and experience.
\nAs our last example in this chapter of the impact of technology in medicine, consider the “3D” printing (3DP) of oral drugs. While it may sound novel and revolutionary, drug manufacturing using 3DP technology is actually a combination of well-established technologies first developed to meet the needs of engineering prototypes [13], namely building objects by creating sequentially added layers.
\nThere are a few driving forces behind the 3DP of oral drugs: personalization, on-demand capability, and the ability to manufacture drugs in new, decentralized locations. A recent study suggests that the key to the success of utilizing 3DP technology for healthcare and medicine is to maximize patient benefits while providing production efficiency, and that 3DP has a proven track record. As such, they argue, its future is clearly viable in three fields, namely preclinical, within a pharmaceutics framework; innovative drug delivery concepts; and decentralizing the drug manufacturing process [13].
\nAlthough this technology is currently niche and not an alternative to mainstream mass production processes, there is a clear place for 3DP in healthcare and medicine and its role will be more clearly defined in the future by incorporating considerations such as ideal population product profile, drug formulation, and engineering, as well as the management of regulatory and supply chain factors [13].
\nDue to the technological advances described above along with the growing need for smarter, preventive, more accurate, and effective medicine, the healthcare industry is advancing into the digital age—the digital health revolution. The digital health revolution is made possible by advances in medical information technologies—information storage, data analysis, mobile, sensors, and genetic information. All this will enable the capture and analysis of vast amounts of information about patients, populations, environments, and the lifestyle in which they live, and thus adapt personalized treatment accordingly.
\nThe technological advances facilitating personalized medicine enable the capture of major challenges of the health system and chronic diseases [3]. The reason that chronic diseases are the major financial burden on the healthcare system is because most chronic disorders develop outside healthcare settings, and patients with these conditions require continuous interventions to make behavioral and lifestyles changes needed to effectively manage the disease.
\nThe challenge with chronic diseases is the transition from health to disease with late-onset symptoms that can be irreversible. Coincidentally, the majority of chronic diseases can be prevented or delayed in life through interventions as described above, which results in an extended health span (the duration of individual life spent in a state of wellness, free of disease). Current chronic disease management is characterized by fragmented interventions and communication and recommendations from specialists, becoming constitutive only following the onset of disease symptoms. At the stage where an individual is free of symptoms, preventive activities management is done mostly by individuals themselves.
\nDue to the growing evidence that links patients’ activation, defined as the patients’ willingness and ability to take independent actions to manage their health and care, to their health and cost outcomes, methods and tools need to be developed to increase patient activation and engagement to accelerate the needed behavior change.
\nEncompassing both the design thinking approach and behavioral economics can motivate people to change their current behavioral health-related habits to improve their health. This underscores the need to devise a personalized, preventive medical infrastructure with recommendations and motivation mechanisms taken from behavioral economics.
\nBehavioral economics aims at realizing the human irrational decision process underpinning suboptimal outcomes, which in our context translates to unhealthy behavior patterns. In recent years, government agencies around the world have been employing behavioral economics models and methods as complementing means to standard public-policy tools that are implemented by decision-makers. These measures, based on the “Nudge” theory [14], are used for preventing policy-implementation failures and positively impacting motivation and decision-making by individuals and groups. Thus far, this theory has inspired a variety of applications in areas such as education, health, safety and environment. Extensive applied research, performed in the UK by the Department for Environment, Food & Rural Affairs [15], has outlined nine principles influencing human behavior, based on research in social psychology and behavioral economics.
\nIntegrating elements from persuasive technologies for supporting extrinsic motivation factors stemming from communication and social aspects, such as incentives and norms, will have a great impact on the implantation and engagement of the patient. These technologies provide effective means for supporting the operationalization of “Nudge” theory, for example by producing email messages for raising awareness regarding fulfillment of required assignments, delivering informative messages related to the performance of these assignments, and promoting a climate that reflects social norms within online social networks. Studies have shown that nudging could also incorporate various approaches that focus on changing physical or social environments to increase the likelihood of certain behaviors. This could include the provision of social norm feedback, which will increase the likelihood of healthy behaviors, altering the defaults surrounding how food and drinks are served, or even changing the layout of buildings to encourage physical activity ([16]: p. 263). Nudging focuses on a set of simple and low-cost remedies that may not require any legislation and can be used to solve most of the problems emanating from human contact. On the other hand, nudging could also enhance behaviors that may worsen the health of individuals ([16]: p. 264). For instance, food products may be labeled as healthy, hence causing consumers to ignore the energy content, which may lead to excessive consumption of such products.
\nThe value of technologies that increase patient activation and engagement is paramount due to the increasing incidence of chronic diseases. Therefore, developing “patient-centered” technologies will increase adoption and diffusion of these technologies.
\n"Open access contributes to scientific excellence and integrity. It opens up research results to wider analysis. It allows research results to be reused for new discoveries. And it enables the multi-disciplinary research that is needed to solve global 21st century problems. Open access connects science with society. It allows the public to engage with research. To go behind the headlines. And look at the scientific evidence. And it enables policy makers to draw on innovative solutions to societal challenges".
\n\nCarlos Moedas, the European Commissioner for Research Science and Innovation at the STM Annual Frankfurt Conference, October 2016.
",metaTitle:"About Open Access",metaDescription:"Open access contributes to scientific excellence and integrity. It opens up research results to wider analysis. It allows research results to be reused for new discoveries. And it enables the multi-disciplinary research that is needed to solve global 21st century problems. Open access connects science with society. It allows the public to engage with research. To go behind the headlines. And look at the scientific evidence. And it enables policy makers to draw on innovative solutions to societal challenges.\n\nCarlos Moedas, the European Commissioner for Research Science and Innovation at the STM Annual Frankfurt Conference, October 2016.",metaKeywords:null,canonicalURL:"about-open-access",contentRaw:'[{"type":"htmlEditorComponent","content":"The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
\\n\\nIntechOpen’s co-founders, both scientists themselves, created the company while undertaking research in robotics at Vienna University. Their goal was to spread research freely “for scientists, by scientists’ to the rest of the world via the Open Access publishing model. The company soon became a signatory of the Budapest Initiative, which currently has more than 1000 supporting organizations worldwide, ranging from universities to funders.
\\n\\nAt IntechOpen today, we are still as committed to working with organizations and people who care about scientific discovery, to putting the academic needs of the scientific community first, and to providing an Open Access environment where scientists can maximize their contribution to scientific advancement. By opening up access to the world’s scientific research articles and book chapters, we aim to facilitate greater opportunity for collaboration, scientific discovery and progress. We subscribe wholeheartedly to the Open Access definition:
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The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
\n\nIntechOpen’s co-founders, both scientists themselves, created the company while undertaking research in robotics at Vienna University. Their goal was to spread research freely “for scientists, by scientists’ to the rest of the world via the Open Access publishing model. The company soon became a signatory of the Budapest Initiative, which currently has more than 1000 supporting organizations worldwide, ranging from universities to funders.
\n\nAt IntechOpen today, we are still as committed to working with organizations and people who care about scientific discovery, to putting the academic needs of the scientific community first, and to providing an Open Access environment where scientists can maximize their contribution to scientific advancement. By opening up access to the world’s scientific research articles and book chapters, we aim to facilitate greater opportunity for collaboration, scientific discovery and progress. We subscribe wholeheartedly to the Open Access definition:
\n\n“By “open access” to [peer-reviewed research literature], we mean its free availability on the public internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, crawl them for indexing, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than those inseparable from gaining access to the internet itself. The only constraint on reproduction and distribution, and the only role for copyright in this domain, should be to give authors control over the integrity of their work and the right to be properly acknowledged and cited” (reference: http://www.budapestopenaccessinitiative.org)
\n\nOAI-PMH
\n\nAs a firm believer in the wider dissemination of knowledge, IntechOpen supports the Open Access Initiative Protocol for Metadata Harvesting (OAI-PMH Version 2.0). Read more
\n\nLicense
\n\nBook chapters published in edited volumes are distributed under the Creative Commons Attribution 3.0 Unported License (CC BY 3.0). IntechOpen upholds a very flexible Copyright Policy. There is no copyright transfer to the publisher and Authors retain exclusive copyright to their work. All Monographs/Compacts are distributed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). Read more
\n\nPeer Review Policies
\n\nAll scientific works are Peer Reviewed prior to publishing. Read more
\n\nOA Publishing Fees
\n\nThe Open Access publishing model employed by IntechOpen eliminates subscription charges and pay-per-view fees, enabling readers to access research at no cost. In order to sustain operations and keep our publications freely accessible we levy an Open Access Publishing Fee for manuscripts, which helps us cover the costs of editorial work and the production of books. Read more
\n\nDigital Archiving Policy
\n\nIntechOpen is committed to ensuring the long-term preservation and the availability of all scholarly research we publish. We employ a variety of means to enable us to deliver on our commitments to the scientific community. Apart from preservation by the Croatian National Library (for publications prior to April 18, 2018) and the British Library (for publications after April 18, 2018), our entire catalogue is preserved in the CLOCKSS archive.
\n\nOpen Science is transparent and accessible knowledge that is shared and developed through collaborative networks.
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\n\nOpen Science refers to doing traditional science with more transparency involved at various stages, for example by openly sharing code and data. It implies a growing set of practices - within different disciplines - aiming at:
\n\nWe aim at improving the quality and availability of scholarly communication by promoting and practicing:
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After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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The literature source was Web of Science and SSCI, SCI-EXPANDED, A&HCI, CPCI-S, CPCI-SSH, and ESCI indexes. Fifty-two articles were reviewed; however, 14 of them were not been included in the study. As a result, 38 articles were examined. Level of education, field of education, and material types of AR used in education and reported educational advantages of AR have been investigated. All articles are categorized according to target groups, which are early childhood education, primary education, secondary education, high school education, graduate education, and others. AR technology has been mostly carried out in primary and graduate education. “Science education” is the most explored field of education. Mobile applications and marker-based materials on paper have been mostly preferred. The major advantages indicated in the articles are “Learning/Academic Achievement,” “Motivation,” and “Attitude”.",book:{id:"6543",slug:"state-of-the-art-virtual-reality-and-augmented-reality-knowhow",title:"State of the Art Virtual Reality and Augmented Reality Knowhow",fullTitle:"State of the Art Virtual Reality and Augmented Reality Knowhow"},signatures:"Rabia M. Yilmaz",authors:[{id:"225838",title:"Dr.",name:"Rabia",middleName:null,surname:"Yilmaz",slug:"rabia-yilmaz",fullName:"Rabia Yilmaz"}]},{id:"59468",doi:"10.5772/intechopen.74344",title:"Virtual and Augmented Reality: New Frontiers for Clinical Psychology",slug:"virtual-and-augmented-reality-new-frontiers-for-clinical-psychology",totalDownloads:2315,totalCrossrefCites:13,totalDimensionsCites:21,abstract:"In the last decades, the applied approach for the use of virtual reality (VR) and augmented reality (AR) on clinical and health psychology has grown exponentially. These technologies have been used to treat several mental disorders, for example, phobias, stress-related disorders, depression, eating disorders, and chronic pain. The importance of VR/AR for the mental health field comes from three main concepts: (1) VR/AR as an imaginal technology, people can feel “as if they are” in a reality that does not exist in external world; (2) VR/AR as an embodied technology, the experience to feel user’s body inside the virtual environment; and (3) VR/AR as connectivity technology, the “end of geography’. In this chapter, we explore the opportunities provided by VR/AR as technologies to improve people’s quality of life and to discuss new frontiers for their application in mental health and psychological well-being promotion.",book:{id:"6543",slug:"state-of-the-art-virtual-reality-and-augmented-reality-knowhow",title:"State of the Art Virtual Reality and Augmented Reality Knowhow",fullTitle:"State of the Art Virtual Reality and Augmented Reality Knowhow"},signatures:"Sara Ventura, Rosa M. 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Cooperative learning is the foundation on which many of the active learning procedures are based. Cooperative learning is the instructional use of small groups so that students work together to maximize their own and each other’s learning. Most of the active learning procedures, such as problem-based learning, team-learning, collaborative learning, and PALS, require that students work cooperatively in small groups to achieve joint learning goals. Cooperative learning is based on two theories: Structure-Process-Outcome theory and Social Interdependence theory. Four types of cooperative learning have been derived: formal cooperative learning, informal cooperative learning, cooperative base groups, and constructive controversy. There is considerable research confirming the effectiveness of cooperative learning. To be cooperative, however, five basic elements must be structured into the situation: positive interdependence, individual accountability, promotive interaction, social skills, and group processing.",book:{id:"6929",slug:"active-learning-beyond-the-future",title:"Active Learning",fullTitle:"Active Learning - Beyond the Future"},signatures:"David W. Johnson and Roger T. 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Currently, you can hear a lot of criticism that the classroom has not changed significantly compared to the last century or even like two centuries ago. Do the teachers succeed in modern changes? The purpose of the chapter is to summarize the current changes in didactics for the use of innovative teaching methods and study the understanding of changes by teachers. In this chapter, we consider four areas: the expansion of the subject of pedagogy, environmental approach to teaching, the digital generation and the changes taking place, and innovation in teaching. The theory of education, figuratively speaking, has two levels. At the macro-level, in the “education-society” relationship, decentralization and diversification, internationalization of education, and the introduction of digital technologies occur. At the micro-level in the “teacher-learner” relationship, there is an active mix of traditional and innovative methods, combination of an activity approach with an energy-informational environment approach, cognition with constructivism and connectivism.",book:{id:"5980",slug:"new-pedagogical-challenges-in-the-21st-century-contributions-of-research-in-education",title:"New Pedagogical Challenges in the 21st Century",fullTitle:"New Pedagogical Challenges in the 21st Century - Contributions of Research in Education"},signatures:"Aigerim Mynbayeva, Zukhra Sadvakassova and Bakhytkul\nAkshalova",authors:[{id:"201997",title:"Dr.",name:"Aigerim",middleName:null,surname:"Mynbayeva",slug:"aigerim-mynbayeva",fullName:"Aigerim Mynbayeva"},{id:"209208",title:"Dr.",name:"Zukhra",middleName:null,surname:"Sadvakassova",slug:"zukhra-sadvakassova",fullName:"Zukhra Sadvakassova"},{id:"209210",title:"Dr.",name:"Bakhytkul",middleName:null,surname:"Akshalova",slug:"bakhytkul-akshalova",fullName:"Bakhytkul Akshalova"}]},{id:"64583",doi:"10.5772/intechopen.81714",title:"Evaluating a Course for Teaching Advanced Programming Concepts with Scratch to Preservice Kindergarten Teachers: A Case Study in Greece",slug:"evaluating-a-course-for-teaching-advanced-programming-concepts-with-scratch-to-preservice-kindergart",totalDownloads:1388,totalCrossrefCites:13,totalDimensionsCites:17,abstract:"Coding is a new literacy for the twenty-first century, and as a literacy, coding enables new ways of thinking and new ways of communicating and expressing ideas, as well as new ways of civic participation. A growing number of countries, in Europe and beyond, have established clear policies and frameworks for introducing computational thinking (CT) and computer programming to young children. In this chapter, we discuss a game-based approach to coding education for preservice kindergarten teachers using Scratch. The aim of using Scratch was to excite students’ interest and familiarize them with the basics of programming in an open-ended, project-based, and personally meaningful environment for a semester course in the Department of Preschool Education in the University of Crete. For 13 weeks, students were introduced to the main Scratch concepts and, afterward, were asked to prepare their projects. For the projects, they were required to design their own interactive stories to teach certain concepts about mathematics or physical science to preschool-age students. The results we obtained were more satisfactory than expected and, in some regards, encouraging if one considers the fact that the research participants had no prior experiences with computational thinking.",book:{id:"6936",slug:"early-childhood-education",title:"Early Childhood Education",fullTitle:"Early Childhood Education"},signatures:"Stamatios Papadakis and Michail Kalogiannakis",authors:null}],mostDownloadedChaptersLast30Days:[{id:"58060",title:"Pedagogy of the Twenty-First Century: Innovative Teaching Methods",slug:"pedagogy-of-the-twenty-first-century-innovative-teaching-methods",totalDownloads:8685,totalCrossrefCites:13,totalDimensionsCites:17,abstract:"In the twenty-first century, significant changes are occurring related to new scientific discoveries, informatization, globalization, the development of astronautics, robotics, and artificial intelligence. This century is called the age of digital technologies and knowledge. How is the school changing in the new century? How does learning theory change? Currently, you can hear a lot of criticism that the classroom has not changed significantly compared to the last century or even like two centuries ago. Do the teachers succeed in modern changes? The purpose of the chapter is to summarize the current changes in didactics for the use of innovative teaching methods and study the understanding of changes by teachers. In this chapter, we consider four areas: the expansion of the subject of pedagogy, environmental approach to teaching, the digital generation and the changes taking place, and innovation in teaching. The theory of education, figuratively speaking, has two levels. At the macro-level, in the “education-society” relationship, decentralization and diversification, internationalization of education, and the introduction of digital technologies occur. At the micro-level in the “teacher-learner” relationship, there is an active mix of traditional and innovative methods, combination of an activity approach with an energy-informational environment approach, cognition with constructivism and connectivism.",book:{id:"5980",slug:"new-pedagogical-challenges-in-the-21st-century-contributions-of-research-in-education",title:"New Pedagogical Challenges in the 21st Century",fullTitle:"New Pedagogical Challenges in the 21st Century - Contributions of Research in Education"},signatures:"Aigerim Mynbayeva, Zukhra Sadvakassova and Bakhytkul\nAkshalova",authors:[{id:"201997",title:"Dr.",name:"Aigerim",middleName:null,surname:"Mynbayeva",slug:"aigerim-mynbayeva",fullName:"Aigerim Mynbayeva"},{id:"209208",title:"Dr.",name:"Zukhra",middleName:null,surname:"Sadvakassova",slug:"zukhra-sadvakassova",fullName:"Zukhra Sadvakassova"},{id:"209210",title:"Dr.",name:"Bakhytkul",middleName:null,surname:"Akshalova",slug:"bakhytkul-akshalova",fullName:"Bakhytkul Akshalova"}]},{id:"61746",title:"Facilitation of Teachers’ Professional Development through Principals’ Instructional Supervision and Teachers’ Knowledge- Management Behaviors",slug:"facilitation-of-teachers-professional-development-through-principals-instructional-supervision-and-t",totalDownloads:3288,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"With the rise of global competition and the focus on teacher quality, teacher professional development is becoming increasingly crucial, and the stress and challenges for principals are more severe than ever. Teachers can improve their professional abilities through principals’ instructional supervision and their own knowledge-management (KM) behaviors to benefit students. Thus, this chapter analyzes the relationship among principals’ instructional supervision, teachers’ KM, and teachers’ professional development. The author believes that principals’ instructional supervision and effective KM can facilitate the professional development of teachers. The author also believes the readers can know the relationships among them, and teachers’ professional development can be improved through principal’s instructional supervision and teachers’ KM behaviors.",book:{id:"6674",slug:"contemporary-pedagogies-in-teacher-education-and-development",title:"Contemporary Pedagogies in Teacher Education and Development",fullTitle:"Contemporary Pedagogies in Teacher Education and Development"},signatures:"Chien-Chin Chen",authors:[{id:"232569",title:"Ph.D.",name:"Chien Chih",middleName:null,surname:"Chen",slug:"chien-chih-chen",fullName:"Chien Chih Chen"}]},{id:"75908",title:"From the Classroom into Virtual Learning Environments: Essential Knowledge, Competences, Skills and Pedagogical Strategies for the 21st Century Teacher Education in Kenya",slug:"from-the-classroom-into-virtual-learning-environments-essential-knowledge-competences-skills-and-ped",totalDownloads:478,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"As teachers in Kenya begin to migrate from the classroom to virtual learning spaces following COVID 19 pandemic, there is pressing need to realign Teacher Education to requisite Knowledge, competences, skills, and attitudes that will support online teaching. This chapter explores these needs using a combination of lived experiences and literature review that captured a meta-analysis of research trends on e-learning. While trends in Teacher Education indicate progression towards adoption of technology, there are disparities between the theory and practice. Evidence from recent research and reports; and the recollected experiences confirmed knowledge, competence, skills and pedagogical gaps in the implementation of online learning, that have been exacerbated by COVID-19. The researcher recommends that teacher education should sensitize and train teacher trainees on how to access, analyze and use new knowledge emerging with technology; they also should be coached on how learners learn with technology and on fundamentals of the communication process. Particularly the course on educational technology, should focus on how to create and manage online courses. The 5-stage E-Moderator Model and Universal Design for Learning (UDL) are recommended as effective pedagogical scaffold for online teaching.",book:{id:"10229",slug:"teacher-education-in-the-21st-century-emerging-skills-for-a-changing-world",title:"Teacher Education in the 21st Century",fullTitle:"Teacher Education in the 21st Century - Emerging Skills for a Changing World"},signatures:"Catherine Adhiambo Amimo",authors:[{id:"333482",title:"Dr.",name:"Catherine Adhiambo",middleName:null,surname:"Amimo",slug:"catherine-adhiambo-amimo",fullName:"Catherine Adhiambo Amimo"}]},{id:"75224",title:"Decoding the Digital Gap in Teacher Education: Three Perspectives across the Globe",slug:"decoding-the-digital-gap-in-teacher-education-three-perspectives-across-the-globe",totalDownloads:525,totalCrossrefCites:0,totalDimensionsCites:3,abstract:"Educational use of technology is regularly assessed, and results often show a gap between educational policies and what is actually practiced. This chapter will help clarify how teacher educators experience the changing educational contexts due to the digital revolution, how their meaning-making shifts, and how outside forces influence those processes. The results are based on comparative international studies. Central for this study is practitioners’ professional digital competence, their attitudes towards digital technology and the use of digital technology in education. We found that the influence and contribution of digital practice is carried out quite differently across the globe. Our research questions were: How do practitioners experience teaching in a rapidly changing context? How do attitudes change due to top-down governing of education? and What motivates teacher educators to implement digital technology?",book:{id:"10229",slug:"teacher-education-in-the-21st-century-emerging-skills-for-a-changing-world",title:"Teacher Education in the 21st Century",fullTitle:"Teacher Education in the 21st Century - Emerging Skills for a Changing World"},signatures:"Steinar Thorvaldsen and Siri Sollied Madsen",authors:[{id:"332624",title:"Associate Prof.",name:"Siri Sollied",middleName:null,surname:"Madsen",slug:"siri-sollied-madsen",fullName:"Siri Sollied Madsen"},{id:"332626",title:"Prof.",name:"Steinar",middleName:null,surname:"Thorvaldsen",slug:"steinar-thorvaldsen",fullName:"Steinar Thorvaldsen"}]},{id:"75416",title:"Self-Study Research: Challenges and Opportunities in Teacher Education",slug:"self-study-research-challenges-and-opportunities-in-teacher-education",totalDownloads:665,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"This article aims to describe what self-study research is, why self-study can be a good approach to teacher educators’ professional development and improvements in practice and highlight some challenges and opportunities in this research approach. In addition, the article will shed light on some methodological aspects related to self-study. Self-study refers to teacher educators who in an intentionally and systematically way examine their practice to improve it, based on a deeper understanding of practice, as well as the context practice takes place. In the article, I argue that engaging in self-study is a learning and development process and an approach to developing personal professionalism, collective professionalism and improvements in practice.",book:{id:"10229",slug:"teacher-education-in-the-21st-century-emerging-skills-for-a-changing-world",title:"Teacher Education in the 21st Century",fullTitle:"Teacher Education in the 21st Century - Emerging Skills for a Changing World"},signatures:"Kåre Hauge",authors:[{id:"332053",title:"Associate Prof.",name:"Kåre",middleName:null,surname:"Hauge",slug:"kare-hauge",fullName:"Kåre Hauge"}]}],onlineFirstChaptersFilter:{topicId:"265",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81018",title:"Item Analysis: Concept and Application",slug:"item-analysis-concept-and-application",totalDownloads:46,totalDimensionsCites:0,doi:"10.5772/intechopen.100138",abstract:"In the field of medical education, Item analysis is a statistical analysis of student’s responses on exam items and the relationship between them. It provides constructive feedback about items quality, increases the effectiveness of the exam, and supports exam validity and reliability. The decision of adding or removing an item should depends mainly on the result of the item analysis. The feedback of item analysis can support modification of instruction methods. This chapter provides a comprehensive review of item analysis (psychometric analysis) and also can be used as methodological guidance to perform an informative analysis. The chapter discusses item analysis under the following headings, importance of item analysis, factors affecting item analysis, parameters of item analysis and application. The parameters of item analysis includes the indices of the internal consistency, difficulty, discrimination, and distractor analysis.",book:{id:"11004",title:"Medical Education for the 21st Century",coverURL:"https://cdn.intechopen.com/books/images_new/11004.jpg"},signatures:"Assad Ali Rezigalla"},{id:"81000",title:"Technology Integration on Teaching Writing in the Foundation Phase Classrooms in the Eastern Cape Province, South Africa",slug:"technology-integration-on-teaching-writing-in-the-foundation-phase-classrooms-in-the-eastern-cape-pr",totalDownloads:17,totalDimensionsCites:0,doi:"10.5772/intechopen.103666",abstract:"Teachers play a significant role in developing writing. They are responsible for teaching the younger generations exposed to technology through various gadgets. This study aims to better integrate technology in teaching writing in the Foundation Phase (FP). The premise for this study is the need to integrate technology in the Foundation Phase in order to attain educational goals. A qualitative case study was conducted that involved semi-structured interviews and the draw and talk/write method to gain in-depth knowledge of integrating technology to develop writing skills. For this study, the cognitive theory of multimedia learning (CTML) and sociocultural theory of learning were used as a theoretical framework. The participants were four Grade 3 teachers and 12 learners from two primary schools. This study indicated the importance of integrating technology in teaching writing, which subsequently led to more positive learning experiences for the FP learners. The study’s key finding is that FP teachers are technologically illiterate. As a result, it is suggested that a set of curriculum guidelines based on the interests of this generation of learners be produced to enable teachers and students in successfully integrate teaching and technology in the FP.",book:{id:"11196",title:"New Updates in E-Learning",coverURL:"https://cdn.intechopen.com/books/images_new/11196.jpg"},signatures:"Pretty Thandiswa Mpiti and Bulelwa Makena"},{id:"79401",title:"A Conceptual Model for Conformance with Accessible Gamification",slug:"a-conceptual-model-for-conformance-with-accessible-gamification",totalDownloads:17,totalDimensionsCites:0,doi:"10.5772/intechopen.98195",abstract:"There currently remains limited Gamification awareness and training for developers on WCAG conformance. Studies indicate an increased interest from developers to raise their acceptance, awareness, and technical abilities for designing accessible digital products. This article explores and presents a conceptual module to improve web developers’ capabilities and knowledge of accessible digital design. By leveraging the standards put forth by WCAG 2.0, developers can create accessible content for users who identify with various forms of abilities. Four primary principles comprise WCAG 2.0 and 12 standards, and 12 standards deliver fundamental objectives as best practices for developers. These guidelines were employed for gaming content design and development, permitting users to regulate reality and Gamification associations whereas immersing in the game. The goal is to apply diverse processes for each stage of the game to allow challenges and motivation for users to determine novel processes while understanding the guidelines. Assistive Technology was used to navigate each stage. To suit independence or self-reliance, the conceptual model supports players’ personalization while completing the game activities. Likewise, employing complex, advanced, and reward dashboards satisfies the proficiency component, and social network communications to other players provide the opportunity for interconnectedness. The conceptual model presented in this paper underpins Gamification and the potential to incorporate evidence-based accessibility principles developed by W3C. The previous examinations focused on instruments (e.g., software, feature, components) to achieve WCAG conformance. This examination presents a distinction from prior studies as this conceptual model recognizes consciousness and self-determination as the initial starting point.",book:{id:"10858",title:"MOOC (Massive Open Online Courses)",coverURL:"https://cdn.intechopen.com/books/images_new/10858.jpg"},signatures:"Keyonda Smith"},{id:"80472",title:"Strategy as Plan for Technology Integration to Reposition Lecturers for the New Normal in Higher Education",slug:"strategy-as-plan-for-technology-integration-to-reposition-lecturers-for-the-new-normal-in-higher-edu",totalDownloads:24,totalDimensionsCites:0,doi:"10.5772/intechopen.102078",abstract:"This chapter reports on the strategy as plan using ICT policy that could impact on repositioning the lecturers for the integration of technology for the new normal in education. Global, the COVID-19 pandemic distinctly exposed the unpreparedness of lecturers to integrate technology in teaching and learning when the shutdown of the higher institutions was announced. The participants consisted of 37 lecturers from four departments in the School of Education at a university of technology in South Africa. A qualitative case study method was used. An open-ended questionnaire, individual interviews and document analysis were used to collect data. Atlas.ti was used to analyse data. The findings revealed that the study University does not have the eLearning policy to enforce technology integration. Hence the unpreparedness of lecturers to integrate was discovered during Covid-19. It is recommended the study university develops an ICT policy, involving lecturers as stakeholders to promote ownership and conformability.",book:{id:"11196",title:"New Updates in E-Learning",coverURL:"https://cdn.intechopen.com/books/images_new/11196.jpg"},signatures:"Sibongile R. Ngcapu, Sibongile Simelane-Mnisi and Andile Mji"},{id:"75120",title:"Mainstreaming Blended Learning in a Low-Income University",slug:"mainstreaming-blended-learning-in-a-low-income-university",totalDownloads:30,totalDimensionsCites:0,doi:"10.5772/intechopen.96143",abstract:"Due to the COVID-19 pandemic, Maseno University (MU) began to consider institutional shift from traditional face-to-face (F2F) instructions to online and blended modes of teaching and learning. The university was able to draw from its experience with adapted flexible and blended learning (FBL) approaches for high enrollment common courses already offered to students on the Learning Management System (LMS). Several questions have been raised: How to preserve what most lecturers consider as most essential — the regular student interaction, the freewheeling give-and-take discussion sessions — if the class cannot be together in the same physical space at the same time? How to make a synchronous activity dependent course and make it work in a completely asynchronous environment? How to handle the practical based subjects on the online platform? And even if the university is able to find acceptable answers to these questions, where would it begin? However, MU did not try to reinvent the wheel. There were already examples of good practice in a number of common courses had been running on the LMS. The available courses already had a blend of both theory and practical base. The university sought assistance from schools and departments that already had parts of their programmes running on the LMS. They were able to tap into their expertise and get introduced to a valuable collection of resources about online distance teaching and learning (ODTL). That, in turn, assisted the university to develop online or blended versions of its regular F2F courses that far surpassed expectations, judging from how well their courses performed, and get ready for any other unexpected circumstance equal or similar to which the world has had to live through the COVID-19 pandemic.",book:{id:"9974",title:"E-Learning and Digital Education in the Twenty-First Century",coverURL:"https://cdn.intechopen.com/books/images_new/9974.jpg"},signatures:"Mildred Atieno Ayere"},{id:"78235",title:"Clinical Curriculum Revolution to Integrity and “Attunity”",slug:"clinical-curriculum-revolution-to-integrity-and-attunity",totalDownloads:34,totalDimensionsCites:0,doi:"10.5772/intechopen.99460",abstract:"Reviewing the history of clinical educational curricula reveals enormous change and progress through successive antiquity up-to the current 21th century. Surely, there are stable fundamental criteria which are pillars in designing any curriculum; however there are torrential inevitable reforms which are important in filling the changeable gaps and fulfilling the ecological and temporal aspects. Over the last 20th century, numerous new paradigms for curricula reforms were constructed to adapt ebullient millennium needs, interactive pedagogical approaches and psychological/sociological learning theories. These reforms fostered clinical practice, integrating core competencies and reflection on designing, and achieving clinical curricula depending on outcome-based models such as clinical competences milestones. On the other hand, systematic approach of Kern′s framework adopts curriculum development through six consecutive interlinked and intersected steps which are refined to eight steps later. Moreover, taking contextual factors into account during curricula planning was evolved in other models such as PRISMS model. Despite all these pearly efforts, there are still caveats about inclusive gaps negligence between education process and overall health system. 3P-6Cs toolkit is deemed a recent novel paradigm that enrolls this role of health systems in clinical training during curricula design.",book:{id:"11004",title:"Medical Education for the 21st Century",coverURL:"https://cdn.intechopen.com/books/images_new/11004.jpg"},signatures:"Samhaa Abd Elmoneim"}],onlineFirstChaptersTotal:49},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:8,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:286,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:106,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:9,numberOfPublishedChapters:101,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:11,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"13",title:"Veterinary Medicine and Science",doi:"10.5772/intechopen.73681",issn:"2632-0517",scope:"Paralleling similar advances in the medical field, astounding advances occurred in Veterinary Medicine and Science in recent decades. These advances have helped foster better support for animal health, more humane animal production, and a better understanding of the physiology of endangered species to improve the assisted reproductive technologies or the pathogenesis of certain diseases, where animals can be used as models for human diseases (like cancer, degenerative diseases or fertility), and even as a guarantee of public health. Bridging Human, Animal, and Environmental health, the holistic and integrative “One Health” concept intimately associates the developments within those fields, projecting its advancements into practice. This book series aims to tackle various animal-related medicine and sciences fields, providing thematic volumes consisting of high-quality significant research directed to researchers and postgraduates. It aims to give us a glimpse into the new accomplishments in the Veterinary Medicine and Science field. By addressing hot topics in veterinary sciences, we aim to gather authoritative texts within each issue of this series, providing in-depth overviews and analysis for graduates, academics, and practitioners and foreseeing a deeper understanding of the subject. Forthcoming texts, written and edited by experienced researchers from both industry and academia, will also discuss scientific challenges faced today in Veterinary Medicine and Science. In brief, we hope that books in this series will provide accessible references for those interested or working in this field and encourage learning in a range of different topics.",coverUrl:"https://cdn.intechopen.com/series/covers/13.jpg",latestPublicationDate:"May 14th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:9,editor:{id:"38652",title:"Dr.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",institutionURL:null,country:{name:"Portugal"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"19",title:"Animal Science",coverUrl:"https://cdn.intechopen.com/series_topics/covers/19.jpg",isOpenForSubmission:!0,annualVolume:11415,editor:{id:"259298",title:"Dr.",name:"Edward",middleName:null,surname:"Narayan",slug:"edward-narayan",fullName:"Edward Narayan",profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",biography:"Dr. Edward Narayan graduated with Ph.D. degree in Biology from the University of the South Pacific and pioneered non-invasive reproductive and stress endocrinology tools for amphibians - the novel development and validation of non-invasive enzyme immunoassays for the evaluation of reproductive hormonal cycle and stress hormone responses to environmental stressors. \nDr. Narayan leads the Stress Lab (Comparative Physiology and Endocrinology) at the University of Queensland. A dynamic career research platform which is based on the thematic areas of comparative vertebrate physiology, stress endocrinology, reproductive endocrinology, animal health and welfare, and conservation biology. \nEdward has supervised 40 research students and published over 60 peer reviewed research.",institutionString:null,institution:{name:"University of Queensland",institutionURL:null,country:{name:"Australia"}}},editorTwo:null,editorThree:null},{id:"20",title:"Animal Nutrition",coverUrl:"https://cdn.intechopen.com/series_topics/covers/20.jpg",isOpenForSubmission:!0,annualVolume:11416,editor:{id:"175967",title:"Dr.",name:"Manuel",middleName:null,surname:"Gonzalez Ronquillo",slug:"manuel-gonzalez-ronquillo",fullName:"Manuel Gonzalez Ronquillo",profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",biography:"Dr. Manuel González Ronquillo obtained his doctorate degree from the University of Zaragoza, Spain, in 2001. He is a research professor at the Faculty of Veterinary Medicine and Animal Husbandry, Autonomous University of the State of Mexico. He is also a level-2 researcher. He received a Fulbright-Garcia Robles fellowship for a postdoctoral stay at the US Dairy Forage Research Center, Madison, Wisconsin, USA in 2008–2009. He received grants from Alianza del Pacifico for a stay at the University of Magallanes, Chile, in 2014, and from Consejo Nacional de Ciencia y Tecnología (CONACyT) to work in the Food and Agriculture Organization’s Animal Production and Health Division (AGA), Rome, Italy, in 2014–2015. He has collaborated with researchers from different countries and published ninety-eight journal articles. He teaches various degree courses in zootechnics, sheep production, and agricultural sciences and natural resources.\n\nDr. Ronquillo’s research focuses on the evaluation of sustainable animal diets (StAnD), using native resources of the region, decreasing carbon footprint, and applying meta-analysis and mathematical models for a better understanding of animal production.",institutionString:null,institution:{name:"Universidad Autónoma del Estado de México",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null},{id:"28",title:"Animal Reproductive Biology and Technology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/28.jpg",isOpenForSubmission:!0,annualVolume:11417,editor:{id:"177225",title:"Prof.",name:"Rosa Maria Lino Neto",middleName:null,surname:"Pereira",slug:"rosa-maria-lino-neto-pereira",fullName:"Rosa Maria Lino Neto Pereira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9wkQAC/Profile_Picture_1624519982291",biography:"Rosa Maria Lino Neto Pereira (DVM, MsC, PhD and) is currently a researcher at the Genetic Resources and Biotechnology Unit of the National Institute of Agrarian and Veterinarian Research (INIAV, Portugal). 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