Description of genes associated with neuroplasticity and cognition. Information taken from the NCBI—Genbank platform (Supplementary table).
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"5136",leadTitle:null,fullTitle:"Recent Progress in Some Aircraft Technologies",title:"Recent Progress in Some Aircraft Technologies",subtitle:null,reviewType:"peer-reviewed",abstract:"The book describes the recent progress in some engine technologies and active flow control and morphing technologies and in topics related to aeroacoustics and aircraft controllers. Both the researchers and students should find the material useful in their work.",isbn:"978-953-51-2482-5",printIsbn:"978-953-51-2481-8",pdfIsbn:"978-953-51-6675-7",doi:"10.5772/61381",price:119,priceEur:129,priceUsd:155,slug:"recent-progress-in-some-aircraft-technologies",numberOfPages:204,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"6855bfb94011b56313a07020fa05ead6",bookSignature:"Ramesh K. Agarwal",publishedDate:"September 8th 2016",coverURL:"https://cdn.intechopen.com/books/images_new/5136.jpg",numberOfDownloads:16750,numberOfWosCitations:16,numberOfCrossrefCitations:15,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:21,numberOfDimensionsCitationsByBook:1,hasAltmetrics:1,numberOfTotalCitations:52,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 23rd 2015",dateEndSecondStepPublish:"October 31st 2015",dateEndThirdStepPublish:"January 31st 2016",dateEndFourthStepPublish:"April 17th 2016",dateEndFifthStepPublish:"May 17th 2016",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"38519",title:"Prof.",name:"Ramesh K.",middleName:null,surname:"Agarwal",slug:"ramesh-k.-agarwal",fullName:"Ramesh K. Agarwal",profilePictureURL:"https://mts.intechopen.com/storage/users/38519/images/system/38519.jpg",biography:"Professor Ramesh K. Agarwal is William Palm Professor of Engineering at Washington University in St. Louis, USA. From 1994 to 2001, he was Sam Bloomfield Distinguished Professor and Executive Director of the National Institute for Aviation Research at Wichita State University in Kansas. From 1978 to 1994, he worked in various scientific and managerial positions at McDonnell Douglas Research Laboratories in St. Louis; he became the Program Director and McDonnell Douglas Fellow in 1990. Dr. Agarwal received a PhD in Aeronautical Sciences from Stanford University in 1975, an MS in Aeronautical Engineering from the University of Minnesota in 1969, and a BS in Mechanical Engineering from the Indian Institute of Technology, Kharagpur, India in 1968. Dr. Agarwal has worked in computational fluid dynamics and its applications to problems in aerospace and mechanical engineering, and energy and the environment.",institutionString:"Washington University in St. Louis",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"5",totalChapterViews:"0",totalEditedBooks:"5",institution:{name:"Washington University in St. Louis",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"683",title:"Aeronautics",slug:"aeronautics"}],chapters:[{id:"50737",title:"Progress in Experimental Research of Turbine Aeroacoustics",doi:"10.5772/62431",slug:"progress-in-experimental-research-of-turbine-aeroacoustics",totalDownloads:1910,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Modifications on the intermediate turbine duct in order to reduce noise emissions by changing interaction frequencies and/or modes capable to propagate are presented. Also different turbine exit casings are described that are optimised to reduce interaction noise that is propagating through the engine and is one of the major noise sources during landing (operating point approach). The most promising modifications to reduce sound power levels are described. Depending on different modifications at specific operating points, the reduction of sound power level is between 5 dB and 10 dB, which is a significant reduction. However, some of these measures show an increase in aerodynamic losses. Therefore, a compromise has to be found between higher losses during a short duration (e.g. landing) and significant noise reduction. The chapter focuses on experimental results obtained in the test facilities of the Institute for Thermal Turbomachinery and Machine Dynamics at Graz University of Technology.",signatures:"Andreas Marn, Christian Faustmann and Thorsten Selic",downloadPdfUrl:"/chapter/pdf-download/50737",previewPdfUrl:"/chapter/pdf-preview/50737",authors:[{id:"178221",title:"Dr.",name:"Andreas",surname:"Marn",slug:"andreas-marn",fullName:"Andreas Marn"},{id:"178535",title:"Dr.",name:"Christian",surname:"Faustmann",slug:"christian-faustmann",fullName:"Christian Faustmann"},{id:"178536",title:"Dr.",name:"Thorsten",surname:"Selic",slug:"thorsten-selic",fullName:"Thorsten Selic"}],corrections:null},{id:"50064",title:"Lubricants for Turbine Engines",doi:"10.5772/62394",slug:"lubricants-for-turbine-engines",totalDownloads:2568,totalCrossrefCites:3,totalDimensionsCites:6,hasAltmetrics:1,abstract:"The lubricant systems used in turbine engine applications are discussed with respect to the particular problems associated with aircraft applications. After initially describing the relevant specifications, the typical basestocks are described along with some common degradation schemes. The additive systems, including antioxidants, anti-foaming agents, and anti-wear additives needed to achieve the typical specifications, are described along with their mechanism of action and degradation mechanisms. The methods used for the monitoring of lubricant health, including in-line and offline methods, are also discussed. Finally, future changes in specifications, basestocks, and additives are discussed with respect to new, high-performance bearing materials.",signatures:"David W. Johnson",downloadPdfUrl:"/chapter/pdf-download/50064",previewPdfUrl:"/chapter/pdf-preview/50064",authors:[{id:"178441",title:"Dr.",name:"David",surname:"Johnson",slug:"david-johnson",fullName:"David Johnson"}],corrections:null},{id:"50409",title:"Active Flow Control by Using Plasma Actuators",doi:"10.5772/62720",slug:"active-flow-control-by-using-plasma-actuators",totalDownloads:2881,totalCrossrefCites:7,totalDimensionsCites:9,hasAltmetrics:1,abstract:"Active flow control has recently received an increasing attention since it allows to directly manipulate the flow-field around a surface only when it is effectively requested. Aerodynamic plasma actuators supplied by a dielectric barrier discharge (DBD) can be used for this purpose. Usually, sinusoidal voltages in the range 5–50 kV peak and frequencies between 1 and 100 kHz are utilized to ignite this plasma typology. The surface discharge produced by these devices is able to tangentially accelerate the flow field by means of the electrohydrodynamic (EHD) interaction. DBDs generate non-thermal plasmas characterized by low input energies and limited temperature increments. Plasma actuators can be easily designed by following the shape of the aerodynamic body and can be used over heat-sensitive surfaces. These aerodynamic devices have demonstrated to produce boundary layer modifications with induced speeds up to 10 m/s. Their use over airfoils, flaps, and blades have shown the possibility to delay the transition between laminar to turbulent regime, to prevent flow separation enhancing lift and reducing drag. Moreover, the adoption of these actuators over landing gears and trailing edges may induce a noise reduction effect. Dielectric materials, electrodes configuration, and supplying waveforms are most relevant parameters to be considered to enhance actuator performance. On a parallel plane, on/off actuation strategy is a key point in the use of these devices when utilized over aerodynamic surfaces impinged within an external flow.",signatures:"Gabriele Neretti",downloadPdfUrl:"/chapter/pdf-download/50409",previewPdfUrl:"/chapter/pdf-preview/50409",authors:[{id:"178403",title:"Dr.",name:"Gabriele",surname:"Neretti",slug:"gabriele-neretti",fullName:"Gabriele Neretti"}],corrections:null},{id:"50414",title:"Loads Simulator System for Testing and Qualification of Flight Actuators",doi:"10.5772/62710",slug:"loads-simulator-system-for-testing-and-qualification-of-flight-actuators",totalDownloads:1773,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The flight actuation system plays important role in the accurate guidance of the flight vehicles. The actuators driving the control surfaces are aerodynamically loaded during flight. The design, testing and selection process of the flight actuators play important role to ensure the stable and safe flight. Since a reliable flight actuation system can ensure appropriate guidance, the importance of qualification process cannot be neglected. Qualification of the actuators through field trials is a very costly and time-consuming process. The testing process using real flights takes more time and is costly. For ground testing, aerodynamic loading systems are used. The aerodynamic loading system is ground-based hardware in the loop (HWIL) simulator that can be used for exerting aerodynamic loads on actuation system of flight vehicles in real-time experiment. The actuation system under test is directly connected to the loading motor through a stiff shaft and the aerodynamics loading is applied in real time according to the flight trajectory generated by a flight computer.",signatures:"Nasim Ullah",downloadPdfUrl:"/chapter/pdf-download/50414",previewPdfUrl:"/chapter/pdf-preview/50414",authors:[{id:"179559",title:"Dr.",name:"Nasim",surname:"Ullah",slug:"nasim-ullah",fullName:"Nasim Ullah"}],corrections:null},{id:"50748",title:"Morphing Technologies: Adaptive Ailerons",doi:"10.5772/63645",slug:"morphing-technologies-adaptive-ailerons",totalDownloads:2067,totalCrossrefCites:3,totalDimensionsCites:3,hasAltmetrics:0,abstract:"European Union is involving increasing amount of resources on research projects that will dramatically change the costs of building and operating aircraft in the near future. Morphing structures are a key to turn current airplanes to more efficient and versatile means of transport, operating into a wider range of flight conditions.",signatures:"Ignazio Dimino, Gianluca Amendola, Francesco Amoroso, Rosario\nPecora and Antonio Concilio",downloadPdfUrl:"/chapter/pdf-download/50748",previewPdfUrl:"/chapter/pdf-preview/50748",authors:[{id:"178973",title:"Ph.D.",name:"Ignazio",surname:"Dimino",slug:"ignazio-dimino",fullName:"Ignazio Dimino"},{id:"182346",title:"Dr.",name:"Rosario",surname:"Pecora",slug:"rosario-pecora",fullName:"Rosario Pecora"},{id:"182347",title:"Mr.",name:"Gianluca",surname:"Amendola",slug:"gianluca-amendola",fullName:"Gianluca Amendola"},{id:"182348",title:"Dr.",name:"Antonio",surname:"Concilio",slug:"antonio-concilio",fullName:"Antonio Concilio"},{id:"182349",title:"Dr.",name:"Francesco",surname:"Amoroso",slug:"francesco-amoroso",fullName:"Francesco Amoroso"}],corrections:null},{id:"50553",title:"Self-Healing Control Framework Against Actuator Fault of Single-Rotor Unmanned Helicopters",doi:"10.5772/62480",slug:"self-healing-control-framework-against-actuator-fault-of-single-rotor-unmanned-helicopters",totalDownloads:1117,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Unmanned helicopters (UHs) develop quickly because of their ability to hover and low speed flight. Facing different work conditions, UHs require the ability to safely operate under both external environment constraints, such as obstacles, and their own dynamic limits, especially after faults occurrence. To guarantee the postfault UH system safety and maximum ability, a self‐healing control (SHC) framework is presented in this chapter which is composed of fault detection and diagnosis (FDD), fault‐tolerant control (FTC), trajectory (re‐)planning, and evaluation strategy. More specifically, actuator faults and saturation constraints are considered at the same time. Because of the existence of actuator constraints, usable actuator efficiency would be reduced after actuator fault occurrence. Thus, the performance of the postfault UH system should be evaluated to judge whether the original trajectory and reference is reachable, and the SHC would plan a new trajectory to guarantee the safety of the postfault system under environment constraints. At last, the effectiveness of proposed SHC framework is illustrated by numerical simulations.",signatures:"Xin Qi, Zhong Liu, Yuqing He, Liying Yang, Yuqing He and Jianda\nHan",downloadPdfUrl:"/chapter/pdf-download/50553",previewPdfUrl:"/chapter/pdf-preview/50553",authors:[{id:"9884",title:"Dr.",name:"Yuqing",surname:"He",slug:"yuqing-he",fullName:"Yuqing He"},{id:"9921",title:"Prof.",name:"Jianda",surname:"Han",slug:"jianda-han",fullName:"Jianda Han"},{id:"29225",title:"Dr.",name:"Dalei",surname:"Song",slug:"dalei-song",fullName:"Dalei Song"},{id:"71619",title:"Dr.",name:"Liying",surname:"Yang",slug:"liying-yang",fullName:"Liying Yang"},{id:"179295",title:"Dr.",name:"Xin",surname:"Qi",slug:"xin-qi",fullName:"Xin Qi"},{id:"185017",title:"Dr.",name:"Zhong",surname:"Liu",slug:"zhong-liu",fullName:"Zhong Liu"}],corrections:null},{id:"51026",title:"A Hierarchical Tracking Controller for Quadrotor Without Linear Velocity Measurements",doi:"10.5772/62442",slug:"a-hierarchical-tracking-controller-for-quadrotor-without-linear-velocity-measurements",totalDownloads:1626,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"This chapter deals with the position control of quadrotor unmanned aerial vehicle (UAV) when quadrotor’s linear velocity is unavailable. We propose a hierarchical tracking controller for quadrotor UAV. The proposed controller does not require measurements of linear velocity of quadrotor. A nonlinear filter that avoids the need for measurements of linear velocity has proposed such that a global stability result is obtained for the position tracking error. However, backstepping based on barrier Lyapunov function has been used for the attitude controller. The control design is achieved by means of the hierarchical control, that is, design the position controller and attitude controller separately. This allows us to choose different nonlinear techniques for each controller.",signatures:"Yassine Jmili, Nuradeen Fethalla, Jawhar Ghomam and Maarouf\nSaad",downloadPdfUrl:"/chapter/pdf-download/51026",previewPdfUrl:"/chapter/pdf-preview/51026",authors:[{id:"179087",title:"Prof.",name:"Jawhar",surname:"Ghommam",slug:"jawhar-ghommam",fullName:"Jawhar Ghommam"},{id:"179582",title:"MSc.",name:"Yassine",surname:"Jimli",slug:"yassine-jimli",fullName:"Yassine Jimli"},{id:"179583",title:"Dr.",name:"Nurradeen",surname:"Fathallah",slug:"nurradeen-fathallah",fullName:"Nurradeen Fathallah"}],corrections:null},{id:"50173",title:"Studies on Effects of Aircraft Noise on Behavior of Rats, Their Plasma Norepinephrine Levels and Cell Morphology of the Temporal Lobe",doi:"10.5772/62586",slug:"studies-on-effects-of-aircraft-noise-on-behavior-of-rats-their-plasma-norepinephrine-levels-and-cell",totalDownloads:1324,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"To study the physiological effects of airport noise exposure on organisms, Sprague-Dawley (SD) rats were exposed in soundproof chambers to previously recorded aircraft-related noise for 65 d. As a comparison, unexposed control rats were also used. According to aircraft flight schedules, aircraft noise was replayed and its weighted equivalent continuous perceived noise levels (LWECPN) were adjusted to 75 and 80 dB for the two experimental groups. Rat behaviors were observed through an open field test and the concentrations of plasma norepinephrine (NE) were tested by high-performance liquid chromatography-fluorimetric detection (HPLC-FLD). The morphologies of neurons and synapses in the temporal lobe were also examined by transmission electron microscopy (TEM). Our results indicated that SD rats of experiment group exposed to airport noise of 80 dB had significantly lower line crossing number (P < 0.05) and significantly longer center area duration (P < 0.05) compared with that of control group. After 29 d of airport noise exposure, the concentrations of plasma NE of experiment group were significantly higher than that of control group (P < 0.05). It was determined that the neuron and synapsis of the temporal lobe of experiment group exposed to 80 dB for 65 d showed signs of damage. In conclusion, exposing rats to long-term aircraft noise affects their behaviors, plasma NE levels, and cell morphology of the temporal lobe. Of course, the differences in the hearing sensitivity to different sound frequencies and circadian rhythms between rats and humans can bring variances in physiological effects under the same noise exposure. Therefore, if this study results are applied into humans, it should be further confirmed.",signatures:"Guo-qing Di",downloadPdfUrl:"/chapter/pdf-download/50173",previewPdfUrl:"/chapter/pdf-preview/50173",authors:[{id:"179520",title:"Associate Prof.",name:"Di",surname:"Guoqing",slug:"di-guoqing",fullName:"Di Guoqing"}],corrections:null},{id:"50209",title:"Numerical Study of Support Interferences on the SOAR Separation Wind Tunnel Test",doi:"10.5772/62241",slug:"numerical-study-of-support-interferences-on-the-soar-separation-wind-tunnel-test",totalDownloads:1489,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"A process of support design for wind tunnel models and the evaluation of interferences effect are described in this chapter. The work was performed at the Von Karman Institute for Fluid Dynamics (VKI; Sint-Genesius-Rode, Belgium), and it was commissioned by the S3-Swiss Space System company. The work concerns the separation wind tunnel test of the Suborbital Aircraft Reusable (SOAR) vehicle from an Airbus commercial plane carrier. The supports are designed for future separation wind tunnel test of the SOAR version V10 in the VKI-S1 wind tunnel. They are designed in scale 1:180 for the test of the SOAR in the presence of the Airbus and in scale 1:80 for the SOAR alone test. Two different shapes of support (circular and elliptic) are tested in each case. First there are the supports designed, then the results of the finite element method (FEM) static structural analysis and vibrational analysis, and finally the result of the computational fluid dynamics (CFD) campaign. The flow and the force interferences caused by the support are investigated by comparing simulations with and without support. The behavior of the two shapes and of the dimensional variations are investigated at an angle of attack between 0° and 15° and at Mach 0.7.",signatures:"Alberto Ghiraldo, Sebastien Paris and Ernesto Benini",downloadPdfUrl:"/chapter/pdf-download/50209",previewPdfUrl:"/chapter/pdf-preview/50209",authors:[{id:"11393",title:"Dr.",name:"Ernesto",surname:"Benini",slug:"ernesto-benini",fullName:"Ernesto Benini"},{id:"178175",title:"M.Sc.",name:"Alberto",surname:"Ghiraldo",slug:"alberto-ghiraldo",fullName:"Alberto Ghiraldo"},{id:"183603",title:"Dr.",name:"Sebastien",surname:"Paris",slug:"sebastien-paris",fullName:"Sebastien Paris"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"1992",title:"Recent Advances in Aircraft Technology",subtitle:null,isOpenForSubmission:!1,hash:"67fa903d68a094013f66d01b38882107",slug:"recent-advances-in-aircraft-technology",bookSignature:"Ramesh K. 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As results of such studies, actually we have an unprecedented state to understand the relationship between brain and intelligence [1]. Brain function and its dysfunction throughout life are determined by the interaction of genetic factors with internal and external environmental events, signals, and stimuli [2]. Most of this process occur early in life and exert many effects that persist throughout adulthood. In this scenario, the hippocampus is one of the targets that plays a crucial role in learning, memory storage and retrieval, and in general cognitive function; the study and management of hippocampal neuronal networks, open the real possibility to induce adaption by increasing its function, as a base for a real hippocampal rehabilitation combined therapies [3, 4, 5].
This chapter presents the main results of our investigations in the Down syndrome global gene expression from an integrative approach of functional neurogenomics (FN) as the interface of neurosciences and omics sciences (OS). NF emerges as an integrative research approach which applies several methods of computational sciences and OS strategies, to get understanding of how their gene-product interacts in complex networks and regulates the brain homeostasis. The information derived from the functional neurogenomics approach, could serve in the future, to develop new promising therapeutic protocols and genome editing strategies for trustworthy cognitive rehabilitation based on the hippocampal neuroplasticity [6, 7, 8, 9].
Down syndrome (DS) is the most common aneuploidy in children caused by an extra 21 chromosome, affecting worldwide 1 in 600 live births and 1 in 150 conceptions [10]; however, remarkable differences are registered among countries that depend on sociocultural variables [11]. The triplication of genes on HSA21 causes a wide spectrum of neurological phenotypes in DS, including intellectual and cognitive disabilities. Patients with DS display not only delayed linguistic skills and a variable degrees of cognitive and intellectual disabilities, but also behavioral issues such as attention-deficit disorder (ADD, sometimes with hyperactivity) and autism spectrum disorder (ASD) [12, 13, 14, 15, 16]. The cognitive impairments extend further after development, as individuals with DS are more prone to develop Alzheimer’s type dementia [17]. In addition, patients with DS are susceptible to epilepsy in the form of infantile spasms and tonic-clonic seizures with myoclonus at early ages [16].
It was reported that brain of Down syndrome has a reduction of size and diminishing number of neuron density. Part of the cognitive dysfunction in DS, lies not only in the progressive neuronal degeneration/cell death and impaired neurogenesis seen in this developmental and degenerative disorder, but also in the reduction in dendrite formation and spine density, which result in a disruption of synaptic function. These pathological abnormalities in humans are, in part, replicated in DS animal models which show defects in learning, social interactions, memory, and seizures [18, 19, 20, 21, 22].
The spectacular advances in OS, had led to obtain comprehensive global information regarding the transcriptome of some neurological diseases [23]. In this regard, the use of DNA microarrays to study global transcription is widely spread. This methodology has allowed performing comprehensive analysis of changes in transcriptional expression of many genes associated with the pathophysiology of DS [24]. In addition, previous studies have shown the importance of using postmortem brain tissue to analyze the transcriptome of different conditions and different regions of the human brain including those individuals with DS [25]. The gene expression profile of the central nervous system (CNS) is unique. At least 30–50% of approximately 22,000 known protein-coding genes are expressed across all structures of the human brain [26]. Moreover, the human brain has the highest level of gene expression compared with other mammal species [27]. Neurogenomics research applies genomic strategies to identify and analyze genes that are involved in the function of nervous system. One of the main goals is to build a really systemic approach that contributes to explain the brain development, function, plasticity, and associated diseases [6, 7, 28, 29].
As shown in Figure 1, the major goal in functional neurogenomics is to analyze the global gene expression among different structures of the brain in order to identify the normal regulation of transcription and characterize genes associated with several neurological pathologies with cognitive and intellectual disabilities phenotypes [28, 29, 30, 31].
The experimental and analytical procedures applies in functional neurogenomics. The flow of procedures starts with the analysis of global gene expression profiles, using the technology of DNA microarray, which is followed by a trend of bioinformatics and statistical analysis of the results of the big data generated by DNA microarray experiments. As a result of the integrative analysis, the functional correlation between global gene expression and several interaction processes are obtained.
The functional neurogenomic analysis starts with planning of global gene expression in brain. In this sense, DNA microarray experiments are a powerful experimental tool to study the transcriptome profile of brain which varies within specific regions and changes with age and with internal and external environmental conditions [32, 33].
DNA microarray experiments generate large amounts of data; for example, in a gene expression microarray study, 22,000 genes x 100 samples will generate 2.2 million data points. This terabyte amount data of information is necessary to be analyzed by computational simulation procedures that use bioinformatics analysis tools to get information about the spatial and temporal gene expression. Moreover, the bioinformatics analysis permits to extract information about genes which are expressed in normal and pathological samples of postmortem brains [34, 35].
In addition, genomic experiments are often noisy and are not normally distributed, and usually contain missing values in the expression matrix. To overcome such problem and to obtain biological relevant interpretations of the genome expression data, robust biostatistical analyses are required [36, 37]. In general, statistical analyses of genomic data can be divided into two major categories: supervised and unsupervised methods [36]. Supervised analysis is used to identify genes that are differentially expressed between groups of samples, as well as to find genes that can be used to accurately predict the characteristics of groups. The unsupervised approaches characterize genomic data without prior input or knowledge of predetermined pattern. Unsupervised analysis is used to identify internal structure in the genomic data set. The most commonly used unsupervised analysis tool is Hierarchical clustering and Principal Components Analysis (PCA) [37].
The final result of the flow of analytical process previously described, is to correlate the gene expression profiles variation within specific regions of the brain to obtain a better knowledge about the functional correlations. In this sense, DNA microarray experiments showed that the transcriptome profile of the CNS is specific of brain structure and also the signals that modulate it [38, 39].
Cognition refers to the mental processes that are involved in acquiring knowledge and comprehension. These processes include thinking, knowing, remembering, judging, and problem solving. All of them are higher level functions of the brain and encompass language, imagination, perception, and planning [40]. Neuroplasticity is the ability of the nervous system to adapt to different environmental conditions and stimuli; it requires a well-conserved and flexible repertoire of molecular mechanisms [41]. Neural plasticity, allows neurons to regenerate both anatomically as well as functionally, in a process call neurogenesis; also to form new synaptic connections—synaptogenesis, and in some cases of new dendrites generation—dendritogenesis [42, 43]. Because neuroplasticity is based on the ability of brain to recover and restructure itself, it allows us to consider that its adaptive potential to recover after disorders or injuries, would be a point of departure for developing therapeutic strategies toward reducing the effects of altered structures due to cognitive associated pathologies including DS among others [44].
The point of departure of our studies lies in the fact that a failure in the crosstalk between cognitive process and neuroplasticity would be a major effector for cognitive disability (CD) in DS brain [45, 46, 47, 48]. Some genetic mechanisms or even alteration of brain development homeostasis has important neurodevelopmental consequences produced by CD [49].
In order to test our proposal, the initial approach started with a bibliographic search of full papers in PubMed of publications reported neuroplasticity and CD in Down syndrome. We used the following crossed descriptors to perform that search: DS, neuroplasticity and cognition and cognitive disability, and genes associated. We filtered six full papers describing genes that involved in cognition and neuroplasticity in DS. Information consigned in this article led us to pick up 106 genes involved in neuroplasticity and cognitive process such as memory and learning. Those genes were the initial background to perform our computational simulations and identify their functional roles in several structures of brain cortex. Moreover from gender and age gene expression values, we obtain data about their temporal and spatial regulations. The list and main characteristics of selected genes are consigned in Supplementary Table 1.
ID | Gen symbol | Name | Locus | Function—gene ontology (GO) |
---|---|---|---|---|
90 | ACVR1 | Activin A receptor type 1 | 2q24.1 | ATP binding |
9509 | ADAMTS2 | ADAM metallopeptidase with thrombospondin type 1 motif 2 | 5q35.3 | Metalloendopeptidase activity, metallopeptidase activity |
9370 | ADIPOQ | Adiponectin | 3q27.3 | Cytokine activity, hormone activity |
152 | ADRA2C | Adrenoceptor alpha 2C | 4p16.3 | Alpha-2A adrenergic receptor binding, epinephrine binding |
8906 | AP1G2 | Adaptor related protein complex 1 gamma 2 subunit | 14q11.2 | Protein transporter activity |
361 | AQP4 | Aquaporin 4 | 18q11.2 | Protein binding |
10317 | B3GALT5 | Beta-1,3-galactosyltransferase 5 | 21q22.2 | Protein glycosylation |
25825 | BACE2 | Beta-site APP-cleaving enzyme 2 | 21q22.2–q22.3 | Amyloid-beta metabolic process |
627 | BDNF | Brain-derived neurotrophic factor | 11p14.1 | Neurotrophin TRKB receptor binding |
666 | BOK | BCL2 family apoptosis regulator | 2q37.3 | BH domain binding |
54014 | BRWD1 | Bromodomain and WD repeat domain containing 1 | 21q22.2 | Cytoskeleton organization |
55969 | C20orf24 | Chromosome 20 open reading frame 24 | 20q11.23 | Olfactory receptor activity |
114041 | B3GALT5-AS1 | B3GALT5 antisense RNA 1 | 21q22.2 | Putative uncharacterized |
721 | C4B | Complement C4B | 6p21.33 | Carbohydrate binding, endopeptidase inhibitor activity |
23562 | CLDN14 | Claudin 14 | 21q22.13 | Protein complex assembly |
54102 | CLIC6 | Chloride intracellular channel 6 | 21q22.12 | NOT glutathione metabolic process |
1277 | COL1A1 | Collagen type I alpha 1 chain | 17q21.33 | Protease binding, extracellular matrix structural constituent, protein binding |
1278 | COL1A2 | Collagen type I alpha 2 chain | 7q21.3 | SMAD binding, identical protein binding |
1476 | CSTB | Cystatin B | 21q22.3 | Adult locomotory behavior |
7852 | CXCR4 | C-X-C motif chemokine receptor 4 | 2q22.1 | C-C chemokine binding |
51523 | CXXC5 | CXXC finger protein 5 | 5q31.2 | Sequence-specific DNA binding, signal transducer activity, transcription factor binding |
147991 | DPY19L3 | DPY-19-like 3 | 19q13.11 | Mannosyltransferase activity, transferase activity |
1812 | DRD1 | Dopamine receptor D1 | 5q35.2 | Dopamine binding |
3920 | DSCAM | DS cell adhesion molecule | 21q22.2 | Nervous system development, Locomotory behavior, dendrite morphogenesis |
10311 | DSCR3 | DSCR3 arrestin fold containing | 21q22.13 | Intracellular protein transport |
53820 | DSCR6 | Ripply transcriptional repressor 3 | 21q22.13 | Negative regulation of cell proliferation |
84677 | DSCR8 | Down syndrome critical region 8 (non-protein coding) | 21q22.13 | Biological_process |
1846 | DUSP4 | Dual specificity phosphatase 4 | 8p12 | MAP kinase serine/threonine phosphatase activity |
1859 | DYRK1A | Dual specificity tyrosine phosphorylation regulated kinase 1A | 21q22.13 | Circadian rhythm |
1958 | EGR1 | Early growth response 1 | 5q31.2 | RNA polymerase II regulatory region sequence-specific DNA binding |
2078 | ERG | ERG, ETS transcription factor | 21q22.2 | Cell proliferation |
2114 | ETS2 | ETS proto-oncogene 2, transcription factor | 21q22.2 | Skeletal system development |
2199 | FBLN2 | Fibulin 2 | 3p25.1 | Extracellular matrix binding, calcium ion binding |
252995 | FNDC5 | Fibronectin type III domain containing 5 | 1p35.1 | Hormone activity, molecular_function |
2487 | FRZB | Frizzled-related protein | 2q32.1 | Wnt-activated receptor activity, G protein-coupled receptor activity |
2670 | GFAP | Glial fibrillary acidic protein | 17q21.31 | Structural constituent of cytoskeleton, protein binding |
2719 | GPC3 | Glypican 3 | Xq26.2 | Heparan sulfate proteoglycan binding, peptidyl-dipeptidase inhibitor activity |
10457 | GPNMB | Glycoprotein nmb | 7p15.3 | Integrin binding, heparin binding, chemoattractant activity |
3141 | HLCS | Holocarboxylase synthetase | 21q22.13 | Enzyme binding |
3150 | HMGN1 | High mobility group nucleosomal binding domain 1 | 21q22.2 | Transcription-coupled nucleotide-excision repair |
9456 | HOMER1 | Homer scaffolding protein 1 | 5q14.1 | G protein-coupled glutamate receptor binding |
9454 | HOMER3 | Homer scaffolding protein 3 | 19p13.11 | G protein-coupled glutamate receptor binding |
3479 | IGF1 | Insulin-like growth factor 1 | 12q23.2 | Growth factor activity, hormone activity, insulin-like growth factor receptor binding, insulin-like growth factor receptor binding |
3488 | IGFBP5 | Insulin-like growth factor binding protein 5 | 2q35 | Fibronectin binding, protein binding |
3489 | IGFBP6 | Insulin-like growth factor binding protein 6 | 12q13.13 | Growth factor binding, receptor binding |
3600 | IL15 | Interleukin 15 | 4q31.21 | Cytokine activity, cytokine receptor binding |
3623 | INHA | Inhibin alpha subunit | 2q35 | Cytokine activity, growth factor activity |
3708 | ITPR1 | Inositol 1,4,5-trisphosphate receptor 1 | 3p26.1 | Calcium channel inhibitor activity |
170850 | KCNG3 | Potassium voltage-gated channel modifier subfamily G member 3 | 2p21 | Delayed rectifier potassium channel activity |
3772 | KCNJ15 | Potassium voltage-gated channel subfamily J member 15 | 21q22.13-q22.2 | Potassium ion import |
3775 | KCNK1 | Potassium two pore domain channel subfamily K member 1 | 1q42.2 | Inward rectifier potassium channel activity |
57576 | KIF17 | Kinesin family member 17 | 1p36.12 | Microtubule motor activity, ATP binding, microtubule binding, |
7071 | KLF10 | Kruppel-like factor 10 | 8q22.3 | RNA polymerase II core promoter proximal region sequence-specific DNA binding |
11202 | KLK8 | Kallikrein related-peptidase 8 | 19q13.41 | Serine-type endopeptidase activity |
150082 | LCA5L | LCA5L, lebercilin like | 21q22.2 | Protein binding |
9663 | LPIN2 | Lipin 2 | 18p11.31 | Phosphatidate phosphatase activity |
4058 | LTK | Leukocyte receptor tyrosine kinase | 15q15.1 | ATP binding, protein binding |
4147 | MATN2 | Matrilin 2 | 8q22.1-q22.2 | Calcium ion binding |
4239 | MFAP4 | Microfibril associated protein 4 | 17p11.2 | Protein binding |
283078 | MKX | Mohawk homeobox | 10p12.1 | Sequence-specific DNA binding |
25902 | MTHFD1L | Methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1 like | 6q25.1 | Formate-tetrahydrofolate ligase activity, methylenetetrahydrofolate dehydrogenase (NADP+) activity |
1463 | NCAN | Neurocan | 19p13.11 | Calcium ion binding |
4885 | NPTX2 | Neuronal pentraxin 2 | 7q22.1 | Carbohydrate binding |
51299 | NRN1 | Neuritin 1 | 6p25.1 | C-terminal protein lipidation |
51559 | NT5DC3 | 5′-Nucleotidase domain containing 3 | 12q23.3 | Metal ion binding |
4908 | NTF3 | Neurotrophin 3 | 12p13.31 | Chemoattractant activity, neurotrophin p75 receptor binding |
64881 | PCDH20 | Protocadherin 20 | 13q21.2 | RNA binding, calcium ion binding |
5121 | PCP4 | Purkinje cell protein 4 | 21q22.2 | Positive regulation of neuron differentiation |
5179 | PENK | Proenkephalin | 8q12.1 | Neuropeptide hormone activity |
51227 | PIGP | Phosphatidylinositol glycan anchor biosynthesis class P | 21q22.13 | Preassembly of GPI anchor in ER membrane |
130271 | PLEKHH2 | Pleckstrin homology, MyTH4 and FERM domain containing H2 | 2p21 | Actin binding, identical protein binding |
57460 | PPM1H | Protein phosphatase, Mg2+/Mn2+ dependent 1H | 12q14.1-q14.2 | Phosphoprotein phosphatase activity, protein serine/threonine phosphatase activity |
3275 | PRMT2 | Protein arginine methyltransferase 2 | 21q22.3 | Developmental cell growth |
8624 | PSMG1 | Proteasome assembly chaperone 1 | 21q22.2 | Proteasome assembly |
754 | PTTG1IP | PTTG1 interacting protein | 21q22.3 | Protein import into nucleus |
51655 | RASD1 | RAS related dexamethasone induced 1 | 17p11.2 | GTPase activity, GTP binding |
10633 | RASL10A | RAS like family 10 member A | 22q12.2 | Signal transduction, small GTPase mediated signal transduction |
1827 | RCAN1 | Regulator of calcineurin 1 | 21q22.12 | Central nervous system development |
5997 | RGS2 | Regulator of G protein signaling 2 | 1q31.2 | G-protein alpha-subunit binding |
85397 | RGS8 | Regulator of G protein signaling 8 | 1q25.3 | GTPase activator activity |
56475 | RPRM | Reprimo, TP53 dependent G2 arrest mediator homolog | 2q23.3 | Protein binding |
861 | RUNX1 | Runt related transcription factor 1 | 21q22.12 | Peripheral nervous system neuron development |
347735 | SERINC2 | Serine incorporator 2 | 1p35.2 | L-serine transmembrane transporter activity |
5271 | SERPINB8 | Serpin family B member 8 | 18q22.1 | Serine-type endopeptidase inhibitor activity |
6450 | SH3BGR | SH3 domain binding glutamate rich protein | 21q22.2 | Positive regulation of signal transduction |
6470 | SHMT1 | Serine hydroxymethyltransferase 1 | 17p11.2 | L-allo-threonine aldolase activity, glycine hydroxymethyltransferase activity |
6493 | SIM2 | Single-minded family bHLH transcription factor 2 | 21q22.13 | Embryonic pattern specification |
6574 | SLC20A1 | Solute carrier family 20 member 1 | 2q14.1 | High-affinity inorganic phosphate:sodium symporter activity |
65012 | SLC26A10 | Solute carrier family 26 member 10 | 12q13.3 | Anion:anion antiporter activity |
57709 | SLC7A14 | Solute carrier family 7 member 14 | 3q26.2 | Amino acid transmembrane transporter activity |
114826 | SMYD4 | SET and MYND domain containing4 | 17p13.3 | Metal ion binding, methyltransferase activity |
6651 | SON | SON DNA binding protein | 21q22.11 | Negative regulation of apoptotic process |
6664 | SOX11 | SRY-box 11 | 2p25.2 | RNA polymerase II core promoter sequence-specific DNA binding |
8869 | ST3GAL5 | ST3 beta-galactoside alpha-2,3-sialyltransferase 5 | 2p11.2 | Beta-galactoside (CMP) alpha-2,3-sialyltransferase activity |
27090 | ST6GALNAC4 | ST6 N-acetylgalactosaminide alpha-2,6-sialyltransferase 4 | 9q34.11 | Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase activity |
7058 | THBS2 | Thrombospondin 2 | 6q27 | Heparin binding, protein binding |
7059 | THBS3 | Thrombospondin 3 | 1q22 | Heparin binding, calcium ion binding |
7074 | TIAM1 | T-cell lymphoma invasion and metastasis 1 | 21q22.11 | Neuron projection extension |
757 | TMEM50B | Transmembrane protein 50B | 21q22.11 | Biological_process |
7109 | TRAPPC10 | Trafficking protein particle complex 10 | 21q22.3 | Early endosome to Golgi transport |
10098 | TSPAN5 | Tetraspanin 5 | 4q23 | Enzyme binding |
7267 | TTC3 | Tetratricopeptide repeat domain 3 | 21q22.13 | Protein K48-linked ubiquitination |
84959 | UBASH3B | Ubiquitin associated and SH3 domain containing B | 11q24.1 | Identical protein binding, phosphoprotein binding |
221044 | UCMA | Upper zone of growth plate and cartilage matrix associated | 10p13 | Negative regulation of osteoblast differentiation |
7422 | VEGFA | Vascular endothelial growth factor A | 6p21.1 | Chemoattractant activity, cytokine activity |
7485 | WRB | Tryptophan rich basic protein | 21q22.2 | Tail-anchored membrane protein insertion into ER membrane |
Description of genes associated with neuroplasticity and cognition. Information taken from the NCBI—Genbank platform (Supplementary table).
As a source to calculate the values of expression for selected gene, this initial bibliographic search was crossed with DNA microarray experiments consigned in the database of GEO DataSet of NCBI (https://www.ncbi.nlm.nih.gov/gds/). Combining the descriptors: Down syndrome and global transcription and neuroplasticity and cognition and brain, we found nine DNA microarray experiments. However, only one of them fitted the statistical significance sample size to obtain trustable information about the functional neurogenomics in DS.
We used the log10 transformed expression values of a DNA microarray experiment whose registration code and free access in the GEO database was GSE59630 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE59630), previously deposited by Olmos et al. [50]. The microarray experiment selected included gene expression data of 47,000 probes from 58 DS patients (25 females and 33 males) and 58 healthy controls (25 females and 33 males) of postmortem brain samples classified by gender and age, and in 11 structures of cerebral cortex.
Free use Cytoscape 3.2 open software platform was used for visualizing and analyzing the genetic interaction networks among the selected human genes associated with cognition and neuroplasticity processes. Biological Networks Gene Ontology v2.6 plugin (BiNGO tool) was used to search which gene ontology (GO) categories are significantly overrepresented in a set of genes. A hypergeometric test was applied to determine which categories were significantly represented (P-value < 0.05); significant values were adjusted for multiple hypotheses testing using the Bonferroni family wise error rate correction [51]. From network analyzer plugin of the Max Planck Institute Informatik, network topology parameters were calculated.
The raw intensity data for each gene in the DNA microarray experiment was log10 transformed and then used for the calculation of Z score [52]. Z scores were calculated by subtracting the mean log gene intensities (within a single experiment) from the log intensity data for each gene, and dividing that result by the SD of all measured log intensities, according to the Z-score transformation (1):
All Z-score values were normalized on a linear scale −3.0 < 0 > +3.0. In this, the corresponding gene is overexpressed if the value of Z-score is greater than zero; on the contrary, it is under-expressed, if its value is negative.
Nonparametric analyses for comparing median values of Z-score were performed among gender and age variables between DS patients and healthy control. Wilcoxon signed-rank test was used to calculate differences between medians of two samples.
Data of Z-score values of samples from DS and controls were compared to establish significant difference in gender in DS and controls and by age ranks since 16 weeks of gestation to 6 months; since 7 months up to 1 year; 2–3 years; 10–19 years; and 22 years and older groups. Moreover, Z-scores for the genes included in the study, were compared between DS and control samples in 11 structures of brain cortex including: dorsolateral prefrontal cortex (DFC), visual cortex (V1C), cerebellar cortex (CBC), orbitofrontal cortex (OFC), ventral frontal cortex (VFC), inferior temporal cortex (ITC), hippocampus (HIP), medial frontal cortex (MFC), somatosensory cortex (S1C), inferior parietal cortex (IPC), and superior temporal cortex (STC). To perform the HCA, Euclidean distance was used as a measure of distance between DS and control samples of Z-score values in several structures of brain cortex; p < 0.05 was defined as a threshold [53].
A total of 3135 protein interactions among genes associated with cognition and neuroplasticity process expressed in brains of DS subjects were recorded (Figure 2A and B). The central proteins of the main node of the network corresponded to RUNX1 (runt related transcription factor 1) at 21q22.12; SON (SON DNA binding protein) at 21q22.11; RGS2 (regulator of G protein signaling 2) at 1q31.2; UBASH3B (ubiquitin associated and SH3 domain containing B) at 11q24.1; DYRK1A (dual specificity tyrosine phosphorylation regulated kinase 1A) at 21q22.13; GFAP (glial fibrillary acidic protein) at 17q21.31; TIAM1 (T-cell lymphoma invasion and metastasis 1) at 21q22.11; and THBS3 (thrombospondin-3) at 1q22. The most important topological parameters of the network were: clustering coefficient with a value of 0.33; average number of neighbors 2367; network density 0.001 and 12 connected components (Table 2).
Protein-protein interaction (PPI) networks of genes associated with cognition and neuroplasticity constructed from data experiments of DNA microarray of genes expressed in Down syndrome postmortem brain samples. Data of log2 intensity values were obtained from DNA microarray experiment by Olmos-Serrano et al. [
Topological parameter | Value |
---|---|
Clustering coefficient | 0.33 |
Connected components | 12 |
Network diameter | 12 |
Network radius | 1 |
Network centralization | 0.056 |
Shortest paths | 3.454.424 (93%) |
Characteristics path length | 5.340 |
Avg. number of neighbors | 2.367 |
Number of nodes | 1919 |
Network density | 0.001 |
Network heterogeneity | 3.105 |
Isolated nodes | 0 |
Number of self-loops | 25 |
Multi-edge node pairs | 595 |
Values of the main topological parameters of the protein interaction network including 106 genes associated with cognitive and neuroplasticity process in brain of DS patients.
From GeneMANIA Cytoscape plugin, we identified the top five functions of that genes. They corresponded to regulation of behavior, behavior, muscle cell migration, hormone activity, and G coupled glutamate receptor.
Overall no statistical differences between the median values in Z-score of the 108 gene in controls and DS patients were recorded (Controls 0.2869 vs. DS 0.3318; Wilcoxon rank test p > 0.05). However, significant differences in the medians of Z-score in some genes were determined. Thus, in the DS brains, the overexpression levels corresponded to genes CXXC5 (Controls −1.2376 vs. DS 0.7492), EGR1 (controls −1.2266 vs. DS 0.5442), and NCAN (controls −1.2901 vs. DS 0.5440).
The main GO categories of brains processes associated with DS involved in its etiopathogenesis included: respiratory electron transport chain (3.31E − 41), positive regulation of cell death (1.17E − 39), positive regulation of release of cytochrome c from mitochondria (9.19E − 37), negative regulation of cell motility involved in cerebral cortex radial glia guided migration (5.20E − 35), telomere maintenance (1.16E − 34), negative regulation of angiogenesis (4.11E − 32), and axonogenesis (1.40E − 31) (Table 3). Moreover, focal adhesion (P-value 7.69E − 23) and neurotrophin signaling pathway (P-value 3.62E − 19) were also important pathways associated with cognitive and neuroplasticity process in brains of DS individuals.
GO_ID | Process | P-value* |
---|---|---|
9987 | Respiratory electron transport chain | 3.31E – 41 |
48522 | Positive regulation of cell death | 1.17E − 39 |
48518 | Positive regulation of release of cytochrome c from mitochondria | 9.19E − 37 |
48523 | Negative regulation of cell motility involved in cerebral cortex radial glia guided migration | 5.20E − 35 |
44260 | Telomere maintenance | 1.16E − 34 |
48519 | Negative regulation of angiogénesis | 4.11E − 32 |
16043 | Axonogenesis | 1.40E − 31 |
43170 | Glycoprotein biosynthetic process | 3.33E − 30 |
10604 | Positive regulation of telomerase activity | 1.82E − 29 |
9893 | Positive regulation of protein processing in phagocytic vesicle | 5.01E – 28 |
The top 10 GO categories of brains processes associated with DS involved in its etiopathogenesis.
P-values were calculated using the correction of Bonferroni.
Ontology v2.6 plugin (BiNGO tool) was used to search gene ontology (GO) categories.
We observed differential brain expression in 72 genes associated with CD among women and men. Medians of brain gene expression in men patients with DS were higher than in DS women (p < 0.005 Kruskal-Wallis test) (Figure 4A). Such difference were statically significant for the expression of DMXL2 (Z-score of men 1.33 vs. −1.75 in women); CAMTA1 (Z-score of men 1.16 vs. −1.73 in women); HCN1 (Z-score of 1.05 vs. −1.73 in women); and ATL1 (Z-score of men 0.85 vs. −1.73 in women). On the contrary, we recorded non-significant differences by gender in medians values of genes associated with neuroplasticity in brains of DS.
Global gene expression among the different ranks of age in DS brains was variable and dependent of the type of gene. However, slight differences of expression in brain genes associated with neuroplasticity process of Down syndrome and its age dependency were recorded in samples of DS brains in comparison with that of normal controls in age ranks since 16 weeks of gestation to more than 22 years old. It is noteworthy that DYRK1A, NCAM AND TSPN5 genes were under-expressed in prenatal brains (Figure 3A–G).
Differential values of median Z-score by age rank for six principal genes associated with cognitive disability and neuroplasticity expressed in brain samples of Down syndrome. (1) 16 Weeks of gestation to 6 months; (2) 7 months to 1 year; (3) 2–3 years; (4) 8–18 years; and (5) over 22 years of age. Y-axis values are the median of Z-score.
Some of the most differentially expressed genes across the cerebral cortex are shown in Figure 4A–H. In particular, expression in S1C showed significant differences for SERPIB8 (Control 0.2288 vs. DS −2.0288), SHMT1 (control 0.1542 vs. DS −2.1269) and THBSH3 (control 0.1542 vs. −2.0709) genes. In hippocampus, we recorded differential expression for EGR1 (control 0.8084 vs. DS −1.4648), SMYD4 (control 0.3946 vs. −1.8171), PCDH20 (control 0.7462 vs. DS −1.3194), DYRK1A (control 1.4284 vs. DS −1.7390), and VEGFA (control 0.6648 vs. DS −1.3280). In S1C, the most under expressed genes in Down syndrome were MFAP4 (control 0.1711 vs. DS −2.1461), BDNF (control 0.2136 vs. DS −2.1039), RGS8 (control 0.4013 vs. DS −1.9024), and SERINC2 (control 0.2584 vs. DS −1.8843). Finally in V1C, ADIPOQ (control −0.0035 vs. DS −2.1880), and TSPAN5 (control 0.7392 vs. DS −1.3315) were the most under-expressed genes in DS samples.
Differential gene expression in different structures of brain cortex of genes associated with cognitive disability and neuroplasticity in DS samples of brain. DFC, dorso lateral prefrontal cortex; V1C, visual cortex; CBC, cerebellar cortex; OFC, orbito frontal cortex; VFC, ventral frontal cortex; ITC, inferior temporal cortex; HIP, hippocampus; MFC, medial frontal; S1C, cortex somatosensory cortex; IPC, inferior parietal cortex and STC, superior temporal cortex. Y-axis values are the median of Z-score.
In general, our results provided strong evidence to propose that in brains of DS, a fail in the cross talk of global expression between genes associated with cognition and neuroplasticity process (most of them located out of chromosome 21), is complex and is associated not only with pathological profiles but with gender, age, and is also dependent of the brain cortex structures. However, according with the functional roles, differential expression of particular groups of genes would cause a considerable impact on the metabolic pathways, in which they participate and are directly or indirectly involved in the regulation of molecular events associated with cognition and neuroplasticity in brain of patients with DS.
Overall, this study also support the hypothesis of a systemic imbalance of brain protein homeostasis, or proteostasis network as an important effect of trisomy not only in loci of chromosome 21 but also in genes located in other chromosomes [54]. Together our results and others collectively suggest that disturbance in the proteostasis network of cognitive and neuroplasticity process, could contribute to the accumulation of protein aggregates, such as amyloid deposits and NFTs, which occur very early in DS. It is likely that a sub-optimal functioning of degradative systems occur in DS neurons, which in turn provide the basis for further accumulation of toxic protein aggregates which have an indirect impact on the neuroplastic process in several structures of brain cortex [55, 56].
According to our results and with the information reviewed in literature, V-CAM1, SPTAN1, DYNC1H1, PAFAH1B1, H3F3A, ACVR1, THBS3, and TSPAN5 were the proteins with the highest number of protein interactions. All of them directly or even indirectly regulate several brain processes associated with cognition and neuroplasticity [57, 58]. In this sense, it is relevant to get more knowledge about the implication in those neurophysiological processes whose function is altered by either overexpression or by disruption in the network functional interaction architecture in DS brains.
For the first time, we obtain strong evidence that brain of male DS had, in general, a higher gene expression of cognitive and neuroplasticity process in comparison with that of females. The outstanding differences were specifically for DMXL2 (RKPM = 8.02 ± 1.61), CAMTA1 (RKPM = 4977 ± 1.246), HCN1 (RKPM = 4.88 ± 2.29), and ATL1 (RKPM = 34.764 ± 11.66) genes, all of them highly expressed in human brain. Previous evidence indicates that male-biased genes are highly enriched for genes involved in neurological and psychiatric disorders such as schizophrenia, bipolar disorder, Alzheimer’s disease, and autism, while no such pattern was seen for the female-biased genes, suggesting that the differences in brain disorder susceptibility between males and females are likely rooted from the sex-biased gene expression regulation during brain development [59]. Moreover, it was previously reported that the excess of male cases with Down syndrome is not restricted to free trisomy 21 alone, but appears in translocation cases [60] and with the life expectancy found in males with DS, which is significantly greater in females [61]. Collectively, our and others analyses reveal the important role of sex-biased genes in brain development and neurodevelopmental disorders including the effects in cognitive disability in DS.
DYRK1A, BDNF, PENK, and DRD1 genes are strongly under-expressed in dorsolateral prefrontal cortex, hippocampus, orbitofrontal cortex, and ventral frontal cortex in subjects with DS in contrast with non-trisomic. Prefrontal cortex is implicated in planning complex cognitive behavior, personality expression, decision-making, and moderating social behavior [62], and also plays key roles in cell proliferation and survival, neuronal differentiation, synaptic plasticity, and neurodegeneration (for review, see [63, 64]). Supporting our proposal, it has been reported that DYRK1A/RCAN1 and NFAT lead to neurodevelopmental alterations that might have an impact not only in the brain size and neuronal density, but also in the altered common features found in patients with DS [65]. Additionally, a reduction of vesicular GABA transporter punctate specifically on parvalbumin-positive interneurons was identified [66, 67]. Overall, our results and others suggest that dysfunction of cortical fast-spiking interneurons might be central to the pathophysiology of DS.
The under-expression of key genes for brain function correlates with previous reports that showed that DS brains are smaller than normal brains and they exhibit neuronal deficits in several regions, including the cerebral cortex structures [68]. Moreover, infants with DS also present hypocellularity in this brain structure [69, 70], indicating that defects in prenatal development are a major determinant of the deficit in adults. Indeed, fewer cells and disorganized laminas are evident in the cerebral cortex of DS fetuses from as early as the second trimester of gestation [71, 72]. Altogether, the different lines of evidence support the hypothesis that DS brain is severely affected by the disturbance of proteostatic network, which is major responsible for the cerebral phenotype of DS.
Differential gene expression in hippocampus visual cortex, and somatosensory cortex of DYRK1A (dual specificity tyrosine-phosphorylation-regulated kinase 1A), TSPAN5 (tetraspanin 5), DRD1 (dopamine receptor D1), EGR1 (early growth response 1), GFAP (glial fibrillary acidic protein), and PENK (proenkephalin), which encode proteins that play important roles in several brain processes of cognition, learning and the maintenance of homeostasis, lead us to proposed them as functional potential predictors to follow up the homeostatic imbalance in DS brain.
Finally, this study showed that the integration of knowledge and use of cross talk between neurotranscriptomics and bioinformatics is a powerful work to develop transdisciplinary and systems biology studies to deal with many insight still remains to be solve in Down syndrome. We recommend continuing to study much deeper the complexity of interaction networks in the DS etiopathogenesis and brain homeostasis. On the other hand, our approach could serve as a starting point for the implementation of strategies to the management of cognitive and mental disabilities based on functional neurogenomics and the hippocampal neuroplasticity.
The current role of the insurer is extremely different according to country-specific health and welfare policies. Nevertheless, health insurance could contribute to improve current conditions or even solve dilemmas such as how to cope with a rising number of people while keeping them in a good health state and at the same time protected.
\nThe World Health Organization’s new 5-year strategic plan addresses what they have identified as the major ten threats to global health in 2019—including noncommunicable diseases, such as diabetes, cancer, and heart disease which are collectively responsible for over 70% of all deaths worldwide [1]. The plan aims to ensure that 1 billion more people benefit from access to universal health coverage, 1 billion more people are protected from health emergencies, and 1 billion more people enjoy better health and well-being. To reach this goal, different types of solutions are required, and all means and mediums available should be employed.
\nInsurers play an important role in the health-care system and could effectively contribute to such an objective as the one set by WHO toward the benefit of the global health. Though it may seem perhaps altruistic to associate insurers with such a noble scope, the reality is that they, insurers, would also be benefiting from such a scenario. Some forward-looking companies worldwide have understood this opportunity, and so there are examples of insurers that have started to use the “insurer as partner” approach which implies an active role in prevention rather than just being reactive and paying claims when an undesirable event occurs. This new approach has been made, in great part, possible by what we now call “connected insurance” which encompasses Internet of things (IoT), wearables, and other monitoring devices. The reshaping of the insurance industry has already begun, and it will continue based on new technologies at hand. The aim of this chapter is to briefly illustrate the concept of “connected insurance” with specific focus on “connected health” and “wearables” and to present two case studies: (1) Discovery’s Vitality program presented in parallel with Matteo Carbone’s “five value creation levers” insurance model and the company’s aim to create healthier lifestyles for its customers through the use of wearables, gamification, and rewards and (2) Maugeri’s MOSAIC EU-funded project based on AI and predictive models aimed at helping with treatment management, reducing complications, and improving quality of life in type 2 diabetes patients.
\nConnected health insurance presents great potential for both insurer and insured. But let us define the term in a more accurate way. Connected health, as defined in a paper by Deloitte [2], is the convergence of health technology, digital media, and mobile devices and has the aim of helping patients, caregivers, and health-care professionals to access data in a swifter way while improving the outcomes of health and social care. Connected insurance on the other hand refers to an evolution of the insurance business model based on the adoption of IoT technologies which allow the direct connection between all actors of the ecosystem: customers, insurers, and players from other industries [3]. Based on the above, we can say that connected health insurance is a mix of different types of technologies used in health insurance in order to collect data, determine patterns, and create effective incentives and engagement programs aimed at reducing costs related to healthcare and at improving the quality of life of the insureds.
\nThe potential of connected health insurance can be harnessed in a profitable way by properly measuring the risks associated to the clients and presenting them with an improved, better-priced value proposition that may also contribute to improve their general health conditions. For this to happen, the insurance company will have to seek partners from both the technological innovation sphere and medical providers, keeping in mind that its role in the health system is changing from “payer” to “pivot.”
\nIf creating partnerships in order to get more specialized is something that many insurers do nowadays, matters are completely different when it comes to big data analytics and creating efficient customer experiences. There is so much space for innovation, but legacy systems certainly play their role in making the task of innovating more difficult.
\nThe technologies range from consumer-driven devices, such as Apple Watch and Google Glass, to those developed specifically for certain applications, such as wrist-worn sensor for measuring the onset of seizure and so on [4].
\nThe uses of wearables are many, but while some are more immediate and easier to apply, others need more time and research to show how they can influence major health issues worldwide. Wearables can be a noninvasive underwriting evidence source thanks to the capacity to collect data and assess risk based on this data in a shorter period compared to a full medical exam. They can also help people improve their lifestyles and habits and at the same time provide added customer value beyond insurance protection. On a more serious note, wearables can reduce the incidence of early deaths from chronic conditions such as diabetes and heart disease, but it can also empower people to manage chronic disease better and even act as early identification system for diabetes and heart disease.
\nThe impact of wearable devices is closely related to statistics and life habits: “the only way to move from a palliative health approach to a preventive model is by increasing the volume of data generated and feeding it with algorithms capable of interpreting them” [5].
\nThe big tech players have also been deeply involved in creating innovative connected health solutions and ecosystems.
\nGoogle, for example, aims to build headphones that can track one’s health. The company was granted a patent in July 2018 titled “in-ear health monitoring,” which combines auditory experiences with health tracking. The aim is to use in-ear devices to collect data on users’ health as they listen to their favorite music via their smartphones, tablets, or smart watches. While playing the content, the device would also capture users’ body temperatures, effectively creating a database of temperature norms. Over time, the device would be able to compare a person’s daily reading against his or her baseline and recognize unhealthy variations in temperature. In the patent description, Google claims that such a feature could lead to “early detection of a contagious disease or other malady” with global health implications, even keeping under control disease outbreaks such as Ebola and swine flu [6]. Nest, who merged with Google, has recently carried out acquisitions such as Senosis, a spinoff from the University of Washington working on health monitoring systems using a smartphone.
\nApple recently unveiled an API for application developers to use data stored in its health application so that with the appropriate level of supervision, people can share data with doctors, hospitals, etc. and receive reminders to follow treatment and other administrative tasks [5].
\nVirtual assistants are an evolved form of e-health, and it’s estimated that this type of service could save the health-care industry $20 billion annually. Since virtual nurses are available 24/7, they can answer questions, monitor patients, and provide quick answers. Most applications of virtual nursing assistants today allow for more regular communication between patients and care providers between office visits to prevent hospital readmission or unnecessary hospital visits [7]. If virtual assistants may ease the workload of doctors, another major part of the connected health trend are virtual medical visits performed by real doctors. According to a survey by Mercer, a typical charge for a telemedicine visit is $40, compared to $125 for an office visit, in the USA [8]. When presented with the opportunity, health-care consumers would use virtual care for a variety of activities—from e-visits to diagnosis to group therapy. According to a survey by Accenture, nearly three-quarters of health-care consumers (73%) would use virtual care for an after-hours appointment, and about two-thirds (65%) would use it for a follow-up appointment after seeing a doctor or other health-care professional in person [9].
\nAmazon is also a heavy investor in healthcare. In 2017, it invested into genomics cancer detection company GRAIL. In addition, Amazon’s recent partnership with JP Morgan and Berkshire Hathaway to provide employees with better health insurance signals broader ambitions to upend traditional healthcare [8].
\nThe question remains, how can connected health insurance transform the insurance company from a simple payer of premiums to a proactive player in the customer health journey? Insurers need to stay profitable, and that is perfectly achievable with such a model (insurer that takes “care” of the customer and not just help with the “cure” after a person is ill). There are five main value creation levers to take into consideration according to the theory proposed by Carbone and explained in the book
Enhancing the underwriting phase with a temporary monitoring based on dedicated devices. As far as the risk selection layer is concerned, connected devices can be indirectly or directly used to select risks at an underwriting stage resulting in low-risk customer acquisition and connected reduction in fraudulent intents.
\nLoyalty and behavior modification programs lead the client toward risk-free behavior. Behavioral programs are basically approaches that exploit information gathered on behavior to direct clients toward less risky solutions. To this scope a reward system that stimulates safer client behaviors is a key element in this evolved insurance landscape, and programs based on innovative gamification approaches are a must in order to keep clients engaged.
\nIn other words, developing client-tailored ancillary services allows the insurer to play as an omnichannel medical concierge.
\nValue-added services consist in the proposition to clients of policy-related services that have a double aim: on the one hand to guide clients toward desired behavior and, on the other hand, to offer perceived value through services to clients. Some ancillary services are proposed to the insured clients in order to exploit relevant data detected; these services could be directly supplied by the insurance company or by means of specialized partners.
\nConnected insurance allows to use registered data in order to limit the portfolio loss ratio, and it enables the development of claims management processes that permits the insurance company to act more proactively and make the whole process faster and more efficient.
\nRisk-based pricing consists in developing insurance policies with pricing linked to client behaviors. Monitoring the “quantity” and “level” of risk exposure during coverage period has become possible. In this sense, the risk can be calculated based on gathered information monitoring with a direct impact on pricing applied to the single customer.
\nInsurers are beginning to use wearable technology and health apps to reduce risk and improve technical results. Some are educating customers on looking after their own health resulting also in higher customer engagement. Big data gathering and analysis sit at the base of an improved design and product pricing which in turn can encourage clients to adopt a healthier lifestyle. Finally, the very effectiveness of medical treatments can be improved through technology.
\nInsurance companies have begun to have a more proactive approach by staying in contact with their customers even when they are in completely good health and not only when they seek help themselves. This can be done using innovative systems like wearables and reward schemes. Thanks to the integration between intelligence, connectivity, and better usability, wearable devices can offer interesting opportunities in health and activity monitoring, tracking, personal notifications, and virtual assistance.
\nIn order to better grasp the actual benefits for clients and not just for insurers that adopt such an innovative approach, we should take a closer look at the South African insurance player Discovery that can be considered the benchmark when it comes to engaging members and improving their quality of life. Its Vitality program has managed to create a system that not only raises the loyalty of customers but improves their lifestyle and overall state from a health point of view. They apply the five value creation levers mentioned above in a way that brings concrete results for the company and for the insured.
\nIn the case of Vitality, it is applied as a reward system that stimulates safer client behavior through gamification to keep customers engaged. The gamification strategy used by Vitality is run with the support of an extended network of partners and with the help of wearables and smart objects alongside the well-known smartphone. They create mini challenges related to shopping for food, physical and sporting activities, medical checkups, and so on that if accomplished are rewarded with cash-back, discounts, or other types of incentives. As a consequence, the individuals end up having a more active life (engaged Vitality members exercise 25% more than non-Vitality members), and according to a study released by Discovery [12], they live longer than non-Vitality members: to be more precise, the average life expectance of an insured South African is 67 years, while the average life expectancy of an insured Vitality member is 81 years. Incentivizing behavior change has led to improved health and lower risk—and as a result lower premiums—for members and improved lapse and claim rates for Discovery. Lapse rates for Vitality status are as much as 67% lower than for those policy holders who do not engage with Vitality, while mortality risk is 72% lower for Vitality Gold and Diamond members who are physically active at least twice a week [13].
\nCustomer loyalty is also intertwined, in Vitality, with value-added services. Vitality offers extra services linked to the insurance cover, which have a double aim: on the one hand to guide clients toward desired behavior and, on the other hand, to offer perceived value through services to clients. Very often these services are provided by means of specialized partners. Clients are also rewarded for making healthier choices through PayBack benefit, which has paid out a total of R 2.4 billion to healthier clients since launch.
\nAlthough it is easier to apply this lever to telematics-based auto insurance where monitoring objective data about driving style is relatively easy, the method can also be used when referring to health insurance. The use of connected devices gives the insurer (Discovery) precious data on people’s lifestyle and health condition. This helps create a clearer segmentation and thus the ability to select risk in a more effective way. But maybe even more important, the Vitality program attracts younger and healthier people to start with, precisely because this category is proportionately more attracted by the technological, more digital insurance.
\nMonitoring the “quantity” and “level” of risk exposure during the coverage period has now become possible. In this sense, the risk can be calculated based on collected information with a direct impact on pricing applied to the single customer. We do not have enough data to confirm that this is being applied through the Vitality program, but it is becoming a standard practice for telematics-based car insurance where the object of the insurance coverage is easier to evaluate than in the case of a living breathing person.
\nBy using connected devices with their customers, Discovery possesses an “early warning” mechanism that can anticipate serious health problems and more expensive claims.
\nAccording to Discovery, Vitality Gold status members with heart disease have 41% lower risk claims than members with no Vitality membership. If we are to look at data regarding diabetics, it seems that Vitality Gold members living with this condition have 53% lower risk claims [14].
\nAnother interesting claim coming from a recent presentation by Discovery Vitality at DIA Amsterdam 2018 deserves our attention. According to the results, there is an 18% reduction of hospital and chronic claim costs for the batch of Vitality members that use the Vitality Active Rewards (VAR) alongside the Apple Watch, compared to the group of insured who do not use an Apple Watch. VAR is a smartphone application based on fitness points, which is designed to encourage Vitality members to increase their activity levels by setting weekly personalized physical activity goals and then rewarding users for achieving them. Nevertheless Discovery specifies that the above data are based on a cross-sectional view of the relative claim experience, and it is premature to show the improvement over time given the lower frequency of health claim events. In any case, I show that certain wearables together with the right reward system may have significantly positive results but have yet to be observed over a longer period of time. This is backed up by the data presented by Discovery regarding Apple Watch owners enrolled in the program. It seems that these users are 35% more active than prior to getting the watch. Since the VAR system was launched, there has been a 36% increase in physical activity [14].
\nThe data are very telling, and the implications for ensuring healthy lives and promoting well-being are significant. The Vitality model should be further investigated in order to understand if and how it could work for the general population, not only for specific segments, and to see to what degree innovation driven by insurers and technology companies can be used to benefit citizens in general. The transition to a “prevention-centered” approach is actually a pragmatic decision for insurers because in time, the portfolio tends to change its structure, passing from a majority of so-called “sick” clients to a majority of relatively “in good health” clients [15, 16].
\nDiabetes is a chronic disease that occurs either when the pancreas does not produce enough insulin or when the body cannot effectively use the insulin it produces. In 2014, 8.5% of adults aged 18 years and older had diabetes. In 2016, diabetes was the direct cause of 1.6 million deaths, and in 2012, high blood glucose was the cause of another 2.2 million deaths [17]. It is estimated that diabetic patients worldwide will be 629 million by 2045 [18].
\nDiabetic patients have significantly higher risk to develop severe complications generated by the evolution of the pathology compared to nondiabetic patients. Complications arising from the evolution of this disease are peripheral neuropathy, retinopathy, nephropathy, and cardiovascular diseases.
\nIt is well known that insurers either do not cover diabetic patients or, if they do, they require a significantly high premium. This is due to the difficulty to measure the probability of the occurrence of risks associated to these clients.
\nTherefore, the insurance sector is leaving uncovered a market that is becoming more and more relevant.
\nICS Maugeri is a major group of hospitals specialized in rehabilitation medicine offering a multidisciplinary approach in treating diseases and disabilities. ICS Maugeri’s research team has developed, in partnership with the University of Pavia, an instrument called MOSAIC aimed at improving the clinical management of patients affected by diabetes mellitus type 2 (T2DM) that can calculate the risk of developing complications related to T2DM in different time scenarios.
\nMOSAIC uses AI and machine learning which is based on algorithms able to learn patterns and decision rules from data. These machine learning algorithms have been embedded into data mining pipelines, which can combine them with classical statistical strategies, to extract knowledge from data. Within the EU-funded MOSAIC project, a data mining pipeline has been used to derive a set of predictive models of type 2 diabetes mellitus (T2DM) complications based on electronic health record data of nearly 1000 patients.
\nBased on the results expressed in the research paper, the team has been able “to predict the onset of retinopathy, neuropathy, or nephropathy, at different time scenarios, at 3, 5, and 7 years from the first visit at the Hospital Center for Diabetes (not from the diagnosis). Considered variables are gender, age, time from diagnosis, body mass index (BMI), glycated hemoglobin (HbA1c), hypertension, and smoking habit.” The final models are thus able to provide up to 83.8% accuracy in predicting the probability for a diabetic to develop the three main complications and are easy to apply in clinical practice.
\nIt is furthermore demonstrated that intensive multifactorial pharmacological intervention (compared to conventional therapy) leads to significant improvements [19]:
Additional 7.9 years life span compared to cases where conventional treatment is applied.
First complication appeared 8.1 years later than in patients with normal treatment.
General reduction of microvascular complications.
In insurers’ terms, this shows that not only risk associated to diabetes can be estimated but also that a proper management of diabetic patients could lead to significant reduction of the risk itself. The question is how can insurers make sure that diabetic patients follow the required therapeutic path?
\nIn fact, diabetic patients are required to follow a rigorous clinical, diagnostic, and therapeutic path in order to manage and control their pathology and try to limit and/or slow down the consequences of this chronic disease. This path involves periodic medical checks, diagnostic tests, as well as continuous and intensive drug therapies, requiring significant effort for patients and their caregivers. Most of the time, the scheduling of such periodic checks must be autonomously managed by the patient, resulting in a progressive reduction of adherence to the required clinical paths. This may lead to severe deterioration of the health state of diabetic patients.
\nThe MOSAIC project has developed algorithms that allow to predict the onset of diabetes-related pathologies, and furthermore, it has developed a platform that allows a real-time monitoring of main risk factors (e.g., hypoglycemia). As part of the program, a face-to-face general examination with a medical doctor is carried out at least yearly, to estimate main risk factors and to identify a personalized clinical, diagnostic, and therapeutic program. The patient follows the prescribed program and is monitored through wearables and telemedicine; this allows to (i) personalize, update, and modify pharmacological treatments, (ii) identify and update the diagnostic path to be performed in order to monitor and reduce the risk of complications, and (iii) identify on-time criticalities that may require timely investigations.
\nThe patient follows the indicated diagnostic-therapeutic program and is also monitored through wearables and telemedicine. As a consequence, this approach allows a significant risk control and, potentially, reduction, allowing the insurance to update the premium yearly.
\nWe are all witnesses to a major shift in the way that medical services are delivered. The insurance industry is slowly passing from a one-size-fits-all approach to a personalized approach that looks at individuals and their habits, needs, and their environment. As the World Health Organization predicts a 13 million doctors’ deficit at worldwide level by 2035 [20], it’s essential for connected health and connected health insurance to evolve in such a way that will allow primary health-care providers to be much more versatile and flexible in reaching their patients. Clearly, the new paradigm in connected insurance will face several challenges posed by rate of adoption, cost barriers, resistance to change, and privacy aspects, but nevertheless the potential benefits could be significant based on Discovery Vitality case study, for both insurance companies and customers alike. On the one hand, insurance carriers could be able to reduce their costs and at the same time positively influence the health state of their customers. On the other hand, citizens will have improved access to better medical care and health advices at a convenient cost. Further research needs to be done: (1) of Discovery Vitality programs worldwide in order to understand how results vary over time and from country to country and (2) of similar connected insurance programs promoted by other insurance companies with the objective of understanding how changes in the rewards/engagement system reflect on the results.
\nAccording to the World Health Organization, just four decisions, physical inactivity, poor nutrition, smoking, and alcohol use, lead to four illnesses—cancer, heart and artery diseases, lung disease, and diabetes—that cause around 60% of global deaths [21]. Based on this information, one can argue that Discovery’s model combined with a predictive system such as MOSAIC’s could have an even greater impact on avoiding unhealthy behavior and more specifically keeping under control diabetes type 2 cases worldwide by ensuring that patients are correctly managing their condition. The insurer would be increasing its insureds base while helping diabetic patients take control of their chronic disease while also keeping costs in check.
\nThe concept of loyalty and behavior modification programs utilized by Carbone and discussed above could be an evolution or add-on to MOSAIC’s approach when applied by an insurer like Discovery. A reward-based system could work as an additional incentive toward keeping diabetics effectively engaged. Taking for granted that diabetics will follow a program step by step and change their behavior toward a desired goal is not something an insurer should do. Here comes the reward as an element that can help in reaching that goal and at the same time give the insureds something to look forward. Even if the real stake for diabetics in such cases is their own life expectancy—which should be motivation enough—the reward element could be a good and fun extra incentive for reaching health goals.
\nAs estimated costs with lifestyle-related conditions (including diabetes) will be 47 trillion by 2030 [22], insurers, the health-care systems, clinical providers, and patients could all benefit in some way from such a program. It would be interesting to look at how this approach could be extended to other chronic diseases and what the state of research is in these other fields.
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\n\nThe first step in obtaining funds for your Open Access publication begins with your institution or library. IntechOpen’s publishing standards align with most institutional funding programs. Our advice is to petition your institution for help in financing your Open Access publication.
\n\nHowever, as Open Access becomes a more commonly used publishing option for the dissemination of scientific and scholarly content, in addition to institutions, there are a growing number of funders who allow the use of grants for covering OA publication costs, or have established separate funds for the same purpose.
\n\nPlease consult our Open Access Funding page to explore some of these funding opportunities and learn more about how you could finance your IntechOpen publication. Keep in mind that this list is not definitive, and while we are constantly updating and informing our Authors of new funding opportunities, we recommend that you always check with your institution first.
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Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Bacterial Infectious Diseases",value:3,count:2},{group:"subseries",caption:"Parasitic Infectious Diseases",value:5,count:4},{group:"subseries",caption:"Viral Infectious Diseases",value:6,count:7}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:2},{group:"publicationYear",caption:"2021",value:2021,count:4},{group:"publicationYear",caption:"2020",value:2020,count:3},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:249,paginationItems:[{id:"274452",title:"Dr.",name:"Yousif",middleName:"Mohamed",surname:"Abdallah",slug:"yousif-abdallah",fullName:"Yousif Abdallah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274452/images/8324_n.jpg",biography:"I certainly enjoyed my experience in Radiotherapy and Nuclear Medicine, particularly it has been in different institutions and hospitals with different Medical Cultures and allocated resources. Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University, Kuwait. His research interests include optimization, computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, and intelligent systems. Prof. Sarfraz has been a keynote/invited speaker at various platforms around the globe. He has advised/supervised more than 110 students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He has authored and/or edited around seventy books. Prof. Sarfraz is a member of various professional societies. He is a chair and member of international advisory committees and organizing committees of numerous international conferences. He is also an editor and editor in chief for various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:"Beijing University of Technology",institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Lakhno Igor Victorovich was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPhD – 1999, Kharkiv National Medical Univesity.\nDSc – 2019, PL Shupik National Academy of Postgraduate Education \nLakhno Igor has been graduated from an international training courses on reproductive medicine and family planning held in Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor of the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s a professor of the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education . He’s an author of about 200 printed works and there are 17 of them in Scopus or Web of Science databases. Lakhno Igor is a rewiever of Journal of Obstetrics and Gynaecology (Taylor and Francis), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for DSc degree \\'Pre-eclampsia: prediction, prevention and treatment”. Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: obstetrics, women’s health, fetal medicine, cardiovascular medicine.",institutionString:"V.N. Karazin Kharkiv National University",institution:{name:"Kharkiv Medical Academy of Postgraduate Education",country:{name:"Ukraine"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"243698",title:"M.D.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:"Shanxi Eye Hospital",institution:{name:"Shanxi Eye Hospital",country:{name:"China"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRZkkQAG/Profile_Picture_2022-05-09T12:55:18.jpg",biography:null,institutionString:null,institution:null},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. 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\r\n\tPollution is caused by a wide variety of human activities and occurs in diverse forms, for example biological, chemical, et cetera. In recent years, significant efforts have been made to ensure that the environment is clean, that rigorous rules are implemented, and old laws are updated to reduce the risks towards humans and ecosystems. However, rapid industrialization and the need for more cultivable sources or habitable lands, for an increasing population, as well as fewer alternatives for waste disposal, make the pollution control tasks more challenging. Therefore, this topic will focus on assessing and managing environmental pollution. It will cover various subjects, including risk assessment due to the pollution of ecosystems, transport and fate of pollutants, restoration or remediation of polluted matrices, and efforts towards sustainable solutions to minimize environmental pollution.
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",annualVolume:11967,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/39.jpg",editor:{id:"137040",title:"Prof.",name:"Jose",middleName:null,surname:"Navarro-Pedreño",fullName:"Jose Navarro-Pedreño",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRAXrQAO/Profile_Picture_2022-03-09T15:50:19.jpg",institutionString:"Miguel Hernández University of Elche, Spain",institution:null},editorTwo:null,editorThree:null,editorialBoard:[{id:"177015",title:"Prof.",name:"Elke Jurandy",middleName:null,surname:"Bran Nogueira Cardoso",fullName:"Elke Jurandy Bran Nogueira Cardoso",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRGxzQAG/Profile_Picture_2022-03-25T08:32:33.jpg",institutionString:"Universidade de São Paulo, Brazil",institution:null},{id:"211260",title:"Dr.",name:"Sandra",middleName:null,surname:"Ricart",fullName:"Sandra Ricart",profilePictureURL:"https://mts.intechopen.com/storage/users/211260/images/system/211260.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}}]},{id:"40",title:"Ecosystems and Biodiversity",keywords:"Ecosystems, Biodiversity, Fauna, Taxonomy, Invasive species, Destruction of habitats, Overexploitation of natural resources, Pollution, Global warming, Conservation of natural spaces, Bioremediation",scope:"