Cerebellar abnormalities in mouse models of ASD.
\\n\\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\\n\\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\nFeel free to share this news on social media and help us mark this memorable moment!
\\n\\n\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/237"}},components:[{type:"htmlEditorComponent",content:'
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\nIntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\n\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\nFeel free to share this news on social media and help us mark this memorable moment!
\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{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"}]},book:{item:{type:"book",id:"709",leadTitle:null,fullTitle:"Inflammatory Bowel Disease - Advances in Pathogenesis and Management",title:"Inflammatory Bowel Disease",subtitle:"Advances in Pathogenesis and Management",reviewType:"peer-reviewed",abstract:"This book is dedicated to inflammatory bowel disease, and the authors discuss the advances in the pathogenesis of inflammatory bowel disease, as well as several new parameters involved in the etiopathogeny of Crohn's disease and ulcerative colitis, such as intestinal barrier dysfunction and the roles of TH 17 cells and IL 17 in the immune response in inflammatory bowel disease. 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My areas of interest are esophageal diseases",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Hôpital La Rabta",institutionURL:null,country:{name:"Tunisia"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1021",title:"Hepatology",slug:"gastroenterology-hepatology"}],chapters:[{id:"26838",title:"The Role of COX-2 Inhibitors on Experimental Colitis",doi:"10.5772/26069",slug:"review-article-the-role-of-selective-cox-2-inhibitors-on-experimental-colitis",totalDownloads:2499,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Ana Paula R. Paiotti, Ricardo Artigiani-Neto, Daniel A. Ribeiro, Sender J. 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Autism spectrum disorder (ASD) represents a group of heterogeneous neurodevelopmental conditions characterized by deficits in social cognition, together with the presence of restricted and/or repetitive patterns of behaviors, activities, or interests [1]. Social cognition refers to those cognitive processes that allow individuals to successfully navigate the challenges of living in a social group. Thus, a functional social cognitive system involves the integration of several domains of behavior including attention, memory, emotion, and motivation to be able to understand identity, potential actions, social hierarchy, and emotional status of a conspecific and therefore guide the appropriate behavioral response [2]. In autism, deficits in social cognition processes are found at multiple levels, such as failure to initiate or respond to social interactions, lack of interest in social situations, abnormal social approach, difficulties expressing and understanding verbal and nonverbal communication (i.e., body language and facial expressions), and problems adjusting behavior to different social situations, among others [1]. Autism affects roughly 1 in 59 children, becoming one of the primary mental health issues worldwide [3]. In addition to the main symptoms, ASD is usually associated with other behavioral and/or neurological problems, such as hyperactivity, epilepsy, aggression, irritability, sleep problems, gastrointestinal symptoms, and sensory processing abnormalities [4].
Although currently accepted to be highly genetic (over 90% of the risk of developing ASD is due to genetic variation) [5], the etiology of ASD is complex, and its genetic architecture is diverse. Common allelic variation with small effect sizes is responsible for most cases, while rare but highly penetrant mutations that usually lead to other syndromes associated with autism are observed in about 20% of the cases [6]. In addition to genetic factors, exposition to some environmental factors during prenatal periods has also been associated with autism. Some of the most replicated are the intake of valproic acid, a drug used to treat epilepsy, during pregnancy and maternal infections. In all, the combination of interactions between genetic predisposition and environmental factors will determine the development of the disorder [7]. Given the clinical and etiological heterogeneity of ASD, the investigation of its pathophysiology has been challenging. From a research point of view, the study of “single gene” causes of autism, although rare in the population, has been proven to be useful to understand its pathophysiology and develop targeted treatments. In addition, animal models of monogenic causes of autism are easily generated and constitute a critical component of research. Research from both human and animal studies converge in a series of key brain structures and circuits involved in social cognition and their dysfunction in autism. Within these circuits, the cerebellum, traditionally associated with movement control, is becoming an important player in the social brain network. In this chapter, we will first start by describing the social brain circuitry traditionally thought to be affected in autism; we will then present evidence for the role of the cerebellum as a new player in the social circuitry and its role in the pathophysiology of ASD; finally, we will present data from animal models of monogenic causes of ASD in which a cerebellar pathology has been described such as Fragile X syndrome
In humans, brain regions implicated in social cognition have been identified mainly by lesion studies or by functional magnetic resonance imaging (fMRI) detecting differential activation in response to social versus nonsocial cues. Accordingly, a network of key brain structures involved in the perception, integration, and coding of social cues have been identified, receiving the denomination of “the social brain.” These structures comprise brain areas traditionally involved in
The cerebellum, conventionally associated with motor functions, is lately being considered a key structure within the social circuitry [18]. In fact, cerebellar neuroanatomical alterations, including the reduced size and number of Purkinje cells, are among the most replicated findings in postmortem brain samples of individuals with autism [19]. In addition, cerebellar defects have been proposed to affect the functioning of distal brain areas to which the cerebellum projects [20]. For example, the PFC long-range connection deficits observed in ASD mentioned above include the cerebellum [13]. The
Although human neuroanatomical and functional studies have been very useful in the identification of the brain regions involved in social cognition, animal studies are critical to understand how information is processed at the circuit and molecular level, from the perception of the stimulus to the expression of a behavioral response. The mouse (
Brain circuits linked to social cognition in mice. Olfactory signals from a social stimulus are perceived through the olfactory bulb and transferred to the amygdala (AMYG) and probably other structures to be processed. This social cue will modulate the activity of several structures. One of such, the ventral tegmental area (VTA), mainly composed of dopaminergic neurons, projects to the PFC (executive function) and NAcc (reward system). Of note, the cerebellum modulates VTA activity implying a role in social behavior and reward. Adapted from [
The cerebellum (Latin,
Structurally, the cerebellum is constituted of ten lobules: lobules I through V (which form the anterior lobe), lobules VI through IX (posterior lobe), and lobule X (flocculonodular lobe). Lobules VII and VIII are further subdivided (VIIA and VIIB and VIIIA and VIIIB); besides, the hemispheric extension of lobe VIIA is expanded and forms two major lobules, Crus I and Crus II. Dividing the cerebellum ventrally into two hemispheres, there is a central midline called the vermis (Figure 2) [20]. Within this anatomical division, a functional division according to the connection of each lobe can be found, establishing a topographic organization (see Subsection 3.2).
Structural anatomy of the human cerebellum. Representation of the cerebellar lobules: anterior, posterior, and flocculonodular and their subdivisions. Lobules VII and VIII are further subdivided into lobules A and B. Crus I/Crus II constitutes further subdivisions of lobule VIIA. The vermis represents a midline separating the cerebellum in two hemispheres. Modified from [
At the cellular level, the cerebellum is composed of an outer cortex constituted of gray matter, the cerebellar cortex, and an inner core formed mainly by white matter which encloses the deep cerebellar nuclei, the sole output channel of the cerebellum (see below). The cerebellar cortex is structured in three different cell layers: (1)
Neurons in the deep cerebellar nuclei represent virtually all the output from the cerebellum. They receive inhibitory information from the PC and excitatory inputs from outside the cerebellum through the mossy and climbing fibers. The
Main cerebellar circuits. The mossy and climbing fibers carry the input information toward the cerebellum. The PC transmit the information to the deep cerebellar nuclei, which are the cerebellar output. The interactions between the cells are represented with (+) in case of excitatory connections and (−) when connections are inhibitory. Modified from [
The cerebellum has a unique topographic organization such as each region is attributed with a separate function based on their specific connectivity. Thus, the anterior lobe and lobule VIII contain the representation of the sensorimotor cerebellum; lobules VI and VII (including Crus I/Crus II and lobule VIIB) of the posterior lobe comprise the cognitive cerebellum; and the posterior vermis encompasses the limbic cerebellum. Dysfunction in the connection of these cerebellar areas with the spinal cord or cerebral regions will result in alterations in movement or cognitive functions, respectively [30, 31]. More specifically, the cerebellum has been proposed to have an important role in language by means of its connections with cortical areas implicated in this process. Studies using viral tracing in nonhuman primates report the existence of strong connections between right Crus I/Crus II and different cortical regions implicated in language, such as Brodmann’s area BA46 in the PFC [32]. In fact, dysfunction in cerebellar-prefrontal loops might underlie poorer performance on measures of language-related executive function in human patients with cerebellar abnormalities [33]. The cerebellum also seems to play a role in several social and affective processes. For example, imitation is a critical skill for implicit learning of social rules, and fMRI studies in humans show that during a task that involves observation and imitation of an action performed by a human model, activation of the Crus I/Crus II regions in the posterior cerebellum is increased [34]. Also, during a passive viewing paradigm, a stronger activation in the posterior cerebellum (lobules VI, VII, and X) has been found when comparing social versus nonsocial stimuli [35]. In fact, a recent meta-analysis of over 350 fMRI studies exploring the role of the cerebellum in social cognition supports that it plays a crucial role in several social paradigms such as mirroring (i.e., observation of human motion) and mentalizing (i.e., interpreting other people’s thoughts and intentions) [36, 37].
In the recent years, there has been increasing evidence showing a crucial role for the cerebellum in the etiology of ASD [38, 39, 40]. Although the field of cerebellar research in disorders of social cognition such as autism is still in its early stages, below we will describe the main structural and functional cerebellar abnormalities that have been described to date in autism, which provide strong evidence to grant further research.
The cerebellum is actually one of the most consistent sites of neural abnormalities found in autism [41]. Specifically, the reduced size and number of PCs are among the most replicated findings in postmortem brain tissue of individuals with autism [19]. This reduction in PC in autism patients has been found to be more pronounced in the Crus I/Crus II region of lobule VIIA [42]. Accordingly, a reduction in gray matter volume, smaller ratio of gray to white matter, and smaller vermis lobules VI–VII have been found in children with autism compared to controls [43, 44]. Further, in ASD patients, the degree of reduction in gray matter of Crus I/Crus II has been repeatedly found to correlate with the severity of symptoms in the social interaction and communication behavioral domains of ASD [39, 45]. Of note, some reports using adult brains indicate the presence of gliosis as an accompanying factor to the reduction of PC [46]. Other observed cerebellar cellular abnormalities are the presence of neuro-inflammatory processes [47].
Besides structural and cellular alterations, molecular abnormalities have also been reported in the cerebellum of ASD individuals. Alterations in the distribution of the mRNA levels of glutamic acid decarboxylase 67 (GAD67), an enzyme involved in the synthesis of the inhibitory neurotransmitter GABA, have been found. Thus, decreased GAD67 mRNA has been reported in PC [48], while increased GAD67 mRNA has been reported in cerebellar interneurons [49]. These cerebellar imbalances could account for the proposed E/I disequilibrium in ASD, as they could affect cerebro-cerebellar circuits [50].
Studies in humans using resting-state functional connectivity (rsFC) techniques have reported connectivity alterations between cerebellar and cortical areas in autism compared to typically developing individuals. Overall, a general cerebro-cerebellar over-connectivity has been found in the ASD group. However, both hyper-connectivity and hypo-connectivity have been reported depending on the regions analyzed. For example, cerebellar-sensorimotor FC (premotor and primary motor cortices, somatosensory temporal cortex, and occipital lobe) has been found to be atypically increased in ASD, while cerebellar-supramodal FC (prefrontal cortex, posterior parietal cortex, and inferior and middle temporal gyri) has been found to be decreased [51]. Analysis of cerebellar FC with language-related areas revealed a significantly reduced FC in ASD between the cerebellum and Broca’s area and Wernicke’s area [52], suggesting that the cerebellum plays a role in language functioning. Studies aiming at assessing the developmental pattern of cerebello-cerebral FC also report developmental alterations in ASD. FC between the cerebellum and subcortical regions was found to decrease in neurotypical individuals, while it increased in ASD [53]. It must be noted that no specific correlation between FC patterns and autism behavior has been detected, although reduced connectivity seems to be accompanied by an increase in the severity of the disorder [52], as assessed by the Social Communication Questionnaire, an ASD screening measure consisting of a brief (40-item) parent report that focuses on ASD symptomatology likely to be observed by a primary caregiver.
Few studies have investigated to date the FC between the cerebellum and cortical areas during task performance in ASD. During a sequential finger-tapping task, activations in motor circuits were found in both cases and controls. However, children with typical development showed activation of cerebellar structures that were silent in autistic children (lobules IV/V and anterior cerebellum). In addition, a reduced FC between premotor areas and the cerebellum was observed in autistic children, suggesting alterations in long-range cerebro-cerebellar connections [54]. In a task that requires perception and imitation of human actions, fMRI detected an engagement between the posterior superior temporal sulcus (pSTS) and the cerebellar region Crus I [55]. Interestingly, the degree of functional coactivation of pSTS and Crus I could predict social deficits in ASD in the “mentalizing skills” questionnaire, a parent report for specific social cognition skills based on imaginative mental activity that allows an understanding of the behavior of other people (intentions, needs, desires, or goals). Thus, stronger Crus I-pSTS interactions were associated with better mentalizing ability [55]. On a similar note, during a task that involves decoding the interactions between animated figures, aimed at examining the “theory of mind” network, that is, the ability to attribute mental states to others, a reduced cerebellar activation, particularly in Crus I, in participants with ASD was found [56]. Although many more studies are needed, overall the above-presented data indicate a role for cerebellar connections with key cortical social brain sites and, specifically for region Crus I/Crus II, in the pathogenesis of ASD.
The clinical and genetic heterogeneity present in ASD has made the study of the pathophysiology of the disease challenging. The study of genetically defined autism, as in the case of monogenic forms of ASD, which show a relatively homogeneous and well-characterized clinical manifestation, allows us to understand cellular and molecular mechanisms relevant to the disease. Although monogenic causes of ASD are often syndromic and not all patients with the syndrome show autistic features, by studying patients with and without ASD, we can start deciphering the pathomechanisms that lead to the disorder. As shown below, human postmortem and brain imaging studies of syndromic forms of ASD support the role of the cerebellum in the pathophysiology of the disease. Animal models of monogenic autism are easily generated and provide opportunities for direct manipulation of these brain regions and circuits to test their precise functions in social behavior paradigms. We will describe below the main syndromes with reported cerebellar dysfunction and supporting data from animal models (Table 1). In all, human and animal data point out a role for the cerebellum in social deficits in ASD.
Mouse model | Structural abnormalities | Functional abnormalities | Refs. |
---|---|---|---|
Fmr1 KO |
|
| [57, 58, 59, 60] |
Fmr1-PC cKO |
|
| [60] |
TSC1-PC cKO +/− |
|
| [61, 62] |
TSC1-PC cKO −/− |
|
| [61, 62] |
TSC2-PC cKO+/− |
| N/A | [63] |
SHANK2 KO | N/A |
| [64] |
SHANK3 ΔC |
|
| [62] |
Cerebellar abnormalities in mouse models of ASD.
Fragile X syndrome (FXS) is the most common form of inherited intellectual disability, and ~30% of FXS patients are also diagnosed with ASD. FXS is considered also as the most common genetic cause of ASD, representing around 3% of ASD individuals. FXS arises from loss of function mutations in the X-linked FMR1 gene, which result in either total absence or functional inactivation of the encoded protein (FMRP), an mRNA-binding protein involved in translational regulation [65]. Although FXS affects many brain regions, cerebellar PC loss and cell displacement, as seen in idiopathic autism, have been reported in human postmortem studies of FXS [66]. Interestingly, imaging studies have identified specific abnormalities in the posterior cerebellar vermis (lobules VI–VII) in FXS patients with ASD that are not seen in FXS patients without comorbid ASD diagnosis. Further, these lobules are also abnormal in non-syndromic ASD [57]. Moreover, positive correlations between the size of the posterior vermis and several subscales of the autism behavior checklist, a list of nonadaptive behaviors that represent an individual’s challenges to respond appropriately to daily life situations, in persons with FXS, have been reported [58]. On a different note, recent postmortem work has shown reductions in FMRP in cerebella and frontal cortices of subjects with autism who do not carry a mutation for FXS [59].
The Fmr1 knockout (KO) mouse is a validated and widely studied animal model of ASD. By means of high-resolution MRI imaging to study brain structure, the cerebellum in Fmr1 KO mice was found to show significant volume alterations comparing with wild-type controls. Specifically, the deep cerebellar nuclei, which transfer the output of the cerebellar cortex to the thalamus and cerebral cortex, were smaller in Fmr1 mice. Moreover, this reduced volume was accompanied by loss of neurons and increase in astrocytes, as measured by immunohistochemical techniques [60]. Later, the same authors also identified a volume reduction in the cerebellar cortex in these mice [67]. Further, a detailed study by diffusion tensor imaging of postnatal development in the Fmr1 KO mouse showed reduced cerebellar volume in the first few weeks after birth [68]. In addition to the full KO, a conditional Fmr1 KO mouse (Fmr1 cKO) has also been generated. Deletion of Fmr1 specifically in PC leads to several structural and functional abnormalities in the cerebellum also seen in the full Fmr1 KO, such as a reduction of cerebellar volume, cellular loss in the cerebellar nuclei, and longer spines in PC. Functionally, an enhanced LTD induction at the parallel fiber synapses that innervate these spines is seen [63]. In addition, both Fmr1 KO and PC-Fmr1 cKO mice present alterations in classical delay eyeblink conditioning, a Pavlovian associative learning where subjects learn to execute an appropriately timed eyeblink in response to a previously neutral conditioning stimulus in which the cerebellum plays a key role. Specifically, the percentage of conditioned responses and their peak amplitude and peak velocity were reduced. [63]. Interestingly, FXS patients were found to display the same cerebellar deficits in eyeblink conditioning as mutant mice [63]. Together these results suggest that the deficits in eyeblink conditioning are likely due to the loss of FMRP in PC.
Tuberous sclerosis (TS) is another rare syndromic disorder associated with ASD. TS is characterized by the development of non-cancerous tumors in the brain and other organs leading to neurological symptoms such as developmental delay, epilepsy, and ASD. It is an autosomal dominant condition caused by mutations in either the TSC1 or TSC2 genes, which form a tumor suppressor complex involved in the regulation of the mTOR signaling pathway. Approximately 40% of TS patients are co-diagnosed with ASD, and, interestingly, those with cerebellar lesions have been found to have a more severe ASD diagnosis [61]. Further, PC loss has been found in postmortem cerebellum samples from TSC patients [62].
Several lines of mutant TSC mice have been generated and studied in detail. A mutant mouse in which the Tsc2 gene was selectively deleted from PCs starting at postnatal day 6 was generated to mimic patients with one nonfunctioning TSC2 allele [62]. The haploinsufficiency of TSC2 caused a progressive increase in PC cell size and subsequent death from apoptosis. TSC2-null PCs showed increased endoplasmic reticulum and oxidative stress, which were rescued by treatment with the mTOR inhibitor rapamycin. In a subsequent study, the authors reported that PC-TSC2-haploinsufficient mice showed social deficits and repetitive behaviors [64]. These observations indicate that selective loss of TSC2 in PCs in a TSC2-haploinsufficient background is enough to lead to autistic-like behavioral deficits. A conditional PC-TSC1 KO mouse has also been generated. Both heterozygous and homozygous losses of TSC1 in mouse cerebellar PCs result in autistic-like behaviors, including abnormal social interaction and repetitive behavior and vocalizations, in addition to decreased PC excitability. Similar to TSC2 mutants, treatment of TSC1 mutant mice with the mTOR inhibitor, rapamycin, prevented the pathological and behavioral deficits. Strikingly, PC-TSC1 homozygous mice, but not PC-TSC1 heterozygous mice, showed PC loss at 2 months of age. The fact that PC-TSC1 heterozygous mice showed autistic symptoms and PC excitability alterations in the absence of PC loss suggests that the decrease in PC excitability is likely driving the phenotype [69]. Further, this model has also been reported to show deficits in eyeblink conditioning; they specifically show lower percentage of conditioned response in this test [70]. These findings demonstrate new roles for TSC1/TSC2 in PC function and define a molecular basis for a cerebellar contribution to cognitive disorders such as autism.
Phelan-McDermid syndrome (PMS) is due to heterozygous chromosome 22q13 deletions and is often co-diagnosed with ASD. The clinical manifestations of PMS include global developmental delay/intellectual disability and absent or delayed speech [71]. Although the deletion encompasses numerous genes, a good candidate that could account for ASD symptoms is SHANK3, a gene within which mutations have independently been associated with non-syndromic ASD. ASD patients with SHANK3 deletions are also known to have severe core symptoms and mental disabilities [72]. Although to our knowledge there is no data addressing the effect of SHANK3 mutations on cerebellar anatomy and function, recent research suggests that mutations in
Multiple mouse lines with SHANK3 mutations exist, and several display behaviors analogous to the core symptoms of autism, including isoform-specific SHANK3B KO [76], SHANK3 (∆exons4–9) deleting major isoforms of the gene [77], and SHANK3 (∆C), deleting the C-terminal region of the gene [78]. SHANK3 (∆C) mice present a decreased density of PC compared to controls [70], and they show deficits in the eyeblink conditioning task, showing lower percentage of conditioning response and a delay in the response latency [70].
Interestingly, mutations in other proteins from the SHANK family, such as SHANK2, have been also linked to ASD. A KO mouse for SHANK2 shows alterations in social and repetitive behaviors and presents changes in PC electrophysiological characteristics, such as decreased intrinsic PC plasticity, synaptic strength at the PC-parallel fiber synapse, and enhanced inhibitory input into PC. Further PC-specific SHANK2 KO replicated these findings, arguing for a cerebellar role in autistic-like behaviors [79].
The cerebellum has been recently indicated as a key structure not only for sensorimotor control but also for language, social cognition, and emotion, via its extensive connections with cortical areas. In the present work, we aimed to provide an up-to-date overview of current findings on cerebellar involvement in the pathophysiology of ASD. Anatomical studies report cerebellar abnormalities in postmortem brain tissue from autistic individuals, neuroimaging studies indicate abnormal cerebellar activation when performing social paradigms, and animal models of monogenic forms of autism converge on the cerebellum as one of the common sites of abnormalities. The cerebellum represents an emerging field of interest for ASD research, based on the hypothesis that ASD is a connectivity disorder and cerebellar dysfunction could impact other brain areas within the social network, leading to the core ASD symptoms. Although the literature in this new field is at a very early stage, based on the presented data, future studies should not exclude the cerebellum in analyses of structural and functional differences in ASD.
This work was supported by the following grants: Spanish Ministry of Economy and Competitiveness/European Regional Development Fund (MINECO/FEDER grant SAF2015-64163-R). OP is a Ramon y Cajal Fellow (RYC-2013-12558), MF is supported by a predoctoral fellowship from the Spanish Ministry of Economy and Competitiveness MINECO (BES-2016-078420), and TS-A is supported by a predoctoral fellowship from the Basque Government.
A slope is an inclined ground surface formed naturally or by excavation for different human activities. Its stability is the major consideration in civil engineering infrastructural projects such as open-pit mining operations, road cut or embankment slopes as its failure causes considerable damage on the infrastructure, human life and property.
Instability of slope can be occurred due to internal or external factors which causes failure either by reducing the shear strength of slope material or by increasing the shear stress on the slope [1]. Different processes such as increased pore pressure, cracking, swelling, decomposition of clayey rock fills, creep under sustained loads, leaching, weathering, and cyclic loading are responsible to a reduction in shear strengths [2]. In contrast to this, the shear stress in slopes may increase due to additional loads at the top of the slope, increase in water pressure, increase in soil weight due to saturation, excavation at the bottom of the slope, and seismic effects [1]. Also, it must be noted that, slope geometry, state of stress, and erosion contributes to the failure of slope. The mechanism of slope failure varies and takes place as speed or slow rate, depending on the type of material, slope geometry, and types of triggering factors. Slide, fall, earth flow, debris flow, topple, planar and wedge failure are the common methods of slope failure.
As both natural and human activities are responsible for the failure of slopes, it is difficult to avoid the problem entirely. However, the level of damage can be significantly reduced by assessing the stability condition and adopting different preventive measures on it. There are various remedial measures applied during and after construction to reduce the impact of slope failure and these can be grouped into four general classes i.e. geometric modification, drainage control, slope reinforcement, and retaining structure [3].
Now a day slope stability studies have been attracted researcher’s attention as their understanding on the impact of slope failure in human life and infrastructural development increases. Numerous slope stability studies were carried around the world so far and better understandings are established about causes of failure, mechanisms of failure, methods of analysis, and possible remedial measures. However, the damages due to slope failure are increasing from year to year and still the major difficulty for the development of infrastructural constructions in Ethiopia. A review of previous slope stability assessments [4, 5, 6] indicates that slope failures are the main constraint for road and railway construction in Ethiopia. To overcome this problem and acquire better solutions a continuous effort is needed. Hence, this study was carried to evaluate the performance of geometric modification i.e. slope profiles (single slope, multi slope and multi slope) on slope stability using numerical methods.
The study area is located at Adama city in Ethiopia on a newly constructed ring road project. The area is in the east African refit valley system which is dominated by escarpments of various landscapes and bordering. The slope is formed by excavation of volcanic ridges and its height extends up to 40 m with 3 m bench every 10 m. Reddish to brownish color residual soils formed by a physical and chemical process from parent rock and volcanic rocks of different degree of weathering are the major type of materials found in the cut slope (Figure 1).
Location of the study area and slope section of the road.
Geometry is among the most critical factors controlling the stability of the slope [7, 8]. Generally, slope height, slope angle and slope profile are the major parameters in geometric modification. Cut and embankment slopes can be formed using one of the three profiles i.e. single slope, multi slope and bench slope. But depending on the composition of slope material, height of the slope, and hydrological conditions these profiles have different performance in the stability of slope.
Single slope profile is used in cut and embankments of dense soils with enough resistance against failure with a limited height [9]. Increasing height (h) and angle of slope (α) will increase the shear stress and decrease normal stress on the potential rupture plane [2]. As a result, h and α are major parameters control the performance of single slope profile.
Multi-sloped profiles are provided in cuts where the stratigraphy of soil consists of two or more layers with different strength characteristics [9]. The method allows the use of both steep and gentle slopes in stiff and weaker layer of the slope section respectively.
Bench slope profile is a technique in which the overall slope is divided into multiple small slopes. It reduces the driving forces above the failure surface by reducing the weight of slope [8]. Bench slope, bench height and bench width are the major parameters control the performance of bench slopes (Figure 2).
Geometric profiles of cut slope.
To investigate the performance of slope profiles a newly constructed road cut slope in Adama city was used. Under this investigation the effect of slope profiles and its parameters (slope height, slope angle, bench width, no of bench, and bench angle) on the stability of slope was evaluated interims of FS and deformation. The performance of multi-slope and bench slope profiles was evaluated with respect to single slope profiles and further comparison was made between them interims of construction difficulty, appearance or esthetic value, drainage control, and accessibility for maintenance.
For this FE modeling an elastic perfectly plastic Mohr-Coulomb material model was used. The model uses material stiffness (E and v) as elasticity parameter, material strength (𝜑, and c) as soil plasticity and 𝜓 as angle of dilatancy [10]. The slope section used for this investigation has both soil and rock layers, hence to determine the parameters both field and laboratory tests were carried. The soil shear strength parameters were obtained from direct shear test and its stiffness parameters were correlated with SPT data. Similarly, the strength and deformation parameters of rock layers were determined by correlating field and laboratory tests with rock data software. The geometric and material data used for this investigation were summarized in Figure 3 and Table 1.
Cross-section of the newly constructed road cut slope.
Sample code | Description of soil and rocks | C (kN/m2) | E (MPa) | V | ||||
---|---|---|---|---|---|---|---|---|
SSC-22 | Clayey sand | 20.1 | 16.4 | 14.57 | 27.89 | 0 | 25 | 0.215 |
SSC-21 | Sand with clay and gravel | 20.1 | 16.6 | 9.7 | 35.75 | 5.75 | 35 | 0.261 |
RSC-11 | Slightly to moderately weathered rock | 21.3 | 20.1 | 130 | 29.21 | 0 | 1962.8 | 0.35 |
RSC-12 | Highly weathered rock | 19.8 | 18.7 | 600 | 20.32 | 0 | 686.9 | 0.38 |
Material properties used in numerical modeling.
To evaluate the stability of slope in different profiles first initial stress and pore water pressure distribution was generated using 𝑘0 procedure and phreatic water level respectively. Then the deformation and safety analysis were carried with plastic calculation and phi-c reduction method for the same loading conditions. Phi-c reduction is a method where the shear strength parameters (c and tan∅) are successively reduced until the failure occurs [13]. During the process the strength reduction factor (∑ 𝑀𝑠𝑓) is increased start from 1. The global safety factor is equal to the total multipliers ∑ 𝑀𝑠𝑓 at the point of failure which is expressed as the ratio of initial and reduced strength parameters [10].
To validate the numerical model a slope section for this study was evaluated using Fellenius method (analytical solution) and the result was compared with numerical value both in FEM (plaxis) and LEM (slide) software’s (Figure 4).
FS determination using analytical solutions.
Validation also made using slope section first introduced by Zhang [14] and later used by numerous investigators i.e. Ferdlund and Krahn [15], Chen et al. [16], Griffiths and Marquez [17], Zhang et al. [18], and Chaowei et al. [19] to validate their 2D and 3D slope stability evaluations (Figure 5). The section was modeled using a slide, Plaxis-2D, and Plaxis-3D software with the same material and boundary condition. The result in Figure 6 shows a drift of ± 5% from previous investigators. Generally, from both validations the result from numerical modeling shows good agreement with the analytical solution and the previous works.
Modeling of slope section used for validation in slide, Plaxis-2D, and Plaxis-3D.
FS from different researchers and this study on Zhang [
Increasing angle and height of slope affects the stability by increasing the shear stress and decreasing shear strength on the potential rupture plane. To examine the effect of these parameters numerical models on Figure 3 was made for different slope height and slope angles.
Figure 7A shows FS of slope for 27°, 34°, 45°, 63°, and 73° (i.e. increasing slope angle reduces the FS). Similarly, Figure 7B shows the effect of slope height on FS in an ideally sandy lean clay slope for different slope heights (i.e. increasing slope height increases the deformation and decrease the FS of the slope). Hence it is recognized that both slope height and slope angle reduce the FS of slope in the same principle i.e. increasing self-weight (driving force) above the failure surface and decreasing the normal force on the failure surface.
Effect of slope angle and slope height on the performance of single slope profile.
Bench width, cut angle and no bench are the major parameters which control the performance of bench slope profile. To examine the performance of benching and its parameters on the stability of slopes a typical slope section given in Figure 3 was used. Figure 8A shows the FS of slope for 1, 2, 3, 4, 5 and 6 m bench width with a constant 10 m bench height. As the figure indicates stability increases with increasing bench width (i.e. FS increases in 3.5%, 7.7%, and 12% from single slope profile in 1:1 slope ratio for 1 m, 2 m and 3 m bench widths respectively). The percentage change of FS from equivalent single slope profile is 1.7%, 3.6%, 7.7% and 17.4% for 27°, 34°, 45° and 63° respectively in a constant 2 m bench width as shown in Figure 8B. Hence the use of benching is more effective in steep slopes.
Effect of bench width, bench slope and bench height on the performance of bench slope profiles.
Similarly, the effect of bench height was evaluated using uniform clayey sand soil in two cases (i.e. case 1, when the overall cut varies with constant slope within bench. Case 2, when overall cut is constant with varied slope within bench as shown in Figure 8C). Accordingly, decreasing bench height (increasing no of bench) increases the FS of slope in case 1. However, it has no significant effect in case 2. Generally, benches improve stability of slope in the opposite principle of slope height and slope angle by decreasing the driving force of the slope above the failure surface. The method is effective to avoid the use of gentle and high slopes in the design of cut slope.
To assess the performance of multi slope profile in stratified soils a layered slope section shown in Figure 3B is evaluated for different combinations of slope angle (i.e. in the weaker and stronger section). Table 2 and Figure 9 shows FS for different combination of weaker and stiffer slope section. Accordingly, FS is improved up to 30% from a single slope profile by adjustment of cut angle (i.e. decreasing weaker section and increasing stiffer section). But it should be reminded that the amount of change in FS depends on the strength characteristics of the slope section. Generally, multi slope profile allows the use of steep and gentle slope in stiff and loses materials respectively in stratified soil.
Slope | a (stronger layer) | 45 | 48 | 51.3 | 55 | 59 | 63.4 | 68 | 78.67 | 90 |
b (weaker layer) | 45 | 42.3 | 39.8 | 37.5 | 35.5 | 33.69 | 32 | 29 | 26.5 | |
FS | 1.202 | 1.251 | 1.325 | 1.414 | 1.472 | 1.513 | 1.55 | 1.5 | 1.45 |
FS for different combination multi-slope profiles (a= stronger slope & b= weaker slope).
FS and its change from single slope in % for d/t combination of multi-slope profiles.
Further comparison was made on the performance of profiles by evaluating the slope section in Figure 10A for single, multi, bench slope and combination both. Figure 10B shows the result of the comparison i.e. FS changes in 13%, 22.7%, and 37.5% from single slope profile in bench, multi-slope, and the combinations of both methods respectively. Hence the use of bench slope, multi slope and combination them provide effective stability in high and stratified slope.
FS and deformation for different slope profiles.
From the above evaluation, it is recognized that modification of slope geometry is one and the very first economical alternative of slope stability improvement. Although this investigation is made in a specific type of slope material there is no doubt in the role of geometric modification in slope stability. However, the selection of these slope geometry should depend on site-specific parameters i.e. susceptibility of the slope to erosion and infiltration, the variability of slope material, the height of slope, and adjacent area of the slope.
According to the evaluation result, the use of a single slope profile is effective in homogenous stiff slope material when the height of the slope is low. Otherwise, the method may not be safe and economical choice as weak and high slope sections need very gentle slopes. Multi slope profiles are suitable in slopes where there is material strength variability. It provides a very economical slope design without extra excavation by making adjustments only within the slope section. Especially the method is ideal in slopes comprise both rock and soil. The use of bench is an effective geometric measure when the height of the slope is large. It increases FS by reducing the driving force above the failure surface. In addition to this the use of bench slope can provide the following advantages. (1) It reduces the area of the slope exposed to rainfall infiltration as it allows the use of steep slope between every benching. (2) It provides effective drainage control by collecting the rainwater from each slope profile and draining it laterally to ditches. (3) It provides access to side slopes for maintenance, plantation of vegetation, and decoration. (4) It uses for collection of debris falls above it. (5) It provides esthetic value and better appearance for slopes especially when it located around towns. In general slope profiles have advantages and limitations depending on site specific conditions as shown in Figure 11.
Advantages and limitations of slope profiles.
The performance evaluation of slope profiles in this study was made for the objective of creating awareness on the effect and its suitable condition of different geometric profiles on slope stability. The effect of geometric parameters like slope height, slope angle, bench width, no of bench and bench angle on slope stability were evaluated interims of FS and deformation on selected critical slope sections from the newly constructed road cut slope. From the result, it has been seen that geometric modification will provide better and economical slope stability compared to other structural remedies.
Accordingly, the stability of slope decreases with an increase in slope height and slope angle in single slope profile leading to an uneconomical design of high slopes in a single slope profile. Benching provides an important stability for cut slope especially for slopes having larger height and its performance is more effective in steep slopes. Bench width and bench height also parameters which affect the performance of benching. Multi-slope profile provides an effective slope stability in a stratified soil of varied strength. It allows economical slope design without extra excavation by making adjustments only within the slope section. In addition to its direct effect on the FS, slope profiles have different performance on drainage control, access to maintenance, and its esthetic value. Therefore, the selection of slope profiles during design should be based on site-specific considerations.
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\\n"}]'},components:[{type:"htmlEditorComponent",content:'IntechOpen’s Retraction and Correction Policy has been developed in accordance with the Committee on Publication Ethics (COPE) publication guidelines relating to scientific misconduct and research ethics:
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\n\nA Retraction of a Chapter will be issued by the Academic Editor, either following an Author’s request to do so or when there is a 3rd party report of scientific misconduct. Upon receipt of a report by a 3rd party, the Academic Editor will investigate any allegations of scientific misconduct, working in cooperation with the Author(s) and their institution(s).
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\n\nAny suggestions or comments on this Policy are welcome and may be sent to permissions@intechopen.com.
\n\nPolicy last updated: 2017-09-11
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Cramer’s rules for special cases when two equations are one-sided, namely the system of the equations A1X=C1, XB2=C2, and the system of the equations A1X=C1, A2X=C2 are studied as well. Since the Moore-Penrose inverse is a necessary tool to solve matrix equations, we use its determinantal representations previously obtained by the author in terms of row-column determinants as well.",book:{id:"6526",slug:"matrix-theory-applications-and-theorems",title:"Matrix Theory",fullTitle:"Matrix Theory - Applications and Theorems"},signatures:"Ivan I. 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We provide an expression for the derivative of a product, of a ratio, of the inverse of vectors, and we also find the equivalent of the summation by parts theorem of continuous functions. 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He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"7",title:"Bioinformatics and Medical Informatics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",isOpenForSubmission:!0,editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",slug:"slawomir-wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",biography:"Professor Sławomir Wilczyński, Head of the Chair of Department of Basic Biomedical Sciences, Faculty of Pharmaceutical Sciences, Medical University of Silesia in Katowice, Poland. 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He completed a one-year Post-Doctoral Fellowship awarded by the DFAIT (Foreign Affairs and International Trade Canada) at the Institute of Biomedical Engineering of the University of New Brunswick (Canada) in 2010. Currently, he is Professor in the Faculty of Electrical Engineering (UFU). He has authored and co-authored more than 200 peer-reviewed publications in Biomedical Engineering. He has been a researcher of The National Council for Scientific and Technological Development (CNPq-Brazil) since 2009. He has served as an ad-hoc consultant for CNPq, CAPES (Coordination for the Improvement of Higher Education Personnel), FINEP (Brazilian Innovation Agency), and other funding bodies on several occasions. He was the Secretary of the Brazilian Society of Biomedical Engineering (SBEB) from 2015 to 2016, President of SBEB (2017-2018) and Vice-President of SBEB (2019-2020). He was the head of the undergraduate program in Biomedical Engineering of the Federal University of Uberlândia (2015 - June/2019) and the head of the Centre for Innovation and Technology Assessment in Health (NIATS/UFU) since 2010. He is the head of the Postgraduate Program in Biomedical Engineering (UFU, July/2019 - to date). He was the secretary of the Parkinson's Disease Association of Uberlândia (2018-2019). Dr. Andrade's primary area of research is focused towards getting information from the neuromuscular system to understand its strategies of organization, adaptation and controlling in the context of motor neuron diseases. 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His fields of interest are anterior segment disease, keratoconus, glaucoma, corneal dystrophies, and cataracts. His research topics include\nintraocular lens power calculation, eye modification induced by refractive surgery, glaucoma progression, and validation of new diagnostic devices in ophthalmology. \nHe has published more than 100 papers in international and Italian scientific journals, more than 60 in journals with impact factors, and chapters in international and Italian books. He has also edited two international books and authored more than 150 communications or posters for the most important international and Italian ophthalmology conferences.",institutionString:'University of Campania "Luigi Vanvitelli"',institution:{name:'University of Campania "Luigi Vanvitelli"',institutionURL:null,country:{name:"Italy"}}}]},{type:"book",id:"7560",title:"Non-Invasive Diagnostic Methods",subtitle:"Image Processing",coverURL:"https://cdn.intechopen.com/books/images_new/7560.jpg",slug:"non-invasive-diagnostic-methods-image-processing",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Mariusz Marzec and Robert Koprowski",hash:"d92fd8cf5a90a47f2b8a310837a5600e",volumeInSeries:3,fullTitle:"Non-Invasive Diagnostic Methods - Image Processing",editors:[{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",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. 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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:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}}]},{type:"book",id:"6843",title:"Biomechanics",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6843.jpg",slug:"biomechanics",publishedDate:"January 30th 2019",editedByType:"Edited by",bookSignature:"Hadi Mohammadi",hash:"85132976010be1d7f3dbd88662b785e5",volumeInSeries:4,fullTitle:"Biomechanics",editors:[{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",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. 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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. 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Prof. Sarfraz is also an editor-in-chief and editor of 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:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{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:{name:"University of Silesia",country:{name:"Poland"}}},{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:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{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:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:{name:"Medical University Plovdiv",country:{name:"Bulgaria"}}},{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:"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:"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:"Igor Victorovich Lakhno 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.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in 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 been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), 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 a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). 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: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",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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Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. 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