Comparision of ABA-based interventions and NICE [64] recommendation
\r\n\tIt has been established that energy/nutrient depletion, calcium flux injury, or oxidative stress disrupt endoplasmic reticulum homeostasis and even induce accumulation of misfolded/unfolded proteins leading to endoplasmic reticulum stress. Under endoplasmic reticulum stress conditions, an adaptive mechanism of coordinated signaling pathways, defined unfolded protein response (UPR), is activated to return the endoplasmic reticulum to its healthy functioning state. The aging causes a decrease of the protective adaptive response of the UPR and an increase of the pro-apoptotic pathway together with endoplasmic reticulum ultrastructural injury. Controlling endoplasmic reticulum stress response, maintaining the appropriate endoplasmic reticulum ultrastructure and homeostasis, and retaining mitochondria interplay are crucial aspects for cellular health.
\r\n\r\n\tThis book presents a comprehensive overview of endoplasmic reticulum, including, but not limited to, endoplasmic reticulum ultrastructural anatomy, MAMs, endoplasmic reticulum stress, and their implication in health and diseases. Additionally, identifying perturbations in the endoplasmic reticulum stress response could lead to early detection of age-related disease and may help develop therapeutic approaches.
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Most individuals on the autism spectrum also experience differences in sensory perception. Some individuals on the spectrum are ‘high-functioning’ and able to cope in every day environments, while others are severely affected, non-verbal, and may have co-occurring diagnoses, such as intellectual disability, epilepsy, and/or obsessional, conduct, or mental health disorders. These individuals require substantial support, caring and careful management, and evidence-based, effective interventions.
ASD diagnosis can be detected from as early as 6-months to 1-year of age, although it is more common that children are aged 2-3 years before diagnosis is affirmed. Frequently, higher functioning individuals are not diagnosed until adolescence, or even adulthood. Present figures indicate that approximately 1:50 children are affected worldwide [97], with parent reported prevalence rates even higher in some countries, e.g., 1:38 (2. 6%) in South Korea (Kim, Leventhal, Koh et al., 2011) and 1:29 (3. 5%) in the UK, based on data of 11-year old children (n=13, 287) from the Millennium Cohort Study [19]. Similar prevalence rates have been found across racial, ethnic and socioeconomic groups; it seems that boys are affected more frequently than girls (estimated ration of 4:1), although this may be due to under diagnosis in girls.
The exact etiology of ASD remains unknown even though genetic, immunological, neurological, neurotoxins, electromagnetic radiation, and allergenic causes have been investigated. Early theories of maternal unresponsiveness have been discredited as mentalistic and sexist, while recent neurological studies have shown physical differences in early brain growth and functioning. Sibling and twin studies point to the possibility of genetic links. Ultimately, it is likely that ASD is caused by a combination of genetic and environmental risk factors [11]. In fact, it is to be expected that one day we will be able to differentiate symptomatology along the spectrum much more precisely and different ‘causes’ will be linked with different manifestations along the autism spectrum.
General Practitioners (GP) are the first port of call for most parents who are concerned about their children’s behaviour. A referral is made to an assessment team, commonly lead by a pediatrician working in collaboration with a team of allied health professionals. A full diagnosisis based on behavioural observations and caregiver reports of their behavioural observations [19]. Although presently, there are no medical tests, ASD remains a medical diagnosis that requires a medical as well as educational response.
The Vice President for State Government Affairs of Autism Speaks, the world’s largest autism charity, Professor Lorri [87] made this point clearly when arguing for health cover:
Autism is diagnosed by a doctor, not a school principal. Treatment is prescribed by a doctor, not a teacher. Here are some things autism families deal with daily: swallowing aggression, teeth grinding, feces eating, depression, tantrum, drooling, elective mutism, food refusal, food theft, genital stimulation, hallucinations, hyperactive behaviour, hyperventilation, inappropriate vocalizations, insomnia, public disrobing, rectal digging, seizure behaviour, self-injurious behaviour, tongue protrusion and vomiting. Does anyone think these should be treated in our school classrooms? (p. 1)
Of course not everyone agrees. Proponents of the neurodiversity movement [48, 58, 66] argue that autism represents a neurological difference that should be celebrated rather than treated with interventions. [44] maintain that these arguments are valid with regards to rights, recognition and acceptance, however, they rightly argue that ‘only a narrow conception of neurodiversity, referring exclusively to high-functioning autists, is reasonable’ (p. 20).
For ‘low-functioning’ individuals with ASD, the lifetime cost to society is estimated to bein excess of £1. 4 million and these figures are similar internationally [7]. Of course, the cost for quality of life for the individual and their family is much higher. For example, 86% of parents of children with disabilities have to pay above average childcare costs and 72% of these families have given up work or reduced their working hours, because of childcare problems [9] and only about 15% of adults with ASD are in gainful employment [79]. The potential positive impact of effective interventions is enormous.
It is not surprising, therefore, that the intervention market is booming [17, 32]. As governmental investments into ASD services are increasing, fad treatments abound. In fact, the struggle for a slice of the market has been called the ‘Autism Wars’ [31]. Primary care, allied health, social care, and education professionals have a key role to play in protecting families and individuals affected by ASD from fads and ineffective, controversial, or even dangerous treatments that are peddled by self-proclaimed autism experts for commercial reasons [15].
Given that there are no medical indicators for ASD, it is not surprising that currently there are no pharmacological treatments for the core symptoms of autism. There are, however, pharmacological treatments for some of the co-occurring symptoms, but due to lack of evidence of effectiveness and potentially serious side effects, the National Institute for Clinical Excellence [64] advises against the use of pharmacological interventions.
There are some commercially available intervention packages. However, commonly they are very expensive and make unsubstantiated claims and promises of recovery or ‘cure’ for autism. These claims are predatory on vulnerable parents, especially since there is generally very little evidence of effectiveness. The very few studies that exist for some of these commercial packages are usually not very rigorous and/or conducted by people who have a financial interest [38].
Some interventions have been developed and are frequently used or recommended by allied health professionals despite the fact that, after a thorough review of all available research evidence was carried out by the large team of multidisciplinary professionals for National Autism Centre [63], these interventions have been categorised as
Facilitated Communication is another
Virtually all interventions that have been categorised as
It is important to know that the term \'behaviour\' when used by behaviour analysts refers to anything we do and therefore includes feeling and thinking [16].
The evidence for ABA-based interventions spans all valid and recognised research methodologies, including Single-System Design (SSD), Randomised Controlled Trials (RCT), Meta-analysis and Sequential Meta-analysis, Systematic Reviews, Social Validity studies, Neuroscience studies, and Cost-benefit analysis.
Hundreds, if not thousands, of Single-System Design (SSD) studies have been published evidencing the effectiveness of ABA for individuals with autism [22]. While most of these studies are published in flagship journals, such as
A good example of an SSD is Garcia-Albea, Reeve, Brothers, and Reeve (2014), who used a multiple-probe design across participants to teach 4 boys with autism to initiate and participate in social interactions without vocal prompts from adults. The procedure involved the use of a script and script-fading procedure. The boys quickly learned to talk independently about a whole range of relevant things in their environment without the help of adults. While this kind of research methodology lends itself particularly well to the action-based researcher/scientist-practitioner model inherent in ABA, it can be usefully employed in a range of different settings [49].
While RCTs may have their utility in relatively clear-cut medical research, there are many problems when they are used in social care or educational research, not least the ethical dimension of withholding a potentially beneficial treatment from the control group. Of course, there are safeguards, such as cross-over designs or the Hippocratic Oath to ‘do no harm’ [90].
However, some of the main drawbacks in autism research are that, for RCT results to be valid, all members of the ‘treatment group’ have to receive the exact same treatment and this has to be held stable for the agreed duration of the intervention. Of course, when interventions are based on a functional analysis of behaviour, as is the case in ABA, they are tailored to the needs of the individual, i. e., they are person/child-centered. Data-based decisions are made with regards to intervention adjustments, that are implemented immediately, for ethical reasons, in order to avoid harm and enhance treatment effects [14]. These kinds of progressive, systematic, individualized, data-based intervention revisions and adjustments would invalidate RCT data (see Single-System Designs).
Of course ABA (i. e., the application of the scientific discipline of behaviour analysis) itself cannot be assessed via RCTs, yet some specific intervention packages, such as Early Intensive Behaviour Interventions (EIBI) or the Early Start Denver Model, have been assessed in RCTs. A good example is Howard, Sparkman, Cohen, Green, and Stanislaw [39], who evaluated 29 pre-school children who received intensive behaviour analytic intervention (treatment group) and two matched control groups of 16 children each, receiving either intensive or non-intensive ‘‘eclectic’’ interventions. While the scores for cognitive, language, and adaptive skills were similar at intake, at follow-up the treatment group had statistically significant higher mean standard scores in all areas. These data were confirmed at the 2 year follow-up [40].
Other RCTs or quasi-experimental control studies have compared Treatment as Usual with ABA-based interventions, such as specific commercially available intervention packages [34), high vs low intensity ABA-based interventions [30, 59], or waitlist controls [67].
With regards to autism interventions, a recent overview of meta-analyses [77] found that early intensive ABA-based treatment was significantly related to enhanced outcomes (effect sizes 0. 30 to > 1). Further meta analyses [22, 23, 24, 72] and a recent sequential meta-analysis [54] have confirmed these findings [1].
The number of systematic reviews of ASD interventions has risen recently [77]. By-and-large ABA-based interventions, in particular Early Intensive Behavioural Interventions (EIBI), are endorsed by systematic reviews. A good example of a comprehensive systematic review was carried out by the large scale multidisciplinary team of the National Autism Center [63] ; 11 interventions were designated as established, of these all but one are explicitly based on ABA; 22 intervetions were categorised as emerging, most of these were also based on ABA. All other systematic reviews came to similar conclusions [6, 36, 70, 75, 91].
The review by [43] is the notable exception, in that it does not fully concur with these conclusions. Howlin et al. concluded that ‘this review provides evidence for the effectiveness of EIBI for some, but not all, preschool children with autism’ (p. 20). Given that this review is frequently cited in the UK as a basis against the roll-out of EIBI for all children with ASD who need it [42], it is important to note here that Howlin et al. misinterpret a number of important points. First, it is in the mathematical nature of all group average data (such as those calculated for RCTs) that some individual data are above while others are below the average; such is the nature of group averages (see also [77]; second, Howlin et al. ‘cherry pick’ results by ignoring the fact that obviously some children must do extremely well, otherwise the group average would not be what it is. Thus, Howlin et al. contradict themselves in their conclusions. First they call for large sample comparisons and group averages (i. e., RCTs) and then they do not accurately interpret group data.
In a subsequent paper, Howlin and colleagues [99] report extremely poor long-term outcomes in a 40-year follow-up study of children diagnosed with autism at the Institute of Psychiatry/Maudsley Hospital, London between 1950 and 1979. Intriguingly, they explicitly link these findings to the fact that none of these children had received early intensive behavioural interventions and claim that EIBI is available now. Praising the potential positive effects of EIBI stands in contrast to their earlier conclusions [42, 43]. It will be interesting to see how this new evidence will translate into advice given to government bodies.
Given that group average scores are neither sensitive to individual differences nor offer sufficient generality, most behaviour analytic researchers prefer to rely on replicated single-system designs (SSD) instead of group averages [14, 18, 29]. Clearly, SSD research data cannot be ignored and should find their rightful place in future reviews of autism intervention guidelines, such as NICE Guideline 170 [64].
A number of studies have shown clear evidence of high social validity of ABA-based interventions, especially those that include parent participation and training [18, 92]. Interestingly, while there is evidence of increased parental stress in families affected by ASD [10, 17], there is evidence of parental stress reduction when effective interventions for children are in place [17]. This is also true for education staff [26].
There is further evidence that early behaviour analytic intervention can lead to measurable change in brain activity [12]. For example, [28] found that ABA-based interventions not only lead to behavioural improvements, with some optimal outcome individuals becoming ‘indistinguishable’ from neuro-typical peers, but that they also lead to improved neurological development, i. e., neurological plasticity allowing for compensatory development.
There is evidence that effective ABA-based interventions can reduce this cost substantially in the long-term, i. e., $1+million per year [45]. However, due to the fact that intensive interventions generally are rather costly in the short-term, there has been resistance to their implementation. The key question is how effective high-quality programs can be delivered in a more cost-effective sustainable model, without losing out on effectiveness [1].
All of these studies supply ample evidence of the effectiveness and efficacy of ABA-based interventions, in achieving individual potential in a full range of areas, including intellectual, social, and verbal, functioning, ASD symptomatology, and challenging behaviour.
On the basis of this evidence, ABA-based interventions are now widely endorsed in the USA, Canada, Australia, and some European countries. On a federal level in the USA, for example, Medicaid now covers ABA-based interventions and the Affordable Care Act covers behavioural health treatments [83], which include ABA-based interventions generally, and is not restricted to ASD diagnosis.
In the USA, interventions for individuals with ASD that are based on ABA are endorsed as medically, as well as educationally, necessary and covered by health insurance in the vast majority of States [2]. In fact, they are now considered ‘treatment as usual’ [28]. As early as 1999 the [84] endorsed ABA-based interventions:
Thirty
More recently, [94] recommended
that principles of applied behaviour analysis (ABA) and behaviour intervention strategies be included as important elements in any intervention program for young children with autism. (p. 33)
[8] recognized that:
in areas such as social engagement, language, coping, and reduction of difficult behaviours… Applied behavioural analysis is usually needed to assist a child to gain skills and reduce negative or undesirable behaviours. (p. 10)
The Federal U. S. Office of Personnel Management responsible for all federal government employees concluded that ABA-based interventions should be covered not only for educational but also for medical reasons:
based on ample scientific and empirical evidence, ABA therapy qualifies as a medical treatment, rather than purely educational. [5], p. 1)
In Canada, ABA-based interventions are supported, for example by the Ontario Department of Education Policy/Program Memorandum [73] that support[s] incorporation of ABA methods into school boards’ practices. . . The use of ABA instructional approaches may also be effective for students with other special education needs. (p. 1)
The Maine Administrators of Services for Children with Disabilities confirmed their support in the Report of the Autism Task Force [6]
It is important to note that ABA is frequently perceived to be synonymous with discrete trial teaching. However, ABA is comprised of a broad scope of empirically derived behavioural principles used in interventions. (p. 25)
Despite this general endorsement of evidence-based behaviour analytic interventions across most of the English speaking world, the highly controversial approach taken by governments across the UK and Ireland is to support an ‘eclectic’ approach. There are no clear guidelines as to what an ‘eclectic’ approach entails and not a single study is published anywhere to show the effectiveness of an eclectic approach being equal or superior to ABA-based interventions [14]. In fact, [21] and [39] findings show clearly that ABA-based interventions are superior to an eclectic approach. Individually tailoring behavioural interventions to match child characteristics is key to effectiveness [82].
Yet in the UK, the National Institute for Clinical Excellence’s [64] response to stakeholders, who asked for ABA-based interventions to be included in the NICE guidelines for the management of children with ASD, was the following:
In the review of evidence, the Guideline Development Group found no evidence to support ABA, and therefore could not make a recommendation about ABA. (pp. 5& 8)
They also asserted that:
NICE clinical guidelines are based on the best quality evidence and are developed according to rigorous and robust methodologies. The developers were unable to identify high quality evidence of effectiveness of the ABA approach in managing children and young people with autism. (pp. 5 & 8)
This view is informed mainly by relatively few, but well rehearsed anti-ABA arguments that continue to circulate misinformation and misleading anti-ABA propaganda. As [33] points out:
The most concerning issue affecting the quality of practices and policies in the helping professions is the play of propaganda, which misleads us regarding what is a problem, how (or if) it can be detected, its causes, and how (or if) it can be remedied. Propaganda is defined as encouraging beliefs and actions with the least thought possible. Censorship is integral to propaganda including hiding well-argued alternatives and lack of evidence for claims. Evidence-based practice was developed in part because of misleading claims in the professional literature. If propaganda is an integral part of our society, we cannot escape its influence. But we can become aware of it, encouraged by ethical obligations to avoid harming in the name of helping. (p. 302)
Anti-ABA propaganda generally comes from people not trained in the science (e.g., [41, 47]. Censorship comes in the form of excluding behaviour analysts from review bodies [14] or ignoring data presented to review panels [68]. As a consequence of this exclusion, ABA remains a ‘new idea’ in the UK, despite its extensively documented history and evidence base accessible in the English language.
The German philosopher Alfred Schoppenhauer (1788-1860) recognised that:
All new ideas pass through three stages. First, they are ridiculed. Second, they are violently opposed. Third, they are accepted as being self-evident.
This is true for the evolution of the arguments by ABA opponents [15]. First, they ridicule ABA as‘ one approach for autism’, while promoting the rather ill-defined eclectic approach. Of course, one could argue that the eclectic approach is one approach as it precludes any other approach, such as the dual approach taken in Germany, where psychotherapists are trained in either behaviour therapy and psychotherapy, and the service user has the choice which service they prefer to use [17]. In reality then, eclecticism is ‘one approach’ to autism intervention. When opponents of ABA state that they do not want one approach for all, they cannot at the same time say that they promote the one approach called ‘the eclectic approach’.
There are of course further problems with eclecticism.
Staff training in all possible autism treatments is impossible. Training and skills of eclectic practitioners necessarily remain limited to a certain number of preferred interventions. The decision about what to include/exclude in an eclectic treatment package therefore is not based on the child’s needs but on the practitioner skills.
There is no coherent theoretical knowledge base and the potential for conflicting interventions means that synergy effects cannot be controlled.
There is no evidence of effectiveness.
On the other hand as mentioned earlier, ABA is not ‘one approach to autism’ [16], it is the application of the scientific discipline of behaviour analysis.
ABA aims to discover and understand the underlying principles of behaviour with the function of a particular behaviour considered in the design of behaviour change interventions. Interventions are designed for the individual, recognizing that the function of behaviour varies based on complex combinations of variables. [6], p. 25)
There is nothing wrong with using one approach, if this ‘one approach’ is science [15]. Countless procedures have been developed from the science of behaviour analysis, many specifically for ASD, e.g., Discrete Trail Teaching (DTT); Pivotal Response Training (PRT); Natural Environment Training (NET); Verbal Behaviour Approach (VB); while other procedures have been developed for more general applications, e.g., Functional Analysis and Functional Assessment; Preference Assessments; shaping, forward chaining, backward chaining; differential reinforcement of low or zero rate and/or incompatible or alternative behaviours; Time-out from Positive Reinforcement (TOR); etc. . Some of these procedures have been combined into comprehensive packages for autism, such as Early Intensive Behavioural Interventions (EIBI) or Early Start Denver Model (ESDM), while others are used more generally, e.g., Programmed Instruction, Generative Instruction; Peer Tutoring; Habit Reversal Training; etc. Given that the science of behaviour analysis underpins all of these programmes/procedures and continuous data-based decision making is part and parcel of ABA, new procedures and progammes are developed continuously to meet the individual or group needs of service users.
ABA has been further ridiculed and accused of intending to change the person, while others pride themselves for accepting the person for who they are [69, 80]. In fact, the targets of ABA-based interventions are socially relevant behaviours, linked to cultural and personal norms and preferences [4]. The curricula are agreed with individuals with ASD and/or their caregivers. They are generally based on wide-ranging target behaviours, including life skills, such as dressing, toileting, attending; social skills, such as playing or imitation; academic skills, including attending, reading, drawing, writing, and maths, and work/employment based skills, including interviewing or team work.
Basically, the aim of ABA is to enhance all skills necessary to lead a fulfilled life for individuals who would otherwise be limited in the quality of life they experience. These are the same aims that most parents have for all of their children, irrespective of a diagnosis. As such, ABA does not intend to ‘change the person’, but to enhance skills and help individuals to break down barriers to learning and achieve their full potential. After all, enhancing skills development increases choice.
Once a new idea can no longer be ridiculed, the second point Schoppenhauer made comes to play: the new idea is opposed. In the case of ABA, this refers to statements such as there is no evidence to support ABA and therefore no recommendation can be made [64]. We have outlined the wealth of evidence in favour of ABA-based interventions earlier in this chapter. Given that behaviour analysts commonly are not included in review bodies, at least in Europe, this mountain of evidence generally is excluded from reviews [68].
When the evidence can no longer be denied, the opposition turns to the behaviour analytic scientists themselves, stating that research conducted by behaviour analysts is biased and therefore not to be taken seriously. The idea, that it is objectionable that scientist conduct scientific research in their own subject area is rather intriguing. Given that it is against ethical guidelines of all social and health care as well as education professionals to work outside their own area of expertise [90], clearly, multidisciplinary practice and interdisciplinary research teams in ASD, should routinely include behaviour analysts, not least because others are not qualified to make authoritative statements about behaviour analysis [16].
Once ridicule and opposition are not longer tenable, the third point of Schoppenhauer’s concept of the evolution of a new idea comes to play, when finally, new ideas are considered self-evident. Intriguingly, this is now starting to happen with regards to ABA. There is evidence of a claim that all teachers and psychologists use ABA techniques. However, being able to conduct one or two behavioural techniques [16] clearly does not equate to training in applied behaviour analysis to international standards [3]. For example, clinical psychology training typically includes (under Psychological Therapies) ‘competency in two evidence-based therapeutic approaches including CBT and one other (e.g. psychodynamic, systemic, social constructionist)’ [76]. Other professionals commonly receive no training in behaviour analysis and either none or very little training in ASD [19].
A Board Certified Behaviour Analyst (BCBA®) has received fully approved training in the science of behaviour analysis either at Masters or doctoral level, including at least 270 hours of course work and 1500 hours of supervised practice in ABA [3].
While NICE [64] did not make any recommendations regarding ABA or staff qualifications, they recommend a ‘social-communication intervention’ that includes play-based strategies with parents, carers and teachers to increase joint attention, engagement and reciprocal communication in the child or young person.
Table 1 offers a direct comparison of the basics of ABA-based interventions that were stipulated by the [8] and the NICE [64] recommendations.
\n\t\t\t | \n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
Curriculum decision | \n\t\t\tThe curriculum is organized around typical developmental expectations; Individualized approach is used to determine developmental level of programme; Functional analysis identifies the communicative role of behavior; Language- and communication-intensive; Socialization and play are actively stimulated; | \n\t\t\tA specific social-communication intervention for the core features of autism in children and young people; Be adjusted to the child or young person\'s developmental level; To increase joint attention, engagement and reciprocal communication; | \n\t\t
Methods | \n\t\t\tAn individualized approach is used to select or develop developmentally appropriate methods; Procedures are based on applied behaviour analysis; Includes structured as well as natural environment training. | \n\t\t\tIncludes play-based strategies; Include techniques of therapist modelling and video-interaction feedback; Include techniques to expand the child or young person\'s communication, interactive play and social routines; | \n\t\t
Monitoring | \n\t\t\tA formalized assessment of skills (cognitive, language, socialization, adaptive behavior, fine and gross motor, and play) is conducted at regular intervals; Data are recorded to monitor progress and to troubleshoot; Assessment results are used as a guide for planning what skills to teach next; Integration of research and practice is used; | \n\t\t\t\n\t\t |
Generalisation & Maintenance | \n\t\t\tGeneralization and maintenance of skills are built into the program; | \n\t\t\t\n\t\t |
Outcome targets | \n\t\t\tMainstreaming opportunities with typically developing peers are built into the program; Transitional support is provided when the child leaves one program and moves to the next. The skills needed in the next situation are taught and support needed is considered; | \n\t\t\tAim to increase the parents\', carers\', teachers\' or peers\' understanding of, and sensitivity and responsiveness to, the child or young person\'s patterns of communication and interaction; | \n\t\t
Parent involvement | \n\t\t\tParent training and family support are used; Education about options for intervention is provided; Training is culturally acceptable to individual families; | \n\t\t\tWith parents, carers and teachers; | \n\t\t
Staffing | \n\t\t\tCollaboration of all team members is used; Related services are included (i.e., speech, occupational therapy, adapted physical therapy, and/or augmentative communication); Ongoing teacher/therapist training is included to consider what new and experienced personnel need to know. | \n\t\t\tThe intervention should be delivered by a trained professional. For pre‑school children consider parent, carer or teacher mediation. For school‑aged children consider peer mediation. | \n\t\t
Comparision of ABA-based interventions and NICE [64] recommendation
In a recent review for the Canadian Medical Journal, [1] summed up the evidence for ABA-based intervention in ASD when they stated:
Current best practices for preschool-aged children with ASD include a focus on improving language, cognitive and adaptive skills using applied behaviour analysis (ABA) techniques. Applied behaviour analysis refers to the application of empirically derived learning principles (i. e., the antecedent–behaviour–consequence contingency) to produce meaningful changes in behaviour. Such strategies are carefully engineered and implemented through a variety of approaches (e.g., discrete trial teaching to more naturalistic learning contexts) to teach skills and reduce problem behaviour. Applied behaviour analysis interventions can be provided in a variety of settings (e.g., home, specialized treatment centres, specialized or public schools) by a range of front-line therapists, ideally supervised by a psychologist or board-certified behaviour analyst who specializes in ASD. (p. 515)
It is, therefore, not surprising that increasingly reports link ABA-based intervention with optimal outcomes. Individuals previously diagnosed with ASD are now living independent productive happy lives or no longer meeting diagnostic criteria. Mukaddes, Tutkunkardas, Sari, Aydin, and Kozanoglu (2014) suggested that ‘[i]t could be concluded that a group of children with an autism diagnosis could lose the diagnosis of autism upon early intervention’ (p. 1). [65] for example, report a strong statistical significance of early intensive behaviour analytic interventions for children previously reported to have optimal outcomes [28], while [85] report on reductions of restricted and repetitive behaviours and [85] focus on improvements in academic skills following early intensive behavioural interventions.
Evidently, ABA translates into evidence-based interventions that allow individuals with ASD to overcome barriers by ensuring choice, human rights, equality and true active participation. ABA helps achieve potential by cherishing the person for who they really are and, by accepting difference, it values the difference we can make in people’s lives.
DCs represent an important link between innate and adaptive immunity. DCs are heterogeneous population of antigen-presenting cells that are crucial to initiate and polarize the immune response. Although, all DCs are capable of capturing, processing, and presenting antigens to T cells, DCs subtypes differ in origin, location, migration patterns, and specialized immunological roles [1]. All the DCs are continuously renewed by hematopoietic stem cell progenitor cell located in bone marrow, except of Langerhans cells (LCs) that develop from embryonic macrophages in the yolk sac and fetal liver, that are recruited in the epidermis during embryonic life. The process is not clearly, but hematopoietic stem cell is differentiated into granulocyte-macrophage progenitors (GMP) and multilymphoid progenitors (MLP), that have the potential to differentiate into macrophage-dendritic precursor (MPD) or common dendritic cell progenitor (CDP) like progenitor. These progenitors are subsequently differentiated into common monocyte progenitor (cMoPs), plasmacytoid dendritic cells (pDCs) and human equivalent of pre-DC, those are the most important to differentiate all subsets of DCs. cMoPs develop into blood monocytes, which differentiate into monocyte-derived DCs (MoDCs) in inflamed tissues, and fully mature pDCs along with unmatured pre-DCs migrate through the blood tissue. Immature human pre-DCs differentiate either in the bloodstream or in tissues following migration, developing thus in different DCs subsets (Figure 1) [2, 3, 4].
Dendritic cell lineage development. The hematopoietic stem cell located in bone morrow is the progenitor of all DCs. Here the differentiation in multi-lymphoid progenitor and granulocyte-macrophage can become the human equivalent of macrophage-dendritic precursor (MPD) or dendritic cell progenitor (CDP). From this cell arise three important progenitor cells (cMoPs), pDCs and pre-DC, these last cells migrate to bloodstream or target tissue/organ to maturate and differentiate to become one of the different subsets of DCs. Explanation in the text. Figure modified by the authors from reference [
The DCs are present in lymph organs and non-lymphoid organs, also in blood stream, afferent lymph, and mucous membranes. There are different ways to classify DCs, by its linage, as mentioned above there are cMoPs and pDCs. The cMocPs express typical myeloid antigens as CD11c, but lack of CD14 or CD16 and may be split in CD1c + and CD141+ fractions. While pDCs have expression of CD123, CD303 and CD304, with high or low expression of CD123, CD303 or CD304; the cluster of differentiation is determined in the differentiation of their precursor. These cells cMoPs and pDCs are classified into blood DCs [5, 6].
Inflammatory DCs derived from classical CD14+ blood monocytes, using granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4. Monocytes are highly plastic, and they differentiate into DCs or different forms of macrophages (M1/M2). Human inflammatory exudates contain distinct inflammatory DC-like and macrophage-like cells and transcriptional profiling suggests a common monocyte origin. Key features of these cells are the expression of CD1c, CD1a, CD206, FcεR1, Sirpα but lack of CD16 and CD209. Non-classical monocytes and antigen 6-Sulpho LacNac DCs are a heterogeneous population and CD16+ monocytes possess distinct characteristics including higher major histocompatibility complex (MHC) class II and co-stimulatory antigen expression, classify as a type of blood DCs [5].
The functional-anatomical classification of DCs is widely vast, the classification of DCs are dependent of anatomical location or function, for example, DCs in heart are known as interstitial cells, in ganglia are known as interdigitating cells, but when DCs are in the afferent lymph are called veiled cells. Also, the function of these are different but sequential [5, 6]. Intestinal DCs are found in small intestine, lamina propia and gut associated lymphoid tissue. This DCs express CD103 and Sirpα in three different ways, such as CD103 + Sirpα- DCs, The CD103 + Sirpα+ DCs and CD103- Sirpα+ DCs. Most of these cells are located deeper into lamina propia, and express CD45, human leukocyte antigen-DR isotype (HLA-DR), CD14, CD64 and high levels of CX3C chemokine receptor 1(CX3CR1), and since these cells do not migrate to the lymph nodes, they have been depicted as intestinal macrophages. In the mesenteric lymph node DCs are a mixture of cells found in the peripheral blood. Such as peripheral blood, where soluble food bioactives may also be directly available for internalization by DCs in the draining lymph nodes
LCs and microglia are two specialized self-renewing DCs, found them in stratified squamous epithelium and parenchyma of the brain, respectively. The LCs differentiate into migratory DCs, whereas microglia are considered as a type of specialized macrophage. There are DCs found in tissues and lymph nodes with marker CD14+, a subset of CD11c+, found in interstitial DCs; but they are more monocyte-like or macrophage-like, that may arise from classical monocytes [5].
Immatures and matures DCs have different morphologic, immatures DCs monocyte-derived are spherical, irregular shape, with little cytoplasmatic projections, also abundant phase-dense granules (birbeck’s granules or bodies) and irregular nucleus with small nucleoli. Once the DCs maturates shows stellate process, giving veiled appearance, with more extended dendrites projecting in many directions from the body cell [6, 8].
The DCs have 3 stages precursor, immature and mature stage, but some authors do not count the precursor phase [6, 9]. Precursor phase course with any of the principal precursor as cMoPs, pDCs or Human equivalent of pre-DCs. It migrates from bone morrow to specific tissue or area, process leaded by chemokine chemoreceptors such as C-C chemokine receptor type 1 (CCR1), CCR5 and CCR6 and by adhesion molecules CD26P ligand. When the cell arrives to the corresponding tissue or place, it becomes immature DC. The immature DC express CCR1 and CCR3, where its ligand is in endothelium and inflammatory cells, promoting its migration to different organs and inflammatory tissues. This immature DC is capable of capture antigens by different receptors like Fc receptor, integrins, type C lectin and scavenger receptors such as lectin-type oxidized LDL receptor 1 (LOX-1) and CD91. Immature DC is characterized for various amounts of chemokines, so it can be extravasated to inflammatory tissue [6].
Once the DC has captured the antigen, this one is degraded to peptides that will get bind to MHC class I or class II. The endogenous antigens are processed by MHC class I, while exogenous antigens are processed by MHC class II. The lipidic antigens are presented by different molecules CD1(a-d) to T cell receptor (TCR) or natural killer T (NKT) cell. The differentiation process of immature DC to mature DC needs different signals to complete the process. To the immature DC gets mature, needs to stimulate T lymphocyte. This is possible when the antigen is presented to T lymphocyte by MHC class I or class II to TCR receptor and interaction of costimulatory molecules (CD28, CD40, CD54, CD58, CD80, CD83 and CD86) to activate T lymphocyte. Other molecules like adhesion (CD58, CD54) danger signal (CD40 ligand, tumor necrosis factor (TNF)-α, IL-1, IL-6, Interferon (INF)-α and Toll-like receptors (TLRs) agonist) [6, 8]. When the DC becomes mature, decreases the chemokine receptor expression of CCR1 and CCR5, whereas CCR7 increases. The CCR7 ligand is in ganglia walls and ganglionic paracortical zone. There, the mature DC secretes chemokines such as thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC) or interferon gamma-induced protein 10 (IP-10), which recruits different types of T lymphocytes, monocytes, regulated on activation, normal T cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1α and MIP-β, to the local microenvironment [6].
DCs cells have many functions, but these can be globed within three functions. The first one is the main function as antigen presentation and activation of T lymphocytes as inducing adaptative immunity, with important release of cytokines for example IL-12 to differentiate T lymphocytes in T helper cell or cytotoxic lymphocytes. DCs have a wide range of properties including potent stimulation of native CD4+ T cells, cross-presentation to CD8+ T cells and production of pro-inflammatory cytokines IL-1, IL-6, TNF-α, IL-12 and IL-23 [5, 9, 10]. The second function to induce tolerance. There are 2 types of tolerance central and peripheral. Central tolerance develops in thymus where a tolerance upon our own antigens occurs, and the reactive T lymphocytes to those antigens are destroyed, this also happen in bone morrow for B lymphocytes. The peripheral tolerance occurs when costimulatory molecules, last step of antigen presentation is not complete, there is a failure in activation of T lymphocyte, so the T lymphocyte become tolerogenic [6, 9, 10]. The third function to maintain immune memory in tandem with B cells. As mentioned before, there are population of DCs in ganglia, in the germinal center are found the follicular DCs which seems to be a reservoir of antigen and antibody complexes, that last an exceptionally long time up to months or years. This allows a constant stimulation of B cells to maintain memory [9].
There are others important functions of DCs, as their role in innate immunity, the DCs have pattern recognition receptor (PRR) and pathogen-associated molecular pattern (PAMPs) [10]. These receptor patterns activate TLR pathways, type C lectins and release pro-inflammatory cytokines to activate innate immunity system [8]. Also, DCs have been related to B lymphocytes proliferation and induction of T lymphocytes to suppress the immune response by missing of costimulatory molecules without IL-12, inducing T lymphocytes to secrete IL-10 and transforming growth factor (TGF)-β [6, 9].
Since the discovery of DCs [11], the knowledge of the innate and adaptive immune response has been increasing significantly. At present, DCs are considered a key cell in immune response activation with multiple functions including the virus recognition, processing of viral antigen and as antigen-presenting cells to cells of specific immune response, serving as a bridge between innate and adaptive response [12]. DCs are bone marrow-derived cells and they can be found in different parts of the organism including mucous membrane, the skin, and lymphoid tissue [13]. Depending on surface markers, DCs can be classified as immature or mature myeloid DCs and plasmacytoid DCs [14, 15].
Immature DCs are inactive cell with high capacity to capture viral antigen. They are present in virtually all tissue with high probability to capture invading viruses. Immature DCs lack the capacity of antigen presentation. On the other hand, mature MDC is generated by an immature DC that was activated when recognized and processed viral antigen. Mature DCs function as antigen presenting cells (APCs). They express MHC-II molecules and different co-stimulators surface molecules that give them the antigen presentation capacity. Mature DCs also produce different cytokines to initiate antiviral immune response [16].
Likewise, plasmacytoid DCs also sense viral pathogen. They are called plasmacytoid DCs by its high resemblance to plasma cells. Although pDC has the ability of antigen-presenting, this function is low compared with MDC. However, pDCs contribute to both inflammatory process and antiviral state. They are specialized DCs that produce proinflammatory cytokines and high levels of IFN type I [17]. Both MDC and pDCs are present in lymphatic nodes where they are capable to present viral antigen to naïve T cell [18, 19].
Immature DCs are considered the sentinels of the immune response. These cells are distributed in practically all the body where they have the capacity of interact with the invading virus. They carry out the function against viral infection by different mechanisms. They can be infected by viruses or they can respond to molecules produced and secreted by other virus infected cells. When they are infected, DCs can respond in various ways, firstly, DCs have different receptors distributed on cell surface, cytoplasm, and specialized endosomes. TLRs and C-type lectins receptors (CLRs) are present in cell surface and some TLRs in endosomes, while retinoic acid-inducible gene (RIG), melanoma differentiation-associated protein 5 (MDA5) and nucleotide-binding oligomerization domain 2 (NOD2) are only present in cytosol [20, 21, 22]. TLRs have N-terminal ectodomains (ECDs) which recognize molecules of viruses. This ECDs are constructed by a tandem motif of leucine-rich repeats (LRRs) and forms a horseshoe structures [23]. Binding of TLRs with their ligand depends on these structures [24]. However, diverse receptors respond to an extensive repertoire of viral PAMPs. These viral PAMPs can be glycoproteins present on the viral external surface, viral genome, or replication intermediates formed during viral replication [25].
Depending on the activated receptor, DCs can produce proinflammatory cytokines or IFN. During maturation process DCs interact with the antigen and upregulate MHC-II to present antigen to naïve CD4+T cells. In addition, DCs produce diverse surface molecules such as CCR7 which is necessary in trafficking into lymphatic nodes and CD40, CD80, and CD86 which are co-stimulatory surface factors that enable them to activate T naïve cell to initiate the adaptive immune responses [26, 27].
DCs is the main cell used to establish an effective immune response. At present, four subsets with different functions have been identify in human. Each subset of DC has different markers and a functional distinction that enable them to participate in different states to orchestrate an antiviral immune response. Each type of DC expresses different receptors that can be membrane-associated molecules or free in the cytoplasm. Activation of these receptors ends in different cytokine-proinflammatory production and interferon. Depending on cytokine produced, naïve CD4+T cells is differentiated into T helper effector cell [14].
Myeloid DCs, called classical or conventional DCs (cDCs) detect viral proteins through expression of membrane surface receptors such TLR-4 and DC-specific intercellular adhesion molecule 3 (ICAM3)-grabbing non-integrin (DC-SIGN) (see Figure 2) [28]. DC-SIGN support the initial immune response between T cells and DCs, but when DC-SIGN have contact with viral glycoproteins results in activation of signal transduction pathways than cause modulation of immune responses [29]. The signaling pathway triggered by DC-SIGN recruits Ras and the subsequent phosphorylation of the kinase RAF1 which is mediated by p21-activated kinases (PAKs) and Src Kinases. The activation of RAF1 induces phosphorylation of nuclear factor (NF)-κB increasing the transcriptional activation from IL-18, IL-10 and IL-12 promoter [29, 30].
Signaling pathway and cytokines production of DCs during viral infection. (A) Myeloid DCs and (B) Plasmacytoid DCs. Description in the text (figure created by Muñoz-Carrillo
The association of viral proteins through concave surface of TLR4-ECD induces two different pathways [31]. Myeloid differentiation primary response 88 (MyD88)-Dependent Pathway initiates with the recruitment of MyD88 adapter and subsequent activation of tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6). Then TRAF6 activates the NF-κB essential modulator (NEMO), which is the regulatory subunit IKK complex and activates NF-κB causing its translocation to the nucleus, where induces gene expression such as IL-6 and IL-12 [21]. MyD88-Independent pathway recruits TIR-domain-containing adapter-inducing interferon-β (TRIF) [32]. TRIF activates TRAF3 and finally induce interferon regulatory transcription factor (IRF-3) activation and the subsequent IFN-β expression [21].
In addition to membrane surface receptors cDCs also have endosomal TLRs such as TLR-3 and TLR-7/TLR-8 which sense dsRNA and ssRNA respectively. Each receptor has a specific signaling pathways [14]. TLR-3 sense viral dsRNA through its largely uniform and flat horseshoe structure of TLR-ECD [33]. TLR3 has the same MyD88-Independent pathway with the activation of TRAF3 and subsequent IFN-β expression [32]. Viral ssRNA are sense by TLR-7 and TLR-8, these receptors activate MyD88 pathway with the recruitment of TRAF6 and TRAF3. Finally, activation of IRF-3 and IRF-7 induces IFN-β and IFN-α expression respectively (see Figure 2A) [21, 34].
In addition to DC-SIGN and TLRs, the viral genome can be exposed in the cytoplasm during the replicative processes or during direct penetration into the cell. NOD2 and RNA helicases such melanoma differentiation-associated protein 5 (MDA5) and RIG-1 detect dsRNA in the cytoplasm [35]. Interferon promoter stimulator-1 (IPS-1) interacts with MDA5, RIG-1 and NOD2
On the other hand, pDCs not express DC-SIGN but express CD4 that can sense glycoproteins of viruses as human immunodeficiency virus (HIV). The viruses can enter through direct fusion with the cell membrane or through receptor-mediated endocytosis and activates different signaling pathways (see Figure 2B) [40, 41]. The endosomal receptors TLR-7 and TLR-9 are selectively express in pDCs and sense RNA or DNA respectively. This engage activates downstream signaling pathway [42]. TLR-9 and TLR-7 activates IRF-3 and IRF-7 like in cDCs signaling with final IFN-β and IFN-α expression respectively [43]. TLR-9 signaling pathways include the recruitment of Interleukin-1 receptor-associated kinase 4 (IRAK4) through its death domain. Activated IRAK4 interacts with IRAK2. This complex associates with TRAF6 to final activation and nucleus translocation of NF-κB and leads TNF-α and IL-6 production [17, 44, 45]. pDCs can also be infected by direct penetration of virus and the viral genome can be sense by RIG-1, MDA5 and NOD2. The signaling in the pDCs is through IPS-1 pathways as the same way that on cDCs [20, 22]. This pathway activates NFκB, IRF-3 and IRF-7 to express IL-12, IFN-β and IFN-α respectively [38, 39].
Other subsets of DCs are the LCs and Interstitial DCs (IDCs), these kinds of DCs are commonly the first DCs that have contact with some virus [46]. LCs are localized in mucosal stratified squamous epithelium and skin epidermis. LCs express different CLR: CD207 or Langerin. Moreover, LC has a low expression of TLR4 and expression of TLR-3, −7 and − 8 [14, 47]. LCs activated finally express IL-8, IL-6, TNF-α [48]. On the other hand, the IDCs are localized in the epidermis and express similar receptors that cDCs like DC-SIGN and TLR-3, -4, -7 and -8 and have similar signaling pathways [14].
Activation of the antiviral response generated by immune system depends largely on the activation of dendritic cells. Each subtype of this family of antigen-presenting cells have an important role by processing viral antigens that trigger different signaling pathways through their distinct receptors. The consequence of this signaling pathway results in the expression of various cytokines involved in the activation of immune cells. For this reason, a better knowledge about how different immune cells subtypes can induce distinct pathways is required for a better vision of whole antiviral response.
In parasitic infections is difficult to generalize about the mechanisms of antiparasitic immunity because there is a great variety of different parasites that have different morphology and reside in different locations of tissues and hosts during their life cycles [49]. For this reason, we will talk about the role of dendritic cells in protozoa and helminths infection, two of the main parasites of medical importance for human health.
DCs have the capacity to recognize different molecules in the surface of parasites and are efficient phagocytes; thus, several intracellular parasites reside inside DCs. Once DCs phagocytose intracellular parasites, they can exert their microbicidal capacities, although it has been shown that they are not as efficient in the destruction of microorganisms as other phagocytes such as macrophages and neutrophils. Once internalized, DCs process antigens for presentation to T cells [50].
Protozoan parasites are pathogens that have developed additional and sophisticated strategies to escape the immune attack of the host. This is because their life cycles generally involve several stages of specific antigenicity, which facilitates their survival and propagation within different cells, tissues, and hosts [51]. Frequently, the host is unable to eliminate protozoan infections, which often results in chronic disease or irreparable infections, in which the host continues to act as a reservoir of parasites, a cause of great concern due to their prevalence, morbidity and mortality [52, 53]. This host resistance to protozoa infections depends mainly on the development of a T helper type 1 (Th1) response and on the production of IL-12 by APCs [54]. Therefore, the classical reaction of the host to infections by protozoan parasites is the maturation of different subsets of DC, and in some cases, the activity of these cells leads to a response that is effective in controlling the infection [55].
Among the most important protozoan parasites are those that living in human blood and tissues, which can cause fatal diseases. The immune response against protozoan infections involves a strong innate immune response followed by predominantly a Th1 response. The innate immune system is comprised of several cell types, including DCs. Recognition of pathogens by these cell types leads to phagocytosis in some cases, and the production of pro-inflammatory cytokines, which assist in shaping the subsequent adaptive immune response (see Figure 3) [56].
Role of DCs in protozoan infections. Polarization of Th1 response through interactions between PAMPs and PRRs (TLR-2, -4, -9, -11 and -12), which in a signal-dependent manner (involving the activation of MAPKs p38/JNK and MyD88) induce the expression of Th1 cytokines such as IL-12, Il-6, IFN-γ and TNF-α. the PRRs from protozoa induce the presentation of antigens, the co-stimulation, and the expression of the cytokine IL-12, IFN-γ production by DCs during Ag presentation, by signaling pathway STAT-4. Description in the text. (figure created by Muñoz-Carrillo
During the parasitic protozoan infections different PRRs present in DCs are involved in the recognition PAMPs of parasites. In trypanosomiasis, the glycoinositolophospholipids (GIPLs) and glucosylphosphatidylinositol (GPI) anchors from Trypanosoma cruzi are recognized by TLR-4 and TLR-2, respectively, inducing the inflammatory cytokines production [57, 58]. Likewise, the DNA of
Helminth parasites, like protozoan parasites, have significant differences in their biological life cycles, which are reflected in the differences in clinical outcomes seen among helminth parasites. Pathological consequences of most helminth infections have been associated with both with the parasite intensity (or burden) and the relative acuteness or chronicity of the infection, because the helminth parasites modulate/regulate the host response to themselves (parasite-specific immunoregulation) [84].
The immune response against helminths is characterized by the induction of an early immune response of type Th1, with subsequent predominance of a Th2 type immune response, resulting in a mixture of both Th1/Th2 responses [85, 86], which are dependent on the immune responses mediated by CD4+ T cells [87]. These CD4+ T cells can function as APCs and play a key role in establishment the cytokine environment, thus directing their differentiation either by suppressing or favoring the inflammatory response at the intestinal level, which is crucial for the expulsion and elimination of the parasite (see Figure 4) [88].
Role of DCs in helminth infections. The immune response against helminths is characterized by the induction of an early immune response of type Th1, with subsequent predominance of a Th2 type immune response, resulting in a mixture of both Th1/Th2 responses. The polarization of the cellular immune response to a Th1/Th2 type immune response depends on the type of signal derived from DCs. Description in the text. (figure created by Muñoz-Carrillo
This implies that the helminths have developed strategies, such as the evasion or suppression of the host immune response, which prevent their expulsion and allow their long-term survival. It is believed that the modulating effects of the immune system arise from the ability of the helminth to regulate the host immune response, developing mechanisms for the modulation of DCs as key players in the initiation and polarization of adaptive immune responses [89, 90, 91].
During the intestinal infection by helminths, the polarization of the cellular immune response to a Th1 type immune response depends on the type of signal derived from DCs. For example,
Intestinal DCs are classified according to their unique or combined expression of CD11b and CD103, as well as the dependence on either interferon regulatory factor 4 or 8 (IRF4 or IRF8) for their development and/or survival. The intestinal DCs are capable of process antigens, migrating to mesenteric lymph nodes upon activation, and priming naive T cells. However, IRF8-dependent CD103+ DCs are important for the generation of type 1 responses of both helper and cytotoxic T cells, thus promoting
On the other hand, the PRRs from helminths can also activate the DCs for the induction of the Th2 response by interacting with the TLR and CLR. This interaction may promote Th2 responses by suppressing antigen presentation, co-stimulation and/or expression of Th1-promoting cytokines by directly interfering with these pathways. DCs that drive Th2 responses typically exhibit specialized markers, such as CD301b, PDL2, and CD11b, and several receptors for the Th2-related cytokines IL-4R, IL-13R, IL-25R, TSLP-R, and IL-33R. Additionally, the extracellular signal-regulated kinase (ERK) and signal transducer and activator of transcription 4 (STAT4) pathway upregulates the costimulatory molecules, CD40, OX40L, and Jagged. Activation of the major transcription factors interferon regulatory factor 4 (IRF4) and KLF4 inhibits IL-12 production and increased IL-10 secretion. These factors typically act individually or in concert to orchestrate Th2 responses in helminth infections [106, 107, 108].
In
Activated DCs are involved in the response to infections, which induces an increase in MHC expression, adhesion, and costimulatory molecules. The recognition of intracellular pathogens derived from mycobacterial cell wall components (lipids/glycolipids) such as phosphatidyl-myo-inositol mannoside, lipo-mannan, lipoarabinomannan, mycolic acids, lipopeptides, and phosphoinositol-containing lipids is given through the TLR-2, TLR-4, TLR-9, TLR-8 and the TLR1/TLR6 that heterodimerize with the TLR-2 [114, 115]. The signaling pathway that occurs in almost all TLRs is through MYD88, while for TLR4 the signaling pathway can be through MYD88 and TRIF [116, 117]. The activation of these receptors induces the activation of mitogen-activated protein kinase (MAPK) and NF-κB producing proinflammatory cytokines in DCs (see Figure 5). Other antigens derived from
Role of DCs in bacterial infections. The TLRs are involved in the recognition of mycobacterial antigens. The activation of TLR-4 and TLR-2 by these antigens leads to an intracellular signaling pathway, leading to a Th1 and Th2 response, respectively. NOD-like receptors (NOD 1 and NOD 2) recognize bacterial peptidoglycans (DAP and MDP), the downstream signaling activates NF-κB and MAPK generating a Th1 response. Description in the text (figure created by Muñoz-Carrillo
On the other hand, DCs infection with other bacteria of the type
Other receptors involved in the response to pathogens are NOD1 and NOD2 receptors make up the family of NOD-like receptors containing a CARD domain (NLRC) [137]. These receptors are highly expressed in DCs and act as intracellular PRRs that recognize bacterial peptidoglycans [138, 139, 140]. NOD1 mainly recognizes γ-D-Glu-meso-diaminopimelic acid (DAP) while NOD2 recognizes muramyl dipeptide (MDP) [141]. Once the activation of these receptors occur, the downstream signaling activates NFκB through the union of its CARD domain to the protein kinase RIP2, which in turn recruits IRAK2, TRAF6, TAK1 binding protein (TAB1) and transforming growth factor-β-activated kinase 1 (TAK1) to activate the IKK complex, these events result in the degradation of IκBα inhibitor which leads to the translocation of NFκB to the nucleus and induce the expression of proinflammatory mediators [142]. In addition to the NFκB pathway, the stimulation of NOD1 and NOD2 leads to the activation of MAP kinases p38, ERK, and JNK pathway
Role of DCs in fungal infection. Antigens derived from fungi such as b-glucan which are recognized by Dectin-1, this leads to a downstream signaling pathway activating NF-kB producing IL-6 and IL-23 leading to a Th17 phenotype. The union of Dectin-1 whit b-glucan also leads to the activation of ROS, which can NLRP3 inflammasome assembly activating caspase-1 which cuts the pro-IL-1 and pro-IL-18 generating its active forms, which together with IL-23 activates the Th17 phenotype. Description in the text (figure created by Muñoz-Carrillo
Infections caused by opportunistic fungal pathogens include
DCs are the only ones capable of decoding information related to fungi [146]. The activation of the various immunity mechanisms is carried out efficiently by the DC that decode the signals sent by the fungi and translate them into an immune response of T helper (Th)
Inflammatory DCs generate the responses of Th17 and Th2 antifungal cells
It has also been reported that NLRP3 linked with ASC and caspase 1, is triggering inflammation activated by pathogenic fungi such as
Many types of cells, including macrophages and DCs, produce IL-1β induces the differentiation of Th17 cells, which are necessary for effective defense of the host against
DCs are considered key cells as the first line of defense against viruses and to induce adaptive defense. In the innate immune response, they can exert virus phagocytosis and produce cytokines to activate NK cells to eliminate virus infected cells. In adaptive immune response, DCs induce differentiation of Th1-cells that in turn induce activation of antigen specific cytotoxic cells, macrophages, and antibody production to participate in viral clearance.
For the elimination of bacteria, a specific immune response is required, for intracellular bacteria a Th1 response is required as well as cytotoxic T lymphocytes, the latter to produce IFN-γ and can kill the cells that have been infected, in this response the Il −12 is important and its production by DCs requires stimuli derived from pathogens as well as from CD4+ T-cells; on the other hand, for extracellular bacteria a Th17 response is required, in this response DCs play an important role in producing pro-inflammatory cytokines so that a Th17 response can be given, thus these cells coordinate the recruitment of neutrophils that phagocytize extracellular bacteria and thus eliminate the bacterial infection.
DCs participate in the immune response against different opportunistic fungi, the latter are capable of producing different diseases including vulvovaginal candidiasis, oral candidiasis or disseminated candidiasis (
During parasitic infections, DCs play an important role, since, through them, the body can mount a specific immune response, mainly mediated by T lymphocytes. The DCs recognize the antigens of the parasites, and in the first instance, they induce a Th1-type immune response, characterized mainly by the production of pro-inflammatory cytokines and mediators. Nevertheless, parasites have the ability to polarize, through the activation of DCs, towards a Th2-type immune response, characterized mainly by the production of anti-inflammatory cytokines, eosinophilia and mastocytosis. However, due to the great diversity of parasites that exist, as well as their phenotypic variability, which involves different stages of antigenicity, conditioned by the life cycle of the parasite itself, these microorganisms have the ability to develop strategies that allow them to evade the immune system and facilitate their survival and spread in the host. Despite the different immune responses that the host assembles in contact with the different diseases caused by these microorganisms, DCs are very important, since they represent the junction point between the innate and adaptive immune responses, allowing the host to differentiate the type of microorganism by which it has been invaded and thus be able to mount a specific immune response.
Dendritic cells are a key cell type in the recognition of intracellular and extracellular pathogens through the different receptors that they express. The maturation of the DCs is an important event since through this mechanism these cells acquire the ability to express MHC as well as costimulatory molecules, thus conditioning the presentation of the antigen, producing cytokines and mounting immune in order to kill the invading pathogen. The response can be mediated by the PRRs as they will recognize different structures of the invading microorganism and execute a defensive response with the purpose of eliminating the invading microorganism through the production of antimicrobial cytokines and intermediaries, as well as activating transcription factors to produce cytokines that have an important role in the polarization of the T helper cell during priming by DCs.
Thanks to the authors who collaborated in the writing of this chapter: Dr. en C. José Luis Muñoz-Carrillo; Dr. en C. Oscar Gutiérrez-Coronado; Dr. en C. Juan Francisco Contreras-Cordero; Dra. en C. Paola Trinidad Villalobos-Gutiérrez; Dr. Luis Guillermo Ramos-Gracia, and Dra. Jazmín Monserrat Vargas-Barboza; as well as the Universities involved: Cuauhtémoc University Aguascalientes, University of Guadalajara, and Autonomous University of Nuevo Leon for financial support for chapter publication.
We have no conflict of interest related to this work.
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Abdel Rahman and Hosam El-Din Mostafa Saleh",coverURL:"https://cdn.intechopen.com/books/images_new/5154.jpg",editedByType:"Edited by",editors:[{id:"92718",title:"Prof.",name:"Rehab O.",middleName:"O.",surname:"Abdel Rahman",slug:"rehab-o.-abdel-rahman",fullName:"Rehab O. Abdel Rahman"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:1,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"50376",doi:"10.5772/62434",title:"Tungsten-Based Composites for Nuclear Fusion Applications",slug:"tungsten-based-composites-for-nuclear-fusion-applications",totalDownloads:2365,totalCrossrefCites:7,totalDimensionsCites:10,abstract:"This chapter provides a comprehensive knowledge about the potential role of tungsten-based composites in fusion reactors and the research work which has been done in this very important area of nuclear materials. The characteristics of tungsten, which make it the most potential candidate for plasma-facing applications, have been presented along with the shortcomings in pure tungsten. The research work that has been done so far in the field of tungsten-based composites to overcome the problems with pure tungsten has been included. The fabrication, characterization, types of reinforcements and the classes of composites have been reviewed. The behavior of tungsten-based composites under various kinds of loads (i.e. mechanical and thermal) and environments (radiations and oxidizing etc.) has been summarized.",book:{id:"5154",slug:"nuclear-material-performance",title:"Nuclear Material Performance",fullTitle:"Nuclear Material Performance"},signatures:"Owais A. Waseem and Ho Jin Ryu",authors:[{id:"178474",title:"Prof.",name:"Ho Jin",middleName:null,surname:"Ryu",slug:"ho-jin-ryu",fullName:"Ho Jin Ryu"},{id:"184864",title:"Mr.",name:"Owais Ahmed",middleName:null,surname:"Waseem",slug:"owais-ahmed-waseem",fullName:"Owais Ahmed Waseem"}]},{id:"50182",doi:"10.5772/62594",title:"Developing Tailor-Made Microbial Consortium for Effluent Remediation",slug:"developing-tailor-made-microbial-consortium-for-effluent-remediation",totalDownloads:1576,totalCrossrefCites:4,totalDimensionsCites:8,abstract:"The work describes a biofilm-based soluble sulphate reduction system, which can treat up to 1600 ppm of soluble sulphate within 3.5 hours of incubation to discharge level under ambient condition using a well-characterized sulphate-reducing bacterial (SRB) consortium. This system ensures the treatment of 1509 litres of sulphate solution in 24 hours using a 220-litre bioreactor. Performance of the system during series operation was compromised, indicating the presence of inhibitor in solution at a toxic level. A single unit bioreactor would be the ideal configuration for this consortium. Modified designs of bioreactors were tested for optimization of the process using response surface methodology (RSM), where the system could function optimally at an initial sulphate concentration of 1250 ppm with a flow rate of 1.8 litre/hour. The time course of sulphate reduction yielded a parabolic profile (with coefficient of determination r\n2 = 0.99 and p value < 0.05). The rate of sulphate reduction was found to be independent of seasonal variation as well as the specific design characteristic.",book:{id:"5154",slug:"nuclear-material-performance",title:"Nuclear Material Performance",fullTitle:"Nuclear Material Performance"},signatures:"Shaon Ray Chaudhuri, Indranil Mukherjee, Debabrata Datta,\nChaitali Chanda, Ganesh Prasath Krishnan, Swati Bhatt, Paulami\nDatta, Shashi Bhushan, Sourav Ghosh, Pinaki Bhattacharya, Ashoke\nRanjan Thakur, Debanik Roy and Parthasarathi Barat",authors:[{id:"179765",title:"Dr.",name:"Shaon",middleName:null,surname:"Ray Chaudhuri",slug:"shaon-ray-chaudhuri",fullName:"Shaon Ray Chaudhuri"}]},{id:"51035",doi:"10.5772/62856",title:"Introductory Chapter: Introduction to Current Trends in Nuclear material Research and Technology",slug:"introductory-chapter-introduction-to-current-trends-in-nuclear-material-research-and-technology",totalDownloads:2153,totalCrossrefCites:1,totalDimensionsCites:5,abstract:null,book:{id:"5154",slug:"nuclear-material-performance",title:"Nuclear Material Performance",fullTitle:"Nuclear Material Performance"},signatures:"Rehab O. Abdel Rahman",authors:[{id:"92718",title:"Prof.",name:"Rehab O.",middleName:"O.",surname:"Abdel Rahman",slug:"rehab-o.-abdel-rahman",fullName:"Rehab O. Abdel Rahman"}]},{id:"51107",doi:"10.5772/63652",title:"Gamma Uranium Molybdenum Alloy: Its Hydride and Performance",slug:"gamma-uranium-molybdenum-alloy-its-hydride-and-performance",totalDownloads:2257,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"The high density metastable gamma uranium molybdenum alloy (γ‐UMo) is being qualified as a nuclear fuel for the conversion of high enriched uranium (HEU) to low enriched uranium (LEU) fuels in research nuclear reactors. γ‐UMo, with compositions between 7 and 10 wt.% molybdenum, has excellent properties to allocate fission gases but unacceptable behavior in contact with aluminum in the matrix of dispersed fuels. Development and processing alternatives are welcome to decide final working paths and new nuclear fuels design. A historical introduction on the development of materials testing reactors (MTR) nuclear fuels is presented to illustrate comings and goings to reach desired qualification objectives. Several studies performed on UMo probes, miniplates and full size plates are mentioned to contribute to the knowledge of fuel properties and to incorporate new process technologies. Focus is directed to the discovery of the gamma uranium molybdenum hydride and the hot rolling colamination of monolithic UMo with nonaluminum claddings. A scalable process of hydriding, milling and dehydriding (HMD) to comminute the ductile UMo was developed. Monolithic UMo miniplates with Zircaloy‐4 (Zry4) cladding was colaminated for the first time and under irradiation conditions showed excellent performance after high burn‐up.",book:{id:"5154",slug:"nuclear-material-performance",title:"Nuclear Material Performance",fullTitle:"Nuclear Material Performance"},signatures:"Enrique E. Pasqualini",authors:[{id:"178951",title:"Dr.",name:"Enrique E.",middleName:null,surname:"Pasqualini",slug:"enrique-e.-pasqualini",fullName:"Enrique E. Pasqualini"}]},{id:"50261",doi:"10.5772/62572",title:"Monte Carlo Simulations of Nuclear Fuel Burnup",slug:"monte-carlo-simulations-of-nuclear-fuel-burnup",totalDownloads:2740,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"In the operation of a nuclear power plant, it is very important to determine the time evolution of material composition and radionuclide inventory during the entire operation of the plant. In the experiments, the Monte Carlo N-Particle eXtended (MCNPX) code was found to be accurate in predicting the uranium fuel depletion, the plutonium production and the buildup of most of the fission products in a nuclear reactor. The goal in this chapter is to analyze the effect of different nuclear fuel grades on the total radioactivity of the reactor core by employing nuclear burnup calculations for the three different fuels: mixed oxide fuel (MOX), uranium oxide fuel (UOX) and commercially enriched uranium (CEU), utilizing simulations with MCNPX code. The calculated results indicate that there is a buildup of plutonium isotopes for UOX and CEU, whereas there is a decline in the plutonium radioisotopes for MOX fuel with burnup time. The study of reactor neutronic parameters showed UOX fuel performs better relative to MOX and CEU. Zircaloy, with low thermal neutron absorption cross-section and high thermal conductivity, produced better results for the effective multiplication factor Keff and hence proved to be a much more effective clad material.",book:{id:"5154",slug:"nuclear-material-performance",title:"Nuclear Material Performance",fullTitle:"Nuclear Material Performance"},signatures:"Raghava R. Kommalapati, Fiifi Asah-Opoku, Hongbo Du and Ziaul\nHuque",authors:[{id:"179935",title:"Dr.",name:"Raghava",middleName:"R",surname:"Kommalapati",slug:"raghava-kommalapati",fullName:"Raghava Kommalapati"},{id:"180165",title:"Dr.",name:"Hongbo",middleName:null,surname:"Du",slug:"hongbo-du",fullName:"Hongbo Du"},{id:"180166",title:"Prof.",name:"Ziaul",middleName:null,surname:"Huque",slug:"ziaul-huque",fullName:"Ziaul Huque"},{id:"180167",title:"Mr.",name:"Fiifi",middleName:null,surname:"Asah-Opoku",slug:"fiifi-asah-opoku",fullName:"Fiifi Asah-Opoku"}]}],mostDownloadedChaptersLast30Days:[{id:"50261",title:"Monte Carlo Simulations of Nuclear Fuel Burnup",slug:"monte-carlo-simulations-of-nuclear-fuel-burnup",totalDownloads:2740,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"In the operation of a nuclear power plant, it is very important to determine the time evolution of material composition and radionuclide inventory during the entire operation of the plant. In the experiments, the Monte Carlo N-Particle eXtended (MCNPX) code was found to be accurate in predicting the uranium fuel depletion, the plutonium production and the buildup of most of the fission products in a nuclear reactor. The goal in this chapter is to analyze the effect of different nuclear fuel grades on the total radioactivity of the reactor core by employing nuclear burnup calculations for the three different fuels: mixed oxide fuel (MOX), uranium oxide fuel (UOX) and commercially enriched uranium (CEU), utilizing simulations with MCNPX code. The calculated results indicate that there is a buildup of plutonium isotopes for UOX and CEU, whereas there is a decline in the plutonium radioisotopes for MOX fuel with burnup time. The study of reactor neutronic parameters showed UOX fuel performs better relative to MOX and CEU. Zircaloy, with low thermal neutron absorption cross-section and high thermal conductivity, produced better results for the effective multiplication factor Keff and hence proved to be a much more effective clad material.",book:{id:"5154",slug:"nuclear-material-performance",title:"Nuclear Material Performance",fullTitle:"Nuclear Material Performance"},signatures:"Raghava R. Kommalapati, Fiifi Asah-Opoku, Hongbo Du and Ziaul\nHuque",authors:[{id:"179935",title:"Dr.",name:"Raghava",middleName:"R",surname:"Kommalapati",slug:"raghava-kommalapati",fullName:"Raghava Kommalapati"},{id:"180165",title:"Dr.",name:"Hongbo",middleName:null,surname:"Du",slug:"hongbo-du",fullName:"Hongbo Du"},{id:"180166",title:"Prof.",name:"Ziaul",middleName:null,surname:"Huque",slug:"ziaul-huque",fullName:"Ziaul Huque"},{id:"180167",title:"Mr.",name:"Fiifi",middleName:null,surname:"Asah-Opoku",slug:"fiifi-asah-opoku",fullName:"Fiifi Asah-Opoku"}]},{id:"51107",title:"Gamma Uranium Molybdenum Alloy: Its Hydride and Performance",slug:"gamma-uranium-molybdenum-alloy-its-hydride-and-performance",totalDownloads:2257,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"The high density metastable gamma uranium molybdenum alloy (γ‐UMo) is being qualified as a nuclear fuel for the conversion of high enriched uranium (HEU) to low enriched uranium (LEU) fuels in research nuclear reactors. γ‐UMo, with compositions between 7 and 10 wt.% molybdenum, has excellent properties to allocate fission gases but unacceptable behavior in contact with aluminum in the matrix of dispersed fuels. Development and processing alternatives are welcome to decide final working paths and new nuclear fuels design. A historical introduction on the development of materials testing reactors (MTR) nuclear fuels is presented to illustrate comings and goings to reach desired qualification objectives. Several studies performed on UMo probes, miniplates and full size plates are mentioned to contribute to the knowledge of fuel properties and to incorporate new process technologies. Focus is directed to the discovery of the gamma uranium molybdenum hydride and the hot rolling colamination of monolithic UMo with nonaluminum claddings. A scalable process of hydriding, milling and dehydriding (HMD) to comminute the ductile UMo was developed. Monolithic UMo miniplates with Zircaloy‐4 (Zry4) cladding was colaminated for the first time and under irradiation conditions showed excellent performance after high burn‐up.",book:{id:"5154",slug:"nuclear-material-performance",title:"Nuclear Material Performance",fullTitle:"Nuclear Material Performance"},signatures:"Enrique E. Pasqualini",authors:[{id:"178951",title:"Dr.",name:"Enrique E.",middleName:null,surname:"Pasqualini",slug:"enrique-e.-pasqualini",fullName:"Enrique E. Pasqualini"}]},{id:"50376",title:"Tungsten-Based Composites for Nuclear Fusion Applications",slug:"tungsten-based-composites-for-nuclear-fusion-applications",totalDownloads:2365,totalCrossrefCites:7,totalDimensionsCites:10,abstract:"This chapter provides a comprehensive knowledge about the potential role of tungsten-based composites in fusion reactors and the research work which has been done in this very important area of nuclear materials. The characteristics of tungsten, which make it the most potential candidate for plasma-facing applications, have been presented along with the shortcomings in pure tungsten. The research work that has been done so far in the field of tungsten-based composites to overcome the problems with pure tungsten has been included. The fabrication, characterization, types of reinforcements and the classes of composites have been reviewed. The behavior of tungsten-based composites under various kinds of loads (i.e. mechanical and thermal) and environments (radiations and oxidizing etc.) has been summarized.",book:{id:"5154",slug:"nuclear-material-performance",title:"Nuclear Material Performance",fullTitle:"Nuclear Material Performance"},signatures:"Owais A. Waseem and Ho Jin Ryu",authors:[{id:"178474",title:"Prof.",name:"Ho Jin",middleName:null,surname:"Ryu",slug:"ho-jin-ryu",fullName:"Ho Jin Ryu"},{id:"184864",title:"Mr.",name:"Owais Ahmed",middleName:null,surname:"Waseem",slug:"owais-ahmed-waseem",fullName:"Owais Ahmed Waseem"}]},{id:"50829",title:"Dedicated Monte Carlo Procedures Applied in Gamma-ray Spectrometry Used in Decommissioning of Nuclear Facilities",slug:"dedicated-monte-carlo-procedures-applied-in-gamma-ray-spectrometry-used-in-decommissioning-of-nuclea",totalDownloads:1884,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Because the experimental efficiency calibration is limited to several measurement geometries and cannot be applied directly to all measurement configurations, the efficiency transfer method for the efficiency computation was applied using ETNA software. An approach using efficiencies measured with point sources combined with theoretical procedures was applied for obtaining the peak efficiency ε(E) for disk sources measured with a NaI(Tl) detector. The transfer method was applied for the computation of the efficiency of an HPGe detector using as a reference a point source placed at 10 cm height from the face of the detector. The method was applied both for point sources and volume sources with varied compositions and densities. To correct the experimental values of the efficiencies, coincidence summing effects were evaluated using GESPECOR Monte Carlo code. The study of the response function characterization of the ISOCART and Segmented Gamma Scanner WS1100 gamma-ray spectrometry systems was related. GEANT 3.21 Monte Carlo code was used to simulate the spectra expected to be obtained for the photon energy range from 50 to 2000 keV. A big volume represented by a 220l cylindrical source was considered to be measured with the two systems. The full energy peak efficiency and the total efficiency were evaluated.",book:{id:"5154",slug:"nuclear-material-performance",title:"Nuclear Material Performance",fullTitle:"Nuclear Material Performance"},signatures:"Daniela Gurau",authors:[{id:"178770",title:"Dr.",name:"Daniela",middleName:null,surname:"Gurau",slug:"daniela-gurau",fullName:"Daniela Gurau"}]},{id:"51079",title:"Oxidation, Embrittlement, and Growth of TREAT Zircaloy-3 Cladding",slug:"oxidation-embrittlement-and-growth-of-treat-zircaloy-3-cladding",totalDownloads:1678,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"This chapter analyzes the effects of oxidation, embrittlement, and cladding growth on the Zircaloy-3 alloy used for 25 mil thick TREAT fuel assembly cladding. The fuel cladding is a protective shell which is used to prevent damage to the enclosed fuel. Therefore, its integrity is important to guarantee this protection. The above three factors which can affect the Zircaloy-3 cladding are considered in this chapter and investigated. Limits to operation are determined. The oxidation of Zircaloy-3 in air is of interest to air-cooled reactors and Zircaloy-2 and 4 for accidents in fuel storage pools. The temperature range of interest is from room temperature where the fuel is stored for long periods of time, through the temperature range encountered in normal operation (400 to 600°C) to the highest temperatures which are possible in extreme accident situations. This temperature range is considered in this chapter to be from room temperature to 1200°C.",book:{id:"5154",slug:"nuclear-material-performance",title:"Nuclear Material Performance",fullTitle:"Nuclear Material Performance"},signatures:"Charles W. Solbrig, Anthony LaPorta, Katelyn M. Wachs and James\nR. 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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. 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He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University, Kuwait. His research interests include optimization, computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, and intelligent systems. Prof. Sarfraz has been a keynote/invited speaker at various platforms around the globe. He has advised/supervised more than 110 students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He has authored and/or edited around seventy books. Prof. Sarfraz is a member of various professional societies. He is a chair and member of international advisory committees and organizing committees of numerous international conferences. He is also an editor and editor in chief for various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:"Beijing University of Technology",institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Lakhno Igor Victorovich was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPhD – 1999, Kharkiv National Medical Univesity.\nDSc – 2019, PL Shupik National Academy of Postgraduate Education \nLakhno Igor has been graduated from an international training courses on reproductive medicine and family planning held in Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor of the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s a professor of the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education . He’s an author of about 200 printed works and there are 17 of them in Scopus or Web of Science databases. Lakhno Igor is a rewiever of Journal of Obstetrics and Gynaecology (Taylor and Francis), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for DSc degree \\'Pre-eclampsia: prediction, prevention and treatment”. Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: obstetrics, women’s health, fetal medicine, cardiovascular medicine.",institutionString:"V.N. Karazin Kharkiv National University",institution:{name:"Kharkiv Medical Academy of Postgraduate Education",country:{name:"Ukraine"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"243698",title:"M.D.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:"Shanxi Eye Hospital",institution:{name:"Shanxi Eye Hospital",country:{name:"China"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRZkkQAG/Profile_Picture_2022-05-09T12:55:18.jpg",biography:null,institutionString:null,institution:null},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. 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Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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