In study one, the executive functioning of 19 high-functioning (HFA) and 19 low-functioning (LFA) children with ASD were compared to 28 children with normal development using a battery of neuropsychological tests. Results not only confirmed previous knowledge that children with ASD had significant executive dysfunctions compared with children with normal development, but also extended it to show that LFA children were significantly more impaired than HFA children. Study two built on this knowledge and examined whether immunological abnormalities are associated with the differential executive dysfunctions in 18 HFA and 19 LFA children. Results indicated that LFA children showed greater executive dysfunctions as well as higher levels of total lymphocyte, T lymphocyte and suppressor/cytotoxic T lymphocyte levels than HFA children. In addition, executive dysfunctions were significantly associated with the three lymphocyte levels, lending support to the notion that immunological factors may play a role in the cognitive dysfunctions in individuals with ASD. Study three further examined whether the differential executive dysfunctions and immunologic levels in LFA and HFA children are associated with their neural connectivity. Results on 17 HFA and 14 LFA children showed that LFA children had significantly elevated theta coherence in the anterior network, as well as at the left intra-hemispheric and right-to-left inter-hemisphere connections than HFA children. LFA children also had significantly elevated immunologic level specifically in suppressor/cytotoxic T lymphocytes. Furthermore, the executive dysfunctions, disordered neural connectivity, and abnormal immunologic levels were found to be associated. / Recent evidence suggests that deficient executive functions are fundamental to the cognitive deficits in Autism spectrum disorders (ASD). It has been suggested that individuals with ASD have disrupted neural connectivity including that in the frontal lobes that mediate executive functions. With reports of immunologic abnormalities in children with ASD, it is plausible that such abnormalities disrupt the neural connectivity in the brains of individuals with ASD. There is, however, relatively little empirical evidence to support the notion. This dissertation reports on three studies to examine whether the executive dysfunction in children with ASD is associated with their immunologic abnormalities and disordered neural connectivity. / These findings have provided some initial evidence to support the notion that immunologic factors may play a role in causing neuronal damage in the anterior region of the brains of children with ASD, which is manifested in their disordered neural connectivity of that region, and their executive dysfunctions mediated by that same region. / Han, Yvonne Ming Yee. / Adviser: Agnes Chan. / Source: Dissertation Abstracts International, Volume: 73-01, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 103-132). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Introdução: O transtorno do espectro autista (TEA) atualmente é definido como um distúrbio do desenvolvimento neurológico caracterizado por déficits na comunicação e interação social e padrões restritos e repetitivos de comportamento, interesses e atividades. Estima-se que aproximadamente 1% da população mundial seja diagnosticada com esta desordem. O TEA manifesta-se por uma variedade de sintomas nas áreas cognitiva, emocional e neurocomportamental. Além dos sintomas característicos como estereotipias, ecolalia, déficits de comunicação, algumas manifestações envolvendo a alimentação podem ser observadas nesses pacientes. As desordens alimentares podem envolver aversão a determinados alimentos, insistência em comer um número limitado de alimentos e recusa de provar alimentos novos. O estado nutricional desses pacientes pode ser alterado pelo inadequado consumo alimentar e fatores relacionados ao comportamento alimentar. Objetivos: avaliar o estado nutricional [antropometria e bioimpedância elétrica (BIA)], o consumo e o comportamento alimentar em crianças e adolescentes com TEA, bem como os sentimentos e estratégias dos pais/cuidadores desses pacientes frente a esse comportamento. Métodos: Para a avaliação antropométrica foram realizadas medidas de peso (kg), altura (cm) e circunferência da cintura (CC). A composição corporal (massa magra e massa gorda) e o ângulo de fase foram verificados através da BIA. Foi calculado o Índice de Massa Corporal (IMC) e classificado o estado nutricional de cada participante. A avaliação do consumo alimentar foi realizada através do preenchimento do registro alimentar de 3 dias, posteriormente os nutrientes foram calculados no software NutriBase® e comparado com os valores das Dietary Reference Intake (DRIs) de acordo com o sexo e idade. O questionário Behavior Pediatrics Feeding Assessment Scale (BPFA) foi utilizado para avaliar o comportamento alimentar dos participantes e as estratégias e sentimentos dos pais/cuidadores referentes ao momento da alimentação das crianças e adolescentes. Resultados: De acordo com o percentual de gordura corporal obtido pela BIA e a CC um amplo percentual desta amostra apresentou adiposidade central e total elevada (49,2%). Segundo o IMC 38,9% apresentaram sobrepeso, 36,5% obesidade e 15,8% baixo peso. O grupo TEA ingeriu em média mais calorias do que o grupo controle apresentou repertório limitado de alimentos consumidos, e alta prevalência de inadequação no consumo de cálcio, sódio, ferro, vitamina B5, ácido fólico, e vitamina C. Os escores do BPFA foram maiores no grupo TEA comparados com controles para todos os domínios. Independente da frequência da manifestação de problemas alimentares estes impactam fortemente os pais/cuidadores. Conclusões: Esta dissertação fornece evidencias sobre seletividade alimentar que não parecem estar associadas com a redução da ingestão de calorias, mas sim com a qualidade da alimentação, sendo assim um potencial fator de risco para doenças nutricionais. Esses resultados contribuem para a importância da avaliação nutricional (antropométrica, da composição corporal e de problemas alimentares) dentro da rotina clínica de pacientes com TEA e seus familiares, sempre considerando as características singulares de cada paciente. / Introduction: The autism spectrum disorder (ASD) is currently defined as a neurodevelopmental disorder characterized by communication and social interaction deficits and restricted and repetitive patterns of behavior, interests and activities. Approximately 1% of the population have ASD diagnoses. ASD is manifested by a wide variety of cognitive, emotional, and neurobehavioral symptoms. In addition to the characteristic symptoms such as stereotypies, echolalia, communication deficits, some events involving nutrition aspects may be observed in these patients. Feeding problems may involve aversion to certain foods, insistence on eating only a small selection of foods and refusal to try new foods. Consequently, nutritional status can be changed by inadequate food consumption and factors related to feeding behavior. Objectives: evaluate the nutritional status [anthropometry and bioelectrical impedance (BIA)], consumption and feeding problems in children and adolescents with ASD. Methods: Anthropometric measurements - weight (kg), height (cm), waist circumference (WC) - were performed and the test of body composition (fat mass, fat free mass) and phase angle was held by BIA. The body mass index (BMI) was calculated and nutritional status of each participant was classified. The food intake evaluation was carried out by a 3-day food record, and nutrients subsequently calculated on the NutriBase® software and compared with the reference values according to sex and age in the Dietary Reference Intake (DRIs). The Behavior Pediatrics Feeding Assessment Scale (BPFA) questionnaire was used to evaluate the feeding problems of the participants and the strategies and feelings of parents / caregivers regarding the mealtime. Results: According to the body fat percentage obtained by BIA and WC, a large percentage of this sample showed a high central and total adiposity (49.2%). According to BMI 38.9% were overweight, 36.5% obesity and 15.8% underweight. The ASD group consumed on average more calories than the control group, showed limited repertoire of foods consumed, and high prevalence of inadequate calcium, sodium, iron, vitamin B5, folic acid, and vitamin C consumption. BPFA scores were higher in the ASD group when compared to controls for all domains. Independently of how often children and adolescents denote feeding problems, when they occur, it impacts strongly on their parents. Conclusions: These studies provides evidence on food selectivity that seem to be associated with the food quality, rather than the reduced calorie intake, thus being a potential risk factor for nutritional diseases. These results contribute to the importance of the nutritional assessment (anthropometric, body composition and eating problems) within the clinical setting in patients with ASD and parents/caregivers, always considering the unique characteristics of each patient.

Ainda pouco se sabe sobre as causas do transtorno do espectro autista (TEA) e seus efeitos na funcionalidade cerebral, porém, diversas pesquisas apontam que a condição esteja relacionada à uma conectividade diferenciada entre regiões do cérebro. A conectividade córtico-cerebelar tem sido tema de pesquisas nas últimas décadas em decorrência de novos achados que indicam que esta conectividade está relacionada ao aprendizado e refinamento de diversas funcionalidades do córtex. Acredita-se que uma falha na conectividade córtico-cerebelar poderia estar relacionada à falhas em funções sensorimotoras, cognitivas e emocionais. A investigação de regiões cuja conectividade córtico-cerebelar está alterada no TEA contribui para uma melhor compreensão deste transtorno. Assim, o objetivo deste trabalho é identificar regiões do cérebro cuja conectividade funcional com o cerebelo seja diferente entre indivíduos com desenvolvimento típico (DT) e diagnosticados com TEA. Para isto, utilizamos imagens de ressonância magnética funcional (fMRI) de 708 indivíduos em estado de repouso (432 DT e 276 TEA) com idades entre 6 e 58 anos coletados pelo consórcio ABIDE. Os dados foram pré-processados e divididos conforme regiões anatômicas do cérebro que foram adotadas como regiões de interesse (ROIs). Para determinar a conectividade funcional de cada região do córtex com o cerebelo, aplicamos o método de análise de componentes principais (PCA) nas ROIs do cerebelo e utilizamos um modelo regressão linear para cada ROI do córtex, sendo a série temporal da ROI do córtex a variável resposta e as componentes principais (PCs) do cerebelo as variáveis preditoras. Em seguida, identificamos as regiões com conectividade funcional diferente entre indivíduos com DT e diagnosticados com TEA através de um modelo linear que inclui como covariáveis, idade, gênero e local de coleta do dado. Identificamos cinco regiões do córtex que apresentam reduzida conectividade funcional com o cerebelo nos indivíduos com TEA, sendo elas: (i) giro fusiforme direito, (ii) giro pós-central direito, (iii) giro temporal superior direito e (iv) giro temporal médio direito e (v) esquerdo. Todas as cinco regiões são parte do sistema sensorimotor, e estão relacionadas à funções ligadas à sintomas característicos do quadro de TEA, como: sensibilidade à estímulos sensoriais, dislexia, prosopagnosia (dificuldade para reconhecer faces), dificuldade de compreensão de linguagem e dificuldade de reconhecimento de emoções em faces. Nossos resultados mostram que existem regiões do sistema sensorimotor que apresentam conectividade funcional com o cerebelo atipicamente reduzida em TEA, como corroborado por estudos de imageamento com tarefa específica e como hipotetizado por estudos de conectividade estrutural. Nós acreditamos que a conectividade córtico-cerebelar reduzida dessas regiões esteja prejudicando o processamento e aprendizado de funções sensorimotoras, levando ao surgimento de sintomas típicos do TEA. / Little is known about the causes of autism spectrum disorder (ASD) and its effects on brain functions. Several researches point that it may be related to differentiated connections between brain regions. The cortico-cerebellar connectivity has been theme of researches over the last decade given the new discoveries suggesting that this connection is associated with learning and tuning of diverse brain functionalities. It is believed that cortico-cerebellar connectivity impairment may be related to impairments on sensorimotor, cognitive, and emotional functions. For a better understanding of the condition, we aim at identifying brain regions that present a impaired cortico-cerebellar connectivity between TD and ASD. Thus, our goal is to identify brain regions where the functional connectivity with the cerebellum is different between subjects with typical development (TD) and ASD. We used functional magnetic resonance images (fMRI) of 708 subjects under resting state protocol (432 TD and 276 ASD) with ages between 6 and 58 years old collected by the ABIDE Consortium. Data was pre-processed, splited in anatomical brain regions, which were adopted as regions of interest (ROIs). To establish the functional connectivity of each cortical ROI to the cerebellum, first we applied the principal component analysis (PCA) on cerebellar ROIs. Next, we used a linear regression model to each cortical ROI time series as response variable and the cerebellum principal components (PCs) as the predictive variables. After that, we identified regions of different connections between TD and ASD subjects applying a linear model including age, gender, and data collection site as covariables. We identified five cortical regions with reduced functional connectivity with cerebellum on the ASD subjects, namely: (i) right fusiform gyrus, (ii) right postcentral gyrus, (iii) right superior temporal gyrus, (iv) right middle temporal gyrus, and (v) left middle temporal gyrus. All five regions are part of the sensorimotor system, and contribute to functions typically associated with ASD, such as: sensitivity to external stimulus, dyslexia, prosopagnosia (difficulty to recognize faces), language comprehension impairments, and recognition of emotional expressions impairment. Our results show that there are brain regions with atypical cortico-cerebellar connectivity impairment on ASD, in accordance with results from previous studies of tactography and task driven fMRI. We believe that the decreased cortico-cerebellar connectivity of these regions are affecting the learning process of sensorimotor functionalities, leading to typical ASD symptoms.

Submitted by Filipe dos Santos (fsantos@pucsp.br) on 2018-03-20T12:47:08Z No. of bitstreams: 1 Luciana Maria Galvão Wolff.pdf: 905504 bytes, checksum: 075c5fa7927dda297ac0a30f867142ab (MD5) / Made available in DSpace on 2018-03-20T12:47:08Z (GMT). No. of bitstreams: 1 Luciana Maria Galvão Wolff.pdf: 905504 bytes, checksum: 075c5fa7927dda297ac0a30f867142ab (MD5) Previous issue date: 2018-02-26 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Introduction: There is a considerable increase in the number of children diagnosed with Autism Spectrum Disorder (ASD) and being this population with a great chance of presenting complex communication needs, the speech language pathology intervention with Augmentative and Alternative Communication (AAC) is essential. The scientific knowledge production on these areas, specifically on the construction of language assessment instruments considering communication possibilities with AAC on this population is still incipient. Thus, it is justified by the development of an assessment tool proposed here. Aim: This research was developed through two integrated studies: Study 1 - development and content validation on language assessment instrument (CSA_Linguagem) in small children with complex communication needs using AAC. Study 2 - Application of this instrument in children diagnosed with ASD. Method: Study 1: the instrument was prepared from a bibliographic review, along with the clinical experience of the researcher. The instrument was then evaluated by expert judges in the area and a new final version was constructed with the collaborations computed. Study 2, the instrument was applied on children with ASD, on interaction situations, using AAC graphic symbols. Results: Study 1: The Instrument was improved with the judges contribution. Study 2: it was possible to observe the communication form chosen by the child, and the possibility of some communication effect, in the use of the AAC. The instrument proved to be operational, easy to apply and low cost / Introdução: Existe um aumento considerável do número de crianças diagnosticadas com Transtorno do Espectro do Autismo (TEA) e tendo essa população grandes chances de apresentar necessidades complexas de comunicação, a intervenção fonoaudiológica com a Comunicação Suplementar e Alternativa (CSA) deve ser considerada. A produção de conhecimento científico nessas áreas especificamente na elaboração de instrumentos de avaliação de linguagem considerando as possibilidades de comunicação por meio da CSA com essa população é ainda incipiente. Dessa forma, justifica-se a elaboração do instrumento de avaliação aqui proposto. Objetivo: Essa pesquisa foi desenvolvida por meio de dois estudos integrados: Estudo 1 - Elaboração e validação de conteúdo do instrumento de avaliação de linguagem (CSA_Linguagem) em crianças pequenas com necessidades complexas de comunicação utilizando a CSA. Estudo 2 - Aplicação desse instrumento em crianças diagnosticadas com TEA. Método: Estudo 1 - o instrumento foi elaborado a partir de revisão bibliográfica, em conjunto com a experiência clínica do pesquisador. Em seguida o instrumento foi avaliado por juízes especialistas na área e uma nova versão foi construída, incorporando as colaborações dos juízes. Estudo 2 - o instrumento foi aplicado em crianças com TEA, em situações de interação com a utilização de símbolos gráficos da CSA. Resultados: Estudo 1: o instrumento foi aprimorado com a contribuição dos juízes. Estudo 2: foi possível observar a forma de comunicação eleita pela criança, e a possibilidade de efeitos na comunicação com o uso da CSA. O instrumento se mostrou operacional, de fácil aplicação e baixo custo

Submitted by Filipe dos Santos (fsantos@pucsp.br) on 2018-03-21T12:11:53Z No. of bitstreams: 1 Roseli Cristina Campos do Carmo.pdf: 745259 bytes, checksum: 890afe24a1ed24e904198529872b46b5 (MD5) / Made available in DSpace on 2018-03-21T12:11:53Z (GMT). No. of bitstreams: 1 Roseli Cristina Campos do Carmo.pdf: 745259 bytes, checksum: 890afe24a1ed24e904198529872b46b5 (MD5) Previous issue date: 2018-02-22 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Introduction Patients with ASD show a lot of changes in their communicative performance that may end up banning and / or tarnishing the development of social and linguistic features of the subject. For this reason communication has become the key focus on speech therapy interventions in these cases. Recent researches, contrary to what traditionally is postulated, have pointed out that the working with communication in teen and adult patients also have effective results. This project aimed to discuss, through a clinical case study, the effects of speech therapy in the communication of a patient with ASD, through the use of a therapeutic device, Kitchen Workshop. The choice of this device was determined not only by the adoption, in this discussion, of certain theoretical perspectives on language and subjectivity, and hence the communication itself, but also by the recognition of its effectiveness in speech therapy, as shown in some studies. Objective: describe and analyze the effects of using KW therapeutic device as a communication treatment for a teenager with ASD. Method It is a clinical case study of a 19-year-old male adolescent presenting diagnosis of autism spectrum disorder. The patient participated in ten Kitchen Workshop therapeutic group sessions. Conclusion: This study may clarify that working with adolescents is effective, unlike that postulated by the maturational views. If the clinical structure can ensure the patient to establish a broad discursive and subjective movement, just as the therapeutic device KW allows, which will consequently create opportunities for proper circulation in communicative scenes / Introdução: Os pacientes com TEA apresentam muitas alterações em seu desempenho comunicativo, que acabam interditando e/ou maculando o desenvolvimento das funções sociais e linguísticas do sujeito. Por essa razão a comunicação passou a ser o foco fundamental nas intervenções fonoaudiológicas nestes casos. Pesquisas recentes, na contramão do que tradicionalmente se postula, têm apontado que os trabalhos com a comunicação de pacientes adolescente e adultos também apresentam resultados eficazes. O presente projeto visou discutir, através de um estudo de caso clinico, os efeitos de uma intervenção fonoaudiológica na comunicação de um paciente com TEA, através do uso de um dispositivo terapêutico, a Oficina de Cozinha. A escolha deste dispositivo determinou-se não somente pela adoção, nesta discussão, de certas perspectivas teóricas sobre linguagem e subjetividade e, consequentemente, da própria comunicação, mas, também, pelo reconhecimento de sua eficácia no trabalho fonoaudiológico, já apresentada em alguns estudos. Objetivo: Descrever e analisar os efeitos do uso do dispositivo terapêutico OC no trabalho com a comunicação de um adolescente com TEA. Método: trata-se de um estudo clinico de caso de um adolescente de 19 anos de idade do gênero masculino que apresenta diagnostico incluído no transtorno do espectro autismo. O paciente participou de dez sessões de um processo terapêutico grupal em Oficina de Cozinha. Conclusão: Este estudo pode esclarecer que o trabalho com adolescentes é eficaz, diferentemente do que postulam as visões maturacionais, se a estrutura clínica for tal que assegure ao paciente o estabelecimento de uma ampla circulação discursiva e subjetiva, exatamente como o dispositivo terapêutico OC possibilita, o que vai gerar consequentemente, oportunidade de uma adequada circulação nas cenas comunicativas

The thesis Inclusion of Pupils with Autistic Spectrum Disorder at Primary School focuses on the inclusion of pupils with autism spectrum disorders and on how to work with them at primary school. The first chapter of the theoretical part describes the inclusion and its legislative framework. This chapter shows an overview of the support and counselling system in school education. The following chapters are devoted to the description of autism, its types and diagnostics of pupils with autistic spectrum disorders. The final theoretical part pays attention to devoted to educational methods and strategies for pupils with autistic spectrum disorders. It describes how to communicate with such pupils and what didactic systems can be used when working with them. The empirical part of the thesis describes the development of application for pupils with autistic spectrum disorder and its verification for the android mobile platform. The author of this thesis has developed the application mentioned above. This chapter describes both the design and the technical development of the application. The application is validated by using the research method of a controlled interview with parents and pupils where the application was tested for two months and these interviews are subsequently evaluated. The end of the...

Les troubles du spectre autistique (TSA) affectent un individu sur 100 et sont caractérisés par des déficits de la communication et des interactions sociales, et par des comportements restreints et répétitifs. Les TSA présentent une forte composante génétique ; les premiers gènes impliqués ont été identifiés au laboratoire et codent des protéines d’adhérence ou d’échafaudage localisées à la synapse : les neuroligines (NLGN) et SHANK. Nous nous sommes intéressés à l’implication dans les TSA des contactines (CNTN), un groupe de six molécules d’adhérence neurales de la superfamille des immunoglobulines. Ces protéines sont ancrées à la membrane plasmique par un groupement glycosyl phosphatidylinositol (GPI) et peuvent être sécrétées par clivage du GPI. Elles interviennent dans des processus variés du développement neuronal comme la croissance neuritique, le guidage et la fasciculation des axones ou la myélinisation. Des études génétiques ont suggéré l’implication des contactines 4 à 6 dans les TSA, mais aucune étude fonctionnelle n’a confirmé cette hypothèse. Ce travail de thèse associe une analyse génétique, une analyse fonctionnelle sur des cultures de neurones primaires de rat et une analyse structurale par modélisation moléculaire. Nous avons identifié plusieurs "Copy-Number Variants" (CNV) dans les gènes CNTN (essentiellement des délétions affectant CNTN5 et CNTN6) et observé une tendance à l’enrichissement chez les patients par rapport aux individus témoins. Le séquençage des exons codants de CNTN5 et CNTN6 chez plus de 200 patients et 200 témoins nous a ensuite permis d’identifier des variants ponctuels non synonymes. Les variants privés (présents chez un seul individu ou dans une seule famille) sont plus fréquents chez les patients que chez les témoins. Les CNV et les variants ponctuels sont hérités, de parents pour la plupart non atteints, ce qui suggère que les altérations des contactines constituent des facteurs de vulnérabilité aux TSA plutôt que des facteurs causaux. Afin de déterminer l’effet fonctionnel des variants ponctuels rares, nous avons comparé l’effet sur la neuritogenèse des CNTN mutées à celui des CNTN sauvages. Nous avons ainsi analysé, sur plusieurs centaines de neurones par condition, la longueur et la ramification des neurites dans un système de co-culture avec des cellules HEK surexprimant la CNTN. La plupart des protéines CNTN5 et CNTN6 mutées présentent des effets différents de ceux des protéines sauvages (inhibition ou augmentation des effets positifs de celles-ci). Le dernier objectif de cette étude consistait à évaluer l’influence de certains de ces variants sur l’interaction des CNTN, via les domaines immunoglobuline (Ig) 2 et 3, avec l’un de leurs ligands, le récepteur à activité tyrosine phosphatase PTPRG. Par homologie avec la structure cristallographique déjà résolue pour les quatre premiers domaines Ig de CNTN4 de souris, nous avons modélisé cette région pour les CNTN5 et 6 humaines, sauvages et mutées. Nous avons ainsi pu prédire que certains variants étaient susceptibles de modifier les liaisons ioniques ou l’encombrement stérique dans cette région d’interaction. L’ensemble de nos résultats démontre l’existence d’effets fonctionnels délétères de plusieurs variants rares des contactines retrouvés chez les patients atteints de TSA. La présence de ces variants rares chez des apparentés non atteints indique que les altérations des CNTN s’inscrivent dans un modèle de "multiple hit", qui propose que l’autisme puisse résulter de la combinaison de plusieurs atteintes génétiques, chacune représentant un facteur de risque à effet modéré et n’entraînant pas, à elle seule, le développement du trouble. Le séquençage d’exomes et de génomes entiers, en cours au laboratoire, permettra une meilleure compréhension de ces atteintes génétiques multiples. / Autism Spectrum Disorders (ASDs) affect one individual out of 100 and are characterised by deficits in communication and social interactions, and by restricted and repetitive behaviours. ASDs display a strong genetic component ; the first genes involved were identified in our laboratory and encode for cell-adhesion or scaffolding proteins localised at the synapse : neuroligins (NLGNs) and SHANKs. We were interested in the implication, in the ASDs, of contactins (CNTNs), a group of six neural cell-adhesion molecules of the immunoglobulin superfamily. These proteins are anchored to the plasma membrane by a glycosyl phosphatidylinositol (GPI) and can be secreted by cleavage of this anchor. They participate in various processes of neuronal development such as neurite outgrowth, axon guidance and fasciculation, and myelination. Genetic studies have suggested the involvement of contactins 4, 5 and 6 in the ASDs, but no functional study has confirmed this hypothesis. The present work combines a genetic analysis, a functional analysis on cultured primary rat cortical neurons and a structural analysis by molecular modelling. We identified several "Copy-Number Variants" (CNVs) in CNTN genes (mainly deletions affecting CNTN5 and CNTN6) and observed a trend of enrichment in patients compared to control individuals. Subsequent sequencing of CNTN5 and CNTN6 coding exons in more than 200 patients and 200 controls allowed us to identify non synonymous single-nucleotide variants (SNVs). Private variants (present only in one individual or one family) are enriched in patients compared to controls. CNVs and SNVs are inherited, mainly from unaffected parents, which suggests that impairments in contactins represent susceptibility factors for ASDs, rather than causal factors. In order to determine the functional effects of rare SNVs, we compared the effect on neuritogenesis of mutant CNTNs to that of WT CNTNs. We therefore analysed, on several hundreds of neurons per condition, the length and branching of neurites in a co-culture system with HEK cells overexpressing a CNTN protein. Most of CNTN5 and CNTN6 mutant proteins either inhibited or increased the positive effects of WT proteins. The last aim of the present study consisted in evaluating the influence of some of these variants on the interaction of CNTNs, via their immunoglobulin (Ig) domains 2 and 3, with one of their ligands, the protein tyrosine phosphatase receptor PTPRG. Using homology with the crystal structure that had already been solved for the first four Ig domains Ig of mouse CNTN4, we modelled this region for human CNTN5 and CNTN6, WT and mutated. We have thus been able to predict that some variants were likely to alter ionic bonds or steric constraints in this interaction module. Taken as a whole, our results demonstrate that several rare CNTN variants found in patients with ASD have deleterious functional effects. The presence of these rare variants in unaffected relatives indicates that CNTN impairments fit into a "multiple hit" model, according to which autism may result from the combination of several genetic defects, each being a risk factor with moderate effect but not triggering, in itself, the development of the disorder. Sequencing of exomes and whole genomes, ongoing in the laboratory, will allow better understanding of those multiple genetic impairments.

Autism spectrum disorder (ASD) is recognized the world over as a major public health issue. Autism is highly prevalent, persists across the lifespan, and is characterized by behaviors that can profoundly impair typical functioning. Interventions based on behavioral strategies have proven effective, but there are significant barriers to care, including cost, intensity of treatment, and access to qualified practitioners. The impact of ASD and obstacles to appropriate care are magnified by systemic limitations in developing countries. Parent training holds promise as a method of disseminating therapy to underserved areas. This study investigated the effectiveness of a pyramidal parent training intervention in Macedonia. Fifteen parents of children with ASD were trained in three specific strategies for promoting prosocial skills: eye contact, compliance, reducing restricted repetitive behaviors (RRB). Parents reported daily ratings of these skills and their own confidence, action or engagement, and family distress. Participants were ethnic Macedonians from the capital of Skopje with at least one child with ASD between the ages of 2 and 13 years. This study utilized a single case research design. Data were collected per and post intervention using an interrupted time series design. Individual response was analyzed visually and Tau U effect sizes were calculated. Moderator and mediator effect was considered following the method initially established by Gaynor and Harris (2008). Effect sizes were small but significant for the group overall for all variables except restricted repetitive behaviors (RRB). The program was especially effective for younger children, those with comorbid hyperactivity, those with low to moderate symptomology, and those with no prior special education services.

The following study looks to examine the effect of an iPad application on the English Language Arts (ELA) skills of listening comprehension for students with significant disabilities. The procedure was evaluated using a multiple probe across participants single case design. Outcomes were measured for improved ELA skills after intervention and were also measured for student engagement. Building upon the research of recent studies that have sought to develop and adapt grade-level literature for students with moderate and severe disabilities, this study seeks to find the effectiveness of an adapted text version of To Kill a Mockingbird, by Harper Lee for high school students diagnosed with intellectual disability and/or autism. The implementation of this adapted text included evidenced-based supports such as time delay, the system of least prompts and picture supports taught in conjunction with the use of the iPad application. The need for future research and implications for practice will be discussed.

Methods for Teaching Students with Autism Spectrum Disorders is the most comprehensive text available, aimed at helping pre-service and in-service teachers and related service professionals understand the importance of evidence-based practices in the education of learners with Autism Spectrum Disorders (ASD) from a family and longitudinal learning perspective. With its emphasis on the theme of family and professional partnerships and collaboration and consultation, the book includes learning aids such as suggested print and web-based resources, graphic organizers, and points for reflection; child and family vignettes, “Consider This” features, and examples of exemplary programs and practices; and the most up-to-date information and latest trends in the field. / https://dc.etsu.edu/etsu_books/1122/thumbnail.jpg