Activation of the maternal immune system and resultant maternal cytokine expression due to prenatal infection has been implicated as a significant contributor to the pathology of neuropsychiatric and neurodevelopmental disorders such as schizophrenia and Autism Spectrum Disorder (ASD). Increased maternal interleukin-6 (IL-6) expression, observed clinically and in animal models of prenatal infection, and resultant activation of key signaling pathways, has been shown to be a biological indicator of pathology, and a central component of the pathological mechanism. In animal models of prenatal infection and clinically in pregnancy disorders hallmarked by immunological irregularities and increased IL-6 expression, inhibition of IL-6 has been shown to reduce pathological symptoms both maternally and in the exposed offspring. This study aims to demonstrate the ability of IL-6 expression, resulting from prenatal infection, to induce neuropathological and behavioral outcomes that mirror clinical observations seen in disorders such as ASD. More importantly, it shows how flavones luteolin and diosmin, a subclass of the flavonoid family, through inhibition of IL-6 mediated activation of Signal Transducer and Activator of Transcription-3 (Stat3) can reduce these pathologies both in vitro and in vivo. Evidence suggests that flavonoids, a polyphenolic class of naturally occurring plant secondary metabolites, are potent anti-inflammatory agents that can attenuate the expression of cytokines such as IL-6, possibly through the modulation of tyrosine kinase activity. They have been shown to have significant therapeutic potential in disorders hallmarked by increased inflammation or disruptions in immune regulation, such as neurodegenerative disorders and certain cancers. Members such as diosmin have also been shown to be safe during pregnancy, and are currently utilized in the treatment of certain vascular disorders associated with pregnancy. In vitro work undertaken in this study showed that co-administration of luteolin with IL-6 in neural stem cells (NSC) was able to attenuate pathological outcomes induced by IL-6 including aberrant proliferation, over expression of astroglial marker, glial fibrillary acidic protein (GFAP) and changes in cellular morphology. In vivo studies involving luteolin and diosmin further confirmed the therapeutic efficacy of these compounds as similar attenuation of IL-6 mediated maternal and fetal pro-inflammatory cytokine expression and abnormal behaviors in prenatally exposed offspring was observed. Mechanistically, these effects were mediated through inhibition of Stat3 activation although other pathways activated by IL-6 were modulated by flavone co-treatment. Flavonoid treatment during periods of prenatal infection may prove to be a therapeutic intervention for the resultant pathological outcomes seen in offspring through attenuation of the maternal and fetal immune response to infection as well as modulation of signaling pathways in the fetal brain. These compounds may prove therapeutically efficacious for the application in perinatal conditions hallmarked by increased inflammation during pregnancy.

Thesis (MNutr)--Stellenbosch University, 2012. / ENGLISH ABSTRACT: Objectives: Children with autism spectrum disorder (ASD) are known to have feeding difficulties. This study gathered information from parents/caregivers with children diagnosed with ASD. The following aspects were investigated: early feeding history, food preferences, sensory issues, current dietary practices and the use of nutritional supplements and special diets. The study also gathered information regarding these families’ experience with dietitians in supporting them with advice related to dietary problems. Methodology: An online questionnaire was used and the link to the study was placed on the National Autistic Society (NAS) of the United Kingdom’s website to recruit participants. Parents/ caregivers of children aged between 3-16 years and diagnosed with ASD, who resided in England, could take part in the study. Results: Three hundred and twenty five parents/ caregivers participated in the study. The mean age of children was 9.5 years. The majority of children were male (85%). The most common feeding problem was the transition from stage 1 weaning foods to more textured food (55.6%). Sensory problems played a large role in food acceptance. Clear preferences were made for crunchy (81.5%) or dry foods (79%), followed by food with a smooth consistency (69.8%) such as yogurt. Food appearance and presentation (64%) was the main determinant of food acceptance and specific brands and packaging played a major role. Habitual food intake and continually choosing the same foods for meals were present in the majority of children (75.6%). Specific preference was given to the following foods: starchy vegetables (62.6%), refined carbohydrates (81%), processed meat products (69.2%) and dairy products (68.6%). The use of ‘special’ and exclusion diets were not popular. However, where specifically gluten and/ or casein were excluded (19%, n=55), it was generally excluded for more than one year. Reported observations with these exclusions were: improvement in bowel habits, sleep, concentration, behaviour and social communication. The use of nutritional supplements were significantly higher (p<0.5) where exclusion diets were used. A large number of children (43.4%, n=23) on exclusion diets, have not been consulted by a dietitian. Most parents /caregivers (58.1%) had the perception that dietitians were lacking knowledge of ASD and had inadequate knowledge of current dietary interventions for children with ASD (61.7%). However, parents felt that it was reassuring to consult a dietitian, that practical advice was given to improve dietary intake and that generally it reduced their concern regarding their child’s dietary intake. Conclusion: The study highlights the complexity of ASD and the variable effect it has on eating, behaviour and dietary intake. The use of the gluten and casein free (GFCF) diet may improve general wellbeing in some children with ASD when used appropriately and warrants further investigation. It is concerning that only a minority of children on exclusion diets are consulted by dietitians to ensure nutritional adequacy. Due to the complexity of ASD and in the absence of clear guidance for dietary interventions, dietitians who work with children with ASD need to be supported by continued training opportunities in order to enhance their competencies and optimise their service delivery. / AFRIKAANSE OPSOMMING: Doelwitte: Kinders wat aan Outismespektrum-steuring (OSS) lei is geneig om voedingsprobleme te hê. Die studie het inligting ingesamel van ouers en versorgers met kinders wat met OSS gediagnoseer is. Die volgende aspekte is ondersoek: vroeë voedingsgeskiedenis, voedsel voorkeure, sensoriese probleme, huidige eetgewoontes en die gebruik van nutriëntaanvullings en spesiale diëte. Die studie het ook inligting ingesamel aangaande gesinne se ondervinding met dieetkundiges en ondersteuning met dieetprobleme. Metodologie: ‘n Elektroniese vraellys is gebruik en die skakel na die studie was op die webwerf van die National Autistic Society (NAS) van die Verenigde Koninkryk geplaas om deelnemers te werf. Ouers/ versorgers van kinders tussen die ouderdomme van 3-16 jaar, met ‘n diagnose van OSS en woonagtig in Engeland, kon deelneem aan die studie. Resultate: Drie honderd vyf en twintig ouers/ versorgers het deelgeneem aan die studie. Die gemiddelde ouderdom van die kinders was 9.5 jaar en 85% was manlik. Die mees algemene voedingsprobleem vir kinders met OSS was die oorgangsfase van gladde speningsvoedsel na growwer voedsel (55.6%). Sensoriese probleme het ‘n groot rol gespeel in voedselaanvaarding. Daar was duidelike voorkeure vir bros (81.5%) en droë voedsel (79%), gevolg deur voedsel met ‘n gladde tekstuur soos jogurt (69.8%). Die voorkoms en aanbieding van voedsel het grootliks bepaal of voedsel aanvaarbaar (64%) is. Spesifieke handelsmerke of verpakkings het ‘n groot rol gespeel (64.7%). Die meeste van die kinders (75.6%) het vaste eetgewoontes gehad en dieselfde kos tydens maaltye gekies. Die volgende voedselsoorte was verkies: styselryke groente (62.6%), verfynde koolhidrate (81%), geprosesseerde vleis produkte (69.2%) en suiwel produkte (68.6%). Die gebruik van spesiale en uitsluitingsdiëte was ongewild. Waar gluten- en kaseïen-uitsluitingsdiëte (19%, n=55) gebruik is, is dit meestal vir langer as een jaar gebruik. Met die gebruik van uitsluitingsdiëte is verbeteringe waargeneem in stoelgang gewoontes, slaap, konsentrasie, gedrag en sosiale kommunikasie. Die gebruik van nutriëntsupplemente was beduidend hoër (p<0.5) in die groep waar uitsluitingsdiëte gebruik is. ‘n Hoë persentasie kinders (43.4%, n=23) wat op uitsluitingsdiëte was, is nie deur dieetkundiges gekonsulteer nie. Die meeste ouers /versorgers (58.1%) het gevoel dat dieetkundiges gebrekkige kennis oor OSS en dieetverwante probleme het, asook onvoldoende kennis van huidige dieet intervensies vir kinders met OSS (61.7%). Ouers het wel gevoel dat dit gerusstellend was om dieetkundiges te gaan spreek vir praktiese raad om dieet inname te verbeter. Dit het ook hul kommer veminder aangaande kinders se diëte. Gevolgtrekking: Die studie benadruk die kompleksiteit van OSS en die wisselende effek wat dit op eetgewoontes, gedrag en voedsel inname het. Die gebruik van die gluten- en kaseïenvrye diëte kan moontlik die gesondheid en welsyn van sommige kinders met outisme verbeter mits dit reg gebruik word, maar vereis verdere navorsing. Dit was kommerwekkend dat ‘n minderheid van die kinders op uitsluitingsdiëte deur dieetkundiges gekonsulteer word om voldoende nutriëntinname te verseker. Aangesien OSS ‘n komplekse toestand is en daar ‘n gebrek is aan duidelike riglyne vir dieet intervensies, word dit aanbeveel dat dieetkundiges wat met kinders met OSS werk ondersteun word deur opleidingsgeleenthede om hul vaardighede te verbeter en dienslewering te optimaliseer.

O Transtorno do Espectro do Autismo (TEA) compõe um universo amplo e complexo com dificuldades relacionadas às áreas do comportamento, da interação social e da comunicação. A falta de um marcador biológico exige que o diagnóstico aconteça por meio da observação clínica e, na maioria dos casos, se compõe como um desafio aos/às profissionais responsáveis em fazê-lo. As abordagens de atendimento mais comuns são: Treatment and Education of Autistic and Communication Handicapped Children (TEACCH), Applied Behavior Analysis (ABA) e Picture Exchange Communication System (PECS), baseadas em teorias behavioristas. Estes programas estão relacionados ao desenvolvimento de rotina, de habilidades para uso cotidiano e de estratégias de comunicação. No contexto da família, o transtorno exige uma reorganização e um planejamento baseado em torno do cuidado da pessoa com TEA. Frente a esta realidade a discussão da dignidade humana se compõe como uma reflexão necessária e, principalmente, relacionada aos direitos humanos, que se constitua como concreta. Assim sendo, a constituição da dignidade humana como imago Dei se estabelece na relação do ser humano com o Criador, com o humano e com o todo da criação. Também no âmbito dos direitos humanos, construídos historicamente, é possível discutir a dignidade humana enquanto processo constitutivo do ser humano através da convivência, da alteridade, do reconhecimento e da participação que pretende a visibilidade das pessoas em suas características específicas. Esta forma de entender a dignidade humana procura situá-la para além de um adereço e que de fato contribua para que se avance em práticas de políticas públicas. Desta maneira torna-se possível que os direitos relacionados ao atendimento socioeducacional às pessoas com TEA se transformem em ações reais. Destarte, compreendendo a análise do conteúdo das entrevistas realizadas com os/as familiares de pessoas com TEA, fica evidente que questões como atendimento socioeducacional adequado, profissionais dispostos/as ao cuidado e capacitados/as, e políticas públicas efetivas, se constituem como elementos imprescindíveis apontados pelos/as familiares para o desenvolvimento cotidiano da pessoa com TEA. / Autism Spectrum Disorder (ASD) makes up a broad and complex universe with difficulties related to the areas of behavior, of social interaction and of communication. The lack of a biological marker demands that the diagnostic take place through clinical observation and, in most cases, it presents a challenge to the professionals responsible for making the diagnosis. The most common treatment approaches are: Treatment and Education of Autistic and Communication Handicapped Children (TEACCH), Applied Behavior Analysis (ABA) and Picture Exchange Communication System (PECS), based on behaviorist theories. These programs are related to the development of routines, of skills for daily use and of communication strategies. In the context of the family, the disorder demands a reorganization and planning around the care of the person with ASD. Confronted with this reality the discussion of human dignity is set as a necessary reflection and mainly related to human rights which are constituted as concrete. Thus, the constitution of human dignity as imago Dei is established in the relation of the human being with the Creator, with the human and with all of creation. In the area of human rights, historically constituted, it is also possible to discuss human dignity as a constitutive process of the human being through communal interaction, through otherness, through recognition and participation which aims at the visibility of the people in their specific characteristics. This form of understanding human dignity seeks to situate it beyond a mere prop and aims at truly contributing to the advancement of practices in public policies. In this way it becomes possible for the rights related to the socio-educational treatment of persons with ASD to be transformed into real actions. Thus, understanding the analysis of the content of the interviews carried out with family members of persons with ASD, it becomes evident that issues such as: adequate socioeducational treatment; capacitated and willing professionals for care; and effective public policies constitute essential elements pointed out by the family members for the daily development of the person with ASD.

Autism is a lifelong neurodevelopmental disorder. The etiology of autism still remains unclear due to the heterogeneous and complex nature of the disorder, however synergistic actions between genetic components and environmental factors have been suggested. Acetaminophen (APAP) is one of the most popular over-the-counter drugs that possess antipyretic and analgesic effects. It is considered a relatively safe and effective within therapeutic doses. Recently, early exposure to APAP has been suggested to be one of the underlying cause of autism. Children are often prescribed APAP to lessen fever or irritability after vaccination during the first year, and APAP may adversely affect the normal brain development. In order to better understand the association with APAP and autism, we used an inbred mouse strain BTBR T+tf/J (BTBR). BTBR exhibits behavioral deficits that mimic the core behavioral deficits of human autism. In the study, investigated 1) if BTBR mice showed differences in thiol biochemistry and EAAT3 levels in brain compared with C57BL/6J (C57) mice, 2) if early exposure to APAP induced behavioral changes worsening the autistic phenotypes of BTBR in adolescence, and 3) if APAP exposure in neonatal mice induced possible toxicity at various doses. As a result, we observed that BTBR mice have significantly lower plasma sulfate levels and EAAT expression levels in the frontal cortex compared to C57 mice. Surprisingly, neonatal therapeutic dose of APAP administration did not induce behavioral changes in both C57 and BTBR in adolescence. However, we showed that a supratheraputic dose of APAP significantly elevated levels of oxidative stress marker in the brain. Overall, the results suggested that BTBR mice would be a useful mouse model to investigate effects of various environmental factors that have been associated with autism. In addition, early exposure to APAP at supratherapeutic doses may negatively affect normal brain development.

Autism Spectrum Disorder (ASD) is a heterogeneous group of neurodevelopmental disorders that affects about 1% of the worldwide population and has a strong genetic component. Stereotyped behavior and restricted interests, as well as problems of social interaction and communication characterize ASD. Moreover, in 10% of cases, ASD occurs as a secondary condition in addition to a syndrome, such as Phelan-McDermid syndrome (PMS), which is associated with a great clinical variability. Among genetic factors, copy number variations (CNVs) are one of the most important. However, the clinical significance of many CNVs remains nuclear and there is an underrepresentation of small CNVs associated with ASD in the literature. In this context, this project aimed to 1) characterize large and small CNVs in Brazilian patients with ASD using an array-CGH previously customized in our laboratory. 2) Clinically and genetically describe a cohort of Brazilian patients with PMS, as well as to determine the frequency of this syndrome among Brazilian patients with ASD and other neurodevelopmental disorders. In result, we 1) further validated the customized array-CGH, 2) provided additional evidence of association with ASD for 27 candidate genes, 3) described 15 CNVs never reported in the literature in association with this disorder, 4) presented evidence that around 70% of CNVs found in our cohort are not polymorphism of our population and 5) reinforced the idea of shared molecular pathways among different neurodevelopmental disorders. In addition, we described for the first time a Brazilian cohort of patients with PMS and contributed to the molecular and clinical characterization of this syndrome. We also provided additional evidence of genotype-phenotype association with regard to the presence of renal problems and speech status in patients with PMS and estimated the frequency of this syndrome among Brazilian patients with ASD and intellectual disability (syndromic or not). With these results, we hope to contribute to better understand the ASD and PMS etiology, especially in our population / O Transtorno do Espectro Autista (TEA) corresponde ao um grupo heterogêneo de alterações no neurodesenvolvimento que afeta cerca de 1% da população mundial e apresenta um forte componente genético. O TEA é caracterizado pela presença de comportamento estereotipado e interesses restritos, além de problemas de interação social e comunicação. Além disso, em 10% dos casos, o TEA ocorre como uma condição secundária somada a uma síndrome. Um exemplo é a síndrome de Phelan-McDermid (PMS), associada a uma grande variabilidade clínica. Dentre os fatores genéticos, as variações no número de cópias (CNVs) são um dos mais importantes. No entanto, o significado clínico de muitas CNVs permanece incerto, além de haver juma sub-representação de CNVs pequenas associadas ao TEA na literatura. Dentro deste contexto, este projeto teve como objetivos 1) caracterizar CNVs grandes e pequenas em pacientes brasileiros com TEA utilizando uma lâmina de array-CGH previamente customizada no Laboratório de Genética do Desenvolvimento - USP. 2) descrever clínica e geneticamente uma casuística de pacientes brasileiros com PMS, bem como determinar a frequência desta síndrome em pacientes com TEA e com outras alterações de neurodesenvolvimento. Como resultados, nós 1) validamos a lâmina customizada, 2) fornecemos evidencia adicional de associação com o TEA para 27 genes, 3) descrevemos 15 CNVs nunca reportadas em associação com o transtorno 4) apresentamos evidências de que cerca de 70% das CNVs encontradas em nossa coorte não são polimorfismo de nossa população e 5) reforçamos a ideia de vias moleculares compartilhadas entre diferentes alterações do neurodesenvolvimento. Além disso, descrevemos pela primeira vez uma casuística brasileira de pacientes com PMS e contribuímos para a síndrome. Fornecemos evidência adicional de associação genótipo-fenótipo no que diz respeito à presença de problemas renais e status de fala em pacientes com PMS e estimamos a frequência da síndrome entre pacientes brasileiros com TEA e com deficiência intelectual (sindrômica ou não). Com estes resultados, esperamos ter contribuído para o entendimento da etiologia tanto do TEA, quanto da PMS, sobretudo na nossa população

Les Troubles du Spectre de l’Autisme (TSA) représentent la deuxième pathologie neuro-développementale la plus fréquente chez l’enfant. Le handicap est présent tout au long de la vie et a des conséquences majeures sur le fonctionnement de la personne mais aussi sur l’entourage familial et notamment les parents. Comme souligné par le dernier Plan Autisme, il est urgent de développer les offres d’accompagnement des aidants familiaux. L’objectif de cette recherche est d’étudier l’ajustement et les besoins parentaux dans les Troubles du Spectre de l’Autisme en vue de développer un programme d’éducation thérapeutique et d’en mesurer son impact. Trois études ont été réalisées successivement à partir d’une méthodologie soit qualitative (Etude 1) soit quantitative (Etudes 2 et 3). Notre première étude a permis d’identifier les besoins des parents d’enfant avec un TSA par rapport à des parents tout-venants (N=162). Des cibles d’accompagnement ont été formulées à partir des besoins matériel, d’information, de guidance parentale et de soutien émotionnel rapportés majoritairement par les parents d’enfant avec un TSA. Notre seconde étude visait à étudier les déterminants de l’ajustement parental dans les TSA (N=115). Les variables liées au contexte étaient davantage associées à l’ajustement parental que les variables individuelles. Du point de vue contextuel, les caractéristiques de l’environnement familial et l’accès de l’enfant à une scolarisation semblent être des déterminants importants de l’ajustement. Du point de vue individuel la présence de comorbidités chez l’enfant et d’un phénotype autistique élargie chez le parent étaient associés à un moins bon ajustement parental. Enfin, notre troisième étude a permis de développer et d’évaluer l’impact du programme d’éducation thérapeutique ETAP auprès de parents d’enfant avec un TSA (N=40). Le programme comporte 7 séances collectives structurées. Une bonne acceptabilité ainsi que des améliorations significatives de la qualité de vie et de la symptomatologie dépressive ont été notées. En conclusion, les besoins et les difficultés d’ajustement relevés chez les parents confirment la nécessité d’accompagner, de façon plus systématique, les pères et les mères d’enfant avec un TSA. Dans une logique de prévention, il est primordial d’évaluer, de manière précoce et continue, les besoins d’accompagnement et la qualité de l’ajustement parental. Cette évaluation doit s’appuyer sur une vision globale de la situation parentale et intégrer des aspects individuels et contextuels. On retrouve ces éléments au sein du programme ETAP qui apparaît comme un dispositif prometteur pour accompagner les parents d’enfant avec un TSA. La proposition d’un modèle de compréhension de l’ajustement parental dans les TSA permet d’articuler les résultats des trois volets de cette recherche. / Autism Spectrum Disorders (ASD) are the second most common childhood neurodevelopmental disorder. Disability is present throughout life and has major implications for the individual functioning but also on the family environment, especially on parents. As highlighted by the last French Autism Plan, it is crucial to develop support programs for parents. The goal of this research is to study the adjustment and parental needs in ASD in order to develop and evaluate a therapeutic education program. Three studies were carried out successively using a qualitative method (Study 1) or quantitative method (Studies 2 and 3). The first study aimed at identifying needs in two groups: parents of children with ASD compared to parents of typically developing children (N = 162). Support targets were formulated from reported needs by parents with ASD child in the following areas: material, information, parental guidance and emotional support. Our second study considered the determinants of parental adjustment in ASD (N = 115). The contextual variables were more involved in parental adjustment than individual measures. From a contextual perspective, the characteristics of the family environment and children school access are important determinants of adjustment. From an individual perspective, comorbidities in children and a broader autism phenotype in parents were associated with lower parental adjustment. Finally, the last study developed and evaluated the impact of therapeutic education program to parents of children with ASD (N = 40). The program consists in seven group-structured sessions. Good acceptability as well as significant improvements in quality of life and depressive symptoms was noted. In conclusion, the parents’ needs and adjustment difficulties confirm the relevance to support fathers and mothers of children with ASD. From a prevention way, it is important to early and continually assess support needs and parental adjustment. This assessment should be based on a global vision of parental status and to consider individual and contextual aspects. These elements are present in the ETAP program, which appears as a promising device to support parents of children with ASD. A theoretical model of parental adjustment in ASD is proposed from the results of the three components of this research.

<p>  </p> <p><em>Syngap1+/-</em> is a mouse mode for intellectual disability and autism spectrum disorder where haploinsufficiency of the <em>Syngap1</em> gene and therefore downregulation of SynGAP1 leads to early maturation of synapses within the brain within post-natal days fourteen and sixteen instead of at the normal developmental schedule of post-natal day thirty. This early-shifted timeline falls directly before the visual critical where binocular matching between inputs from the two eyes occurs, and during a period where neurons become selective to specific orientations. High-level visual and cognitive issues observed in autism spectrum disorder patients might follow from deficits in basic sensory processing development, but it is not yet understand how <em>Syngap1</em> haploinsufficiency affects visual development and visual processing. Therefore, to characterize visual processing within the <em>Syngap1+/-</em> mouse model of autism spectrum disorder, acute electrophysiological recordings were performed within the monocular and binocular regions of the mouse visual cortex (V1). Responses to a series of visual stimuli were analyzed to measure and compare receptive field size, orientation selectivity, and binocularity between <em>Syngap1+/-</em> mice and littermate controls. In order to understand how potential deficits in physiology could translate into visual perception, a behavioral training protocol was implemented which isolated visual acuity in mice. In accordance with known developmental timelines in the visual cortex, it was found that the receptive field sizes of V1 neurons in <em>Syngap1+/-</em> mice were unchanged from wild type controls. However, these same neurons had wider tuning curves and lower firing rates than neurons in littermate controls. Ocular dominance was unaltered between <em>Syngap1+/-</em> and wild type mice, but this was possibly due to low sample sizes of neurons from the binocular regions of V1. At the behavioral level, lower visual acuities were discovered in <em>Syngap1+/-</em> mice with a size degree difference compared to littermate controls – a minor but significant difference. These results indicate a reduction in SynGAP1 expression has a perceivable effect on V1 development and function at both physiological and behavioral levels.</p>

Background: Autism Spectrum Disorder (ASD) is a complex neurodevelopmen-tal disorder that affects social communication, behavior, and cognitive development.Patients with autism have a variety of difficulties, such as sensory impairments, at-tention issues, learning disabilities, mental health issues like anxiety and depression,as well as motor and learning issues. The World Health Organization (WHO) es-timates that one in 100 children have ASD. Although ASD cannot be completelytreated, early identification of its symptoms might lessen its impact. Early identifi-cation of ASD can significantly improve the outcome of interventions and therapies.So, it is important to identify the disorder early. Machine learning algorithms canhelp in predicting ASD. In this thesis, Support Vector Machine (SVM) and RandomForest (RF) are the algorithms used to predict ASD. Objectives: The main objective of this thesis is to build and train the models usingmachine learning(ML) algorithms with the default parameters and with the hyper-parameter tuning and find out the most accurate model based on the comparison oftwo experiments to predict whether a person is suffering from ASD or not. Methods: Experimentation is the method chosen to answer the research questions.Experimentation helped in finding out the most accurate model to predict ASD. Ex-perimentation is followed by data preparation with splitting of data and by applyingfeature selection to the dataset. After the experimentation followed by two exper-iments, the models were trained to find the performance metrics with the defaultparameters, and the models were trained to find the performance with the hyper-parameter tuning. Based on the comparison, the most accurate model was appliedto predict ASD. Results: In this thesis, we have chosen two algorithms SVM and RF algorithms totrain the models. Upon experimentation and training of the models using algorithmswith hyperparameter tuning. SVM obtained the highest accuracy score and f1 scoresfor test data are 96% and 97% compared to other model RF which helps in predictingASD. Conclusions: The models were trained using two ML algorithms SVM and RF andconducted two experiments, in experiment-1 the models were trained using defaultparameters and obtained accuracy, f1 scores for the test data, and in experiment-2the models were trained using hyper-parameter tuning and obtained the performancemetrics such as accuracy and f1 score for the test data. By comparing the perfor-mance metrics, we came to the conclusion that SVM is the most accurate algorithmfor predicting ASD.

[pt] Estudar como ocorre o desenvolvimento da criança diagnosticada com Transtorno do Espectro Autista, em espaços que não sejam somente o da escola, nos faz pensar como esta constrói suas interações sociais e também pode exercer os seus direitos e liberdades fundamentais como sujeito com deficiência, visando sua inclusão social e cidadania. Assim, o objetivo deste estudo foi investigar os modos e frequência de participação das crianças no TEA em espaços urbanos de lazer como fator relevante para seu desenvolvimento cognitivo, emocional e social. Realizou-se um estudo qualitativo que envolveu a análise do discurso de 16 cuidadores de uma clínica de Neuroreabilitação, localizada no Rio de Janeiro. Os resultados revelaram que as interações entre pais/cuidadores e filhos autistas quando são mútuas e colaborativas, juntamente com estratégias parentais igualitárias, são favoráveis e capazes de conduzir a criança a pensar a respeito de suas atitudes, logo, podem incentivar a conduta pró-social da criança. O estudo concluiu que a interação e a convivência entre pais/cuidadores e a criança autista em outros espaços, que não seja somente o da escola. Mostrou-se importante, mas que ainda existem muitos obstáculos e limitações impostos em relação ao TEA, no que diz respeito às suas potencialidades, resistências e preconceitos. Entretanto, apesar dos desafios, as iniciativas e a dedicação representam um enorme passo para encontrar maneiras dessas crianças se apropriarem do conhecimento e possivelmente desenvolverem suas habilidades. / [en] Studying how the development of children diagnosed with Autism Spectrum Disorder occurs, in spaces that are not only the school, makes us think about how they build their social interactions and also how they can exercise their fundamental rights and freedoms as a subject with disabilities, aiming at their social inclusion and citizenship. Thus, the objective of this study was to investigate the participation of children with Autism Spectrum Disorder (ASD) in urban spaces, as a relevant factor for their cognitive, social and emotional development. A qualitative study was carried out that involved the analysis of the speech of 16 caregivers of a Neurorehabilitation clinic, located in Rio de Janeiro. The results revealed that interactions between parents/caregivers and autistic children, when they are mutual and collaborative, together with egalitarian parenting strategies, are favorable and capable of leading the child to think about their attitudes, therefore, they can encourage prosocial behavior. of child. The study concluded that the interaction and coexistence between parents/caregivers and the autistic child in other spaces, other than the school, proved to be important, but that there are still many obstacles and limitations imposed in relation to ASD, in terms of concerns its potentialities, resistances and prejudices. However, despite the challenges, the initiatives and dedication represent a huge step towards finding ways for these children to appropriate knowledge and possibly develop their skills.

Core symptoms of Autism Spectrum Disorder (ASD) impact the child's abilities to interact with others, especially with the primary caregivers. Most research has focused on investigating the mother-child dyad, but the paternal role in interaction with children with ASD is mainly unexplored (e.g., Rankin, Paisley, Tomeny &amp; Eldred, 2019; Flippin &amp; Crais, 2011). For this, the project's first aim is to examine paternal interactive characteristics and behaviors and compare father-child and mother-child interactions with children with ASD, delineating the strengths and weaknesses of both caregivers in a complementary system. Based on this investigation, we implemented a personalized and parent-specific early intensive intervention that may guarantee better developmental trajectories for children with ASD. Consequently, the project's second aim is to assess the impact of intervention with parental involvement through cognitive, socio-communicative, and dyadic behavioral measures using a longitudinal study with pre- and post-assessments. At this point, it is fundamental to evaluate how several traits of children and caregivers might impact the treatment response. To reach this aim, while assessing developmental trajectories, we wanted to identify a-priori individual differences at both child and caregiver’s level and dyad dynamics that may influence intervention outcomes. We identified markers of better developmental trajectories and discussed implications for clinical practice in providing practitioners with more information about areas to be targeted during the intervention.