Pubmed du 24/05/19

vendredi 24 mai 2019

1. Althoff CE, Dammann CP, Hope SJ, Ausderau KK. Parent-Mediated Interventions for Children With Autism Spectrum Disorder : A Systematic Review. Am J Occup Ther. 2019 ; 73(3) : 7303205010p1-p13.

OBJECTIVE : The purpose of this systematic review was to evaluate the evidence for the effectiveness of parent-mediated interventions on occupational performance of children with autism spectrum disorder (ASD). METHOD : We conducted a search of academic databases using terms such as autism spectrum disorder, parent, caregiver, and intervention. Five hundred eighty-two articles were reviewed, and 109 were selected for full-text review. The final analysis included 13 articles. RESULTS : Strong evidence was found for the efficacy of parent-mediated intervention for increasing child joint attention. Moderate evidence was found for the improvement of language scores, expressive language, nonverbal communication, initiation and response to interaction, behavior, play, adaptive functioning, ASD symptoms, and social communication. CONCLUSION : This systematic review suggests that parent-mediated interventions for children with ASD can improve various aspects of communication and ASD symptoms, with emerging support for occupational performance. Occupational therapy practitioners are well suited to facilitate these interventions to support families with children with autism.

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2. Budman I, Meiri G, Ilan M, Faroy M, Langer A, Reboh D, Michaelovski A, Flusser H, Menashe I, Donchin O, Dinstein I. Quantifying the social symptoms of autism using motion capture. Sci Rep. 2019 ; 9(1) : 7712.

Autism Spectrum Disorder (ASD) is a remarkably heterogeneous condition where individuals exhibit a variety of symptoms at different levels of severity. Quantifying the severity of specific symptoms is difficult, because it either requires long assessments or observations of the ASD individual, or reliance on care-giver questionnaires, which can be subjective. Here we present a new technique for objectively quantifying the severity of several core social ASD symptoms using a motion capture system installed in a clinical exam room. We present several measures of child-clinician interaction, which include the distance between them, the proportion of time that the child approached or avoided the clinician, and the direction that the child faced in relation to the clinician. Together, these measures explained 30% of the variance in ADOS scores, when using only 5 minute segments of "free play" from the recorded ADOS assessments. These results demonstrate the utility of motion capture for aiding researchers and clinicians in the assessment of ASD social symptoms. Further development of this technology and appropriate motion capture measures for use in kindergartens and at home is likely to yield valuable information that will aid in quantifying the initial severity of core ASD symptoms and their change over time.

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3. Gilbertson KE, Jackson HL, Dziuban EJ, Sherman SL, Berry-Kravis EM, Erickson CA, Valdez R. Preventive care services and health behaviors in children with fragile X syndrome. Disability and health journal. 2019.

BACKGROUND : This is the first description of preventive care services specifically received by children and young adults with fragile X syndrome (FXS). We compare these rates to those of other pediatric populations and identify care disparities within our cohort. OBJECTIVE : Describe the frequency of preventive care services and health behaviors by young people with FXS, and identify disparities in care. METHODS : We assessed four preventive care outcomes and the total number of preventive care guidelines met among individuals under 21 years from the ongoing Fragile X Online Registry with Accessible Research Database (N=406) using data from 2012 to 2015. We used adjusted odds ratios (AORs) from multiple logistic regression models to describe associations between demographic factors and preventive care outcomes. RESULTS : Seventy-five percent of our sample met dental care guidelines, 55.4% met influenza vaccination guidelines, 92.1% met immunization guidelines, and 24.4% met physical activity (PA) guidelines. Compared to children six to 10 years, younger children were less likely to have seen a dentist as recommended (AOR : 0.26) and young adults aged 16-20 were less likely to have received immunizations (AOR : 0.14) or to have engaged in recommended PA (AOR : 0.29). Black participants (AOR : 0.25) were less likely to have received an influenza vaccination than white participants. Individuals with autism (AOR : 0.25) were less likely to have sufficient PA, while individuals with hypersensitivity were more likely to have sufficient PA (AOR : 2.37) than unaffected individuals. CONCLUSIONS : The proportion of young people with FXS that meet basic recommendations in preventive care guidelines varies according to health condition and demographic characteristics. This proportion could be increased for some groups, particularly in the cases of influenza vaccination and physical activity.

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4. Guo BQ, Li HB, Liu YY. Association between hair lead levels and autism spectrum disorder in children : A systematic review and meta-analysis. Psychiatry Res. 2019 ; 276 : 239-49.

A number of studies measured lead levels in hair from children with autism spectrum disorder (ASD) to detect the relationship between cumulated lead exposure and the development of ASD, but results are inconsistent. We aimed to conduct a systematic review and meta-analysis using the published studies to explore the actual association of hair lead levels with ASD in children. We searched PubMed, Embase, PsycINFO, and Cochrane Library databases (up to December 11, 2018). The random-effects model was applied to summarize effect sizes. Subgroup and meta-regression analyses were performed simultaneously. Twenty eligible studies involving 1787 participants (941 autistic children and 846 healthy subjects) were included. Our results of primary analysis showed that there were no statistically significant differences in the levels of hair lead between children with ASD and healthy individuals (Hedges’s g=0.251 ; 95% confidence interval : -0.121, 0.623 ; P=0.187). We identified 2 sources of between-study heterogeneity : analytical technology and the sample size of patients. Additionally, no publication bias was observed in this meta-analysis. In conclusion, this study does not support the association of hair lead levels with ASD in children, and the involvement of cumulated lead exposure in the occurrence of ASD.

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5. Hosie S, Ellis M, Swaminathan M, Ramalhosa F, Seger GO, Balasuriya GK, Gillberg C, Rastam M, Churilov L, McKeown SJ, Yalcinkaya N, Urvil P, Savidge T, Bell CA, Bodin O, Wood J, Franks AE, Bornstein JC, Hill-Yardin EL. Gastrointestinal dysfunction in patients and mice expressing the autism-associated r451c mutation in neuroligin-3. Autism Res. 2019.

Gastrointestinal (GI) problems constitute an important comorbidity in many patients with autism. Multiple mutations in the neuroligin family of synaptic adhesion molecules are implicated in autism, however whether they are expressed and impact GI function via changes in the enteric nervous system is unknown. We report the GI symptoms of two brothers with autism and an R451C mutation in Nlgn3 encoding the synaptic adhesion protein, neuroligin-3. We confirm the presence of an array of synaptic genes in the murine GI tract and investigate the impact of impaired synaptic protein expression in mice carrying the human neuroligin-3 R451C missense mutation (NL3(R451C) ). Assessing in vivo gut dysfunction, we report faster small intestinal transit in NL3(R451C) compared to wild-type mice. Using an ex vivo colonic motility assay, we show increased sensitivity to GABAA receptor modulation in NL3(R451C) mice, a well-established Central Nervous System (CNS) feature associated with this mutation. We further show increased numbers of small intestine myenteric neurons in NL3(R451C) mice. Although we observed altered sensitivity to GABAA receptor modulators in the colon, there was no change in colonic neuronal numbers including the number of GABA-immunoreactive myenteric neurons. We further identified altered fecal microbial communities in NL3(R451C) mice. These results suggest that the R451C mutation affects small intestinal and colonic function and alter neuronal numbers in the small intestine as well as impact fecal microbes. Our findings identify a novel GI phenotype associated with the R451C mutation and highlight NL3(R451C) mice as a useful preclinical model of GI dysfunction in autism. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : People with autism commonly experience gastrointestinal problems, however the cause is unknown. We report gut symptoms in patients with the autism-associated R451C mutation encoding the neuroligin-3 protein. We show that many of the genes implicated in autism are expressed in mouse gut. The neuroligin-3 R451C mutation alters the enteric nervous system, causes gastrointestinal dysfunction, and disrupts gut microbe populations in mice. Gut dysfunction in autism could be due to mutations that affect neuronal communication.

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6. Krol M, Krol M. The world as we know it and the world as it is : Eye-movement patterns reveal decreased use of prior knowledge in individuals with autism. Autism Res. 2019.

We used a perceptual closure task with Mooney images as stimuli to record eye-movement patterns in response to the same degraded image before and after perceptual learning in 21 adolescents and young adults with ASD and 23 sex-, age-, and IQ-matched typically developing individuals. In the control group, we observed changes in the eye-movement patterns between the first and the last presentation of the degraded stimulus, reflecting top-down optimization of eye-movement patterns, that is, a decrease in the number of fixations and interfixation distance, coupled with an increase in the duration of fixations. This effect was attenuated in individuals with autism, pointing to a decreased rate of perceptual learning. We also found that participants with autism displayed decreased scanpath stability, that is, a lower recurrence of fixation locations between different presentations of the same image, which may suggests a lower rate of perceptual learning or decreased predictability in the eye-movement patterns. These results provide evidence for decreased use of prior knowledge in perceptual decisions in autism. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : We showed autistic and typically developing participants some degraded images that were difficult to recognize for the first time, but once you knew what they represent, you could see it easily. We found that the eye-movement patterns of persons with autism did not change as much after learning what the pictures represented as in the case of typically developing participants. This means that previous experiences and knowledge change the way people with autism perceive things to a smaller extent.

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7. Lee CE, Burke MM, Stelter CR. Exploring the Perspectives of Parents and Siblings Toward Future Planning for Individuals With Intellectual and Developmental Disabilities. Intellectual and developmental disabilities. 2019 ; 57(3) : 198-211.

Parents often provide the bulk of caregiving supports for their adult offspring with intellectual and developmental disabilities (IDD). Given the longer lives of people with IDD, however, such caregiving roles may transition to siblings. Thus, it is critical to conduct future planning among family members (e.g., parents, siblings) to prepare for the transition of caregiving roles. To this end, we interviewed 10 parent-sibling dyads (N = 20) of people with IDD about long-term planning. Both parents and siblings reported family-related and systemic barriers to developing future plans. Siblings (unlike parents) reported wanting more communication among family members about planning. Implications for future research and practice are discussed.

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8. Lee YC, Lin CH, Tsai CH, Li HJ, Lin SK, Chen KL. Association Between Executing Theory of Mind in a Limited Experimental Context and Executing It in Daily Contexts in Children With Autism Spectrum Disorder : A Cross-Sectional Study. Am J Occup Ther. 2019 ; 73(3) : 7303205150p1-p11.

IMPORTANCE : Theory of mind (ToM) can be divided into two constructs : capacity and performance. Although severity of autism traits and verbal comprehension have been identified as being associated with ToM capacity, no study has yet verified their role in predicting the ToM performance of children with autism spectrum disorder (ASD). OBJECTIVE : To examine the differences and associations between ToM capacity and ToM performance and to verify the role of autism traits and verbal comprehension in predicting ToM performance in children with ASD. DESIGN : Cross-sectional study. SETTING : Pediatric rehabilitation hospitals and clinics. PARTICIPANTS : One hundred four children with ASD who met the inclusion criteria. OUTCOMES AND MEASURES : We examined ToM capacity and ToM performance with the Theory of Mind Task Battery (ToMTB) and the Theory of Mind Inventory-2-Chinese version (ToMI-2-C). Severity of autism traits and verbal comprehension were assessed with the Social Responsiveness Scale, Second Edition (SRS-2), and the Verbal Comprehension Index (VCI) of either the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition or the Wechsler Intelligence Scale for Children-Fourth Edition. We conducted correlation and hierarchical regression analyses. RESULTS : Scores on the ToMI-2-C were significantly correlated with those on the ToMTB, SRS-2, and VCI (rs = .613, -.344, and .566, respectively ; p < .01). CONCLUSIONS AND RELEVANCE : ToM capacity is significantly correlated with ToM performance. Both severity of autism traits and verbal comprehension played an important role in predicting ToM performance of children with ASD after controlling for ToM capacity. WHAT THIS ARTICLE ADDS : ToM capacity, severity of autism traits, and verbal comprehension were all significant predictors of ToM performance. Improving ToM capacity, severity of autism traits, and verbal comprehension of children with ASD would be beneficial to their ToM performance.

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9. Lei J, Ashwin C, Brosnan M, Russell A. Developing an Online Tool to Measure Social Network Structure and Perceived Social Support Amongst Autistic Students in Higher Education : A Feasibility Study. J Autism Dev Disord. 2019.

The academic, daily-living, and social challenges all students face during university transition can become magnified for many autistic students, who might struggle to adapt to changes in their social network structure (SNS) and perceived social support (PSS). This study assessed the development, feasibility, and convergent validity of a novel online tool (Social Network and Perceived Social Support-SNaPSS) designed to quantitatively and qualitatively evaluate SNS and PSS during university transition. SNaPSS demonstrated good feasibility for completion amongst autistic students (Study 1, n = 10, 17-19 years), and adequate convergent validity against other PSS, autism symptom severity, and social anxiety measures amongst autistic (n = 28) and typically developing students (Study 2, n = 112, 17-19 years). Broader implications of SNaPSS to measure SNS/PSS are discussed.

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10. Mahoney WJ, Ceballos J, Amir N. Occupational Therapy Practitioners’ Perceptions About Older Adults With Developmental Disabilities in Traditional Health Care Settings. Am J Occup Ther. 2019 ; 73(3) : 7303345010p1-p6.

IMPORTANCE : Health care providers’ knowledge of and comfort working with adults with developmental disabilities (DD) affect the quality of care this growing population receives. Previous research on this topic has not included occupational therapy practitioners. OBJECTIVE : To determine occupational therapy practitioners’ views about working with older adults with DD in traditional health care settings. DESIGN : Quantitative survey over 4 mo. PARTICIPANTS : A random sample of 310 practitioners from the American Occupational Therapy Association’s Gerontology and Physical Disabilities Special Interest Sections working in traditional health care settings. OUTCOMES AND MEASURES : A researcher-developed survey to assess occupational therapy practitioners’ comfort, knowledge, challenge, and supports and barriers in regard to working with older adults with DD. RESULTS : In the 310 included surveys (31% response rate), most occupational therapy practitioners reported feeling comfortable (76.1%-80.0%) and knowledgeable (66.5%-68.4%) working with older adults with DD. Approximately 93% reported that work with older adults with DD was at least somewhat challenging. Key perceived barriers included clients’ cognitive needs, lack of caregiver collaboration, and challenging behavior. CONCLUSION AND RELEVANCE : Most occupational therapy practitioners in traditional health care settings found working with older adults with DD challenging, and many did not feel sufficiently knowledgeable to meet the needs of this population. Similar to other health professionals, occupational therapy practitioners may benefit from additional resources to provide services to this population. WHAT THIS ARTICLE ADDS : Older adults with DD receive occupational therapy services in hospitals, rehabilitation centers, nursing homes, and other medical settings. Because clients such as these are not common in these settings, occupational therapy practitioners who work there would like more tools to help provide good care.

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11. Marks B, Sisirak J, Magallanes R, Krok K, Donohue-Chase D. Effectiveness of a HealthMessages Peer-to-Peer Program for People With Intellectual and Developmental Disabilities. Intellectual and developmental disabilities. 2019 ; 57(3) : 242-58.

Effective strategies to improve health education, food choices, and physical activity are vital for people with intellectual and developmental disabilities (IDD), as their sedentary lifestyles and high fat diets are contributing to poor health, such as cardiovascular disease, osteoporosis, hypertension, Type II diabetes, and obesity. This study examined the effectiveness of a peer-led health promotion program for people with IDD. One group pre/post-test design was used to test the feasibility and effectiveness of the 12-week HealthMessages Program for three groups : peer health coaches (PHCs), mentors, and peer participants. A total of 379 volunteers participated including PHCs people with IDD (n = 33), mentors-staff from community organizations (n = 35), and peer participants-peers with IDD (n = 311). Following the intervention and 12-week HealthMessages Program, PHCs had significant changes in physical activity and hydration knowledge, mentors had significant changes in self-efficacy scores, and peer participants had significant changes in physical activity and hydration knowledge, social supports, and total health behaviors. A dyad approach supported PHCs and mentors to implement a successful HealthMessages Program with their peers.

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12. Rogan EL, Ranson CA, Mori TK, Park SK, Lam HM, Legaspi JF, Tran LK, Cameros CJM, Blackburn AN, Lee ST, Valle-Oseguera CS, Pham CN, Woelfel JA, Patel RA. Exploring the Valley of Savings : Minimizing Part D Costs and Optimizing Drug Therapy Outcomes in Medicare Beneficiaries With Developmental Disability. Intellectual and developmental disabilities. 2019 ; 57(3) : 234-41.

Nonelderly disabled Medicare beneficiaries have a higher prevalence of chronic conditions, higher utilization of prescription medications, and increased demand for clinical services when compared to beneficiaries 65 years of age and older who are not disabled. Out-of-pocket costs and medication-related problems are major barriers to medication compliance and achievement of therapeutic goals. A school of pharmacy partnered with a nonprofit organization that provides care to individuals with developmental disabilities. The present study highlights outcomes resulting from (a) providing Medicare Part D plan optimization services to lower prescription drug costs and (b) Medication Therapy Management services to evaluate safe and effective medication use in this beneficiary population. Provided interventions were shown to reduce overall medication costs and identify significant medication-related problems.

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13. Safer-Lichtenstein J, Hamilton JC, McIntyre LL. Examining Demographics in Randomized Controlled Trials of Group-Based Social Skills Interventions for Individuals with Autism Spectrum Disorder. J Autism Dev Disord. 2019.

We reviewed the demographic reporting practices and diversity of participants in published randomized controlled trial studies of group-based social skills interventions (GSSIs) for individuals with autism spectrum disorder (ASD). A total of 17 studies met inclusionary criteria. Results of this review suggest that the majority of published RCTs reported on participant gender and race/ethnicity, with fewer studies including details on household income and caregiver education. Study samples generally lacked diversity, with an overrepresentation of participants who were male, White, and from upper-middle class backgrounds. Additionally, we found that nearly all GSSI studies focused on participants with average or high IQs, or were specifically classified as having a higher functioning sub-diagnosis within ASD. Implications and future directions for research are discussed.

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14. Squillaro T, Alessio N, Capasso S, Di Bernardo G, Melone MAB, Peluso G, Galderisi U. Senescence Phenomena and Metabolic Alteration in Mesenchymal Stromal Cells from a Mouse Model of Rett Syndrome. International journal of molecular sciences. 2019 ; 20(10).

Chromatin modifiers play a crucial role in maintaining cell identity through modulation of gene expression patterns. Their deregulation can have profound effects on cell fate and functions. Among epigenetic regulators, the MECP2 protein is particularly attractive. Mutations in the Mecp2 gene are responsible for more than 90% of cases of Rett syndrome (RTT), a progressive neurodevelopmental disorder. As a chromatin modulator, MECP2 can have a key role in the government of stem cell biology. Previously, we showed that deregulated MECP2 expression triggers senescence in mesenchymal stromal cells (MSCs) from (RTT) patients. Over the last few decades, it has emerged that senescent cells show alterations in the metabolic state. Metabolic changes related to stem cell senescence are particularly detrimental, since they contribute to the exhaustion of stem cell compartments, which in turn determine the falling in tissue renewal and functionality. Herein, we dissect the role of impaired MECP2 function in triggering senescence along with other senescence-related aspects, such as metabolism, in MSCs from a mouse model of RTT. We found that MECP2 deficiencies lead to senescence and impaired mitochondrial energy production. Our results support the idea that an alteration in mitochondria metabolic functions could play an important role in the pathogenesis of RTT.

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15. Vorland CJ, Brown AW, Dickinson SL, Gelman A, Allison DB. Comment on : Comprehensive Nutritional and Dietary Intervention for Autism Spectrum Disorder-A Randomized, Controlled 12-Month Trial, Nutrients 2018, 10, 369. Nutrients. 2019 ; 11(5).

We commend Adams et al [...].

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16. Wilkinson CL, Levin AR, Gabard-Durnam LJ, Tager-Flusberg H, Nelson CA. Reduced frontal gamma power at 24 months is associated with better expressive language in toddlers at risk for autism. Autism Res. 2019.

Frontal gamma power has been associated with early language development in typically developing toddlers, and gamma band abnormalities have been observed in individuals with autism spectrum disorder (ASD), as well as high-risk infant siblings (those having an older sibling with ASD), as early as 6 months of age. The current study investigated differences in baseline frontal gamma power and its association with language development in toddlers at high versus low familial risk for autism. Electroencephalography recordings as well as cognitive and behavioral assessments were acquired at 24 months as part of prospective, longitudinal study of infant siblings of children with and without autism. Diagnosis of autism was determined at 24-36 months, and data were analyzed across three outcome groups-low-risk without ASD (n = 43), high-risk without ASD (n = 42), and high-risk with ASD (n = 16). High-risk toddlers without ASD had reduced baseline frontal gamma power (30-50 Hz) compared to low-risk toddlers. Among high-risk toddlers increased frontal gamma was only marginally associated with ASD diagnosis (P = 0.06), but significantly associated with reduced expressive language ability (P = 0.007). No association between gamma power and language was present in the low-risk group. These findings suggest that differences in gamma oscillations in high-risk toddlers may represent compensatory mechanisms associated with improved developmental outcomes. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : This study looked at differences in neural activity in the gamma range and its association with language in toddlers with and without increased risk for ASD. At 2 years of age, gamma power was lower in high-risk toddlers without ASD compared to a low-risk comparison group. Among high-risk toddlers both with and without later ASD, reduced gamma power was also associated with better language outcomes, suggesting that gamma power may be a marker of language development in high-risk children.

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17. Yang Y, Geng Y, Jiang D, Ning L, Kim HJ, Jeon NL, Lau A, Chen L, Lin MZ. Kinase pathway inhibition restores PSD95 induction in neurons lacking fragile X mental retardation protein. Proceedings of the National Academy of Sciences of the United States of America. 2019.

Fragile X syndrome (FXS) is the leading monogenic cause of autism and intellectual disability. FXS is caused by loss of expression of fragile X mental retardation protein (FMRP), an RNA-binding protein that regulates translation of numerous mRNA targets, some of which are present at synapses. While protein synthesis deficits have long been postulated as an etiology of FXS, how FMRP loss affects distributions of newly synthesized proteins is unknown. Here we investigated the role of FMRP in regulating expression of new copies of the synaptic protein PSD95 in an in vitro model of synaptic plasticity. We find that local BDNF application promotes persistent accumulation of new PSD95 at stimulated synapses and dendrites of cultured neurons, and that this accumulation is absent in FMRP-deficient mouse neurons. New PSD95 accumulation at sites of BDNF stimulation does not require known mechanisms regulating FMRP-mRNA interactions but instead requires the PI3K-mTORC1-S6K1 pathway. Surprisingly, in FMRP-deficient neurons, BDNF induction of new PSD95 accumulation can be restored by mTORC1-S6K1 blockade, suggesting that constitutively high mTORC1-S6K1 activity occludes PSD95 regulation by BDNF and that alternative pathways exist to mediate induction when mTORC1-S6K1 is inhibited. This study provides direct evidence for deficits in local protein synthesis and accumulation of newly synthesized protein in response to local stimulation in FXS, and supports mTORC1-S6K1 pathway inhibition as a potential therapeutic approach for FXS.

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