Pubmed du 18/01/20

samedi 18 janvier 2020

1. Correction : Quantification of speech and synchrony in the conversation of adults with autism spectrum disorder. PLoS One ;2020 ;15(1):e0227387.

[This corrects the article DOI : 10.1371/journal.pone.0225377.].

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2. Autism spectrum disorder. Nat Rev Dis Primers ;2020 (Jan 16) ;6(1):6.

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3. Barbaro J, Yaari M. Study protocol for an evaluation of ASDetect - a Mobile application for the early detection of autism. BMC Pediatr ;2020 (Jan 18) ;20(1):21.

BACKGROUND : Autism Spectrum Conditions (ASC) can be reliably diagnosed by 24 months of age. However, despite the well-known benefits of early intervention, there is still a research-practice gap in the timely identification of ASC, particularly in low-resourced settings. The Social Attention and Communication Surveillance (SACS) tool, which assesses behavioural markers of autism between 12 to 24 months of age, has been implemented in Maternal and Child Health (MCH) settings, with excellent psychometric properties. ASDetect is a free mobile application based on the SACS, which is designed to meet the need for an effective, evidence-based tool for parents, to learn about children’s early social-communication development and assess their child’s ’likelihood’ for ASC. STUDY AIMS : The primary aim of this study is to evaluate the psychometric properties of ASDetect in the early detection of children with ASC. A secondary aim is to assess ASDetect’s acceptability and parental user experience with the application. METHODS : Families are recruited to download the application and participate in the study via social media, health professionals (e.g., MCH nurses, paediatricians) and word of mouth. All participating caregivers complete a demographic questionnaire, survey regarding their user experience, and the Social Responsiveness Scale-2 (SRS-2), an autism screening questionnaire ; they are also invited to participate in focus groups. Children identified at ’high likelihood’ for ASC based on the ASDetect results, the SRS-2 or parental and/or professional concerns undergo a formal, gold-standard, diagnostic assessment. Receiver Operating Characteristic analyses will be used to assess psychometric properties of ASDetect. Thematic analyses will be used to explore themes arising in the focus groups to provide insights regarding user experiences with the app. Multiple regression analyses will be carried out to determine the extent to which demographic factors, parental stress and beliefs on health surveillance and child results on ASDetect are associated with the parental user-experience of the application. DISCUSSION : With a strong evidence-base and global access, ASDetect has the potential to empower parents by providing them with knowledge of their child’s social-communication development, validating and reassuring any parental concerns, and supporting them in communicating with other health professionals, ultimately enhancing child and family outcomes and well-being.

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4. Castelijns B, Baak ML, Timpanaro IS, Wiggers CRM, Vermunt MW, Shang P, Kondova I, Geeven G, Bianchi V, de Laat W, Geijsen N, Creyghton MP. Hominin-specific regulatory elements selectively emerged in oligodendrocytes and are disrupted in autism patients. Nat Commun ;2020 (Jan 16) ;11(1):301.

Speciation is associated with substantial rewiring of the regulatory circuitry underlying the expression of genes. Determining which changes are relevant and underlie the emergence of the human brain or its unique susceptibility to neural disease has been challenging. Here we annotate changes to gene regulatory elements (GREs) at cell type resolution in the brains of multiple primate species spanning most of primate evolution. We identify a unique set of regulatory elements that emerged in hominins prior to the separation of humans and chimpanzees. We demonstrate that these hominin gains perferentially affect oligodendrocyte function postnatally and are preferentially affected in the brains of autism patients. This preference is also observed for human-specific GREs suggesting this system is under continued selective pressure. Our data provide a roadmap of regulatory rewiring across primate evolution providing insight into the genomic changes that underlie the emergence of the brain and its susceptibility to neural disease.

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5. Cavinato L, Cardinaux A, Jain K, Jamal W, Kjelgaard M, Sinha P, Barbieri R. Characterizing autonomic response to arousing visual-auditory multi-modal task in Autism Spectrum Disorder (ASD). Conf Proc IEEE Eng Med Biol Soc ;2019 (Jul) ;2019:4942-4945.

Sensory abnormalities are widespread in Autism Spectrum Disorder (ASD). However, their definition is still quite subjective and vague. Here we propose a novel approach for characterization of Autonomic Nervous System responses to sensory stimulation based on electrocardiogram (ECG) assessment. In particular, we develop a preliminary study where autonomic responses of both autistic (ASD = 5) and neurotypical (NT = 5) participants have been evaluated in terms of changes in responsiveness to repeated stimuli. Autonomic control has been estimated via high-frequency heart rate variability (HF-HRV) and low-frequency HRV (LF-HRV). Results show significant differences among groups for the HRV measures (p value = 0.0158), supported by expected changes of HF (p value = 0.0079) and LF (p value = 0.0079) trends over stimulations. We thus conclude that an overall decrease in autonomic arousal can give important insights for devising new habituation metrics in NT and ASD individuals.

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6. Elbattah M, Carette R, Dequen G, Guerin JL, Cilia F. Learning Clusters in Autism Spectrum Disorder : Image-Based Clustering of Eye-Tracking Scanpaths with Deep Autoencoder. Conf Proc IEEE Eng Med Biol Soc ;2019 (Jul) ;2019:1417-1420.

Autism spectrum disorder (ASD) is a lifelong condition characterized by social and communication impairments. This study attempts to apply unsupervised Machine Learning to discover clusters in ASD. The key idea is to learn clusters based on the visual representation of eye-tracking scanpaths. The clustering model was trained using compressed representations learned by a deep autoencoder. Our experimental results demonstrate a promising tendency of clustering structure. Further, the clusters are explored to provide interesting insights into the characteristics of the gaze behavior involved in autism.

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7. Geminiani A, Santos L, Casellato C, Farabbi A, Farella N, Santos-Victor J, Olivieri I, Pedrocchi A. Design and validation of two embodied mirroring setups for interactive games with autistic children using the NAO humanoid robot. Conf Proc IEEE Eng Med Biol Soc ;2019 (Jul) ;2019:1641-1644.

Socially assistive robots have shown potential benefits in therapy of child and elderly patients with social and cognitive deficits. In particular, for autistic children, humanoid robots could enhance engagement and attention, thanks to their simplified toy-like appearance and the reduced set of possible movements and expressions. The recent focus on autism-related motor impairments has increased the interest on developing new robotic tools aimed at improving not only the social capabilities but also the motor skills of autistic children. To this purpose, we have designed two embodied mirroring setups using the NAO humanoid robot. Two different tracking systems were used and compared : Inertial Measurement Units and the Microsoft Kinect, a marker-less vision based system. Both platforms were able to mirror upper limb basic movements of two healthy subjects, an adult and a child. However, despite the lower accuracy, the Kinect-based setup was chosen as the best candidate for embodied mirroring in autism treatment, thanks to the lower intrusiveness and reduced setup time. A prototype of an interactive mirroring game was developed and successfully tested with the Kinect-based platform, paving the way to the development of a versatile and powerful tool for clinical use with autistic children.

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8. Gorodetski A, Dinstein I, Zigel Y. Speaker diarization during noisy clinical diagnoses of autism. Conf Proc IEEE Eng Med Biol Soc ;2019 (Jul) ;2019:2593-2596.

Autism Spectrum Disorder (ASD) is characterized by difficulties in social communication, social interactions and repetitive behaviors. Some of these difficulties are apparent in the speech characteristics of ASD children who are verbal. Developing algorithms that can extract and quantify speech features that are unique to ASD children is, therefore, extremely valuable for assessing the initial state of each child and their development over time. An important component of such algorithms is speaker diarization in the noisy clinical environments where ASD children are diagnosed. Here we present a Gaussian Mixture Model (GMM) approach for speaker diarization that was applied to 34 recordings from clinical assessments using the Autism Diagnostic Observation Schedule (ADOS). We used mel-frequency cepstral coefficients (MFCC) and pitch based features to classify segments containing speech of the child, therapist, parent, movement noises (chair, toys, etc.) and simultaneous speech. We achieved an accuracy of 89% in identifying segments with children’s speech and an accuracy of 74.5% in identifying children’s and therapists’ speech segments. These accuracy rates are similar to the diarization accuracy rates reported by previous similar studies, thereby demonstrating a promising route for the automated assessment of speech in children with ASD.

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9. Harvy J, Ewen JB, Thakor N, Bezerianos A, Li J. Cortical Functional Connectivity during Praxis in Autism Spectrum Disorder. Conf Proc IEEE Eng Med Biol Soc ;2019 (Jul) ;2019:333-336.

Abnormal functional connectivity was reported as one of the underlying characteristics of autism spectrum disorder (ASD). Considering the motor deficits in ASD, we utilized praxis to investigate the neural mechanisms of ASD during motor task. Since the previous functional connectivity studies reported divergent results, we explored the properties of the functional connectivity using graph metrics to address brain organization alterations of ASD. We proposed the use of eLORETA to investigate the cortical connectivity during praxis based on a cohort of 45 high-functioning ASD (HFA) children and 45 typically developing (TD) children. The between-group comparison revealed higher clustering coefficient and lower global efficiency for HFA relative to TD while the between-phase comparison suggested decreasing global efficiency, increasing characteristic path length for TD. Nodal metrics exhibited significant differences between groups in frontal and occipital regions. These regions also showed significant changes of nodal metrics and connection strengths between baseline and praxis execution for TD. However, there were no significant changes in global, nodal metrics and connection strengths between phases for HFA. Our study suggested that cortical connectivity in ASD exhibited lower overall efficiency and a deficit in reorganization, which deepens the understanding of abnormal brain organization in ASD.

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10. Ichikawa T, Shigeta M, Urakawa T, Sawatome A, Tanaka M, Kurita Y, Araki O, Ichikawa H, Takemura H. Correlation Between Gait Perception and Autistic Traits in the General Population : A Study on Event-Related Evoked Potentials. Conf Proc IEEE Eng Med Biol Soc ;2019 (Jul) ;2019:3135-3138.

Previous studies have shown that people with autistic traits have difficulties in motion perception, such as human gait as depicted on a point-light display. A recent study reported that adults with autism spectrum disorders showed atypical visual event-related evoked potentials (ERPs) in response to radial optic flow. To determine the correlation between gait perception and autistic traits in the general population, the present study recorded ERPs time-locked to the onset of approaching and receding point-light walkers. ERPs were measured using an 8-channel system in 19 adults and the correlation between the ERP components and the Subthreshold Autism Trait Questionnaire (SATQ) score were assessed to quantitatively measure autistic traits in the general population. The results showed that the higher SATQ score was, the longer the latency of the ERP component for an approaching walker was. In conclusion, people with autistic traits have trouble perceiving the approach of other people.

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11. Jiang M, Francis SM, Srishyla D, Conelea C, Zhao Q, Jacob S. Classifying Individuals with ASD Through Facial Emotion Recognition and Eye-Tracking. Conf Proc IEEE Eng Med Biol Soc ;2019 (Jul) ;2019:6063-6068.

Individuals with Autism Spectrum Disorder (ASD) have been shown to have atypical scanning patterns during face and emotion perception. While previous studies characterized ASD using eye-tracking data, this study examined whether the use of eye movements combined with task performance in facial emotion recognition could be helpful to identify individuals with ASD. We tested 23 subjects with ASD and 35 controls using a Dynamic Affect Recognition Evaluation (DARE) task that requires an individual to recognize one of six emotions (i.e., anger, disgust, fear, happiness, sadness, and surprise) while observing a slowly transitioning face video. We observed differences in response time and eye movements, but not in the recognition accuracy. Based on these observations, we proposed a machine learning method to distinguish between individuals with ASD and typically developing (TD) controls. The proposed method classifies eye fixations based on a comprehensive set of features that integrate task performance, gaze information, and face features extracted using a deep neural network. It achieved an 86% classification accuracy that is comparable with the standardized diagnostic scales, with advantages of efficiency and objectiveness. Feature visualization and interpretations were further carried out to reveal distinguishing features between the two subject groups and to understand the social and attentional deficits in ASD.

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12. Leader G, Tuohy E, Chen JL, Mannion A, Gilroy SP. Feeding Problems, Gastrointestinal Symptoms, Challenging Behavior and Sensory Issues in Children and Adolescents with Autism Spectrum Disorder. J Autism Dev Disord ;2020 (Jan 18)

Frequency of feeding problems, gastrointestinal (GI) symptoms, challenging behavior, sensory problems and comorbid psychopathology were assessed using the following questionnaires : Screening Tool for Feeding Problems for Children, GI Symptoms Inventory, Behavior Problems Inventory Short Form, Short Sensory Profile, and Autism Spectrum Disorder-Comorbidity Child (ASD-CC) in 136 children and adolescents with ASD. Eighty-four percent had food selectivity, followed by food refusal (78.7%), rapid eating (76.5%), chewing problems (60.3%), food stealing (49.3%) and vomiting (19.1%). Higher rates of GI symptoms, challenging behavior, and sensory issues were found in those who presented with rapid eating, food refusal and food stealing than those without these problems. Comorbid psychopathology predicted rapid eating, food selectivity and food refusal.

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13. Liu Y, Zhang Y, Zarrei M, Dong R, Yang X, Zhao D, Scherer SW, Gai Z. Refining critical regions in 15q24 microdeletion syndrome pertaining to autism. Am J Med Genet B Neuropsychiatr Genet ;2020 (Jan 18)

Chromosome 15q24 microdeletion syndrome is characterized by developmental delay, facial dysmorphism, hearing loss, hypotonia, recurrent infection, and other congenital malformations including microcephaly, scoliosis, joint laxity, digital anomalies, as well as sometimes having autism spectrum disorder (ASD) and attention deficit hyperactivity disorder. Here, we report a boy with a 2.58-Mb de novo deletion at chromosome 15q24. He is diagnosed with ASD and having multiple phenotypes similar to those reported in cases having 15q24 microdeletion syndrome. To delineate the critical genes and region that might be responsible for these phenotypes, we reviewed all previously published cases. We observe a potential minimum critical region of 650 kb (LCR15q24A-B) affecting NEO1 among other genes that might pertinent to individuals with ASD carrying this deletion. In contrast, a previously defined minimum critical region downstream of the 650-kb interval (LCR15q24B-D) is more likely associated with the developmental delay, facial dysmorphism, recurrent infection, and other congenital malformations. As a result, the ASD phenotype in this individual is potentially attributed by genes particularly NEO1 within the newly proposed critical region.

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14. Lord C, Brugha TS, Charman T, Cusack J, Dumas G, Frazier T, Jones EJH, Jones RM, Pickles A, State MW, Taylor JL, Veenstra-VanderWeele J. Autism spectrum disorder. Nat Rev Dis Primers ;2020 (Jan 16) ;6(1):5.

Autism spectrum disorder is a construct used to describe individuals with a specific combination of impairments in social communication and repetitive behaviours, highly restricted interests and/or sensory behaviours beginning early in life. The worldwide prevalence of autism is just under 1%, but estimates are higher in high-income countries. Although gross brain pathology is not characteristic of autism, subtle anatomical and functional differences have been observed in post-mortem, neuroimaging and electrophysiological studies. Initially, it was hoped that accurate measurement of behavioural phenotypes would lead to specific genetic subtypes, but genetic findings have mainly applied to heterogeneous groups that are not specific to autism. Psychosocial interventions in children can improve specific behaviours, such as joint attention, language and social engagement, that may affect further development and could reduce symptom severity. However, further research is necessary to identify the long-term needs of people with autism, and treatments and the mechanisms behind them that could result in improved independence and quality of life over time. Families are often the major source of support for people with autism throughout much of life and need to be considered, along with the perspectives of autistic individuals, in both research and practice.

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15. Oyarzabal A, Xiol C, Castells AA, Grau C, O’Callaghan M, Fernandez G, Alcantara S, Pineda M, Armstrong J, Altafaj X, Garcia-Cazorla A. Comprehensive Analysis of GABAA-A1R Developmental Alterations in Rett Syndrome : Setting the Focus for Therapeutic Targets in the Time Frame of the Disease. Int J Mol Sci ;2020 (Jan 14) ;21(2)

Rett syndrome, a serious neurodevelopmental disorder, has been associated with an altered expression of different synaptic-related proteins and aberrant glutamatergic and gamma-aminobutyric acid (GABA)ergic neurotransmission. Despite its severity, it lacks a therapeutic option. Through this work we aimed to define the relationship between MeCP2 and GABAA.-A1 receptor expression, emphasizing the time dependence of such relationship. For this, we analyzed the expression of the ionotropic receptor subunit in different MeCP2 gene-dosage and developmental conditions, in cells lines, and in primary cultured neurons, as well as in different developmental stages of a Rett mouse model. Further, RNAseq and systems biology analysis was performed from post-mortem brain biopsies of Rett patients. We observed that the modulation of the MeCP2 expression in cellular models (both Neuro2a (N2A) cells and primary neuronal cultures) revealed a MeCP2 positive effect on the GABAA.-A1 receptor subunit expression, which did not occur in other proteins such as KCC2 (Potassium-chloride channel, member 5). In the Mecp2+/- mouse brain, both the KCC2 and GABA subunits expression were developmentally regulated, with a decreased expression during the pre-symptomatic stage, while the expression was variable in the adult symptomatic mice. Finally, the expression of the gamma-aminobutyric acid (GABA) receptor-related synaptic proteins from the postmortem brain biopsies of two Rett patients was evaluated, specifically revealing the GABA A1R subunit overexpression. The identification of the molecular changes along with the Rett syndrome prodromic stages strongly endorses the importance of time frame when addressing this disease, supporting the need for a neurotransmission-targeted early therapeutic intervention.

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16. Posar A, Visconti P. Long-term outcome of autism spectrum disorder. Turk Pediatri Ars ;2019 ;54(4):207-212.

In most cases, autism spectrum disorder is a life-long condition, often severely affecting the quality of life of the patient and his/her family, but nowadays this diagnosis should not be considered a final sentence without appeal. Although even today the recovery from the autism spectrum is an unlikely possibility, a timely psycho-educational intervention can significantly improve the level of autonomy reached by the individual and therefore favorably modify the outcome. Some predictors of long-term outcome are known, primarily childhood intelligence quotient and early language/communication ability, but today this issue is still open. The lack of studies evaluating the long-term effects of the most important intervention programmes should be filled with adequate research. Community support and social integration may be very important in improving outcomes for individuals with autism spectrum disorder. But a real social integration involves a work activity and this is still a great problem today. An adequate and timely preparation of the working career of these individuals is fundamental for their future, and it should be done by choosing, as far as possible, suitable activities for them. Finally, in creating a dignified future for people with autism, we must never forget to listen to their point of view, whenever possible, in order to meet their particular needs.

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17. Raz A, Lehavi A, Fein S. Cesarean Delivery Under General Anesthesia Causing Autistic Spectrum Disorders : Not Very Likely. J Autism Dev Disord ;2020 (Jan 16)

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18. Schnider P, Bissantz C, Bruns A, Dolente C, Goetschi E, Jakob-Roetne R, Kunnecke B, Mueggler T, Muster W, Parrott N, Pinard E, Ratni H, Risterucci C, Rogers-Evans M, von Kienlin M, Grundschober C. Discovery of Balovaptan, a Vasopressin 1a Receptor Antagonist for the Treatment of Autism Spectrum Disorder. J Med Chem ;2020 (Jan 17)

We recently reported the discovery of a potent, selective, and brain-penetrant V1a receptor antagonist, which was not suitable for full development. Nevertheless, this compound was found to improve surrogates of social behavior in adults with autism spectrum disorder in an exploratory proof-of-mechanism study. Here we describe scaffold hopping that gave rise to triazolobenzodiazepines with improved pharmacokinetic properties. The key to balancing potency and selectivity while minimizing P-gp mediated efflux was fine-tuning of hydrogen bond acceptor basicity. Ascertaining a V1a antagonist specific brain activity pattern by pharmacological magnetic resonance imaging in the rat played a seminal role in guiding optimization efforts, culminating in the discovery of balovaptan (RG7314, RO5285119) 1. In a 12-week clinical phase 2 study in adults with autism spectrum disorder balovaptan demonstrated improvements in Vineland-II Adaptive Behavior Scales, a secondary end point comprising communication, socialization, and daily living skills. Balovaptan entered phase 3 clinical development in August 2018.

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19. Torres EB, Rai R, Mistry S, Gupta B. Hidden Aspects of the Research ADOS Are Bound to Affect Autism Science. Neural Comput ;2020 (Jan 17):1-47.

The research-grade Autism Diagnostic Observational Schedule (ADOS) is a broadly used instrument that informs and steers much of the science of autism. Despite its broad use, little is known about the empirical variability inherently present in the scores of the ADOS scale or their appropriateness to define change and its rate, to repeatedly use this test to characterize neurodevelopmental trajectories. Here we examine the empirical distributions of research-grade ADOS scores from 1324 records in a cross-section of the population comprising participants with autism between five and 65 years of age. We find that these empirical distributions violate the theoretical requirements of normality and homogeneous variance, essential for independence between bias and sensitivity. Further, we assess a subset of 52 typical controls versus those with autism and find a lack of proper elements to characterize neurodevelopmental trajectories in a coping nervous system changing at nonuniform, nonlinear rates. Repeating the assessments over four visits in a subset of the participants with autism for whom verbal criteria retained the same appropriate ADOS modules over the time span of the four visits reveals that switching the clinician changes the cutoff scores and consequently influences the diagnosis, despite maintaining fidelity in the same test’s modules, room conditions, and tasks’ fluidity per visit. Given the changes in probability distribution shape and dispersion of these ADOS scores, the lack of appropriate metric spaces to define similarity measures to characterize change and the impact that these elements have on sensitivity-bias codependencies and on longitudinal tracking of autism, we invite a discussion on readjusting the use of this test for scientific purposes.

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20. Vabalas A, Gowen E, Poliakoff E, Casson AJ. Kinematic features of a simple and short movement task to predict autism diagnosis. Conf Proc IEEE Eng Med Biol Soc ;2019 (Jul) ;2019:1421-1424.

Autism is a developmental condition primarily identified by social and communication deficits. However, over 70% of autistic individuals also show motor function deficits, which are evident even when simple stereotyped movements are performed. In this study, we have asked 24 autistic and 22 non-autistic adults to perform pointing movements between two markers 30 cm apart as quickly and as accurately as they can for 10 seconds. Motion tracking was employed to collect data and calculate kinematic features of the movement and aiming accuracy. At the group level, the results showed that autistic individuals performed pointing movements slower but more accurately compared to non-autistic individuals. At the individual level, we have used Machine Learning methods to predict autism diagnosis. Nested result Cross-Validation was used, which in contrast to commonly used K-fold Cross-Validation avoids pooling training and testing data and provides robust performance estimates. Our developed models achieved a statistically significant classification accuracy of 71% and showed that even a simple and short motor task enables discrimination between autistic and non-autistic individuals.

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