No abstract

This randomized controlled trial evaluated the efficacy of a computer software (i.e., Mind Reading) and in vivo rehearsal treatment on the emotion decoding and encoding skills, autism symptoms, and social skills of 43 children, ages 7-12 years with high-functioning autism spectrum disorder (HFASD). Children in treatment (n = 22) received the manualized protocol over 12 weeks. Primary analyses indicated significantly better posttest performance for the treatment group (compared to controls) on 3 of the 4 measures of emotion decoding and encoding and these were maintained at 5-week follow-up. Analyses of secondary measures favored the treatment group for 1 of the 2 measures; specifically, ASD symptoms were significantly lower at posttest and follow-up.

So as to assess how emerging science and new tools can be applied to study multiple stressors at a large (ecosystem) scale and to facilitate greater integration of approaches among different scientific disciplines, a workshop was organised on 10–12 September 2014 at the Sydney Institute of Marine Sciences, Sydney, Australia. The present paper discusses the limitations of the current risk-assessment approaches and how multiple stressors at large scales can be better evaluated in ecological risk assessments to inform the development of more efficient and preventive management policies based on adaptive management in the future. A future risk-assessment paradigm that overcomes these limitations is presented. This paradigm includes cultural and ecological protection goals, the development of ecological scenarios, the establishment of the relevant interactions among species, potential sources of stressors, their interactions and the development of cause–effect models. It is envisaged that this will be achievable through a greater integration of approaches among different scientific disciplines and through the application of new and emerging tools such as 'big data', ecological modelling and the incorporation of ecosystem service endpoints.

This replication randomized clinical trial examined the efficacy of a comprehensive psychosocial intervention for children aged 7 to 12 years with high‐functioning autism spectrum disorders (HFASDs). Participants were randomly assigned to treatment or wait‐list conditions. Treatment included instruction and therapeutic activities targeting social skills, face‐emotion recognition, interest expansion, and interpretation of non‐literal language. A response‐cost program was used to reduce problem behaviors and increase skills acquisition. Significant treatment effects were found for five of seven primary outcome measures (parent ratings and direct child measures). Secondary measures (i.e., staff ratings) corroborated gains reported by parents. Children maintained social gains 2 to 3 months post‐treatment. High levels of parent, child, and staff satisfaction were found, along with high levels of treatment fidelity. Standardized effect size estimates were predominantly in the medium and large ranges for significant outcome variables.

Aggregation of α-synuclein, the hallmark of α-synucleinopathies such as Parkinson’s disease, occurs in various glycosphingolipidoses. Although α-synuclein aggregation correlates with deficiencies in the lysosomal degradation of glycosphingolipids (GSL), the mechanism(s) involved in this aggregation remains unclear. We previously described the aggregation of α-synuclein in Krabbe’s disease (KD), a neurodegenerative glycosphingolipidosis caused by lysosomal deficiency of galactosyl-ceramidase (GALC) and the accumulation of the GSL psychosine. Here, we used a multi-pronged approach including genetic, biophysical and biochemical techniques to determine the pathogenic contribution, reversibility, and molecular mechanism of aggregation of α-synuclein in KD. While genetic knock-out of α-synuclein reduces, but does not completely prevent, neurological signs in a mouse model of KD, genetic correction of GALC deficiency completely prevents α-synuclein aggregation. We show that psychosine forms hydrophilic clusters and binds the C-terminus of α-synuclein through its amino group and sugar moiety, suggesting that psychosine promotes an open/aggregation-prone conformation of α-synuclein. Dopamine and carbidopa reverse the structural changes of psychosine by mediating a closed/aggregation-resistant conformation of α-synuclein. Our results underscore the therapeutic potential of lysosomal correction and small molecules to reduce neuronal burden in α-synucleinopathies, and provide a mechanistic understanding of α-synuclein aggregation in glycosphingolipidoses.