Visual attention and autistic behavior in infants with fragile X syndrome

Fragile X syndrome (FXS) is the leading known inherited cause of intellectual disability and the most common known biological cause of autism. Approximately 25% to 50% of males with FXS meet full diagnostic criteria for autism. Despite the high comorbidity between FXS and autism and the ability to diagnose FXS prenatally or at birth, no studies have examined indicators of autism in infants with FXS. The current study focused on indices of visual attention, one of the earliest and most robust behavioral indicators of autism in idiopathic (non-FXS) autism. Analyses revealed lower HR variability, shallower HR decelerations, and prolonged look durations in 12-month old infants with FXS that were correlated with severity of autistic behavior but not mental age

Thinking together: What makes Communities of Practice work?

In this article, we develop the founding elements of the concept of Communities of Practice by elaborating on the learning processes happening at the heart of such communities. In particular, we provide a consistent perspective on the notions of knowledge, knowing and knowledge sharing that is compatible with the essence of this concept – that learning entails an investment of identity and a social formation of a person. We do so by drawing richly from the work of Michael Polanyi and his conception of personal knowledge, and thereby we clarify the scope of Communities of Practice and offer a number of new insights into how to make such social structures perform well in professional settings. The conceptual discussion is substantiated by findings of a qualitative empirical study in the UK National Health Service. As a result, the process of ‘thinking together’ is conceptualized as a key part of meaningful Communities of Practice where people mutually guide each other through their understandings of the same problems in their area of mutual interest, and this way indirectly share tacit knowledge. The collaborative learning process of ‘thinking together’, we argue, is what essentially brings Communities of Practice to life and not the other way round

Comparing the immune response to a novel intranasal nanoparticle PLGA vaccine and a commercial BPI3V vaccine in dairy calves

peer-reviewedBackground There is a need to improve vaccination against respiratory pathogens in calves by stimulation of local immunity at the site of pathogen entry at an early stage in life. Ideally such a vaccine preparation would not be inhibited by the maternally derived antibodies. Additionally, localized immune response at the site of infection is also crucial to control infection at the site of entry of virus. The present study investigated the response to an intranasal bovine parainfluenza 3 virus (BPI3V) antigen preparation encapsulated in PLGA (poly dl-lactic-co-glycolide) nanoparticles in the presence of pre-existing anti-BPI3V antibodies in young calves and comparing it to a commercially available BPI3V respiratory vaccine. Results There was a significant (P < 0.05) increase in BPI3V-specific IgA in the nasal mucus of the BPI3V nanoparticle vaccine group alone. Following administration of the nanoparticle vaccine an early immune response was induced that continued to grow until the end of study and was not observed in the other treatment groups. Virus specific serum IgG response to both the nanoparticle vaccine and commercial live attenuated vaccine showed a significant (P < 0.05) rise over the period of study. However, the cell mediated immune response observed didn’t show any significant rise in any of the treatment groups. Conclusion Calves administered the intranasal nanoparticle vaccine induced significantly greater mucosal IgA responses, compared to the other treatment groups. This suggests an enhanced, sustained mucosal-based immunological response to the BPI3V nanoparticle vaccine in the face of pre-existing antibodies to BPI3V, which are encouraging and potentially useful characteristics of a candidate vaccine. However, ability of nanoparticle vaccine in eliciting cell mediated immune response needs further investigation. More sustained local mucosal immunity induced by nanoparticle vaccine has obvious potential if it translates into enhanced protective immunity in the face of virus outbreak

Intensive intervention for children and adolescents with autism in a community setting in Italy: a single-group longitudinal study

<p>Abstract</p> <p>Background</p> <p>Previous studies have shown favourable results with intensive behavioural treatment for children with autism: evidence has emerged that treatment can be successfully implemented in a community setting and in adolescent participants. The aim of this study was to describe the 2-year adaptive functioning outcome of children and adolescents with autism treated intensively within the context of special autism centres, as well as to evaluate family satisfaction with the activity of the centres.</p> <p>Methods</p> <p>Sixty participants with autism (20 females and 40 males, aged between 4 and 18 years) attending the semi-residential rehabilitation centres for autism located in the Abruzzo region (Central Italy) were followed up and their adaptive functioning was evaluated both at baseline and after one and two years using the Vineland Adaptive Behaviour Scales (VABS). Parents' satisfaction with the service was evaluated using the Orbetello Satisfaction Scale for Children and Adolescent Mental Health.</p> <p>Results</p> <p>The increase in VABS scores was significant on several domains in the different gender and age categories. It is worth noting that male children had improved a great deal (roughly, an effect size >0.20) in the domains of communication, daily living and motor skills (effect sizes 0.34, 0.45 and 0.27 respectively) whereas in male adolescents, a notable increase in VABS scores was recorded in the domain of socialization only (effect size 0.23). On the other hand, adaptive behaviour in female children increased in the domains of socialization and motor skills (effect sizes 0.27 and 0.42 respectively) whereas in female adolescents, good results were achieved in the domains of daily living, socialization and motor skills (effect sizes 0.22, 0.26 and 0.20 respectively).</p> <p>The level of satisfaction of users of the service over time was found to be substantial, even when they had recently started the program.</p> <p>Conclusions</p> <p>Our results support the implementation of special autism treatment community centres, based on a parent co-directed rehabilitative, intensive and early intervention. Further experimental research designed to document the effectiveness of services provided to children and adolescents with autism in the community is recommended.</p

Does routine child health surveillance contribute to the early detection of children with pervasive developmental disorders? – An epidemiological study in Kent, U.K.

BACKGROUND: Recently changed guidelines for child health surveillance in the United Kingdom (U.K.) suggest targeted checks only, instead of the previously conducted routine or universal screening at 2 years and 3.5 years. There are concerns that these changes could lead to a delay in the detection of children with autism and other pervasive developmental disorders (PDD). Recent U.K. studies have suggested that the prevalence of PDD is much higher than previously estimated. This study establishes to which extent the routine checks contributed to the early detection and assessment of cases of PDD. Simultaneously we have evaluated the process involved and estimate the prevalence of PDD in our district. METHODS: Retrospective study design utilising community medical files. Headteachers of schools (n = 75) within Maidstone district (Kent) were asked to report all children with an established diagnosis of autism or PDD attending year 4 (born '91 and '92 / n = 2536) in October 2000 based on educational records. RESULTS: 59 schools (78.7%) took part in the study. A total of 33 children were reported. 21 fulfilled the inclusion criteria (12 falsely reported). The prevalences were (per 10,000): PDD 82.8 (male to female ratio 6:1), childhood autism 23.7, Asperger's syndrome 11.8 and autistic spectrum disorder 47.3. Co-existing medical conditions were noted in 14.3%; 52.4% were attending mainstream schools. In 63.2% of cases concerns – mainly in the area of speech and language development (SLD) – had been documented at the 2 year check. At the 3.5 year check concerns were noted in 94.1% – the main area was again SLD (76.5%), although behavioural abnormalities were becoming more frequent (47.1%). A total of 13 children (68.4%) were referred for further assessment as a direct result of the checks. CONCLUSIONS: The prevalences for different types of PDD were similar to figures published recently, but much higher than reported a few years ago. Analysis of our data suggests that routine surveillance is a valuable contributing factor for the early detection of PDD and thereby facilitates early intervention. Thus, if routine surveillance ceases, then an alternative method of early detection should be put in place

Epithelial-to-mesenchymal transition supports ovarian carcinosarcoma tumorigenesis and confers sensitivity to microtubule-targeting with eribulin

Ovarian carcinosarcoma (OCS) is an aggressive and rare tumour type with limited treatment options. OCS is hypothesised to develop via the combination theory, with a single progenitor resulting in carcinomatous and sarcomatous components, or alternatively via the conversion theory, with the sarcomatous component developing from the carcinomatous component through epithelial-to-mesenchymal transition (EMT). In this study, we analysed DNA variants from isolated carcinoma and sarcoma components to show that OCS from 18 women is monoclonal. RNA sequencing indicated the carcinoma components were more mesenchymal when compared with pure epithelial ovarian carcinomas, supporting the conversion theory and suggesting that EMT is important in the formation of these tumours. Preclinical OCS models were used to test the efficacy of microtubule-targeting drugs, including eribulin, which has previously been shown to reverse EMT characteristics in breast cancers and induce differentiation in sarcomas. Vinorelbine and eribulin more effectively inhibited OCS growth than standard-of-care platinum-based chemotherapy, and treatment with eribulin reduced mesenchymal characteristics and N-MYC expression in OCS patient-derived xenografts (PDX). Eribulin treatment resulted in an accumulation of intracellular cholesterol in OCS cells, which triggered a down-regulation of the mevalonate pathway and prevented further cholesterol biosynthesis. Finally, eribulin increased expression of genes related to immune activation and increased the intratumoral accumulation of CD8+ T cells, supporting exploration of immunotherapy combinations in the clinic. Together, these data indicate EMT plays a key role in OCS tumourigenesis and support the conversion theory for OCS histogenesis. Targeting EMT using eribulin could help improve OCS patient outcomes