Can improving working memory prevent academic difficulties? A school based randomised controlled trial.

BACKGROUND: Low academic achievement is common and is associated with adverse outcomes such as grade repetition, behavioural disorders and unemployment. The ability to accurately identify these children and intervene before they experience academic failure would be a major advance over the current 'wait to fail' model. Recent research suggests that a possible modifiable factor for low academic achievement is working memory, the ability to temporarily store and manipulate information in a 'mental workspace'. Children with working memory difficulties are at high risk of academic failure. It has recently been demonstrated that working memory can be improved with adaptive training tasks that encourage improvements in working memory capacity. Our trial will determine whether the intervention is efficacious as a selective prevention strategy for young children at risk of academic difficulties and is cost-effective. METHODS/DESIGN: This randomised controlled trial aims to recruit 440 children with low working memory after a school-based screening of 2880 children in Grade one. We will approach caregivers of all children from 48 participating primary schools in metropolitan Melbourne for consent. Children with low working memory will be randomised to usual care or the intervention. The intervention will consist of 25 computerised working memory training sessions, which take approximately 35 minutes each to complete. Follow-up of children will be conducted at 6, 12 and 24 months post-randomisation through child face-to-face assessment, parent and teacher surveys and data from government authorities. The primary outcome is academic achievement at 12 and 24 months, and other outcomes include child behaviour, attention, health-related quality of life, working memory, and health and educational service utilisation. DISCUSSION: A successful start to formal learning in school sets the stage for future academic, psychological and economic well-being. If this preventive intervention can be shown to be efficacious, then we will have the potential to prevent academic underachievement in large numbers of at-risk children, to offer a ready-to-use intervention to the Australian school system and to build international research partnerships along the health-education interface, in order to carry our further studies of effectiveness and generalisability.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Susceptibility of the human retrovirus XMRV to antiretroviral inhibitors

<p>Abstract</p> <p>Background</p> <p>XMRV (xenotropic murine leukemia virus-related virus) is the first known example of an exogenous gammaretrovirus that can infect humans. A limited number of reports suggest that XMRV is intrinsically resistant to many of the antiretroviral drugs used to treat HIV-1 infection, but is sensitive to a small subset of these inhibitors. In the present study, we used a novel marker transfer assay to directly compare the antiviral drug sensitivities of XMRV and HIV-1 under identical conditions in the same host cell type.</p> <p>Results</p> <p>We extend the findings of previous studies by showing that, in addition to AZT and tenofovir, XMRV and HIV-1 are equally sensitive to AZddA (3'-azido-2',3'-dideoxyadenosine), AZddG (3'-azido-2',3'-dideoxyguanosine) and adefovir. These results indicate that specific 3'-azido or acyclic nucleoside analog inhibitors of HIV-1 reverse transcriptase (RT) also block XMRV infection with comparable efficacy <it>in vitro</it>. Our data confirm that XMRV is highly resistant to the non-nucleoside RT inhibitors nevirapine and efavirenz and to inhibitors of HIV-1 protease. In addition, we show that the integrase inhibitors raltegravir and elvitegravir are active against XMRV, with EC₅₀values in the nanomolar range.</p> <p>Conclusions</p> <p>Our analysis demonstrates that XMRV exhibits a distinct pattern of nucleoside analog susceptibility that correlates with the structure of the pseudosugar moiety and that XMRV is sensitive to a broader range of antiretroviral drugs than has previously been reported. We suggest that the divergent drug sensitivity profiles of XMRV and HIV-1 are partially explained by specific amino acid differences in their respective protease, RT and integrase sequences. Our data provide a basis for choosing specific antiretroviral drugs for clinical studies in XMRV-infected patients.</p

To what extent is the variation in cardiac rehabilitation quality associated with patient characteristics?

BACKGROUND: Huge variability in quality of service delivery of cardiac rehabilitation (CR) in the UK. This study aimed to ascertain whether the variation in quality of CR delivery is associated with participants' characteristics. METHODS: Individual patient data from 1 April 2013 to 31 March 2014 were collected electronically from the UK's National Audit of Cardiac Rehabilitation database. Quality of CR delivery is categorised as low, middle, and high based on six service-level criteria. The study included a range of patient variables: patient demographics, cardiovascular risk factors, comorbidities, physical and psychosocial health measures, and index of multiple deprivation. RESULTS: The chance that a CR patient with more comorbidities attended a high-quality programme was 2.13 and 1.85 times higher than the chance that the same patient attended a low- or middle-quality programme, respectively. Patients who participated in high-quality CR programmes tended to be at high risk (e.g. increased waist size and high blood pressure); high BMI, low physical activity levels and high Hospital Anxiety and Depression Scale scores; and were more likely to be smokers, and be in more socially deprived groups than patients in low-quality programmes. CONCLUSIONS: These findings show that the quality of CR delivery can be improved and meet national standards by serving a more multi-morbid population which is important for patients, health providers and commissioners of healthcare. In order for low-quality programmes to meet clinical standards, CR services need to be more inclusive in respect of patients' characteristics identified in the study. Evaluation and dissemination of information about the populations served by CR programmes may help low-quality programmes to be more inclusive

Biofluid Biomarkers in Huntington's Disease

Huntington's disease (HD) is a chronic progressive neurodegenerative condition where new markers of disease progression are needed. So far no disease-modifying interventions have been found, and few interventions have been proven to alleviate symptoms. This may be partially explained by the lack of reliable indicators of disease severity, progression, and phenotype.Biofluid biomarkers may bring advantages in addition to clinical measures, such as reliability, reproducibility, price, accuracy, and direct quantification of pathobiological processes at the molecular level; and in addition to empowering clinical trials, they have the potential to generate useful hypotheses for new drug development.In this chapter we review biofluid biomarker reports in HD, emphasizing those we feel are likely to be closest to clinical applicability

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field