15 research outputs found

    Task-specific training versus usual care to improve upper limb function after stroke: The “Task-AT Home” randomised controlled trial protocol

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    Background: Sixty percent of people have non-functional arms 6 months after stroke. More effective treatments are needed. Cochrane Reviews show low-quality evidence that task-specific training improves upper limb function. Our feasibility trial showed 56 h of task-specific training over 6 weeks resulted in an increase of a median 6 points on the Action Research Arm test (ARAT), demonstrating the need for more definitive evidence from a larger randomised controlled trial. Task-AT Home is a two-arm, assessor-blinded, multicentre randomised, controlled study, conducted in the home setting. Aim: The objective is to determine whether task-specific training is a more effective treatment than usual care, for improving upper limb function, amount of upper limb use, and health related quality of life at 6 weeks and 6 months after intervention commencement. Our primary hypothesis is that upper limb function will achieve a ≥ 5 point improvement on the ARAT in the task-specific training group compared to the usual care group, after 6 weeks of intervention. Methods: Participants living at home, with remaining upper limb deficit, are recruited at 3 months after stroke from sites in NSW and Victoria, Australia. Following baseline assessment, participants are randomised to 6 weeks of either task-specific or usual care intervention, stratified for upper limb function based on the ARAT score. The task-specific group receive 14 h of therapist-led task-specific training plus 42 h of guided self-practice. The primary outcome measure is the ARAT at 6 weeks. Secondary measures include the Motor Activity Log (MAL) at 6 weeks and the ARAT, MAL and EQ5D-5 L at 6 months. Assessments occur at baseline, after 6 weeks of intervention, and at 6 months after intervention commencement. Analysis will be intention to treat using a generalised linear mixed model to report estimated mean differences in scores between the two groups at each timepoint with 95% confidence interval and value of p. Discussion: If the task-specific home-based training programme is more effective than usual care in improving arm function, implementation of the programme into clinical practice would potentially lead to improvements in upper limb function and quality of life for people with stroke. Clinical Trial Registration: ANZCTR.org.au/ACTRN12617001631392p.asp

    The Developing Human Connectome Project Neonatal Data Release

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    The Developing Human Connectome Project has created a large open science resource which provides researchers with data for investigating typical and atypical brain development across the perinatal period. It has collected 1228 multimodal magnetic resonance imaging (MRI) brain datasets from 1173 fetal and/or neonatal participants, together with collateral demographic, clinical, family, neurocognitive and genomic data from 1173 participants, together with collateral demographic, clinical, family, neurocognitive and genomic data. All subjects were studied in utero and/or soon after birth on a single MRI scanner using specially developed scanning sequences which included novel motion-tolerant imaging methods. Imaging data are complemented by rich demographic, clinical, neurodevelopmental, and genomic information. The project is now releasing a large set of neonatal data; fetal data will be described and released separately. This release includes scans from 783 infants of whom: 583 were healthy infants born at term; as well as preterm infants; and infants at high risk of atypical neurocognitive development. Many infants were imaged more than once to provide longitudinal data, and the total number of datasets being released is 887. We now describe the dHCP image acquisition and processing protocols, summarize the available imaging and collateral data, and provide information on how the data can be accessed

    Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

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    Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

    Coexisting Sedges in Northern Wisconsin Forests are Functionally Similar and May be Distantly Related in Evolutionary History

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    Color poster with text, charts, and images.Organisms coexist either by having similar functional traits that match habitat requirements or by having non-similar traits to reduce competition. A classic study showed that coexisting oak trees in Florida tend to be functionally similar and phylogenetically diverse, meaning certain functional traits associated with habitat filtering evolved. We are investigating whether the hyperdiverse plant genus Carex (sedges) shows similar ecological filtering and convergent evolution.University of Wisconsin--Eau Claire Office of Research and Sponsored Program

    Functional Community Assembly is Increasingly Deterministic at Larger Spatial Grain Sizes

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    Color poster with text and graphs.Community assembly is the result of ecological selection processes, dispersal processes, and random drift processes. Selection processes can cause coexisting species to be more similar or more different in traits, depending on the strength of environmental filtering or the strength of competition. Scale in terms of the spatial extent can influence how trait similarity differs from random drift. For example, a grassland could have higher than expected trait diversity by having tall, medium and short species in most samples. But if the scale is expanded to include forests with tall trees, then the grassland plants may have lower than expected trait diversity. Scale also includes the sample scale or grain size. We sampled forest vegetation Northern Wisconsin at three grain sizes (0.1 m2, 1 m2, and 10 m2) to investigate how grain size and spatial extent influence our conclusions about community assembly.University of Wisconsin--Eau Claire Office of Research and Sponsored Program

    Leukoencephalopathy with calcifications and cysts:Genetic and phenotypic spectrum

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    Biallelic mutations in SNORD118, encoding the small nucleolar RNA U8, cause leukoencephalopathy with calcifications and cysts (LCC). Given the difficulty in interpreting the functional consequences of variants in nonprotein encoding genes, and the high allelic polymorphism across SNORD118 in controls, we set out to provide a description of the molecular pathology and clinical spectrum observed in a cohort of patients with LCC. We identified 64 affected individuals from 56 families. Age at presentation varied from 3 weeks to 67 years, with disease onset after age 40 years in eight patients. Ten patients had died. We recorded 44 distinct, likely pathogenic, variants in SNORD118. Fifty two of 56 probands were compound heterozygotes, with parental consanguinity reported in only three families. Forty nine of 56 probands were either heterozygous (46) or homozygous (three) for a mutation involving one of seven nucleotides that facilitate a novel intramolecular interaction between the 5′ end and 3′ extension of precursor-U8. There was no obvious genotype–phenotype correlation to explain the marked variability in age at onset. Complementing recently published functional analyses in a zebrafish model, these data suggest that LCC most often occurs due to combinatorial severe and milder mutations, with the latter mostly affecting 3′ end processing of precursor-U8
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