Lack of replication of thirteen single-nucleotide polymorphisms implicated in Parkinson's disease: a large-scale international study

Background: A genome-wide association study identified 13 single-nucleotide polymorphisms (SNPs) significantly associated with Parkinson's disease. Small-scale replication studies were largely non-confirmatory, but a meta-analysis that included data from the original study could not exclude all SNP associations, leaving relevance of several markers uncertain. Methods: Investigators from three Michael J Fox Foundation for Parkinson's Research-funded genetics consortia-comprising 14 teams-contributed DNA samples from 5526 patients with Parkinson's disease and 6682 controls, which were genotyped for the 13 SNPs. Most (88%) participants were of white, non-Hispanic descent. We assessed log-additive genetic effects using fixed and random effects models stratified by team and ethnic origin, and tested for heterogeneity across strata. A meta-analysis was undertaken that incorporated data from the original genome-wide study as well as subsequent replication studies. Findings: In fixed and random-effects models no associations with any of the 13 SNPs were identified (odds ratios 0·89 to 1·09). Heterogeneity between studies and between ethnic groups was low for all SNPs. Subgroup analyses by age at study entry, ethnic origin, sex, and family history did not show any consistent associations. In our meta-analysis, no SNP showed significant association (summary odds ratios 0·95 to 1.08); there was little heterogeneity except for SNP rs7520966. Interpretation: Our results do not lend support to the finding that the 13 SNPs reported in the original genome-wide association study are genetic susceptibility factors for Parkinson's disease. © 2006 Elsevier Ltd. All rights reserved

A game changer: the use of digital technologies in the management of upper limb rehabilitation

Hemiparesis is a symptom of residual weakness in half of the body, including the upper extremity, which affects the majority of post stroke survivors. Upper limb function is essential for daily life and reduction in movements can lead to tremendous decline in quality of life and independence. Current treatments, such as physiotherapy, aim to improve motor functions, however due to increasing NHS pressure, growing recognition on mental health, and close scrutiny on disease spending there is an urgent need for new approaches to be developed rapidly and sufficient resources devoted to stroke disease. Fortunately, a range of digital technologies has led to revived rehabilitation techniques in captivating and stimulating environments. To gain further insight, a meta-analysis literature search was carried out using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) method. Articles were categorized and pooled into the following groups; pro/anti/neutral for the use of digital technology. Additionally, most literature is rationalised by quantitative and qualitative findings. Findings displayed, the majority of the inclusive literature is supportive of the use of digital technologies in the rehabilitation of upper extremity following stroke. Overall, the review highlights a wide understanding and promise directed into introducing devices into a clinical setting. Analysis of all four categories; (1) Digital Technology, (2) Virtual Reality, (3) Robotics and (4) Leap Motion displayed varying qualities both—pro and negative across each device. Prevailing developments on use of these technologies highlights an evolutionary and revolutionary step into utilizing digital technologies for rehabilitation purposes due to the vast functional gains and engagement levels experienced by patients. The influx of more commercialised and accessible devices could alter stroke recovery further with initial recommendations for combination therapy utilizing conventional and digital resources