https://ogma.newcastle.edu.au/vital/access/ /manager/Index en-au 5 A phase III, multi-arm multi-stage covariate-adjusted response-adaptive randomized trial to determine optimal early mobility training after stroke (AVERT DOSE) https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51317  2) and hemorrhagic stroke. With four arms per stratum (reference arm retained throughout), only the single treatment arm demonstrating the highest proportion of favorable outcomes at the first stage will proceed to the second stage in each stratum, resulting in a final comparison with the reference arm. Three prognostic covariates of age, geographic region and reperfusion interventions, as well as previously observed mRS 0-2 responses inform the adaptive randomization procedure. Participants randomized receive prespecified mobility training regimens (functional task-specific), provided by physiotherapists/nurses until discharge or 14 days. Interventions replace usual mobility training. Fifty hospitals in seven countries (Australia, Malaysia, United Kingdom, Ireland, India, Brazil, Singapore) are expected to participate. Summary: Our novel adaptive trial design will evaluate a wider variety of mobility regimes than a traditional two-arm design. The data-driven adaptions during the trial will enable a more efficient evaluation to determine the optimal early mobility intervention for patients with mild and moderate ischemic stroke.]]> Wed 28 Feb 2024 15:05:25 AEDT ]]> Genome-wide studies of verbal declarative memory in nondemented older people: the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27385 -6) was sought in 10,617 participants of European descent, 3811 African-Americans, and 1561 young adults. Results: rs4420638, near APOE, was associated with poorer delayed recall performance in discovery (p = 5.57 x 10-10) and replication cohorts (p = 5.65 x 10-8). This association was stronger for paragraph than word list delayed recall and in the oldest persons. Two associations with specific tests, in subsets of the total sample, reached genome-wide significance in combined analyses of discovery and replication (rs11074779 [HS3ST4], p = 3.11 x 10-8, and rs6813517 [SPOCK3], p = 2.58 x 10-8) near genes involved in immune response. A genetic score combining 58 independent suggestive memory risk variants was associated with increasing Alzheimer disease pathology in 725 autopsy samples. Association of memory risk loci with gene expression in 138 human hippocampus samples showed cis-associations with WDR48 and CLDN5, both related to ubiquitin metabolism. Conclusions: This largest study to date exploring the genetics of memory function in ~40,000 older individuals revealed genome-wide associations and suggested an involvement of immune and ubiquitin pathways.]]> Sat 24 Mar 2018 07:34:11 AEDT ]]>