https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48705 Wed 29 Mar 2023 17:38:49 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49987 Wed 28 Feb 2024 16:27:03 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:24389 -6 and performed in silico association analyses in an independent sample of ≤1003 cases and 7745 controls. Results: One stroke susceptibility locus at 10q25 reached genome-wide significance in the combined analysis of all samples from the discovery and follow-up stages (rs11196288; odds ratio =1.41; P=9.5x10^-9). The associated locus is in an intergenic region between TCF7L2 and HABP2. In a further analysis in an independent sample, we found that 2 single nucleotide polymorphisms in high linkage disequilibrium with rs11196288 were significantly associated with total plasma factor VII.activating protease levels, a product of HABP2. Conclusions: HABP2, which encodes an extracellular serine protease involved in coagulation, fibrinolysis, and inflammatory pathways, may be a genetic susceptibility locus for early-onset stroke.]]> Wed 15 Dec 2021 16:09:44 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51667 2) based on acute neuroimaging data in a Bayesian hierarchical framework. Lesions encompassing bilateral subcortical nuclei and left-lateralized regions in proximity to the insula explained outcomes across men and women (area under the curve = 0.81). A pattern of left-hemispheric posterior circulation brain regions, combining left hippocampus, precuneus, fusiform and lingual gyrus, occipital pole and latero-occipital cortex, showed a substantially higher relevance in explaining functional outcomes in women compared to men [mean difference of Bayesian posterior distributions (men – women) = −0.295 (90% highest posterior density interval = −0.556 to −0.068)]. Once validated in prospective studies, our findings may motivate a sex-specific approach to clinical stroke management and hold the promise of enhancing outcomes on a population level.]]> Wed 13 Sep 2023 10:08:36 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51991 Tue 26 Sep 2023 11:00:58 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47666 Tue 24 Jan 2023 15:47:40 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:43840 Tue 21 Mar 2023 17:30:07 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:39658 Tue 21 Mar 2023 17:22:55 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51452 2) were modeled within purpose-built Bayesian linear and logistic regression frameworks. Interaction effects between stroke lesions and a high vs low WMH burden were integrated via hierarchical model structures. Models were adjusted for age, age2, sex, total DWI lesion and WMH volumes, and comorbidities. Data were split into derivation and validation cohorts. Results: A total of 928 patients with AIS contributed to acute stroke severity analyses (age: 64.8 [14.5] years, 40% women) and 698 patients to long-term functional outcome analyses (age: 65.9 [14.7] years, 41% women). Stroke severity was mainly explained by lesions focused on bilateral subcortical and left hemispherically pronounced cortical regions across patients with both a high and low WMH burden. Lesions centered on left-hemispheric insular, opercular, and inferior frontal regions and lesions affecting right-hemispheric temporoparietal regions had more pronounced effects on stroke severity in case of high compared with low WMH burden. Unfavorable outcomes were predominantly explained by lesions in bilateral subcortical regions. In difference to the lesion location–specific WMH effects on stroke severity, higher WMH burden increased the odds of unfavorable outcomes independent of lesion location. Discussion: Higher WMH burden may be associated with an increased stroke severity in case of stroke lesions involving left-hemispheric insular, opercular, and inferior frontal regions (potentially linked to language functions) and right-hemispheric temporoparietal regions (potentially linked to attention). Our findings suggest that patients with specific constellations of WMH burden and lesion locations may have greater benefits from acute recanalization treatments. Future clinical studies are warranted to systematically assess this assumption and guide more tailored treatment decisions.]]> Tue 05 Sep 2023 18:01:19 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:52122  2) was modeled in a Bayesian logistic regression framework. Effects of individual brain regions were captured as two compound effects for (i) six bilateral rich club and (ii) all further non-rich club regions. In spatial specificity analyses, we randomized the split into "rich club" and "non-rich club" regions and compared the effect of the actual rich club regions to the distribution of effects from 1000 combinations of six random regions. In sex-specific analyses, we introduced an additional hierarchical level in our model structure to compare male and female-specific rich club effects. A total of 822 patients (age: 64.7[15.0], 39% women) were analyzed. Rich club regions had substantial relevance in explaining unfavorable functional outcome (mean of posterior distribution: 0.08, area under the curve: 0.8). In particular, the rich club-combination had a higher relevance than 98.4% of random constellations. Rich club regions were substantially more important in explaining long-term outcome in women than in men. All in all, lesions in rich club regions were associated with increased odds of unfavorable outcome. These effects were spatially specific and more pronounced in women.]]> Thu 28 Sep 2023 15:03:53 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27208 Sat 24 Mar 2018 07:32:26 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:39002 3 ) was associated with age (β −0.3 [per 14.4 years]), male sex (β 1.0), and prior stroke (β −0.2). In the multivariable outcome model, brain volume was an independent predictor of modified Rankin Scale score (β −0.233), with reduced odds of worse long-term functional outcomes (odds ratio, 0.8; 95% CI, 0.7-0.9) in those with larger brain volumes. Conclusion: Larger brain volume quantified on clinical magnetic resonance imaging of patients with AIS at the time of stroke purports a protective mechanism. The role of brain volume as a prognostic, protective biomarker has the potential to forge new areas of research and advance current knowledge of the mechanisms of poststroke recovery.]]> Mon 29 Jan 2024 17:46:50 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42483 p = 1.1 x 10⁻⁸). By contrast, the causal effect of LDL-C was much weaker for IS (OR 1.12, 95% CI 0.96−1.30, p = 0.14; p for heterogeneity = 2.6 x 10⁻³) and, in particular, for cardioembolic stroke (OR 1.06, 95% CI 0.84−1.33, p = 0.64; p for heterogeneity = 8.6 x 10⁻³) when compared with that for CHD. Conclusions: In contrast with the consistent effects of LDL-C-lowering therapies on IS and CHD, genetic variants that confer lifelong LDL-C differences show a weaker effect on IS than on CHD. The relevance of etiologically distinct IS subtypes may contribute to the differences observed.]]> Fri 26 Aug 2022 13:56:54 AEST ]]>