INTRODUCTION: Stroke is an established risk factor for all-cause dementia, though meta-analyses are needed to quantify this risk. METHODS: We searched Medline, PsycINFO and Embase for studies assessing prevalent or incident stroke versus a no-stroke comparison group and the risk of all-cause dementia. Random effects meta-analysis was used to pool adjusted estimates across studies and meta-regression was used to investigate potential effect modifiers. RESULTS: We identified 36 studies of prevalent stroke (1.9 million participants) and 12 studies of incident stroke (1.3 million participants). For prevalent stroke, the pooled hazard ratio for all-cause dementia was 1.69 (95% CI: 1.49–1.92; p<0.00001; I2 = 87%). For incident stroke, the pooled risk ratio was 2.18 (95% CI: 1.90–2.50; p<0.00001; I2 = 88%). Study characteristics did not modify these associations, with the exception of sex which explained 50.2% of between-study heterogeneity for prevalent stroke. DISCUSSION: Stroke is a strong, independent, and potentially modifiable risk factor for all-cause dementia.

Background: Median overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is ~4 years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for OS in patients with HGSOC. Patients and methods: Expression of 513 genes, selected from a meta-analysis of 1455 tumours and other candidates, was measured using NanoString technology from formalin-fixed paraffin-embedded tumour tissue collected from 3769 women with HGSOC from multiple studies. Elastic net regularization for survival analysis was applied to develop a prognostic model for 5-year OS, trained on 2702 tumours from 15 studies and evaluated on an independent set of 1067 tumours from six studies. Results: Expression levels of 276 genes were associated with OS (false discovery rate < 0.05) in covariate-adjusted single-gene analyses. The top five genes were TAP1, ZFHX4, CXCL9, FBN1 and PTGER3 ( P < 0.001). The best performing prognostic signature included 101 genes enriched in pathways with treatment implications. Each gain of one standard deviation in the gene expression score conferred a greater than twofold increase in risk of death [hazard ratio (HR) 2.35, 95% confidence interval (CI) 2.02–2.71; P < 0.001]. Median survival [HR (95% CI)] by gene expression score quintile was 9.5 (8.3 to –), 5.4 (4.6–7.0), 3.8 (3.3–4.6), 3.2 (2.9–3.7) and 2.3 (2.1–2.6) years. Conclusion: The OTTA-SPOT (Ovarian Tumor Tissue Analysis consortium - Stratified Prognosis of Ovarian Tumours) gene expression signature may improve risk stratification in clinical trials by identifying patients who are least likely to achieve 5-year survival. The identified novel genes associated with the outcome may also yield opportunities for the development of targeted therapeutic approaches.

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Poaching is rapidly extirpating African forest elephants (Loxodonta cyclotis) from most of their historical range, leaving vast areas of elephant-free tropical forest. Elephants are ecological engineers that create and maintain forest habitat; thus, their loss will have large consequences for the composition and structure of Afrotropical forests. Through a comprehensive literature review, we evaluated the roles of forest elephants in seed dispersal, nutrient recycling, and herbivory and physical damage to predict the cascading ecological effects of their population declines. Loss of seed dispersal by elephants will favor tree species dispersed abiotically and by smaller dispersal agents, and tree species composition will depend on the downstream effects of changes in elephant nutrient cycling and browsing. Loss of trampling and herbivory of seedlings and saplings will result in high tree density with release from browsing pressures. Diminished seed dispersal by elephants and high stem density are likely to reduce the recruitment of large trees and thus increase homogeneity of forest structure and decrease carbon stocks. The loss of ecological services by forest elephants likely means Central African forests will be more like Neotropical forests, from which megafauna were extirpated thousands of years ago. Without intervention, as much as 96% of Central African forests will have modified species composition and structure as elephants are compressed into remaining protected areas. Stopping elephant poaching is an urgent first step to mitigating these effects, but long-term conservation will require land-use planning that incorporates elephant habitat into forested landscapes that are being rapidly transformed by industrial agriculture and logging.

Systolic interarm differences in blood pressure have been associated with all-cause mortality and cardiovascular disease. We undertook individual participant data meta-analyses to (1) quantify independent associations of systolic interarm difference with mortality and cardiovascular events; (2) develop and validate prognostic models incorporating interarm difference, and (3) determine whether interarm difference remains associated with risk after adjustment for common cardiovascular risk scores. We searched for studies recording bilateral blood pressure and outcomes, established agreements with collaborating authors, and created a single international dataset: the Inter-arm Blood Pressure Difference - Individual Participant Data (INTERPRESS-IPD) Collaboration. Data were merged from 24 studies (53 827 participants). Systolic interarm difference was associated with all-cause and cardiovascular mortality: continuous hazard ratios 1.05 (95% CI, 1.02–1.08) and 1.06 (95% CI, 1.02–1.11), respectively, per 5 mm Hg systolic interarm difference. Hazard ratios for all-cause mortality increased with interarm difference magnitude from a ≥5 mm Hg threshold (hazard ratio, 1.07 [95% CI, 1.01–1.14]). Systolic interarm differences per 5 mm Hg were associated with cardiovascular events in people without preexisting disease, after adjustment for Atherosclerotic Cardiovascular Disease (hazard ratio, 1.04 [95% CI, 1.00–1.08]), Framingham (hazard ratio, 1.04 [95% CI, 1.01–1.08]), or QRISK cardiovascular disease risk algorithm version 2 (QRISK2) (hazard ratio, 1.12 [95% CI, 1.06–1.18]) cardiovascular risk scores. Our findings confirm that systolic interarm difference is associated with increased all-cause mortality, cardiovascular mortality, and cardiovascular events. Blood pressure should be measured in both arms during cardiovascular assessment. A systolic interarm difference of 10 mm Hg is proposed as the upper limit of normal. Registration: URL: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42015031227