The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Management matter? Effects of charcoal production management on woodland regeneration in Senegal

In Senegal, as in many parts of Africa, nearly 95% of its growing urban population depends on charcoal as their primary cooking energy. Extraction of wood for charcoal production is perceived to drive forest degradation. The Senegalese government and international donor agencies have created different forest management types with the ultimate goal of sustainably managing forests. This research combines local ecological knowledge, ecological surveys and remote sensing analysis to better understand questions related to how extraction for charcoal production and forest management affect Senegalese forests. Information derived from 36 semi-structured interviews suggests that the forests are degrading, but are depended on for income, grazing and energy. Interviewees understand the rules governing forest management types, but felt they had limited power or responsibility to enforce forest regulations. Ecological survey results confirmed that plots harvested for charcoal production are significantly different in forest structure and tree species composition than undisturbed sites. Across harvested and undisturbed and within forest management types the Combretum glutinosum species dominated (53% of all individuals and the primary species used for charcoal production) and demonstrated robust regenerative capacity. Few large, hardwood or fruiting trees were observed and had insufficient regenerative capacity to replace current populations. Species diversity was higher in co-managed areas, but declined after wood was harvested for charcoal production. Proximity to villages, roads and park edges in harvested and undisturbed plots and within forest management types had little impact on forest structure and tree diversity patterns with the harvesting of trees for charcoal spread consistently throughout the landscape. Remote sensing analysis with the MISR derived k(red) parameter demonstrated its ability to accurately classify broad land classes and showed potential when differentiating between pre- and post-harvest conditions over a three year time period, but could not accurately detect subtle changes in forest cover of known harvest time since last harvest in a single MISR scene. This research demonstrated the utility of multidisciplinary research in assessing the effects of charcoal production and forest management types on Senegalese forests; concluding that the effects of charcoal production on forest characteristics and regenerative capacity are consistent throughout all forest management types

Apixaban for Extended Treatment of Venous Thromboembolism

BACKGROUND: Apixaban, an oral factor Xa inhibitor that can be administered in a simple, fixed-dose regimen, may be an option for the extended treatment of venous thromboembolism. METHODS: In this randomized, double-blind study, we compared two doses of apixaban (2.5 mg and 5 mg, twice daily) with placebo in patients with venous thromboembolism who had completed 6 to 12 months of anticoagulation therapy and for whom there was clinical equipoise regarding the continuation or cessation of anticoagulation therapy. The study drugs were administered for 12 months. RESULTS: A total of 2486 patients underwent randomization, of whom 2482 were included in the intention-to-treat analyses. Symptomatic recurrent venous thromboembolism or death from venous thromboembolism occurred in 73 of the 829 patients (8.8%) who were receiving placebo, as compared with 14 of the 840 patients (1.7%) who were receiving 2.5 mg of apixaban (a difference of 7.2 percentage points; 95% confidence interval [CI], 5.0 to 9.3) and 14 of the 813 patients (1.7%) who were receiving 5 mg of apixaban (a difference of 7.0 percentage points; 95% CI, 4.9 to 9.1) (P<0.001 for both comparisons). The rates of major bleeding were 0.5% in the placebo group, 0.2% in the 2.5-mg apixaban group, and 0.1% in the 5-mg apixaban group. The rates of clinically relevant nonmajor bleeding were 2.3% in the placebo group, 3.0% in the 2.5-mg apixaban group, and 4.2% in the 5-mg apixaban group. The rate of death from any cause was 1.7% in the placebo group, as compared with 0.8% in the 2.5-mg apixaban group and 0.5% in the 5-mg apixaban group. CONCLUSIONS: Extended anticoagulation with apixaban at either a treatment dose (5 mg) or a thromboprophylactic dose (2.5 mg) reduced the risk of recurrent venous thromboembolism without increasing the rate of major bleeding. (Funded by Bristol-Myers Squibb and Pfizer; AMPLIFY-EXT ClinicalTrials.gov number, NCT00633893.)