Microbial community structure across the tree of life in the extreme Río Tinto

Understanding biotic versus abiotic forces that shape community structure is a fundamental aim of microbial ecology. The acidic and heavy metal extreme Río Tinto (RT) in southwestern Spain provides a rare opportunity to conduct an ecosystem-wide biodiversity inventory at the level of all three domains of life, because diversity there is low and almost exclusively microbial. Despite improvements in high-throughput DNA sequencing, environmental biodiversity studies that use molecular metrics and consider entire ecosystems are rare. These studies can be prohibitively expensive if domains are considered separately, and differences in copy number of eukaryotic ribosomal RNA genes can bias estimates of relative abundances of phylotypes recovered. In this study we have overcome these barriers (1) by targeting all three domains in a single polymerase chain reaction amplification and (2) by using a replicated sampling design that allows for incidence-based methods to extract measures of richness and carry out downstream analyses that address community structuring effects. Our work showed that combined bacterial and archaeal richness is an order of magnitude higher than eukaryotic richness. We also found that eukaryotic richness was highest at the most extreme sites, whereas combined bacterial and archaeal richness was highest at less extreme sites. Quantitative community phylogenetics showed abiotic forces to be primarily responsible for shaping the RT community structure. Canonical correspondence analysis revealed co-occurrence of obligate symbionts and their putative hosts that may contribute to biotic forces shaping community structure and may further provide a possible mechanism for persistence of certain low-abundance bacteria encountered in the RT

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.)