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Effect of Antidepressant Switching vs Augmentation on Remission Among Patients With Major Depressive Disorder Unresponsive to Antidepressant Treatment: The VAST-D Randomized Clinical Trial.
ImportanceLess than one-third of patients with major depressive disorder (MDD) achieve remission with their first antidepressant.ObjectiveTo determine the relative effectiveness and safety of 3 common alternate treatments for MDD.Design, setting, and participantsFrom December 2012 to May 2015, 1522 patients at 35 US Veterans Health Administration medical centers who were diagnosed with nonpsychotic MDD, unresponsive to at least 1 antidepressant course meeting minimal standards for treatment dose and duration, participated in the study. Patients were randomly assigned (1:1:1) to 1 of 3 treatments and evaluated for up to 36 weeks.InterventionsSwitch to a different antidepressant, bupropion (switch group, n = 511); augment current treatment with bupropion (augment-bupropion group, n = 506); or augment with an atypical antipsychotic, aripiprazole (augment-aripiprazole group, n = 505) for 12 weeks (acute treatment phase) and up to 36 weeks for longer-term follow-up (continuation phase).Main outcomes and measuresThe primary outcome was remission during the acute treatment phase (16-item Quick Inventory of Depressive Symptomatology-Clinician Rated [QIDS-C16] score ≤5 at 2 consecutive visits). Secondary outcomes included response (≥50% reduction in QIDS-C16 score or improvement on the Clinical Global Impression Improvement scale), relapse, and adverse effects.ResultsAmong 1522 randomized patients (mean age, 54.4 years; men, 1296 [85.2%]), 1137 (74.7%) completed the acute treatment phase. Remission rates at 12 weeks were 22.3% (n = 114) for the switch group, 26.9% (n = 136)for the augment-bupropion group, and 28.9% (n = 146) for the augment-aripiprazole group. The augment-aripiprazole group exceeded the switch group in remission (relative risk [RR], 1.30 [95% CI, 1.05-1.60]; P = .02), but other remission comparisons were not significant. Response was greater for the augment-aripiprazole group (74.3%) than for either the switch group (62.4%; RR, 1.19 [95% CI, 1.09-1.29]) or the augment-bupropion group (65.6%; RR, 1.13 [95% CI, 1.04-1.23]). No significant treatment differences were observed for relapse. Anxiety was more frequent in the 2 bupropion groups (24.3% in the switch group [n = 124] vs 16.6% in the augment-aripiprazole group [n = 84]; and 22.5% in augment-bupropion group [n = 114]). Adverse effects more frequent in the augment-aripiprazole group included somnolence, akathisia, and weight gain.Conclusions and relevanceAmong a predominantly male population with major depressive disorder unresponsive to antidepressant treatment, augmentation with aripiprazole resulted in a statistically significant but only modestly increased likelihood of remission during 12 weeks of treatment compared with switching to bupropion monotherapy. Given the small effect size and adverse effects associated with aripiprazole, further analysis including cost-effectiveness is needed to understand the net utility of this approach.Trial registrationclinicaltrials.gov Identifier: NCT01421342
Inhibiting DNA Methylation Causes an Interferon Response in Cancer via dsRNA Including Endogenous Retroviruses
sPlotOpen:an environmentally balanced, open-access, global dataset of vegetation plots
Abstract
Motivation: Assessing biodiversity status and trends in plant communities is critical for understanding, quantifying and predicting the effects of global change on ecosystems. Vegetation plots record the occurrence or abundance of all plant species co-occurring within delimited local areas. This allows species absences to be inferred, information seldom provided by existing global plant datasets. Although many vegetation plots have been recorded, most are not available to the global research community. A recent initiative, called ‘sPlot’, compiled the first global vegetation plot database, and continues to grow and curate it. The sPlot database, however, is extremely unbalanced spatially and environmentally, and is not open-access. Here, we address both these issues by (a) resampling the vegetation plots using several environmental variables as sampling strata and (b) securing permission from data holders of 105 local-to-regional datasets to openly release data. We thus present sPlotOpen, the largest open-access dataset of vegetation plots ever released. sPlotOpen can be used to explore global diversity at the plant community level, as ground truth data in remote sensing applications, or as a baseline for biodiversity monitoring.
Main types of variable contained: Vegetation plots (n = 95,104) recording cover or abundance of naturally co-occurring vascular plant species within delimited areas. sPlotOpen contains three partially overlapping resampled datasets (c. 50,000 plots each), to be used as replicates in global analyses. Besides geographical location, date, plot size, biome, elevation, slope, aspect, vegetation type, naturalness, coverage of various vegetation layers, and source dataset, plot-level data also include community-weighted means and variances of 18 plant functional traits from the TRY Plant Trait Database.
Spatial location and grain: Global, 0.01–40,000 m².
Time period and grain: 1888–2015, recording dates.
Major taxa and level of measurement: 42,677 vascular plant taxa, plot-level records.
Software format: Three main matrices (.csv), relationally linked
Analysis of the genome sequence of the flowering plant Arabidopsis thaliana
The flowering plant Arabidopsis thaliana is an important model system for identifying genes and determining their functions. Here we report the analysis of the genomic sequence of Arabidopsis. The sequenced regions cover 115.4 megabases of the 125-megabase genome and extend into centromeric regions. The evolution of Arabidopsis involved a whole-genome duplication, followed by subsequent gene loss and extensive local gene duplications, giving rise to a dynamic genome enriched by lateral gene transfer from a cyanobacterial-like ancestor of the plastid. The genome contains 25,498 genes encoding proteins from 11,000 families, similar to the functional diversity of Drosophila and Caenorhabditis elegans - the other sequenced multicellular eukaryotes. Arabidopsis has many families of new proteins but also lacks several common protein families, indicating that the sets of common proteins have undergone differential expansion and contraction in the three multicellular eukaryotes. This is the first complete genome sequence of a plant and provides the foundations for more comprehensive comparison of conserved processes in all eukaryotes, identifying a wide range of plant-specific gene functions and establishing rapid systematic ways to identify genes for crop improvement
Characterization and Drug Resistance Patterns of Ewing's Sarcoma Family Tumor Cell Lines
sPlot:a new tool for global vegetation analyses
Abstract
Aims: Vegetation‐plot records provide information on the presence and cover or abundance of plants co‐occurring in the same community. Vegetation‐plot data are spread across research groups, environmental agencies and biodiversity research centers and, thus, are rarely accessible at continental or global scales. Here we present the sPlot database, which collates vegetation plots worldwide to allow for the exploration of global patterns in taxonomic, functional and phylogenetic diversity at the plant community level.
Results: sPlot version 2.1 contains records from 1,121,244 vegetation plots, which comprise 23,586,216 records of plant species and their relative cover or abundance in plots collected worldwide between 1885 and 2015. We complemented the information for each plot by retrieving climate and soil conditions and the biogeographic context (e.g., biomes) from external sources, and by calculating community‐weighted means and variances of traits using gap‐filled data from the global plant trait database TRY. Moreover, we created a phylogenetic tree for 50,167 out of the 54,519 species identified in the plots. We present the first maps of global patterns of community richness and community‐weighted means of key traits.
Conclusions: The availability of vegetation plot data in sPlot offers new avenues for vegetation analysis at the global scale
Analysis of Outcomes in Ischemic vs Nonischemic Cardiomyopathy in Patients With Atrial Fibrillation A Report From the GARFIELD-AF Registry
IMPORTANCE Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes