Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Microbial response to salinity change in Lake Chaka, a hypersaline lake on Tibetan plateau

Previous investigations of the salinity effects on the microbial community composition have largely been limited to dynamic estuaries and coastal solar salterns. In this study, the effects of salinity and mineralogy on microbial community composition was studied by using a 900-cm sediment core collected from a stable, inland hypersaline lake, Lake Chaka, on the Tibetan Plateau, north-western China. This core, spanning a time of 17 000 years, was unique in that it possessed an entire range of salinity from freshwater clays and silty sands at the bottom to gypsum and glauberite in the middle, to halite at the top. Bacterial and archaeal communities were studied along the length of this core using an integrated approach combining mineralogy and geochemistry, molecular microbiology (16S rRNA gene analysis and quantitative polymerase chain reaction), cultivation and lipid biomarker analyses. Systematic changes in microbial community composition were correlated with the salinity gradient, but not with mineralogy. Bacterial community was dominated by the Firmicutes-related environmental sequences and known species (including sulfate-reducing bacteria) in the freshwater sediments at the bottom, but by halophilic and halotolerant Betaproteobacteria and Bacteroidetes in the hypersaline sediments at the top. Succession of proteobacterial groups along the salinity gradient, typically observed in free-living bacterial communities, was not observed in the sediment-associated community. Among Archaea, the Crenarchaeota were predominant in the bottom freshwater sediments, but the halophilic Halobacteriales of the Euryarchaeota was the most important group in the hypersaline sediments. Multiple isolates were obtained along the whole length of the core, and their salinity tolerance was consistent with the geochemical conditions. Iron-reducing bacteria were isolated in the freshwater sediments, which were capable of reducing structural Fe(III) in the Fe(III)-rich clay minerals predominant in the source sediment. These data have important implications for understanding how microorganisms respond to increased salinity in stable, inland water bodies. © 2007 The Authors.link_to_subscribed_fulltex

Pervasive chromosomal instability and karyotype order in tumour evolution

Chromosomal instability in cancer consists of dynamic changes to the number and structure of chromosomes. The resulting diversity in somatic copy number alterations (SCNAs) may provide the variation necessary for tumour evolution. Here we use multi-sample phasing and SCNA analysis of 1,421 samples from 394 tumours across 22 tumour types to show that continuous chromosomal instability results in pervasive SCNA heterogeneity. Parallel evolutionary events, which cause disruption in the same genes (such as BCL9, MCL1, ARNT (also known as HIF1B), TERT and MYC) within separate subclones, were present in 37% of tumours. Most recurrent losses probably occurred before whole-genome doubling, that was found as a clonal event in 49% of tumours. However, loss of heterozygosity at the human leukocyte antigen (HLA) locus and loss of chromosome 8p to a single haploid copy recurred at substantial subclonal frequencies, even in tumours with whole-genome doubling, indicating ongoing karyotype remodelling. Focal amplifications that affected chromosomes 1q21 (which encompasses BCL9, MCL1 and ARNT), 5p15.33 (TERT), 11q13.3 (CCND1), 19q12 (CCNE1) and 8q24.1 (MYC) were frequently subclonal yet appeared to be clonal within single samples. Analysis of an independent series of 1,024 metastatic samples revealed that 13 focal SCNAs were enriched in metastatic samples, including gains in chromosome 8q24.1 (encompassing MYC) in clear cell renal cell carcinoma and chromosome 11q13.3 (encompassing CCND1) in HER2(+) breast cancer. Chromosomal instability may enable the continuous selection of SCNAs, which are established as ordered events that often occur in parallel, throughout tumour evolution

Observation in the MINOS far detector of the shadowing of cosmic rays by the sun and moon

The shadowing of cosmic ray primaries by the moon and sun was observed by the MINOS far detector at a depth of 2070 mwe using 83.54 million cosmic ray muons accumulated over 1857.91 live-days. The shadow of the moon was detected at the 5.6 σ level and the shadow of the sun at the 3.8 σ level using a log-likelihood search in celestial coordinates. The moon shadow was used to quantify the absolute astrophysical pointing of the detector to be 0.17 ± 0.12°. Hints of interplanetary magnetic field effects were observed in both the sun and moon shadow. © 2010 Elsevier B.V. All rights reserved

Observation in the MINOS far detector of the shadowing of cosmic rays by the sun and moon

The shadowing of cosmic ray primaries by the moon and sun was observed by the MINOS far detector at a depth of 2070 mwe using 83.54 million cosmic ray muons accumulated over 1857.91 live-days. The shadow of the moon was detected at the 5.6 σ level and the shadow of the sun at the 3.8 σ level using a log-likelihood search in celestial coordinates. The moon shadow was used to quantify the absolute astrophysical pointing of the detector to be 0.17 ± 0.12°. Hints of interplanetary magnetic field effects were observed in both the sun and moon shadow