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

Controlling the high temperature mechanical behavior of Al alloys by precipitation and severe straining

The aim of this work was to investigate the influence of the precipitate distribution on the microstructure and on the room and high temperature mechanical properties of an age-hardenable aluminium AA6082 alloy following severe straining by high-pressure torsion (HPT). With this goal, specimens in the as-cast and T6 peak-aged conditions were processed by HPT using 0.5, 1 and 5 turns at room temperature. At high strain levels (?&gt;100), similar saturation grain sizes (~250 nm), high-angle boundary fractions (~80%) and hardness values (Hv~160) were obtained for both initial conditions. Grain refinement led to significant strengthening and to good ductility values at room temperature. Analysis by TEM and EDS elemental mapping revealed that HPT processing of the as-cast condition led to fracture of the stable ?-phase into many small precipitates located preferentially along grain boundaries and triple junctions. By contrast, HPT processing of the T6 peak-aged specimens revealed a partial dissolution of the needle-shaped nanoprecipitates. The different evolutions of the precipitate distributions following straining in the as-cast and peak-aged conditions gave rise to dramatic differences in the mechanical properties and the operative deformation mechanisms at warm temperatures. These results provide evidence that the high temperature mechanical behavior of age-hardenable Al alloys may be conveniently controlled by altering the precipitate distribution followed by severe straining

The role of tandem duplicator phenotype in tumour evolution in high-grade serous ovarian cancer

High-grade serous ovarian carcinoma (HGSOC) is characterized by genomic instability, ubiquitous TP53 loss, and frequent development of platinum resistance. Loss of homologous recombination (HR) is a mutator phenotype present in 50% of HGSOCs and confers hypersensitivity to platinum treatment. We asked which other mutator phenotypes are present in HGSOC and how they drive the emergence of platinum resistance. We performed whole-genome paired-end sequencing on a model of two HGSOC cases, each consisting of a pair of cell lines established before and after clinical resistance emerged, to describe their structural variants (SVs) and to infer their ancestral genomes as the SVs present within each pair. The first case (PEO1/PEO4), with HR deficiency, acquired translocations and small deletions through its early evolution, but a revertant BRCA2 mutation restoring HR function in the resistant lineage re-stabilized its genome and reduced platinum sensitivity. The second case (PEO14/PEO23) had 216 tandem duplications and did not show evidence of HR or mismatch repair deficiency. By comparing the cell lines to the tissues from which they originated, we showed that the tandem duplicator mutator phenotype arose early in progression in vivo and persisted throughout evolution in vivo and in vitro, which may have enabled continual evolution. From the analysis of SNP array data from 454 HGSOC cases in The Cancer Genome Atlas series, we estimate that 12.8% of cases show patterns of aberrations similar to the tandem duplicator, and this phenotype is mutually exclusive with BRCA1/2 carrier mutations

The Emergence of Ontogenic Scaffolding in a Stochastic Development Environment

Evolutionary designs based upon Artificial Ontogenies are beginning to cross from virtual to real environments. In such systems the evolved genotype is an indirect, procedural representation of the final structure. To date, most Artificial Ontogenies have relied upon an error-free development process to generate their phenotypic structure