123 research outputs found
Increasing Post-Myocardial Infarction Heart Failure Incidence in Elderly Patients A Call for Action⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Cardiac Resynchronization With Sequential Biventricular Pacing for the Treatment of Moderate-to-Severe Heart Failure
ObjectivesThe InSync III study evaluated sequential cardiac resynchronization therapy (CRT) in patients with moderate-to-severe heart failure and prolonged QRS.BackgroundSimultaneous CRT improves hemodynamic and clinical performance in patients with moderate-to-severe heart failure (HF) and a wide QRS. Recent evidence suggests that sequentially stimulating the ventricles might provide additional benefit.MethodsThis multicenter, prospective, nonrandomized, six-month trial enrolled a total of 422 patients to determine the effectiveness of sequential CRT in patients with New York Heart Association (NYHA) functional class III or IV HF and a prolonged QRS. The study evaluated: whether patients receiving sequential CRT for six months experienced improvement in 6-min hall walk (6MHW) distance, NYHA functional class, and quality of life (QoL) over control group patients from the reported Multicenter InSync Randomized Clinical Evaluation (MIRACLE) trial; whether sequential CRT increased stroke volume compared to simultaneous CRT; and whether an increase in stroke volume translated into greater clinical improvements compared to patients receiving simultaneous CRT.ResultsInSync III patients experienced greater improvement in 6MHW, NYHA functional class, and QoL at six months compared to control (all p < 0.0001). Optimization of the sequential pacing increased (median 7.3%) stroke volume in 77% of patients. No additional improvement in NYHA functional class or QoL was seen compared to the simultaneous CRT group; however, InSync III patients demonstrated greater exercise capacity.ConclusionsSequential CRT provided most patients with a modest increase in stroke volume above that achieved during simultaneous CRT. Patients receiving sequential CRT had improved exercise capacity, but no change in functional status or QoL
Learning to recommend descriptive tags for questions in social forums
10.1145/2559157ACM Transactions on Information Systems321-ATIS
Low water pH depressed growth and early development of giant freshwater prawn Macrobrachium rosenbergii larvae
Macrobrachium rosenbergii is one of the shellfish species with high aquaculture value due to its increasing market demand. However, the comparatively low production volume compared to demand coupled with the rapid decline of the natural environment, consequently, drives the potential depletion of the wild population. The decrease in water pH related to anthropogenic pollution is one of the most critical factors affecting the early life performances of M. rosenbergii. Therefore, this study was designed to examine the effect of low water pH on feeding, growth and development of M. rosenbergii early life stages. Experimental water pH was set as neutral (7.7 ± 0.4); mild-acidic (6.4 ± 0.5) and acidic (5.4 ± 0.2) with triplication at a stocking density of 2 larvae/L for 30 days. As expected, M. rosenbergii larvae were highly sensitive to acidic pH with no larvae survived beyond 48 h of exposure. Feeding, survival and growth of larvae were adversely affected by mild-acidic pH exposure as compared to neutral pH. Larvae exposed to mild-acidic water pH experienced a prolonged larval period and only metamorphosed to the post-larval stage at day-30. Whilst under neutral water pH, larval that metamorphosed to post-larval was first observed on day-23. The negative impact of decreased pH, even in mild-acidic pH exposure, on the feeding, survival, growth and development of M. rosenbergii larvae highlights the urgency of periodic pH monitoring during M. rosenbergii larviculture
Pan-cancer analysis of whole genomes
Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe
Arsenic, vinyl chloride, viral hepatitis, and hepatic angiosarcoma: A hospital-based study and review of literature in Taiwan
Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples
Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts
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Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing
Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer
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