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

The ‘Nate Silver effect’ on political journalism: Gatecrashers, gatekeepers, and changing newsroom practices around coverage of public opinion polls

This article presents findings from 41 in-depth interviews with political journalists, media analysts, and public opinion pollsters in the United States. These interviews document several trends in how journalists assess and cover public opinion. The article shows (1) a growing interest in and reliance on polling aggregator websites fueled by demands for precise predictions, (2) the erosion of news organizations’ abilities to assert independent gatekeeping standards around individual poll results, (3) concerns about the level of in-house expertise within newsrooms to adjudicate between surveys, and (4) changing attitudes about the importance of gatekeeping around public opinion data. These findings reflect an increasingly complex landscape of opinion data, which conventional news organizations appear ill-equipped to navigate

Effect of storage in water and thermocycling on hardness and roughness of resin materials for temporary restorations

PURPOSE: This study evaluated the effect of storage in water and thermocycling on hardness and roughness of resin materials for temporary restorations. MATERIAL AND METHODS: Three acrylic resins (Dencor-De, Duralay-Du, and Vipi Cor-VC) were selected and one composite resin (Opallis-Op) was used as a parameter for comparison. The materials were prepared according to the manufacturers' instructions and were placed in stainless steel moulds (20 mm in diameter and 5 mm thick). Thirty samples of each resin were made and divided into three groups (n = 10) according to the moment of Vickers hardness (VHN) and roughness (Ra) analyses: C (control group): immediately after specimen preparation; Sw: after storage in distilled water at 37 °C for 24 hours; Tc: after thermocycling (3000 cycles; 5-55 °C, 30 seconds dwell time). Data were submitted to 2-way ANOVA followed by Tukey's test (&#945; = 0.05). RESULTS: Op resin had higher surface hardness values (p < 0.0001; 25.4 ± 3.4) than the other ones (De = 4.5 ± 0.6; Du = 5.5 ± 0.4; VC = 6.1 ± 0.9). There was no statistical difference (p > 0.05) in roughness among materials (De = 0.31 ± 0.07; Du = 0.51 ± 0.20; VC = 0.41 ± 0.15; Op = 0.42 ± 0.18). Storage in water did not change hardness and roughness of the tested materials (p > 0.05). There was a significant increase in roughness after thermocycling (p < 0.05), except for material Du, which showed no significant change in roughness in any evaluated period (p = 0.99). CONCLUSION: Thermocycling increased the roughness in most tested materials without affecting hardness, while storage in water had no significant effect in the evaluated properties