5 research outputs found

    Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

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    [This corrects the article DOI: 10.1186/s13054-016-1208-6.]

    Pan-cancer analysis of whole genomes

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    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

    Advances in coastal disasters risk management: Lessons from the 2011 Tohoku tsunami

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    The earthquake and tsunami of March 2011 led to death and destruction in coastal areas in Japan. A seminar was held in June 2012 for Japanese and Dutch coastal researchers to discuss lessons for the management of the risks in coastal areas associated with tsunamis, typhoons and storm surges. The seminar has highlighted important practical and theoretical issues in coastal protection, risk and emergency management, and climate change and sea level rise research that are of importance for the Netherlands and Japan and other coastal regions. The performance of the system during historical events gives important lessons for the (re)design of resilient coastal protection systems in the future. It has also been discussed how risk assessments can be utilized to determine how an effective combination of prevention, land use planning and emergency management can be implemented to minimize future risks in the coastal zone.Hydraulic EngineeringCivil Engineering and Geoscience

    Global GRACE Data Assimilation for Groundwater and Drought Monitoring: Advances and Challenges

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    The scarcity of groundwater storage change data at the global scale hinders our ability to monitor groundwater resources effectively. In this study, we assimilate a state-of-the-art terrestrial water storage product derived from Gravity Recovery and Climate Experiment (GRACE) satellite observations into NASA's Catchment land surface model (CLSM) at the global scale, with the goal of generating groundwater storage time series that are useful for drought monitoring and other applications. Evaluation using in situ data from nearly 4,000 wells shows that GRACE data assimilation improves the simulation of groundwater, with estimation errors reduced by 36% and 10% and correlation improved by 16% and 22% at the regional and point scales, respectively. The biggest improvements are observed in regions with large interannual variability in precipitation, where simulated groundwater responds too strongly to changes in atmospheric forcing. The positive impacts of GRACE data assimilation are further demonstrated using observed low-flow data. CLSM and GRACE data assimilation performance is also examined across different permeability categories. The evaluation reveals that GRACE data assimilation fails to compensate for the lack of a groundwater withdrawal scheme in CLSM when it comes to simulating realistic groundwater variations in regions with intensive groundwater abstraction. CLSM-simulated groundwater correlates strongly with 12-month precipitation anomalies in low-latitude and midlatitude areas. A groundwater drought indicator based on GRACE data assimilation generally agrees with other regional-scale drought indicators, with discrepancies mainly in their estimated drought severity.Water Resource

    Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

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