A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

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

Reassessing global change research priorities in mediterranean terrestrial ecosystems: How far have we come and where do we go from here?

Aim: Mediterranean terrestrial ecosystems serve as reference laboratories for the investigation of global change because of their transitional climate, the high spatiotemporal variability of their environmental conditions, a rich and unique biodiversity and a wide range of socio-economic conditions. As scientific development and environmental pressures increase, it is increasingly necessary to evaluate recent progress and to challenge research priorities in the face of global change. Location: Mediterranean terrestrial ecosystems. Methods: This article revisits the research priorities proposed in a 1998 assessment. Results: A new set of research priorities is proposed: (1) to establish the role of the landscape mosaic on fire-spread; (2) to further research the combined effect of different drivers on pest expansion; (3) to address the interaction between drivers of global change and recent forest management practices; (4) to obtain more realistic information on the impacts of global change and ecosystem services; (5) to assess forest mortality events associated with climatic extremes; (6) to focus global change research on identifying and managing vulnerable areas; (7) to use the functional traits concept to study resilience after disturbance; (8) to study the relationship between genotypic and phenotypic diversity as a source of forest resilience; (9) to understand the balance between C storage and water resources; (10) to analyse the interplay between landscape-scale processes and biodiversity conservation; (11) to refine models by including interactions between drivers and socio-economic contexts; (12) to understand forest-atmosphere feedbacks; (13) to represent key mechanisms linking plant hydraulics with landscape hydrology. Main conclusions: (1) The interactive nature of different global change drivers remains poorly understood. (2) There is a critical need for the rapid development of regional- and global-scale models that are more tightly connected with large-scale experiments, data networks and management practice. (3) More attention should be directed to drought-related forest decline and the current relevance of historical land use

Spatial Analysis of Childhood Cancer: A Case/Control Study

Childhood cancer was the leading cause of death among children aged 1-14 years for 2012 in Spain. Leukemia has the highest incidence, followed by tumors of the central nervous system (CNS) and lymphomas (Hodgkin lymphoma, HL, and Non-Hodgkin's lymphoma, NHL). Spatial distribution of childhood cancer cases has been under concern with the aim of identifying potential risk factors.The two objectives are to study overall spatial clustering and cluster detection of cases of the three main childhood cancer causes, looking to increase etiological knowledge.We ran a case-control study. The cases were children aged 0 to 14 diagnosed with leukemia, lymphomas (HL and NHL) or CNS neoplasm in five Spanish regions for the period 1996-2011. As a control group, we used a sample from the Birth Registry matching every case by year of birth, autonomous region of residence and sex with six controls. We geocoded and validated the address of the cases and controls. For our two objectives we used two different methodologies. For the first, for overall spatial clustering detection, we used the differences of K functions from the spatial point patterns perspective proposed by Diggle and Chetwynd and the second, for cluster detection, we used the spatial scan statistic proposed by Kulldorff with a level for statistical significance of 0.05.We had 1062 cases of leukemia, 714 cases of CNS, 92 of HL and 246 of NHL. Accordingly we had 6 times the number of controls, 6372 controls for leukemia, 4284 controls for CNS, 552 controls for HL and 1476 controls for NHL. We found variations in the estimated empirical D(s) for the different regions and cancers, including some overall spatial clustering for specific regions and distances. We did not find statistically significant clusters.The variations in the estimated empirical D(s) for the different regions and cancers could be partially explained by the differences in the spatial distribution of the population; however, according to the literature, we cannot discard environmental hazards or infections agents in the etiology of these cancers

Mortality after surgery in Europe: a 7 day cohort study

Background: Clinical outcomes after major surgery are poorly described at the national level. Evidence of heterogeneity between hospitals and health-care systems suggests potential to improve care for patients but this potential remains unconfirmed. The European Surgical Outcomes Study was an international study designed to assess outcomes after non-cardiac surgery in Europe.Methods: We did this 7 day cohort study between April 4 and April 11, 2011. We collected data describing consecutive patients aged 16 years and older undergoing inpatient non-cardiac surgery in 498 hospitals across 28 European nations. Patients were followed up for a maximum of 60 days. The primary endpoint was in-hospital mortality. Secondary outcome measures were duration of hospital stay and admission to critical care. We used χ² and Fisher’s exact tests to compare categorical variables and the t test or the Mann-Whitney U test to compare continuous variables. Significance was set at p<0·05. We constructed multilevel logistic regression models to adjust for the differences in mortality rates between countries.Findings: We included 46 539 patients, of whom 1855 (4%) died before hospital discharge. 3599 (8%) patients were admitted to critical care after surgery with a median length of stay of 1·2 days (IQR 0·9–3·6). 1358 (73%) patients who died were not admitted to critical care at any stage after surgery. Crude mortality rates varied widely between countries (from 1·2% [95% CI 0·0–3·0] for Iceland to 21·5% [16·9–26·2] for Latvia). After adjustment for confounding variables, important differences remained between countries when compared with the UK, the country with the largest dataset (OR range from 0·44 [95% CI 0·19 1·05; p=0·06] for Finland to 6·92 [2·37–20·27; p=0·0004] for Poland).Interpretation: The mortality rate for patients undergoing inpatient non-cardiac surgery was higher than anticipated. Variations in mortality between countries suggest the need for national and international strategies to improve care for this group of patients.Funding: European Society of Intensive Care Medicine, European Society of Anaesthesiology