Association of early life factors and brain tumour risk in a cohort study

Using population-based linked birth and cancer registry data, we investigated whether the risk of brain tumour in childhood (n=155) was associated with perinatal risk factors. This population-based cohort showed that being born into a larger family or to a mother with a history of miscarriage may increase childhood brain tumour risk

Continuation-Passing C: compiling threads to events through continuations

In this paper, we introduce Continuation Passing C (CPC), a programming language for concurrent systems in which native and cooperative threads are unified and presented to the programmer as a single abstraction. The CPC compiler uses a compilation technique, based on the CPS transform, that yields efficient code and an extremely lightweight representation for contexts. We provide a proof of the correctness of our compilation scheme. We show in particular that lambda-lifting, a common compilation technique for functional languages, is also correct in an imperative language like C, under some conditions enforced by the CPC compiler. The current CPC compiler is mature enough to write substantial programs such as Hekate, a highly concurrent BitTorrent seeder. Our benchmark results show that CPC is as efficient, while using significantly less space, as the most efficient thread libraries available.Comment: Higher-Order and Symbolic Computation (2012). arXiv admin note: substantial text overlap with arXiv:1202.324

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

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

Impact of agriculture and urban development on the community structure of wetland birds in East Central Minnesota

Wetlands are one of the fastest disappearing habitats in America. Many wetlands are also being altered due to the effects of various types of land use. Because wetlands provide important habitat for many types of birds, these species can be affected by changes in wetlands due to land use. The impacts of several wetland features, including wetland size, proximity to other wetlands, and vegetation, on bird communities have been debated in the literature. While some studies have found landscape-level features, such as connectivity to other sites to be the most important factors for explaining bird diversity, others have found within-patch characteristics to be more important. It is also unclear how these variables affect rates of nest predation in wetlands. The purpose of this study was to analyze the effects of several wetland features on wetland bird assemblages and nest predation rates at several spatial scales. Bird surveys, vegetation surveys, and measurements of nest predation were conducted at the Cedar Creek Natural History Area in East Bethel, Minnesota. Landscape analyses were conducted at four different spatial scales. Results showed that wetlands are used extensively, not only by species that breed in wetlands, but by species that breed in other environments as well, particularly by woodland birds. Results also indicated that diversity in vegetation structure is associated with an increase in the number of species using wetlands. Low bird species richness in wetlands was associated with increased amounts of agriculture and urban development, which was due to the reduction in trees in agricultural and developed areas. Unlike studies of upland species, birds responded the same way to urban development as to agriculture in the landscape. Features at both the habitat level and at broader landscape scales were found to be significantly correlated with features of the bird communities, indicating the importance of implementing conservation plans at multiple spatial scales. Results suggest that for restoration and construction of wetlands, increasing the variation in both vertical and horizontal structure within the wetland and in the surrounding landscape will increase the bird diversity within the wetland. The results of this study suggest that further encroachment of development and agriculture on wetlands in East Central Minnesota will lead to a decline in wetland bird diversity, particularly with respect to woodland birds that use the wetlands for foraging purposes. The data suggest that woodland obligates will disappear first from the area, followed by sensitive wetland obligates