An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Contingent self-definition and amorphous regions: a dynamic approach to place brand architecture

This article explores the concept of contingent self-definition, whereby place brands employ flexible self-definitional approaches in constructing their place brand architecture. Adopting a view of regions as social constructs, the article builds on and extends previous work on place brand architecture by identifying the underlying factors that drive contingent self-definition decisions. Based on an empirical study of professionals tasked with managing region brands in the Netherlands, eleven factors are identified as drivers of contingent self-definition by place brands. These factors are grouped into four thematic categories: i) external perceptions, ii) proximity, iii) brand relationships, and iv) politics and power. A dynamic approach to place brand architecture is advocated, foregrounding the amorphous character of regions as social constructs that defy reification solely as fixed territorial-administrative spaces

Hemispheric asymmetry in ocean change and the productivity of ecosystem sentinels

Climate change and other human activities are causing profound effects on marine ecosystem productivity. We show that the breeding success of seabirds is tracking hemispheric differences in ocean warming and human impacts, with the strongest effects on fish-eating, surface-foraging species in the north. Hemispheric asymmetry suggests the need for ocean management at hemispheric scales. For the north, tactical, climate-based recovery plans for forage fish resources are needed to recover seabird breeding productivity. In the south, lower-magnitude change in seabird productivity presents opportunities for strategic management approaches such as large marine protected areas to sustain food webs and maintain predator productivity. Global monitoring of seabird productivity enables the detection of ecosystem change in remote regions and contributes to our understanding of marine climate impacts on ecosystems

Hemispheric asymmetry in ocean change and the productivity of ecosystem sentinels

Climate change and other human activities are causing profound effects on marine ecosystem productivity. We show that the breeding success of seabirds is tracking hemispheric differences in ocean warming and human impacts, with the strongest effects on fish-eating, surface-foraging species in the north. Hemispheric asymmetry suggests the need for ocean management at hemispheric scales. For the north, tactical, climate-based recovery plans for forage fish resources are needed to recover seabird breeding productivity. In the south, lower-magnitude change in seabird productivity presents opportunities for strategic management approaches such as large marine protected areas to sustain food webs and maintain predator productivity. Global monitoring of seabird productivity enables the detection of ecosystem change in remote regions and contributes to our understanding of marine climate impacts on ecosystems

Mechanical properties, microstructure and crystallographic texture of magnesium AZ91-D alloy welded by Friction Stir Welding (FSW)

The objective of the study was to characterize the properties of a magnesium alloy welded by friction stir welding (FSW). The results led to a better understanding of the relationship between this process and the microstructure and anisotropic properties of alloy materials. Welding principally leads to a large reduction in grain size in welded zones due to the phenomenon of dynamic recrystallization. The most remarkable observation was that crystallographic textures appeared from a base metal without texture in two zones: the thermo-mechanically affected and stir welded zones. The latter zone has the peculiarity of possessing a marked texture with two components on the basal plane and the pyramidal plane. These characteristics disappeared in the TMAZ, which had only one component following the basal plane. These modifications have been explained by the nature of the plastic deformation in these zones, which occurs at a moderate temperature in the TMAZ and high temperature in the SWZ

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy

Measurement of the forward-backward asymmetry in Λ0b and Λ¯0b baryon production in pp¯ collisions at s√=1.96 TeV

We measure the forward-backward asymmetry in the production of Λ0b and Λ¯0b baryons as a function of rapidity in pp¯ collisions at s√=1.96  TeV using 10.4  fb−1 of data collected with the D0 detector at the Fermilab Tevatron collider. The asymmetry is determined by the preference of Λ0b or Λ¯0b particles to be produced in the direction of the beam protons or antiprotons, respectively. The measured asymmetry integrated over rapidity y in the range 0.1<|y|<2.0 is A=0.04±0.07(stat)±0.02(syst)

Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas

We analyzed 921 adenocarcinomas of the esophagus, stomach, colon, and rectum to examine shared and distinguishing molecular characteristics of gastrointestinal tract adenocarcinomas (GIACs). Hypermutated tumors were distinct regardless of cancer type and comprised those enriched for insertions/deletions, representing microsatellite instability cases with epigenetic silencing of MLH1 in the context of CpG island methylator phenotype, plus tumors with elevated single-nucleotide variants associated with mutations in POLE. Tumors with chromosomal instability were diverse, with gastroesophageal adenocarcinomas harboring fragmented genomes associated with genomic doubling and distinct mutational signatures. We identified a group of tumors in the colon and rectum lacking hypermutation and aneuploidy termed genome stable and enriched in DNA hypermethylation and mutations in KRAS, SOX9, and PCBP1. Liu et al. analyze 921 gastrointestinal (GI) tract adenocarcinomas and find that hypermutated tumors are enriched for insertions/deletions, upper GI tumors with chromosomal instability harbor fragmented genomes, and a group of genome-stable colorectal tumors are enriched in mutations in SOX9 and PCBP1

Macrosocial determinants of population health in the context of globalization

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55738/1/florey_globalization_2007.pd