Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival

Colorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1, MUTYH, MAP2K4, FETUB, and TGFBR2 as additional genes significantly mutated in CRC. We find that among hypermutated tumors, an increased mutation burden is associated with improved CRC-specific survival (HR=0.42, 95% CI: 0.21-0.82). Mutations in TP53 are associated with poorer CRC-specific survival, which is most pronounced in cases carrying TP53 mutations with predicted 0% transcriptional activity (HR=1.53, 95% CI: 1.21-1.94). Furthermore, we observe differences in mutational frequency of several genes and pathways by tumor location, stage, and sex. Overall, this large study provides deep insights into somatic mutations in CRC, and their potential relationships with survival and tumor features. Large scale sequencing study is of paramount importance to unravel the heterogeneity of colorectal cancer. Here, the authors sequenced 205 cancer genes in more than 2000 tumours and identified additional mutated driver genes, determined that mutational burden and specific mutations in TP53 are associated with survival odds

Scaphoid Waist Internal Fixation for Fractures Trial (SWIFFT) protocol : a pragmatic multi-centre randomised controlled trial of cast treatment versus surgical fixation for the treatment of bi-cortical, minimally displaced fractures of the scaphoid waist in adults

BACKGROUND: A scaphoid fracture is the most common type of carpal fracture affecting young active people. The optimal management of this fracture is uncertain. When treated with a cast, 88 to 90 % of these fractures unite; however, for the remaining 10-12 % the non-union almost invariably leads to arthritis. The alternative is surgery to fix the scaphoid with a screw at the outset. METHODS/DESIGN: We will conduct a randomised controlled trial (RCT) of 438 adult patients with a "clear" and "bicortical" scaphoid waist fracture on plain radiographs to evaluate the clinical effectiveness and cost-effectiveness of plaster cast treatment (with fixation of those that fail to unite) versus early surgical fixation. The plaster cast treatment will be immobilisation in a below elbow cast for 6 to 10 weeks followed by mobilisation. If non-union is confirmed on plain radiographs and/or Computerised Tomogram at 6 to 12 weeks, then urgent surgical fixation will be performed. This is being compared with immediate surgical fixation with surgeons using their preferred technique and implant. These treatments will be undertaken in trauma units across the United Kingdom. The primary outcome and end-point will be the Patient Rated Wrist Evaluation (a patient self-reported assessment of wrist pain and function) at 52 weeks and also measured at 6, 12, 26 weeks and 5 years. Secondary outcomes include an assessment of radiological union of the fracture; quality of life; recovery of wrist range and strength; and complications. We will also qualitatively investigate patient experiences of their treatment. DISCUSSION: Scaphoid fractures are an important public health problem as they predominantly affect young active individuals in the more productive working years of their lives. Non-union, if untreated, can lead to arthritis which can disable patients at a very young age. There is a rapidly increasing trend for immediate surgical fixation of these fractures but there is insufficient evidence from existing RCTs to support this. The SWIFFT Trial is a rigorously designed and adequately powered study which aims to contribute to the evidence-base to inform clinical decisions for the treatment of this common fracture in adults. TRIAL REGISTRATION: The trial is registered with the International Standard Randomised Controlled Trial Register ( ISRCTN67901257 ). Date registration assigned was 13/02/2013

Review of The Middle West: Its Meaning in American Culture.

This book is a well-argued analysis of a variety of sources in the tradition of Henry Nash Smith\u27s Virgin Land and Leo Marx\u27s The Machine in the Garden. While Shortridge does not attempt to lay to rest the question of the objective existence of a midwestern culture or examine the nature of that culture and its origins, his work will nevertheless stimulate a good deal of debate and further research

Accelerating silphium domestication: An opportunity to develop new crop ideotypes and breeding strategies informed by multiple disciplines

Silphium perfoliatum L. (cup plant, silphie) and S. integrifolium Michx. (rosinweed, silflower) are in the same subfamily and tribe as sunflower (Helianthus annuus L.). Silphium perfoliatum has been grown in many countries as a forage or bioenergy crop with forage quality approaching that of alfalfa (Medicago sativa L.) and biomass yield close to maize (Zea mays L.) in some environments. Silphium integrifolium has large seeds with taste and oil quality similar to traditional oilseed sunflower. Silphium species are all long-lived, diploid perennials. Crops from this genus could improve the yield stability, soil, and biodiversity of agricultural landscapes because, in their wild state, they are deep rooted and support a wide diversity of pollinators. In contrast with premodern domestication, de novo domestication should be intentional and scientific. We have the luxury and obligation at this moment in history to expand the domestication ideotype from food and energy production to include (i) crop-driven ecosystem services important for sustainability, (ii) genetic diversity to enable breeding progress for centuries, (iii) natural adaptations and microbiome associations conferring resource use efficiency and stress tolerance, and (iv) improving domestication theory itself by monitoring genetic and ecophysiological changes from predomestication baselines. Achieving these goals rapidly will require the use of next-generation sequencing for marker development and an international, interdisciplinary team committed to collaboration and strategic planning.Fil: Van Tassel, David. Land Institute; Estados UnidosFil: Albrecht, Kenneth A.. University Of Wisconsin Madison;Fil: Bever, James D.. University of Kansas; Estados UnidosFil: Boe, Arvid A.. South Dakota State University; Estados UnidosFil: Brandvain, Yaniv. University of Minnesota; Estados UnidosFil: Crews, Timothy E.. Land Institute; Estados UnidosFil: Gansberger, Markus. Austrian Agency For Health And Food Safety; AustriaFil: Gerstberger, Pedro. University of Bayreuth; AlemaniaFil: González Paleo, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Museo Paleontológico Egidio Feruglio; ArgentinaFil: Hulke, Brent S.. United States Department of Agriculture. Agriculture Research Service; Estados UnidosFil: Kane, Nolan C.. University of Colorado; Estados UnidosFil: Johnson, Paul J.. Insect Biodiversity Laboratory; Estados UnidosFil: Pestsova, Elena G.. Heinrich Heine Universitat;Fil: Picasso Risso, Valentín D.. University of Wisconsin; Estados UnidosFil: Prasifka, Jarrad R.. United States Department of Agriculture. Agriculture Research Service; Estados UnidosFil: Ravetta, Damián Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Museo Paleontológico Egidio Feruglio; ArgentinaFil: Schlautman, Brandon. Land Institute; Estados UnidosFil: Sheaffer, Craig C.. University of Minnesota; Estados UnidosFil: Smith, Kevin P.. University of Minnesota; Estados UnidosFil: Speranza, Pablo R.. Universidad de la República; Urugua