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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.

Total maximum daily load (TMDL) implementation at a southern California beach involved ultraviolet treatment of watershed drainage that provided97% reduction in fecal indicator bacteria (FIB) concentrations. However, this pollutant control measure did not provide sufficient improvement of beach water quality, prompting further assessment. Investigation included microbial source tracking (MST) for human, gull, and canine fecal sources, monitoring of enterococci and fecal coliform, and measurement of chemical and physical water quality parameters for samples collected from watershed, groundwater, and beach sites, including a beach scour pond and tidal creek. FIB variability remained poorly modeled in regression analysis. However, MST revealed correlations between FIB and gull source tracking markers, leading to recommendations to manage gulls as a pollutant source. Beach conditions were followed for three years after implementation of a best management practice (BMP) to abate gulls using a falconry program for the beach and an upland landfill. The gull abatement BMP was associated with improved beach water quality, and this appears to be the first report of falconry in the context of TMDL implementation. Overall, MST data enabled management action despite an inability to fully model FIB dynamics in the coupled watershed-beach system.

Past experience with an industrial, classroom‐based educational model for aboriginal students has revealed severe limitations that have resulted in secondary graduation levels far below those of the Canadian population in general. Distance education has the potential to redress many of the traditional model's inherent weaknesses, including the reduction of problems associated with cultural assimilation. Distance education also has the potential to enhance the multimedia resources of band‐controlled schools, schools that have shown good promise in raising retention and attainment rates. This article reviews the current situation pertaining to education in Canadian aboriginal communities, discusses the strengths and weaknesses of two distance education programs for aboriginals, and concludes with key guidelines for future distance education endeavors.

Despite the regulatory mandate to maintain “natural water quality”, there are ⩾271 storm drain discharges that potentially threaten the 14 designated marine water quality protected areas in Southern California called Areas of Special Biological Significance (ASBS). After sampling 35 site-events, the geomean concentrations of total suspended solids, nutrients, total and dissolved trace metals, and polycyclic aromatic hydrocarbons in the ocean following storm events were similar between reference drainages and ASBS discharge sites. Concentrations of chlorinated hydrocarbons were nondetectable and no post-storm sample exhibited significant toxicity to the endemic purple sea urchin ( Strongylocentrotus purpuratus ) near ASBS discharge sites. A reference-based threshold was developed and, despite the similarities in average concentrations, there were some individual ASBS discharge sites that were greater than reference background. Cumulatively across all ASBS, the constituents that were most frequently greater than the reference-based threshold were nutrients and general constituents, followed by dissolved and total trace metals.