Characteristics of men responding to an invitation to undergo testing for prostate cancer as part of a randomised trial

BackgroundSocio-demographic characteristics are associated with participating in cancer screening and trials. We compared the characteristics of those responding with those not responding to a single invitation for PSA testing for prostate cancer as part of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP).MethodsAge, rurality and deprivation among 197,763 men from 271 cluster-randomised primary care centres in the UK were compared between those responding (n=90,300) and not responding (n=100,953) to a prostate cancer testing invitation.Results There was little difference in age between responders and non-responders. Responders were slightly more likely to come from urban rather than rural areas and were slightly less deprived than those who did not respond. ConclusionThese data indicate similarities in age and only minor differences in deprivation and urban location between responders and non-responders. These differences were smaller, but in the same direction as observed in other screening trials

Methanethiol-dependent dimethylsulfide production in soil environments

Dimethylsulfide (DMS) is an environmentally important trace gas with roles in sulfur cycling, signalling to higher organisms and in atmospheric chemistry. DMS is believed to be predominantly produced in marine environments via microbial degradation of the osmolyte dimethylsulfoniopropionate (DMSP). However, significant amounts of DMS are also generated from terrestrial environments, for example, peat bogs can emit ~6 μmol DMS m−2 per day, likely via the methylation of methanethiol (MeSH). A methyltransferase enzyme termed ‘MddA’, which catalyses the methylation of MeSH, generating DMS, in a wide range of bacteria and some cyanobacteria, may mediate this process, as the mddA gene is abundant in terrestrial metagenomes. This is the first study investigating the functionality of MeSH-dependent DMS production (Mdd) in a wide range of aerobic environments. All soils and marine sediment samples tested produced DMS when incubated with MeSH. Cultivation-dependent and cultivation-independent methods were used to assess microbial community changes in response to MeSH addition in a grassland soil where 35.9% of the bacteria were predicted to contain mddA. Bacteria of the genus Methylotenera were enriched in the presence of MeSH. Furthermore, many novel Mdd+ bacterial strains were isolated. Despite the abundance of mddA in the grassland soil, the Mdd pathway may not be a significant source of DMS in this environment as MeSH addition was required to detect DMS at only very low conversion rates

Risk management to prioritise the eradication of new and emerging invasive non-native species

Robust tools are needed to prioritise the management of invasive non-native species (INNS). Risk assessment is commonly used to prioritise INNS, but fails to take into account the feasibility of management. Risk management provides a structured evaluation of management options, but has received little attention to date. We present a risk management scheme to assess the feasibility of eradicating INNS that can be used, in conjunction with existing risk assessment schemes, to support prioritisation. The Non-Native Risk Management scheme (NNRM) can be applied to any predefined area and any taxa. It uses semi-quantitative response and confidence scores to assess seven key criteria: Effectiveness, Practicality, Cost, Impact, Acceptability, Window of opportunity and Likelihood of re-invasion. Scores are elicited using expert judgement, supported by available evidence, and consensus-building methods. We applied the NNRM to forty-one INNS that threaten Great Britain (GB). Thirty-three experts provided scores, with overall feasibility of eradication assessed as ‘very high’ (8 species), ‘high’ (6), ‘medium’ (8), ‘low’ (10) and ‘very low’ (9). The feasibility of eradicating terrestrial species was higher than aquatic species. Lotic freshwater and marine species scored particularly low. Combining risk management and existing risk assessment scores identified six established species as priorities for eradication. A further six species that are not yet established were identified as priorities for eradication on arrival as part of contingency planning. The NNRM is one of the first INNS risk management schemes that can be used with existing risk assessments to prioritise INNS eradication in any area

Profiling Critical Cancer Gene Mutations in Clinical Tumor Samples

Background: Detection of critical cancer gene mutations in clinical tumor specimens may predict patient outcomes and inform treatment options; however, high-throughput mutation profiling remains underdeveloped as a diagnostic approach. We report the implementation of a genotyping and validation algorithm that enables robust tumor mutation profiling in the clinical setting. Methodology: We developed and implemented an optimized mutation profiling platform (“OncoMap”) to interrogate ∼400 mutations in 33 known oncogenes and tumor suppressors, many of which are known to predict response or resistance to targeted therapies. The performance of OncoMap was analyzed using DNA derived from both frozen and FFPE clinical material in a diverse set of cancer types. A subsequent in-depth analysis was conducted on histologically and clinically annotated pediatric gliomas. The sensitivity and specificity of OncoMap were 93.8% and 100% in fresh frozen tissue; and 89.3% and 99.4% in FFPE-derived DNA. We detected known mutations at the expected frequencies in common cancers, as well as novel mutations in adult and pediatric cancers that are likely to predict heightened response or resistance to existing or developmental cancer therapies. OncoMap profiles also support a new molecular stratification of pediatric low-grade gliomas based on BRAF mutations that may have immediate clinical impact. Conclusions: Our results demonstrate the clinical feasibility of high-throughput mutation profiling to query a large panel of “actionable” cancer gene mutations. In the future, this type of approach may be incorporated into both cancer epidemiologic studies and clinical decision making to specify the use of many targeted anticancer agents

Silicon isotopes in Arctic and sub-Arctic glacial meltwaters:The role of subglacial weathering in the silicon cycle

Glacial environments play an important role in high-latitude marine nutrient cycling, potentially contributing significant fluxes of silicon (Si) to the polar oceans, either as dissolved silicon (DSi) or as dissolvable amorphous silica (ASi). Silicon is a key nutrient in promoting marine primary productivity, contributingto atmosphericCO2 removal.We present the current understanding of Si cycling in glacial systems,focusingontheSiisotope(δ30Si)composition of glacial meltwaters. We combine existing glacial δ30Si data with new measurements from 20 subArctic glaciers, showing that glacial meltwaters consistently export isotopically light DSi compared with non-glacial rivers (+0.16‰ versus +1.38‰). Glacial δ30SiASi composition ranges from −0.05‰ to −0.86‰ but exhibits low seasonal variability. Silicon fluxes and δ30Si composition from glacial systems are not commonly included in global Si budgets and isotopic mass balance calculations at present. We discuss outstanding questions, including the formation mechanism of ASi and the export of glacial nutrients from fjords. Finally, we provide a contextual framework for the recent advances in our understanding of subglacial Si cycling and highlight critical research avenues for assessing potential future changes in these environments

Insights into silicon cycling from ice sheet to coastal ocean from isotope geochemistry

The polar regions are biologically productive and play a critical role in regional and global biogeochemical cycling. A key nutrient is dissolved silicon, required for the growth of siliceous phytoplankton, diatoms, which form an important component of polar ecosystems. Glacial weathering is thought to be an important dissolved silicon source to coastal waters, especially critical in regions experiencing seasonal silicon limitation of diatom growth. However, complex physical and biogeochemical interactions in fjords and coastal regions modulate the downstream supply of dissolved and particulate nutrients, including silicon. Here, we review the biogeochemical complexities of glaciated margins and the insights into this system that silicon isotope geochemistry offer. We show that stable and radioisotopic measurements and biogeochemical numerical modelling provide a quantitative mechanistic understanding of subglacial silica mobilisation and its cycling across the land-ocean continuum. Subglacial weathering produces isotopically light amorphous silica, which dissolves in seawater to release dissolved silicon. Our findings show that isotopically light, detrital silica, likely containing glacial material, reaches the ocean and there could support a substantial proportion of diatom productivity, especially in the Arctic. Outstanding questions about silicon cycling in these crucial environments will be addressed through novel and cross-discipline approaches that overcome traditionally viewed ecosystem boundaries

Patterns in microbial assemblages exported from the meltwater of Arctic and sub-Arctic glaciers

Meltwater streams connect the glacial cryosphere with downstream ecosystems. Dissolved and particulate matter exported from glacial ecosystems originates from contrasting supraglacial and subglacial environments, and exported microbial cells have the potential to serve as ecological and hydrological indicators for glacial ecosystem processes. Here, we compare exported microbial assemblages from the meltwater of 24 glaciers from six (sub)Arctic regions – the southwestern Greenland Ice Sheet, Qeqertarsuaq (Disko Island) in west Greenland, Iceland, Svalbard, western Norway, and southeast Alaska – differing in their lithology, catchment size, and climatic characteristics, to investigate spatial and environmental factors structuring exported meltwater assemblages. We found that 16S rRNA gene sequences of all samples were dominated by the phyla Proteobacteria, Bacteroidetes, and Actinobacteria, with Verrucomicrobia also common in Greenland localities. Clustered OTUs were largely composed of aerobic and anaerobic heterotrophs capable of degrading a wide variety of carbon substrates. A small number of OTUs dominated all assemblages, with the most abundant being from the genera Polaromonas, Methylophilus, and Nitrotoga. However, 16–32% of a region’s OTUs were unique to that region, and rare taxa revealed unique metabolic potentials and reflected differences between regions, such as the elevated relative abundances of sulfur oxidizers Sulfuricurvum sp. and Thiobacillus sp. at Svalbard sites. Meltwater alpha diversity showed a pronounced decrease with increasing latitude, and multivariate analyses of assemblages revealed significant regional clusters. Distance-based redundancy and correlation analyses further resolved associations between whole assemblages and individual OTUs with variables primarily corresponding with the sampled regions. Interestingly, some OTUs indicating specific metabolic processes were not strongly associated with corresponding meltwater characteristics (e.g., nitrification and inorganic nitrogen concentrations). Thus, while exported assemblage structure appears regionally specific, and probably reflects differences in dominant hydrological flowpaths, OTUs can also serve as indicators for more localized microbially mediated processes not captured by the traditional characterization of bulk meltwater hydrochemistry. These results collectively promote a better understanding of microbial distributions across the Arctic, as well as linkages between the terrestrial cryosphere habitats and downstream ecosystems