Molecular profiling of signet ring cell colorectal cancer provides a strong rationale for genomic targeted and immune checkpoint inhibitor therapies

We would like to thank all patients whose samples were used in this study. We are also thankful to the Northern Ireland Biobank and Grampian Biorepository for providing us with tissue blocks and patient data; and Dr HG Coleman (Queen’s University Belfast) for her advice on statistical analyses. This work has been carried out with financial support from Cancer Research UK (grant: C11512/A18067), Experimental Cancer Medicine Centre Network (grant: C36697/A15590 from Cancer Research UK and the NI Health and Social Care Research and Development Division), the Sean Crummey Memorial Fund and the Tom Simms Memorial Fund. The Northern Ireland Biobank is funded by HSC Research and Development Division of the Public Health Agency in Northern Ireland and Cancer Research UK through the Belfast CRUK Centre and the Northern Ireland Experimental Cancer Medicine Centre; additional support was received from Friends of the Cancer Centre. The Northern Ireland Molecular Pathology Laboratory which is responsible for creating resources for the Northern Ireland Biobank has received funding from Cancer Research UK, Friends of the Cancer Centre and Sean Crummey Foundation.Peer reviewedPublisher PD

Mapping the cold dust temperatures and masses of nearby Kingfish galaxies with Herschel

Taking advantage of the sensitivity and angular resolution of the Herschel Space Observatory at far-infrared and submm wavelengths, we aim to characterize the physical properties of cold dust within nearby galaxies and study the robustness of the parameters we derive using different modified blackbody models. For a pilot subsample of the KINGFISH program, we perform 2 temperature fits of the Spitzer and Herschel photometric data (24 to 500um), with a warm and a cold component, globally and in each resolution element.At global scales, we observe ranges of values for beta_c(0.8 to 2.5) and Tc(19.1 to 25.1K).We compute maps of our parameters with beta fixed or free to test the robustness of the temperature and dust surface density maps we deduce. When the emissivity is fixed, we observe temperature gradients as a function of radius.When the emissivity is fitted as a free parameter, barred galaxies tend to have uniform fitted emissivities.Gathering resolved elements in a Tc-beta_c diagram underlines an anti-correlation between the two parameters.It remains difficult to assess whether the dominant effect is the physics of dust grains, noise, or mixing along the line of sight and in the beam. We finally observe in both cases that the dust column density peaks in central regions of galaxies and bar ends (coinciding with molecular gas density enhancements usually found in these locations).We also quantify how the total dust mass varies with our assumptions about the emissivity index as well as the influence of the wavelength coverage used in the fits. We show that modified blackbody fits using a shallow emissivity (beta_c < 2.0) lead to significantly lower dust masses compared to the beta_c < 2.0 case, with dust masses lower by up to 50% if beta_c=1.5 for instance.The working resolution affects our total dust mass estimates: masses increase from global fits to spatially-resolved fits.Comment: 26 pages, 12 figures, 4 tables, accepted for publication in MNRAS, 2012 June 2

The evolution of the dust and gas content in galaxies

We use deep Herschel observations taken with both PACS and SPIRE imaging cameras to estimate the dust mass of a sample of galaxies extracted from the GOODS-S, GOODS-N and the COSMOS fields. We divide the redshift–stellar mass (M star )–star formation rate (SFR) parameter space into small bins and investigate average properties over this grid. In the first part of the work we investigate the scaling relations between dust mass, stellar mass and SFR out to z = 2.5. No clear evolution of the dust mass with redshift is observed at a given SFR and stellar mass. We find a tight correlation between the SFR and the dust mass, which, under reasonable assumptions, is likely a consequence of the Schmidt-Kennicutt (S-K) relation. The previously observed correlation between the stellar content and the dust content flattens or sometimes disappears when considering galaxies with the same SFR. Our finding suggests that most of the correlation between dust mass and stellar mass obtained by previous studies is likely a consequence of the correlation between the dust mass and the SFR combined with the main sequence, i.e., the tight relation observed between the stellar mass and the SFR and followed by the majority of star-forming galaxies. We then investigate the gas content as inferred from dust mass measurements. We convert the dust mass into gas mass by assuming that the dust-to-gas ratio scales linearly with the gas metallicity (as supported by many observations). For normal star-forming galaxies (on the main sequence) the inferred relation between the SFR and the gas mass (integrated S-K relation) broadly agrees with the results of previous studies based on CO measurements, despite the completely different approaches. We observe that all galaxies in the sample follow, within uncertainties, the same S-K relation. However, when investigated in redshift intervals, the S-K relation shows a moderate, but significant redshift evolution. The bulk of the galaxy population at z ∼ 2 converts gas into stars with an efficiency (star formation efficiency, SFE = SFR/M gas , equal to the inverse of the depletion time) about 5 times higher than at z ∼ 0. However, it is not clear what fraction of such variation of the SFE is due to an intrinsic redshift evolution and what fraction is simply a consequence of high-z galaxies having, on average, higher SFR, combined with thesuper-linear slope of the S-K relation (whileother studies finda linear slope). We confirm that the gas fraction (f gas = M gas /(M gas + M star )) decreases with stellar mass and increases with the SFR. We observe no evolution with redshift once M star and SFR are fixed. We explain these trends by introducing a universal relation between gas fraction, stellar mass and SFR that does not evolve with redshift, at least out to z ∼ 2.5. Galaxies move across this relation as their gas content evolves across the cosmic epochs. We use the 3D fundamental f gas –M star –SFR relation, along with the evolution of the main sequence with redshift, to estimate the evolution of the gas fraction in the average population of galaxies as a function of redshift and as a function of stellar mass: we find that M star > ∼ 10 11 M ? galaxies show the strongest evolution at z > ∼ 1.3 and a flatter trend at lower redshift, while f gas decreases more regularly over the entire redshift range probed in M star < ∼ 10 11 Mo galaxies, in agreement with a downsizing scenario

Contrasting Patterns of Coral Bleaching Susceptibility in 2010 Suggest an Adaptive Response to Thermal Stress

Background: \ud Coral bleaching events vary in severity, however, to date, the hierarchy of susceptibility to bleaching among coral taxa has been consistent over a broad geographic range and among bleaching episodes. Here we examine the extent of spatial and temporal variation in thermal tolerance among scleractinian coral taxa and between locations during the 2010 thermally induced, large-scale bleaching event in South East Asia.\ud \ud Methodology/Principal Findings: \ud Surveys to estimate the bleaching and mortality indices of coral genera were carried out at three locations with contrasting thermal and bleaching histories. Despite the magnitude of thermal stress being similar among locations in 2010, there was a remarkable contrast in the patterns of bleaching susceptibility. Comparisons of bleaching susceptibility within coral taxa and among locations revealed no significant differences between locations with similar thermal histories, but significant differences between locations with contrasting thermal histories (Friedman = 34.97; p,0.001). Bleaching was much less severe at locations that bleached during 1998, that had greater historical temperature variability and lower rates of warming. Remarkably, Acropora and Pocillopora, taxa that are typically highly susceptible, although among the most susceptible in Pulau Weh (Sumatra, Indonesia) where respectively, 94% and 87% of colonies died, were among the least susceptible in Singapore, where only 5% and 12% of colonies died.\ud \ud Conclusions/Significance: \ud The pattern of susceptibility among coral genera documented here is unprecedented. A parsimonious explanation for these results is that coral populations that bleached during the last major warming event in 1998 have adapted and/or acclimatised to thermal stress. These data also lend support to the hypothesis that corals in regions subject to more variable temperature regimes are more resistant to thermal stress than those in less variable environments

Management of colorectal cancer presenting with synchronous liver metastases

Up to a fifth of patients with colorectal cancer (CRC) present with synchronous hepatic metastases. In patients with CRC who present without intestinal obstruction or perforation and in whom comprehensive whole-body imaging confirms the absence of extrahepatic disease, evidence indicates a state of equipoise between several different management pathways, none of which has demonstrated superiority. Neoadjuvant systemic chemotherapy is advocated by current guidelines, but must be integrated with surgical management in order to remove the primary tumour and liver metastatic burden. Surgery for CRC with synchronous liver metastases can take a number of forms: the 'classic' approach, involving initial colorectal resection, interval chemotherapy and liver resection as the final step; simultaneous removal of the liver and bowel tumours with neoadjuvant or adjuvant chemotherapy; or a 'liver-first' approach (before or after systemic chemotherapy) with removal of the colorectal tumour as the final procedure. In patients with rectal primary tumours, the liver-first approach can potentially avoid rectal surgery in patients with a complete response to chemoradiotherapy. We overview the importance of precise nomenclature, the influence of clinical presentation on treatment options, and the need for accurate, up-to-date surgical terminology, staging tests and contemporary management options in CRC and synchronous hepatic metastatic disease, with an emphasis on multidisciplinary care

Variation in the provision and practice of implant-based breast reconstruction in the UK: Results from the iBRA national practice questionnaire

Introduction The introduction of biological and synthetic meshes has revolutionised the practice of implant-based breast reconstruction (IBBR) but evidence for effectiveness is lacking. The iBRA (implant Breast Reconstruction evAluation) study is a national trainee-led project that aims to explore the practice and outcomes of IBBR to inform the design of a future trial. We report the results of the iBRA National Practice Questionnaire (NPQ) which aimed to comprehensively describe the provision and practice of IBBR across the UK. Methods A questionnaire investigating local practice and service provision of IBBR developed by the iBRA Steering Group was completed by trainee and consultant leads at breast and plastic surgical units across the UK. Summary data for each survey item were calculated and variation between centres and overall provision of care examined. Results 81 units within 79 NHS-hospitals completed the questionnaire. Units offered a range of reconstructive techniques, with IBBR accounting for 70% (IQR:50–80%) of participating units' immediate procedures. Units on average were staffed by 2.5 breast surgeons (IQR:2.0–3.0) and 2.0 plastic surgeons (IQR:1.0–3.0) performing 35 IBBR cases per year (IQR:20-50). Variation was demonstrated in the provision of novel different techniques for IBBR especially the use of biological (n = 62) and synthetic (n = 25) meshes and in patient selection for these procedures. Conclusions The iBRA-NPQ has demonstrated marked variation in the provision and practice of IBBR in the UK. The prospective audit phase of the iBRA study will determine the safety and effectiveness of different approaches to IBBR and allow evidence-based best practice to be explored

Validation of the Body Concealment Scale for Scleroderma (BCSS): Replication in the Scleroderma Patient-centered Intervention Network (SPIN) Cohort

© 2016 Elsevier Ltd Body concealment is an important component of appearance distress for individuals with disfiguring conditions, including scleroderma. The objective was to replicate the validation study of the Body Concealment Scale for Scleroderma (BCSS) among 897 scleroderma patients. The factor structure of the BCSS was evaluated using confirmatory factor analysis and the Multiple-Indicator Multiple-Cause model examined differential item functioning of SWAP items for sex and age. Internal consistency reliability was assessed via Cronbach's alpha. Construct validity was assessed by comparing the BCSS with a measure of body image distress and measures of mental health and pain intensity. Results replicated the original validation study, where a bifactor model provided the best fit. The BCSS demonstrated strong internal consistency reliability and construct validity. Findings further support the BCSS as a valid measure of body concealment in scleroderma and provide new evidence that scores can be compared and combined across sexes and ages

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)