Tumour invasiveness, the local and systemic environment and the basis of staging systems in colorectal cancer

background: The present study aimed to examine the relationship between tumour invasiveness (T stage), the local and systemic environment and cancer-specific survival (CSS) of patients with primary operable colorectal cancer. methods: The tumour microenvironment was examined using measures of the inflammatory infiltrate (Klintrup-Makinen (KM) grade and Immunoscore), tumour stroma percentage (TSP) and tumour budding. The systemic inflammatory environment was examined using modified Glasgow Prognostic Score (mGPS) and neutrophil:lymphocyte ratio (NLR). A 5-year CSS was examined. results: A total of 331 patients were included. Increasing T stage was associated with colonic primary, N stage, poor differentiation, margin involvement and venous invasion (P<0.05). T stage was significantly associated with KM grade (P=0.001), Immunoscore (P=0.016), TSP (P=0.006), tumour budding (P<0.001), and elevated mGPS and NLR (both P<0.05). In patients with T3 cancer, N stage stratified survival from 88 to 64%, whereas Immunoscore and budding stratified survival from 100 to 70% and from 91 to 56%, respectively. The Glasgow Microenvironment Score, a score based on KM grade and TSP, stratified survival from 93 to 58%. conclusions: Although associated with increasing T stage, local and systemic tumour environment characteristics, and in particular Immunoscore, budding, TSP and mGPS, are stage-independent determinants of survival and may be utilised in the staging of patients with primary operable colorectal cancer

Evaluation of the PPAR-γ agonist pioglitazone in mild asthma: a double-blind randomized controlled trial

Background Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a nuclear receptor that modulates inflammation in models of asthma. To determine whether pioglitazone improves measures of asthma control and airway inflammation, we performed a single-center randomized, double-blind, placebo-controlled, parallel-group trial. Methods Sixty-eight participants with mild asthma were randomized to 12 weeks pioglitazone (30 mg for 4 weeks, then 45 mg for 8 weeks) or placebo. The primary outcome was the adjusted mean forced expiratory volume in one second (FEV1) at 12 weeks. The secondary outcomes were mean peak expiratory flow (PEF), scores on the Juniper Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ), fractional exhaled nitric oxide (FeNO), bronchial hyperresponsiveness (PD20), induced sputum counts, and sputum supernatant interferon gamma-inducible protein-10 (IP-10), vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), and eosinophil cationic protein (ECP) levels. Study recruitment was closed early after considering the European Medicines Agency’s reports of a potential increased risk of bladder cancer with pioglitazone treatment. Fifty-five cases were included in the full analysis (FA) and 52 in the per-protocol (PP) analysis. Results There was no difference in the adjusted FEV1 at 12 weeks (-0.014 L, 95% confidence interval [CI] -0.15 to 0.12, p = 0.84) or in any of the secondary outcomes in the FA. The PP analysis replicated the FA, with the exception of a lower evening PEF in the pioglitazone group (-21 L/min, 95% CI -39 to -4, p = 0.02). Conclusions We found no evidence that treatment with 12 weeks of pioglitazone improved asthma control or airway inflammation in mild asthma

Deriving stage at diagnosis from multiple population-based sources: colorectal and lung cancer in England.

BACKGROUND: Stage at diagnosis is a strong predictor of cancer survival. Differences in stage distributions and stage-specific management help explain geographic differences in cancer outcomes. Stage information is thus essential to improve policies for cancer control. Despite recent progress, stage information is often incomplete. Data collection methods and definition of stage categories are rarely reported. These inconsistencies may result in assigning conflicting stage for single tumours and confound the interpretation of international comparisons and temporal trends of stage-specific cancer outcomes. We propose an algorithm that uses multiple routine, population-based data sources to obtain the most complete and reliable stage information possible. METHODS: Our hierarchical approach derives a single stage category per tumour prioritising information deemed of best quality from multiple data sets and various individual components of tumour stage. It incorporates rules from the Union for International Cancer Control TNM classification of malignant tumours. The algorithm is illustrated for colorectal and lung cancer in England. We linked the cancer-specific Clinical Audit data (collected from clinical multi-disciplinary teams) to national cancer registry data. We prioritise stage variables from the Clinical Audit and added information from the registry when needed. We compared stage distribution and stage-specific net survival using two sets of definitions of summary stage with contrasting levels of assumptions for dealing with missing individual TNM components. This exercise extends a previous algorithm we developed for international comparisons of stage-specific survival. RESULTS: Between 2008 and 2012, 163 915 primary colorectal cancer cases and 168 158 primary lung cancer cases were diagnosed in adults in England. Using the most restrictive definition of summary stage (valid information on all individual TNM components), colorectal cancer stage completeness was 56.6% (from 33.8% in 2008 to 85.2% in 2012). Lung cancer stage completeness was 76.6% (from 57.3% in 2008 to 91.4% in 2012). Stage distribution differed between strategies to define summary stage. Stage-specific survival was consistent with published reports. CONCLUSIONS: We offer a robust strategy to harmonise the derivation of stage that can be adapted for other cancers and data sources in different countries. The general approach of prioritising good-quality information, reporting sources of individual TNM variables, and reporting of assumptions for dealing with missing data is applicable to any population-based cancer research using stage. Moreover, our research highlights the need for further transparency in the way stage categories are defined and reported, acknowledging the limitations, and potential discrepancies of using readily available stage variables

An experimental study of executive function and social impairment in Cornelia de Lange syndrome

Background Extreme shyness and social anxiety is reported to be characteristic of adolescents and adults with Cornelia de Lange syndrome (CdLS); however, the nature of these characteristics is not well documented. In this study, we develop and apply an experimental assessment of social anxiety in a group of adolescents and adults with CdLS to determine the nature of the social difficulties and whether they are related to impairments in executive functioning. Methods A familiar and unfamiliar examiner separately engaged in socially demanding tasks comprising three experimental conditions with a group of individuals with CdLS (n = 25; % male = 44; mean age = 22.16; SD = 8.81) and a comparable group of individuals with Down syndrome (DS; n = 20; % male = 35; mean age = 24.35; SD = 5.97). Behaviours indicative of social anxiety were coded. The Behavior Rating Inventory of Executive Function-Preschool version, an informant measure of executive function, was completed by participants’ caregivers. Results Significantly less verbalisation was observed in the CdLS group than the DS group in conditions requiring the initiation of speech. In the CdLS group, impairments in verbalisation were not associated with a greater degree of intellectual disability but were significantly correlated with impairments in both planning and working memory. This association was not evident in the DS group. Conclusions Adolescents and adults with CdLS have a specific difficulty with the initiation of speech when social demands are placed upon them. This impairment in verbalisation may be underpinned by specific cognitive deficits, although further research is needed to investigate this fully

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

The Formation of the First Massive Black Holes

Supermassive black holes (SMBHs) are common in local galactic nuclei, and SMBHs as massive as several billion solar masses already exist at redshift z=6. These earliest SMBHs may grow by the combination of radiation-pressure-limited accretion and mergers of stellar-mass seed BHs, left behind by the first generation of metal-free stars, or may be formed by more rapid direct collapse of gas in rare special environments where dense gas can accumulate without first fragmenting into stars. This chapter offers a review of these two competing scenarios, as well as some more exotic alternative ideas. It also briefly discusses how the different models may be distinguished in the future by observations with JWST, (e)LISA and other instruments.Comment: 47 pages with 306 references; this review is a chapter in "The First Galaxies - Theoretical Predictions and Observational Clues", Springer Astrophysics and Space Science Library, Eds. T. Wiklind, V. Bromm & B. Mobasher, in pres

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

On invariant Gibbs measures for the generalized KdV equations

International audienceWe consider the defocusing generalized KdV equations on the circle. In particular, we construct global-in-time solutions with initial data distributed according to the Gibbs measure and show that the law of the random solutions, at any time, is again given by the Gibbs measure. In handling a nonlinearity of an arbitrary high degree, we make use of the Hermite polynomials and the white noise functional

Effects of conversion of native cerrado vegetation to pasture on soil hydro-physical properties, evapotranspiration and streamflow on the Amazonian agricultural frontier

Understanding the impacts of land-use change on landscape-hydrological dynamics is one of the main challenges in the Northern Brazilian Cerrado biome, where the Amazon agricultural frontier is located. Motivated by the gap in literature assessing these impacts, we characterized the soil hydro-physical properties and quantified surface water fluxes from catchments under contrasting land-use in this region. We used data from field measurements in two headwater micro-catchments with similar physical characteristics and different land use, i.e. cerrado sensu stricto vegetation and pasture for extensive cattle ranching. We determined hydraulic and physical properties of the soils, applied ground-based remote sensing techniques to estimate evapotranspiration, and monitored streamflow from October 2012 to September 2014. Our results show significant differences in soil hydro-physical properties between the catchments, with greater bulk density and smaller total porosity in the pasture catchment. We found that evapotranspiration is smaller in the pasture (639 ± 31% mm yr-1) than in the cerrado catchment (1,004 ± 24% mm yr-1), and that streamflow from the pasture catchment is greater with runoff coefficients of 0.40 for the pasture and 0.27 for the cerrado catchment. Overall, our results confirm that conversion of cerrado vegetation to pasture causes soil hydro-physical properties deterioration, reduction in evapotranspiration reduction, and increased streamflow