PATRIOT: A phase I study to assess the tolerability, safety and biological effects of a specific ataxia telangiectasia and Rad3-related (ATR) inhibitor (AZD6738) as a single agent and in combination with palliative radiation therapy in patients with solid tumours.

PATRIOT is a phase I study of the ATR inhibitor, AZD6738, as monotherapy, and in combination with palliative radiotherapy. Here, we describe the protocol for this study, which opened in 2014 and is currently recruiting and comprises dose escalation of both drug and radiotherapy, and expansion cohorts

Developing a predictive modelling capacity for a climate change-vulnerable blanket bog habitat: Assessing 1961-1990 baseline relationships

Aim: Understanding the spatial distribution of high priority habitats and developing predictive models using climate and environmental variables to replicate these distributions are desirable conservation goals. The aim of this study was to model and elucidate the contributions of climate and topography to the distribution of a priority blanket bog habitat in Ireland, and to examine how this might inform the development of a climate change predictive capacity for peat-lands in Ireland. Methods: Ten climatic and two topographic variables were recorded for grid cells with a spatial resolution of 1010 km, covering 87% of the mainland land surface of Ireland. Presence-absence data were matched to these variables and generalised linear models (GLMs) fitted to identify the main climatic and terrain predictor variables for occurrence of the habitat. Candidate predictor variables were screened for collinearity, and the accuracy of the final fitted GLM was evaluated using fourfold cross-validation based on the area under the curve (AUC) derived from a receiver operating characteristic (ROC) plot. The GLM predicted habitat occurrence probability maps were mapped against the actual distributions using GIS techniques. Results: Despite the apparent parsimony of the initial GLM using only climatic variables, further testing indicated collinearity among temperature and precipitation variables for example. Subsequent elimination of the collinear variables and inclusion of elevation data produced an excellent performance based on the AUC scores of the final GLM. Mean annual temperature and total mean annual precipitation in combination with elevation range were the most powerful explanatory variable group among those explored for the presence of blanket bog habitat. Main conclusions: The results confirm that this habitat distribution in general can be modelled well using the non-collinear climatic and terrain variables tested at the grid resolution used. Mapping the GLM-predicted distribution to the observed distribution produced useful results in replicating the projected occurrence of the habitat distribution over an extensive area. The methods developed will usefully inform future climate change predictive modelling for Irelan

Immunopharmacological aspects of methylprednisolone and interferon-beta therapies in multiple sclerosis

SIGLEAvailable from British Library Document Supply Centre- DSC:DXN060027 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Hints on the nature of dark matter from the properties of Milky Way satellites

The nature of dark matter is still unknown and one of the most fundamental scientific mysteries. Although successfully describing large scales, the standard cold dark matter model (CDM) exhibits possible shortcomings on galactic and sub-galactic scales. It is exactly at these highly non-linear scales where strong astrophysical constraints can be set on the nature of the dark matter particle. While observations of the Lyman-α forest probe the matter power spectrum in the mildly non-linear regime, satellite galaxies of the Milky Way provide an excellent laboratory as a test of the underlying cosmology on much smaller scales. Here we present results from a set of high resolution simulations of a Milky Way sized dark matter halo in eight distinct cosmologies: CDM, warm dark matter (WDM) with a particle mass of 2 keV and six different cold plus warm dark matter (C+WDM) models, varying the fraction, fwdm, and the mass, mwdm, of the warm component. We used three different observational tests based on Milky Way satellite observations: the total satellite abundance, their radial distribution and their mass profile. We show that the requirement of simultaneously satisfying all three constraints sets very strong limits on the nature of dark matter. This shows the power of a multi-dimensional small scale approach in ruling out models which would be still allowed by large scale observations