Figures of merit and constraints from testing General Relativity using the latest cosmological data sets including refined COSMOS 3D weak lensing

We use cosmological constraints from current data sets and a figure of merit (FoM) approach to probe any deviations from general relativity (GR) at cosmological scales. The FoM approach is used to study the constraining power of various combinations of data sets on modified gravity (MG) parameters. We use recently refined HST-COSMOS weak-lensing tomography data, ISW-galaxy cross correlations from 2MASS and SDSS LRG surveys, matter power spectrum from SDSS-DR7 (MPK), WMAP7 temperature and polarization spectra, BAO from 2DF and SDSS-DR7, and Union2 compilation of supernovae, in addition to other bounds from H_0 measurements and BBN. We use 3 parametrizations of MG parameters that enter the perturbed field equations. In order to allow for variations with redshift and scale, the first 2 parametrizations use recently suggested functional forms while the third is based on binning methods. Using the first parametrization, we find that CMB + ISW + WL provides the strongest constraints on MG parameters followed by CMB+WL or CMB+MPK+ISW. Using the second parametrization or binning methods, CMB+MPK+ISW consistently provides some of the strongest constraints. This shows that the constraints are parametrization dependent. We find that adding up current data sets does not improve consistently uncertainties on MG parameters due to tensions between best-fit MG parameters preferred by different data sets. Furthermore, some functional forms imposed by the parametrizations can lead to an exacerbation of these tensions. Next, unlike some studies that used the CFHTLS lensing data, we do not find any deviation from GR using the refined HST-COSMOS data, confirming previous claims in those studies that their result may have been due to some systematic effect. Finally, we find in all cases that the values corresponding to GR are within the 95% confidence level contours for all data set combinations. (abridged)Comment: 18 pages, 6 figures, matches version published in PR

Constraints and tensions in testing general relativity from Planck and CFHTLenS data including intrinsic alignment systematics

We present constraints on testing general relativity (GR) at cosmological scales using recent data sets and assess the impact of galaxy intrinsic alignment in the CFHTLenS lensing data on those constraints. We consider data from Planck temperature anisotropies, the galaxy power spectrum from the WiggleZ survey, weak-lensing tomography shear-shear cross-correlations from the CFHTLenS survey, integrated Sachs Wolfe-galaxy cross-correlations, and baryon acoustic oscillation data. We use three different parametrizations of modified gravity (MG), one that is binned in redshift and scale, a parametrization that evolves monotonically in scale but is binned in redshift, and a functional parametrization that evolves only in redshift. We present the results in terms of the MG parameters Q and Sigma. We employ an intrinsic alignment model with an amplitude A(CFHTLenS) that is included in the parameter analysis. We find an improvement in the constraints on the MG parameters corresponding to a 40-53% increase on the figure of merit compared to previous studies, and GR is found consistent with the data at the 95% confidence level. The bounds found on ACFHTLenS are sensitive to the MG parametrization used, and the correlations between ACFHTLenS and MG parameters are found to be weak to moderate. For all three MG parametrizations ACFHTLenS is found to be consistent with zero when the whole lensing sample is used; however, when using the optimized early-type galaxy sample a significantly nonzero A(CFHTLenS) is found for GR and the scale-independent MG parametrization. We find that the tensions observed in previous studies persist, and there is an indication that cosmic microwave background (CMB) data and lensing data prefer different values for MG parameters, particularly for the parameter Sigma. The analysis of the confidence contours and probability distributions suggest that the bimodality found follows that of the known tension in the sigma(8) parameter

Targeted agents and immunotherapies: optimizing outcomes in melanoma

Treatment options for patients with metastatic melanoma, and especially BRAF-mutant melanoma, have changed dramatically in the past 5 years, with the FDA approval of eight new therapeutic agents. During this period, the treatment paradigm for BRAF-mutant disease has evolved rapidly: the standard-of-care BRAF-targeted approach has shifted from single-agent BRAF inhibition to combination therapy with a BRAF and a MEK inhibitor. Concurrently, immunotherapy has transitioned from cytokine-based treatment to antibody-mediated blockade of the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and, now, the programmed cell-death protein 1 (PD-1) immune checkpoints. These changes in the treatment landscape have dramatically improved patient outcomes, with the median overall survival of patients with advanced-stage melanoma increasing from approximately 9 months before 2011 to at least 2 years - and probably longer for those with BRAF-V600-mutant disease. Herein, we review the clinical trial data that established the standard-of-care treatment approaches for advanced-stage melanoma. Mechanisms of resistance and biomarkers of response to BRAF-targeted treatments and immunotherapies are discussed, and the contrasting clinical benefits and limitations of these therapies are explored. We summarize the state of the field and outline a rational approach to frontline-treatment selection for each individual patient with BRAF-mutant melanoma

Inflammation and Nutritional Science for Programs/Policies and Interpretation of Research Evidence (INSPIRE).

An increasing recognition has emerged of the complexities of the global health agenda-specifically, the collision of infections and noncommunicable diseases and the dual burden of over- and undernutrition. Of particular practical concern are both 1) the need for a better understanding of the bidirectional relations between nutritional status and the development and function of the immune and inflammatory response and 2) the specific impact of the inflammatory response on the selection, use, and interpretation of nutrient biomarkers. The goal of the Inflammation and Nutritional Science for Programs/Policies and Interpretation of Research Evidence (INSPIRE) is to provide guidance for those users represented by the global food and nutrition enterprise. These include researchers (bench and clinical), clinicians providing care/treatment, those developing and evaluating programs/interventions at scale, and those responsible for generating evidence-based policy. The INSPIRE process included convening 5 thematic working groups (WGs) charged with developing summary reports around the following issues: 1) basic overview of the interactions between nutrition, immune function, and the inflammatory response; 2) examination of the evidence regarding the impact of nutrition on immune function and inflammation; 3) evaluation of the impact of inflammation and clinical conditions (acute and chronic) on nutrition; 4) examination of existing and potential new approaches to account for the impact of inflammation on biomarker interpretation and use; and 5) the presentation of new approaches to the study of these relations. Each WG was tasked with synthesizing a summary of the evidence for each of these topics and delineating the remaining gaps in our knowledge. This review consists of a summary of the INSPIRE workshop and the WG deliberation