Combined BRAF and MEK inhibition, as compared with BRAF inhibition alone, delays the emergence of resistance and reduces toxic effects in patients who have melanoma with BRAF V600E or V600K ...mutations.
In this phase 3 trial, we randomly assigned 423 previously untreated patients who had unresectable stage IIIC or stage IV melanoma with a BRAF V600E or V600K mutation to receive a combination of dabrafenib (150 mg orally twice daily) and trametinib (2 mg orally once daily) or dabrafenib and placebo. The primary end point was progression-free survival. Secondary end points included overall survival, response rate, response duration, and safety. A preplanned interim overall survival analysis was conducted.
The median progression-free survival was 9.3 months in the dabrafenib-trametinib group and 8.8 months in the dabrafenib-only group (hazard ratio for progression or death in the dabrafenib-trametinib group, 0.75; 95% confidence interval CI, 0.57 to 0.99; P=0.03). The overall response rate was 67% in the dabrafenib-trametinib group and 51% in the dabrafenib-only group (P=0.002). At 6 months, the interim overall survival rate was 93% with dabrafenib-trametinib and 85% with dabrafenib alone (hazard ratio for death, 0.63; 95% CI, 0.42 to 0.94; P=0.02). However, a specified efficacy-stopping boundary (two-sided P=0.00028) was not crossed. Rates of adverse events were similar in the two groups, although more dose modifications occurred in the dabrafenib-trametinib group. The rate of cutaneous squamous-cell carcinoma was lower in the dabrafenib-trametinib group than in the dabrafenib-only group (2% vs. 9%), whereas pyrexia occurred in more patients (51% vs. 28%) and was more often severe (grade 3, 6% vs. 2%) in the dabrafenib-trametinib group.
A combination of dabrafenib and trametinib, as compared with dabrafenib alone, improved the rate of progression-free survival in previously untreated patients who had metastatic melanoma with BRAF V600E or V600K mutations. (Funded by GlaxoSmithKline; Clinical Trials.gov number, NCT01584648.).
We report the results of an 87 deg{sup 2} point-source survey centered at R.A. 5{sup h}30{sup m}, decl. -55{sup 0} taken with the South Pole Telescope at 1.4 and 2.0 mm wavelengths with arcminute ...resolution and milli-Jansky depth. Based on the ratio of flux in the two bands, we separate the detected sources into two populations, one consistent with synchrotron emission from active galactic nuclei and the other consistent with thermal emission from dust. We present source counts for each population from 11 to 640 mJy at 1.4 mm and from 4.4 to 800 mJy at 2.0 mm. The 2.0 mm counts are dominated by synchrotron-dominated sources across our reported flux range; the 1.4 mm counts are dominated by synchrotron-dominated sources above {approx}15 mJy and by dust-dominated sources below that flux level. We detect 141 synchrotron-dominated sources and 47 dust-dominated sources at signal-to-noise ratio S/N >4.5 in at least one band. All of the most significantly detected members of the synchrotron-dominated population are associated with sources in previously published radio catalogs. Some of the dust-dominated sources are associated with nearby (z << 1) galaxies whose dust emission is also detected by the Infrared Astronomy Satellite. However, most of the bright, dust-dominated sources have no counterparts in any existing catalogs. We argue that these sources represent the rarest and brightest members of the population commonly referred to as submillimeter galaxies (SMGs). Because these sources are selected at longer wavelengths than in typical SMG surveys, they are expected to have a higher mean redshift distribution and may provide a new window on galaxy formation in the early universe.
We study the stellar, brightest cluster galaxy (BCG) and intracluster medium (ICM) masses of 14 South Pole Telescope (SPT) selected galaxy clusters with median redshift z = 0.9 and mass M
...500 = 6 × 1014 M⊙. We estimate stellar masses for each cluster and BCG using six photometric bands, the ICM mass using X-ray observations and the virial masses using the SPT Sunyaev–Zel'dovich effect signature. At z = 0.9, the BCG mass
$M_{\star }^{\mathrm{BCG}}$
constitutes 0.12 ± 0.01 per cent of the halo mass for a 6 × 1014 M⊙ cluster, and this fraction falls as
$M_{500}^{-0.58\pm 0.07}$
. The cluster stellar mass function has a characteristic mass M
0 = 1011.0 ± 0.1 M⊙, and the number of galaxies per unit mass in clusters is larger than in the field by a factor of 1.65 ± 0.20. We combine our SPT sample with previously published samples at low redshift and correct to a common initial mass function and for systematic virial mass differences. We then explore mass and redshift trends in the stellar fraction f
⋆, the ICM fraction f
ICM, the collapsed baryon fraction f
c and the baryon fraction f
b. At a pivot mass of 6 × 1014 M⊙ and redshift z = 0.9, the characteristic values are f
⋆ = 1.1 ± 0.1 per cent, f
ICM = 9.6 ± 0.5 per cent, f
c = 10.7 ± 1.1 per cent and f
b = 10.7 ± 0.6 per cent. These fractions all vary with cluster mass at high significance, with higher mass clusters having lower f
⋆ and f
c and higher f
ICM and f
b. When accounting for a 15 per cent systematic virial mass uncertainty, there is no statistically significant redshift trend at fixed mass. Our results support the scenario where clusters grow through accretion from subclusters (higher f
⋆, lower f
ICM) and the field (lower f
⋆, higher f
ICM), balancing to keep f
⋆ and f
ICM approximately constant since z ∼ 0.9.
We present a catalog of emissive point sources detected in the SPT-SZ survey, a contiguous 2530 square degree area surveyed with the South Pole Telescope (SPT) from 2008-2011 in three bands centered ...at 95, 150, and 220 GHz. The catalog contains 4845 sources measured at a significance of 4.5 or greater in at least one band, corresponding to detections above approximately 9.8, 5.8, and 20.4 mJy in 95, 150, and 220 GHz, respectively. The spectral behavior in the SPT bands is used for source classification into two populations based on the underlying physical mechanisms of compact, emissive sources that are bright at millimeter wavelengths: synchrotron radiation from active galactic nuclei and thermal emission from dust. The latter population includes a component of high-redshift sources often referred to as submillimeter galaxies (SMGs). In the relatively bright flux ranges probed by the survey, these sources are expected to be magnified by strong gravitational lensing. The survey also contains sources consistent with protoclusters, groups of dusty galaxies at high redshift undergoing collapse. We cross-match the SPT-SZ catalog with external catalogs at radio, infrared, and X-ray wavelengths and identify available redshift information. The catalog splits into 3980 synchrotron-dominated and 865 dust-dominated sources, and we determine a list of 506 SMGs. Ten sources in the catalog are identified as stars. We calculate number counts for the full catalog, and synchrotron and dusty components, using a bootstrap method and compare our measured counts with models. This paper represents the third and final catalog of point sources in the SPT-SZ survey.
Abstract
We use galaxy dynamical information to calibrate the richness–mass scaling relation of a sample of 428 galaxy clusters that are members of the CODEX sample with redshifts up to z ∼ 0.7. ...These clusters were X-ray selected using the ROSAT All-Sky Survey (RASS) and then cross-matched to associated systems in the redMaPPer (the red sequence Matched-filter Probabilistic Percolation) catalogue from the Sloan Digital Sky Survey. The spectroscopic sample we analyse was obtained in the SPIDERS program and contains ∼7800 red member galaxies. Adopting NFW mass and galaxy density profiles and a broad range of orbital anisotropy profiles, we use the Jeans equation to calculate halo masses. Modelling the scaling relation as $\lambda \propto \text{A}_{\lambda } {M_{\text{200c}}}^{\text{B}_{\lambda }} ({1+z})^{\gamma _{\lambda }}$, we find the parameter constraints $\text{A}_{\lambda }=38.6^{+3.1}_{-4.1}\pm 3.9$, $\text{B}_{\lambda }=0.99^{+0.06}_{-0.07}\pm 0.04$, and $\gamma _{\lambda }=-1.13^{+0.32}_{-0.34}\pm 0.49$, where we present systematic uncertainties as a second component. We find good agreement with previously published mass trends with the exception of those from stacked weak lensing analyses. We note that although the lensing analyses failed to account for the Eddington bias, this is not enough to explain the differences. We suggest that differences in the levels of contamination between pure redMaPPer and RASS + redMaPPer samples could well contribute to these differences. The redshift trend we measure is more negative than but statistically consistent with previous results. We suggest that our measured redshift trend reflects a change in the cluster galaxy red sequence (RS) fraction with redshift, noting that the trend we measure is consistent with but somewhat stronger than an independently measured redshift trend in the RS fraction. We also examine the impact of a plausible model of correlated scatter in X-ray luminosity and optical richness, showing it has negligible impact on our results.
Two studies were conducted to investigate a revised and extended version of the Lesbian and Gay Identity Scale (Mohr & Fassinger, 2000): the 27-item Lesbian, Gay, and Bisexual Identity Scale (LGBIS). ...This revision features more inclusive and less stigmatizing language than the previous version and includes 2 new subscales assessing identity affirmation and centrality. In Study 1, an exploratory factor analysis (n = 297) and a confirmatory factor analysis (n = 357) supported an 8-factor solution assessing acceptance concerns, concealment motivation, identity uncertainty, internalized homonegativity, difficulty with the identity development process, identity superiority, identity affirmation, and identity centrality. Predicted associations with measures of identity-related constructs and psychosocial functioning provided preliminary validity evidence for LGBIS scores in a college student population. Study 2 (N = 51) provided evidence of the test-retest and internal consistency reliability of LGBIS scores. These studies suggest that the LGBIS may offer researchers an efficient means of assessing multiple dimensions of sexual orientation minority identity.
The mammalian gastrointestinal tract harbors a microbial community with metabolic activity critical for host health, including metabolites that can modulate effector functions of immune cells. Mice ...treated with vancomycin have an altered microbiome and metabolite profile, exhibit exacerbated T helper type 2 cell (Th2) responses, and are more susceptible to allergic lung inflammation. Here we show that dietary supplementation with short-chain fatty acids (SCFAs) ameliorates this enhanced asthma susceptibility by modulating the activity of T cells and dendritic cells (DCs). Dysbiotic mice treated with SCFAs have fewer interleukin-4 (IL4)-producing CD4
T cells and decreased levels of circulating immunoglobulin E (IgE). In addition, DCs exposed to SCFAs activate T cells less robustly, are less motile in response to CCL19 in vitro, and exhibit a dampened ability to transport inhaled allergens to lung draining nodes. Our data thus demonstrate that gut dysbiosis can exacerbate allergic lung inflammation through both T cell- and DC-dependent mechanisms that are inhibited by SCFAs.
We report the 2018 self-consistent values of constants and conversion factors of physics and chemistry recommended by the Committee on Data of the International Science Council (CODATA). The ...recommended values can also be found at physics.nist.gov/constants. The values are based on a least-squares adjustment that takes into account all theoretical and experimental data available through 31 December 2018. A discussion of the major improvements as well as inconsistencies within the data is given. The former include a decrease in the uncertainty of the dimensionless fine-structure constant and a nearly two orders of magnitude improvement of particle masses expressed in units of kg due to the transition to the revised International System of Units (SI) with an exact value for the Planck constant. Further, because the elementary charge, Boltzmann constant, and Avogadro constant also have exact values in the revised SI, many other constants are either exact or have significantly reduced uncertainties. Inconsistencies remain for the gravitational constant and the muon magnetic-moment anomaly. The proton charge radius puzzle has been partially resolved by improved measurements of hydrogen energy levels.
Abstract
We present a detailed study of the galaxy cluster thermal Sunyaev–Zel'dovich effect (SZE) signal Y and pressure profiles using Magneticum Pathfinder hydrodynamical simulations. With a sample ...of 50 000 galaxy clusters (M
500c > 1.4 × 1014 M⊙) out to z = 2, we find significant variations in the shape of the pressure profile with mass and redshift and present a new generalized NFW (Navarro–Frenk–White) model that follows these trends. We show that the thermal pressure at R
500c accounts for only 80 per cent of the pressure required to maintain hydrostatic equilibrium, and therefore even idealized hydrostatic mass estimates would be biased at the 20 per cent level. We compare the cluster SZE signal extracted from a sphere with different virial-like radii, a virial cylinder within a narrow redshift slice and the full light-cone, confirming small scatter (σln Y
≃ 0.087) in the sphere and showing that structure immediately surrounding clusters increases the scatter and strengthens non-self-similar redshift evolution in the cylinder. Uncorrelated large-scale structure along the line of sight leads to an increase in the SZE signal and scatter that is more pronounced for low-mass clusters, resulting in non-self-similar trends in both mass and redshift and a mass-dependent scatter, that is, ∼0.16 at low masses. The scatter distribution is consistent with lognormal in all cases. We present a model of the offsets between the centre of the gravitational potential and the SZE centre that follows the variations with cluster mass and redshift.
A newly modified fast temperature-stepping thermodenuder (TD) was coupled to a High Resolution Time-of-Flight Aerosol Mass Spectrometer for rapid determination of chemically resolved volatility of ...organic aerosols (OA) emitted from individual sources. The TD-AMS system was used to characterize primary OA (POA) from biomass burning, trash burning surrogates (paper and plastic), and meat cooking as well as chamber-generated secondary OA (SOA) from α-pinene and gasoline vapor. Almost all atmospheric models represent POA as nonvolatile, with no allowance for evaporation upon heating or dilution, or condensation upon cooling. Our results indicate that all OAs observed show semivolatile behavior and that most POAs characterized here were at least as volatile as SOA measured in urban environments. Biomass-burning OA (BBOA) exhibited a wide range of volatilities, but more often showed volatility similar to urban OA. Paper-burning resembles some types of BBOA because of its relatively high volatility and intermediate atomic oxygen-to-carbon (O/C) ratio, while meat-cooking OAs (MCOA) have consistently lower volatility than ambient OA. Chamber-generated SOA under the relatively high concentrations used in traditional experiments was significantly more volatile than urban SOA, challenging extrapolation of traditional laboratory volatility measurements to the atmosphere. Most OAs sampled show increasing O/C ratio and decreasing H/C (hydrogen-to-carbon) ratio with temperature, further indicating that more oxygenated OA components are typically less volatile. Future experiments should systematically explore a wider range of mass concentrations to more fully characterize the volatility distributions of these OAs.
PDF
