Adjusting for treatment switching in the METRIC study shows further improved overall survival with trametinib compared with chemotherapy

Trametinib, a selective inhibitor of mitogen-activated protein kinase kinase 1 (MEK1) and MEK2, significantly improves progression-free survival compared with chemotherapy in patients with BRAF V600E/K mutation–positive advanced or metastatic melanoma (MM). However, the pivotal clinical trial permitted randomized chemotherapy control group patients to switch to trametinib after disease progression, which confounded estimates of the overall survival (OS) advantage of trametinib. Our purpose was to estimate the switching-adjusted treatment effect of trametinib for OS and assess the suitability of each adjustment method in the primary efficacy population. Of the patients randomized to chemotherapy, 67.4% switched to trametinib. We applied the rank-preserving structural failure time model, inverse probability of censoring weights, and a two-stage accelerated failure time model to obtain estimates of the relative treatment effect adjusted for switching. The intent-to-treat (ITT) analysis estimated a 28% reduction in the hazard of death with trametinib treatment (hazard ratio [HR], 0.72; 95% CI, 0.52–0.98) for patients in the primary efficacy population (data cut May 20, 2013). Adjustment analyses deemed plausible provided OS HR point estimates ranging from 0.48 to 0.53. Similar reductions in the HR were estimated for the first-line metastatic subgroup. Treatment with trametinib, compared with chemotherapy, significantly reduced the risk of death and risk of disease progression in patients with BRAF V600E/K mutation–positive advanced melanoma or MM. Adjusting for switching resulted in lower HRs than those obtained from standard ITT analyses. However, CI are wide and results are sensitive to the assumptions associated with each adjustment method

The Fine Line Between Normal and Starburst Galaxies

Recent literature suggests that there are two modes through which galaxies grow their stellar mass - a normal mode characterized by quasi-steady star formation, and a highly efficient starburst mode possibly triggered by stochastic events such as galaxy mergers. While these differences are established for extreme cases, the population of galaxies in-between these two regimes is poorly studied and it is not clear where the transition between these two modes of star formation occurs. We utilize ALMA observations of the CO J=3-2 line luminosity in a sample of 20 infrared luminous galaxies that lie in the intermediate range between normal and starburst galaxies at z ~ 0.25-0.6 in the COSMOS field to examine the gas content and star formation efficiency of these galaxies. We compare these quantities to the galaxies' deviation from the well-studied "main sequence" correlation between star formation rate and stellar mass (MS) and find that at log($SFR/SFR_{MS}$) < 0.6, a galaxy's distance to the main sequence is mostly driven by increased gas content, and not a more efficient star formation process.Comment: 21 pages, 10 figure

The masses of Local Group dwarf spheroidal galaxies: The death of the universal mass profile

We investigate the claim that all dwarf spheroidal galaxies (dSphs) reside within halos that share a common, universal mass profile as has been derived for dSphs of the Galaxy. By folding in kinematic information for 25 Andromeda dSphs, more than doubling the previous sample size, we find that a singular mass profile can not be found to fit all the observations well. Further, the best-fit dark matter density profile measured for solely the Milky Way dSphs is marginally discrepant (at just beyond the 1 sigma level) with that of the Andromeda dSphs, where a profile with lower maximum circular velocity, and hence mass, is preferred. The agreement is significantly better when three extreme Andromeda outliers, And XIX, XXI and XXV, all of which have large half-light radii (>600pc) and low velocity dispersions (sigma_v < 5km/s) are omitted from the sample. We argue that the unusual properties of these outliers are likely caused by tidal interactions with the host galaxy.Comment: ApJ in press, 16 pages, 7 figures. Updated to address referee comment

A kinematic study of the Andromeda dwarf spheroidal system

We present a homogeneous kinematic analysis of red giant branch stars within 18 of the 28 Andromeda dwarf spheroidal (dSph) galaxies, obtained using the Keck I LRIS and Keck II DEIMOS spectrographs. Based on their g-i colors (taken with the CFHT MegaCam imager), physical positions on the sky, and radial velocities, we assign probabilities of dSph membership to each observed star. Using this information, the velocity dispersions, central masses and central densities of the dark matter halos are calculated for these objects, and compared with the properties of the Milky Way dSph population. We also measure the average metallicity ([Fe/H]) from the co-added spectra of member stars for each M31 dSph and find that they are consistent with the trend of decreasing [Fe/H] with luminosity observed in the Milky Way population. We find that three of our studied M31 dSphs appear as significant outliers in terms of their central velocity dispersion, And XIX, XXI and XXV, all of which have large half-light radii (>700 pc) and low velocity dispersions (sigma_v<5 km/s). In addition, And XXV has a mass-to-light ratio within its half-light radius of just [M/L]_{half}=10.3^{+7.0}_{-6.7}, making it consistent with a simple stellar system with no appreciable dark matter component within its 1 sigma uncertainties. We suggest that the structure of the dark matter halos of these outliers have been significantly altered by tides.Comment: 41 pages, 23 figures. Accepted for publication in Ap

Resource-Area-Dependence Analysis: inferring animal resource needs from home-range and mapping data

An animal’s home-range can be expected to encompass the resources it requires for surviving or reproducing. Thus, animals inhabiting a heterogeneous landscape, where resource patches vary in size, shape and distribution, will naturally have home-ranges of varied sizes, so that each home-range encompasses a minimum required amount of a resource. Home-range size can be estimated from telemetry data, and often key resources, or proxies for them such as the areas of important habitat types, can be mapped. We propose a new method, Resource-Area-Dependence Analysis (RADA), which uses a sample of tracked animals and a categorical map to i) infer in which map categories important resources are accessible, ii) within which home range cores they are found, and iii) estimate the mean minimum areas of these map categories required for such resource provision. We provide three examples of applying RADA to datasets of radio-tracked animals from southern England: 15 red squirrels Sciurus vulgaris, 17 gray squirrels S. carolinensis and 114 common buzzards Buteo buteo. The analyses showed that each red squirrel required a mean (95% CL) of 0.48 ha (0.24–-0.97) of pine wood within the outermost home-range, each gray squirrel needed 0.34 ha (0.11–1.12) ha of mature deciduous woodland and 0.035–0.046 ha of wheat, also within the outermost home-range, while each buzzard required 0.54 ha (0.35–0.82) of rough ground close to the home-range center and 14 ha (11–17) of meadow within an intermediate core, with 52% of them also relying on 0.41 ha (0.29–0.59) of suburban land near the home-range center. RADA thus provides a useful tool to infer key animal resource requirements during studies of animal movement and habitat use

A Turnover in the Galaxy Main Sequence of Star Formation at M∗∼1010M⊙M_{*} \sim 10^{10} M_{\odot} for Redshifts z<1.3z < 1.3

The relationship between galaxy star formation rates (SFR) and stellar masses ($M_\ast$) is re-examined using a mass-selected sample of $\sim$62,000 star-forming galaxies at $z \le 1.3$ in the COSMOS 2-deg$^2$ field. Using new far-infrared photometry from $Herschel$-PACS and SPIRE and $Spitzer$-MIPS 24 $\mu$m, along with derived infrared luminosities from the NRK method based on galaxies' locations in the restframe color-color diagram $(NUV - r)$ vs. $(r - K)$, we are able to more accurately determine total SFRs for our complete sample. At all redshifts, the relationship between median $SFR$ and $M_\ast$ follows a power-law at low stellar masses, and flattens to nearly constant SFR at high stellar masses. We describe a new parameterization that provides the best fit to the main sequence and characterizes the low mass power-law slope, turnover mass, and overall scaling. The turnover in the main sequence occurs at a characteristic mass of about $M_{0} \sim 10^{10} M_{\odot}$ at all redshifts. The low mass power-law slope ranges from 0.9-1.3 and the overall scaling rises in SFR as a function of $(1+z)^{4.12 \pm 0.10}$. A broken power-law fit below and above the turnover mass gives relationships of $SFR \propto M_{*}^{0.88 \pm 0.06}$ below the turnover mass and $SFR \propto M_{*}^{0.27 \pm 0.04}$ above the turnover mass. Galaxies more massive than $M_\ast \gtrsim 10^{10}\ M_{\rm \odot}$ have on average, a much lower specific star formation rate (sSFR) than would be expected by simply extrapolating the traditional linear fit to the main sequence found for less massive galaxies.Comment: 16 pages, 7 figures. Accepted for publication in Ap

Exposure to Household Air Pollution from Biomass Cookstoves and Levels of Fractional Exhaled Nitric Oxide (FeNO) among Honduran Women

Household air pollution is estimated to be responsible for nearly three million premature deaths annually. Measuring fractional exhaled nitric oxide (FeNO) may improve the limited understanding of the association of household air pollution and airway inflammation. We evaluated the cross-sectional association of FeNO with exposure to household air pollution (24-h average kitchen and personal fine particulate matter and black carbon; stove type) among 139 women in rural Honduras using traditional stoves or cleaner-burning Justastoves. We additionally evaluated interaction by age. Results were generally consistent with a null association; we did not observe a consistent pattern for interaction by age. Evidence from ambient and household air pollution regarding FeNO is inconsistent, and may be attributable to differing study populations, exposures, and FeNO measurement procedures (e.g., the flow rate used to measure FeNO)