Possible thermochemical disequilibrium in the atmosphere of the exoplanet GJ 436b

The nearby extrasolar planet GJ 436b--which has been labelled as a 'hot Neptune'--reveals itself by the dimming of light as it crosses in front of and behind its parent star as seen from Earth. Respectively known as the primary transit and secondary eclipse, the former constrains the planet's radius and mass, and the latter constrains the planet's temperature and, with measurements at multiple wavelengths, its atmospheric composition. Previous work using transmission spectroscopy failed to detect the 1.4-\mu m water vapour band, leaving the planet's atmospheric composition poorly constrained. Here we report the detection of planetary thermal emission from the dayside of GJ 436b at multiple infrared wavelengths during the secondary eclipse. The best-fit compositional models contain a high CO abundance and a substantial methane (CH4) deficiency relative to thermochemical equilibrium models for the predicted hydrogen-dominated atmosphere. Moreover, we report the presence of some H2O and traces of CO2. Because CH4 is expected to be the dominant carbon-bearing species, disequilibrium processes such as vertical mixing and polymerization of methane into substances such as ethylene may be required to explain the hot Neptune's small CH4-to-CO ratio, which is at least 10^5 times smaller than predicted

Spitzer IRAC Secondary Eclipse Photometry of the Transiting Extrasolar Planet HAT-P-1b

We report Spitzer/IRAC photometry of the transiting giant exoplanet HAT-P-1b during its secondary eclipse. This planet lies near the postulated boundary between the pM and pL-class of hot Jupiters, and is important as a test of models for temperature inversions in hot Jupiter atmospheres. We derive eclipse depths for HAT-P-1b, in units of the stellar flux, that are: 0.080% +/- 0.008%,[3.6um], 0.135% +/- 0.022%,[4.5um],0.203% +/- 0.031%,[5.8um], and $0.238% +/- 0.040%,[8.0um]. These values are best fit using an atmosphere with a modest temperature inversion, intermediate between the archetype inverted atmosphere (HD209458b) and a model without an inversion. The observations also suggest that this planet is radiating a large fraction of the available stellar irradiance on its dayside, with little available for redistribution by circulation. This planet has sometimes been speculated to be inflated by tidal dissipation, based on its large radius in discovery observations, and on a non-zero orbital eccentricity allowed by the radial velocity data. The timing of the secondary eclipse is very sensitive to orbital eccentricity, and we find that the central phase of the eclipse is 0.4999 +/- 0.0005. The difference between the expected and observed phase indicates that the orbit is close to circular, with a 3-sigma limit of |e cosw| < 0.002.Comment: 5 pages, 6 figures, 1 table. Accepted by The Astrophysical Journal, 10 Nov 200

Transit and Eclipse Analyses of Exoplanet HD 149026b Using BLISS Mapping

The dayside of HD 149026b is near the edge of detectability by the Spitzer Space Telescope. We report on eleven secondary-eclipse events at 3.6, 4.5, 3 x 5.8, 4 x 8.0, and 2 x 16 microns plus three primary-transit events at 8.0 microns. The eclipse depths from jointly-fit models at each wavelength are 0.040 +/- 0.003% at 3.6 microns, 0.034 +/- 0.006% at 4.5 microns, 0.044 +/- 0.010% at 5.8 microns, 0.052 +/- 0.006% at 8.0 microns, and 0.085 +/- 0.032% at 16 microns. Multiple observations at the longer wavelengths improved eclipse-depth signal-to-noise ratios by up to a factor of two and improved estimates of the planet-to-star radius ratio (Rp/Rs = 0.0518 +/- 0.0006). We also identify no significant deviations from a circular orbit and, using this model, report an improved period of 2.8758916 +/- 0.0000014 days. Chemical-equilibrium models find no indication of a temperature inversion in the dayside atmosphere of HD 149026b. Our best-fit model favors large amounts of CO and CO2, moderate heat redistribution (f=0.5), and a strongly enhanced metallicity. These analyses use BiLinearly-Interpolated Subpixel Sensitivity (BLISS) mapping, a new technique to model two position-dependent systematics (intrapixel variability and pixelation) by mapping the pixel surface at high resolution. BLISS mapping outperforms previous methods in both speed and goodness of fit. We also present an orthogonalization technique for linearly-correlated parameters that accelerates the convergence of Markov chains that employ the Metropolis random walk sampler. The electronic supplement contains light-curve files and supplementary figures.Comment: Accepted for publication in Ap

Near-infrared photoimmunotherapy targeting EGFR-Shedding new light on glioblastoma treatment

Glioblastomas (GBMs) are high-grade brain tumors, differentially driven by alterations (amplification, deletion or missense mutations) in the epidermal growth factor receptor (EGFR), that carry a poor prognosis of just 12–15 months following standard therapy. A combination of interventions targeting tumor-specific cell surface regulators along with convergent downstream signaling pathways may enhance treatment efficacy. Against this background, we investigated a novel photoimmunotherapy approach combining the cytotoxicity of photodynamic therapy with the specificity of immunotherapy. An EGFR-specific affibody (ZEGFR:03115) was conjugated to the phthalocyanine dye, IR700DX, which when excited with near-infrared light produces a cytotoxic response. ZEGFR:03115–IR700DX EGFR-specific binding was confirmed by flow cytometry and confocal microscopy. The conjugate showed effective targeting of EGFR positive GBM cells in the brain. The therapeutic potential of the conjugate was assessed both in vitro, in GBM cell lines and spheroids by the CellTiter-Glo® assay, and in vivo using subcutaneous U87-MGvIII xenografts. In addition, mice were imaged pre- and post-PIT using the IVIS/Spectrum/CT to monitor treatment response. Binding of the conjugate correlated to the level of EGFR expression in GBM cell lines. The cell proliferation assay revealed a receptor-dependent response between the tested cell lines. Inhibition of EGFRvIII+ve tumor growth was observed following administration of the immunoconjugate and irradiation. Importantly, this response was not seen in control tumors. In conclusion, the ZEGFR:03115–IR700DX showed specific uptake in vitro and enabled imaging of EGFR expression in the orthotopic brain tumor model. Moreover, the proof-of-concept in vivo PIT study demonstrated therapeutic efficacy of the conjugate in subcutaneous glioma xenografts

Observing the LMC with APEX: Signatures of Large-scale Feedback in the Molecular Clouds of 30 Doradus

Stellar feedback plays a crucial role in star formation and the life cycle of molecular clouds. The intense star formation region 30 Doradus, which is located in the Large Magellanic Cloud (LMC), is a unique target for detailed investigation of stellar feedback owing to the proximity of the hosting galaxy and modern observational capabilities that together allow us to resolve individual molecular clouds $-$ nurseries of star formation. We study the impact of large-scale feedback on the molecular gas using the new observational data in the $^{12}$CO(3$-$2) line obtained with the APEX telescope. Our data cover an unprecedented area of 13.8 sq. deg. of the LMC disc with a spatial resolution of 5 pc and provide an unbiased view of the molecular clouds in the galaxy. Using this data, we located molecular clouds in the disc of the galaxy, estimated their properties, such as the areal number density, relative velocity and separation, width of the line profile, CO line luminosity, size, and virial mass, and compared these properties of the clouds of 30 Doradus with those in the rest of the LMC disc. We find that, compared with the rest of the observed molecular clouds in the LMC disc, those in 30 Doradus show the highest areal number density; they are spatially more clustered, they move faster with respect to each other, and they feature larger linewidths. In parallel, we do not find statistically significant differences in such properties as the CO line luminosity, size, and virial mass between the clouds of 30 Doradus and the rest of the observed field. We interpret our results as signatures of gas dispersal and fragmentation due to high-energy large-scale feedback.Comment: Accepted for publication in A&A. 13 pages, 7 figures, 4 table

The melanoma-specific graded prognostic assessment does not adequately discriminate prognosis in a modern population with brain metastases from malignant melanoma

The melanoma-specific graded prognostic assessment (msGPA) assigns patients with brain metastases from malignant melanoma to 1 of 4 prognostic groups. It was largely derived using clinical data from patients treated in the era that preceded the development of newer therapies such as BRAF, MEK and immune checkpoint inhibitors. Therefore, its current relevance to patients diagnosed with brain metastases from malignant melanoma is unclear. This study is an external validation of the msGPA in two temporally distinct British populations.Performance of the msGPA was assessed in Cohort I (1997-2008, n=231) and Cohort II (2008-2013, n=162) using Kaplan-Meier methods and Harrell's c-index of concordance. Cox regression was used to explore additional factors that may have prognostic relevance.The msGPA does not perform well as a prognostic score outside of the derivation cohort, with suboptimal statistical calibration and discrimination, particularly in those patients with an intermediate prognosis. Extra-cerebral metastases, leptomeningeal disease, age and potential use of novel targeted agents after brain metastases are diagnosed, should be incorporated into future prognostic models.An improved prognostic score is required to underpin high-quality randomised controlled trials in an area with a wide disparity in clinical care

Thermal Emission of WASP-14b Revealed with Three Spitzer Eclipses

Exoplanet WASP-14b is a highly irradiated, transiting hot Jupiter. Joshi et al. calculate an equilibrium temperature Teq of 1866 K for zero albedo and reemission from the entire planet, a mass of 7.3 +/- 0.5 Jupiter masses and a radius of 1.28 +/- 0.08 Jupiter radii. Its mean density of 4.6 g/cm3 is one of the highest known for planets with periods less than 3 days. We obtained three secondary eclipse light curves with the Spitzer Space Telescope. The eclipse depths from the best jointly fit model are $0.224\%$ +/- $0.018\%$ at 4.5 {\mu}m and $0.181\%$ +/- $0.022\%$ at 8.0 {\mu}m. The corresponding brightness temperatures are 2212 +/- 94 K and 1590 +/- 116 K. A slight ambiguity between systematic models suggests a conservative 3.6 {\mu}m eclipse depth of $0.19\%$ +/- $0.01\%$ and brightness temperature of 2242 +/- 55 K. Although extremely irradiated, WASP-14b does not show any distinct evidence of a thermal inversion. In addition, the present data nominally favor models with day night energy redistribution less than $~30\%$. The current data are generally consistent with oxygen-rich as well as carbon-rich compositions, although an oxygen-rich composition provides a marginally better fit. We confirm a significant eccentricity of e = 0.087 +/- 0.002 and refine other orbital parameters.Comment: 16 pages, 16 figure

Cluster-Randomized Trial of a Behavioral Intervention to Incorporate a Treat-to-Target Approach to Care of US Patients With Rheumatoid Arthritis

OBJECTIVE: To assess the feasibility and efficacy of implementing a treat-to-target approach versus usual care in a US-based cohort of rheumatoid arthritis patients. METHODS: In this behavioral intervention trial, rheumatology practices were cluster-randomized to provide treat-to-target care or usual care. Eligible patients with moderate/high disease activity (Clinical Disease Activity Index [CDAI] score \u3e 10) were followed for 12 months. Both treat-to-target and usual care patients were seen every 3 months. Treat-to-target providers were to have monthly visits with treatment acceleration at a minimum of every 3 months in patients with CDAI score \u3e 10; additional visits and treatment acceleration were at the discretion of usual care providers and patients. Coprimary end points were feasibility, assessed by rate of treatment acceleration conditional on CDAI score \u3e 10, and achievement of low disease activity (LDA; CDAI score \u3c /=10) by an intent-to-treat analysis. RESULTS: A total of 14 practice sites per study arm were included (246 patients receiving treat-to-target and 286 receiving usual care). The groups had similar baseline demographic and clinical characteristics. Rates of treatment acceleration (treat-to-target 47% versus usual care 50%; odds ratio [OR] 0.92 [95% confidence interval (95% CI) 0.64, 1.34]) and achievement of LDA (treat-to-target 57% versus usual care 55%; OR 1.05 [95% CI 0.60, 1.84]) were similar between groups. Treat-to-target providers reported patient reluctance and medication lag time as common barriers to treatment acceleration. CONCLUSION: This study is the first to examine the feasibility and efficacy of a treat-to-target approach in typical US rheumatology practice. Treat-to-target care was not associated with increased likelihood of treatment acceleration or achievement of LDA, and barriers to treatment acceleration were identified