Beyond Concurrent Chemoradiation: The Emerging Role of PD-1/PD-L1 Inhibitors in Stage III Lung Cancer.

Concurrent chemoradiation (cCRT) with platinum-based chemotherapy is standard-of-care therapy for patients with stage III unresectable non-small cell lung cancer (NSCLC). Although cCRT is potentially curative, 5-year overall survival has hovered around 20%, despite extensive efforts to improve outcomes with increasing doses of conformal radiation and intensification of systemic therapy with either induction or consolidation chemotherapy. PD-1/PD-L1 immune checkpoint inhibitors have demonstrated unprecedented efficacy in patients with stage IV NSCLC. In addition, preclinical and early clinical evidence suggests that chemotherapy and radiation may work synergistically with anti-PD-1/PD-L1 therapy to promote antitumor immunity, which has led to the initiation of clinical trials testing these drugs in patients with stage III NSCLC. A preliminary report of a randomized phase III trial, the PACIFIC trial, demonstrated an impressive increase in median progression-free survival with consolidative durvalumab, a PD-L1 inhibitor, compared with observation after cCRT. Here, we discuss the clinical and translational implications of integrating PD-1/PD-L1 inhibitors in the management of patients with unresectable stage III NSCLC

MUSTANG 3.3 Millimeter Continuum Observations of Class 0 Protostars

We present observations of six Class 0 protostars at 3.3 mm (90 GHz) using the 64-pixel MUSTANG bolometer camera on the 100-m Green Bank Telescope. The 3.3 mm photometry is analyzed along with shorter wavelength observations to derive spectral indices (S_nu ~ nu^alpha) of the measured emission. We utilize previously published dust continuum radiative transfer models to estimate the characteristic dust temperature within the central beam of our observations. We present constraints on the millimeter dust opacity index, beta, between 0.862 mm, 1.25 mm, and 3.3 mm. Beta_mm typically ranges from 1.0 to 2.4 for Class 0 sources. The relative contributions from disk emission and envelope emission are estimated at 3.3 mm. L483 is found to have negligible disk emission at 3.3 mm while L1527 is dominated by disk emission within the central beam. The beta_mm^disk <= 0.8 - 1.4 for L1527 indicates that grain growth is likely occurring in the disk. The photometry presented in this paper may be combined with future interferometric observations of Class 0 envelopes and disks.Comment: 19 pages, 3 figures, AJ accepted, in pres

The Radio - 2 mm Spectral Index of the Crab Nebula Measured with GISMO

We present results of 2 mm observations of the Crab Nebula, obtained using the Goddard-IRAM Superconducting 2 Millimeter Observer (GISMO) bolometer camera on the IRAM 30 m telescope. Additional 3.3 mm observations with the MUSTANG bolometer array on the Green Bank Telescope are also presented. The integrated 2 mm flux density of the Crab Nebula provides no evidence for the emergence of a second synchrotron component that has been proposed. It is consistent with the radio power law spectrum, extrapolated up to a break frequency of log(nu_{b} [GHz]) = 2.84 +/- 0.29 or nu_{b} = 695^{+651}_{-336} GHz. The Crab Nebula is well-resolved by the ~16.7" beam (FWHM) of GISMO. Comparison to radio data at comparable spatial resolution enables us to confirm significant spatial variation of the spectral index between 21 cm and 2 mm. The main effect is a spectral flattening in the inner region of the Crab Nebula, correlated with the toroidal structure at the center of the nebula that is prominent in the near-IR through X-ray regime.Comment: Accepted for publication in the Ap

Observations of M87 and Hydra A at 90 GHz

This paper presents new observations of the AGNs M87 and Hydra A at 90 GHz made with the MUSTANG bolometer array on the Green Bank Telescope at 8.5" resolution. A spectral analysis is performed combining this new data and archival VLA data on these objects at longer wavelengths. This analysis can detect variations in spectral index and curvature expected from energy losses in the radiating particles. M87 shows only weak evidence for steepening of the spectrum along the jet suggesting either re-acceleration of the relativistic particles in the jet or insufficient losses to affect the spectrum at 90 GHz. The jets in Hydra A show strong steepening as they move from the nucleus suggesting unbalanced losses of the higher energy relativistic particles. The difference between these two sources may be accounted for by the different lengths over which the jets are observable, 2 kpc for M87 and 45 kpc for Hydra A.Comment: 11 pages, submitted to Ap

MUSTANG: 90 GHz Science with the Green Bank Telescope

MUSTANG is a 90 GHz bolometer camera built for use as a facility instrument on the 100 m Robert C. Byrd Green Bank radio telescope (GBT). MUSTANG has an 8 by 8 focal plane array of transition edge sensor bolometers read out using time-domain multiplexed SQUID electronics. As a continuum instrument on a large single dish MUSTANG has a combination of high resolution (8") and good sensitivity to extended emission which make it very competitive for a wide range of galactic and extragalactic science. Commissioning finished in January 2008 and some of the first science data have been collected.Comment: 9 Pages, 5 figures, Presented at the SPIE conference on astronomical instrumentation in 200

Galaxy Cluster Pressure Profiles as Determined by Sunyaev Zel'dovich Effect Observations with MUSTANG and Bolocam I: Joint Analysis Technique

We present a technique to constrain galaxy cluster pressure profiles by jointly fitting Sunyaev-Zel'dovich effect (SZE) data obtained with MUSTANG and Bolocam for the clusters Abell 1835 and MACS0647. Bolocam and MUSTANG probe different angular scales and are thus highly complementary. We find that the addition of the high resolution MUSTANG data can improve constraints on pressure profile parameters relative to those derived solely from Bolocam. In Abell 1835 and MACS0647, we find gNFW inner slopes of $\gamma = 0.36_{-0.21}^{+0.33}$ and $\gamma = 0.38_{-0.25}^{+0.20}$, respectively when $\alpha$ and $\beta$ are constrained to 0.86 and 4.67 respectively. The fitted SZE pressure profiles are in good agreement with X-ray derived pressure profiles.Comment: 12 pages, 12 figures. Submitted to Ap

CMB observations with the Jodrell Bank - IAC interferometer at 33 GHz

The paper presents the first results obtained with the Jodrell Bank - IAC two-element 33 GHz interferometer. The instrument was designed to measure the level of the Cosmic Microwave Background (CMB) fluctuations at angular scales of 1 - 2 degrees. The observations analyzed here were taken in a strip of the sky at Dec = +41 deg with an element separation of 16.7 lambda, which gives a maximum sensitivity to ~1.6 deg structures on the sky. The data processing and calibration of the instrument are described. The sensitivity achieved in each of the two channels is 7 micro K per resolution element. A reconstruction of the sky at Dec = +41 deg using a maximum entropy method shows the presence of structure at a high level of significance. A likelihood analysis, assuming a flat CMB spatial power spectrum, gives a best estimate of the level of CMB fluctuations of Delta Tl = 43 (+13,-12) micro K for the range l = 109 +/- 19; the main uncertainty in this result arises from sample variance. We consider that the contamination from the Galaxy is small. These results represent a new determination of the CMB power spectrum on angular scales where previous results show a large scatter; our new results are in agreement with the theoretical predictions of the standard inflationary cold dark matter models.Comment: 11 pages, 11 figures. Web site at http://www.jb.man.ac.uk/research/cmb/ Accepted for publication in MNRA

90GHz and 150GHz observations of the Orion M42 region. A sub-millimeter to radio analysis

We have used the new 90GHz MUSTANG camera on the Robert C. Byrd Green Bank Telescope (GBT) to map the bright Huygens region of the star-forming region M42 with a resolution of 9" and a sensitivity of 2.8mJy/beam. 90GHz is an interesting transition frequency, as MUSTANG detects both the free-free emission characteristic of the HII region created by the Trapezium stars, normally seen at lower frequencies, and thermal dust emission from the background OMC1 molecular cloud, normally mapped at higher frequencies. We also present similar data from the 150GHz GISMO camera taken on the IRAM telescope. This map has 15" resolution. By combining the MUSTANG data with 1.4, 8, and 21GHz radio data from the VLA and GBT, we derive a new estimate of the emission measure (EM) averaged electron temperature of Te = 11376K by an original method relating free-free emission intensities at optically thin and optically thick frequencies. Combining ISO-LWS data with our data, we derive a new estimate of the dust temperature and spectral emissivity index within the 80" ISO-LWS beam toward OrionKL/BN, Td = 42K and Beta=1.3. We show that both Td and Beta decrease when going from the HII region and excited OMC1 interface to the denser UV shielded part of OMC1 (OrionKL/BN, Orion S). With a model consisting of only free-free and thermal dust emission we are able to fit data taken at frequencies from 1.5GHz to 854GHz.Comment: 18 pages, 8 figures, submitted to the Astrophysical Journa

The GUCY2C Tumor Suppressor is the Nexus of a Paracrine Hormone Axis Preventing Radiotherapy-Induced Gastrointestinal (GI) Toxicity

Purpose/Objective: Radiation-induced GI toxicity is the primary dose limitation compromising therapy in cancer patients treated with radiation therapy. GUCY2C is the intestinal receptor for diarrheagenic bacterial enterotoxins and the endogenous paracrine hormones guanylin and uroguanylin. Following genomic insult, cyclic (c)GMP produced by ligand activation of GUCY2C enhances DNA damage sensing and repair in intestinal cells. Here, we show that the GUCY2C-cGMP axis mediates p53-dependent radioprotection of intestinal epithelial cells. American Society for Therapeutic Radiation Oncology (ASTRO) 52nd Annual Meeting October 31 - November 4, San Diego, C