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

From livelihoods to leisure and back: refugee ‘self-reliance’ as collective practices in Lebanon, India and Greece

Over the last two decades, leading humanitarian agencies in the Global North have increasingly promoted a policy of self-reliance, understood as making individual refugees financially independent from aid assistance through livelihood programmes. However, individual economic autonomy offers an incomplete picture of refugee well-being. Based on fieldwork conducted over 2017 in Halba (Lebanon), Delhi (India) and Thessaloniki (Greece), this multi-site study shows that non-camp refugees build on collective strategies at household, social network and community levels in efforts to develop mechanisms of survival and enfranchisement. These strategies include social and leisure activities as well as income-generating activities which are often organised compartmentally in humanitarian programming. We argue that while leisure and social mingling alone cannot ensure economic sustainability, they are fundamental dimensions of self-reliance as seen by refugees and should therefore be systematically included in livelihood programming. “It is on a living tree that the vine grows” (Ghanaian proverb teaching support, growth and interdependence on one another within the community)

Radiation therapy after radical prostatectomy for prostate cancer: evaluation of complications and influence of radiation timing on outcomes in a large, population-based cohort.

PURPOSE: To evaluate the influence of timing of salvage and adjuvant radiation therapy on outcomes after prostatectomy for prostate cancer. METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare linked database, we identified prostate cancer patients diagnosed during 1995-2007 who had one or more adverse pathological features after prostatectomy. The final cohort of 6,137 eligible patients included men who received prostatectomy alone (n = 4,509) or with adjuvant (n = 894) or salvage (n = 734) radiation therapy. Primary outcomes were genitourinary, gastrointestinal, and erectile dysfunction events and survival after treatment(s). RESULTS: Radiation therapy after prostatectomy was associated with higher rates of gastrointestinal and genitourinary events, but not erectile dysfunction. In adjusted models, earlier treatment with adjuvant radiation therapy was not associated with increased rates of genitourinary or erectile dysfunction events compared to delayed salvage radiation therapy. Early adjuvant radiation therapy was associated with lower rates of gastrointestinal events that salvage radiation therapy, with hazard ratios of 0.80 (95% CI, 0.67-0.95) for procedure-defined and 0.70 (95% CI, 0.59, 0.83) for diagnosis-defined events. There was no significant difference between ART and non-ART groups (SRT or RP alone) for overall survival (HR = 1.13 95% CI = (0.96, 1.34) p = 0.148). CONCLUSIONS: Radiation therapy after prostatectomy is associated with increased rates of gastrointestinal and genitourinary events. However, earlier radiation therapy is not associated with higher rates of gastrointestinal, genitourinary or sexual events. These findings oppose the conventional belief that delaying radiation therapy reduces the risk of radiation-related complications

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

Novel actions of next-generation taxanes benefit advanced stages of prostate cancer.

PURPOSE: To improve the outcomes of patients with castration-resistant prostate cancer (CRPC), there is an urgent need for more effective therapies and approaches that individualize specific treatments for patients with CRPC. These studies compared the novel taxane cabazitaxel with the previous generation docetaxel, and aimed to determine which tumors are most likely to respond. EXPERIMENTAL DESIGN: Cabazitaxel and docetaxel were compared via in vitro modeling to determine the molecular mechanism, biochemical and cell biologic impact, and cell proliferation, which was further assessed ex vivo in human tumor explants. Isogenic pairs of RB knockdown and control cells were interrogated in vitro and in xenograft tumors for cabazitaxel response. RESULTS: The data herein show that (i) cabazitaxel exerts stronger cytostatic and cytotoxic response compared with docetaxel, especially in CRPC; (ii) cabazitaxel induces aberrant mitosis, leading to pyknotic and multinucleated cells; (iii) taxanes do not act through the androgen receptor (AR); (iv) gene-expression profiling reveals distinct molecular actions for cabazitaxel; and (v) tumors that have progressed to castration resistance via loss of RB show enhanced sensitivity to cabazitaxel. CONCLUSIONS: Cabazitaxel not only induces improved cytostatic and cytotoxic effects, but also affects distinct molecular pathways, compared with docetaxel, which could underlie its efficacy after docetaxel treatment has failed in patients with CRPC. Finally, RB is identified as the first potential biomarker that could define the therapeutic response to taxanes in metastatic CRPC. This would suggest that loss of RB function induces sensitization to taxanes, which could benefit up to 50% of CRPC cases

Therapeutic Challenge with a CDK 4/6 Inhibitor Induces an RB-Dependent SMAC-Mediated Apoptotic Response in Non-Small Cell Lung Cancer.

Purpose: The retinoblastoma tumor suppressor (RB), a key regulator of cell-cycle progression and proliferation, is functionally suppressed in up to 50% of non-small cell lung cancer (NSCLC). RB function is exquisitely controlled by a series of proteins, including the CyclinD-CDK4/6 complex. In this study, we interrogated the capacity of a CDK4/6 inhibitor, palbociclib, to activate RB function. Experimental Design and Results: We employed multiple isogenic RB-proficient and -deficient NSCLC lines to interrogate the cytostatic and cytotoxic capacity of CDK 4/6 inhibition in vitro and in vivo We demonstrate that while short-term exposure to palbociclib induces cellular senescence, prolonged exposure results in inhibition of tumor growth. Mechanistically, CDK 4/6 inhibition induces a proapoptotic transcriptional program through suppression of IAPs FOXM1 and Survivin, while simultaneously augmenting expression of SMAC and caspase-3 in an RB-dependent manner. Conclusions: This study uncovers a novel function of RB activation to induce cellular apoptosis through therapeutic administration of a palbociclib and provides a rationale for the clinical evaluation of CDK 4/6 inhibitors in the treatment of patients with NSCLC

Genomic Classifier Augments the Role of Pathological Features in Identifying Optimal Candidates for Adjuvant Radiation Therapy in Patients With Prostate Cancer: Development and Internal Validation of a Multivariable Prognostic Model.

Purpose Despite documented oncologic benefit, use of postoperative adjuvant radiotherapy (aRT) in patients with prostate cancer is still limited in the United States. We aimed to develop and internally validate a risk-stratification tool incorporating the Decipher score, along with routinely available clinicopathologic features, to identify patients who would benefit the most from aRT. Patient and Methods Our cohort included 512 patients with prostate cancer treated with radical prostatectomy at one of four US academic centers between 1990 and 2010. All patients had ≥ pT3a disease, positive surgical margins, and/or pathologic lymph node invasion. Multivariable Cox regression analysis tested the relationship between available predictors (including Decipher score) and clinical recurrence (CR), which were then used to develop a novel risk-stratification tool. Our study adhered to the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis guidelines for development of prognostic models. Results Overall, 21.9% of patients received aRT. Median follow-up in censored patients was 8.3 years. The 10-year CR rate was 4.9% vs. 17.4% in patients treated with aRT versus initial observation ( P \u3c .001). Pathologic T3b/T4 stage, Gleason score 8-10, lymph node invasion, and Decipher score \u3e 0.6 were independent predictors of CR (all P \u3c .01). The cumulative number of risk factors was 0, 1, 2, and 3 to 4 in 46.5%, 28.9%, 17.2%, and 7.4% of patients, respectively. aRT was associated with decreased CR rate in patients with two or more risk factors (10-year CR rate 10.1% in aRT v 42.1% in initial observation; P = .012), but not in those with fewer than two risk factors ( P = .18). Conclusion Using the new model to indicate aRT might reduce overtreatment, decrease unnecessary adverse effects, and reduce risk of CR in the subset of patients (approximately 25% of all patients with aggressive pathologic disease in our cohort) who benefit from this therapy

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

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