First Report of NRG Oncology/Radiation Therapy Oncology Group 0622: A Phase 2 Trial of Samarium-153 Followed by Salvage Prostatic Fossa Irradiation in High-Risk Clinically Nonmetastatic Prostate Cancer After Radical Prostatectomy.

PURPOSE: To investigate the utility of 153Sm lexidronam (Quadramet) in the setting of men with prostate cancer status post radical prostatectomy who develop biochemical failure with no clinical evidence of osseous metastases. PATIENTS AND METHODS: Trial NRG Oncology RTOG 0622 is a single-arm phase 2 trial that enrolled men with pT2-T4, N0-1, M0 prostate cancer status post radical prostatectomy, who meet at least 1 of these biochemical failure criteria: (1) prostate-specific antigen (PSA) \u3e 1.0 ng/mL; (2) PSA \u3e 0.2 ng/mL if Gleason score 9 to 10; or (3) PSA \u3e 0.2 ng/mL if N1. Patients received 153Sm (2.0 mCi/kg intravenously × 1) followed by salvage external beam radiation therapy (EBRT) to the prostatic fossa (64.8-70.2 Gy in 1.8-Gy daily fractions). No androgen deprivation therapy was allowed. The primary objective was PSA response within 12 weeks of receiving 153Sm. The secondary objectives were to: (1) assess the completion rate for the regimen of 153Sm and EBRT; (2) evaluate the hematologic toxicity and other adverse events (AEs) at 12 and 24 weeks; and (3) determine the freedom from progression rate at 2 years. RESULTS: A total of 60 enrolled eligible patients were included in this analysis. Median follow-up was 3.97 years. A PSA response was achieved in 7 of 52 evaluable patients (13.5%), compared with the 25% hypothesized. The 2-year freedom from progression rate was 25.5% (95% confidence interval 14.4%-36.7%), and the biochemical failure rate was 64.4% (95% CI 50.5%-75.2%). Samarium-153 was well tolerated, with 16 (of 60) grade 3 to 4 hematologic AEs and no grade 5 hematologic AEs. Radiation therapy was also well tolerated, with no grade 3 to 5 acute radiation therapy-related AEs and 1 grade 3 to 4 and no grade 5 late radiation therapy-related AEs. CONCLUSIONS: Trial NRG Oncology RTOG 0622 did not meet its primary endpoint of PSA response, although the regimen of 153Sm and salvage EBRT was well tolerated. Although the toxicity profile supports study of 153Sm in high-risk disease, it may not be beneficial in men receiving EBRT

Assessing the sensitivity of information distortion to four potential influences in studies of risky choice

The emergence of a leading alternative during the course of a decision is known to bias the evaluation of new information in a manner that favors that alternative. We report 3 studies that address the sensitivity of predecisional information distortion and its effects in hypothetical risky decisions with regard to 4 potential influences: choice domain, repeated choice, memory requirements, and intermediate progress questions. In Experiment 1 (N = 515), the magnitude of information distortion was similar in 5 choice domains (varied between participants) involving monetary gambles, song downloads, frequent-flyer miles, political decisions, or medical decisions. Information distortion mediated the relationship between our manipulation of initial preferences and participants’ final choices, with the magnitude of the indirect effect being roughly similar across domains. These results replicate and extend previous findings. Additionally, distortion decreased significantly over 4 similar decision problems (within participants), but remained significant in the fourth problem. In Experiment 2 (N = 214), information distortion increased significantly when previously viewed information remained available, apparently because reiterating that information strengthened emerging preferences. In Experiment 3 (N = 223), the removal of intermediate progress questions that measure information distortion and emerging preferences did not significantly affect final choices, again replicating previous results. We conclude that predecisional information distortion is a relatively stable and robust phenomenon that deserves a prominent role in descriptive theories of choice

Sensitivity Projections for Dark Matter Searches with the Fermi Large Area Telescope

The nature of dark matter is a longstanding enigma of physics; it may consist of particles beyond the Standard Model that are still elusive to experiments. Among indirect search techniques, which look for stable products from the annihilation or decay of dark matter particles, or from axions coupling to high-energy photons, observations of the $\gamma$-ray sky have come to prominence over the last few years, because of the excellent sensitivity of the Large Area Telescope (LAT) on the Fermi Gamma-ray Space Telescope mission. The LAT energy range from 20 MeV to above 300 GeV is particularly well suited for searching for products of the interactions of dark matter particles. In this report we describe methods used to search for evidence of dark matter with the LAT, and review the status of searches performed with up to six years of LAT data. We also discuss the factors that determine the sensitivities of these searches, including the magnitudes of the signals and the relevant backgrounds, considering both statistical and systematic uncertainties. We project the expected sensitivities of each search method for 10 and 15 years of LAT data taking. In particular, we find that the sensitivity of searches targeting dwarf galaxies, which provide the best limits currently, will improve faster than the square root of observing time. Current LAT limits for dwarf galaxies using six years of data reach the thermal relic level for masses up to 120 GeV for the $b\bar{b}$ annihilation channel for reasonable dark matter density profiles. With projected discoveries of additional dwarfs, these limits could extend to about 250 GeV. With as much as 15 years of LAT data these searches would be sensitive to dark matter annihilations at the thermal relic cross section for masses to greater than 400 GeV (200 GeV) in the $b\bar{b}$ ($\tau^+ \tau^-$) annihilation channels.Comment: Updated with a few additional and corrected references; otherwise, text is identical to previous version. Submitted on behalf of the Fermi-LAT collaboration. Accepted for publication in Physics Reports, 59 pages, 34 figures; corresponding author: Eric Charles ([email protected]

The ACS Fornax Cluster Survey. VI. The Nuclei of Early-Type Galaxies in the Fornax Cluster

The Advanced Camera for Surveys (ACS) Fornax Cluster Survey is a Hubble Space Telescope program to image 43 early-type galaxies in the Fornax cluster, using the F475W and F850LP bandpasses of the ACS. We employ both 1D and 2D techniques to characterize the properties of the stellar nuclei in these galaxies, defined as the central "luminosity excesses" relative to a Sersic model fitted to the underlying host. We find 72+/-13% of our sample (31 galaxies) to be nucleated, with only three of the nuclei offset by more than 0.5" from their galaxy photocenter, and with the majority of nuclei having colors bluer than their hosts. The nuclei are observed to be larger, and brighter, than typical Fornax globular clusters, and to follow different structural scaling relations. A comparison of our results to those from the ACS Virgo Cluster Survey reveals striking similarities in the properties of the nuclei belonging to these different environments. We briefly review a variety of proposed formation models and conclude that, for the low-mass galaxies in our sample, the most important mechanism for nucleus growth is probably infall of star clusters through dynamical friction, while for higher mass galaxies, gas accretion triggered by mergers, accretions and tidal torques is likely to dominate, with the relative importance of these two processes varying smoothly as a function of galaxy mass. Some intermediate-mass galaxies in our sample show a complexity in their inner structure that may be the signature of "hybrid nuclei" that arose through parallel formation channels.Comment: 34 pages, 27 figures, accepted for publication in ApJ

Historical and future changes in global flood magnitude - evidence from a model-observation investigation

To improve the understanding of trends in extreme flows related to flood events at the global scale, historical and future changes of annual maxima of 7 d streamflow are investigated, using a comprehensive streamflow archive and six global hydrological models. The models' capacity to characterise trends in annual maxima of 7 d streamflow at the continental and global scale is evaluated across 3666 river gauge locations over the period from 1971 to 2005, focusing on four aspects of trends: (i) mean, (ii) standard deviation, (iii) percentage of locations showing significant trends and (iv) spatial pattern. Compared to observed trends, simulated trends driven by observed climate forcing generally have a higher mean, lower spread and a similar percentage of locations showing significant trends. Models show a low to moderate capacity to simulate spatial patterns of historical trends, with approximately only from 12 % to 25 % of the spatial variance of observed trends across all gauge stations accounted for by the simulations. Interestingly, there are statistically significant differences between trends simulated by global hydrological models (GHMs) forced with observational climate and by those forced by bias-corrected climate model output during the historical period, suggesting the important role of the stochastic natural (decadal, inter-annual) climate variability. Significant differences were found in simulated flood trends when averaged only at gauged locations compared to those averaged across all simulated grid cells, highlighting the potential for bias toward well-observed regions in our understanding of changes in floods. Future climate projections (simulated under the RCP2.6 and RCP6.0 greenhouse gas concentration scenarios) suggest a potentially high level of change in individual regions, with up to 35 % of cells showing a statistically significant trend (increase or decrease; at 10 % significance level) and greater changes indicated for the higher concentration pathway. Importantly, the observed streamflow database under-samples the percentage of locations consistently projected with increased flood hazards under the RCP6.0 greenhouse gas concentration scenario by more than an order of magnitude (0.9 % compared to 11.7 %). This finding indicates a highly uncertain future for both flood-prone communities and decision makers in the context of climate change. © Author(s) 2020

NASA Exploration Mission 2 Mission Design

Exploration Mission 2 (EM-2) will be NASAs first manned flight on the Space Launch System (SLS) and Orion Spacecraft. The mission has been changed from an SLS Block 1B configuration to Block 1. This change has necessitated a reexamination of the flight profile to determine what changes must be made in order to accommodate the reduced launch vehicle performance on the Block 1. Launch availability and orbital debris risk will be traded to find the best flight profile for both SLS and Orion

D-cycloserine augmentation of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders: a systematic review and meta-analysis of individual participant data

Importance: Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear. Objective: To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables. Data Sources: PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked. Study Selection: Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder. Data Extraction and Synthesis: Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies. Results: Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes. Conclusions and Relevance: D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.2018-05-0

SDSSJ103913.70+533029.7: A Super Star Cluster in the Outskirts of a Galaxy Merger

We describe the serendipitous discovery in the spectroscopic data of the Sloan Digital Sky Survey of a star-like object, SDSSJ103913.70+533029.7, at a heliocentric radial velocity of +1012 km/s. Its proximity in position and velocity to the spiral galaxy NGC 3310 suggests an association with the galaxy. At this distance, SDSSJ103913.70+533029.7 has the luminosity of a super star cluster and a projected distance of 17 kpc from NGC 3310. Its spectroscopic and photometric properties imply a mass of > 10^6 solar masses and an age close to that of the tidal shells seen around NGC 3310, suggesting that it formed in the event which formed the shells.Comment: Accepted by AJ: 4 figures (1 color

Valuing innovative endoscopic techniques: prophylactic clip closure after endoscopic resection of large colon polyps

Background and Aims Clip closure of the mucosal defect after resecting large (≥20 mm) nonpedunculated colorectal polyps reduces postprocedure bleeding and is cost saving for payers. Clip costs are not reimbursed by payers, posing a major barrier to adoption of this technique in the community. We aimed to determine appropriate clip costs to support broader use of this procedure in practice. Methods We performed budget impact analysis using our recent decision analytic model, comparing prophylactic clip closure with no clip closure on national cost and outcomes data, to determine the maximum feasible clip price while maintaining cost savings in practice. Sensitivity analyses were performed on important clinical factors. Results In the original model, the baseline postprocedure bleeding risk was 6.8%, increasing cost of care by $614.11 averaged among all patients undergoing large polyp resection without clip closure. Prophylactic clip closure of only large right-sided polyps reduced postprocedure bleeding risk by 70.7$100 or less. Comparatively, prophylactic clip closure of large left-sided polyps had no clinical benefit and was not cost saving. Clip closure strategies focused only on extra-large polyps (≥40 mm), or patients taking antithrombotics regardless of polyp characteristics, were only minimally cost saving. Cost savings and maximum tolerated clip prices depended on medical comorbidity, which directly influences the costs of care to manage postprocedure bleeding. Conclusions Prophylactic clip closure after endoscopic resection of large colon polyps, particularly those in the right colon segment, is cost saving but requires clip costs less than $100. Translating these findings into practice requires gastroenterology practices to obtain reimbursement from payers for improved clinical outcomes and to align commercial clip prices with this clinical indication

Test of variables of attention (TOVA) as a predictor of early attention complaints, an antecedent to dementia

The goal of this study was to determine if impairments detected by the test of variables of attention (TOVA) may be used to predict early attention complaints and memory impairments accurately in a clinical setting. We performed a statistical analysis of outcomes in a patient population screened for attention deficit hyperactivity disorder or attention complaints, processing errors as measured by TOVA and the Wechsler Memory Scale (WMS-III) results. Attention deficit disorder (ADD) checklists, constructed using the Diagnostic and Statistical Manual of Mental Disorders 4th Edition criteria, which were completed by patients at PATH Medical, revealed that 72.8% of the patients had more than one attention complaint out of a total of 16 complaints, and 41.5% had more than five complaints. For the 128 males with a significant number of ADD complaints, individuals whose scores were significantly deviant or borderline (SDB) on TOVA, had a significantly greater number of attention complaints compared with normals for omissions (P < 0.02), response time (P < 0.015), and variability (P < 0.005), but not commissions (P > 0.50). For males, the mean scores for auditory, visual, immediate, and working memory scores as measured by the WMS-III were significantly greater for normals versus SDBs on the TOVA subtest, ie, omission (P < 0.01) and response time (P < 0.05), but not variability or commissions. The means for auditory, visual, and immediate memory scores were significantly greater for normals versus SDBs for variability (P < 0.045) only. In females, the mean scores for visual and working memory scores were significantly greater for normals versus SDBs for omissions (P < 0.025). The number of SDB TOVA quarters was a significant predictor for “impaired” or “normal” group membership for visual memory (P < 0.015), but not for the other three WMS-III components. For males, the partial correlation between the number of attention complaints and the number of SDB TOVA quarters was also significant (r = 0.251, P < 0.005). For the 152 females with a significant number of attention complaints, no significant differences between SDBs and normals were observed (P > 0.15). This is the first report, to our knowledge, which provides evidence that TOVA is an accurate predictor of early attention complaints and memory impairments in a clinical setting. This finding is more robust for males than for females between the ages of 40 and 90 years