The signature of positron annihilation, namely the 511 keV γ-ray line, was first detected coming from the direction of the Galactic center in the 1970s, but the source of Galactic positrons still ...remains a puzzle. The measured flux of the annihilation corresponds to an intense steady source of positron production, with an annihilation rate on the order of ∼1043 . The 511 keV emission is the strongest persistent Galactic γ-ray line signal, and it shows a concentration toward the Galactic center region. An additional low-surface brightness component is aligned with the Galactic disk; however, the morphology of the latter is not well constrained. The Compton Spectrometer and Imager (COSI) is a balloon-borne soft γ-ray (0.2-5 MeV) telescope designed to perform wide-field imaging and high-resolution spectroscopy. One of its major goals is to further our understanding of Galactic positrons. COSI had a 46-day balloon flight in 2016 May-July from Wanaka, New Zealand, and here we report on the detection and spectral and spatial analyses of the 511 keV emission from those observations. To isolate the Galactic positron annihilation emission from instrumental background, we have developed a technique to separate celestial signals using the COMPTEL Data Space. With this method, we find a 7.2 detection of the 511 keV line. We find that the spatial distribution is not consistent with a single point source, and it appears to be broader than what has previously been reported.
We study relationships between star-formation rate (SFR) and the accretion luminosity and nuclear obscuration of X-ray selected active galactic nuclei (AGNs) using a combination of deep far-infrared ...(FIR) and X-ray data in three key extragalactic survey fields (GOODS-South, GOODS-North and COSMOS), as part of the PACS Evolutionary Probe (PEP) program. The use of three fields with differing areas and depths enables us to explore trends between the global FIR luminosity of the AGN hosts and the luminosity of the active nucleus across 4.5 orders of magnitude in AGN luminosity (LAGN) and spanning redshifts from the Local Universe to z = 2.5. Using imaging from the Herschel/PACS instrument in 2−3 bands, we combine FIR detections and stacks of undetected objects to arrive at mean fluxes for subsamples in bins of redshift and X-ray luminosity. We constrain the importance of AGN-heated dust emission in the FIR and confirm that the majority of the FIR emission of AGNs is produced by cold dust heated by star-formation in their host galaxies. We uncover characteristic trends between the mean FIR luminosity (L60) and accretion luminosity of AGNs, which depend both on LAGN and redshift. At low AGN luminosities, accretion and SFR are uncorrelated at all redshifts, consistent with a scenario where most low-luminosity AGNs are primarily fueled by secular processes in their host galaxies. At high AGN luminosities, a significant correlation is observed between L60 and LAGN, but only among AGNs at low and moderate redshifts (z < 1). We interpret this observation as a sign of the increasing importance of major-mergers in driving both the growth of super-massive black holes (SMBHs) and global star-formation in their hosts at high AGN luminosities. We also find evidence that the enhancement of SFR in luminous AGNs weakens or disappears at high redshifts (z > 1) suggesting that the role of mergers is less important at these epochs. At all redshifts, we find essentially no relationship between L60 and nuclear obscuration across five orders of magnitude in obscuring Hydrogen column density (NH), suggesting that various mechanisms are likely to be responsible for obscuring X-rays in active galaxies. We discuss a broad scenario which can account for these trends: one in which two different modes of AGN fueling operate in the low- and high-luminosity regimes of SMBH accretion. We postulate that the dominant mode of accretion among high-luminosity AGNs evolves with redshift. Our study, as well as a body of evidence from the literature and emerging knowledge about the properties of high redshift galaxies, supports this scenario.
We present the first full catalog and science results for the Nuclear Spectroscopic Telescope Array (NuSTAR) serendipitous survey. The catalog incorporates data taken during the first 40 months of ...NuSTAR operation, which provide 20 Ms of effective exposure time over 331 fields, with an areal coverage of 13 deg2, and 497 sources detected in total over the 3-24 keV energy range. There are 276 sources with spectroscopic redshifts and classifications, largely resulting from our extensive campaign of ground-based spectroscopic follow-up. We characterize the overall sample in terms of the X-ray, optical, and infrared source properties. The sample is primarily composed of active galactic nuclei (AGNs), detected over a large range in redshift from z = 0.002 to 3.4 (median of ), but also includes 16 spectroscopically confirmed Galactic sources. There is a large range in X-ray flux, from to −11, and in rest-frame 10-40 keV luminosity, from to 46, with a median of 44.1. Approximately 79% of the NuSTAR sources have lower-energy (<10 keV) X-ray counterparts from XMM-Newton, Chandra, and Swift XRT. The mid-infrared (MIR) analysis, using WISE all-sky survey data, shows that MIR AGN color selections miss a large fraction of the NuSTAR-selected AGN population, from 15% at the highest luminosities ( erg s−1) to 80% at the lowest luminosities ( erg s−1). Our optical spectroscopic analysis finds that the observed fraction of optically obscured AGNs (i.e., the type 2 fraction) is , for a well-defined subset of the 8-24 keV selected sample. This is higher, albeit at a low significance level, than the type 2 fraction measured for redshift- and luminosity-matched AGNs selected by <10 keV X-ray missions.
Advanced prostate cancer etiology is poorly understood. Few studies have examined associations of anthropometric factors (e.g. early adulthood obesity) with advanced prostate cancer risk.
We carried ...out pooled analyses to examine associations between body fatness, height, and prostate cancer risk. Among 830 772 men, 51 734 incident prostate cancer cases were identified, including 4762 advanced (T4/N1/M1 or prostate cancer deaths) cases, 2915 advanced restricted (same as advanced, but excluding localized cancers that resulted in death) cases, 9489 high-grade cases, and 3027 prostate cancer deaths. Cox proportional hazards models were used to calculate study-specific hazard ratios (HR) and 95% confidence intervals (CI); results were pooled using random effects models.
No statistically significant associations were observed for body mass index (BMI) in early adulthood for advanced, advanced restricted, and high-grade prostate cancer, and prostate cancer mortality. Positive associations were shown for BMI at baseline with advanced prostate cancer (HR = 1.30, 95% CI = 0.95–1.78) and prostate cancer mortality (HR = 1.52, 95% CI = 1.12–2.07) comparing BMI ≥35.0 kg/m2 with 21–22.9 kg/m2. When considering early adulthood and baseline BMI together, a 27% higher prostate cancer mortality risk (95% CI = 9% to 49%) was observed for men with BMI <25.0 kg/m2 in early adulthood and BMI ≥30.0 kg/m2 at baseline compared with BMI <25.0 kg/m2 in early adulthood and BMI <30.0 kg/m2 at baseline. Baseline waist circumference, comparing ≥110 cm with <90 cm, and waist-to-hip ratio, comparing ≥1.00 with <0.90, were associated with significant 14%–16% increases in high-grade prostate cancer risk and suggestive or significant 20%–39% increases in prostate cancer mortality risk. Height was associated with suggestive or significant 33%–56% risks of advanced or advanced restricted prostate cancer and prostate cancer mortality, comparing ≥1.90 m with <1.65 m.
Our findings suggest that height and total and central adiposity in mid-to-later adulthood, but not early adulthood adiposity, are associated with risk of advanced forms of prostate cancer. Thus, maintenance of healthy weight may help prevent advanced prostate cancer.
•Few have examined the role of early adulthood BMI and adult BMI changes on risk of advanced forms of prostate cancer.•Height in mid/late adulthood was positively associated with advanced prostate cancer risk and mortality.•BMI and waist circumference in mid/late adulthood was positively associated with advanced prostate cancer risk and mortality.•Change in BMI from early to mid/late adulthood were positively associated with advanced prostate cancer risk and mortality.•BMI in early adulthood was not associated with risk of advanced forms of prostate cancer and prostate cancer mortality.
Background
As part of a randomized phase II trial in patients with isolated resectable colorectal peritoneal metastases (CPMs), the present study compared patient-reported outcomes (PROs) of patients ...treated with perioperative systemic therapy versus cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS–HIPEC) alone. Also, PROs of patients receiving perioperative systemic therapy were explored.
Patients and Methods
Eligible patients were randomized to perioperative systemic therapy (experimental) or CRS–HIPEC alone (control). PROs were assessed using EORTC QLQ-C30, QLQ-CR29, and EQ-5D-5L questionnaires at baseline, after neoadjuvant treatment (experimental), and at 3 and 6 months postoperatively. Linear mixed modeling was used to compare five predefined PROs (visual analog scale, global health status, physical functioning, fatigue, C30 summary score) between arms and to longitudinally analyze PROs in the experimental arm.
Results
Of 79 analyzed patients, 37 (47%) received perioperative systemic therapy. All predefined PROs were comparable between arms at all timepoints and returned to baseline at 3 or 6 months postoperatively. The experimental arm had worsening of fatigue mean difference (MD) + 14,
p
= 0.001, loss of appetite (MD + 15,
p
= 0.003), hair loss (MD + 18,
p
< 0.001), and loss of taste (MD + 27,
p
< 0.001) after neoadjuvant treatment. Except for loss of appetite, these PROs returned to baseline at 3 or 6 months postoperatively.
Conclusions
In patients with resectable CPM randomized to perioperative systemic therapy or CRS–HIPEC alone, PROs were comparable between arms and returned to baseline postoperatively. Together with the trial’s previously reported feasibility and safety data, these findings show acceptable tolerability of perioperative systemic therapy in this setting.
We present measurements of the relative abundances of cosmic-ray nuclei in the energy range of 500-3980 GeV/nucleon from the second flight of the Cosmic Ray Energetics And Mass balloon-borne ...experiment. Particle energy was determined using a sampling tungsten/scintillating-fiber calorimeter, while particle charge was identified precisely with a dual-layer silicon charge detector installed for this flight. The resulting element ratios C/O, N/O, Ne/O, Mg/O, Si/O, and Fe/O at the top of atmosphere are 0.919 {+-} 0.123{sup stat} {+-} 0.030{sup syst}, 0.076 {+-} 0.019{sup stat} {+-} 0.013{sup syst}, 0.115 {+-} 0.031{sup stat} {+-} 0.004{sup syst}, 0.153 {+-} 0.039{sup stat} {+-} 0.005{sup syst}, 0.180 {+-} 0.045{sup stat} {+-} 0.006{sup syst}, and 0.139 {+-} 0.043{sup stat} {+-} 0.005{sup syst}, respectively, which agree with measurements at lower energies. The source abundance of N/O is found to be 0.054 {+-} 0.013{sup stat} {+-} 0.009{sup syst+0.010esc} {sub -0.017}. The cosmic-ray source abundances are compared to local Galactic (LG) abundances as a function of first ionization potential and as a function of condensation temperature. At high energies the trend that the cosmic-ray source abundances at large ionization potential or low condensation temperature are suppressed compared to their LG abundances continues. Therefore, the injection mechanism must be the same at TeV/nucleon energies as at the lower energies measured by HEAO-3, CRN, and TRACER. Furthermore, the cosmic-ray source abundances are compared to a mixture of 80% solar system abundances and 20% massive stellar outflow (MSO) as a function of atomic mass. The good agreement with TIGER measurements at lower energies confirms the existence of a substantial fraction of MSO material required in the {approx}TeV per nucleon region.
We present an X-ray point-source catalogue from the XMM-Large Scale Structure (XMMLSS) survey region, one of the XMM-Spitzer Extragalactic Representative Volume Survey (XMM-SERVS) fields. We target ...the XMM-LSS region with 1.3 Ms of new XMM-Newton AO-15 observations, transforming the archival X-ray coverage in this region into a 5.3 deg2 contiguous field with uniform X-ray coverage totaling 2.7 Ms of flare-filtered exposure, with a 46 ks median PN exposure time. We provide an X-ray catalogue of 5242 sources detected in the soft (0.5-2 keV), hard (2-10 keV), and/or full (0.5-10 keV) bands with a 1 per cent expected spurious fraction determined from simulations. A total of 2381 new X-ray sources are detected compared to previous source catalogues in the same area. Our survey has flux limits of 1.7 × 10-15, 1.3 × 10-14, and 6.5 × 10-15 erg cm-2 s-1 over 90 per cent of its area in the soft, hard, and full bands, respectively, which is comparable to those of the XMM-COSMOS survey. We identify multiwavelength counterpart candidates for 99.9 per cent of the X-ray sources, of which 93 per cent are considered as reliable based on their matching likelihood ratios. The reliabilities of these high-likelihood-ratio counterparts are further confirmed to be ≈97 per cent reliable based on deep Chandra coverage over ≈5 per cent of the XMM-LSS region. Results of multiwavelength identifications are also included in the source catalogue, along with basic optical-to-infrared photometry and spectroscopic redshifts from publicly available surveys. We compute photometric redshifts for X-ray sources in 4.5 deg2 of our field where forced-aperture multiband photometry is available; > 70 per cent of the X-ray sources in this subfield have either spectroscopic or high-quality photometric redshifts.
This study was designed to compare the degree of inhibition of platelet aggregation (IPA) of prasugrel with that of clopidogrel in stable aspirin-treated patients with coronary artery disease (CAD).
...Subjects (n=101) were randomly assigned to the following loading dose (LD) (day 1)/maintenance dose (MD) (days 2-28) combinations: prasugrel, 40 mg/5 mg; 40 mg/7.5 mg; 60 mg/10 mg; 60 mg/15 mg; or clopidogrel, 300 mg/75 mg. Turbidometric platelet aggregation was measured at multiple timepoints during the study. At 4 h after dosing, with 20 microM ADP, both prasugrel LDs achieved significantly higher mean IPA levels (60.6% and 68.4 vs. 30.0%, respectively; all P<0.0001) and lower percentage (3 vs. 52%, P<0.0001) of pharmacodynamic non-responders (defined as IPA <20%) than clopidogrel. Prasugrel 10 and 15 mg MDs achieved consistently higher mean IPA than clopidogrel 75 mg at day 28 (all P<0.0001). At pre-MD on day 28, there were no non-responders in the 10 and 15 mg prasugrel group, compared with 45% in the clopidogrel group (P=0.0007).
In this population, prasugrel (40-60 mg LD and 10-15 mg MD) achieves greater IPA and a lower proportion of pharmacodynamic non-responders compared with the approved clopidogrel dosing.
Aims/hypothesis TBC1 domain family, member 4 (TBC1D4; also known as AS160) is a cellular signalling intermediate to glucose transport regulated by insulin-dependent and -independent mechanisms. ...Skeletal muscle insulin sensitivity is increased after acute exercise by an unknown mechanism that does not involve modulation at proximal insulin signalling intermediates. We hypothesised that signalling through TBC1D4 is involved in this effect of exercise as it is a common signalling element for insulin and exercise. Methods Insulin-regulated glucose metabolism was evaluated in 12 healthy moderately trained young men 4 h after one-legged exercise at basal and during a euglycaemic-hyperinsulinaemic clamp. Vastus lateralis biopsies were taken before and immediately after the clamp. Results Insulin stimulation increased glucose uptake in both legs, with greater effects (~80%, p < 0.01) in the previously exercised leg. TBC1D4 phosphorylation, assessed using the phospho-AKT (protein kinase B)substrate antibody and phospho- and site-specific antibodies targeting six phosphorylation sites on TBC1D4, increased at similar degrees to insulin stimulation in the previously exercised and rested legs (p < 0.01). However, TBC1D4 phosphorylation on Ser-318, Ser-341, Ser-588 and Ser-751 was higher in the previously exercised leg, both in the absence and in the presence of insulin (p < 0.01; Ser-588, p = 0.09; observed power = 0.39). 14-3-3 binding capacity for TBC1D4 increased equally (p < 0.01) in both legs during insulin stimulation. Conclusion/interpretation We provide evidence for site-specific phosphorylation of TBC1D4 in human skeletal muscle in response to physiological hyperinsulinaemia. The data support the idea that TBC1D4 is a nexus for insulin- and exercise-responsive signals that may mediate increased insulin action after exercise.
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