Inflammation in benign prostate tissue and prostate cancer in the finasteride arm of the Prostate Cancer Prevention Trial

BACKGROUND: A previous analysis of the placebo arm of the Prostate Cancer Prevention Trial (PCPT) reported 82% overall prevalence of intraprostatic inflammation and identified a link between inflammation and higher-grade prostate cancer and serum PSA. Here we studied these associations in the PCPT finasteride arm. METHODS: Prostate cancer cases (N=197) detected either on a clinically indicated biopsy or on protocol-directed end-of-study biopsy, and frequency-matched controls (N=248) with no cancer on an end-of-study biopsy were sampled from the finasteride arm. Inflammation in benign prostate tissue was visually assessed using digital images of H&E stained sections. Logistic regression was used for statistical analysis. RESULTS: In the finasteride arm, 91.6% of prostate cancer cases and 92.4% of controls had at least one biopsy core with inflammation in benign areas; p < 0.001 for difference compared to placebo arm. Overall, the odds of prostate cancer did not differ by prevalence (OR=0.90, 95% CI 0.44-1.84) or extent (P-trend=0.68) of inflammation. Inflammation was not associated with higher-grade disease (prevalence: OR=1.07, 95% CI 0.43-2.69). Furthermore, mean PSA concentration did not differ by the prevalence or extent of inflammationin either cases or controls. CONCLUSION: The prevalence of intraprostatic inflammation was higher in the finasteride than placebo arm of the PCPT, with no association with higher-grade prostate cancer. IMPACT: Finasteride may attenuate the association between inflammation and higher-grade prostate cancer. Moreover, the missing link between intraprostatic inflammation and PSA suggests that finasteride may reduce inflammation-associated PSA elevation

Predictions for ASKAP Neutral Hydrogen Surveys

The Australian Square Kilometer Array Pathfinder (ASKAP) will revolutionise our knowledge of gas-rich galaxies in the Universe. Here we present predictions for two proposed extragalactic ASKAP neutral hydrogen (HI) emission-line surveys, based on semi-analytic models applied to cosmological N-body simulations. The ASKAP HI All-Sky Survey, known as WALLABY, is a shallow 3 Pi survey (z = 0 - 0.26) which will probe the mass and dynamics of over 600,000 galaxies. A much deeper small-area HI survey, called DINGO, aims to trace the evolution of HI from z = 0 - 0.43, a cosmological volume of 40 million Mpc^3, detecting potentially 100,000 galaxies. The high-sensitivity 30 antenna ASKAP core (diameter ~2 km) will provide an angular resolution of 30 arcsec (at z=0). Our simulations show that the majority of galaxies detected in WALLABY (87.5%) will be resolved. About 5000 galaxies will be well resolved, i.e. more than five beams (2.5 arcmin) across the major axis, enabling kinematic studies of their gaseous disks. This number would rise to 160,000 galaxies if all 36 ASKAP antennas could be used; the additional six antennas provide baselines up to 6 km, resulting in an angular resolution of 10 arcsec. For DINGO this increased resolution is highly desirable to minimise source confusion; reducing confusion rates from a maximum of 10% of sources at the survey edge to 3%. We estimate that the sources detected by WALLABY and DINGO will span four orders of magnitude in total halo mass (from 10^{11} to 10^{15} Msol) and nearly seven orders of magnitude in stellar mass (from 10^{5} to 10^{12} Msol), allowing us to investigate the process of galaxy formation across the last four billion years.Comment: 21 pages, accepted for publication in MNRAS, minor updates to published version and fixed links. Movies and images available at http://ict.icrar.org/store/Movies/Duffy12c

Three steps towards metrological traceability for ballistics signature measurements.

Abstract The National Institute of Standards and Technology (NIST) in collaboration with the Bureau of Alcohol, Tobacco, Firearms, and Explosives (ATF) has developed the Standard Reference Material (SRM) bullets and casings. NIST and ATF are proposing to establish a National Ballistics Measurement Traceability and Quality System for ballistics signature measurements and correlations using these materials. In this paper, three key steps towards metrological traceability for ballistics signature measurements are discussed that include: 1) Establishing a reference standard; 2) Establishing an unbroken chain of calibrations; and 3) Evaluating measurement uncertainty

Magnesium biofortification of Italian ryegrass (Lolium multiflorum L.) via agronomy and breeding as a potential way to reduce grass tetany in grazing ruminants

© 2019, The Author(s). Aim: Magnesium (Mg) deficiency (known as grass tetany) is a serious metabolic disorder that affects grazing ruminants. We tested whether Mg-fertiliser can increase Mg concentration of Italian ryegrasses (Lolium multiflorum L.) including a cultivar (cv. Bb2067; ‘Magnet’), bred to accumulate larger concentrations of Mg. Methods: Under controlled environment (CE) conditions, three cultivars (cv. Bb2067, cv. Bb2068, cv. RvP) were grown in low-nutrient compost at six fertiliser rates (0–1500μM MgCl2.6H2O). Under field conditions, the three cultivars in the CE condition and cv. Alamo were grown at two sites, and four rates of MgSO4 fertiliser application rates (0–200kgha−1 MgO). Multiple grass cuts were taken over two-years. Results: Grass Mg concentration increased with increasing Mg-fertiliser application rates in all cultivars and conditions. Under field conditions, cv. Bb2067 had 11–73% greater grass Mg concentration and smaller forage tetany index (FTI) than other cultivars across the Mg-fertiliser application rates, sites and cuts. Grass dry matter (DM) yield of cv. Bb2067 was significantly (p < 0.05) smaller than cv. Alamo. The effect of Mg-fertiliser rate on DM yield was not significant (p ≥ 0.05). Conclusions: Biofortification of grass with Mg through breeding and agronomy can improve the forage Mg concentration for grazing ruminants, even in high-growth spring grass conditions when hypomagnesaemia is most prevalent. Response to agronomic biofortification varied with cultivar, Mg-fertiliser rate, site and weather. The cost:benefit of these approaches and farmer acceptability, and the impact on cattle and sheep grazing on grasses biofortified with Mg requires further investigation

Elective Open Suprarenal Aneurysm Repair in England from 2000 to 2010 an Observational Study of Hospital Episode Statistics

Background: Open surgery is widely used as a benchmark for the results of fenestrated endovascular repair of complex abdominal aortic aneurysms (AAA). However, the existing evidence stems from single-centre experiences, and may not be reproducible in wider practice. National outcomes provide valuable information regarding the safety of suprarenal aneurysm repair. Methods: Demographic and clinical data were extracted from English Hospital Episodes Statistics for patients undergoing elective suprarenal aneurysm repair from 1 April 2000 to 31 March 2010. Thirty-day mortality and five-year survival were analysed by logistic regression and Cox proportional hazards modeling. Results: 793 patients underwent surgery with 14% overall 30-day mortality, which did not improve over the study period. Independent predictors of 30-day mortality included age, renal disease and previous myocardial infarction. 5-year survival was independently reduced by age, renal disease, liver disease, chronic pulmonary disease, and known metastatic solid tumour. There was significant regional variation in both 30-day mortality and 5-year survival after risk-adjustment. Regional differences in outcome were eliminated in a sensitivity analysis for perioperative outcome, conducted by restricting analysis to survivors of the first 30 days after surgery. Conclusions: Elective suprarenal aneurysm repair was associated with considerable mortality and significant regional variation across England. These data provide a benchmark to assess the efficacy of complex endovascular repair of supra-renal aneurysms, though cautious interpretation is required due to the lack of information regarding aneurysm morphology. More detailed study is required, ideally through the mandatory submission of data to a national registry of suprarenal aneurysm repair

Paraherquamide and 2-Deoxy-paraherquamide Distinguish Cholinergic Receptor Subtypes in Ascaris Muscle

Paraherquamide is a novel natural anthelmintic product with a mode of action that is incompletely characterized. Nicotine and cholinergic-anthelmintic agonists of different chemical classes were used to produce contraction in Ascaris muscle strips. Paraherquamide and a semisynthetic derivative, 2-deoxy-paraherquamide, antagonized these responses. Analysis of the actions of the antagonists was made using the simple competitive model and nonlinear regression to estimate the pKB values of the antagonists. The analysis was tested using Clark plots. The pKB values for paraherquamide were: nicotine, 5.86 0.14; levamisole, 6.61 0.19; pyrantel, 6.50 0.11; and bephenium, 6.75 0.15. The pKB of nicotine was significantly different from the pKB values for levamisole, pyrantel, and bephenium, showing that paraherquamide can distinguish a subtype of cholinergic receptors sensitive to nicotine and a subtype of cholinergic receptors sensitive to levamisole, pyrantel, and bephenium. The pKB values for 2-deoxy-paraherquamide were: levamisole, 5.31 0.13; pyrantel, 5.63 0.10; and bephenium, 6.07 0.13. The Clark plots of the antagonism illustrated the degree of fit to the competitive model for 2-deoxy-paraherquamide. 2-Deoxy-paraherquamide selectively antagonized the effects of bephenium; the pKB values of levamisole and pyrantel were significantly different from the pKB of bephenium. Paraherquamide and 2-deoxy-paraherquamide are selective competitive cholinergic antagonists that distinguish subtypes of cholinergic receptor in Ascaris muscle corresponding to nicotine-, levamisole-, and bephenium-sensitive receptors

New Results from the Magellan IMACS Spectroscopic Lyman Alpha Survey: NICMOS Observations of Lyman Alpha emitters at z=5.7

We present NICMOS J110 (rest-frame 1200-2100 A) observations of the three z=5.7 Lyman Alpha emitters discovered in the blind multislit spectroscopic survey by Martin et al. (2008). These images confirm the presence of the two sources which were previously only seen in spectroscopic observations. The third source, which is undetected in our J110 observations has been detected in narrowband imaging of the Cosmic Origins Survey (COSMOS), so our nondetection implies a rest frame equivalent width >146 Angstroms (3 sigma). The two J110-- detected sources have more modest rest frame equivalent widths of 30-40 Angstroms, but all three are typical of high-redshift LAEs. In addition, the J110- detected sources have UV luminosities that are within a factor of two of L*_{UV}, and sizes that appear compact (r_{hl} ~ 0."15) in our NIC2 images -- consistent with a redshift of 5.7. We use these UV-continuum and Lyman Alpha measurements to estimate the i-z colors of these galaxies, and show that at least one, and possibly all three would be missed by the i-dropout LBG selection. These observations help demonstrate the utility of multislit narrowband spectroscopy as a technique for finding faint emission line galaxies.Comment: Accepted to Ap

Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors

Background: Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries. Methods: In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants. Findings: 45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p&lt;0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76–0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39–0·53; approximately 215 mL) in the 14-week group (p&lt;0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p&lt;0·0001 for each) than those observed in the standard frequency groups. Interpretation: Over 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency. Funding: NHS Blood and Transplant, National Institute for Health Research, UK Medical Research Council, and British Heart Foundation

Planetary Candidates Observed by Kepler, III: Analysis of the First 16 Months of Data

New transiting planet candidates are identified in sixteen months (May 2009 - September 2010) of data from the Kepler spacecraft. Nearly five thousand periodic transit-like signals are vetted against astrophysical and instrumental false positives yielding 1,091 viable new planet candidates, bringing the total count up to over 2,300. Improved vetting metrics are employed, contributing to higher catalog reliability. Most notable is the noise-weighted robust averaging of multi-quarter photo-center offsets derived from difference image analysis which identifies likely background eclipsing binaries. Twenty-two months of photometry are used for the purpose of characterizing each of the new candidates. Ephemerides (transit epoch, T_0, and orbital period, P) are tabulated as well as the products of light curve modeling: reduced radius (Rp/R*), reduced semi-major axis (d/R*), and impact parameter (b). The largest fractional increases are seen for the smallest planet candidates (197% for candidates smaller than 2Re compared to 52% for candidates larger than 2Re) and those at longer orbital periods (123% for candidates outside of 50-day orbits versus 85% for candidates inside of 50-day orbits). The gains are larger than expected from increasing the observing window from thirteen months (Quarter 1-- Quarter 5) to sixteen months (Quarter 1 -- Quarter 6). This demonstrates the benefit of continued development of pipeline analysis software. The fraction of all host stars with multiple candidates has grown from 17% to 20%, and the paucity of short-period giant planets in multiple systems is still evident. The progression toward smaller planets at longer orbital periods with each new catalog release suggests that Earth-size planets in the Habitable Zone are forthcoming if, indeed, such planets are abundant.Comment: Submitted to ApJS. Machine-readable tables are available at http://kepler.nasa.gov, http://archive.stsci.edu/kepler/results.html, and the NASA Exoplanet Archiv