Efficacy and safety of tiotropium Respimat® SMI in COPD in two 1-year randomized studies

Two 1-year studies evaluated the long-term efficacy and safety of tiotropium 5 or 10 μg versus placebo, inhaled via the Respimat® Soft Mist™ Inhaler (SMI). The two studies were combined and had 4 co-primary endpoints (trough FEV1 response, Mahler Transition Dyspnea Index [TDI] and St George’s Respiratory Questionnaire scores all at week 48, and COPD exacerbations per patient-year). A total of 1990 patients with COPD participated (mean FEV1: 1.09 L). The mean trough FEV1 response of tiotropium 5 or 10 μg relative to placebo was 127 or 150 mL, respectively (both P < 0.0001). The COPD exacerbation rate was significantly lower with tiotropium 5 μg (RR = 0.78; P = 0.002) and tiotropium 10 μg (RR = 0.73; P = 0.0008); the health-related quality of life and Mahler TDI co-primary endpoints were significantly improved with both doses (both P < 0.0001). Adverse events were generally balanced except anticholinergic class effects, which were more frequent with active treatment. Fatal events occurred in 2.4% (5 μg), 2.7% (10 μg), and 1.6% (placebo) of patients; these differences were not significant. Tiotropium Respimat® SMI 5 μg demonstrated sustained improvements in patients with COPD relative to placebo and similar to the 10 μg dose but with a lower frequency of anticholinergic adverse events

Newly Identified Star Clusters in M33. II. Radial HST/ACS Fields

We present integrated photometry and color-magnitude diagrams for 161 star clusters in M33, of which 115 were previously uncataloged, using the Advanced Camera For Surveys Wide Field Channel onboard the Hubble Space Telescope. The integrated V-band magnitudes of these clusters range from Mv~-9 to as faint as Mv~-4, extending the depth of the existing M33 cluster catalogs by ~1 mag. Comparisons of theoretical isochrones to the color-magnitude diagrams using the Padova models yield ages for 148 of these star clusters. The ages range from Log (t)~7.0 to Log (t)~9.0. Our color-magnitude diagrams are not sensitive to clusters older than ~1 Gyr. We find that the variation of the clusters' integrated colors and absolute magnitudes with age is consistent with the predictions of simple stellar population models. These same models suggest that the masses of the clusters in our sample range from 5x10^3 to 5x10^4 *Msun.Comment: 28 pages, 12 figures, accepted for publication in The Astrophysical Journa

Risk of emergency hospital admission related to adverse events after antibiotic treatment in adults with a common infection: impact of COVID-19 and derivation and validation of risk prediction models

Background: With the global challenge of antimicrobial resistance intensified during the COVID-19 pandemic, evaluating adverse events (AEs) post-antibiotic treatment for common infections is crucial. This study aims to examines the changes in incidence rates of AEs during the COVID-19 pandemic and predict AE risk following antibiotic prescriptions for common infections, considering their previous antibiotic exposure and other long-term clinical conditions. Methods: With the approval of NHS England, we used OpenSAFELY platform and analysed electronic health records from patients aged 18–110, prescribed antibiotics for urinary tract infection (UTI), lower respiratory tract infections (LRTI), upper respiratory tract infections (URTI), sinusitis, otitis externa, and otitis media between January 2019 and June 2023. We evaluated the temporal trends in the incidence rate of AEs for each infection, analysing monthly changes over time. The survival probability of emergency AE hospitalisation was estimated in each COVID-19 period (period 1: 1 January 2019 to 25 March 2020, period 2: 26 March 2020 to 8 March 2021, period 3: 9 March 2021 to 30 June 2023) using the Kaplan–Meier approach. Prognostic models, using Cox proportional hazards regression, were developed and validated to predict AE risk within 30 days post-prescription using the records in Period 1. Results: Out of 9.4 million patients who received antibiotics, 0.6% of UTI, 0.3% of URTI, and 0.5% of LRTI patients experienced AEs. UTI and LRTI patients demonstrated a higher risk of AEs, with a noted increase in AE incidence during the COVID-19 pandemic. Higher comorbidity and recent antibiotic use emerged as significant AE predictors. The developed models exhibited good calibration and discrimination, especially for UTIs and LRTIs, with a C-statistic above 0.70. Conclusions: The study reveals a variable incidence of AEs post-antibiotic treatment for common infections, with UTI and LRTI patients facing higher risks. AE risks varied between infections and COVID-19 periods. These findings underscore the necessity for cautious antibiotic prescribing and call for further exploration into the intricate dynamics between antibiotic use, AEs, and the pandemic

Exploring Prior Antibiotic Exposure Characteristics for COVID-19 Hospital Admission Patients: OpenSAFELY

Previous studies have demonstrated the association between antibiotic use and severe COVID-19 outcomes. This study aimed to explore detailed antibiotic exposure characteristics among COVID-19 patients. Using the OpenSAFELY platform, which integrates extensive health data and covers 40% of the population in England, the study analysed 3.16 million COVID-19 patients with at least two prior antibiotic prescriptions. These patients were compared to up to six matched controls without hospitalisation records. A machine learning model categorised patients into ten groups based on their antibiotic exposure history over the three years before their COVID-19 diagnosis. The study found that for COVID-19 patients, the total number of prior antibiotic prescriptions, diversity of antibiotic types, broad-spectrum antibiotic prescriptions, time between first and last antibiotics, and recent antibiotic use were associated with an increased risk of severe COVID-19 outcomes. Patients in the highest decile of antibiotic exposure had an adjusted odds ratio of 4.8 for severe outcomes compared to those in the lowest decile. These findings suggest a potential link between extensive antibiotic use and the risk of severe COVID-19. This highlights the need for more judicious antibiotic prescribing in primary care, primarily for patients with higher risks of infection-related complications, which may better offset the potential adverse effects of repeated antibiotic use

SN 2011hw: Helium-Rich Circumstellar Gas and the Luminous Blue Variable to Wolf-Rayet Transition in Supernova Progenitors

We present optical photometry and spectroscopy of the peculiar Type IIn/Ibn supernova SN2011hw. Its light curve exhibits a slower decline rate than normal SNeIbc, with a peak absolute magnitude of -19.5 (unfiltered) and a secondary peak of -18.3 mag (R). Spectra of SN2011hw are unusual compared to normal SN types, most closely resembling the spectra of SNeIbn. We center our analysis on comparing SN 2011hw to the well-studied TypeIbn SN2006jc. While the two SNe have many important similarities, the differences are quite telling: compared to SN2006jc, SN2011hw has weaker HeI and CaII lines and relatively stronger H lines, its light curve has a higher luminosity and slower decline rate, and emission lines associated with the progenitor's CSM are narrower. One can reproduce the unusual continuum shape of SN2011hw with equal contributions of a 6000K blackbody and a spectrum of SN2006jc. We attribute this emission component and many other differences between the two SNe to extra opacity from a small amount of additional H in SN2011hw, analogous to the small H mass that makes SNeIIb differ from SNeIb. Slower speeds in the CSM and elevated H content suggest a connection between the progenitor of SN2011hw and the class of Ofpe/WN9 stars, which have been associated with LBVs in their hot quiescent phases between outbursts, and are H-poor - but not H-free like classical Wolf-Rayet (WR) stars. We conclude that the similarities and differences between SN2011hw and SN2006jc can be largely understood if their progenitors exploded at different points in the transitional evolution from an LBV to a WR star.Comment: 11 pages, 7 figures, submitted to MNRA

On-Orbit Data and Validation of Astra\u27s ACE Electric Propulsion System

The first ACE propulsion system reached orbit on July 1st 2021 as part of Spaceflight’s demonstration of the Sherpa-LTE all-electric Orbital Transfer Vehicle (OTV). We are now able to share on-orbit data and have successfully verified the on-orbit performance of the ACE propulsion system, using xenon propellent. The mission objective was to lower altitude and use on-orbit data to derive performance, correlating the propulsion system’s performance to ground test data. The demonstration consisted of activating the propulsion system for 5- minute durations at a total input power of 340 W into the Power Processing Unit (PPU). Altitude change and propellant usage were used to derive thrust and total specific impulse. On-orbit performance is compared to ground test data in Table 1. Averaged performance is within one standard deviation of ground test data. Astra considers this a validation of system performance, as well as the ground test facilities used to test propulsion systems. On-orbit thrust has a large standard deviation as a result of the limited data sampling rate and measurement errors, rather than variability in thruster performance. Figure 1 shows the thruster operating on-orbit. The Astra team gratefully acknowledges the support of Spaceflight, Inc., the U.S. Air Force, and Defense Innovation Unit (DIU) without which this mission would not have been possible

ELUM Year 2 report for Work Package 3 - Network of field sites to measure soil C dynamics and GHG emissions. Report V2

This report describes the second year of Work Package 3 (WP3) activities within the ETI’s Ecosystem Land Use Modelling Project (“ELUM”). It expands upon information reported in the first year and provides a forward look to WP3 activities for the remainder of the project. The soil C (carbon) and GHG (Greenhouse Gas) measurements recorded as part of WP3 are required to help reduce the uncertainty associated with the sustainability of bioenergy crop deployment across the UK. This data will be used to parameterise and test the underlying process models in the WP4 modelling work, as part of the development of the over-arching meta-model. A full review of all the data collected across the WP3 network sites will be reported in the D3.5 deliverable due in May 2014. Progress with the development and testing of novel methods for GHG measurement is also included in this report; these could offer means of improving monitoring resolution, thereby enhancing the collection of GHG flux data. A complete review of this work will follow in May 2014 with the D3.4 deliverable

Combined analysis of weak lensing and X-ray blind surveys

We present a joint weak lensing and X-ray analysis of 4 deg$^2$ from the CFHTLS and XMM-LSS surveys. Our weak lensing analysis is the first analysis of a real survey using shapelets, a new generation weak lensing analysis method. We create projected mass maps of the images, and extract 6 weak-lensing-detected clusters of galaxies. We show that their counts can be used to constrain the power spectrum normalisation $\sigma_8 =0.92_{-0.30}^{+0.26}$ for $\Omega_m=0.24$. We show that despite the large scatter generally observed in the M-T relation derived from lensing masses, tight constraints on both its slope and normalisation $M_*$ can be obtained with a moderate number of sources provided that the covered mass range is large enough. Adding clusters from Bardeau et al. (2007) to our sample, we measure $M_* = 2.71_{-0.61}^{+0.79} 10^{14} h^{-1} M_\odot$. Although they are dominated by shot noise and sample variance, our measurements are consistent with currently favoured values, and set the stage for future surveys. We thus investigate the dependence of those estimates on survey size, depth, and integration time, for joint weak lensing and X-ray surveys. We show that deep surveys should be dedicated to the study of the physics of clusters and groups of galaxies. For a given exposure time, wide surveys provide a larger number of detected clusters and are therefore preferred for the measurement of cosmological parameters such as $\sigma_8$ and $M_*$. We show that a wide survey of a few hundred square degrees is needed to improve upon current measurements of these parameters. More ambitious surveys covering 7000 deg$^2$ will provide the 1% accuracy in the estimation of the power spectrum and the M-T relation normalisations.Comment: MNRAS in press Matches accepted version. References update