Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

GMTIFS: Cryogenic rotary mechanisms for the GMT Integral-Field Spectrograph

A representative range of the rotary mechanisms proposed for use in GMTIFS is described. All are driven by cryogenically rated stepper motors. For each mechanism, angular position is measured by means of eddy current sensors arranged to function as a resolver. These measure the linear displacement of a decentered aluminum alloy target in two orthogonal directions, from which angular position is determined as a function of the displacement ratio. Resolver function and performance is described. For each mechanism, the mechanical design is described and the adequacy of positioning repeatability assessed. Options for improvement are discussed

GMTIFS: The adaptive optics beam steering mirror for the GMT integral-field spectrograph

To achieve the high adaptive optics sky coverage necessary to allow the GMT Integral-Field Spectrograph (GMTIFS) to access key scientific targets, the on-instrument adaptive-optics wavefront-sensing (OIWFS) system must patrol the full 180 arcsecond diameter guide field passed to the instrument. The OIWFS uses a diffraction limited guide star as the fundamental pointing reference for the instrument. During an observation the offset between the science target and the guide star will change due to sources such as flexure, differential refraction and non-sidereal tracking rates. GMTIFS uses a beam steering mirror to set the initial offset between science target and guide star and also to correct for changes in offset. In order to reduce image motion from beam steering errors to those comparable to the AO system in the most stringent case, the beam steering mirror is set a requirement of less than 1 milliarcsecond RMS. This corresponds to a dynamic range for both actuators and sensors of better than 1/180,000. The GMTIFS beam steering mirror uses piezo-walk actuators and a combination of eddy current sensors and interferometric sensors to achieve this dynamic range and control. While the sensors are rated for cryogenic operation, the actuators are not. We report on the results of prototype testing of single actuators, with the sensors, on the bench and in a cryogenic environment. Specific failures of the system are explained and suspected reasons for them. A modified test jig is used to investigate the option of heating the actuator and we report the improved results. In addition to individual component testing, we built and tested a complete beam steering mirror assembly. Testing was conducted with a point source microscope, however controlling environmental conditions to less than 1 micron was challenging. The assembly testing investigated acquisition accuracy and if there was any un-sensed hysteresis in the system. Finally we present the revised beam steering mirror design based on the outcomes and lessons learnt from this prototyping

GMTIFS: The Giant Magellan Telescope integral fields spectrograph and imager

GMTIFS is the first-generation adaptive optics integral-field spectrograph for the GMT, having been selected through a competitive review process in 2011. The GMTIFS concept is for a workhorse single-object integral-field spectrograph, operating at intermediate resolution (R~5,000 & 10,000) with a parallel imaging channel. The IFS offers variable spaxel scales to Nyquist sample the diffraction limited GMT PSF from λ ~ 1-2.5 μm as well as a 50 mas scale to provide high sensitivity for low surface brightness objects. The GMTIFS will operate with all AO modes of the GMT (Natural guide star - NGSAO, Laser Tomography – LTAO, and, Ground Layer - GLAO) with an emphasis on achieving high skycoverage for LTAO observations. We summarize the principle science drivers for GMTIFS and the major design concepts that allow these goals to be achieved

Evidence of Previous Infection with Mycobacterium avium-Mycobacterium intracellulare Complex among Healthy Subjects: An International Study of Dominant Mycobacterial Skin Test Reactions

Skin tests with 0.1 mL of intermediate-strength Mycobacterium tuberculosis purified protein derivative (PPD) and 0.1 mL of Mycobacterium avium sensitin were conducted on 484 healthy subjects from diverse geographic sites. Reactions of ⩾5 mm to one antigen that exceeded the reaction to the other by ⩾3 mm were considered M. avium- or PPD-dominant. PPD-dominant reactions were more frequent at sites where routine Bacille Calmette-Guérin immunization is done or where there are high rates of tuberculosis: New Hampshire, 2%; Boston, 7%; Finland, 14%; Trinidad, 26%; and Kenya, 28%. However, rates of M. avium-dominant reactions ranged from 7% to 12% at all sites. Analysis of dominant reactions based on a more stringent 10-mm minimum reaction size showed similar trends. These data suggest that exposure to MAC is similar in developed and developing countries but that broad mycobacterial immunity is greater in developing countries and may contribute to the lower rates of disseminated MAC infections in AIDS in these areas

Avalanche photo diodes in the observatory environment: Lucky imaging at 1-2.5 microns

The recent availability of large format near-infrared detectors with sub-election readout noise is revolutionizing our approach to wavefront sensing for adaptive optics. However, as with all near infrared detector technologies, challenges exist in moving from the comfort of the laboratory test bench into the harsh reality of the observatory environment. As part of the broader adaptive optics program for the GMT, we are developing a near-infrared Lucky Imaging camera for operational deployment at the ANU 2.3 m telescope at Siding Spring Observatory. The system provides an ideal test-bed for the rapidly evolving Selex/SAPHIRA eAPD technology while providing scientific imaging at angular resolution rivalling the Hubble Space Telescope at wavelengths λ = 1.3-2.5 μ

Review article: animal bites: an update for management with a focus on infections

Technological advances in radiation therapy permit steep dose gradients from the target to spare normal tissue, but increase the risk of geographic miss. Suboptimal target delineation adversely affects clinical outcomes. Prospective peer review is a method for quality assurance of oncologists' radiotherapy plans. Published surveys suggest it is widely implemented. However, it may not be feasible to review every case before commencement of radiation therapy in all departments. The rate of plan changes following peer review of cases without a specific subsite or modality is typically around 10%. Stereotactic body radiation therapy, head and neck, gynaecological, gastrointestinal, haematological and lung cases are associated with higher rates of change of around 25%. These cases could thus be prioritised for peer review. Other factors may limit peer review efficacy including organisational culture, time constraints and the physical environment in which sessions are held. Recommendations for peer review endorsed by the American Society for Radiation Oncology were made available in 2013, but a number of relevant studies have been published since. Here we review and update the literature, and provide an updated suggestion for the implementation of peer review to serve as an adjunct to published guidelines. This may help practitioners evaluate their current processes and maximise the utility and effectiveness of peer review sessions