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

Use of the geochemical and biological sedimentary record in establishing palaeo-environments and climate change in the Lake Ngami basin, NW Botswana

Sediment samples from a continuous 4.6 m profile in the dry bed of Lake Ngami in NW Botswana were analysed for geochemistry and dated using both 14C and TL methods. Certain units in the profile were found to be diatom rich and these, with the geochemical results, were used as indicators of high and low lake levels within the basin. The Lake Ngami sediments contain a high proportion of SiO2 (51–92.5 wt%, avg. 72.4 wt%) and variable levels of Al2O3 (2.04–17.2 wt%, avg. 8.88 wt%). Based on elevated Al2O3 and organic matter (LOIorgC ) results, lacustrine conditions occurred at ca. 42 ka until 40 ka and diatom results suggest that relatively deep but brackish conditions prevailed. At 40 ka, the lacustrine sedimentary record was terminated abruptly, possibly by tectonic activity. At ca. 19 ka, shallow, aerobic, turbulent conditions were prevalent, but lake levels were at this time increasing to deeper water conditions up until ca. 17 ka. This period coincides with the Late Glacial Maximum, a period of increased aridity in the central southern Africa region. Generally, increasing Sr/Ca ratios and decreasing LOIorgC and Al2O3, from ca. 16 to 5 ka, suggest decreasing inflow into the basin and declining lake levels. Based on the enrichment of LREE results, slightly alkaline conditions prevailed at ca. 12 ka. Diatom results also support shallow alkaline conditions around this time. These lake conditions were maintained primarily by local rainfall input as the region experienced a warmer, wetter phase between 16 and 11 ka. Lake levels rose rapidly by 4 ka, probably in response to enhanced rainfall in the Angolan catchment. These results indicate that lake levels in the Lake Ngami basin are responding to rainfall changes in the Angolan catchment area and local rainfall. The results confirm that the present-day anti-phase rainfall relationship between southern Africa and regions of equatorial Africa was extant during the late Quaternary over the Angolan highlands and NW Botswana

Perceived environmental uncertainty; PEU; REF 2014

NoAn important contribution to the literature on perceived environmental uncertainty (PEU) is Milliken’s distinction between state uncertainty, effect uncertainty, and response uncertainty. However, despite its appealing logic in capturing the types of uncertainty managers may experience as they seek to understand and respond to changes in an organization’s environment, there has been no full and rigorous psychometric development and testing of scales to measure the three constructs. Using a two-phase empirical study, this research seeks to develop and test such scales in terms of dimensionality, reliability, and validity (including nomological validity). The results suggest that managers do make a meaningful distinction between different types of uncertainty, that it is worthwhile measuring all three constructs (as they have differential impacts on outcome variables), and that there are linkages between them. Managerial contributions and implications for future research are also discussed