Spiritual formation in secondary education: An investigation into how children use collective worship within secondary education

The past thirty years has witnessed significant changes in the practice of collective worship in UK schools, although the statutory requirements relating to collective worship have not changed since 1988. Predominantly, collective worship in schools is managed and delivered by adults. However I became aware, from my professional context and practice as a chaplain in a faithbased urban secondary school, little attention has been given to the ways children actually experience and make use of collective worship. The aim of my research has therefore been to gain a more child-centred perspective on collective worship, and to generate a deeper understanding of how children might use collective worship to reflect on their relationships and life experiences. My research methods reflect the aim to privilege the children’s voices: the primary data source comes from children’s own accounts of participating in collective worship, using a longitudinal qualitative method across four years. Using a definition drawn from Hay and Nye (1996, 2006) and Hyde (2008), the study employs thematic analysis to interpret the data using the framework of spirituality as relationship with God (or Transcendent), self and other (including people and the world). The results revealed in this study show that children construct collective worship as a sacred space in which they are able to reflect on their own understandings of God, faith and the world. Crucial to this process is an emerging sense of self and its connection with these relationships. Through critical reflection within collective worship children encounter a particular dynamic that I have identified as reluctance-permission-opportunity. I therefore argue this dynamic underpins a child’s evolving sense and awareness of faith and relationship with God, other and self, and represents aspects of a three-dimensional model of spiritual reflection and maturity. The study concludes that the sacred space of collective worship is actively constructed by the children, building on the established frameworks offered by the statutory provision of school-based collective worship. The constructed sacred space of collective worship is – for the children – precious, set apart, revelatory, special and life-changing. As such there is a sense of ownership by the children of this sacred space. This thesis suggests new approaches to researching and understanding children’s spirituality as well as implications for professional practice. It represents a contribution to knowledge by advancing a more nuanced understanding of children’s spiritual development than currently exists. The notion of a three-dimensional dynamic also offers a contribution to theoretical understandings of the concepts of spiritual formation. The findings of the research are seen as having implications for professional practice in collective worship by arguing for a child-centred approach to critical spiritual exploration and reflection, and therefore to the design and provision of collective worship

UK National Ecosystem Assessment Follow-on. Work package 7: Operationalising scenarios in the UK National Ecosystem Assessment Follow-on

Summary Study aims and approach An aim of the UK NEA Follow-on (UK NEAFO) is to develop and communicate the evidence base of the UK NEA and make it relevant to decision and policy making. It also provides an important opportunity for those working on scenario methods and concepts to scrutinise the role of futures thinking in the management of ecosystem services and so develop their effectiveness as decision support tools. In this study we have therefore asked: how can the UK NEA scenarios help us to understand, manage and communicate the consequences of changes in ecosystem services across all scales? There are many different understandings about what scenarios are, and what they should be used for. To clarify the issues surrounding the role of scenarios, we have approached this work from two angles. We have firstly looked at the way the storylines can support decision making processes. Secondly, we have looked at the content of the scenarios themselves and explored how through the use of models the UK NEA scenarios as products might be refined to enhance their value as analytical tools. Scenarios in Action We used the opportunity of a series of meetings with stakeholders to develop the UK NEA scenarios from a process perspective. These meetings took various forms, but throughout the main aim was to find out whether people found the scenarios sufficiently believable, challenging and relevant. In workshops organised by the scenario team in Leeds, Edinburgh and Belfast, we worked with participants on a series of tasks designed to help them immerse themselves in the scenarios and reflect on them critically. While those we worked with had many comments about the scenarios in detail, the evidence we collected from these meetings suggests that the majority of people found the scenarios to be plausible and the projections consistent. The majority also agreed with the proposition that the suite of scenarios as a whole addressed a relevant ranges of issues. We explored with the workshop participants several ways in which the storylines could be enriched, by: developing the narrative about the way people might live in the different scenario worlds; developing time-lines for the scenarios; thinking more deeply about regional and local differences; and, exploring how the scenarios would frustrate or facilitate the embedding of the ecosystem approach in decision making. We found that while all of these elements had value in terms of stimulating discussion and understanding of the scenarios, they were not needed in order to address deficiencies in the original storylines in terms of plausibility or credibility. The evidence we collected therefore suggests that the existing narratives are probably sufficient as an entry point for discussions about the future of ecosystem services in the UK. What was apparent from the observations that we made in the workshops was that it would probably be a mistake to ‘over-engineer’ or ‘over-specify’ the narratives because there needs to be room for discussion and probing. We were struck how people took the existing scenarios and found new features and ideas in them than had not been identified by in the original work. For example, in one session National Security, with its emphasis on resource efficiency, was found to be ‘greener’ than it initially looks. In another Local Stewardship was discovered to need some degree of central control and regulation to work efficiently. These kinds of discussion are evidence of the reflection, deliberation and social learning that can be promoted by using the UK NEA scenarios. UK NEAFO Work Package 7: Operationalising scenarios 7 In the workshop we organised in Belfast we found that the presentation of the scenarios could be tailored to a specific region (i.e. Northern Ireland) and, through area-specific breakout groups during the workshop, to specific localities within it. However, our experiences here emphasised the need for considerable preparation, consultation with the stakeholder community, and changing of the workshop format to make the scenarios intelligible and engaging to local stakeholders. Work on the use of the scenarios in a more explicit decision support role will be reported via the work on response options (WP8), which considered how they could be used to ‘stress-test’ policy response options. The experience gained from the work undertaken in the early stages of UK NEAFO was that the scenarios appeared to provide a suitable platform for the work, but that the stresstesting methodology needed to be refined. During the follow-on we have also interviewed policy leads in Defra, for example, to gain a better picture of policy needs, and the way scenarios might usefully serve them. Apart from the challenge of ‘relevance’ it is clear that the time needed for people to work with scenarios probably means that they are less useful to policy customers in the context of their everyday work but can be useful at a very broad and strategic level. However, there is clearly an opportunity for scenarios to be used more extensively through commissioned work. The importance of commissioned work has been emphasised during the follow-on phase by invitations to observe the work of the CAMERAS1 work in Scotland, and the Noise Study being undertaken for Defra. Both are actively using the UK NEA scenarios. The outcomes of these on-going studies will be reported elsewhere by others. Nevertheless, even though these projects are at a preliminary stage they help us better understand how scenarios can be used to communicate the consequences of changes in ecosystem services to different groups and individuals. Scenarios as products: developing the model base The UK NEA scenarios were initially used to make both qualitative and quantitative projections. The quantitative work mainly involved modelling how land cover would change under the different scenarios (Haines-Young et al. 2011). Although these data were used to make an analysis of the changes in marginal economic values for some ecosystem services during the initial phase of the UK NEA, they have not been fully exploited. At the time it was recognised that there were many gaps in our understanding of the links between land cover and ecosystem services; UK NEAFO has provided the opportunity to address some of these deficiencies. Thus in the follow-on work we have sought to extend the range of models that can be used to explore the UK NEA scenarios. The modelling work has not sought to change the scenarios fundamentally, but to enrich the insights that can be derived from exploring the differences between them in a systematic, and quantitative way. The goal, has been to extend the analysis that can be built up around the narratives and hence enrich the scenarios as ‘products’. Four topic areas were selected as the focus for this work: flood and drought risk (based on an analysis of changes in river flows), biodiversity (farmland birds), marine and cultural ecosystem services. Catchment modelling We looked at the effects of land-use change on river flows under each of the UK NEA scenarios. We modelled hydrological discharge within 34 UK catchments and calculated four hydrological indicators for each catchment: average annual discharge, flood hazard, and Q5 and Q95 (measures of the magnitude of unusually high (Q5) and unusually low (Q95) flows). For our flood hazard indicator we calculated the interval between floods of a size currently occurring every 30 years. Although we kept climate constant in the models, as we wanted to isolate the effects of land cover change, we ran them for both the high and low climate change land cover variants for each scenario. 1 A Coordinated Agenda for Marine, Environment and Rural Affairs Science, 2011-2016. http://www.scotland.gov.uk/Topics/Research/About/EBAR/CAMERASsite In general, the ‘green’ scenarios, Nature@Work and Green and Pleasant Land, as well as National Security, were associated with lower flows than currently occur (when measured using any of the four indicators). However, for a given scenario there was a great deal of variability between catchments in terms of the size and statistical significance of the differences. The magnitude of change across all scenarios and catchments ranged from -13% to 6% for average annual discharge, -14 to 7% for Q5, -24 to 27 % for Q95 and -16 to 36 years for flood hazard. Differences were particularly evident between Nature@Work and World Markets, with the latter associated with higher flows than occur currently, and the majority of the statistically significant increased flows. Some catchments showed significant changes that were different in sign between these two scenarios. Taken together, our results indicate that that in managing change a balance needs to be struck between alleviating the likelihoods of increased drought and increased flooding, depending on the likely effects of these phenomena in the catchment. Farmland birds We looked at the relationship between land use data produced during the first phase of the UK NEA and models of farmland bird populations, in 1kmx1km squares covered by the Breeding Bird Survey (BBS) and Winter Farmland Bird Survey (WFBS). We used Functional Space Models to estimate the annual population growth rate under each scenario of each of the 19 farmland bird species used to calculate the farmland bird index (Gregory et al. 2004). We used this to look at the relationship between land use under the scenarios and: i) the average population growth rate for all 19 species, and ii) a subset of 11 species showing declining population trends under current land use. Overall we found that land use change across the scenarios had relatively little impact. However, the only statistically significant change was for declining species under Green and Pleasant Land, where population growth rates became significantly more negative. We used Mechanistic Models to estimate the number of over-winter ‘bird-days’ for two types of seed-eating farmland birds, a yellowhammer-type and linnet-type These species were chosen because they differ in their food preferences with respect to cereal, oil and weed seeds, but between them are representative of the diversity of seed-eating farmland birds as a whole. We found a significant decline in the ecological value of lowland agricultural areas for these species across all UK NEA scenarios, but the greatest impact was for scenarios with the highest monetised values for ecosystem services, as measured by the first phase of the UK NEA (Nature@Work, Green and Pleasant Land). This appears to be due to the fact that, compared with the baseline, the area of arable crops declines most sharply under these scenarios, due partly to changes in land use but also because of conversion of arable land to other habitats important for ecosystem services (e.g. woodland). Taken together these results imply a trade-off between overall value for ecosystem services and conservation of farmland birds, and highlight the need to consider the specific impacts of land use change on biodiversity, alongside other ecosystem services. Marine ecosystem services Only a limited attempt was made to model marine ecosystem services during the first phase of the UK NEA. In the follow-on we have conducted preliminary work to produce spatially explicit models for three important marine ecosystem services: fisheries landings, aquaculture production and carbon sequestration. We made comparisons between baseline data and time slices for 2015, 2030 UK NEAFO Work Package 7: Operationalising scenarios 9 and 2060 under four of the UK NEA scenarios that were considered most relevant for the sector, and mapped these across UK territorial waters. There is a high degree of uncertainty associated with the models, mainly due to a lack of suitable data and poor knowledge of the drivers of change. In many cases, in the absence of robust quantitative models, we needed to take the qualitative descriptions of the UK NEA scenarios and combine these with expert knowledge to estimate changes in the three types of ecosystem service. We estimated that in three of the four scenarios: Nature@Work, Local Stewardship and National Security, fisheries landings would be, by 2060 only slightly lower or at higher levels than they are today. Under World Markets, however, projected landings would decline significantly by 2060, due to a lack of regulation combined with high levels of investment from private capital. In the light of this, it was interesting that aquaculture was at higher levels under World Markets than under any of the other scenarios, although all of them showed higher levels than the baseline. This was because under this scenario more investment capital would be available to invest in fish farms. We believe that carbon sequestration would be most likely to be impacted by the World Markets and Natural Security, due to higher CO2 emissions causing an increase in ocean acidification. Our results, although tentative, mark a significant first step in attempts to map and project the impact of possible future change on marine ecosystem services. Cultural Ecosystem Services In the first phase of the UK NEA, the relationship between the drivers of change and cultural ecosystem services (CES) was mainly explored through the impact they had on land cover. For UK NEAFO, we additionally used the Monitor of Engagement for the Natural Environment (MENE) dataset. We examined how the UK NEA scenarios can be used as a framework to explore the relationship between the supply of cultural spaces in the landscape and peoples preferences for different types of natural spaces and practices in them. We have developed a Bayesian Belief Network (BBN) that allows users to explore these relationships interactively and look at the potential impacts of changes socio-demographic structure of the kind described by the UK NEA scenarios. Our spatial analysis of the MENE data showed that people tend to select locations with higher woodland cover than the average for the surroundings, when they travel intermediate distances from their home, but that this tendency declines when they travel longer distances. Woodland cover is projected to double under both Nature@Work and Green and Pleasant Land, and both provide more opportunities to visit woodland close to home than under scenarios such as World Markets. However, our analysis shows that on the basis of the current geography of people and woodlands, the way planting is targeting under Green and Pleasant Land has the potential to deliver greater joint benefits from biodiversity change and cultural ecosystem services than Nature@Work. The BBN we have developed using the HUGIN Expert software allows the relationships within the MENE data to be explored interactively; it is hosted on a prototype website that is open to the wider community. By examining the relationships between socio-demographic characteristics of the MENE respondents, the types of natural spaces they visit and the activities they do in them, this BBN tool allows users to explore the impacts of possible future change on the supply and demand of CES. Conclusion How can plausible future scenarios help understand, manage and communicate the consequences of changes in ecosystem services across all scales? In this work we have shown that they can be used to promote understanding by the deliberative processes that they engender. The UK NEA scenarios appear to be sufficiently rich and comprehensive to support debate across a wide range of topic areas relevant to current policy concerns. The scenarios can also help understanding by providing a framework in which current models can be applied and the outcome used both to test the plausibility of the scenarios themselves and to deepen the insights that can be derived from them. These analytical ‘scenario products’ can be equally important both in terms of deepening our understanding of the assumptions on which the scenarios are built and in stimulating debate about their implications. We have shown that the distinction between the ‘process’ and ‘product’ dimensions of scenario thinking is a useful one, given the many ways scenarios can be used. The distinction clarifies some of the different purposes and problems that scenarios work seeks to address. However, our work also demonstrates that both components have their strengths, and neither can be taken isolation. If we are to use scenarios to understand, manage and communicate the consequences of changes in ecosystem services across different scales and in different contexts, then targeted analytical studies developed within the qualitative framework of the UK NEA scenarios, can enrich our understanding of today’s issues and how we might respond to them

Blazars in the Fermi Era: The OVRO 40-m Telescope Monitoring Program

The Large Area Telescope (LAT) aboard the Fermi Gamma-ray Space Telescope provides an unprecedented opportunity to study gamma-ray blazars. To capitalize on this opportunity, beginning in late 2007, about a year before the start of LAT science operations, we began a large-scale, fast-cadence 15 GHz radio monitoring program with the 40-m telescope at the Owens Valley Radio Observatory (OVRO). This program began with the 1158 northern (declination>-20 deg) sources from the Candidate Gamma-ray Blazar Survey (CGRaBS) and now encompasses over 1500 sources, each observed twice per week with a ~4 mJy (minimum) and 3% (typical) uncertainty. Here, we describe this monitoring program and our methods, and present radio light curves from the first two years (2008 and 2009). As a first application, we combine these data with a novel measure of light curve variability amplitude, the intrinsic modulation index, through a likelihood analysis to examine the variability properties of subpopulations of our sample. We demonstrate that, with high significance (7-sigma), gamma-ray-loud blazars detected by the LAT during its first 11 months of operation vary with about a factor of two greater amplitude than do the gamma-ray-quiet blazars in our sample. We also find a significant (3-sigma) difference between variability amplitude in BL Lacertae objects and flat-spectrum radio quasars (FSRQs), with the former exhibiting larger variability amplitudes. Finally, low-redshift (z<1) FSRQs are found to vary more strongly than high-redshift FSRQs, with 3-sigma significance. These findings represent an important step toward understanding why some blazars emit gamma-rays while others, with apparently similar properties, remain silent.Comment: 23 pages, 24 figures. Submitted to ApJ

A Transient Sub-Eddington Black Hole X-ray Binary Candidate in the Dust Lanes of Centaurus A

We report the discovery of a bright X-ray transient, CXOU J132527.6-430023, in the nearby early-type galaxy NGC 5128. The source was first detected over the course of five Chandra observations in 2007, reaching an unabsorbed outburst luminosity of 1-2*10^38 erg/s in the 0.5-7.0 keV band before returning to quiescence. Such luminosities are possible for both stellar-mass black hole and neutron star X-ray binary transients. Here, we attempt to characterize the nature of the compact object. No counterpart has been detected in the optical or radio sky, but the proximity of the source to the dust lanes allows for the possibility of an obscured companion. The brightness of the source after a >100 fold increase in X-ray flux makes it either the first confirmed transient non-ULX black hole system in outburst to be subject to detailed spectral modeling outside the Local Group, or a bright (>10^38 erg/s) transient neutron star X-ray binary, which are very rare. Such a large increase in flux would appear to lend weight to the view that this is a black hole transient. X-ray spectral fitting of an absorbed power law yielded unphysical photon indices, while the parameters of the best-fit absorbed disc blackbody model are typical of an accreting ~10 Msol black hole in the thermally dominant state.Comment: 8 pages, 6 figures, accepted for publication in Ap

Herschel-ATLAS: Blazars in the science demonstration phase field

To investigate the poorly constrained sub-mm counts and spectral properties of blazars we searched for these in the Herschel-ATLAS (H-ATLAS) science demonstration phase (SDP) survey catalog. We cross-matched 500 μm sources brighter than 50 mJy with the FIRST radio catalogue. We found two blazars, both previously known. Our study is among the first blind blazar searches at sub-mm wavelengths, i.e., in the spectral regime where little is still known about the blazar SEDs, but where the synchrotron peak of the most luminous blazars is expected to occur. Our early results are consistent with educated extrapolations of lower frequency counts and question indications of substantial spectral curvature downwardsand of spectral upturns at mm wavelengths. One of the two blazars is identified with a Fermi/LAT Υ-ray source and a WMAP source. The physical parameters of the two blazars are briefly discussed. These observations demonstrate that the H-ATLAS survey will provide key information aboutthe physics of blazars and their contribution to sub-mm counts.We are grateful to the referee, P. Padovani, for very useful comments. Thanks are due to the PACO collaboration for having made available the data on the 2 blazars. M.M. and L.B. thanks the staff at the Australia Telescope Compact Array site, Narrabri (NSW), for the valuable support they provide in running the telescope. Work partially supported by the Italian Space Agency (contract I/016/07/0 "COFIS'' and ASI/INAF Agreement I/072/09/0 for the Planck LFI Activity of Phase E2). This research has made use of the NASA/IPAC Extragalactic Database (NED) which is operated by the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administration

Low-Mass X-ray Binaries and Globular Clusters in Centaurus A

We present results of Hubble Space Telescope and Chandra X-ray Observatory observations of globular clusters (GCs) and low-mass X-ray binaries (LMXBs) in the central regions of Centaurus A. Out of 440 GC candidates we find that 41 host X-ray point sources that are most likely LMXBs. We fit King models to our GC candidates in order to measure their structural parameters. We find that GCs that host LMXBs are denser and more compact, and have higher encounter rates and concentrations than the GC population as a whole. We show that the higher concentrations and masses are a consequence of the dependence of LMXB incidence on central density and size plus the general trend for denser GCs to have higher masses and concentrations. We conclude that neither concentration nor mass are fundamental variables in determining the presence of LMXBs in GCs, and that the more fundamental parameters relate to central density and size.Comment: 4 pages, 2 figures. Accepted for publication in ApJ Letter

Herschel-ATLAS and ALMA: HATLAS J142935.3-002836, a lensed major merger at redshift 1.027

Context. The submillimetre-bright galaxy population is believed to comprise, aside from local galaxies and radio-loud sources, intrinsically active star-forming galaxies, the brightest of which are lensed gravitationally. The latter enable studies at a level of detail beyond what is usually possible by the observation facility. Aims. This work focuses on one of these lensed systems, HATLAS J142935.3−002836 (H1429−0028), selected in the Herschel-ATLAS field. Gathering a rich, multi-wavelength dataset, we aim to confirm the lensing hypothesis and model the background source’s morphology and dynamics, as well as to provide a full physical characterisation. Methods. Multi-wavelength high-resolution data is utilised to assess the nature of the system. A lensing-analysis algorithm that simultaneously fits different wavebands is adopted to characterise the lens. The background galaxy dynamical information is studied by reconstructing the 3D source plane of the ALMA CO (J:4 → 3) transition. Near-IR imaging from HST and Keck-AO allows to constrain rest-frame optical photometry independently for the foreground and background systems. Physical parameters (such as stellar and dust masses) are estimated via modelling of the spectral energy distribution taking source blending, foreground obscuration, and differential magnification into account. Results. The system comprises a foreground edge-on disk galaxy (at zsp = 0.218) with an almost complete Einstein ring around it. The background source (at zsp = 1.027) is magnified by a factor of μ ~ 8−10 depending on wavelength. It is comprised of two components and a tens-of-kpc-long tidal tail resembling the Antennæ merger. As a whole, the background source is a massive stellar system (1.32-0.41+ 0.63 × 1011 M⊙) forming stars at a rate of 394 ± 90  M⊙ yr-1, and it has a significant gas reservoir MISM = 4.6 ± 1.7 × 1010 M⊙. Its depletion time due to star formation alone is thus expected to be τSF = MISM/ SFR = 117 ± 51 Myr. The dynamical mass of one of the components is estimated to be 5.8 ± 1.7 × 1010 M⊙, and, together with the photometric total mass estimate, it implies that H1429−0028 is a major merger system (1:2.8-1.5+1.8)

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570