Marine ecosystem uptake of nuclear reprocessing derived radiocarbon (14C)

The nuclear energy industry produces radioactive waste at various stages of the fuel cycle. In the United Kingdom, spent fuel is reprocessed at the Sellafield facility (formerly known as Windscale), in Cumbria on the north-west coast of England. Waste generated at the site comprises a wide range of radionuclides, including radiocarbon (14C) which, due to its long half-life (5730 years), environmental mobility and high bio-availability, is the largest contributor to collective dose commitment from the entire nuclear industry. 14C is disposed of in various forms, one of which is as highly soluble inorganic carbon within the low-level liquid radioactive effluent, via pipelines, into the Irish Sea. The discharged 14C is then rapidly incorporated into the dissolved inorganic carbon (DIC) pool. This project aimed to better understand the fate of Sellafield discharges of 14C to the marine environment. Investigations of intertidal sites in the Irish Sea and West of Scotland found 14C enrichment above ambient background levels in shell material, including at the most northerly site, located 265 km north of Sellafield. Dissolved inorganic 14C is readily utilised during shell formation by calcifying organisms and mussel shell 14C activities at sites closer to Sellafield appear to be varying in response to the total Sellafield 14C discharge activity over the preceding 5 years. Due to subsequent erosion of this material, 14C is transferred to finer fractions of intertidal sediments where it is accumulating. During photosynthesis, primary producing organisms also utilise carbon derived from the DIC pool. This uptake and the trophic-level transfer of 14C within the Irish Sea and West of Scotland marine environments were examined. The 14C activities of Irish Sea DIC and biota in the east and west basins were enriched and highly variable. A general decrease in 14C activity with distance from Sellafield was observed, although, enriched activities were also found in the West of Scotland where the activities were more homogenous. Organic sediments were significantly less enhanced than associated benthic organisms. This could be due to rapid scavenging of labile, 14C-enriched organic material by organisms and mixing to depth with older, 14C depleted material. Commercially important species were 14C enriched; however, the radiation dose from their consumption is extremely low and radiologically insignificant. To evaluate the transfer of 14C to top predators in the UK marine environment, 14C activities were examined in stranded marine mammals. All Irish Sea samples were enriched, as were most from the West of Scotland, although the 14C activities were lower. In demonstrating transfer of enriched 14C to apex predators for the first time, this study also showed that marine mammal activities correlated significantly with distance from Sellafield and Sellafield 14C discharge activities for 24 months prior to stranding. These measurements also provided some insight into harbour porpoise (Phocoena phocoena) ecology, indicating high foraging fidelity and suggesting the animals stranded on the West of Scotland did not forage in the Irish Sea. The studies in this thesis examined the dispersion of Sellafield-derived 14C to both near- and far-field sites and the subsequent ecosystem uptake and trophic transfer at these locations. However, it is important to attempt to understand the fate of 14C discharges beyond the limitations and scope of analytical investigations. To do so, the first spatial-temporal ecosystem model to predict the ecological fate of Sellafield-derived 14C was developed. The observed trends in 14C activities between different species were predicted by the model which illustrated the integration of 14C in species at higher trophic levels through time

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

Same data, different conclusions : radical dispersion in empirical results when independent analysts operationalize and test the same hypothesis

In this crowdsourced initiative, independent analysts used the same dataset to test two hypotheses regarding the effects of scientists’ gender and professional status on verbosity during group meetings. Not only the analytic approach but also the operationalizations of key variables were left unconstrained and up to individual analysts. For instance, analysts could choose to operationalize status as job title, institutional ranking, citation counts, or some combination. To maximize transparency regarding the process by which analytic choices are made, the analysts used a platform we developed called DataExplained to justify both preferred and rejected analytic paths in real time. Analyses lacking sufficient detail, reproducible code, or with statistical errors were excluded, resulting in 29 analyses in the final sample. Researchers reported radically different analyses and dispersed empirical outcomes, in a number of cases obtaining significant effects in opposite directions for the same research question. A Boba multiverse analysis demonstrates that decisions about how to operationalize variables explain variability in outcomes above and beyond statistical choices (e.g., covariates). Subjective researcher decisions play a critical role in driving the reported empirical results, underscoring the need for open data, systematic robustness checks, and transparency regarding both analytic paths taken and not taken. Implications for organizations and leaders, whose decision making relies in part on scientific findings, consulting reports, and internal analyses by data scientists, are discussed

Same data, different conclusions: Radical dispersion in empirical results when independent analysts operationalize and test the same hypothesis

In this crowdsourced initiative, independent analysts used the same dataset to test two hypotheses regarding the effects of scientists’ gender and professional status on verbosity during group meetings. Not only the analytic approach but also the operationalizations of key variables were left unconstrained and up to individual analysts. For instance, analysts could choose to operationalize status as job title, institutional ranking, citation counts, or some combination. To maximize transparency regarding the process by which analytic choices are made, the analysts used a platform we developed called DataExplained to justify both preferred and rejected analytic paths in real time. Analyses lacking sufficient detail, reproducible code, or with statistical errors were excluded, resulting in 29 analyses in the final sample. Researchers reported radically different analyses and dispersed empirical outcomes, in a number of cases obtaining significant effects in opposite directions for the same research question. A Boba multiverse analysis demonstrates that decisions about how to operationalize variables explain variability in outcomes above and beyond statistical choices (e.g., covariates). Subjective researcher decisions play a critical role in driving the reported empirical results, underscoring the need for open data, systematic robustness checks, and transparency regarding both analytic paths taken and not taken. Implications for organizations and leaders, whose decision making relies in part on scientific findings, consulting reports, and internal analyses by data scientists, are discussed