Using bromide tracer to measure uranium diffusivity in ground water sediments

More than 129 million liters of groundwater are contaminated with uranium at Old Rifle, Colorado – a former uranium-processing site that operated until 1958. The original Department of Energy (DOE) strategy for remediation, involving natural flushing of U from the groundwater through mixing with surface water, has not proven successful. Thin pockets of silt-, clay-, and organic-rich sediments referred to as naturally reduced zones (NRZs) act both as sinks and sources of U to the aquifer, contribute to plume persistence, and appear to be diffusion limited controlled. To better understand how the NRZs are diffusion limited controlled, a bromide tracer was used to measure uranium diffusivity at two depths from the JB-02 well at Old Rifle: one depth in the middle of the NRZ and one depth at the bottom edge of the NRZ. A NaBr reservoir was allowed to diffuse into the sediments for several days with reservoir samples collected twice a day and analyzed using inductively coupled plasma mass spectrometry (ICP-MS) for bromide concentrations. This data was then used to calculate net flux, effective diffusivity, and the tortuosity effect within the sediments, which will inform uranium management strategies not only at the Old Rifle site but potentially other DOE legacy sites including Riverton, Wyoming and Shiprock, New Mexico

Association between soil organic carbon and calcium in acidic grassland soils from Point Reyes National Seashore, CA

Organo-mineral and organo-metal associations play an important role in the retention and accumulation of soil organic carbon (SOC). Recent studies have demonstrated a positive correlation between calcium (Ca) and SOC content in a range of soil types. However, most of these studies have focused on soils that contain calcium carbonate (pH > 6). To assess the importance of Ca-SOC associations in lower pH soils, we investigated their physical and chemical interaction in the grassland soils of Point Reyes National Seashore (CA, USA) at a range of spatial scales. Multivariate analyses of our bulk soil characterisation dataset showed a strong correlation between exchangeable Ca (Ca$_{Exch}$; 5–8.3 c.mol$_{c}$ kg$^{−1}$) and SOC (0.6–4%) content. Additionally, linear combination fitting (LCF) of bulk Ca K-edge X-ray absorption near-edge structure (XANES) spectra revealed that Ca was predominantly associated with organic carbon across all samples. Scanning transmission X-ray microscopy near-edge X-ray absorption fine structure spectroscopy (STXM C/Ca NEXAFS) showed that Ca had a strong spatial correlation with C at the microscale. The STXM C NEXAFS K-edge spectra indicated that SOC had a higher abundance of aromatic/olefinic and phenolic C functional groups when associated with Ca, relative to C associated with Fe. In regions of high Ca-C association, the STXM C NEXAFS spectra were similar to the spectrum from lignin, with moderate changes in peak intensities and positions that are consistent with oxidative C transformation. Through this association, Ca thus seems to be preferentially associated with plant-like organic matter that has undergone some oxidative transformation, at depth in acidic grassland soils of California. Our study highlights the importance of Ca-SOC complexation in acidic grassland soils and provides a conceptual model of its contribution to SOC preservation, a research area that has previously been unexplored

Nitrate-Stimulated Release of Naturally Occurring Sedimentary Uranium

Groundwater uranium (U) concentrations have been measured above the U.S. EPA maximum contaminant level (30 μg/L) in many U.S. aquifers, including in areas not associated with anthropogenic contamination by milling or mining. In addition to carbonate, nitrate has been correlated to uranium groundwater concentrations in two major U.S. aquifers. However, to date, direct evidence that nitrate mobilizes naturally occurring U from aquifer sediments has not been presented. Here, we demonstrate that the influx of high-nitrate porewater through High Plains alluvial aquifer silt sediments bearing naturally occurring U(IV) can stimulate a nitrate-reducing microbial community capable of catalyzing the oxidation and mobilization of U into the porewater. Microbial reduction of nitrate yielded nitrite, a reactive intermediate, which was further demonstrated to abiotically mobilize U from the reduced alluvial aquifer sediments. These results indicate that microbial activity, specifically nitrate reduction to nitrite, is one mechanism driving U mobilization from aquife

Feasibility of Modified Surviving Sepsis Campaign Guidelines in a Resource-Restricted Setting Based on a Cohort Study of Severe S. Aureus Sepsis

[This corrects the article on p. e29858 in vol. 7.]

Energy-Degeneracy-Driven Covalency in Actinide Bonding

Evaluating the nature of chemical bonding for actinide elements represents one of the most important and long-standing problems in actinide science. We directly address this challenge and contribute a Cl K-edge X-ray absorption spectroscopy and relativistic density functional theory study that quantitatively evaluates An–Cl covalency in AnCl62– (AnIV = Th, U, Np, Pu). The results showed significant mixing between Cl 3p- and AnIV 5f- and 6d-orbitals (t1u*/t2u* and t2g*/eg*), with the 6d-orbitals showing more pronounced covalent bonding than the 5f-orbitals. Moving from Th to U, Np, and Pu markedly changed the amount of M–Cl orbital mixing, such that AnIV 6d- and Cl 3p-mixing decreased and metal 5f- and Cl 3p-orbital mixing increased across this series

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

Microbiome to Brain:Unravelling the Multidirectional Axes of Communication

The gut microbiome plays a crucial role in host physiology. Disruption of its community structure and function can have wide-ranging effects making it critical to understand exactly how the interactive dialogue between the host and its microbiota is regulated to maintain homeostasis. An array of multidirectional signalling molecules is clearly involved in the host-microbiome communication. This interactive signalling not only impacts the gastrointestinal tract, where the majority of microbiota resides, but also extends to affect other host systems including the brain and liver as well as the microbiome itself. Understanding the mechanistic principles of this inter-kingdom signalling is fundamental to unravelling how our supraorganism function to maintain wellbeing, subsequently opening up new avenues for microbiome manipulation to favour desirable mental health outcome

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