3 research outputs found
A 2-D, variable-density numerical model of subsurface fluid flow through the Edwards Aquifer, New Braunfels, TX: mechanisms inhibiting flow across the freshwater/saline-water interface
The Edwards aquifer in south-central Texas, U.S., composed of faulted carbonate bedrock, contains freshwater and saline water. In aquifers that are used as a source of drinking water and that contain fresh and saline waters, saline-water intrusion can result in degradation of water quality. Yet, in the Edwards aquifer, limited saline-water intrusion has occurred. The questions addressed are “Why is the saline-water intrusion less than expected,” and “Is there a trigger that will result in saline-water intrusion into the freshwater reservoir?” Three hypotheses were tested. One: an extremely saline water density might prevent mixing across the interface. Two: faults could be acting as a barrier between the freshwater and saline-water zones, preventing movement of the saline water into the freshwater zone. Three: the permeability of the bedrock in the saline water zone might be extremely low, limiting movement of the saline water. A transect of observation wells was chosen in New Braunfels, TX for study. 2-D, variable-density numerical models of groundwater flow were used to determine which factor controlled the lack of saline-water intrusion. Numerical models were produced for each hypothesis using Basin2. It is clear from each model that fault permeability and fault compartmentalization is the primary mechanism inhibiting flow across the freshwater/saline-water interface. When horizontal fault permeability reached 0.01 D, flow was significantly reduced across the interface. When these values reached 0.001 D, flow across the interface ceased. To a lesser extent, saline-water zone permeability controlled the movement of flow across the interface, if permeability values were reduced by three orders of magnitude. However, extremely high saline water densities did not inhibit flow. A trigger that would increase fault permeability would be continued dissolution of the carbonate rocks, but it most likely would take tens of thousands of years for dissolution to significantly increase the permeability of the fault surfaces. In addition, dedolomitization of the saline water zone would be another trigger that would induce flow across the interface, but since little diagenesis in the saline water zone has been observed, dedolomitization is not a pressing issue
New insights into Holocene hydrology and temperature from lipid biomarkers in western Mediterranean alpine wetlands
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Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial
We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19.
In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978.
Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50–72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74–1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67–1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74–1·58]; BRII-196 plus BRII-198 1·00 [0·68–1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91–1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88–1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90.
Neither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19.
US National Institutes of Health and Operation Warp Spee