Microplastics in mainstem Mississippi River fishes

Microplastics are ubiquitous in Earth’s ecosystems and many efforts have begun to understand their distributions. Large rivers, like the Mississippi River, provide a unique system in which to look at large-scale patterns of microplastic distribution. In this study, we sampled four species of widely-distributed fishes from five sites along the mainstem Mississippi River, from Minnesota to Louisiana, United States. Microplastics were found in all fish species and at all sites; however, microplastics increased in occurrence in the Lower Mississippi River. Fragments were the most common morphologies and polypropylene was the most common polymer detected. We also examined the hypothesis that microplastic loads in fishes increased downstream, but found support for this hypothesis only when examining Largemouth Bass; Flathead Catfish, Shortnose Gar, and Bluegill were all found to have similar microplastic loads along the mainstem Mississippi River. It is clear that microplastics are heterogeneously distributed throughout ecosystems, and further understanding of microplastic distributional patterns and varying species burdens are needed to fully understand threats that microplastics present

Hyperimmune immunoglobulin for hospitalised patients with COVID-19 (ITAC): a double-blind, placebo-controlled, phase 3, randomised trial

BACKGROUND: Passive immunotherapy using hyperimmune intravenous immunoglobulin (hIVIG) to SARS-CoV-2, derived from recovered donors, is a potential rapidly available, specific therapy for an outbreak infection such as SARS-CoV-2. Findings from randomised clinical trials of hIVIG for the treatment of COVID-19 are limited. METHODS: In this international randomised, double-blind, placebo-controlled trial, hospitalised patients with COVID-19 who had been symptomatic for up to 12 days and did not have acute end-organ failure were randomly assigned (1:1) to receive either hIVIG or an equivalent volume of saline as placebo, in addition to remdesivir, when not contraindicated, and other standard clinical care. Randomisation was stratified by site pharmacy; schedules were prepared using a mass-weighted urn design. Infusions were prepared and masked by trial pharmacists; all other investigators, research staff, and trial participants were masked to group allocation. Follow-up was for 28 days. The primary outcome was measured at day 7 by a seven-category ordinal endpoint that considered pulmonary status and extrapulmonary complications and ranged from no limiting symptoms to death. Deaths and adverse events, including organ failure and serious infections, were used to define composite safety outcomes at days 7 and 28. Prespecified subgroup analyses were carried out for efficacy and safety outcomes by duration of symptoms, the presence of anti-spike neutralising antibodies, and other baseline factors. Analyses were done on a modified intention-to-treat (mITT) population, which included all randomly assigned participants who met eligibility criteria and received all or part of the assigned study product infusion. This study is registered with ClinicalTrials.gov, NCT04546581. FINDINGS: From Oct 8, 2020, to Feb 10, 2021, 593 participants (n=301 hIVIG, n=292 placebo) were enrolled at 63 sites in 11 countries; 579 patients were included in the mITT analysis. Compared with placebo, the hIVIG group did not have significantly greater odds of a more favourable outcome at day 7; the adjusted OR was 1·06 (95% CI 0·77–1·45; p=0·72). Infusions were well tolerated, although infusion reactions were more common in the hIVIG group (18·6% vs 9·5% for placebo; p=0·002). The percentage with the composite safety outcome at day 7 was similar for the hIVIG (24%) and placebo groups (25%; OR 0·98, 95% CI 0·66–1·46; p=0·91). The ORs for the day 7 ordinal outcome did not vary for subgroups considered, but there was evidence of heterogeneity of the treatment effect for the day 7 composite safety outcome: risk was greater for hIVIG compared with placebo for patients who were antibody positive (OR 2·21, 95% CI 1·14–4·29); for patients who were antibody negative, the OR was 0·51 (0·29–0·90; pinteraction=0·001). INTERPRETATION: When administered with standard of care including remdesivir, SARS-CoV-2 hIVIG did not demonstrate efficacy among patients hospitalised with COVID-19 without end-organ failure. The safety of hIVIG might vary by the presence of endogenous neutralising antibodies at entry. FUNDING: US National Institutes of Health

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

Funder: laura and john arnold foundationBACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care

A Method for Estimating Costs and Benefits of Space Assembly and Servicing By Astronauts and Robots

One aspect of designing future space missions is to determine whether Space Assembly and Servicing (SAS) is useful and, if so, what combination of robots and astronauts provides the most effective means of accomplishing it. Certain aspects of these choices, such as the societal value of developing the means for humans to live in space, do not lend themselves to quantification. However, other SAS costs and benefits can be quantified in a manner that can help select the most cost-effective SAS approach. Any space facility, whether it is assembled and serviced or not, entails an eventual replacement cost due to wear and obsolescence. Servicing can reduce this cost by limiting replacement to only failed or obsolete components. However, servicing systems, such as space robots, have their own logistics cost, and astronauts can have even greater logistics requirements. On the other hand, humans can be more capable than robots at performing dexterous and unstructured tasks, which can reduce logistics costs by allowing a reduction in mass of replacement components. Overall, the cost-effectiveness of astronaut SAS depends on its efficiency; and, if astronauts have to be wholly justified by their servicing usefulness, then the serviced space facility has to be large enough to fully occupy them

Practice patterns and outcomes of repository corticotropin injection (Acthar® Gel) use in childhood nephrotic syndrome: A study of the North American Pediatric Renal Trials and collaborative studies and the Pediatric Nephrology Research Consortium

Objective: We set up a U.S. registry to examine prescription patterns and patient outcomes of repository corticotropin injection (Acthar® Gel) for childhood nephrotic syndrome. Methods: 18 participating U.S. pediatric centers performed retrospective review and prospective observation of patients < 21 years old with nephrotic syndrome treated with Acthar Gel. We captured baseline characteristics, drug regimen and duration, and disease response following treatment. Results: 46 patients, enrolled from 2015 to 2020 were included. 27 (58.7%) were male. 18 patients (39.1%) had a diagnosis of minimal change followed by focal segmental glomerulosclerosis in 16 patients (34.7%). Median age at start of treatment was 12.5 years (IQR 8.5-17.4) compared to 5.3 years at diagnosis (IQR 2.7-10.5 years). 52% were resistant to corticosteroids. The most common Acthar Gel regimen was 80IU twice a week with a median duration of 199 days (IQR 88-365). Among 37 patients with active disease, 18 (49%) were able to achieve partial or complete remission, though all patients that had a positive response were on other immunosuppressants concomitantly. Conclusion: We report the findings of the largest registry cohort of pediatric patients in the U.S. treated with Acthar Gel for clinically challenging cases of nephrotic syndrome. Acthar Gel was successful in inducing remission in approximately half of the patients with active disease at time of treatment. No predictors of response with respect to demographic data, age at start of Acthar Gel therapy, etiology of nephrotic syndrome, presence or absence of comorbidities, or steroid responsiveness was noted

DataSheet1_Microplastics in mainstem Mississippi River fishes.CSV

Microplastics are ubiquitous in Earth’s ecosystems and many efforts have begun to understand their distributions. Large rivers, like the Mississippi River, provide a unique system in which to look at large-scale patterns of microplastic distribution. In this study, we sampled four species of widely-distributed fishes from five sites along the mainstem Mississippi River, from Minnesota to Louisiana, United States. Microplastics were found in all fish species and at all sites; however, microplastics increased in occurrence in the Lower Mississippi River. Fragments were the most common morphologies and polypropylene was the most common polymer detected. We also examined the hypothesis that microplastic loads in fishes increased downstream, but found support for this hypothesis only when examining Largemouth Bass; Flathead Catfish, Shortnose Gar, and Bluegill were all found to have similar microplastic loads along the mainstem Mississippi River. It is clear that microplastics are heterogeneously distributed throughout ecosystems, and further understanding of microplastic distributional patterns and varying species burdens are needed to fully understand threats that microplastics present.</p