AIDS Vaccine for Asia Network (AVAN): Expanding the Regional Role in Developing HIV Vaccines

Yiming Shao and colleagues describe the work of AVAN, the AIDS Vaccine for Asia Network, which aims to strengthen its regional efforts in finding an AIDS vaccine

Genetic Population Structure in the Antarctic Benthos: Insights from the Widespread Amphipod, Orchomenella franklini

Currently there is very limited understanding of genetic population structure in the Antarctic benthos. We conducted one of the first studies of microsatellite variation in an Antarctic benthic invertebrate, using the ubiquitous amphipod Orchomenella franklini (Walker, 1903). Seven microsatellite loci were used to assess genetic structure on three spatial scales: sites (100 s of metres), locations (1–10 kilometres) and regions (1000 s of kilometres) sampled in East Antarctica at Casey and Davis stations. Considerable genetic diversity was revealed, which varied between the two regions and also between polluted and unpolluted sites. Genetic differentiation among all populations was highly significant (FST = 0.086, RST = 0.139, p<0.001) consistent with the brooding mode of development in O. franklini. Hierarchical AMOVA revealed that the majority of the genetic subdivision occurred across the largest geographical scale, with Nem≈1 suggesting insufficient gene flow to prevent independent evolution of the two regions, i.e., Casey and Davis are effectively isolated. Isolation by distance was detected at smaller scales and indicates that gene flow in O. franklini occurs primarily through stepping-stone dispersal. Three of the microsatellite loci showed signs of selection, providing evidence that localised adaptation may occur within the Antarctic benthos. These results provide insights into processes of speciation in Antarctic brooders, and will help inform the design of spatial management initiatives recently endorsed for the Antarctic benthos

The Glasgow 'Deep End' Links Worker Study Protocol: a quasi-experimental evaluation of a social prescribing intervention for patients with complex needs in areas of high socioeconomic deprivation

Background: ‘Social prescribing’ can be used to link patients with complex needs to local (non-medical) community resources. The ‘Deep End’ Links Worker Programme is being tested in general practices serving deprived populations in Glasgow, Scotland. Objectives: To assess the implementation and impact of the intervention at patient and practice levels. Methods: Study design: Quasi-experimental outcome evaluation with embedded theory-driven process evaluation in 15 practices randomized to receive the intervention or not. Complex intervention: Comprising a practice development fund, a practice-based community links practitioner (CLP), and management support. It aims to link patients to local community organizations and enhance practices’ social prescribing capacity. Study population: For intervention practices, staff and adult patients involved in referral to a CLP, and a sample of community organization staff. For comparison practices, all staff and a random sample of adult patients. Sample size: 286 intervention and 484 comparator patients. Outcomes: Primary patient outcome is health-related quality of life (EQ-5D-5L). Secondary patient outcomes include capacity, depression/anxiety, self-esteem, and healthcare utilization. Practice outcome measures include team climate, job satisfaction, morale, and burnout. Outcomes measured at baseline and 9 months. Processes: Barriers and facilitators to implementation of the programme and possible mechanisms through which outcomes are achieved. Analysis plan: For outcome, intention-to-treat analysis with differences between groups tested using mixed-effects regression models. For process, case-study approach with thematic analysis. Discussion: This evaluation will provide new evidence about the implementation and impact of social prescribing by general practices serving patients with complex needs living in areas of high deprivation

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

Background Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

Nano and traditional copper and zinc antifouling coatings: metal release and impact on marine sessile invertebrate communities

Artificial surfaces in coastal waters and offshore oceans, including boat hulls, docks, and offshore structures, are invariably colonized, or fouled, by a host of sessile species known collectively as fouling communities. Fouling has great economic impacts on shipping and other marine industries and plays an important role in the spread of marine invasive species across the globe. The main strategy to prevent fouling of artificial surfaces is application of antifouling coatings containing varying concentrations and mixtures of biocides. Presently, copper and zinc are popular antifouling biocides, and the latter is gaining in usage due to the known toxic characteristics of copper in the marine environment and consequent regulation and consumer opinion. Nanomaterials, including Cu and ZnO nanoparticles, have been explored as a way to efficiently deliver biocides from coating matrices. Here, we examine the efficacy and biocide release characteristics of several copper- and zinc-based antifouling coatings, including formulations containing traditional micron-sized Cu and ZnO particles and two containing copper and ZnO nanoparticles, respectively. Most of the antifouling coatings tested significantly reduced the abundance and biodiversity of the fouling community in the three study locations across California. Invasive species were suppressed by most coatings at similar levels to natives, suggesting that in general, antifouling coatings do not favor invasive species. We found that zinc-based antifouling coatings were similar and in some cases better performing than copper, despite the generally lower toxicity of zinc to aquatic organisms compared with copper. The performance of zinc-based coatings, moreover, was not directly related to the amount of zinc released into the water or their zinc content. Nano-based coatings did not offer any clear advantages over non-nano coatings, either in the degree of Zn leaching or fouling suppression. Coating matrix properties clearly are an important factor affecting the efficacy and biocide leaching rate of antifouling coatings

Nano and traditional copper and zinc antifouling coatings: metal release and impact on marine sessile invertebrate communities

Artificial surfaces in coastal waters and offshore oceans, including boat hulls, docks, and offshore structures, are invariably colonized, or fouled, by a host of sessile species known collectively as fouling communities. Fouling has great economic impacts on shipping and other marine industries and plays an important role in the spread of marine invasive species across the globe. The main strategy to prevent fouling of artificial surfaces is application of antifouling coatings containing varying concentrations and mixtures of biocides. Presently, copper and zinc are popular antifouling biocides, and the latter is gaining in usage due to the known toxic characteristics of copper in the marine environment and consequent regulation and consumer opinion. Nanomaterials, including Cu and ZnO nanoparticles, have been explored as a way to efficiently deliver biocides from coating matrices. Here, we examine the efficacy and biocide release characteristics of several copper- and zinc-based antifouling coatings, including formulations containing traditional micron-sized Cu and ZnO particles and two containing copper and ZnO nanoparticles, respectively. Most of the antifouling coatings tested significantly reduced the abundance and biodiversity of the fouling community in the three study locations across California. Invasive species were suppressed by most coatings at similar levels to natives, suggesting that in general, antifouling coatings do not favor invasive species. We found that zinc-based antifouling coatings were similar and in some cases better performing than copper, despite the generally lower toxicity of zinc to aquatic organisms compared with copper. The performance of zinc-based coatings, moreover, was not directly related to the amount of zinc released into the water or their zinc content. Nano-based coatings did not offer any clear advantages over non-nano coatings, either in the degree of Zn leaching or fouling suppression. Coating matrix properties clearly are an important factor affecting the efficacy and biocide leaching rate of antifouling coatings

Association of Pre-Operative Albuminuria with Post-Operative Outcomes after Coronary Artery Bypass Grafting

The effect on post-operative outcomes after coronary artery bypass graft(CABG) surgery is not clear. Among 17,812 patients who underwent CABG during October 1,2006-September 28,2012 in any Department of US Veterans Affairs(VA) hospital, we identified 5,968 with available preoperative urine albumin-creatinine ratio(UACR) measurements. We examined the association of UACR<30, 30–299 and >=300 mg/g with 30/90/180/365-day and overall all-cause mortality, and hospitalization length >10 days, and with acute kidney injury(AKI). Mean ± SD baseline age and eGFR were 66 ± 8 years and 77 ± 19 ml/min/1.73 m(2), respectively. 788 patients(13.2%) died during a median follow-up of 3.2 years, and 26.8% patients developed AKI(23.1%-Stage 1; 2.9%-Stage 2; 0.8%-Stage 3) within 30 days of CABG. The median lengths of stay were 8 days(IQR: 6–13 days), 10 days(IQR: 7–14 days) and 12 days(IQR: 8–19 days) for groups with UACR < 30 mg/g, 30–299 mg/g and ≥300 mg/g, respectively. Higher UACR conferred 72 to 85% higher 90-, 180-, and 365-day mortality compared to UACR<30 mg/g (odds ratio and 95% confidence interval for UACR≥300 vs. <30 mg/g: 1.72(1.01–2.95); 1.85(1.14–3.01); 1.74(1.15–2.61), respectively). Higher UACR was also associated with significantly longer hospitalizations and higher incidence of all stages of AKI. Higher UACR is associated with significantly higher odds of mortality, longer post-CABG hospitalization, and higher AKI incidence