Heavy metal partitioning in sediments from rivers flowing through coal fields in Mpumalanga, South Africa

The association of elements Cd, Co, Cr, Fe, Mn, Pb, Ti and V with various geochemical phases in the sediments from the Olifants, Klein Olifants, Wilge rivers and a tributary of the Olifants River was studied using a four step sequential extraction scheme. By employing enrichment factors these elements were found to be contaminating the sediments. Sequential extraction enabled partitioning of the metals into exchangeable, reducible, oxidizable and residual fractions. Most of the elements were found to exist in the residual fraction, characterized by stable compounds. Application of risk assessment code (RAC) to the exchangeable fraction revealed that most of the elements posed a medium risk to aquatic life, with the exception of Co, Pb, and Mn which were classified into the high risk category. Non-residual/more bioavailable fractions were examined using statistics. Correlation analysis was employed to understand the interaction between the more bioavailable fractions of the metals with the reducible phase consisting of oxides of Fe-and Mn. These oxides contribute to the adsorption of trace metals onto sediments. Elements Co, V, Pb, Cr and Cd in the reducible fraction were found to be associated with Fe-oxides, while some V, Cr and Ti were associated with Mnoxides, as indicated by significantly high correlation coefficients. Through cluster and factor analysis three anthropogenic activities associated with mining and use of coal and iron and steel manufacturing were found to be contributing metals to the sediments.Tshwane University of Technology (TUT) and the National Research Fund (NRF).http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1863-06692016-06-30hb201

Hormonal Contraceptive Use and Discontinuation Among HIV-Infected Women in Uganda and Zimbabwe

Hormonal contraception (HC) use by HIV-infected women has been identified by the WHO as important strategy for reducing vertical HIV transmission. Little is known about factors associated with HC discontinuation among HIV-infected women

Infection pre-Ad26.COV2.S-vaccination primes greater class switching and reduced CXCR5 expression by SARS-CoV-2-specific memory B cells

Neutralizing antibodies strongly correlate with protection for COVID-19 vaccines, but the corresponding memory B cells that form to protect against future infection are relatively understudied. Here we examine the effect of prior SARS-CoV-2 infection on the magnitude and phenotype of the memory B cell response to single dose Johnson and Johnson (Ad26.COV2.S) vaccination in South African health care workers. Participants were either naïve to SARS-CoV-2 or had been infected before vaccination. SARS-CoV-2-specific memory B-cells expand in response to Ad26.COV2.S and are maintained for the study duration (84 days) in all individuals. However, prior infection is associated with a greater frequency of these cells, a significant reduction in expression of the germinal center chemokine receptor CXCR5, and increased class switching. These B cell features correlated with neutralization and antibody-dependent cytotoxicity (ADCC) activity, and with the frequency of SARS-CoV-2 specific circulating T follicular helper cells (cTfh). Vaccination-induced effective neutralization of the D614G variant in both infected and naïve participants but boosted neutralizing antibodies against the Beta and Omicron variants only in participants with prior infection. In addition, the SARS-CoV-2 specific CD8+ T cell response correlated with increased memory B cell expression of the lung-homing receptor CXCR3, which was sustained in the previously infected group. Finally, although vaccination achieved equivalent B cell activation regardless of infection history, it was negatively impacted by age. These data show that phenotyping the response to vaccination can provide insight into the impact of prior infection on memory B cell homing, CSM, cTfh, and neutralization activity. These data can provide early signals to inform studies of vaccine boosting, durability, and co-morbidities

Responding to salinity in a rural African alluvial valley aquifer system : to boldly go beyond the world of hand-pumped groundwater supply?

Effective response to groundwater salinity in the developing world may critically safeguard drinking-water supplies. Groundwater resources throughout rural Africa are exploited by a vast and increasing number of hand-pumped boreholes for community supply. Our research in TA Ngabu (Shire Valley), Southern Malawi aims to: define groundwater-salinity problem occurrence within its semi-arid alluvial-valley aquifer setting and rural developing-world context; critique current capacity to respond; and, to discuss future response options - in particular considering the need to explore alternative options that boldly go beyond the world of hand-pumped groundwater supply. Salinity problem definition was achieved through survey of 419 hand-pumped boreholes that revealed widespread brackish groundwater causing non-potable (unpalatable) drinking-water supplies. Persistent non-functionality or abandonment of boreholes was typically ascribed to salinity. Whilst salinity is conceptualised to arise from shallow-groundwater evaporation, formation-evaporite dissolution and faulted-area upwelling, sparse data locally renders attribution of salinity sources to individual boreholes difficult. There is a significant need to better resolve the vertical distribution of salinity. Problem response capacity was hampered by multiple factors, including, sector inertia, low drilling costs compromising water-point integrity, and lack of technical vision for alternatives. Various recommendations are made to improve response capacity continuing to work at the hand-pump supply scale. However, in areas where salinity is significant, exploring the feasibility of other options is advocated in conjunction with technical capacity development. Groundwater options may utilise high borehole yields possible from alluvial aquifers, grossly under-exploited by hand pumps. Groundwater at depth, albeit of unknown quality typically, or pipeline transfers of probable good-quality groundwater from valley-margin units, should be considered. Surface-water pipeline supplies may be viable for (growing) population centres. Canal-fed irrigation schemes (pending for the area), should be multiple-use, protective of groundwater and embrace pipeline drinking-water supply and managed-aquifer-recharge opportunities. Advancing desalination technologies, although presently unaffordable, should be kept under review

A Survey of Schedulability Analysis Techniques for Rate-Dependent Tasks

In automotive embedded real-time systems, such as the engine control unit, there are tasks that are activated whenever the crankshaft arrives at a specific angular position. As a consequence the frequency of activation changes with the crankshaft’s angular speed (i.e., engine rpm). Additionally, execution times and deadlines may also depend on angular speeds and positions. This paper provides a survey on schedulability analysis techniques for tasks with this rate-dependent behaviour. It covers different task-models and analysis methods for both fixed priority and earliest deadline first scheduling. A taxonomy of the different analysis methods, classifying them according to the assumptions made and the precision of the analysis, is provided at the end of the pape

Cost-effectiveness of urine-based tuberculosis screening in hospitalised patients with HIV in Africa: a microsimulation modelling study.

BACKGROUND: Testing urine improves the number of tuberculosis diagnoses made among patients in hospital with HIV. In conjunction with the two-country randomised Rapid Urine-based Screening for Tuberculosis to Reduce AIDS-related Mortality in Hospitalised Patients in Africa (STAMP) trial, we used a microsimulation model to estimate the effects on clinical outcomes and the cost-effectiveness of adding urine-based tuberculosis screening to sputum screening for hospitalised patients with HIV. METHODS: We compared two tuberculosis screening strategies used irrespective of symptoms among hospitalised patients with HIV in Malawi and South Africa: a GeneXpert assay (Cepheid, Sunnyvale, CA, USA) for Mycobacterium tuberculosis and rifampicin resistance (Xpert) in sputum samples (standard of care) versus sputum Xpert combined with a lateral flow assay for M tuberculosis lipoarabinomannan in urine (Determine TB-LAM Ag test, Abbott, Waltham, MA, USA [formerly Alere]; TB-LAM) and concentrated urine Xpert (intervention). A cohort of simulated patients was modelled using selected characteristics of participants, tuberculosis diagnostic yields, and use of hospital resources in the STAMP trial. We calibrated 2-month model outputs to the STAMP trial results and projected clinical and economic outcomes at 2 years, 5 years, and over a lifetime. We judged the intervention to be cost-effective if the incremental cost-effectiveness ratio (ICER) was less than US$750/year of life saved (YLS) in Malawi and$940/YLS in South Africa. A modified intervention of adding only TB-LAM to the standard of care was also evaluated. We did a budget impact analysis of countrywide implementation of the intervention. FINDINGS: The intervention increased life expectancy by 0·5-1·2 years and was cost-effective, with an ICER of $450/YLS in Malawi and$840/YLS in South Africa. The ICERs decreased over time. At lifetime horizon, the intervention remained cost-effective under nearly all modelled assumptions. The modified intervention was at least as cost-effective as the intervention (ICERs $420/YLS in Malawi and$810/YLS in South Africa). Over 5 years, the intervention would save around 51 000 years of life in Malawi and around 171 000 years of life in South Africa. Health-care expenditure for screened individuals was estimated to increase by $37 million (10·8$261 million (2·8%), respectively. INTERPRETATION: Urine-based tuberculosis screening of all hospitalised patients with HIV could increase life expectancy and be cost-effective in resource-limited settings. Urine TB-LAM is especially attractive because of high incremental diagnostic yield and low additional cost compared with sputum Xpert, making a compelling case for expanding its use to all hospitalised patients with HIV in areas with high HIV burden and endemic tuberculosis. FUNDING: UK Medical Research Council, UK Department for International Development, Wellcome Trust, US National Institutes of Health, Royal College of Physicians, Massachusetts General Hospital

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB