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Airborne transmission of SARS-CoV-2 aerosol remains contentious. Importantly, whether cough or breath-generated bioaerosols can harbor viable and replicating virus remains largely unclarified. We performed size-fractionated aerosol sampling (Andersen cascade impactor) and evaluated viral culturability in human cell lines (infectiousness), viral genetics, and host immunity in ambulatory participants with COVID-19. Sixty-one percent (27/44) and 50% (22/44) of participants emitted variant-specific culture-positive aerosols  95%). There is considerable heterogeneity in potential infectiousness i.e., only 29% of participants were probably highly infectious (produced culture-positive aerosols

Abstract South Africa was the most affected country in Africa by the coronavirus disease 2019 (COVID-19) pandemic, where over 4 million confirmed cases of COVID-19 and over 102,000 deaths have been recorded since 2019. Aside from clinical methods, artificial intelligence (AI)-based solutions such as machine learning (ML) models have been employed in treating COVID-19 cases. However, limited application of AI for COVID-19 in Africa has been reported in the literature. This study aimed to investigate the performance and interpretability of several ML algorithms, including deep multilayer perceptron (Deep MLP), support vector machine (SVM) and Extreme gradient boosting trees (XGBoost) for predicting COVID-19 mortality risk with an emphasis on the effect of cross-validation (CV) and principal component analysis (PCA) on the results. For this purpose, a dataset with 154 features from 490 COVID-19 patients admitted into the intensive care unit (ICU) of Tygerberg Hospital in Cape Town, South Africa, during the first wave of COVID-19 in 2020 was retrospectively analysed. Our results show that Deep MLP had the best overall performance (F1 = 0.92; area under the curve (AUC) = 0.94) when CV and the synthetic minority oversampling technique (SMOTE) were applied without PCA. By using the Shapley Additive exPlanations (SHAP) model to interpret the mortality risk predictions, we identified the Length of stay (LOS) in the hospital, LOS in the ICU, Time to ICU from admission, days discharged alive or death, D-dimer (blood clotting factor), and blood pH as the six most critical variables for mortality risk prediction. Also, Age at admission, Pf ratio (PaO2/FiO2 ratio), troponin T (TropT), ferritin, ventilation, C-reactive protein (CRP), and symptoms of acute respiratory distress syndrome (ARDS) were associated with the severity and fatality of COVID-19 cases. The study reveals how ML could assist medical practitioners in making informed decisions on handling critically ill COVID-19 patients with comorbidities. It also offers insight into the combined effect of CV, PCA, and SMOTE on the performance of ML models for COVID-19 mortality risk prediction, which has been little explored.

Ecoliteracy is essential for adult educators/activists en route to creating ecoliterate populations. Working cooperatively with other networks in the spirit of a 'solidarity economy', a group within the PIMA network has run a climate justice education programme through a series of webinars. We describe and analyse a case story of an emergent climate justice curriculum in action. We use an ecofeminist analysis to understand the relational entanglement of ecological breakdown, capitalism, colonialism, racism and patriarchy which in part undergird the breaching of planetary boundaries. We identify five inquiry-based themes which are suggestive as coordinates for orientating curricula for adult educators/activists learning climate justice. One of these is the importance of building ecoliterate alliances through collaborative action as we face the 'socio-ecological hurricane' which is bearing down.

This conceptual article examines the role of team-building in outdoor learning, reviews group development theory in relation to teamwork, and outlines the Behaviour Analysis model as a tool to facilitate team-building. Working with this foundation, the theory and model are combined with discussion about team, leader, and facilitator behaviours at each stage of group development. The applications are valid for all clientele in all outdoor settings. Several strong recommendations for practitioner behaviours and future research are presented.

Summary: Background: With limited access to mRNA COVID-19 vaccines in lower income countries, and people living with HIV (PLWH) largely excluded from clinical trials, Part A of the multicentre CoVPN 3008 (Ubuntu) study aimed to assess the safety of mRNA-1273, the relative effectiveness of hybrid versus vaccine immunity, and SARS-CoV-2 viral persistence among PLWH in East and Southern Africa during the omicron outbreak. Methods: Previously unvaccinated adults with HIV and/or other comorbidities associated with severe COVID-19 received either one (hybrid immunity) or two (vaccine immunity) 100-mcg doses of ancestral strain mRNA-1273 in the first month, depending on baseline evidence of prior SARS-CoV-2 infection. In a prospective cohort study design, we used covariate-adjusted Cox regression and counterfactual cumulative incidence methods to determine the hazard ratio and relative risk of COVID-19 and severe COVID-19 with hybrid versus vaccine immunity within six months. The ongoing Ubuntu study is registered on ClinicalTrials.gov (NCT05168813) and this work was conducted from December 2021 to March 2023. Findings: Between December 2021 and September 2022, 14,237 participants enrolled, and 14,002 (83% PLWH, 69% SARS-CoV-2 seropositive) were included in the analyses. Vaccinations were safe and well tolerated. Common adverse events were pain or tenderness at the injection site (26.7%), headache (20.4%), and malaise (20.3%). Severe adverse events were rare (0.8% of participants after the first and 1.1% after the second vaccination), and none were life-threatening or fatal. Among PLWH, the median CD4 count was 635 cells/μl and 18.5% had HIV viraemia. The six-month cumulative incidences in the hybrid immunity and vaccine immunity groups were 2.02% (95% confidence interval [CI] 1.61–2.44) and 3.40% (95% CI 2.30–4.49) for COVID-19, and 0.048% (95% CI 0.00–0.10) and 0.32% (95% CI 0.59–0.63) for severe COVID-19. Among all PLWH the hybrid immunity group had a 42% lower hazard rate of COVID-19 (hazard ratio [HR] 0.58; 95% CI 0.44–0.77; p

Acral melanoma (AM) is the most common type of melanoma arising in people with skin of color. AM is often diagnosed late and associated with poor outcomes. Melanoma outcomes are also impacted by socioeconomic status. Although uncommon, AM is a public health concern in South Africa because of its epidemiology and association with health access issues, which predispose to late diagnosis. South African patients are managed based on staging systems and treatment guidelines developed for other populations. This cohort study aimed to determine the survival outcomes in a cohort of South African AM patients and how these were associated with demographic, clinical, pathological, and management data. The study included patients diagnosed at a referral hospital between 1 January 2010 and 31 December 2021. Analysis occurred in 2022 and 2023. The main outcomes of interest were survival time in months (overall and progression-free, OS and PFS). Survival outcomes were analyzed using Kaplan–Meier survival curves. Survival probabilities were compared between subgroups using log-rank tests. Univariate and multivariable analyses were performed using the Cox proportional hazards models to assess factors associated with survival. Ninety-one patients were included in the analysis. After a median follow-up of 28 months (range: 0–151 months), 48 patients (52.7%) had died. The 3- and 5-year survival rates for the entire cohort were 64.8% and 56.0% respectively. Notably, the OS and PFS were not affected by the population group (p value = 0.628, not significant). The examination of OS and PFS by the clinical stage group demonstrated proportional hazard. Although SLNB comprised a small group, the results appear to be prognostically valid, specifically for OS. The results indicate that the AJCC eighth edition staging is broadly applicable to AM in this population; however, a rigorous comparison was not possible. SLNB appears to be prognostically valid. No difference in survival outcomes by population group was shown.

IntroductionNew biomarkers are urgently needed to detect pancreatic ductal adenocarcinoma (PDAC) at an earlier stage for individualized treatment strategies and to improve outcomes. Autoantibodies (AAbs) in principle make attractive biomarkers as they arise early in disease, report on disease-associated perturbations in cellular proteomes, and are static in response to other common stimuli, yet are measurable in the periphery, potentially well in advance of the onset of clinical symptoms.MethodsHere, we used high-throughput, custom cancer antigen microarrays to identify a clinically relevant autoantibody biomarker combination able to differentially detect PDAC. Specifically, we quantified the serological AAb profiles of 94 PDAC, chronic pancreatitis (CP), other pancreatic- (PC) and prostate cancers (PRC), non-ulcer dyspepsia patients (DYS), and healthy controls (HC).ResultsCombinatorial ROC curve analysis on the training cohort data from the cancer antigen microarrays identified the most effective biomarker combination as CEACAM1-DPPA2-DPPA3-MAGEA4-SRC-TPBG-XAGE3 with an AUC = 85·0% (SE = 0·828, SP = 0·684). Additionally, differential expression analysis on the samples run on the iOme™ array identified 4 biomarkers (ALX1-GPA33-LIP1-SUB1) upregulated in PDAC against diseased and healthy controls. Identified AAbs were validated in silico using public immunohistochemistry datasets and experimentally using a custom PDAC protein microarray comprising the 11 optimal AAb biomarker panel. The clinical utility of the biomarker panel was tested in an independent cohort comprising 223 PDAC, PC, PRC, colorectal cancer (CRC), and HC samples. Combinatorial ROC curve analysis on the validation data identified the most effective biomarker combination to be CEACAM1-DPPA2-DPPA3-MAGEA4-SRC-TPBG-XAGE3 with an AUC = 85·0% (SE = 0·828, SP = 0·684). Subsequently, the specificity of the 11-biomarker panel was validated against other cancers (PDAC vs PC: AUC = 70·3%; PDAC vs CRC: AUC = 84·3%; PDAC vs PRC: AUC = 80·2%) and healthy controls (PDAC vs HC: AUC = 80·9%), confirming that this novel AAb biomarker panel is able to selectively detect PDAC amongst other confounding diseases.ConclusionThis AAb panel may therefore have the potential to form the basis of a novel diagnostic test for PDAC.

Abstract Introduction Adolescent girls and young women (AGYW) account for two‐thirds of new HIV infections in Africa. African AGYW have had high uptake of oral HIV pre‐exposure prophylaxis (PrEP) but low adherence, which might be improved by point‐of‐care adherence monitoring with tailored counselling. Methods From August 2022 to July 2023, we conducted a PrEP demonstration project with sexually active AGYW ages 16−30 years from 20 sites in South Africa, Eswatini, Kenya, Malawi, Uganda and Zambia. Participants were offered oral tenofovir‐based PrEP at enrolment and followed up at 1, 3 and 6 months. PrEP adherence was assessed by a point‐of‐care qualitative lateral flow urine tenofovir (TFV) assay indicating PrEP use in the prior 4 days, which accompanied real‐time adherence counselling that incorporated urine TFV results when testing was available (70.8% of month 1, 35.3% of month 3 and 83.9% of month 6 visits). We estimated overall adherence, correcting for missing test results, and analysed the association of having received urine TFV results at month 1 or 3 with subsequent urine TFV test positivity, using modified Poisson regression. Results Of the 3087 AGYW enrolled, the median age was 24 years (interquartile range 21−27), 75.7% were from South Africa, 2878 (93.2%) initiated PrEP at enrolment and 107 (3.5%) after enrolment. Visit retention was 92.0−96.2% for months 1, 3 and 6, and 2518 (90.1%) exited the study with a PrEP refill. Adherence, based on the point‐of‐care urine tenofovir test positivity rate, was estimated as 72%, 71% and 65% at months 1, 3 and 6, respectively. Women who received one prior urine TFV test had a 42% higher likelihood of a subsequent positive urine TFV test (adjusted odds ratio, OR = 1.42, 95% confidence interval, CI 1.27−1.60), and those having received two prior tests had a 67% higher likelihood (adjusted OR = 1.67; 95% CI 1.41−1.98). Observed HIV incidence was 1.38/100 person‐years (95% CI 0.97−2.08). Conclusions Oral PrEP uptake, recent adherence and persistence were high in a multisite cohort of young African women over 6 months of follow‐up. The use of a novel point‐of‐care tenofovir assay with tailored real‐time adherence counselling was associated with increased adherence to PrEP at subsequent visits, warranting further study. Clinical trials registration clinicaltrials.gov NCT05746065

MDCK/Caco-2 assays serve as essential in vitro tools for evaluating membrane permeability and active transport, especially mediated by P-glycoprotein (P-gp). Despite their utility, challenges remain in quantifying active transport and using the efflux ratio (ER) to determine intrinsic values for active efflux. Such an intrinsic value for P-gp facilitated efflux necessitates knowing whether this transporter transports the neutral or ionic species of a compound. Utilising MDCK-MDR1 assays, we investigate a method for determining transporter substrate fraction preference by studying ER pH-dependence for basic, acidic and non-dissociating compounds. These results are compared with model fits based on various assumptions of transporter species preference. As an unexpected consequence of these assays, we also give evidence for an additional influx transporter at the basolateral membrane, and further extend our model to incorporate this transport. The combined influences of paracellular transport, the previously unaccounted for basolateral influx transporter, as well as potential pH effects on the transporter impedes the extraction of intrinsic values for active transport from the ER. Furthermore, we determined that using inhibitor affects the measurement of paracellular transport. While clear indications of transporter species preference remain elusive, this study enhances understanding of the MDCK system.

Cities can host significant biological diversity. Yet, urbanisation leads to the loss of habitats, species, and functional groups. Understanding how multiple taxa respond to urbanisation globally is essential to promote and conserve biodiversity in cities. Using a dataset encompassing six terrestrial faunal taxa (amphibians, bats, bees, birds, carabid beetles and reptiles) across 379 cities on 6 continents, we show that urbanisation produces taxon-specific changes in trait composition, with traits related to reproductive strategy showing the strongest response. Our findings suggest that urbanisation results in four trait syndromes (mobile generalists, site specialists, central place foragers, and mobile specialists), with resources associated with reproduction and diet likely driving patterns in traits associated with mobility and body size. Functional diversity measures showed varied responses, leading to shifts in trait space likely driven by critical resource distribution and abundance, and taxon-specific trait syndromes. Maximising opportunities to support taxa with different urban trait syndromes should be pivotal in conservation and management programmes within and among cities. This will reduce the likelihood of biotic homogenisation and helps ensure that urban environments have the capacity to respond to future challenges. These actions are critical to reframe the role of cities in global biodiversity loss.

Introduction and Objectives Certolizumab Pegol (CZP) is an anti-TNF agent approved in Brazil for Crohn's disease (CD). There is a lack of data in Brazil and Latin America detailing real-world experiences with CZP. The primary objective was clinical remission in weeks 26 and 54. The secondary endpoints were clinical response in weeks 26 and 54, endoscopic remission, biological switch rates, rates of CD-related surgery, persistence with treatment over time, and adverse events. Remission and clinical response were defined as HBI ≤4 and ≥3 points reduction of HBI, respectively. Endoscopic remission was defined as the complete healing of the intestinal mucosa.

ABSTRACT Background: Low bone mass density (BMD) is an extraintestinal finding in celiac disease (CD). This may result in bone fractures leading to loss in quality of life. Objective: To assess BMD in male CD patients at diagnosis according to the patient’s age. Methods: Descriptive retrospective carried out during the period between 2013 and 2023 in a single office that studied dual-energy X-ray absorptiometry (DXA) results in 28 male patients with a recent diagnosis of CD, divided into three groups: group 1 (age up to 18 years); group 2 (from 19 to 49 years of age) and group 3 (over 50 years of age). Were studied demographic and anthropometric parameters, time delay between symptoms onset and CD diagnosis and fracture occurrence. Results: Celiac patients studied had median age 36.0 years (IQR=16.5-50.7). Among them, 39.3% had osteopenia and 14.3% had osteoporosis. Only 36% of the sample had normal DXA values (group 1 with 37.5%; group 2 with 46% and group 3 with 14.2%). No pathological fracture was observed in this sample. CD diagnosis delay observed had median 1.0 year (IQR=1.0-4.7). When the number of individuals with normal and abnormal DXA results were compared, there was no difference in body mass index, time of diagnosis delay or Marsh classification (P=0.18). Conclusion: Male patients at the time of CD diagnosis showed a high prevalence of low BMD, which was particularly evident in individuals over 50 years of age.

We report a 23% asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) Omicron carriage rate in participants being enrolled into a clinical trial in South Africa, 15-fold higher than in trials before Omicron. We also found lower CD4 + T-cell counts in persons with human immunodeficiency virus (HIV) strongly correlated with increased odds of being SARS-CoV-2 polymerase chain reaction (PCR) positive.

Background: Burn injuries in children in low- and middle-income countries are common, serious, and preventable. Despite the high burden of disease, there is a paucity of data on the profile of paediatric burns in South Africa. Such data are essential to local burn prevention strategies. Methods: A retrospective review of all recorded paediatric burns admissions to the paediatric burns unit at Chris Hani Baragwanath Academic Hospital was performed from 1 January 2015 – 31 December 2020. Ethical approval was obtained. Data extracted anonymously included patient age, sex, mechanism of injury, injury severity, date of injury and residential location. Results: A total of 2980 admissions occurred during the study period. Infants ≤ 1 year accounted for 42.2 % (1259/2980), males 61.4 % (1689/2751), hot water burns 79.1 % (2357/2980), and major injury 40.1 % (1201/2980) of admissions. Most burn injuries occurred in winter (28.2 %, 842/2980), and most admitted patients lived in Soweto 45.5 % (1355/2980). Conclusions: Most burns admissions in the study period were characterised by male children less than one year of age, hot water burns, major burn injuries and admissions in the winter months. These results are similar to national and international data regarding age, sex, mechanism of injury and seasonality of paediatric burns. The results from the study have been utilised to inform Surgeons For Little Lives’ paediatric burns prevention campaigns in Soweto and Gauteng Province.

The Coronavirus disease (COVID-19) pandemic has increased anxiety and stress among teacher education managers and has given rise to the question of whether they have the competencies to execute their operational responsibilities productively. The theories of resilience and transformational leadership underpin this study in which teacher education managers' resilience and their responsiveness to the well-being of staff executing their operational practices in an open distance e-learning context were explored. A qualitative approach was adopted and virtual video conferencing interviews with teacher education managers were used to explore how they mitigated their strategic and operational roles and their managerial functions to ensure the well-being and organisational performance of staff working from home. Results revealed the experiences of distance managers to have been positive in that they implemented organisational strategies to mitigate the challenges faced to ensure wellness and performance among staff working from a distance. Further research applying a mixed-method design should be undertaken to determine how resilient managers and staff working from home are. That may yield different results.

BackgroundPretreatment HIV drug resistance (PDR) undermines individual treatment success and threatens the achievement of UNAIDS 95-95-95 targets. In many African countries, limited data are available on PDR as detection of recent HIV infection is uncommon and access to resistance testing is limited. We describe the prevalence of PDR among South African women with recent HIV infection from the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial.MethodsHIV-uninfected, sexually active women, aged 18-35 years, and seeking contraception were enrolled in the ECHO Trial at sites in South Africa, from 2015 to 2018. HIV testing was done at trial entry and repeated quarterly. We tested stored plasma samples collected at HIV diagnosis from women who seroconverted during follow-up and had a viral load >1000 copies/mL for antiretroviral resistant mutations using a validated laboratory-developed population genotyping assay, which sequences the full protease and reverse transcriptase regions. Mutation profiles were determined using the Stanford Drug Resistance Database.ResultsWe sequenced 275 samples. The median age was 23 years, and majority (98.9%, n = 272) were infected with HIV-1 subtype C. The prevalence of surveillance drug resistance mutations (SDRMs) was 13.5% (n = 37). Nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations were found in 12.4% of women (n = 34). Few women had NRTI (1.8%, n = 5) and protease inhibitor (1.1%, n = 3) mutations. Five women had multiple NRTI and NNRTI SDRMs.ConclusionsThe high levels of PDR, particularly to NNRTIs, strongly support the recent change to the South African national HIV treatment guidelines to transition to a first-line drug regimen that excludes NNRTIs.