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Background. Mental health conditions such as depression, anxiety and post-traumatic stress disorder (PTSD) are being increasingly recognised as common adverse outcomes for critical illness survivors. These conditions can have lasting consequences on their wellbeing, ability to return to their pre-illness level of functioning and health-related quality of life. There is a paucity of South African data in terms of the psychological aspects of the post-intensive care unit (ICU) syndrome. Objective. To identify and characterise patients who suffered from significant symptoms of mental health disease and poor mental health- related quality of life after ICU admission and who may benefit from appropriate referral, further investigation and medical intervention. Methods. Critically ill patients in a multidisciplinary tertiary ICU were prospectively enrolled upon ICU discharge. Survivors were screened for anxiety, depression and post-traumatic stress syndrome at 6 weeks and 6 months after hospital discharge. The Hospital Anxiety and Depression Score (HADS) and the Impact Of Events Scale – Revised (IES-R) were used as screening tools. The mental component summary score (MCS) of the RAND short form-36 was used to determine the effect of psychological symptoms on health-related quality of life (HRQOL). Results. The median age of the 107 ICU survivors was 42 years, and half of them were admitted for complications of COVID-19. Six out of every 10 ICU survivors experienced significant symptoms of anxiety, depression and/or PTSD at follow-up. At the 6-month study visit, 4 out of every 10 patients were experiencing significant psychological symptoms. Those affected had a significantly lower mental HRQOL when compared with those who were unaffected. More than half of those affected had co-occurrence of psychological symptoms. Significant symptoms of anxiety were common, with 5 out of every 10 participants experiencing significant symptoms at either, or both, of the study visits. More than 3 out of 10 of affected patients’ symptoms only occurred after the 6-week visit. Associations for significant psychological symptoms comprised female sex, younger age, a diagnosis of trauma and frightening memories of the ICU admission. Conclusion. The burden of mental health disease in ICU survivors is substantial, affecting their HRQOL. Six out of 10 patients experienced symptoms of anxiety, depression and PTSD, and more than half of those affected experienced co-occurrence of the conditions. A third of those affected developed these symptoms only beyond 6 weeks after hospital discharge. A potentially modifiable association with psychological symptoms was frightening memories of the ICU stay.

Abstract Background Creating an inclusive interprofessional teaching and learning community can enhance student engagement and ultimately develop essential graduate attributes (GA) (also known as generic, transferable, core, soft, work-ready or nontechnical skills). The early practical development of GA within a diverse space is essential in health profession education, as students experience the transition to clinical training as challenging. Aim This paper describes the conceptualization and implementation of an inclusive interprofessional curriculum focused on GA development in the preclinical years. Methods A phased multimethod research design was applied. Phase 1 focused on the conceptualization of a preclinical GA development curriculum through a consensus-seeking process among all staff in the School of Health and Rehabilitation Sciences (N = 36). Subsequently, in Phase 2, quantitative and qualitative data were gathered from participating first-year students (N = 135) as an early curricular implementation review. Descriptive statistical analyses for quantitative and thematic analyses for qualitative data were performed. Results During Phase 1, five themes were identified (Ethics, Professionalism, General principles for interventions, Organizations and institutions, Management) informing preclinical curriculum development. Forty-one first-year students (30%) participated in Phase 2. The majority of participants (87%) indicated that they had a positive learning experience during Phase 2. Students expressed that engagement was encouraged (83%) within a space of mutual respect (83%), with interprofessional groups assisting in building “a trusting environment and a supportive one”. Students indicated they “liked that it [module] wasn’t just about one topic”, as it concretized that “there is more to being a healthcare professional that just treating people”. Conclusion GA development provides an invaluable opportunity for interprofessional engagement. Creating a diverse and inclusive curricular space through multimodal and interprofessional training, GA training was transformed to be more practical and future-focused, creating a positive learning experience. Future research should focus on the longer-term impact of this practical, preclinical GA development during the transition of these students into the clinical training space.

Abstract Pneumonia is a major cause of death among adults living with HIV in South Africa, but the etiology of many cases remains unknown. This study evaluated the utility of a nanofluidic qPCR assay to detect and serotype Streptococcus pneumoniae in urine samples from patients hospitalized with community-acquired pneumonia (CAP). The nanofluidic qPCR assay was optimized to target 13 pneumococcal serotypes and 4 reference genes. Archived urine samples collected from patients > 15 years of age hospitalized with pneumonia between April 2018 and August 2019 were retrospectively tested using the nanofluidic qPCR assay, BinaxNOW urine antigen test, and standard LytA qPCR. Blood culture was undertaken on a subset of the samples at the discretion of the attending physician. Cohens' Kappa statistics were used to determine the concordance between the methods. Of the 828 adults hospitalized for CAP, urine samples were available in 53% (n = 439). Of those, a random subset of 96 (22%) samples underwent testing. Of the participants included in the final analysis, the mean age was 45.8 years (SD 16.2), 49% (n = 47) were female, 98% (n = 94) were black, and 66% (n = 63) were living with HIV infection. The nanofluidic qPCR method was able to detect PCV13 vaccine strains spiked into urine samples; however, the method failed to detect any pneumococcus in clinical samples. In comparison, 19% of the pneumonia cases were attributed to S. pneumoniae using urine antigen testing. Nanofluidic qPCR is unable to detect and serotype Streptococcus pneumoniae in urine samples of South Africans hospitalized with CAP.

Introduction Twin pregnancies have a high risk of extreme preterm birth (PTB) at less than 28 weeks of gestation, which is associated with increased risk of neonatal morbidity and mortality. Currently there is a lack of effective treatments for women with a twin pregnancy and a short cervix or cervical dilatation. A possible effective surgical method to reduce extreme PTB in twin pregnancies with an asymptomatic short cervix or dilatation at midpregnancy is the placement of a vaginal cerclage.Methods and analysis We designed two multicentre randomised trials involving eight hospitals in the Netherlands (sites in other countries may be added at a later date). Women older than 16 years with a twin pregnancy at

Background: Transgender women bear a huge burden of human immunodeficiency virus (HIV) in South Africa. However, they are not fully engaged in healthcare across the HIV continuum of care. In addition, transgender women face multiple facets of stigma and discrimination as well as socio-economic inequalities, which all have a negative impact on antiretroviral therapy (ART) adherence. Objective: The study aimed at exploring and describing the experiences of ART adherence of transgender women living with HIV in the Buffalo City Metro Municipality. Methods: The study employed an interpretative phenomenological analysis (IPA) design. Twelve participants were enrolled using a snowballing sampling technique. Data were collected using semi-structured interviews and analysed using an IPA framework. Results: While exploring determinants to ART adherence among transgender women living with HIV in Buffalo City Metro, two superordinate themes emerged: enablers to ART adherence and psychosocial factors promoting adherence. The study found that factors such as differentiated ART service delivery, ARV medicines-related factors, motivators for taking treatment and support systems facilitated ART adherence. Conclusion: Emerging from this study is the need to scale up differentiated, person-centred ART service deliveries that will enhance access and adherence to treatment for transgender women. Contribution: This study provides unique insights on factors enhancing ART adherence among transgender women. There is a paucity of literature on access to HIV care services for key and vulnerable populations, and these findings will be shared in the country and in the region.

Background: Infection with the human papillomavirus (HPV) is a necessary cause of cervical cancer and is one of the most prevalent sexually transmitted infections worldwide. Primary prevention strategies target reducing HPV acquisition through vaccination, limiting exposure (e.g. delayed sexual debut, barrier contraception) and health education focusing on sexual behaviour and tobacco use. Methods: The ImmunoVACCS study, conducted from 2019 to 2022 in two provinces in South Africa, examined sociodemographic characteristics, sexual practices, and knowledge of cervical cancer and the HPV vaccine among young female vaccine recipients. It encompassed participants from the previously conducted vaccine implementation trials, VACCS 1 and VACCS 2 (2011–2014). Recruitment involved telephonic contact with eligible potential participants. Data were collected through self-administered questionnaires. Results: One hundred and eleven participants took part in the current study (median age: 20 years; age range: 16–22 years). Most sexually active participants had their first engagement in secondary school (96.2%), and 77.2% used contraception during their last sexual activity. Knowledge gaps were evident, with only 13.5% recognising cervical cancer’s cervix origin and 3.6% attributing it to a virus. Despite this, 70.3% had heard of a vaccine for cervical cancer. Less than half knew about the importance of regular Pap smears (49.5%), vaccine protection (44.1%) or condom use (20.7%) against HPV and cervical cancer. Conclusion: The current study demonstrates that young women still lack complete information on cervical cancer and its risk factors even after receiving health education linked with vaccination. Contribution: This study underscores the necessity of ongoing education about HPV, its risks and preventive measures among young women to combat cervical cancer.

Abstract Fetal growth restriction (FGR) remains one of the main obstetrical problems worldwide, with consequences beyond perinatal life. Animal models with developmental and structural similarities to the human are essential to understand FGR long-term consequences and design novel therapeutic strategies aimed at preventing or ameliorating them. Herein, we described the long-term consequences of FGR in pulmonary function, structure, and gene expression, and characterized neurodevelopmental sequelae up to preadolescence in a rabbit model. FGR was induced at gestational day 25 by surgically reducing placental blood supply in one uterine horn, leaving the contralateral horn as internal control. Neonatal rabbits born near term were assigned to foster care in mixed groups until postnatal day (PND) 21. At that time, one group underwent pulmonary biomechanical testing followed by lung morphometry and gene expression analysis. A second group underwent longitudinal neurobehavioral assessment until PND 60 followed by brain harvesting for multiregional oligodendrocyte and microglia quantification. FGR was associated with impaired pulmonary function and lung development at PND 21. FGR rabbits had higher respiratory resistance and altered parenchymal biomechanical properties in the lungs. FGR lungs presented thicker alveolar septal walls and reduced alveolar space. Furthermore, the airway smooth muscle content was increased, and the tunica media of the intra-acinar pulmonary arteries was thicker. In addition, FGR was associated with anxiety-like behavior, impaired memory and attention, and lower oligodendrocyte proportion in the frontal cortex and white matter. In conclusion, we documented and characterized the detrimental pulmonary function and structural changes after FGR, independent of prematurity, and beyond the neonatal period for the first time in the rabbit model, and describe the oligodendrocyte alteration in pre-adolescent rabbit brains. This characterization will allow researchers to develop and test therapies to treat FGR and prevent its sequelae.

Focused ultrasound on the thalamus is employed to relieve tremor in movement disorders. The treatment efficacy is currently assessed by subjective observation of patient tremor during hand movements. The purpose of this study was to create a simple quantitative method to assess tremor based on traditional pen-and-paper spiral drawing that could be employed during treatment and follow-up visits. Image processing was employed to automatically and rapidly clean scanned spiral and line drawings and to isolate the minimal part of the drawing that could provide sufficient data for tremor detection. Sobel edge detection and easily-interpretable statistics of the distribution of edge-angle orientations in the spirals relative to the spiral centres were used as tremor measures. The method was applied to scanned drawings of 122 tremor patients before treatment and in follow-up visits. Discrimination analysis of the tremor measure between drawings in the session before treatment and the follow-up sessions was carried out. The processing yielded correctly cropped and clean spirals. The tremor measure demonstrated consistent tremor reduction in the treated hand drawings in all five follow-up visits during the first year following treatment date in 76 patients from the study cohort. In this study we developed a computational method that rapidly computed tremor severity estimate in an explainable and clinically useful manner from a traditional pen-and-paper spiral drawing. This rapid quantitative and objective tremor assessment can easily be implemented during focused ultrasound treatment and replace the subjective assessment currently employed.

Unhealthy food choices and consumption, coupled with sedentary lifestyles among consumers, intensify public health concerns regarding the quadruple disease burden, despite Primary Health Care (PHC) policy. However, the current relationship between consumer knowledge about healthy foods and following a healthy lifestyle needs to be explored. Our study, therefore, aimed to determine the association between consumers' subjective and objective knowledge about healthy foods and various healthy lifestyle choices. A cross-sectional survey was conducted among employed consumers (N = 157) from South African corporate settings. We used structural equation modelling (SEM) to determine associations between subjective and objective knowledge about healthy foods and healthy lifestyle choices. Our findings showed that most participants scored high on making healthy lifestyle choices relating to avoiding smoking (69.5%) and limiting drinking alcohol (68.7%) but less so for food and sleep (44.4%) while neglecting exercise, relaxation (13.7%), and choices that require dedicated effort (25.2%). On average, participants had high levels of subjective (mean = 3.59; 5-point Likert scale) knowledge and objective knowledge about healthy foods (88.4-95.9% correct responses). However, their objective knowledge about weight and cholesterol had severe deficiencies (36.7%). SEM confirmed an association between subjective knowledge and most healthy lifestyle choice categories, while income contributed to dedicated effort lifestyle choices. By contrast, objective knowledge did not associate with such choices. Our structural model suggests that subjective knowledge about healthy foods contributes to healthy lifestyle choices. Therefore, subjective knowledge and the objective knowledge deficiencies we identified among corporate consumers can serve as a valuable starting point for informed education to promote PHC policy and healthy lifestyle choices.

BackgroundDecentralised and evidence-informed health systems rely on managers and practitioners at all levels having sufficient 'decision space' to make timely locally informed and relevant decisions. Our objectives were to understand decision spaces in terms of constraints and enablers and outline opportunities through which to expand them in an understudied rural context in South Africa.MethodsThis study examined decision spaces within Mpumalanga Province, using data and insights generated through a participatory action research process with local communities and health system stakeholders since 2015, which was combined with published documents and research team participant observation to produce findings on three core domains at three levels of the health system.ResultsAlthough capacity for decision making exists in the system, accessing it is frequently made difficult due to a number of intervening factors. While lines of authority are generally well-defined, personal networks take on an important dimension in how stakeholders can act. This is expressed through a range of informal coping strategies built on local relationships. There are constraints in terms of limited formal external accountability to communities, and internal accountability which is weak in places for individuals and focused more on meeting performance targets set at higher levels and less on enabling effective local leadership. More generally, political and personal factors are clearly identified at higher levels of the system, whereas at sub-district and facility levels, the dominant theme was constrained capacity.ConclusionsBy examining the balance of authority, accountability and capacity across multiple levels of the provincial health system, we are able to identify emergent decision space and areas for enlargement. Creating spaces to support more constructive relationships and dialogue across system levels emerges as important, as well as reinforcing horizontal networks to problem solve, and developing the capacity of link-agents such as community health workers to increase community accountability.

Background and objectivesTransgender and gender diverse (trans) health research has grown rapidly, highlighting the need to characterize the scientific evidence base. We conducted a systematic review of peer-reviewed research on disease burden and correlates in trans adolescents and adults over a 20-month period to identify knowledge gaps and assess methodological characteristics including measurement of gender identity, community engagement, and study quality.Data sources, eligibility criteria, and synthesis methodsWe searched seven databases using terms related to (a) transgender populations and (b) health or disease. Eligible studies were in English, French, or Spanish and reported original quantitative data on mental health or substance use conditions, infectious diseases, or non-communicable conditions in at least 25 trans individuals aged 15+. Quality assessment was performed in duplicate on a 10% sample of articles and findings were summarized using narrative synthesis.ResultsThe 328 included studies were conducted in 45 countries, with most from North America (54%) and limited research from South Asia (3%), Sub-Saharan Africa (3%), and the Middle East and North Africa (2%). Most studies used cross-sectional designs (73%) and convenience sampling (65%). Only 30% of studies reported any form of community engagement. Mental health and substance use disorders were the most studied area (77% of studies) and non-communicable conditions the least (16%). Available data indicated that trans populations experience high disease burden with considerable heterogeneity within and across settings. Of 39 articles assessed for quality, 80% were rated as fair, 18% as poor, and 3% as good quality.Conclusions and implicationsGeographic, gender-specific, and topical gaps remain in trans health, but we found more research from African countries, with transmasculine people, and on non-communicable conditions than previous syntheses. Areas for growth in trans health research include community engagement, non-binary health, chronic and age-related conditions, and health determinants.RegistrationPROSPERO CRD42021234043.

Background Of over 8,000 recorded randomised trials addressing COVID-19, around 80% were of treatments, and 17% have reported results. Approximately 1% were adaptive or platform trials, with 25 having results available, across 29 journal articles and 10 preprint articles. Methods We conducted an extensive literature review to address four questions about COVID-19 trials, particularly the role and impact of platform/adaptive trials and lessons learned. Results The key findings were: Q1. Social value in conducting trials and uptake into policy? COVID-19 drug treatments varied substantially and changed considerably, with drugs found effective in definitive clinical trials replacing unproven drugs. Dexamethasone has likely saved ½-2 million lives, and was cost effective across a range of countries and populations, whereas the cost effectiveness of remdesivir is uncertain. Published economic and health system impacts of COVID-19 treatments were infrequent. Q2. Issues with adaptive trial designs. Of the 77 platform trials registered, 6 major platform trials, with approximately 50 treatment arms, recruited ~135,000 participants with funding over $100 million. Q3. Models of good practice. Streamlined set-up processes such as flexible and fast-track funding, ethics, and governance approvals are vital. To facilitate recruitment, simple and streamlined research processes, and pre-existing research networks to coordinate trial planning, design, conduct and practice change are crucial to success. Q4. Potential conflicts to avoid? When treating patients through trials, balancing individual and collective rights and allocating scarce resources between healthcare and research are challenging. Tensions occur between commercial and non-commercial sectors, and academic and public health interests, such as publication and funding driven indicators and the public good. Conclusion There is a need to (i) reduce small, repetitive, single centre trials, (ii) increase coordination to ensure robust research conducted for treatments, and (iii) a wider adoption of adaptive/platform trial designs to respond to fast-evolving evidence landscape.

This case study describes the successful short-term outcome of staged minimally invasive pectus excavatum correction and endoscopic mitral valve repair in a patient with severe mitral valve regurgitation and pectus excavatum.

Background: Burnout among doctors has been linked with decreased quality of patient care. The coronavirus disease 2019 (COVID-19) pandemic highlighted the need to protect doctors’ mental health and well-being. This study aimed to investigate burnout, resilience and coping strategies among registrars in the MMed programme of the University of the Free State (UFS) in 2020. Methods: In this quantitative, cross-sectional study, a link to an online anonymous self-administered questionnaire with socio-demographic questions, perceived stress, Copenhagen Burnout Inventory (CBI), Connor-Davidson Resilience Scale and Brief Cope was emailed to all 278 registrars. Results: Sixty registrars responded (response rate 21.6%). More than half (55.0%) were male and 73.3% were married. There were 28.3% second- and third-year students, respectively. Most (58.3%) had 5–10 years’ work experience. The CBI personal scale had the highest median value (58.3; interquartile range [IQR]: 43.3; 70.8) with 70% scoring ≥ 50. The median score for resilience was 78 of 100 (IQR: 69; 84). There were weak negative correlations between resilience and burnout scores (r = –0.31 to r = –0.37). Planning, positive reframing and acceptance were the most frequently used adaptive coping mechanisms; self-distraction was the most frequently used maladaptive coping mechanism. There was no association between gender and burnout and resilience scores. Conclusion: Registrars were resilient with low levels of patient- and work-related burnout, and higher personal burnout, using mostly positive coping strategies. Contribution: This study gives insight into the well-being of registrars at the UFS during COVID-19. Continuous monitoring and support for this population are essential to foster mental health and well-being.

Abstract Sensitive tools for detecting concurrent colonizing pneumococcal serotypes are needed for detailed evaluation of the direct and indirect impact of routine pneumococcal conjugate vaccine (PCV) immunization. A high-throughput quantitative nanofluidic real-time PCR (Standard BioTools ‘Fluidigm’) reaction-set was developed to detect and quantify 92 pneumococcal serotypes in archived clinical samples. Nasopharyngeal swabs collected in 2009–2011 from South African children ≤ 5 years-old, previously serotyped with standard culture-based methods were used for comparison. The reaction-set within the ‘Fluidigm’ effectively amplified all targets with high efficiency (90–110%), reproducibility (R2 ≥ 0.98), and at low limit-of-detection ( 80% and specificity > 95% compared with the referent standard, culture based Quellung method. The qPCR method was able to serotype pneumococcal types with good discrimination compared with Quellung (ROC-AUC: > 0.73). The high-throughput nanofluidic real-time PCR method simultaneously detects 57 individual serotypes, and 35 serotypes within 16 serogroups in 96 samples (including controls), within a single qPCR run. This method can be used to evaluate the impact of current PCV formulations on vaccine-serotype and non-vaccine-serotype colonization, including detection of multiple concurrently colonizing serotypes. Our qPCR method can allow for monitoring of serotype-specific bacterial load, as well as emergence or ongoing transmission of minor or co-colonizing serotypes that may have invasive disease potential.

Background. The characteristics and mortality outcomes of patients admitted to South African intensive care units (ICUs) owing to medical conditions are unknown. Available literature is derived from studies based on data from high-income countries. Objectives. To determine ICU utilisation by medical patients and evaluate the scope of admissions and clinical associations with hospital mortality in ICU patients 12 years and older admitted to an Eastern Cape tertiary ICU, particularly in the subset with HIV disease. Methods. A retrospective descriptive one-year cohort study. Data were obtained from the LivAKI study database and demographic data, comorbidities, diagnosis, and mortality outcomes and associations were determined. Results. There were 261 (29.8%) medical ICU admissions. The mean age of the cohort was 40.2 years; 51.7% were female. When compared with the surgical emergencies, the medical subgroup had higher sequential organ failure assessment (SOFA) scores (median score 5 v. 4, respectively) and simplified acute physiology score III (SAPS 3) scores (median 52.7 v. 48.5), a higher incidence of acute respiratory distress syndrome (ARDS) (7.7% v. 2.9%) and required more frequent dialysis (20.3% v. 5.5%). Of the medical admissions, sepsis accounted for 32.4% of admission diagnoses. The HIV seroprevalence rate was 34.0%, of whom 57.4% were on antiretroviral therapy. ICU and hospital mortality rates were 11.1% and 21.5% respectively, while only acute kidney injury (AKI) and sepsis were independently associated with mortality. The HIV-positive subgroup had a higher burden of tuberculosis (TB), higher admission SOFA and SAPS 3 scores and required more organ support. Conclusion. Among medical patients admitted to ICU, there was a high HIV seroprevalence with low uptake of antiretroviral therapy. Sepsis was the most frequently identified ICU admission diagnosis. Sepsis and AKI (not HIV) were independent predictors of mortality. Co-infection with HIV and TB was associated with increased mortality.

Abstract Fetal growth restriction is one of the leading causes of perinatal mortality and morbidity and has consequences that extend well beyond the neonatal period. Current management relies on timely delivery rather than improving placental function. Several prenatal strategies have failed to show benefit in clinical trials after promising results in animal models. Most of these animal models have important developmental and structural differences compared to the human and/or are insufficiently characterized. We aimed to describe placental function and structure in an FGR rabbit model, and to characterize the early brain and lung developmental morbidity using a multimodal approach. FGR was induced in time-mated rabbits at gestational day 25 by partial uteroplacental vessel ligation in one horn. Umbilical artery Doppler was measured before caesarean delivery at gestational day 30, and placentas were harvested for computed microtomography and histology. Neonates underwent neurobehavioral or pulmonary functional assessment the day after delivery, followed by brain or lung harvesting, respectively. Neuropathological assessment included multiregional quantification of neuron density, apoptosis, astrogliosis, cellular proliferation, and oligodendrocyte progenitors. Brain region volumes and diffusion metrics were obtained from ex-vivo brain magnetic resonance imaging. Lung assessment included biomechanical tests and pulmonary histology. Fetal growth restriction was associated with labyrinth alterations in the placenta, driven by fetal capillary reduction, and overall reduced vessels volume. FGR caused altered neurobehavior paralleled by regional neuropathological deficits and reduced fractional anisotropy in the cortex, white matter, and hippocampus. In addition, FGR kittens presented functional alterations in the peripheral lung and structurally underdeveloped alveoli. In conclusion, in a uteroplacental insufficiency FGR rabbit model, placental vascular alterations coincide with neurodevelopmental and pulmonary disruption.

Background. Careful consideration of an increasingly underprepared tertiary student population, the limited use of simulation in South African (SA) healthcare education and a changing healthcare education milieu is required from SA educators when implementing, evaluating and revising simulation integration. Objectives. To develop a conceptual framework for the integration of simulation in the SA undergraduate physiotherapy programme. Methods. A non-experimental descriptive research design was used. A purposive sample of 15 healthcare educationalists from SA and abroad were approached to participate in a modified Delphi survey, informed by the results obtained from a systematic review identifying simulation integration framework elements. Data were analysed as percentages, with feedback provided to panel members following each round. Results. Data saturation was achieved after round 3, with a response rate of 73.3% (n=11). The main findings suggested that student preparation prior to simulation-based learning experiences (SBLEs) should include orientation to SBLE logistics and expectations (73%), and could include informal assessment of theory (64%). Inclusion of the feedback/debriefing process (82%), methods (100%) and timing (85%) as part of student and educator preparation were also deemed essential. Panel members agreed that programme evaluation in line with stakeholder feedback (92%) is vital for guiding adjustments to the programme that is integrating simulation. Conclusion. The developed conceptual framework indicates the necessity of student and educator preparation to ensure optimal SBLE participation and outcome achievement. Programme sustainability should be ensured through programme evaluation and adjustment, in line with stakeholder feedback, best practice and accrediting professional body guidelines.

Background. Research projects frequently include students, a potentially vulnerable population, as participants. Objectives. To determine University of the Free State (UFS) medical students’ experiences as research participants. Response rates to and preferences for hard copy and electronic questionnaires were also investigated. Methods. All 804 UFS undergraduate medical students in 2020 were approached to participate in this cross-sectional survey. Fourth- and fifth-year students and one-half of the third-year class were approached in person to complete anonymous hard copy questionnaires in a class setting. First- and second-year students and the other half of the third-year class were contacted electronically to complete anonymous electronic questionnaires. Results. Response rates to hard copy questionnaires were at least ~45% of the entire year group (and >70% of those to whom the questionnaire was distributed in class) compared with approximately a third of those contacted electronically. Students who responded to electronic questionnaires preferred electronic completion, whereas those who responded to hard copy questionnaires preferred the hard copy format, except fifth-year students. The majority of students (except those in their first year) had previously been approached to participate in research projects. Between a fifth and a third of all year groups indicated that they had refused participation at least once. More than a third of fifth-year students experienced insufficient time to decide on participation. Up to a quarter of third- to fifth-year groups had felt pressurised to participate. Conclusion. Hard copy questionnaires in class, the preferred data collection method for many students, produced better response rates but placed potential pressure on students to participate.

Abstract Several recent studies have argued that large, long-lived and molten magma chambers may not occur in the shallow Earth’s crust. Here we present, however, field-based observations from the Bushveld Complex that provide evidence to the contrary. In the eastern part of the complex, the magmatic layering continuously drapes across a ~ 4-km-high sloping step in the chamber floor. Such deposition of magmatic layering implies that the resident melt column was thicker than the stepped relief of the chamber floor. Prolonged internal differentiation within this thick magma column is further supported by evolutionary trends in crystallization sequence and mineral compositions through the sequence. The resident melt column in the Bushveld chamber during this period is estimated at > 5-km in thickness and > 380,000 km3 in volume. This volume of magma is three orders of magnitude larger than any known super-eruption in the Earth’s history and is only comparable to the extrusive volumes of some of Earth’s large igneous provinces. This suggests that super-large, entirely molten, and long-lived magma chambers occur, at least occasionally, in the geological history of our planet. Therefore, the classical view of magma chambers as ‘big magma tanks’ remains a viable research concept for some of Earth’s magmatic provinces.

Abstract Background The need for healthcare curricula renewal to facilitate a continuum in education from classrooms to diverse healthcare settings is undeniable. Simulation has been recognized as an educational strategy to address healthcare education challenges, with limited reporting on the integration of simulation-based learning experiences in physiotherapy education. The study aimed to describe the finalisation of a framework for integration of healthcare simulation in an undergraduate physiotherapy program. Methods A qualitative descriptive research design was utilized. Five South African experts in the fields of healthcare simulation and/or physiotherapy education contributed to the finalization of the framework during a consensus meeting. Content analysis was employed and credibility was ensured through double coding. Results Structural coding yielded five themes- Planning, Implementation, Program Evaluation, Program Revision and Framework. The five themes consisted of fifteen categories, two sub-categories and 44 codes. The planning theme was most robust with seven categories. The Planning, Implementation, Evaluation, Revision (PIER) framework was developed and finalized by expert participants. following the consensus meeting. Conclusion Needs analyses when planning and incorporating simulation is essential. Collaboration through resource and knowledge sharing is vital in developing a responsive curriculum integrating simulation. Furthermore, facilitator and student preparation are paramount in ensuring active engagement in simulated-based learning experiences. The interconnectedness of all framework elements and integration phases, as well as the implied importance of competent facilitators and prepared students is crucial and highlights careful consideration to be given to these aspects. The PIER framework is generic in nature and represents the continuous process of simulation integration for any healthcare program.

Background. The benefits of simulation in healthcare education are undeniable, and in the current healthcare climate, a drastic change in delivering healthcare training is critical. Therefore, integration of simulation is essential, and necessitates detailed planning and well-trained educators. Objectives. To develop a conceptual framework for the integration of simulation in South African (SA) undergraduate physiotherapy programmes. Methods. A non-experimental descriptive research design using a modified Delphi survey was conducted. Results from a systematic review identifying simulation integration framework elements informed the Delphi survey. A purposive sample of 15 healthcare educationalists from SA and abroad were approached to participate. Data were analysed as percentages, and feedback was provided to panel members following each round. Results. A response rate of 73.3% (n=11) was achieved. Planning was explored as one of the themes. Both institutional- and discipline-specific needs analyses were identified as essential (93%), and societal needs were useful to consider (64%). Resource identification and sharing (84%) were regarded as vital, and expert collaboration in curriculum development (79%) with scaffolded skills integration (75%) was advised. The necessity for trained facilitators (93%) and educator role identification (71%) was evident. Statements related to mastery learning/deliberate practice and the use of simulation for assessment purposes yielded the least consensus. Conclusion. A constructively aligned curriculum based on both student and institutional needs and resource availability in guiding simulation integration was regarded as essential. Educator competency in both the development and delivery of the programme, especially debriefing methods, is vital for optimising student learning.

Background: Stellenbosch University’s (SU) Faculty of Medicine and Health Sciences (FMHS), developed a sexual health course to be integrated throughout the revised medical curriculum. Aim: To use the Sexual Health Education for Professionals Scale (SHEPS) to gather baseline and future follow-up data to inform curriculum development and evaluation. Setting: The first-year medical students (N = 289) of the FMHS SU. Methods: The SHEPS was answered before the start of the sexual health course. The knowledge, communication and attitude sections were answered with a Likert-type scale. Students had to describe their perceived confidence in their knowledge and communication skills to care for patients within specific sexuality-related clinical scenarios. The attitude section measured the students’ level of agreement or disagreement on sexuality-related opinion statements. Results: The response rate was 97%. Most students were female, and 55% of the class were first taught about sexuality in the age group 13–18 years. The students had more confidence in their communication skills than knowledge before any tertiary training. The attitude section revealed a binomial distribution, ranging from acceptance to a more restrictive attitude towards sexual behaviour. Conclusion: It is the first time the SHEPS has been used in a South African context. The results provide novel information about the range of perceived sexual health knowledge, skills and attitudes of first-year medical students before they start tertiary training. Contribution: Findings from this study will guide content development and evaluation of the sexual health course at the institution where the study was conducted, as well as allow for culture sensitive education.

Yeasts associated with lepidopteran pests have been shown to play a role in their survival, development, and oviposition preference. It has been demonstrated that combining these yeasts with existing biological control agents can enhance their efficacy. The tortricid Thaumatotibia leucotreta is a phytosanitary pest in the South African citrus industry, with the baculovirus Cryptophlebia leucotreta granulovirus (CrleGV) being one of the components that can control this pest. Several yeast species were shown to be associated with T. leucotreta larvae, which affected their behaviour and development. A series of detached fruit bioassays were performed to determine whether the combination of yeast with CrleGV enhances its efficacy. These assays included determining the optimal yeast/virus ratio, testing all isolated yeast species in combination with CrleGV, and further improving yeast/virus formulation by adding an adjuvant. The optimal yeast concentration to use alongside CrleGV was determined to be 106 cells·mL−1. Pichia kluyveri, P. kudriavzevii, Kluyveromyces marxianus, and Saccharomyces cerevisiae in combination with CrleGV reduced larval survival compared to CrleGV alone. The addition of molasses and BREAK-THRU® S 240 to P. kudriavzevii and S. cerevisiae in combination with CrleGV did not notably improve their effectiveness; however, there was an observed decrease in larval survival. In future studies, field trials will be conducted with combinations of CrleGV and P. kudriavzevii or S. cerevisiae to investigate whether these laboratory findings can be replicated in orchard conditions.

Background. Up to a quarter of inpatients in high-income countries (HICs) self-report beta-lactam allergy (BLA), which if incorrect,increases the use of alternative antibiotics, worsening individual health outcomes and driving bacterial resistance. In HICs, up to 95% ofself-reported BLAs are incorrect. The epidemiology of BLA in low- and middle-income African countries is unknown.Objectives. To describe the epidemiology and de-labelling outcomes of self-reported BLA in hospitalised South African (SA) patients.Methods. Point-prevalence surveys were conducted at seven hospitals (adult, paediatric, government and privately funded, district andtertiary level) in Cape Town, SA, between April 2019 and June 2021. Ward prescription records and in-person interviews were conductedto identify and risk-stratify BLA patients using the validated PEN-FAST tool. De-labelling was attempted at the tertiary allergy clinic atGroote Schuur Hospital.Results. A total of 1 486 hospital inpatients were surveyed (1 166 adults and 320 children). Only 48 patients (3.2%) self-reported a BLA,with a higher rate in private than in government-funded hospitals (6.3% v. 2.8%; p=0.014). Using the PEN-FAST tool, only 10.4% (n=5/48)of self-reported BLA patients were classified as high risk for true penicillin hypersensitivity. Antibiotics were prescribed to 70.8% (n=34/48)of self-reported BLA patients, with 64.7% (n=22/34) receiving a beta-lactam. Despite three attempts to contact patients for de-labelling atthe allergy clinic, only 3/36 underwent in vivo testing, with no positive results, and 1 patient proceeded to a negative oral challenge.Conclusion. Unlike HICs, self-reported BLA is low among inpatients in SA. The majority of those who self-reported BLA were low risk fortype 1 hypersensitivity, but outpatient de-labelling efforts were largely unsuccessful.

[This corrects the article DOI: 10.1371/journal.pone.0269806.].

Introduction: SARS-CoV-2 has resulted in increased worldwide demand for personal protective equipment (PPE). With pressure from ongoing epidemic and endemic episodes, we assessed an adapted snorkel mask that provides full-face protection for healthcare workers (HCWs), particularly during aerosol-generating procedures. These masks have a custom-made adaptor which allows the fitment of standard medical respiratory filters. The aim of this study was to evaluate the fit, seal and clinical usability of these masks. Methods: This multicentre, non-blinded in-situ simulation study recruited fifty-two HCWs to don and doff the adapted snorkel mask. Negative pressure seal checks and a qualitative fit test were performed. The HCWs completed intubation and extubation of a manikin in a university skills training laboratory, followed by a web-based questionnaire on the clinical usability of the masks. Results: Whilst fit and usability data were generally satisfactory, two of the 52 participants (3.8%) felt that the mask did not span the correct distance from the nose to the chin, and 3 of 34 participants (8.8%) who underwent qualitative testing with a Bitrex test failed. The majority of users reported no fogging, humidity or irritation. It was reportedly easy to speak while wearing the mask, although some participants perceived that they were not always understood. Twenty-one participants (40%) experienced a subjective physiological effect from wearing the mask; most commonly a sensation of shortness of breath. Discussion: A fit-tested modified full-face snorkel mask may offer benefit as a substitute for N95 respirators and face shields. It is, however, important to properly select the correct mask based on size, fit testing, quality of the three-dimensional (3D) printed parts and respiratory filter to be used. Additionally, HCWs should be trained in the use of the mask, and each mask should be used by a single HCW and not shared.

Abstract Current real-time high-throughput Polymerase Chain Reaction (qPCR) methods do not distinguish serotypes 6A from 6B, 18C from 18A/B and 22F from 22A. We established a nanofluidic real-time PCR (Fluidigm) for serotyping that included Dual-Priming-Oligonucleotides (DPO), a Locked-Nucleic-Acid (LNA) probe and TaqMan assay-sets for high-throughput serotyping. The designed assay-sets target capsular gene wciP in serogroup 6, wciX and wxcM in serogroup 18, and wcwA in serogroup 22. An algorithm combining results from published assay-sets (6A/B/C/D; 6C/D; 18A/B/C; 22A/F) and designed assay-sets for 6A/C; 18B/C/F; 18C/F, 18F and 22F was validated through blind analysis of 1973 archived clinical samples collected from South African children ≤ 5-years-old (2009–2011), previously serotyped with the culture-based Quellung method. All assay-sets were efficient (92–101%), had low variation between replicates (R2 > 0.98), and were able to detect targets at a limit of detection (LOD) of

Abstract Habits are inflexible behaviors that develop after extensive repetition, and overreliance on habits is a hallmark of many pathological states. The striatum is involved in the transition from flexible to inflexible responding, and interspersed throughout the striatum are patches, or striosomes, which make up ~15% of the volume of the striatum relative to the surrounding matrix compartment. Previous studies have suggested that patches are necessary for normal habit formation, but it remains unknown exactly how patches contribute to habit formation and expression. Here, using optogenetics, we stimulated striatal patches in Sepw1-NP67 mice during variable interval training (VI60), which is used to establish habitual responding. We found that activation of patches at reward retrieval resulted in elevated responding during VI60 training by modifying the pattern of head entry and pressing. Further, this optogenetic manipulation reduced subsequent responding following reinforcer devaluation, suggesting modified habit formation. However, patch stimulation did not generally increase extinction rates during a subsequent extinction probe, but did result in a small ‘extinction burst’, further suggesting goal-directed behavior. On the other hand, this manipulation had no effect in omission trials, where mice had to withhold responses to obtain rewards. Finally, we utilized fast-scan cyclic voltammetry to investigate how patch activation modifies evoked striatal dopamine release and found that optogenetic activation of patch projections to the substantia nigra pars compacta (SNc) is sufficient to suppress dopamine release in the dorsal striatum. Overall, this work provides novel insight into the role of the patch compartment in habit formation, and provides a potential mechanism for how patches modify habitual behavior by exerting control over dopamine signaling.

Background. Severe theophylline toxicity requiring haemodialysis accounts for approximately one-third of drug toxicity cases admitted to the Livingstone Tertiary Hospital (LTH) intensive care unit (ICU) in Gqeberha, South Africa, imposing a significant resource burden. Objectives. To investigate the characteristics and burden of severe theophylline toxicity in an Eastern Cape Province tertiary hospital adult ICU. Methods. A retrospective review of all severe theophylline toxicity admissions to the ICU from 1 January 2013 to 31 December 2018 was conducted. Demographic and clinical data were captured and analysed. The National Department of Health 2019 fees schedule was used to calculate costs based on duration of ICU stay and number of haemodialysis sessions received. Results. Of the 57 patients included in the study, 84% were cases of deliberate self-harm. The majority were aged 400 µmol/L (sensitivity 88%, specificity 12%). All the 4 patients who died had an initial serum theophylline level >1 000 µmol/L. The mean (SD) cost per admission amounted to ZAR16 897 (10 718), with a mean of one 4-hour dialysis session per admission. Conclusion. Severe theophylline toxicity, usually in the context of deliberate self-harm, is a preventable yet life-threatening toxicity encountered at LTH. Demographic risk factors include young females from certain areas in and around Gqeberha. Risk factors for complications include older age, paradoxically normal or elevated serum potassium levels, elevated serum creatinine kinase levels and an initial serum theophylline level >400 µmol/L. Patients with these clinical features should be closely monitored and treated timeously at an appropriate level of care. The need for ICU admission and dialysis, both limited resources, makes the treatment of severe theophylline toxicity costly. Further studies of the underlying psychosocial drivers, local prescribing practices and preventive interventions related to severe theophylline toxicity are required.

Background. Early identification of patients at high risk of severe disease requiring referral and treatment at a high‐care facility is imperative in the management of COVID‐19 pneumonia in a limited‐resource setting, as transfer of unstable patients can be detrimental. Objectives. To examine the value of the neutrophil‐to‐lymphocyte ratio (NLR) calculated on admission to a healthcare facility as a predictor of the need for early referral to a high‐care facility for further treatment. Methods. We designed a cohort analytical study of 198 patients with COVID‐19 pneumonia admitted to the COVID‐19 unit at Universitas Academic Hospital in Bloemfontein, South Africa, between 20 May and 30 September 2021. Results. Of the 198 patients enrolled in the study, 134 (67.7%) were admitted to high care and 93 (46.9%) died. The median (interquartile range (IQR)) NLR measured on admission to the hospital was 8.09 (4.90 ‐ 14.86), and the NLR ranged from 0.26 to 136.7. The admission NLR was statistically significantly higher in the high‐care group v. the general ward group (p

Background. Human papillomavirus (HPV)-based primary screening guidelines are based on screening test performance and prevalence data generated in high-resource areas with low HIV infection rates. There is an urgent need for local data on infection and disease prevalence, as well as screening test performance, among both HIV-positive and HIV-negative South African (SA) women, in order to inform updated screening guidelines. Objectives. This study describes the baseline characteristics of participants in the cross-sectional phase of the multicentric DIAgnosis in Vaccine And Cervical Cancer Screen (DiaVACCS) screening trial. The objective was to determine the prevalence of positive screening and pre-invasive disease using different tests and strategies in the SA HIV-positive and HIV-negative population. Methods. A total of 1 104 women aged 25 - 65 years and eligible for screening were included, 465 HIV positive and 639 HIV negative. Visual inspection and molecular and cytological screening tests were done on self-sampled and healthcare worker-collected specimens. All participants who screened positive and 49.1% of those who screened negative were invited for colposcopy and biopsy, and those qualifying for treatment were recalled for large loop excision of the transformation zone as part of the trial. The worst histology result for each participant was used, and for untested women, multiple imputation was used to estimate verification bias- adjusted histology values. Results. Visual inspection was positive in 50.4% of HIV-positive v. 20.9% of HIV-negative women, cytology (atypical squamous cells of undetermined significance) in 39.9% v. 17.0%, and high-risk HPV DNA in 41.2% v. 19.6%. Overall, high-grade squamous intraepithelial lesion-positive cytology peaked in the age group 30 - 39 years at 16.7%. After adjustment for verification bias, histological diagnosis of cervical intraepithelial neoplasia (CIN)2+ was suspected in 44.7% v. 23.5% and CIN3+ in 23.3% v. 10.2% of HIV-positive and negative women, respectively. Invasive cancer was diagnosed in 15 women (1.95% of histological studies performed), and verification bias adjustment suggested 20 cases (1.8% of the study population). Conclusion. The baseline findings from the DiaVACCS trial confirm a high prevalence of HPV-related cervical pathology in the SA HIV-negative screening population, showing a clear need to reach these women with a screening programme. Among HIV-positive women, prevalence values were almost doubled. The prevalence of existing invasive cervical cancer was 1 - 2% of all women. Further analysis of the performance of single and multiple screening tests between the two subgroups will contribute to the choice of the most effective strategies to identify women at risk of developing invasive cancer.

Abstract Traumatic brain injury (TBI) is linked to long-term symptoms in a sub-set of patients who sustain an injury, but this risk is not universal, leading us and others to question the nature of individual variability in recovery trajectories. Extracellular vesicles (EVs) are a promising, novel avenue to identify blood-based biomarkers for TBI. Here, our aim was to determine if glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) measured 1-year postinjury in EVs could distinguish patients from controls, and whether these biomarkers relate to TBI severity or recovery outcomes. EV GFAP and EV NfL were measured using an ultrasensitive assay in 72 TBI patients and 20 controls. EV GFAP concentrations were elevated in moderate and severe TBI compared to controls (p’s

Abstract Phenotypic plasticity in life-history traits in response to heterogeneous environments has been observed in a number of fishes. Conversely, genetic structure has recently been detected in even the most wide ranging pelagic teleost fish and shark species with massive dispersal potential, putting into question previous expectations of panmixia. Shallow oceanic seamounts are known aggregation sites for pelagic species, but their role in genetic structuring of widely distributed species remains poorly understood. The yellowtail kingfish (Seriola lalandi), a commercially valuable, circumglobal, epipelagic fish species occurs in two genetically distinct Southern Hemisphere populations (South Pacific and southern Africa) with low levels of gene-flow between the regions. Two shallow oceanic seamounts exist in the ocean basins around southern Africa; Vema and Walters Shoal in the Atlantic and Indian oceans, respectively. We analysed rare samples from these remote locations and from the South African continental shelf to assess genetic structure and population connectivity in S. lalandi and investigated life-history traits by comparing diet, age, growth and maturation among the three sites. The results suggest that yellowtail from South Africa and the two seamounts are genetically and phenotypically distinct. Rather than mere feeding oases, we postulate that these seamounts represent islands of breeding populations with site-specific adaptations.

Toxic metal exposure is a threat to green sea turtles (Chelonia mydas) inhabiting and foraging in coastal seagrass meadows and are of particular concern in local bays of the Great Barrier Reef (GBR), as numerous sources of metal contaminants are located within the region. Seagrass species tend to bioaccumulate metals at concentrations greater than that detected in the surrounding environment. Little is known regarding ecotoxicological impacts of environmental metal loads on seagrass or Chelonia mydas (C. mydas), and thus this study aimed to investigate and describe seagrass metal loads in three central GBR coastal sites and one offshore site located in the northern GBR. Primary seagrass forage of C. mydas was identified, and samples collected from foraging sites before and after the 2018/2019 wet season, and multivariate differences in metal profiles investigated between sites and sampling events. Most metals investigated were higher at one or more coastal sites, relative to data obtained from the offshore site, and cadmium (Cd), cobalt (Co), iron (Fe) and manganese (Mn) were found to be higher at all coastal sites. Principle Component Analysis (PCA) found that metal profiles in the coastal sites were similar, but all were distinctly different from that of the offshore data. Coastal foraging sites are influenced by land-based contaminants that can enter the coastal zone via river discharge during periods of heavy rainfall, and impact sites closest to sources. Bioavailability of metal elements are determined by complex interactions and processes that are largely unknown, but association between elevated metal loads and turtle disease warrants further investigation to better understand the impact of environmental contaminants on ecologically important seagrass and associated macrograzers.

Toxic metal exposure is a threat to green sea turtles (Chelonia mydas) inhabiting and foraging in coastal seagrass meadows and are of particular concern in local bays of the Great Barrier Reef (GBR), as numerous sources of metal contaminants are located within the region. Seagrass species tend to bioaccumulate metals at concentrations greater than that detected in the surrounding environment. Little is known regarding ecotoxicological impacts of environmental metal loads on seagrass or Chelonia mydas (C. mydas), and thus this study aimed to investigate and describe seagrass metal loads in three central GBR coastal sites and one offshore site located in the northern GBR. Primary seagrass forage of C. mydas was identified, and samples collected from foraging sites before and after the 2018/2019 wet season, and multivariate differences in metal profiles investigated between sites and sampling events. Most metals investigated were higher at one or more coastal sites, relative to data obtained from the offshore site, and cadmium (Cd), cobalt (Co), iron (Fe) and manganese (Mn) were found to be higher at all coastal sites. Principle Component Analysis (PCA) found that metal profiles in the coastal sites were similar, but all were distinctly different from that of the offshore data. Coastal foraging sites are influenced by land-based contaminants that can enter the coastal zone via river discharge during periods of heavy rainfall, and impact sites closest to sources. Bioavailability of metal elements are determined by complex interactions and processes that are largely unknown, but association between elevated metal loads and turtle disease warrants further investigation to better understand the impact of environmental contaminants on ecologically important seagrass and associated macrograzers.

Background: Family medical history may help prevent, diagnose and treat inherited non-communicable diseases. Many people are unaware of family medical history, and medical practitioners may not realise its value when dealing with hereditary diseases. The study aimed to determine the knowledge, attitudes and practices (KAPs) regarding family medical history of hereditary diseases amongst undergraduate students at the University of the Free State, Bloemfontein. Methods: A cross-sectional study using a KAP survey was conducted. Questionnaires were distributed electronically to students for voluntary and anonymous completion. Results: There were 651 respondents (response rate 3.1%). Most respondents had good knowledge about their family history of hereditary diseases. Significantly more Health Sciences students reported knowing their family medical history. The majority knew that knowledge of hereditary diseases could improve quality of life, that they had a greater chance of being diagnosed if a family member already had the disease, and that lifestyle changes could improve health. Health Sciences students’ level of knowledge was higher than that of students from other faculties. At least 95% of students indicated that they would change lifestyle habits to prevent early onset of hereditary disease, but their practices regarding good healthcare were poor. Health Sciences students’ practices were significantly better, but less than half of all students had made lifestyle changes or had done screenings based on their family medical history. Conclusion: Although undergraduate respondents had good knowledge of family medical history and positive attitudes about screening, they did not adapt their practises. Health Sciences students’ KAPs reflected the acquisition of core competencies. Institutions could educate students on the importance of early screenings.

Appropriate inspection protocols and mitigation strategies are a critical component of effective biosecurity measures, enabling implementation of sound management decisions. Statistical models to analyze biosecurity surveillance data are integral to this decision-making process. Our research focuses on analyzing border interception biosecurity data collected from a Class A Nature Reserve, Barrow Island, in Western Australia and the associated covariates describing both spatial and temporal interception patterns. A clustering analysis approach was adopted using a generalization of the popular k-means algorithm appropriate for mixed-type data. The analysis approach compared the efficiency of clustering using only the numerical data, then subsequently including covariates to the clustering. Based on numerical data only, three clusters gave an acceptable fit and provided information about the underlying data characteristics. Incorporation of covariates into the model suggested four distinct clusters dominated by physical location and type of detection. Clustering increases interpretability of complex models and is useful in data mining to highlight patterns to describe underlying processes in biosecurity and other research areas. Availability of more relevant data would greatly improve the model. Based on outcomes from our research we recommend broader use of cluster models in biosecurity data, with testing of these models on more datasets to validate the model choice and identify important explanatory variables.

Background: The intestinal ecosystem, including epithelium, immune cells, and microbiota, are influenced by diet and timing of food consumption. The purpose of this study was to evaluate various dietary protocols after ad libitum high fat diet (HFD) consumption on intestinal morphology and mucosal immunity. Methods: C57BL/6 male mice were fed a 45% high fat diet (HFD) for 6 weeks and then randomized to the following protocols; (1) chow, (2) a purified high fiber diet known as the Daniel Fast (DF), HFD consumed (3) ad libitum or in a restricted manner; (4) caloric-restricted, (5) time-restricted (six hours of fasting in each 24 h), or (6) alternate-day fasting (24 h fasting every other day). Intestinal morphology and gut-associated immune parameters were investigated after 2 months on respective protocols. Results: Consuming a HFD resulted in shortening of the intestine and reduction in villi and crypt size. Fasting, while consuming the HFD, did not restore these parameters to the extent seen with the chow and DF diet. Goblet cell number and regulatory T cells had improved recovery with high fiber diets, not seen with the HFD irrespective of fasting. Conclusion: Nutritional content is a critical determinant of intestinal parameters associated with gut health.

Shared decision making near end of life is a balancing act of communicating prognosis to patients and their surrogates/families and engaging them in considering value-concordant management choices. This cross-sectional survey aimed to determine the format in which older patients with chronic illnesses would prefer to receive prognostic information on their treatment options and disease progression, and their desired level of engagement in decision making. With a 60% participation rate, 139 inpatients in two hospitals and five surrogates were presented with six hypothetical scenarios with a randomly assigned sequence: verbal and written summary, graph, table, photo, video, and pamphlet. The majority (76%) of respondents chose the traditional verbal communication of prognosis by their doctor with a written summary as a reference and to share with family; the second choice was a condition-specific pamphlet (63%). Many found the graph and photo to be distressing (36% and 42%, respectively). Most (71%) wanted to know everything about their condition trajectory, and 63% chose shared decision making rather than completely autonomous or full delegation to clinicians or family. There were no gender differentials between wanting to know it all, supporting shared decision making or the preferred format for breaking news (p > 0.05). Older hospitalized patients with chronic conditions are willing to discuss end-of-life issues, learn about their prognosis, and be involved in shared decision making. Innovative formats such as graphs, videos, or photos were not welcome as part of the prognostic discussion.

Adaptations of the lower back to bipedalism are frequently discussed but infrequently demonstrated in early fossil hominins. Newly discovered lumbar vertebrae contribute to a near-complete lower back of Malapa Hominin 2 (MH2), offering additional insights into posture and locomotion in Australopithecus sediba. We show that MH2 possessed a lower back consistent with lumbar lordosis and other adaptations to bipedalism, including an increase in the width of intervertebral articular facets from the upper to lower lumbar column (‘pyramidal configuration’). These results contrast with some recent work on lordosis in fossil hominins, where MH2 was argued to demonstrate no appreciable lordosis (‘hypolordosis’) similar to Neandertals. Our three-dimensional geometric morphometric (3D GM) analyses show that MH2’s nearly complete middle lumbar vertebra is human-like in overall shape but its vertebral body is somewhat intermediate in shape between modern humans and great apes. Additionally, it bears long, cranially and ventrally oriented costal (transverse) processes, implying powerful trunk musculature. We interpret this combination of features to indicate that A. sediba used its lower back in both bipedal and arboreal positional behaviors, as previously suggested based on multiple lines of evidence from other parts of the skeleton and reconstructed paleobiology of A. sediba.

The interaction between the SARS-CoV-2 virus Spike protein receptor binding domain (RBD) and the ACE2 cell surface protein is required for viral infection of cells. Mutations in the RBD are present in SARS-CoV-2 variants of concern that have emerged independently worldwide. For example, the B.1.1.7 lineage has a mutation (N501Y) in its Spike RBD that enhances binding to ACE2. There are also ACE2 alleles in humans with mutations in the RBD binding site. Here we perform a detailed affinity and kinetics analysis of the effect of five common RBD mutations (K417N, K417T, N501Y, E484K, and S477N) and two common ACE2 mutations (S19P and K26R) on the RBD/ACE2 interaction. We analysed the effects of individual RBD mutations and combinations found in new SARS-CoV-2 Alpha (B.1.1.7), Beta (B.1.351), and Gamma (P1) variants. Most of these mutations increased the affinity of the RBD/ACE2 interaction. The exceptions were mutations K417N/T, which decreased the affinity. Taken together with other studies, our results suggest that the N501Y and S477N mutations enhance transmission primarily by enhancing binding, the K417N/T mutations facilitate immune escape, and the E484K mutation enhances binding and immune escape.

BackgroundThe current COVID-19 pandemic is affecting all aspects of society worldwide. To combat the pandemic, measures such as face mask–wearing, hand-washing and -sanitizing, movement restrictions, and social distancing have been introduced. These measures have significantly disrupted education, particularly health professions education, which depends on student-patient contact for the development of clinical competence. The wide-ranging consequences of the pandemic are immense, and health professions education institutions in sub-Saharan Africa have not been spared. ObjectiveThis paper describes a protocol for assessing the preparedness of selected health professions education institutions in sub-Saharan Africa for remote teaching and learning during the COVID-19 pandemic. MethodsA mixed-methods design with a case study approach will be used. The awareness, desire, knowledge, ability, and reinforcement model of change was selected as the conceptual framework to guide the study. Eight higher education institutions in 6 sub-Saharan countries have participated in this study. Data will be collected through electronic surveys from among whole populations of academic staff, students, and administrators in undergraduate medicine and nursing programs. Qualitative and quantitative data from each institution will be analyzed as a case study, which will yield an inventory of similar cases grouped for comparison. Quantitative data will be analyzed for each institution and then compared to determine associations among variables and differences among programs, institutions, or countries. ResultsOur findings will provide information to higher education institutions, particularly those offering health professions education programs, in Africa regarding the preparedness for remote teaching and learning to influence efforts related to web-based teaching and learning, which is envisaged to become the new normal in the future. ConclusionsThis study has not received any funding, and any costs involved were borne by individual consortium members at the various institutions. Ethics approval from the institutional review board was obtained at various times across the participating sites, which were free to commence data collection as soon as approval was obtained. Data collection was scheduled to begin on October 1, 2020, and end on February 28, 2021. As of this submission, data collection has been completed, and a total of 1099 participants have been enrolled. Data analysis has not yet commenced. International Registered Report Identifier (IRRID)DERR1-10.2196/28905

T cells use their T cell receptors (TCRs) to discriminate between lower-affinity self and higher-affinity non-self peptides presented on major histocompatibility complex (pMHC) antigens. Although the discriminatory power of the TCR is widely believed to be near-perfect, technical difficulties have hampered efforts to precisely quantify it. Here, we describe a method for measuring very low TCR/pMHC affinities and use it to measure the discriminatory power of the TCR and the factors affecting it. We find that TCR discrimination, although enhanced compared with conventional cell-surface receptors, is imperfect: primary human T cells can respond to pMHC with affinities as low as KD ∼ 1 mM. The kinetic proofreading mechanism fit our data, providing the first estimates of both the time delay (2.8 s) and number of biochemical steps (2.67) that are consistent with the extraordinary sensitivity of antigen recognition. Our findings explain why self pMHC frequently induce autoimmune diseases and anti-tumour responses, and suggest ways to modify TCR discrimination.

BackgroundPreterm birth (PTB) and particularly late preterm PTB has become a research focus for obstetricians, perinatologists, neonatologists, pediatricians and policy makers alike. Translational models are useful tools to expedite and guide clinical but presently no model exists that contextualizes the late PTB scenario. Herein we aimed to develop a rabbit model that echo's the clinical neurocognitive phenotypes of early and late PTB.MethodsTime mated rabbit does underwent caesarean delivery at a postconceptional age (PCA) of either 28 (n = 6), 29 (n = 5), 30 (n = 4) or 31 (n = 4) days, term = 31 d. Newborn rabbits were mixed and randomly allocated to be raised by cross fostering and underwent short term neurobehavioral testing on corrected post-natal day 1. Open field (OFT), spontaneous alteration (TMT) and novel object recognition (NORT) tests were subsequently performed at 4 and 8 weeks of age.ResultsPTB was associated with a significant gradient of short-term mortality and morbidity inversely related to the PCA. On postnatal day 1 PTB was associated with a significant sensory deficit in all groups but a clear motor insult was only noted in the PCA 29d and PCA 28d groups. Furthermore, PCA 29d and PCA 28d rabbits had a persistent neurobehavioral deficit with less exploration and hyperanxious state in the OFT, less alternation in TMT and lower discriminatory index in the NORT. While PCA 30d rabbits had some anxiety behavior and lower spontaneous alteration at 4 weeks, however at 8 weeks only mild anxiety driven behavior was observed in some of these rabbits.ConclusionsIn this rabbit model, delivery at PCA 29d and PCA 28d mimics the clinical phenotype of early PTB while delivery at PCA 30d resembles that of late PTB. This could serve as a model to investigate perinatal insults during the early and late preterm period.

BackgroundNeuregulin 4 (Nrg4), a novel adipokine enriched in brown adipose tissue has been observed to negatively regulate de novo hepatic lipogenesis and limit nonalcoholic fatty liver disease (NAFLD) progression to nonalcoholic steatohepatitis (NASH) in rodents. However, the role of Nrg4 in human NAFLD remains unclear to date. We analysed Nrg4 plasma levels and its association with liver disease severity together with the transcriptional profile of the Nrg4 pathway in liver and visceral adipose tissue (VAT) of NAFLD patients.MethodsPlasma Nrg4 levels were measured in 65 NAFLD patients and 43 healthy controls (HC). Hepatic steatosis and fibrosis were diagnosed and quantified with chemical shift MRI and transient elastography respectively. Furthermore, blood lipid levels, HOMA-IR and systemic pro-inflammatory cytokines (TNF-α, IL-6 and IFN-γ) were analysed. Microarray analyses to assess differences in the Nrg4 and its receptor family ErbB pathway in liver and VAT from an independent patient group with biopsy proven NAFL (simple steatosis) (n = 4), NASH (n = 5) and normal liver (n = 6) were performed.ResultsPlasma Nrg4 levels were not significantly different between NAFLD patients and HC (p = 0.622). Furthermore, plasma Nrg4 levels did not correlate with the hepatic fat fraction (r = -0.028, p = 0.829) and were not significantly different between NAFLD patients with or without hepatic fibrosis (p = 0.087). Finally, the expression profile of 82 genes related to the Nrg4-ErbB pathway in liver and VAT was not significantly different between NAFL, NASH or obese controls.ConclusionOur study does not support a role for Nrg4 in the pathophysiology of human NAFLD.

IntroductionIn June 2021, United Nations (UN) Member States committed to ambitious targets for scaling up community-led responses by 2025 toward meeting the goals of ending the AIDS epidemic by 2030. These targets build on UN Member States 2016 commitments to ensure that 30% of HIV testing and treatment programmes are community-led by 2030. At its current pace, the world is not likely to meet these nor other global HIV targets, as evidenced by current epidemiologic trends. The COVID-19 pandemic threatens to further slow momentum made to date. The purpose of this paper is to review available evidence on the comparative advantages of community-led HIV responses that can better inform policy making towards getting the world back on track.MethodsWe conducted a scoping review to gather available evidence on peer- and community-led HIV responses. Using UNAIDS' definition of 'community-led' and following PRISMA guidelines, we searched peer-reviewed literature published from January 1982 through September 2020. We limited our search to articles reporting findings from randomized controlled trials as well as from quasi-experimental, prospective, pre/post-test evaluation, and cross-sectional study designs. The overall goals of this scoping review were to gather available evidence on community-led responses and their impact on HIV outcomes, and to identify key concepts that can be used to quickly inform policy, practice, and research.FindingsOur initial search yielded 279 records. After screening for relevance and conducting cross-validation, 48 articles were selected. Most studies took place in the global south (n = 27) and a third (n = 17) involved youth. Sixty-five percent of articles (n = 31) described the comparative advantage of peer- and community-led direct services, e.g., prevention and education (n = 23) testing, care, and treatment programs (n = 8). We identified more than 40 beneficial outcomes linked to a range of peer- and community-led HIV activities. They include improved HIV-related knowledge, attitudes, intentions, self-efficacy, risk behaviours, risk appraisals, health literacy, adherence, and viral suppression. Ten studies reported improvements in HIV service access, quality, linkage, utilization, and retention resulting from peer- or community-led programs or initiatives. Three studies reported structural level changes, including positive influences on clinic wait times, treatment stockouts, service coverage, and exclusionary practices.Conclusions and recommendationsFindings from our scoping review underscore the comparative advantage of peer- and community-led HIV responses. Specifically, the evidence from the published literature leads us to recommend, where possible, that prevention programs, especially those intended for people living with and disproportionately affected by HIV, be peer- and community-led. In addition, treatment services should strive to integrate specific peer- and community-led components informed by differentiated care models. Future research is needed and should focus on generating additional quantitative evidence on cost effectiveness and on the synergistic effects of bundling two or more peer- and community-led interventions.