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Abstract Background Global re-emergence of the zoonotic viral disease, Mpox (Monkeypox) has drawn global attention, leading to its declaration as a Public Health Emergency of International Concern (PHEIC) by World Health Organisation (WHO) in July 2022. Nigeria is a spotlight identified for the viral disease outbreak, with attention drawn on its transmission to non-endemic nations. With the country’s healthcare challenges, care seeking practices particularly amongst low-income urban informal settlement populations are diverse – presenting challenges to both case identification and management during an outbreak. In this study, we examine the social, economic, and behavioural context of Mpox therapeutics. Methods This was an ethnographic study conducted between September 2022 and March 2023, with the purposive selection of urban informal settlements and interlocutors in Oyo, Ogun and Lagos States. We interviewed a total of 28 interlocutors who were either confirmed or suspected cases of Mpox or parents of children who are confirmed or suspected Mpox cases identified by the public health workers. Data were elicited through In-depth interviews and observations technique on the interlocutor’s local knowledge and their lived experiences on the therapeutics of Mpox. Analysis of the transcript was done inductively using thematic analysis process. Findings The study revealed awareness and vague knowledge of Mpox. Furthermore, the behavioural practices on how ailments are understood and managed revealed a commonality in their social actions in terms of local diagnosis and management. Mpox was perceived to be a mild disease, and this had implications on the local characteristics of the PHEIC in the endemic regions. Conclusion Our paper contributes to a more nuanced understanding of not only the health care access barriers, but the complex geographical, economic, and sociocultural factors that shape how and when people seek care for Mpox within the context of urban informal settlements. This further draws attention to behavioral dispositions to the nomenclature of what is perceived as PHEIC. Thus, the global health and security paradigm should give room to local context, expertise, and global politics in shaping epidemic responses.

The population structure and evolution of basidiomycetes like rust fungi are influenced by complex reproductive cycles and dikaryotic life stages where two independent nuclear haplotypes are present in the cell. The ability to alternate between asexual (clonal) and sexual reproduction increases the evolutionary capacity in these species. Furthermore, exchange of intact nuclei (somatic hybridization) in rust fungi can allow for rapid generation of genetic variability outside of the sexual cycle. Puccinia coronata f. sp. avenae (Pca), the causal agent of oat crown rust, is a pathogen of global economic importance that is difficult to control due to rapid breakdown of host genetic resistance. The contribution of sexuality, clonality, and migration to virulence evolution varies across Pca populations. As such, the Pca pathosystem is ideal to address the role of mating type, recombination, mutation, and somatic hybridization in host adaptation. We expanded the existing resources for USA and South African populations by generating whole genome sequencing data of Taiwanese and Australian isolates. An atlas of 30 chromosome-level, fully-phased nuclear haplotypes from six USA isolates and nine Australian isolates was created to capture the genomic composition of key Pca lineages. At the haplotype level, we confirmed previous reports of genetic recombination in the USA population and additionally detected either sexual or cryptic recombination between Australian isolates, contrasting previous evaluations that suggested Pca populations in Australia to be purely clonal. We also identified somatic hybridization events in Pca that are not only associated with significant changes in fitness but also imply intercontinental migration of haplotypes, which provides further impetus for molecular monitoring of rust pathogen populations on a global scale.

Abstract Ratios of glycerol dialkyl glycerol tetraethers (GDGT), which are membrane lipids of bacteria and archaea, are at the base of several paleoenvironmental proxies. They are frequently applied to soils as well as lake‐ and marine sediments to generate records of past temperature and soil pH. To derive meaningful environmental information from these reconstructions, high analytical reproducibility is required. Based on submitted results by 39 laboratories from across the world, which employ a diverse range of analytical and quantification methods, we explored the reproducibility of brGDGT‐based proxies (MBT′5ME, IR, and #ringstetra) measured on four soil samples and four soil lipid extracts. Correct identification and integration of 5‐ and 6‐methyl brGDGTs is a prerequisite for the robust calculation of proxy values, but this can be challenging as indicated by the large inter‐interlaboratory variation. The exclusion of statistical outliers improves the reproducibility, where the remaining uncertainty translates into a temperature offset from median proxy values of 0.3–0.9°C and a pH offset of 0.05–0.3. There is no apparent systematic impact of the extraction method and sample preparation steps on the brGDGT ratios. Although reported GDGT concentrations are generally consistent within laboratories, they vary greatly between laboratories. This large variability in brGDGT quantification may relate to variations in ionization efficiency or specific mass spectrometer settings possibly impacting the response of brGDGTs masses relative to that of the internal standard used. While ratio values of GDGT are generally comparable, quantities can currently not be compared between laboratories.

Abstract Objective Define current practices and protocols in surgical training programs for pregnant trainees. Study Design Cross sectional. Setting Academic surgical training programs in the United States. Methods A validated 20‐question survey was sent via email to program directors and coordinators of US surgical training programs, including otolaryngology head & neck surgery (OHNS), plastic surgery, vascular surgery, and general surgery. The survey was issued in November and December 2022 and data were collected until January 2023. This study was approved for exemption by the Minimal Risk Research IRB at the University of Wisconsin Madison (ID number 2022‐1370). Results Surveys were emailed to 608 surgical programs, and the response rate was 23.5% (143/608) including 45 OHNS programs. When asked if their program has a policy in place for pregnant trainees, 84.4% responded yes, and 82.4% responded that they were satisfied with their policy. Subsequent questions addressed individual policies and risk factors facing pregnant trainees. 60.3% of programs report providing protected time off for miscarriages. Only 36.9% provide information to pregnant trainees regarding workplace exposures that pose a risk of fetal anomaly or miscarriage. Only 47.1% incorporate rest breaks for pregnant trainees, and only 20% protect the number of hours a pregnant trainee operates per week. 24.2% adjust overnight shifts or call schedules for pregnant trainees, and of those that adjust call shifts, 20% require pregnant trainees to “make up” these missed call shifts. Less than half (40%) of programs have a contingency plan in place for supporting nonchild‐bearing residents who may take on the work of their colleagues during pregnancy or postpartum. Conclusion While a majority of training programs report a pregnancy policy in place for trainees, most of these policies appear to be severely deficient in addressing critical aspects of surgical training that place both fetus and mother at significant risk of complications. This data indicates a need for a safe pregnancy protocol in order to protect both surgeon and fetus.

Abstract This study reports that most patients with NSCLC had a significant increase in the nAb response to the currently circulating Omicron variants after bivalent booster vaccination and had Ab titers comparable to healthy participants. Interestingly, though the durability of the nAb response persisted in most of the healthy participants, patients with NSCLC had significantly reduced nAb titers after 4–6 months of vaccination. Our data highlight the importance of COVID-19 bivalent booster vaccination as the standard of care for patients with NSCLC given the evolution of new variants of concern.

Objectives Determine community needs and perspectives as part of planning health service incorporation into Wanang Conservation Area, in support of locally driven sustainable development.Design Clinical and rapid anthropological assessment (individual primary care assessments, key informant (KI) interviews, focus groups (FGs), ethnography) with treatment of urgent cases.Setting Wanang (pop. c189), a rainforest community in Madang province, Papua New Guinea.Participants 129 villagers provided medical histories (54 females (f), 75 males (m); median 19 years, range 1 month to 73 years), 113 had clinical assessments (51f, 62m; median 18 years, range 1 month to 73 years). 26 ≥18 years participated in sex-stratified and age-stratified FGs (f40 years; m>40 years). Five KIs were interviewed (1f, 4m). Daily ethnographic fieldnotes were recorded.Results Of 113 examined, 11 were ‘well’ (a clinical impression based on declarations of no current illness, medical histories, conversation, no observed disease signs), 62 (30f, 32m) were treated urgently, 31 referred (15f, 16m), indicating considerable unmet need. FGs top-4 ranked health issues concorded with KI views, medical histories and clinical examinations. For example, ethnoclassifications of three ((A) ‘malaria’, (B) ‘sotwin’, (C) ‘grile’) translated to the five biomedical conditions diagnosed most ((A) malaria, 9 villagers; (B) upper respiratory infection, 25; lower respiratory infection, 10; tuberculosis, 9; (C) tinea imbricata, 15) and were highly represented in declared medical histories ((A) 75 participants, (B) 23, (C) 35). However, 29.2% of diagnoses (49/168) were limited to one or two people. Treatment approaches included plant medicines, stored pharmaceuticals, occasionally rituals. Travel to hospital/pharmacy was sometimes undertaken for severe/refractory disease. Service barriers included: no health patrols/accessible aid post, remote hospital, unfamiliarity with institutions and medicine costs. Service introduction priorities were: aid post, vaccinations, transport, perinatal/birth care and family planning.Conclusions This study enabled service planning and demonstrated a need sufficient to acquire funding to establish primary care. In doing so, it aided Wanang’s community to develop sustainably, without sacrificing their forest home.

Summary: The contents of the platelet releasate (PR) play significant roles in hemostasis, inflammation, and pathologic sequelae. Careful platelet isolation to ensure quiescence and subsequent activation is key to the successful generation of PR. Here, we describe steps to isolate and aggregate quiescent washed platelets from whole blood of a clinical patient cohort. We then detail the generation of PR from isolated human washed platelets under clinical conditions. This protocol allows the investigation of platelet cargoes released through various activation pathways. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

In clinical settings where airborne pathogens, such as Mycobacterium tuberculosis, are prevalent, they constitute an important threat to health workers and people accessing healthcare. We report key insights from a 3-year project conducted in primary healthcare clinics in South Africa, alongside other recent tuberculosis infection prevention and control (TB-IPC) research. We discuss the fragmentation of TB-IPC policies and budgets; the characteristics of individuals attending clinics with prevalent pulmonary tuberculosis; clinic congestion and patient flow; clinic design and natural ventilation; and the facility-level determinants of the implementation (or not) of TB-IPC interventions. We present modeling studies that describe the contribution of M. tuberculosis transmission in clinics to the community tuberculosis burden and economic evaluations showing that TB-IPC interventions are highly cost-effective. We argue for a set of changes to TB-IPC, including better coordination of policymaking, clinic decongestion, changes to clinic design and building regulations, and budgeting for enablers to sustain implementation of TB-IPC interventions. Additional research is needed to find the most effective means of improving the implementation of TB-IPC interventions; to develop approaches to screening for prevalent pulmonary tuberculosis that do not rely on symptoms; and to identify groups of patients that can be seen in clinic less frequently.

Children with intellectual disability (ID) have a higher risk of long-term health problems in adulthood. India has the highest prevalence of ID of any country with 1.6 million under-five children living with the condition. Despite this, compared with other children, this neglected population is excluded from mainstream disease prevention and health promotion programmes. Our objective was to develop an evidence-based conceptual framework for a needs-based inclusive intervention to reduce the risk of communicable and non-communicable diseases among children with ID in India. From April through to July 2020 we undertook community engagement and involvement activities in ten States in India using a community-based participatory approach, guided by the bio-psycho-social model. We adapted the five steps recommended for the design and evaluation of a public participation process for the health sector. Seventy stakeholders from ten States contributed to the project: 44 parents and 26 professionals who work with people with ID. We mapped the outputs from two rounds of stakeholder consultations with evidence from systematic reviews to develop a conceptual framework that underpins an approach to develop a cross-sectoral family-centred needs-based inclusive intervention to improve health outcomes for children with ID. A working Theory of Change model delineates a pathway that reflected the priorities of the target population. We discussed the models during a third round of consultations to identify limitations, relevance of the concepts, structural and social barriers that could influence acceptability and adherence, success criteria, and integration with existing health system and service delivery. There are currently no health promotion programmes focusing on children with ID in India despite the population being at a higher risk of developing comorbid health problems. Therefore, an urgent next step is to test the conceptual model to determine acceptance and effectiveness within the context of socio-economic challenges faced by the children and their families in the country.

Abstract Background As COVID-19 death rates have risen and health-care systems have experienced increased demand, national testing strategies have come under scrutiny. Utilising qualitative interview data from a larger COVID-19 study, this paper provides insights into influences on and the enactment of national COVID-19 testing strategies for health care workers (HCWs) in English NHS settings during wave one of the COVID-19 pandemic (March–August 2020). Through the findings we aim to inform learning about COVID-19 testing policies and practices; and to inform future pandemic diagnostic preparedness. Methods A remote qualitative, semi-structured longitudinal interview method was employed with a purposive snowball sample of senior scientific advisors to the UK Government on COVID-19, and HCWs employed in NHS primary and secondary health care settings in England. Twenty-four interviews from 13 participants were selected from the larger project dataset using a key term search, as not all of the transcripts contained references to testing. Framework analysis was informed by the non-adoption, abandonment, scale-up, spread, and sustainability of patient-facing health and care technologies implementation framework (NASSS) and by normalisation process theory (NPT). Results Our account highlights tensions between the communication and implementation of national testing developments; scientific advisor and HCW perceptions about infectiousness; and uncertainties about the responsibility for testing and its implications at the local level. Conclusions Consideration must be given to the implications of mass NHS staff testing, including the accuracy of information communicated to HCWs; how HCWs interpret, manage, and act on testing guidance; and the influence these have on health care organisations and services.

Abstract Background Research around the weedkiller Roundup is among the most contentious of the twenty-first century. Scientists have provided inconclusive evidence that the weedkiller causes cancer and other life-threatening diseases, while industry-paid research reports that the weedkiller has no adverse effect on humans or animals. Much of the controversial evidence on Roundup is rooted in the approach used to determine safe use of chemicals, defined by outdated toxicity tests. We apply a system biology approach to the biomedical and ecological model species Daphnia to quantify the impact of glyphosate and of its commercial formula, Roundup, on fitness, genome-wide transcription and gut microbiota, taking full advantage of clonal reproduction in Daphnia. We then apply machine learning-based statistical analysis to identify and prioritize correlations between genome-wide transcriptional and microbiota changes. Results We demonstrate that chronic exposure to ecologically relevant concentrations of glyphosate and Roundup at the approved regulatory threshold for drinking water in the US induce embryonic developmental failure, induce significant DNA damage (genotoxicity), and interfere with signaling. Furthermore, chronic exposure to the weedkiller alters the gut microbiota functionality and composition interfering with carbon and fat metabolism, as well as homeostasis. Using the “Reactome,” we identify conserved pathways across the Tree of Life, which are potential targets for Roundup in other species, including liver metabolism, inflammation pathways, and collagen degradation, responsible for the repair of wounds and tissue remodeling. Conclusions Our results show that chronic exposure to concentrations of Roundup and glyphosate at the approved regulatory threshold for drinking water causes embryonic development failure and alteration of key metabolic functions via direct effect on the host molecular processes and indirect effect on the gut microbiota. The ecological model species Daphnia occupies a central position in the food web of aquatic ecosystems, being the preferred food of small vertebrates and invertebrates as well as a grazer of algae and bacteria. The impact of the weedkiller on this keystone species has cascading effects on aquatic food webs, affecting their ability to deliver critical ecosystem services. Video Abstract

Abstract Objective: There is currently much debate about which patients would benefit more after on- or off-pump coronary artery bypass grafting (CABG). The aim of this meta-analysis and meta-regression is to investigate the effect of age on short-term clinical outcomes after these approaches. Methods: To identify potential studies, systematic searches were carried out in the Excerpta Medica dataBASE (EMBASE), PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL). The search strategy included the key concepts of “cardiopulmonary bypass” AND “coronary artery bypass grafting” AND “off pump” OR “on pump”. This was followed by a meta-analysis and meta-regression investigating the effect of age on the incidences of stroke, myocardial infarction (MI), and mortality. Results: Thirty-seven studies including 15,324 participants were analysed. Overall, there was a significant odds reduction for patients receiving off-pump CABG suffering a stroke (odds ratio [OR] 0.770, 95% confidence intervals [CI] 0.594, 0.998, P=0.048); however, when patients were subdivided according to different age bands, this difference disappeared. There were also no significant differences in the odds of mortality (OR 0.876, 95% CI 0.703, 1.093, P=0.241) or MI (OR 0.937, 95% CI 0.795, 1.105, P=0.439). Meta-regression analysis revealed no significant relationship between age and stroke (P=0.652), age and mortality (P=548), and age and MI (P=0.464). Conclusion: Patients undergoing CABG are becoming older and may suffer from multiple comorbidities increasing their risk profile. However, with respect to short-term clinical outcomes, the patient’s age does not help in determining whether off- or on-pump is superior.

Abstract Background It is well established that mothers with above-normal pre-pregnancy BMI are at increased risk of breastfeeding cessation; however, the impact of pregnancy weight-gain (PWG) is less well-defined. Excess PWG may alter the hormonal preparation of breast tissue for lactation, increase the risk of complications that negatively impact breastfeeding (e.g. Cesarean-section, gestational diabetes), and may make effective latch more difficult to achieve. Methods Our objective was to determine the impact of PWG and pre-pregnancy BMI on the risk of breastfeeding cessation utilizing the Institute of Medicine’s 2009 recommendations. Cox proportional hazards models were utilized to estimate the risk of cessation of exclusive breastfeeding, and cessation of any breastfeeding among women who initiated exclusive and any breastfeeding, respectively, in a cross sectional sample of survey respondents from a New York county (N = 1207). PWG category was interacted with pre-pregnancy BMI (3 levels of pre-pregnancy BMI, 3 levels of PWG). Confounders of the relationship of interest were evaluated using directed acyclic graphs and bivariate analyses; variables not on the proposed causal pathway and associated with the exposure and outcome were included in multivariate models. Results: After adjustment, women of normal and obese pre-pregnancy BMI with greater-than-recommended PWG had 1.39 (1.03–1.86) and 1.48 (1.06–2.07) times the risk of any breastfeeding cessation within the first 3 months postpartum compared to women with normal pre-pregnancy BMI who gained within PWG recommendations. Overweight women with greater-than-recommended PWG were at increased risk of cessation, although not significantly (aHR [95% CI]: 1.29 [0.95–1.75]). No significant relationship was observed for exclusive breastfeeding cessation. Conclusions Pre-pregnancy BMI and PWG may be modifiable risk factors for early breastfeeding cessation. Understanding the mechanism behind this risk should be ascertained by additional studies aimed at understanding the physiological, social, logistical (positioning) and other issues that may lead to early breastfeeding cessation.

Abstract Infection prevention and control (IPC) measures to reduce transmission of drug-resistant and drug-sensitive tuberculosis (TB) in health facilities are well described but poorly implemented. The implementation of TB IPC has been assessed primarily through quantitative and structured approaches that treat administrative, environmental, and personal protective measures as discrete entities. We present an on-going project entitled Umoya omuhle (“good air”), conducted in two provinces of South Africa, that adopts an interdisciplinary, ‘whole systems’ approach to problem analysis and intervention development for reducing nosocomial transmission of Mycobacterium tuberculosis (Mtb) through improved IPC. We suggest that TB IPC represents a complex intervention that is delivered within a dynamic context shaped by policy guidelines, health facility space, infrastructure, organisation of care, and management culture. Methods drawn from epidemiology, anthropology, and health policy and systems research enable rich contextual analysis of how nosocomial Mtb transmission occurs, as well as opportunities to address the problem holistically. A ‘whole systems’ approach can identify leverage points within the health facility infrastructure and organisation of care that can inform the design of interventions to reduce the risk of nosocomial Mtb transmission.

One of the most remarkable features of human societies is our ability to cooperate with each other. However, the benefits of cooperation are not extended to everyone. Indeed, another hallmark of human societies is a division between us and them. Favoritism toward members of our group can result in a loss of empathy and greater tolerance of harm toward those outside our group. The current study sought to investigate how in-group bias impacts the developmental emergence of concerns for fairness and care. We investigated the impact of in-group bias on decisions related to care and fairness in children (N = 95; ages 4–9). Participants made decisions about how to allocate resources between themselves and a peer who was either an in-group or out-group member. In decisions related to care, participants were given two trial types on which they could decide whether to give or throw away a positive or negative resource. In decisions related to fairness participants and peer partners each received one candy and participants decided whether to allocate or throw away an extra candy. If the extra candy was distributed it would place either the participant or their recipient at a relative advantage, whereas if the extra candy was thrown away the distribution would be equal. We found that on fairness trials children’s tendency to allocate resources was similar toward in-group and out-group recipients. Furthermore, children’s tendency to allocate resources changed with age such that younger participants were more likely to allocate extra candies to themselves, whereas older participants were more likely to allocate extra candies to their recipient. On trials related to care we did observe evidence of in-group bias. While distribution of positive resources was greater than negative resources for both in-group and out-group recipients, participants distributed negative resources to out-group recipients more often compared to in-group recipients, a tendency that was heightened for young boys. This pattern of results suggests that fairness and care develop along distinct pathways with independent motivational supports.

Objective To identify the experiences and concerns of health workers (HWs), and how they changed, throughout the first year of the COVID-19 pandemic in the UK. Methods Longitudinal, qualitative study with HWs involved in patient management or delivery of care related to COVID-19 in general practice, emergency departments and hospitals. Participants were identified through snowballing. Semi-structured telephone or video interviews were conducted between February 2020 and February 2021, audio-recorded, summarised, and transcribed. Data were analysed longitudinally using framework and thematic analysis. Results We conducted 105 interviews with 14 participants and identified three phases corresponding with shifts in HWs’ experiences and concerns. (1) Emergency and mobilisation phase (late winter-spring 2020), with significant rapid shifts in responsibilities, required skills, and training, and challenges in patient care. (2) Consolidation and preparation phase (summer-autumn 2020), involving gradual return to usual care and responsibilities, sense of professional development and improvement in care, and focus on learning and preparing for future. (3) Exhaustion and survival phase (autumn 2020-winter 2021), entailing return of changes in responsibilities, focus on balancing COVID-19 and non-COVID care (until becoming overwhelmed with COVID-19 cases), and concerns about longer-term impacts of unceasing pressure on health services. Participants’ perceptions of COVID-19 risk and patient/public attitudes changed throughout the year, and tiredness and weariness turned into exhaustion. Conclusions Results showed a long-term impact of the COVID-19 pandemic on UK HWs’ experiences and concerns related to changes in their roles, provision of care, and personal wellbeing. Despite mobilisation in the emergency phase, and trying to learn from this, HWs’ experiences seemed to be similar or worse in the second wave partly due to many COVID-19 cases. The findings highlight the importance of supporting HWs and strengthening system-level resilience (e.g., with resources, processes) to enable them to respond to current and future demands and emergencies.

Sub-optimal implementation of infection prevention and control (IPC) measures for airborne infections is associated with a rise in healthcare-acquired infections. Research examining contributing factors has tended to focus on poor infrastructure or lack of health care worker compliance with recommended guidelines, with limited consideration of the working environments within which IPC measures are implemented. Our analysis of compromised tuberculosis (TB)-related IPC in South Africa used clinic ethnography to elucidate the enabling environment for TB-IPC strategies. Using an ethnographic approach, we conducted observations, semi-structured interviews, and informal conversations with healthcare staff in six primary health clinics in KwaZulu-Natal, South Africa between November 2018 and April 2019. Qualitative data and fieldnotes were analysed deductively following a framework that examined the intersections between health systems ‘hardware’ and ‘software’ issues affecting the implementation of TB-IPC. Clinic managers and front-line staff negotiate and adapt TB-IPC practices within infrastructural, resource and organisational constraints. Staff were ambivalent about the usefulness of managerial oversight measures including IPC protocols, IPC committees and IPC champions. Challenges in implementing administrative measures including triaging and screening were related to the inefficient organisation of patient flow and information, as well as inconsistent policy directives. Integration of environmental controls was hindered by limitations in the material infrastructure and behavioural norms. Personal protective measures, though available, were not consistently applied due to limited perceived risk and the lack of a collective ethos around health worker and patient safety. In one clinic, positive organisational culture enhanced staff morale and adherence to IPC measures. ‘Hardware’ and ‘software’ constraints interact to impact negatively on the capacity of primary care staff to implement TB-IPC measures. Clinic ethnography allowed for multiple entry points to the ‘problematic’ of compromised TB-IPC, highlighting the importance of capturing dimensions of the ‘enabling environment’, currently not assessed in binary checklists.

Transmission of respiratory pathogens, such as Mycobacterium tuberculosis and severe acute respiratory syndrome coronavirus 2, is more likely during close, prolonged contact and when sharing a poorly ventilated space. Reducing overcrowding of health facilities is a recognised infection prevention and control (IPC) strategy; reliable estimates of waiting times and ‘patient flow’ would help guide implementation. As part of the Umoya omuhle study, we aimed to estimate clinic visit duration, time spent indoors versus outdoors, and occupancy density of waiting rooms in clinics in KwaZulu-Natal (KZN) and Western Cape (WC), South Africa. We used unique barcodes to track attendees’ movements in 11 clinics, multiple imputation to estimate missing arrival and departure times, and mixed-effects linear regression to examine associations with visit duration. 2,903 attendees were included. Median visit duration was 2 hours 36 minutes (interquartile range [IQR] 01:36–3:43). Longer mean visit times were associated with being female (13.5 minutes longer than males; p

Objective: We characterized the relationship between circulating C-reactive protein (CRP) levels and nine anthropometric measures of body fat to identify the best anthropometric predictors of CRP in Ni-Vanuatu women. Sample and Methods: Anthropometric data and blood spot samples were collected from sixty-four Ni-Vanuatu female participants (age 35-78 years) on five islands with varying degrees of market integration, cultural change, and obesity. CRP concentration was determined with a high-sensitivity ELISA (hsCRP) assay and then compared to nine different anthropometric measurements. Results: BMI was significantly correlated with CRP (p=0.047). Among the eight additional anthropometrics, the suprailiac skinfold (p=0.003) and waist-circumference (p=0.009) were better predictors of CRP than BMI. Moreover, our stepwise selection model indicated that the suprailiac skinfold explained ~14% of CRP level variance. Conclusions: The BMI-CRP correlation coefficient for Ni-Vanuatu women falls within the range of previously reported values for East Asian populations with whom they share genetic ancestry. However, the best anthropometric predictors of CRP levels were waist circumference and suprailiac skinfold thickness. These measures capture central adiposity and are more closely associated with elevated CRP level and cardiovascular disease risk than fat distributed elsewhere on the body. Ni-Vanuatu in urban settings with high market integration are at greater risk for obesity, which is associated with elevated CRP levels. However, because nearly all Ni-Vanuatu still retain horticultural knowledge and land ownership, consumption of processed, imported foods is largely determined by degree of market integration and personal choice. Therefore, health interventions focusing on sustainable traditional food practices are feasible.

Abstract Objectives In order to characterize a river-associated, enriched microbiome capable of degrading an anthraquinone dye from the oil blue family, as well as assessing its functional potential, we performed a taxa-specific metagenomic deconvolution analysis based on contact probability maps at the chromosomal level. This study will allow associating the genomic content of “Candidatus Afipia apatlaquensis” strain IBT-C3 with its phenotypic potential in the context of bioremediation of textile dyes. We anticipate that this resource will be very useful in comparative genomic clinical studies, contributing to understanding the genomic basis of Afipia pathogenicity. Data description Here, we report the first draft genome sequence of “Candidatus Afipia apatlaquensis” sp. nov., strain IBT-C3, obtained by deconvolution of a textile-dye degrader microbiome in Mexico. The genome composite was deconvoluted using a Hi-C proximity ligation method. Whole-genome-based comparisons and phylogenomics reconstruction indicate that strain IBT-C3 represents a new species of the genus Afipia. The assembly completeness was 92.5% with 5,604,749 bp in length and 60.72% G+C content. The genome complement of IBT-C3 suggests a functional potential for decolorization of textile dyes, contrasting with previous reports of Afipia genus focused on its pathogenic potential.

Objective: Fibroblast growth factor 21 (FGF21) has been shown to rapidly lower body weight in the Siberian hamster, a preclinical model of adiposity. This induced negative energy balance mediated by FGF21 is associated with both lowered caloric intake and increased energy expenditure. Previous research demonstrated that adipose tissue (AT) is one of the primary sites of FGF21 action and may be responsible for its ability to increase the whole-body metabolic rate. The present study sought to determine the relative importance of white (subcutaneous AT [sWAT] and visceral AT [vWAT]), and brown (interscapular brown AT [iBAT]) in governing FGF21-mediated metabolic improvements using the tissue-specific uptake of glucose and lipids as a proxy for metabolic activity. Methods: We used positron emission tomography-computed tomography (PET-CT) imaging in combination with both glucose (18F-fluorodeoxyglucose) and lipid (18F-4-thiapalmitate) tracers to assess the effect of FGF21 on the tissue-specific uptake of these metabolites and compared responses to a control group pair-fed to match the food intake of the FGF21-treated group. In vivo imaging was combined with ex vivo tissue-specific functional, biochemical, and molecular analyses of the nutrient uptake and signaling pathways. Results: Consistent with previous findings, FGF21 reduced body weight via reduced caloric intake and increased energy expenditure in the Siberian hamster. PET-CT studies demonstrated that FGF21 increased the uptake of glucose in BAT and WAT independently of reduced food intake and body weight as demonstrated by imaging of the pair-fed group. Furthermore, FGF21 increased glucose uptake in the primary adipocytes, confirming that these in vivo effects may be due to a direct action of FGF21 at the level of the adipocytes. Mechanistically, the effects of FGF21 are associated with activation of the ERK signaling pathway and upregulation of GLUT4 protein content in all fat depots. In response to treatment with FGF21, we observed an increase in the markers of lipolysis and lipogenesis in both the subcutaneous and visceral WAT depots. In contrast, FGF21 was only able to directly increase the uptake of lipid into BAT. Conclusions: These data identify brown and white fat depots as primary peripheral sites of action of FGF21 in promoting glucose uptake and also indicate that FGF21 selectively stimulates lipid uptake in brown fat, which may fuel thermogenesis. Keywords: FGF21, β-klotho, White adipose tissue, Brown adipose tissue, Glucose uptake, Lipid uptake

Pilocytic astrocytoma is a low-grade pediatric glioma, characterized by a single BRAF rearrangement. Here, Reitman and colleagues use single-cell RNA sequencing to reveal molecular hallmarks of the disease that might be targeted therapeutically.

Controlling pharmaceutical prescription costs has been an interest in the United States for decades. In 2016, EpiPen experienced a 600% price increase. This exploratory framing study focuses on news coverage of EpiPen’s price increase and related pharmaceutical price increase stories through analyzing three U.S. television news programs’ coverage. Within 30 news segments that discussed EpiPen or medication price increases, analysis revealed four frames: economic, attribution of responsibility, morality and human interest, and conflict and powerlessness. This study provides a larger understanding of how the crisis of medication price increases is understood and implications for practitioners and individuals aiming to make medications more accessible.

Cross-species transmission of pathogens is intimately linked to human and environmental health. With limited healthcare and challenging living conditions, people living in poverty may be particularly susceptible to endemic and emerging diseases. Similarly, wildlife is impacted by human influences, including pathogen sharing, especially for species in close contact with people and domesticated animals. Here we investigate human and animal contacts and human health in a community living around the Bwindi Impenetrable National Park (BINP), Uganda. We used contact and health survey data to identify opportunities for cross-species pathogen transmission, focusing mostly on people and the endangered mountain gorilla. We conducted a survey with background questions and self-reported diaries to investigate 100 participants' health, such as symptoms and behaviours, and contact patterns, including direct contacts and sightings over a week. Contacts were revealed through networks, including humans, domestic, peri-domestic, and wild animal groups for 1) contacts seen in the week of background questionnaire completion, and 2) contacts seen during the diary week. Participants frequently felt unwell during the study, reporting from one to 10 disease symptoms at different intensity levels, with severe symptoms comprising 6.4% of the diary records and tiredness and headaches the most common symptoms. After human-human contacts, direct contact with livestock and peri-domestic animals were the most common. The contact networks were moderately connected and revealed a preference in contacts within the same taxon and within their taxa groups. Sightings of wildlife were much more common than touching. However, despite contact with wildlife being the rarest of all contact types, one direct contact with a gorilla with a timeline including concerning participant health symptoms was reported. When considering all interaction types, gorillas mostly exhibited intra-species contact, but were found to interact with five other species, including people and domestic animals. Our findings reveal a local human population with recurrent symptoms of illness in a location with intense exposure to factors that can increase pathogen transmission, such as direct contact with domestic and wild animals and proximity among animal species. Despite significant biases and study limitations, the information generated here can guide future studies, such as models for disease spread and One Health interventions.

Introduction Neglected tropical diseases (NTDs) causing lower limb lymphoedema such as podoconiosis, lymphatic filariasis (LF) and leprosy are common in Ethiopia. Routine health services for morbidity management and disability prevention (MMDP) of lymphoedema caused by these conditions are still lacking, even though it imposes a huge burden on affected individuals and their communities in terms of physical and mental health, and psychosocial and economic outcomes. This calls for an integrated, holistic approach to MMDP across these three diseases.Methods and analysis The ‘Excellence in Disability Prevention Integrated across NTDs’ (EnDPoINT) implementation research study aims to assess the integration and scale-up of a holistic package of care—including physical health, mental health and psychosocial care—into routine health services for people with lymphoedema caused by podoconiosis, LF and leprosy in selected districts in Awi zone in the North–West of Ethiopia. The study is being carried out over three phases using a wide range of mixed methodologies. Phase 1 involves the development of a comprehensive holistic care package and strategies for its integration into the routine health services across the three diseases, and to examine the factors that influence integration and the roles of key health system actors. Phase 2 involves a pilot study conducted in one subdistrict in Awi zone, to establish the care package’s adoption, feasibility, acceptability, fidelity, potential effectiveness, its readiness for scale-up, costs of the interventions and the suitability of the training and training materials. Phase 3 involves scale-up of the care package in three whole districts, as well as its evaluation in regard to coverage, implementation, clinical (physical health, mental health and psychosocial) and economic outcomes.Ethics and dissemination Ethics approval for the study has been obtained in the UK and Ethiopia. The results will be disseminated through publications in scientific journals, conference presentations, policy briefs and workshops.

Introduction Our project follows community requests for health service incorporation into conservation collaborations in the rainforests of Papua New Guinea (PNG). This protocol is for health needs assessments, our first step in coplanning medical provision in communities with no existing health data.Methods and analysis The study includes clinical assessments and rapid anthropological assessment procedures (RAP) exploring the health needs and perspectives of partner communities in two areas, conducted over 6 weeks fieldwork. First, in Wanang village (population c.200), which is set in lowland rainforest. Second, in six communities (population c.3000) along an altitudinal transect up the highest mountain in PNG, Mount Wilhelm. Individual primary care assessments incorporate physical examinations and questioning (providing qualitative and quantitative data) while RAP includes focus groups, interviews and field observations (providing qualitative data). Given absence of in-community primary care, treatments are offered alongside research activity but will not form part of the study. Data are collected by a research fellow, primary care clinician and two PNG research technicians. After quantitative and qualitative analyses, we will report: ethnoclassifications of disease, causes, symptoms and perceived appropriate treatment; community rankings of disease importance and service needs; attitudes regarding health service provision; disease burdens and associations with altitudinal-related variables and cultural practices. To aid wider use study tools are in online supplemental file, and paper and ODK versions are available free from the corresponding author.Ethics and dissemination Challenges include supporting informed consent in communities with low literacy and diverse cultures, moral duties to provide treatment alongside research in medically underserved areas while minimising risks of therapeutic misconception and inappropriate inducement, and PNG research capacity building. Brighton and Sussex Medical School (UK), PNG Institute of Medical Research and PNG Medical Research Advisory Committee have approved the study. Dissemination will be via journals, village meetings and plain language summaries.

Safeguarding is rapidly rising up the international development agenda, yet literature on safeguarding in related research is limited. This paper shares processes and practice relating to safeguarding within an international research consortium (the ARISE hub, known as ARISE). ARISE aims to enhance accountability and improve the health and well-being of marginalised people living and working in informal urban spaces in low-income and middle-income countries (Bangladesh, India, Kenya and Sierra Leone). Our manuscript is divided into three key sections. We start by discussing the importance of safeguarding in global health research and consider how thinking about vulnerability as a relational concept (shaped by unequal power relations and structural violence) can help locate fluid and context specific safeguarding risks within broader social systems. We then discuss the different steps undertaken in ARISE to develop a shared approach to safeguarding: sharing institutional guidelines and practice; facilitating a participatory process to agree a working definition of safeguarding and joint understandings of vulnerabilities, risks and mitigation strategies and share experiences; developing action plans for safeguarding. This is followed by reflection on our key learnings including how safeguarding, ethics and health and safety concerns overlap; the challenges of referral and support for safeguarding concerns within frequently underserved informal urban spaces; and the importance of reflective practice and critical thinking about power, judgement and positionality and the ownership of the global narrative surrounding safeguarding. We finish by situating our learning within debates on decolonising science and argue for the importance of an iterative, ongoing learning journey that is critical, reflective and inclusive of vulnerable people.

Abstract The study investigates the in-situ strength of sediments across a plate boundary décollement using drilling parameters recorded when a 1180-m-deep borehole was established during International Ocean Discovery Program (IODP) Expedition 370, Temperature-Limit of the Deep Biosphere off Muroto (T-Limit). Information of the in-situ strength of the shallow portion in/around a plate boundary fault zone is critical for understanding the development of accretionary prisms and of the décollement itself. Studies using seismic reflection surveys and scientific ocean drillings have recently revealed the existence of high pore pressure zones around frontal accretionary prisms, which may reduce the effective strength of the sediments. A direct measurement of in-situ strength by experiments, however, has not been executed due to the difficulty in estimating in-situ stress conditions. In this study, we derived a depth profile for the in-situ strength of a frontal accretionary prism across a décollement from drilling parameters using the recently established equivalent strength (EST) method. At site C0023, the toe of the accretionary prism area off Cape Muroto, Japan, the EST gradually increases with depth but undergoes a sudden change at ~ 800 mbsf, corresponding to the top of the subducting sediment. At this depth, directly below the décollement zone, the EST decreases from ~ 10 to 2 MPa, with a change in the baseline. This mechanically weak zone in the subducting sediments extends over 250 m (~ 800–1050 mbsf), corresponding to the zone where the fluid influx was discovered, and high-fluid pressure was suggested by previous seismic imaging observations. Although the origin of the fluids or absolute values of the strength remain unclear, our investigations support previous studies suggesting that elevated pore pressure beneath the décollement weakens the subducting sediments.

Abstract Background In 2011, a decision was made to scale up a pilot innovation involving ‘adherence clubs’ as a form of differentiated care for HIV positive people in the public sector antiretroviral therapy programme in the Western Cape Province of South Africa. In 2016 we were involved in the qualitative aspect of an evaluation of the adherence club model, the overall objective of which was to assess the health outcomes for patients accessing clubs through epidemiological analysis, and to conduct a health systems analysis to evaluate how the model of care performed at scale. In this paper we adopt a complex adaptive systems lens to analyse planned organisational change through intervention in a state health system. We explore the challenges associated with taking to scale a pilot that began as a relatively simple innovation by a non-governmental organisation. Results Our analysis reveals how a programme initially representing a simple, unitary system in terms of management and clinical governance had evolved into a complex, differentiated care system. An innovation that was assessed as an excellent idea and received political backing, worked well whilst supported on a small scale. However, as scaling up progressed, challenges have emerged at the same time as support has waned. We identified a ‘tipping point’ at which the system was more likely to fail, as vulnerabilities magnified and the capacity for adaptation was exceeded. Yet the study also revealed the impressive capacity that a health system can have for catalysing novel approaches. Conclusions We argue that innovation in largescale, complex programmes in health systems is a continuous process that requires ongoing support and attention to new innovation as challenges emerge. Rapid scaling up is also likely to require recourse to further resources, and a culture of iterative learning to address emerging challenges and mitigate complex system errors. These are necessary steps to the future success of adherence clubs as a cornerstone of differentiated care. Further research is needed to assess the equity and quality outcomes of a differentiated care model and to ensure the inclusive distribution of the benefits to all categories of people living with HIV.

Premise Cañahua is a semi‐domesticated crop grown in high‐altitude regions of the Andes. It is an A‐genome diploid (2n = 2x = 18) relative of the allotetraploid (AABB) Chenopodium quinoa and shares many of its nutritional benefits. Cañahua seed contains a complete protein, a low glycemic index, and offers a wide variety of nutritionally important vitamins and minerals. Methods The reference assembly was developed using a combination of short‐ and long‐read sequencing techniques, including multiple rounds of Hi‐C–based proximity‐guided assembly. Results The final assembly of the ~363‐Mbp genome consists of 4633 scaffolds, with 96.6% of the assembly contained in nine scaffolds representing the nine haploid chromosomes of the species. Repetitive element analysis classified 52.3% of the assembly as repetitive, with the most common repeat identified as long terminal repeat retrotransposons. MAKER annotation of the final assembly yielded 22,832 putative gene models. Discussion When compared with quinoa, strong patterns of synteny support the hypothesis that cañahua is a close A‐genome diploid relative, and thus potentially a simplified model diploid species for genetic analysis and improvement of quinoa. Resequencing and phylogenetic analysis of a diversity panel of cañahua accessions suggests that coordinated efforts are needed to enhance genetic diversity conservation within ex situ germplasm collections.

Mincle, the macrophage-inducible C-type lectin also known as CLEC-4E, binds to the mycobacterial glycolipid trehalose dimycolate and initiates a signaling cascade by serving as a receptor for Mycobacterium tuberculosis and other pathogenic mycobacterial species. Studies of the biological functions of human mincle often rely on mouse models, based on the assumption that the biological properties of the mouse receptor mimic those of the human protein. Experimental support for this assumption has been obtained by expression of the carbohydrate-recognition domain of mouse mincle and characterization of its interaction with small molecule analogs of trehalose dimycolate. The results confirm that the ligand-binding properties of mouse mincle closely parallel those of the human receptor. These findings are consistent with the conservation of key amino acid residues that have been shown to form the ligand-binding site in human and cow mincle. Sequence alignment reveals that these residues are conserved in a wide range of mammalian species, suggesting that mincle has a conserved function in binding ligands that may include endogenous mammalian glycans or pathogen glycans in addition to trehalose dimycolate.

The current mpox outbreak has challenged previous understanding of the disease, with human-to-human transmission being a significant mode of transmission, particularly among gay, bisexual, and other men who have sex with men (GBMSM). A knowledge gap exists on MSM’s mpox experiences in Nigeria’s restrictive sociolegal context. This study explored mpox awareness, knowledge, and experiences among MSM in Lagos, Nigeria, through 28 in-depth interviews. We analysed the interview transcripts thematically. Findings showed low awareness and knowledge of mpox among MSM, who prefer seeking healthcare outside public health facilities due to stigma. Intimate contact during sexual intercourse is a likely source of infection among MSM. The Nigerian mpox response does not centre MSM, and centreing them may not be ideal due to potential stigma. MSM seek care through various means, including drugs, herbal remedies, and KP-friendly sexual and reproductive health (SRH) services, but face stressful care-seeking due to limited social support and stigma. The study shows that Nigeria's mpox situation differs from the situation in mpox non-endemic contexts. The homophobic legal and social environment and heterogenous spread require unique disease framing and context-sensitive response. The study concludes that further surveillance is needed to deepen understanding around mpox care seeking among MSM in Nigeria.

This review identifies evidence on supply-side interventions to change the practices of antibiotic prescribers and gatekeepers in low- and middle-income countries (LMICs). A total of 102 studies met the inclusion criteria, of which 70 studies evaluated interventions and 32 provided insight into prescribing contexts. All intervention studies were from human healthcare settings, none were from animal health. Only one context study examined antibiotic use in animal health. The evidence base is uneven, with the strongest evidence on knowledge and stewardship interventions. The review found that multiplex interventions that combine different strategies to influence behaviour tend to have a higher success rate than interventions based on single strategies. Evidence on prescribing contexts highlights interacting influences including health system quality, education, perceptions of patient demand, bureaucratic processes, profit, competition, and cultures of care. Most interventions took place within one health setting. Very few studies targeted interventions across different kinds of providers and settings. Interventions in hospitals were the most commonly evaluated. There is much less evidence on private and informal private providers who play a major role in drug distribution in LMICs. There were no interventions involving drug detailers or the pharmaceutical companies despite their prominent role in the contextual studies.

We previously reported Clostridium difficile in 20% of retail meat in Canada, which raised concerns about potential foodborne transmissibility. Here, we studied the genetic diversity of C. difficile in retail meats, using a broad Canadian sampling infrastructure and 3 culture methods. We found 6.1% prevalence and indications of possible seasonality (highest prevalence in winter).

The fraction of IgG antibodies with anti-oligomeric Aβ affinity and surface sialic acid was compared between Octagam and Gammagard intravenous immunoglobulin (IVIG) using two complementary surface plasmon resonance methods. These comparisons were performed to identify if an elevated fraction existed in Gammagard, which reported small putative benefits in a recent Phase III clinical trial for Alzheimer's Disease. The fraction of anti-oligomeric Aβ IgG was found to be higher in Octagam, for which no cognitive benefits were reported. The fraction and location of surface-accessible sialic acid in the Fab domain was found to be similar between Gammagard and Octagam. These findings indicate that anti-oligomeric Aβ IgG and total surface sialic acid alone cannot account for reported clinical differences in the two IVIG products. A combined analysis of sialic acid in anti-oligomeric Aβ IgG did reveal a notable finding that this subgroup exhibited a high degree of surface sialic acid lacking the conventional α2,6 linkage. These results demonstrate that the IVIG antibodies used to engage oligomeric Aβ in both Gammagard and Octagam clinical trials did not possess α2,6-linked surface sialic acid at the time of administration. Anti-oligomeric Aβ IgG with α2,6 linkages remains untested as an AD treatment.