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Introduction Acute febrile illness (AFI), traditionally attributed to malaria, is a common reason for seeking primary healthcare in rural South and Southeast Asia. However, malaria transmission has declined while health workers are often poorly equipped to manage non-malarial AFIs. This results in indiscriminate antibiotic prescribing and care escalation, which promotes antibiotic resistance and may increase healthcare costs. To address this problem, an electronic clinical decision support algorithm (eCDSA) called ‘Electronic clinical Decision support for Acute fever Management (EDAM)’ has been developed for primary health workers which integrates clinical, epidemiological and vital sign data with simple point-of-care tests to produce a diagnosis and management plan.Methods and analysis This is a pragmatic cluster-randomised trial aiming to assess the effect of EDAM and related training on antibiotic prescribing rates in rural Cambodian primary health centres (PHCs) as the primary outcome, along with a range of secondary outcomes including safety. Patients with AFI are eligible for recruitment if they are aged ≥1 year. A cluster is defined as a PHC and PHCs will be randomised to control (standard of care) and intervention (EDAM and associated training) arms, with 15 PHCs per arm. Patients will be followed up after 7 days to ascertain the safety profile of EDAM. Each PHC will recruit 152 patients (total 4560), based on a baseline antibiotic prescription rate of 25% and expected reduction to 17.5% with EDAM.Ethics and dissemination Results will be published in international peer-reviewed journals to inform the design of future versions of EDAM and of future trials of similar eCDSAs and other digital health interventions targeted towards rural populations. This study was approved by the Oxford University Tropical Research Ethics Committee (550-23) and the Cambodian National Ethics Committee for Health Research (395-NECHR).Trial registration number International Standard Randomized Controlled Trial Number Registry (ISRCTN15157105).

Summary:. Breast neurotization represents an evolving technique that is not widely practiced in most centers specializing in breast cancer treatment. Recognizing the limited educational resources available for breast and plastic surgeons concerning mastectomy techniques that emphasize nerve preservation, our study sought to bridge this gap. Specifically, we aimed to provide a comprehensive exploration of the surgical applied anatomy of breast sensory innervation and a detailed, step-by-step guide for incorporating nerve-sparing mastectomy and breast neurotization into clinical practice. The significance of this work lies in its potential to enhance the understanding and implementation of nerve-preserving techniques in mastectomy procedures, contributing to improved patient outcomes and quality of life post surgery. We hope that by familiarizing breast and reconstructive surgeons with this procedure, we can gain momentum in our research efforts and ultimately enhance the care provided to mastectomy patients.

Introduction In low-income and middle-income countries in Southeast Asia, the burden of diseases among rural population remains poorly understood, posing a challenge for effective healthcare prioritisation and resource allocation. Addressing this knowledge gap, the South and Southeast Asia Community-based Trials Network (SEACTN) will undertake a survey that aims to determine the prevalence of a wide range of non-communicable and communicable diseases, as one of the key initiatives of its first project—the Rural Febrile Illness project (RFI). This survey, alongside other RFI studies that explore fever aetiology, leading causes of mortality, and establishing village and health facility maps and profiles, will provide an updated epidemiological background of the rural areas where the network is operational.Methods and analysis During 2022–2023, a cross-sectional household survey will be conducted across three SEACTN sites in Bangladesh, Cambodia and Thailand. Using a two-stage cluster-sampling approach, we will employ a probability-proportional-to-size sample method for village, and a simple random sample for household, selection, enrolling all members from the selected households. Approximately 1500 participants will be enrolled per country. Participants will undergo questionnaire interview, physical examination and haemoglobin point-of-care testing. Blood samples will be collected and sent to central laboratories to test for chronic and acute infections, and biomarkers associated with cardiovascular disease, and diabetes. Prevalences will be presented as an overall estimate by country, and stratified and compared across sites and participants’ sociodemographic characteristics. Associations between disease status, risk factors and other characteristics will be explored.Ethics and dissemination This study protocol has been approved by the Oxford Tropical Research Ethics Committee, National Research Ethics Committee of Bangladesh Medical Research Council, the Cambodian National Ethics Committee for Health Research, the Chiang Rai Provincial Public Health Research Ethical Committee. The results will be disseminated via the local health authorities and partners, peer-reviewed journals and conference presentations.Trial registration number NCT05389540.

Background Pulmonary arterial hypertension (PAH) exhibits phenotypic heterogeneity and variable response to therapy. The metabolome has been implicated in the pathogenesis of PAH, but previous works have lacked power to implicate specific metabolites. Mendelian randomization (MR) is a method for causal inference between exposures and outcomes. Methods and Results Using genome‐wide association study summary statistics, we implemented MR analysis to test for potential causal relationships between serum concentration of 575 metabolites and PAH. Five metabolites were causally associated with the risk of PAH after multiple testing correction. Next, we measured serum concentration of candidate metabolites in an independent clinical cohort of 449 patients with PAH to check whether metabolite concentrations are correlated with markers of disease severity. Of the 5 candidates nominated by our MR work, serine was negatively associated and homostachydrine was positively associated with clinical severity of PAH via direct measurement in this independent clinical cohort. Finally we used conditional and orthogonal approaches to explore the biology underlying our lead metabolites. Rare variant burden testing was carried out using whole exome sequencing data from 578 PAH cases and 361 675 controls. Multivariable MR is an extension of MR that uses a single set of instrumental single‐nucleotide polymorphisms to measure multiple exposures; multivariable MR is used to determine interdependence between the effects of different exposures on a single outcome. Rare variant analysis demonstrated that loss‐of‐function mutations within activating transcription factor 4, a transcription factor responsible for upregulation of serine synthesis under conditions of serine starvation, are associated with higher risk for PAH. Homostachydrine is a xenobiotic metabolite that is structurally related to l‐proline betaine, which has previously been linked to modulation of inflammation and tissue remodeling in PAH. Our multivariable MR analysis suggests that the effect of l‐proline betaine is actually mediated indirectly via homostachydrine. Conclusions Our data present a method for study of the metabolome in the context of PAH, and suggests several candidates for further evaluation and translational research.

Abstract Background To report sampling of the trabecular meshwork using the TrabEx+ (MicroSurgical Technology, Redmond, Washington, USA) device in ab interno trabeculectomy. Specifically, this series focusses upon preservation of the trabecular meshwork architecture for assessment of glaucomatous features using common histopathological techniques. Patients This series features six glaucomatous eyes undergoing TrabEx+ with or without cataract surgery. Three patients had primary open angle glaucoma and the remaining had pigment dispersion glaucoma, ocular hypertension or uveitic glaucoma. Four eyes had simultaneous cataract surgery. Methods Trabecular meshwork was excised using the TrabEx+ device and retrieved using vitreoretinal forceps. The samples were then processed into formalin-fixed paraffin-embedded 4 micron tissue segments and stained with haematoxylin and eosin, periodic acid–Schiff and elastin Van Gieson. Collagen IV was labelled using immunohistochemistry for the purpose of identifying the basement membrane of trabecular beams. Results Presence of trabecular meshwork was confirmed in five of the six samples taken. One of six samples consisted of blood only, but this was expected following early termination of the procedure due to patient restlessness. In the five positive cases trabecular beams with associated trabecular meshwork cells were identified on hematoxylin-eosin and periodic acid–Schiff staining. The beams retained their lamellar structure. The basement membrane underlying the trabecular cells was evident in three specimens, whilst two specimens were of insufficient size for collagen IV labelling. Conclusions This case series illustrates that TrabEx+ can be utilised to successfully retrieve trabecular meshwork samples with sufficient architectural perseveration of the tissue to enable histopathological and laboratory analysis.

Introduction In the Greater Mekong Subregion, adults are at highest risk for malaria. The most relevant disease vectors bite during daytime and outdoors which makes forest work a high-risk activity for malaria. The absence of effective vector control strategies and limited periods of exposure during forest visits suggest that chemoprophylaxis could be an appropriate strategy to protect forest goers against malaria.Methods and analysis The protocol describes an open-label randomised controlled trial of artemether-lumefantrine (AL) versus multivitamin as prophylaxis against malaria among forest goers aged 16–65 years in rural northeast Cambodia. The primary objective is to compare the efficacy of the artemisinin combination therapy AL versus a multivitamin preparation as defined by the 28-day PCR parasite positivity rate and incidence of confirmed clinical malaria of any species. The sample size is 2200 patient-episodes of duration 1 month in each arm. The duration of follow-up and prophylaxis for each participant is 1, 2 or 3 consecutive 28-day periods, followed by a further 28 days of post-exposure prophylaxis, depending on whether they continue to visit the forest. Analysis will be done both by intention to treat and per protocol.Ethics and dissemination All participants will provide written, informed consent. Ethical approval was obtained from the Oxford Tropical Research Ethics Committee and the Cambodia National Ethics Committee for Health Research. Results will be disseminated by peer-reviewed open access publication together with open data.Trial registration number NCT04041973; Pre-result.

Transport processes between aquaculture facilities activate the stress response in fish. To deal with these situations, the hypothalamic-pituitary-interrenal (HPI) axis releases cortisol, leading to an increase in circulating energy resources to restore homeostasis. However, if the allostatic load generated exceeds fish tolerance limits, stress-related responses will compromise health and welfare of the animals. In this context, anesthetics have arisen as potential agents aiming to reduce negative effects of stress response. Here we assessed the effects of a sedative dose of clove oil (CO) and MS-222 on hallmarks involved in HPI axis regulation and energy management after simulated transport, and further recovery, in gilthead seabream (Sparus aurata L.) juveniles. Fish were placed in a mobile setup of water tanks where transport conditions were simulated for 6 h. Sedation doses of either CO (2.5 mg L−1) or MS-222 (5 mg L−1) were added in the water tanks. A control group without anesthetics was also included in the setup. Half of the animals (n = 12 per group) were sampled immediately after transport, while remaining animals were allowed to recover for 18 h in clean water tanks and then sampled. Our results showed that the HPI axis response was modified at peripheral level, with differences depending on the anesthetic employed. Head kidney gene-expressions related to cortisol production (star and cyp11b1) matched concomitantly with increased plasma cortisol levels immediately after transport in CO-sedated fish, but these levels remained constant in MS-222-sedated fish. Differential changes in the energy management of carbohydrates, lipids and amino acids, depending on the anesthetic employed, were also observed. The use of CO stimulated amino acids catabolism, while MS-222-sedated fish tended to consume liver glycogen and mobilize triglycerides. Further studies, including alternative doses of both anestethics, as well as the assessment of time-course HPI activation and longer recovery periods, are necessary to better understand if the use of clove oil and MS-222 is beneficial for S. aurata under these circumstances.

Purpose: Preliminary dosimetric findings in patients managed with the Contura® Multi-Lumen Balloon (MLB) breast brachytherapy catheter to deliver accelerated partial breast irradiation (APBI) on a multi-institutional phase IV registry trial were reviewed. Material and methods: CT-based 3D planning with dose optimization was performed for all patients. For the study, new ideal dosimetric goals were developed: 1) ≥ 95% of the prescribed dose (PD) covering ≥ 90% of the target volume (TV), 2) a maximum skin dose ≤ 125% of the PD, 3) maximum rib dose ≤ 145% of the PD, and 4) the V150 ≤ 50 cc and V200 ≤ 10 cc. The frequency of concurrently achieving these dosimetric goals using the Contura® MLB was investigated.Results: 194 cases were evaluable. Employing the MLB, all ideal dosimetric criteria were achieved in 76% of cases.Evaluating dosimetric criteria separately, 90% and 89% of cases met the new ideal skin and rib dose criteria, respectively. In 96%, ideal TV coverage goals were achieved and in 96%, dose homogeneity criteria (V150 and V200) were met. For skin spacing ≥ 5-7 mm, the median skin dose was 121% of the PD and when < 5 mm, the median skin dose was 124.4%. For rib distancees < 5 mm, the median rib dose was reduced to 136.4% of the PD. For skin spacing < 7 mm and distance to rib < 5 mm, the median skin and rib doses were concurrently limited to 121% and 142.8% of thePD, respectively. Conclusions: The Contura® MLB catheter provides potential improvements in dosimetric capabilities (i.e., reduced skin and rib doses and improved TV coverage) in many clinical scenarios.

Studies of early fourth-millennium BC Britain have typically focused on the Early Neolithic sites of Wessex and Orkney; what can the investigation of sites located in areas beyond these core regions add? The authors report on excavations (2011-2019) at Dorstone Hill in Herefordshire, which have revealed a remarkable complex of Early Neolithic monuments: three long barrows constructed on the footprints of three timber buildings that had been deliberately burned, plus a nearby causewayed enclosure. A Bayesian chronological model demonstrates the precocious character of many of the site's elements and strengthens the evidence for the role of tombs and houses/halls in the creation and commemoration of foundational social groups in Neolithic Britain. Keywords: Britain, Neolithic, long mounds, causewayed enclosure, Bayesian modelling, social organisation, Introduction Recent years have seen lively discussions of the earliest centuries of the Neolithic period in Britain. The movement of new populations into these islands from the end of the [...]

Abstract Background Helicobacter pylori is an important agent of gastroduodenal disease in Africa and throughout the world. We sought to determine an optimum method for genotyping H. pylori strains from children and adults in The Gambia, West Africa. Results Virulence genes were amplified in 127 of 190 cases tested (121 adults and 6 children); each of 60 bacterial cultures, and 116 from DNA extracted directly from biopsies. The proportion of biopsies that were cagA+, the ratio of vacAs1/s2, and vacAm1/m2, and the proportion of mixed strain populations in individual subjects changed with age. Strains lacking virulence cagA and vacA genes and with apparently homogeneous (one predominant strain) infections were more common among infants than adults. Conclusions In order to detect the range of bacterial genotypes harbored by individual patients, direct PCR proved slightly superior to isolation of H. pylori by biopsy culture, but the techniques were complementary, and the combination of both culture and direct PCR produced the most complete picture. The seemingly higher virulence of strains from adult than infant infections in The Gambia merits further analysis.

Examines distance teaching in Australian higher education, with particular reference to predictions made in the recent West Report ("Learning for Life"), arguing that discussion of technology and change in the universities must be framed in the context of the wider educational system, considering especially the government's construction of educational markets. Market mechanisms, policy formation, and equity issues are explored. (MSE)