Search

INTRODUCTION: Micronutrient deficiencies are prevalent in West Africa, particularly among women of reproductive age (WRA) and young children. Bouillon is a promising food fortification vehicle due to its widespread consumption. This study aims to evaluate the impact of multiple micronutrient-fortified bouillon cubes, compared to control bouillon cubes (fortified with iodine only), on micronutrient status and hemoglobin concentrations among lactating and non-lactating WRA and young children in northern Ghana. METHODS: This randomized, controlled doubly-masked trial will be conducted in the Kumbungu and Tolon districts in the Northern Region of Ghana, where prior data indicate multiple micronutrient deficiencies are common. Participants will be: 1) non-pregnant non-lactating WRA (15-49 y), 2) children 2-5 y, and 3) non-pregnant lactating women 4-18 months postpartum. Eligible participants will be randomly assigned to receive household rations of one of two types of bouillon cubes: 1) a multiple micronutrient-fortified bouillon cube containing vitamin A, folic acid, vitamin B12, iron, zinc, and iodine, or 2) a control cube containing iodine only. Each participants household will receive a ration of bouillon cubes every 2 weeks, and households will be advised to prepare meals as usual, using the study-provided cubes. The trial duration will be 9 months for non-pregnant non-lactating WRA and children, and 3 months for lactating women. The primary outcomes will be changes in biomarkers of micronutrient status and hemoglobin among WRA and children and milk micronutrient concentrations among lactating women. Secondary outcomes will include change in prevalence of micronutrient deficiency and anemia; dietary intake of bouillon and micronutrients; inflammation, malaria, and morbidity symptoms; and child growth and development. DISCUSSION: Evidence from this study will inform discussions about bouillon fortification in Ghana and West Africa. TRIAL REGISTRATION: The trial was registered on ClinicalTrials.gov (NCT05178407) and the Pan-African Clinical Trial Registry (PACTR202206868437931). This manuscript reflects protocol version 4 (August 29, 2022).

Strategies to prevent or delay Alzheimers disease and related dementias (AD/ADRD) are urgently needed, and blood pressure (BP) management is a promising strategy. Yet the effects of different BP control strategies across the life course on AD/ADRD are unknown. Randomized trials may be infeasible due to prolonged follow-up and large sample sizes. Simulation analysis is a practical approach to estimating these effects using the best available existing data. However, existing simulation frameworks cannot estimate the effects of BP control on both dementia and cardiovascular disease. This manuscript describes the design principles, implementation details, and population-level validation of a novel population-health microsimulation framework, the MIchigan ChROnic Disease SIMulation (MICROSIM), for The Effect of Lower Blood Pressure over the Life Course on Late-life Cognition in Blacks, Hispanics, and Whites (BP-COG) study of the effect of BP levels over the life course on dementia and cardiovascular disease. MICROSIM is an agent-based Monte Carlo simulation designed using computer programming best practices. MICROSIM estimates annual vascular risk factor levels and transition probabilities in all-cause dementia, stroke, myocardial infarction, and mortality in a nationally representative sample of US adults 18+ using the National Health and Nutrition Examination Survey (NHANES). MICROSIM models changes in risk factors over time, cognition and dementia using changes from a pooled dataset of individual participant data from 6 US prospective cardiovascular cohort studies. Cardiovascular risks were estimated using a widely used risk model and BP treatment effects were derived from meta-analyses of randomized trials. MICROSIM is an extensible, open-source framework designed to estimate the population-level impact of different BP management strategies and reproduces US population-level estimates of BP and other vascular risk factors levels, their change over time, and incident all-cause dementia, stroke, myocardial infarction, and mortality.

The use of publicly available sequencing datasets as controls (hereafter, "public controls") in studies of rare variant disease associations has great promise but can increase the risk of false-positive discovery. The specific factors that could contribute to inflated distribution of test statistics have not been systematically examined. Here, we leveraged both public controls, gnomAD v2.1 and several datasets sequenced in our laboratory to systematically investigate factors that could contribute to the false-positive discovery, as measured by λΔ95, a measure to quantify the degree of inflation in statistical significance. Analyses of datasets in this investigation found that 1) the significantly inflated distribution of test statistics decreased substantially when the same variant caller and filtering pipelines were employed, 2) differences in library prep kits and sequencers did not affect the false-positive discovery rate and, 3) joint vs. separate variant-calling of cases and controls did not contribute to the inflation of test statistics. Currently available methods do not adequately adjust for the high false-positive discovery. These results, especially if replicated, emphasize the risks of using public controls for rare-variant association tests in which individual-level data and the computational pipeline are not readily accessible, which prevents the use of the same variant-calling and filtering pipelines on both cases and controls. A plausible solution exists with the emergence of cloud-based computing, which can make it possible to bring containerized analytical pipelines to the data (rather than the data to the pipeline) and could avert or minimize these issues. It is suggested that future reports account for this issue and provide this as a limitation in reporting new findings based on studies that cannot practically analyze all data on a single pipeline.

Chandelier (Ch) cells are cortical interneurons with axon terminal structures known as cartridges that synapse on the axon initial segment of excitatory pyramidal neurons. Previous studies indicate that the number of Ch cells is decreased in autism, and that GABA receptors are decreased in the Ch cell synaptic target in the prefrontal cortex. To further identify Ch cell alterations, we examined whether the length of cartridges, and the number, density, and size of Ch cell synaptic boutons, differed in the prefrontal cortex of cases with autism versus control cases. We collected samples of postmortem human prefrontal cortex (Brodmann Area (BA) 9, 46, and 47) from 20 cases with autism and 20 age- and sex-matched control cases. Ch cells were labeled using an antibody against parvalbumin, a marker that labeles soma, cartridges, and synaptic boutons. We found no significant difference in the average length of cartridges, or in the total number or density of boutons in control subjects vs. subjects with autism. However, we found a significant decrease in the size of Ch cell boutons in those with autism. The reduced size of Ch cell boutons may result in reduced inhibitory signal transmission and impact the balance of excitation to inhibition in the prefrontal cortex in autism.

The feeding ecology of broadbill swordfish (Xiphias gladius) in the California Current was described based on analysis of stomach contents collected by fishery observers aboard commercial drift gillnet boats from 2007 to 2014. Prey were identified to the lowest taxonomic level and diet composition was analyzed using univariate and multivariate methods. Of 299 swordfish sampled (74 to 245 cm eye-to-fork length), 292 non-empty stomachs contained remains from 60 prey taxa. Genetic analyses were used to identify prey that could not be identified visually. Diet consisted mainly of cephalopods but also included epipelagic and mesopelagic teleosts. Jumbo squid (Dosidicus gigas) and Gonatopsis borealis were the most important prey based on the geometric index of importance. Swordfish diet varied with body size, location and year. Jumbo squid, Gonatus spp. and Pacific hake (Merluccius productus) were more important for larger swordfish, reflecting the ability of larger specimens to catch large prey. Jumbo squid, Gonatus spp. and market squid (Doryteuthis opalescens) were more important in inshore waters, while G. borealis and Pacific hake predominated offshore. Jumbo squid was more important in 2007-2010 than in 2011-2014, with Pacific hake being the most important prey item in the latter period. Diet variation by area and year probably reflects differences in swordfish preference, prey availability, prey distribution, and prey abundance. The range expansion of jumbo squid that occurred during the first decade of this century may particularly explain their prominence in swordfish diet during 2007-2010. Some factors (swordfish size, area, time period, sea surface temperature) that may influence dietary variation in swordfish were identified. Standardizing methods could make future studies more comparable for conservation monitoring purposes.

Surf zones are highly dynamic marine ecosystems that are subject to increasing anthropogenic and climatic pressures, posing multiple challenges for biomonitoring. Traditional methods such as seines and hook and line surveys are often labor intensive, taxonomically biased, and can be physically hazardous. Emerging techniques, such as baited remote underwater video (BRUV) and environmental DNA (eDNA) are promising nondestructive tools for assessing marine biodiversity in surf zones of sandy beaches. Here we compare the relative performance of beach seines, BRUV, and eDNA in characterizing community composition of bony (teleost) and cartilaginous (elasmobranch) fishes of surf zones at 18 open coast sandy beaches in southern California. Seine and BRUV surveys captured overlapping, but distinct fish communities with 50% (18/36) of detected species shared. BRUV surveys more frequently detected larger species (e.g. sharks and rays) while seines more frequently detected one of the most abundant species, barred surfperch (Amphistichus argenteus). In contrast, eDNA metabarcoding captured 88.9% (32/36) of all fishes observed in seine and BRUV surveys plus 57 additional species, including 15 that frequent surf zone habitats. On average, eDNA detected over 5 times more species than BRUVs and 8 times more species than seine surveys at a given site. eDNA approaches also showed significantly higher sensitivity than seine and BRUV methods and more consistently detected 31 of the 32 (96.9%) jointly observed species across beaches. The four species detected by BRUV/seines, but not eDNA were only resolved at higher taxonomic ranks (e.g. Embiotocidae surfperches and Sygnathidae pipefishes). In frequent co-detection of species between methods limited comparisons of richness and abundance estimates, highlighting the challenge of comparing biomonitoring approaches. Despite potential for improvement, results overall demonstrate that eDNA can provide a cost-effective tool for long-term surf zone monitoring that complements data from seine and BRUV surveys, allowing more comprehensive surveys of vertebrate diversity in surf zone habitats.

Plate-based proteomic sample preparation offers a solution to the large sample throughput demands in the biotechnology field where hundreds or thousands of engineered microbes are constructed for testing is routine. Meanwhile, sample preparation methods that work efficiently on broader microbial groups are desirable for new applications of proteomics in other fields, such as microbial communities. Here, we detail a step-by-step protocol that consists of cell lysis in an alkaline chemical buffer (NaOH/SDS) followed by protein precipitation with high-ionic strength acetone in 96-well format. The protocol works for a broad range of microbes (e.g., Gram-negative bacteria, Gram-positive bacteria, non-filamentous fungi) and the resulting proteins are ready for tryptic digestion for bottom-up quantitative proteomic analysis without the need for desalting column cleanup. The yield of protein using this protocol increases linearly with respect to the amount of starting biomass from 0.5-2.0 OD*mL of cells. By using a bench-top automated liquid dispenser, a cost-effective and environmentally-friendly option to eliminating pipette tips and reducing reagent waste, the protocol takes approximately 30 minutes to extract protein from 96 samples. Tests on mock mixtures showed expected results that the biomass composition structure is in close agreement with the experimental design. Lastly, we applied the protocol for the composition analysis of a synthetic community of environmental isolates grown on two different media. This protocol has been developed to facilitate rapid, low-variance sample preparation of hundreds of samples and allow flexibility for future protocol development.

Luxeptinib (LUX) is a novel oral kinase inhibitor that inhibits FLT3 and also interferes with signaling from the BCR and cell surface TLRs, as well as activation of the NLRP3 inflammasome. Ongoing clinical trials are testing its activity in patients with lymphoma and AML. This study sought to refine understanding of how LUX modulates the earliest steps downstream of the BCR following its activation by anti-IgM in lymphoma cells in comparison to ibrutinib (IB). LUX decreased anti-IgM-induced phosphorylation of BTK at Y551 and Y223 but its ability to reduce phosphorylation of kinases further upstream suggests that BTK is not the primary target. LUX was more effective than IB at reducing both steady state and anti-IgM-induced phosphorylation of LYN and SYK. LUX decreased phosphorylation of SYK (Y525/Y526) and BLNK (Y96) which are necessary regulators of BTK activation. Further upstream, LUX blunted the anti-IgM-induced phosphorylation of LYN (Y397) whose activation is required for phosphorylation of SYK and BLNK. These results indicate that LUX is targeting autophosphorylation of LYN or a step further upstream of LYN in the cascade of signal generated by BCR and that it does so more effectively than IB. The fact that LUX has activity at or upstream of LYN is important because LYN is an essential signaling intermediate in multiple cellular signaling processes that regulate growth, differentiation, apoptosis, immunoregulation, migration and EMT in normal and cancer cells.

Background As diagnostic tests for COVID-19 were broadly deployed under Emergency Use Authorization, there emerged a need to understand the real-world utilization and performance of serological testing across the United States. Methods Six health systems contributed electronic health records and/or claims data, jointly developed a master protocol, and used it to execute the analysis in parallel. We used descriptive statistics to examine demographic, clinical, and geographic characteristics of serology testing among patients with RNA positive for SARS-CoV-2. Results Across datasets, we observed 930,669 individuals with positive RNA for SARS-CoV-2. Of these, 35,806 (4%) were serotested within 90 days; 15% of which occurred 30%) in some datasets—limiting our ability to examine differences in serological testing by race. In datasets where race/ethnicity information was available, we observed a greater distribution of White individuals among those serotested; however, the time between RNA and serology tests appeared shorter in Black compared to White individuals. Test manufacturer data was available in half of the datasets contributing to the analysis. Conclusion Our results inform the underlying context of serotesting during the first year of the COVID-19 pandemic and differences observed between claims and EHR data sources–a critical first step to understanding the real-world accuracy of serological tests. Incomplete reporting of race/ethnicity data and a limited ability to link test manufacturer data, lab results, and clinical data challenge the ability to assess the real-world performance of SARS-CoV-2 tests in different contexts and the overall U.S. response to current and future disease pandemics.

Pangenome analyses are increasingly being utilized to study the evolution of eukaryotic organisms. While pangenomes can provide insight into polymorphic gene content, inferences about the ecological and adaptive potential of such organisms also need to be accompanied by additional supportive genomic analyses. In this study we constructed a pangenome of Claviceps purpurea from 24 genomes and examined the positive selection and recombination landscape of an economically important fungal organism for pharmacology and agricultural research. Together, these analyses revealed that C. purpurea has a relatively large accessory genome (~ 38%), high recombination rates (ρ = 0.044), and transposon mediated gene duplication. However, due to observations of relatively low transposable element (TE) content (8.8%) and a lack of variability in genome sizes, prolific TE expansion may be controlled by frequent recombination. We additionally identified that within the ergoline biosynthetic cluster the lpsA1 and lpsA2 were the result of a recombination event. However, the high recombination rates observed in C. purpurea may be influencing an overall trend of purifying selection across the genome. These results showcase the use of selection and recombination landscapes to identify mechanisms contributing to pangenome structure and primary factors influencing the evolution of an organism.

BackgroundGlobally, the prevalence of chronic non-communicable diseases (C-NCDs) and occurrence of multi-morbidity specifically, has been increasing and will continue to rise as life expectancy increases. The burden of mental health disorders has also been rising globally. In sub-Saharan Africa (SSA), literature on these health issues, which are interrelated, is scarce. This study assesses the prevalence of C-NCDs, and depressive and anxiety symptomology and examines the relationship between these issues among a sample of older adults in Uganda.MethodsBetween 2021-2022, 604 consenting adults aged 35 years and older were surveyed on a broad range of health issues for the ongoing AMBSO Population Health Surveillance (APHS) cohort study in Wakiso district. Descriptive analyses were performed to characterize the burden of C-NCDs (e.g. diabetes, hypertension), depression (PHQ-9 using a cutoff of ResultsMajority of participants were females (63.6%), median age was 46 (IQR: 39-54). Any C-NCDs prevalence was 18.7%, while 18.9% and 11.4%, had screening scores indicative of depressive and anxiety symptomology, respectively. Three percent (3.2%) had PHQ-9 scores indicative of moderate to severe depressive symptomology. In models adjusted for sociodemographic characteristics, there was 12% increased odds of suffering from C-NCDs for every unit increase in PHQ-9 score (AOR = 1.12, 95% CI: 1.10-1.20). Participants with any anxiety symptoms had 2.1 greater odds of suffering from C-NCD compared to those who did not have anxiety symptoms (AOR = 2.10, 95% CI: 1.21-3.70).ConclusionC-NCDs were prevalent in older adults, particularly among those experiencing mental health symptoms. Screening for C-NCDs and mental health disorders should be integrated into routine health care for older adults in the country. Early screening and identification of these health issues through primary health care could significantly reduce the public health burden attributable to mental health disorders and the incidence of multi-morbidity in Uganda.

BackgroundSignificant milestones have been made in the development of COVID19 diagnostics Technologies. Government of the republic of Uganda and the line Ministry of Health mandated Uganda Virus Research Institute to ensure quality of COVID19 diagnostics. Re-testing was one of the methods initiated by the UVRI to implement External Quality assessment of COVID19 molecular diagnostics.Methodparticipating laboratories were required by UVRI to submit their already tested and archived nasopharyngeal samples and corresponding meta data. These were then re-tested at UVRI using the WHO Berlin protocol, the UVRI results were compared to those of the primary testing laboratories in order to ascertain performance agreement for the qualitative & quantitative results obtained. Ms Excel window 12 and GraphPad prism ver 15 was used in the analysis. Bar graphs, pie charts and line graphs were used to compare performance agreement between the reference Laboratory and primary testing Laboratories.ResultsEleven (11) Ministry of Health/Uganda Virus Research Institute COVID19 accredited laboratories participated in the re-testing of quality control samples. 5/11 (45%) of the primary testing laboratories had 100% performance agreement with that of the National Reference Laboratory for the final test result. Even where there was concordance in the final test outcome (negative or positive) between UVRI and primary testing laboratories, there were still differences in CT values. The differences in the Cycle Threshold (CT) values were insignificant except for Tenna & Pharma Laboratory and the UVRI(p = 0.0296). The difference in the CT values were not skewed to either the National reference Laboratory(UVRI) or the primary testing laboratory but varied from one laboratory to another. In the remaining 6/11 (55%) laboratories where there were discrepancies in the aggregate test results, only samples initially tested and reported as positive by the primary laboratories were tested and found to be false positives by the UVRI COVID19 National Reference Laboratory.ConclusionFalse positives were detected from public, private not for profit and private testing laboratories in almost equal proportion. There is need for standardization of molecular testing platforms in Uganda. There is also urgent need to improve on the Laboratory quality management systems of the molecular testing laboratories in order to minimize such discrepancies.

Pneumococcal conjugate vaccines reduce the burden of invasive pneumococcal disease, but the sustained effect of these vaccines can be diminished by an increase in disease caused by non-vaccine serotypes. To describe pneumococcal serotype epidemiology in Botswana following introduction of 13-valent pneumococcal conjugate vaccine (PCV-13) in July 2012, we performed molecular serotyping of 268 pneumococcal strains isolated from 221 children between 2012 and 2017. The median (interquartile range) age of the children included in this analysis was 6 (3,12) months. Fifty-nine percent of the children had received at least one dose of PCV-13 and 35% were fully vaccinated with PCV-13. While colonization by vaccine serotypes steadily declined following PCV-13 introduction, 25% of strains isolated more than 3 years after vaccine introduction were PCV-13 serotypes. We also observed an increase in colonization by non-vaccine serotypes 21 and 23B, which have been associated with invasive pneumococcal disease and antibiotic resistance in other settings.

PurposeTo investigate if accounting for a cup-to-disc ratio (CDR) genetic risk score (GRS) modified the association between large CDR and cognitive function among women.DesignThis was a retrospective study using data from the Women's Health Initiative.MethodsPatients with glaucoma or ocular hypertension were excluded. Large CDR was defined as ≥ 0.6 in either eye. Cognitive function was measured by the Modified Mini-Mental State Examination (3MSE). We used the combined effects from 13 single nucleotide polymorphisms (SNPs) to formulate the GRS for CDR. We used logistic regression to investigate associations between weighted GRS and large CDR, then a linear regression to assess the association between weighted GRS and 3MSE scores, and between weighted GRS, CDR, and 3MSE scores, adjusted for demographic and clinical characteristics.ResultsFinal analyses included 1,196 White women with mean age of 69.60 ± 3.62 years and 7.27% with large CDR. Mean GRS in women with and without large CDR was 1.51 ± 0.31 vs. 1.41 ± 0.36, respectively (p = 0.004). The odds of large CDR for a one unit increase in GRS was 2.30 (95% CI: (1.22, 4.36), p = 0.011). Adding the CDR GRS in the model with CDR and 3MSE, women with large CDR still had statistically significantly lower 3MSE scores than those without large CDR, yielding a predicted mean difference in 3MSE scores of 0.84 (p = 0.007).ConclusionsIndependent of the CDR GRS, women with large CDR had a lower cognitive function.

[This corrects the article DOI: 10.1371/journal.pone.0245064.].

IntroductionIn observational studies, venous thromboembolism (VTE) has been associated with Cushing's syndrome and with persistent mental stress, two conditions associated with higher cortisol levels. However, it remains unknown whether high cortisol levels within the usual range are causally associated with VTE risk. We aimed to assess the association between plasma cortisol levels and VTE risk using Mendelian randomization.MethodsThree genetic variants in the SERPINA1/SERPINA6 locus (rs12589136, rs11621961 and rs2749527) were used to proxy plasma cortisol. The associations of the cortisol-associated genetic variants with VTE were acquired from the INVENT (28 907 cases and 157 243 non-cases) and FinnGen (6913 cases and 169 986 non-cases) consortia. Corresponding data for VTE subtypes were available from the FinnGen consortium and UK Biobank. Two-sample Mendelian randomization analyses (inverse-variance weighted method) were performed.ResultsGenetic predisposition to higher plasma cortisol levels was associated with a reduced risk of VTE (odds ratio [OR] per one standard deviation increment 0.73, 95% confidence interval [CI] 0.62-0.87, p

BackgroundTetanus is a potentially fatal disease that is preventable through vaccination. While the Democratic Republic of the Congo (DRC) has continued to improve implementing routine vaccination activities throughout the country, they have struggled to maintain high childhood vaccine coverage. This study aims to examine the seroprevalence of tetanus in children 6 to 59 months to identify areas for intervention and improvement of vaccination coverage.MethodsIn collaboration with the 2013-2014 Demographic and Health Survey, we assessed the seroprevalence of tetanus antibodies among children in the DRC. Dried blood spot samples collected from children 6-59 months of age were processed using a prototype DYNEX Multiplier® chemiluminescent automated immunoassay instrument with a multiplex measles, mumps, rubella, varicella and tetanus assay. Multivariable logistic regression was used to determine factors associated with tetanus vaccination and seroprotection.ResultsOverall, 36.1% of children 6-59 months of age reported receiving at least 1 dose of tetanus vaccine while 28.7% reported receiving 3 doses; tetanus seroprotection was 40%. Increasing age in children was associated with decreased tetanus seroprotection, but increased number tetanus vaccinations received. Factors related to increased tetanus seroprotection included number of children in the household, wealth index of the family, urban residence compared to rural, level of maternal education, and province and geography.ConclusionsOur findings in this nationally representative sample indicate that serology biomarkers may help identify children who are not fully immunized to tetanus more accurately than reported vaccination. While children may be captured for routine immunization activities, as children age, decreasing seroprevalence may indicate additional need to bolster routine vaccination activities and documentation of vaccination in school aged children. Additionally, the study highlights gaps in rural residential areas and vaccination coverage based on maternal education, indicating that policies targeting maternal education and awareness could improve the coverage and seroprevalence of tetanus antibodies in the DRC.

BackgroundDespite being a priority population for COVID-19 vaccination, limited data are available regarding acceptability of COVID-19 vaccines among people living with HIV (PLWH) in Sub-Saharan Africa. We described COVID-19 vaccine acceptability and factors associated with vaccine acceptability among PLWH in Uganda.MethodsThis was a cross-sectional study conducted among PLWH, aged ≥18 years, enrolled participants who were seeking HIV care from six purposely selected accredited ART clinics in Kampala. We obtained data on vaccine acceptability defined as willingness to accept any of the available COVID-19 vaccines using interviewer-administered questionnaires. In addition, we assessed vaccination status, complacency regarding COVID-19 disease, vaccine confidence, and vaccine convenience. Factors associated with COVID-19 vaccine acceptability were evaluated using modified Poisson regression with robust standard errors.ResultsWe enrolled 767 participants of whom 485 (63%) were women. The median age was 33 years [interquartile range (IQR) 28-40] for women and 40 years [IQR], (34-47) for men. Of the respondents 534 (69.6%,95% confidence interval [CI]: 66.3%-72.8%) reported receiving at least one vaccine dose, with women significantly more likely than men to have been vaccinated (73% vs. 63%; p = 0.003). Among the unvaccinated 169 (72.7%, 95% CI: 66.6%-78.0%) were willing to accept vaccination, had greater vaccine confidence (85.9% had strong belief that the vaccines were effective; 81.9% that they were beneficial and 71% safe for PLWH; 90.5% had trust in health care professionals or 77.4% top government officials), and believed that it would be easy to obtain a vaccine if one decided to be vaccinated (83.6%). Vaccine acceptability was positively associated with greater vaccine confidence (adjusted prevalence ratio [aPR] 1.44; 95% CI: 1.08-1.90), and positive perception that it would be easy to obtain a vaccine (aPR 1.57; 95% CI: 1.26-1.96).Conclusionvaccine acceptance was high among this cohort of PLWH, and was positively associated with greater vaccine confidence, and perceived easiness (convince) to obtained the vaccine. Building vaccine confidence and making vaccines easily accessible should be a priority for vaccination programs targeting PLWH.

IntroductionThe NIH All of Us Research Program will have the scale and scope to enable research for a wide range of diseases, including cancer. The program's focus on diversity and inclusion promises a better understanding of the unequal burden of cancer. Preliminary cancer ascertainment in the All of Us cohort from two data sources (self-reported versus electronic health records (EHR)) is considered.Materials and methodsThis work was performed on data collected from the All of Us Research Program's 315,297 enrolled participants to date using the Researcher Workbench, where approved researchers can access and analyze All of Us data on cancer and other diseases. Cancer case ascertainment was performed using data from EHR and self-reported surveys across key factors. Distribution of cancer types and concordance of data sources by cancer site and demographics is analyzed.Results and discussionData collected from 315,297 participants resulted in 13,298 cancer cases detected in the survey (in 89,261 participants), 23,520 cancer cases detected in the EHR (in 203,813 participants), and 7,123 cancer cases detected across both sources (in 62,497 participants). Key differences in survey completion by race/ethnicity impacted the makeup of cohorts when compared to cancer in the EHR and national NCI SEER data.ConclusionsThis study provides key insight into cancer detection in the All of Us Research Program and points to the existing strengths and limitations of All of Us as a platform for cancer research now and in the future.

BackgroundChildren may be at higher risk for swimming-associated illness following exposure to fecally-contaminated recreational waters. We analyzed a pooled data set of over 80,000 beachgoers from 13 beach sites across the United States to compare risks associated with the fecal indicator bacteria Enterococcus spp. (measured by colony forming units, CFU and quantitative polymerase chain reaction cell equivalents, qPCR CE) for different age groups across different exposures, sites and health endpoints.MethodsSites were categorized according to the predominant type of fecal contamination (human or non-human). Swimming exposures of varying intensity were considered according to degree of contact and time spent in the water. Health endpoints included gastrointestinal and respiratory symptoms and skin rashes. Logistic regression models were used to analyze the risk of illness as a function of fecal contamination in water as measured by Enterococcus spp. among the exposed groups. Non-swimmers (those who did not enter the water) were excluded from the models to reduce bias and facilitate comparison across groups.ResultsGastrointestinal symptoms were the most sensitive health endpoint and strongest associations were observed with Enterococcus qPCR CE at sites impacted by human fecal contamination. Under several exposure scenarios, associations between illness and Enterococcus spp. levels were significantly higher among children compared to adolescents and adults. Respiratory symptoms were also associated with Enterococcus spp. exposures among young children at sites affected by human fecal sources, although small sample sizes resulted in imprecise estimates for these associations.ConclusionUnder many exposure scenarios, children were at higher risk of illness associated with exposure to fecal contamination as measured by the indicator bacteria Enterococcus spp. The source of fecal contamination and the intensity of swimming exposure were also important factors affecting the association between Enterococcus spp. and swimming-associated illness.

Study objectiveFacemask use is associated with reduced transmission of SARS-CoV-2. Most surveys assessing perceptions and practices of mask use miss the most vulnerable racial, ethnic, and socio-economic populations. These same populations have suffered disproportionate impacts from the pandemic. The purpose of this study was to assess beliefs, access, and practices of mask wearing across 15 urban emergency department (ED) populations.MethodsThis was a secondary analysis of a cross-sectional study of ED patients from December 2020 to March 2021 at 15 geographically diverse, safety net EDs across the US. The primary outcome was frequency of mask use outside the home and around others. Other outcome measures included having enough masks and difficulty obtaining them.ResultsOf 2,575 patients approached, 2,301 (89%) agreed to participate; nine had missing data pertaining to the primary outcome, leaving 2,292 included in the final analysis. A total of 79% of respondents reported wearing masks "all of the time" and 96% reported wearing masks over half the time. Subjects with PCPs were more likely to report wearing masks over half the time compared to those without PCPs (97% vs 92%). Individuals experiencing homelessness were less likely to wear a mask over half the time compared to those who were housed (81% vs 96%).ConclusionsStudy participants reported high rates of facemask use. Respondents who did not have PCPs and those who were homeless were less likely to report wearing a mask over half the time and more likely to report barriers in obtaining masks. The ED may serve a critical role in education regarding, and provision of, masks for vulnerable populations.

Genetically regulated gene expression has helped elucidate the biological mechanisms underlying complex traits. Improved high-throughput technology allows similar interrogation of the genetically regulated proteome for understanding complex trait mechanisms. Here, we used the Trans-omics for Precision Medicine (TOPMed) Multi-omics pilot study, which comprises data from Multi-Ethnic Study of Atherosclerosis (MESA), to optimize genetic predictors of the plasma proteome for genetically regulated proteome-wide association studies (PWAS) in diverse populations. We built predictive models for protein abundances using data collected in TOPMed MESA, for which we have measured 1,305 proteins by a SOMAscan assay. We compared predictive models built via elastic net regression to models integrating posterior inclusion probabilities estimated by fine-mapping SNPs prior to elastic net. In order to investigate the transferability of predictive models across ancestries, we built protein prediction models in all four of the TOPMed MESA populations, African American (n = 183), Chinese (n = 71), European (n = 416), and Hispanic/Latino (n = 301), as well as in all populations combined. As expected, fine-mapping produced more significant protein prediction models, especially in African ancestries populations, potentially increasing opportunity for discovery. When we tested our TOPMed MESA models in the independent European INTERVAL study, fine-mapping improved cross-ancestries prediction for some proteins. Using GWAS summary statistics from the Population Architecture using Genomics and Epidemiology (PAGE) study, which comprises ∼50,000 Hispanic/Latinos, African Americans, Asians, Native Hawaiians, and Native Americans, we applied S-PrediXcan to perform PWAS for 28 complex traits. The most protein-trait associations were discovered, colocalized, and replicated in large independent GWAS using proteome prediction model training populations with similar ancestries to PAGE. At current training population sample sizes, performance between baseline and fine-mapped protein prediction models in PWAS was similar, highlighting the utility of elastic net. Our predictive models in diverse populations are publicly available for use in proteome mapping methods at https://doi.org/10.5281/zenodo.4837327.

IntroductionSitting on an unstable surface is a common paradigm to investigate trunk postural control among individuals with low back pain (LBP), by minimizing the influence lower extremities on balance control. Outcomes of many small studies are inconsistent (e.g., some find differences between groups while others do not), potentially due to confounding factors such as age, sex, body mass index [BMI], or clinical presentations. We conducted a systematic review with an individual participant data (IPD) meta-analysis to investigate whether trunk postural control differs between those with and without LBP, and whether the difference between groups is impacted by vision and potential confounding factors.MethodsWe completed this review according to PRISMA-IPD guidelines. The literature was screened (up to 7th September 2023) from five electronic databases: MEDLINE, CINAHL, Embase, Scopus, and Web of Science Core Collection. Outcome measures were extracted that describe unstable seat movements, specifically centre of pressure or seat angle. Our main analyses included: 1) a two-stage IPD meta-analysis to assess the difference between groups and their interaction with age, sex, BMI, and vision on trunk postural control; 2) and a two-stage IPD meta-regression to determine the effects of LBP clinical features (pain intensity, disability, pain catastrophizing, and fear-avoidance beliefs) on trunk postural control.ResultsForty studies (1,821 participants) were included for the descriptive analysis and 24 studies (1,050 participants) were included for the IPD analysis. IPD meta-analyses revealed three main findings: (a) trunk postural control was worse (higher root mean square displacement [RMSdispl], range, and long-term diffusion; lower mean power frequency) among individuals with than without LBP; (b) trunk postural control deteriorated more (higher RMSdispl, short- and long-term diffusion) among individuals with than without LBP when vision was removed; and (c) older age and higher BMI had greater adverse impacts on trunk postural control (higher short-term diffusion; longer time and distance coordinates of the critical point) among individuals with than without LBP. IPD meta-regressions indicated no associations between the limited LBP clinical features that could be considered and trunk postural control.ConclusionTrunk postural control appears to be inferior among individuals with LBP, which was indicated by increased seat movements and some evidence of trunk stiffening. These findings are likely explained by delayed or less accurate corrective responses.Systematic review registrationThis review has been registered in PROSPERO (registration number: CRD42021124658).

IntroductionChildren in boarding schools spend most of their time without their parents or caregivers, causing concerns about the suitability of such schools for children with asthma. This study assessed individuals' opinions regarding the suitability of boarding secondary schools for children with asthma.MethodsA qualitative design was adopted for this study using a focus group discussion held on a social media platform (WhatsApp®) of the Asthma Awareness and Care Group (AACG), The group comprised 150 registered members. The study was guided by a structured protocol and based on a vignette comprising three questions. Data were analysed via thematic analysis using framework principles.ResultsOut of the 150 eligible members, there were responses from only 19 participants. Majority of the respondents were aged ≤ 30 years (n = 17, 89.5%). The three main themes generated from the thematic analysis include the appropriateness of boarding schools for children with asthma; facilities necessary for boarding schools to cater to children with asthma; and outright rejection of children with asthma by boarding schools. Respondents conceptualised the appropriateness of boarding schools for students with asthma in six distinct sub-themes: asthma severity and extent of control, child's self-efficacy and assertiveness, child equipped with tools (knowledge, inhalers, and asthma control diary), school awareness, facilities, and active support, availability of a guardian, and the knowledge and perception of teachers and schoolmates about asthma. The sub-themes associated with the themes were presented, alongside exemplar quotes from respondents. The majority of the respondents (61.5%) were in support of allowing children with asthma attend boarding schools but with some caveats such as without liability to the school, if facilities are unavailable.ConclusionChildren's age, autonomy, asthma management status, and the school's readiness were identified as important considerations for the safe attendance of children with asthma at boarding schools.

BackgroundMild stroke affects more than half the stroke population, yet there is limited evidence characterizing cognition over time in this population, especially with predictive approaches applicable at the individual-level. We aimed to identify patterns of recovery and the best combination of demographic, clinical, and lifestyle factors predicting individual-level cognitive state at 3- and 12-months after mild stroke.MethodsIn this prospective cohort study, the Montreal Cognitive Assessment (MoCA) was administered at 3-7 days, 3- and 12-months post-stroke. Raw changes in MoCA and impairment rates (defined as MoCAResultsParticipants' (n = 119) MoCA scores improved from baseline to 3-months (pConclusionMore than half of mild-stroke survivors are at risk of cognitive decline one year after stroke, even when preceded by a significantly improving pattern in the first 3-months of recovery. Physical activity was the only modifiable factor independently associated with cognitive recovery. Individual-level prediction methods may inform the timing and personalized application of future interventions to maximize cognitive recovery post-stroke.

IntroductionIn Sub Saharan Africa, there is a growing burden of non-communicable diseases, which poses a big challenge to the resource-limited health system in these settings.ObjectiveThe aim of this study was to determine the feasibility and preliminary efficacy of a community health workers (CHWs) home-based lifestyle interventions to improve blood pressure (BP) control and body composition among hypertensive patients in low-income populations of Kiambu County, Kenya.MethodsThis was a randomized controlled trial (RCT) involving 80 patients with uncontrolled high BP (systolic BP (SBP) ≥140mmHg and/or diastolic BP (DBP) ≥90) randomized to either a CHW homebased intervention or a usual care (control) arm and followed up for 6 months. The intervention involved monthly CHW home-visits for health education and audits on behavioral risk factors that affect BP. An adapted WHO stepwise questionnaire and international physical activity questionnaire was used to collect data on behavioral cardiovascular risk factors. To assess the main outcomes of BP, body mass index (BMI) and waist-height-ratio (WHtR), a survey was conducted at baseline, 3 months, and 6 months. Data regarding univariate, bivariate and multivariate (repeated measurements between and within groups) analysis at 5% level of significance were analyzed using STATA 18. Generalized estimating equations (GEE) for repeated measures were used to estimate changes in BP, BMI and WHtR, and to examine the association between the CHW intervention and BP control.ResultsThe study revealed that 77.5% and 92.5% of the participants in usual care and intervention groups completed the follow-up, respectively. After 6 months of follow-up, there was a reduction in the mean SBP and DBP for both arms, and reductions in BMI and WHtR only in the intervention arm. The adjusted mean reduction in SBP (-8.4 mm Hg; 95% CI, -13.4 to -3.3; P = 0.001) and DBP (-5.2 mm Hg 95% CI, -8.3 to -2.0; PConclusionA home-based CHW intervention was significantly associated with reduction in BP among hypertensive patients compared to usual care. Future fully powered RCTs to test the effectiveness of such interventions among low-income populations are recommended.Trial registrationTrial registration number: PACTR202309530525257.

The production of triceps surae plantarflexion moment is complex in that the Achilles tendon moment arm affects the Achilles tendon force by determining the muscle length change and shortening velocity during ankle rotation. In addition, there is evidence for associations between the sizes of muscles and their moment arm at the joints they span. These relationships between muscle architecture and tendon moment arm ultimately affect the muscle's force generating capacity and are thus important for understanding the roles played by muscles in producing locomotion. The purpose of this study was to investigate in vivo the relationship between architecture of two plantarflexors and the Achilles tendon moment arm in a healthy adult population. Ultrasound-based measurements were made of the architecture (fascicle length, muscle volume, physiological cross-sectional area, and anatomical cross-sectional area) of the lateral and medial gastrocnemius and the Achilles tendon moment arm was assessed using a technique that combined ultrasound imaging and motion analysis. Positive correlations were observed between the length (r = 0.499, p = 0.049) and size variables (muscle volume r = 0.621, p = 0.010; ACSA r = 0.536, p = 0.032) of the lateral gastrocnemius and the Achilles tendon moment arm, but correlations were only observed for size variables (muscle volume r = 0.638, p = 0.008; PCSA r = 0.525, p = 0.037; ACSA r = 0.544, p = 0.029), and not the length, of the medial gastrocnemius. These findings suggest lateral gastrocnemius adapts to moment arms to maintain force production throughout the range of motion across individuals, while the medial gastrocnemius does not and is thus better suited for static force generation.

[This corrects the article DOI: 10.1371/journal.pone.0056134.].

IntroductionMuscles play a critical role in supporting joints during activities of daily living, owing, in part, to the phenomenon of short-range stiffness. Briefly, when an active muscle is lengthened, bound cross-bridges are stretched, yielding forces greater than what is predicted from the force length relationship. For this reason, short-range stiffness has been proposed as an attractive mechanism for providing joint stability. However, there has yet to be a forward dynamic simulation employing a cross-bridge model, that demonstrates this stabilizing role. Therefore, the purpose of this investigation was to test whether Huxley-type muscle elements, which exhibit short-range stiffness, can stabilize a joint while at constant activation.MethodsWe analyzed the stability of an inverted pendulum (moment of inertia: 2.7 kg m2) supported by Huxley-type muscle models that reproduce the short-range stiffness phenomenon. We calculated the muscle forces that would provide sufficient short-range stiffness to stabilize the system based in minimizing the potential energy. Simulations consisted of a 50 ms long, 5 Nm square-wave perturbation, with numerical simulations carried out in ArtiSynth.ResultsDespite the initial analysis predicting shared activity of antagonist and agonist muscles to maintain stable equilibrium, the inverted pendulum model was not stable, and did not maintain an upright posture even with fully activated muscles.Discussion & conclusionOur simulations suggested that short-range stiffness cannot be solely responsible for joint stability, even for modest perturbations. We argue that short-range stiffness cannot achieve stability because its dynamics do not behave like a typical spring. Instead, an alternative conceptual model for short-range stiffness is that of a Maxwell element (spring and damper in series), which can be obtained as a first-order approximation to the Huxley model. We postulate that the damping that results from short-range stiffness slows down the mechanical response and allows the central nervous system time to react and stabilize the joint. We speculate that other mechanisms, like reflexes or residual force enhancement/depression, may also play a role in joint stability. Joint stability is due to a combination of factors, and further research is needed to fully understand this complex system.

IntroductionResidents of rural regions may have higher and unique suicide risks. Newfoundland and Labrador (NL) is a Canadian province replete with rural regions. Despite an abundance of rural suicide research, heterogeneity in rural regions may preclude amalgamating findings to inform prevention efforts. Thus, exploring the unique needs of NL is needed. Importantly, health care providers (HCP) may afford unique perspectives on the suicide-related needs or concerns of rural life. We asked HCPs of residents of rural NL their perceived suicide risk factors, concerns, and needs for rural NL.MethodTwelve HCPs of rural residents of NL completed virtual semi-structured interviews. Interviews were analysed using reflexive thematic analysis [13,14].ResultsHCPs noted individual, psychological, social, and practical factors linked to rural-suicide risk and subsequent needs. Findings highlight the unique challenges of residing and providing health care in rural NL and inform prevention and intervention efforts.

Chimeric antigen receptor (CAR)-T cells have demonstrated clinical potential, but current receptors still need improvements to be successful against chronic HIV infection. In this study, we address some requirements of CAR motifs for strong surface expression of a novel anti-HIV CAR by evaluating important elements in the extracellular, hinge, and transmembrane (TM) domains. When combining a truncated CD4 extracellular domain and CD8α hinge/TM, the novel CAR did not express extracellularly but was detectable intracellularly. By shortening the CD8α hinge, CD4-CAR surface expression was partially recovered and addition of the LYC motif at the end of the CD8α TM fully recovered both intracellular and extracellular CAR expression. Mutation of LYC to TTA or TTC showed severe abrogation of CAR expression by flow cytometry and confocal microscopy. Additionally, we determined that CD4-CAR surface expression could be maximized by the removal of FQKAS motif at the junction of the extracellular domain and the hinge region. CD4-CAR surface expression also resulted in cytotoxic CAR T cell killing of HIV Env+ target cells. In this study, we identified elements that are crucial for optimal CAR surface expression, highlighting the need for structural analysis studies to establish fundamental guidelines of CAR designs.

BackgroundDiversiPrEP is a culturally-tailored PrEP program for LMSM offered in South Florida. DiversiPrEP navigates LMSM through their PrEP journey, including education, deciding if PrEP is relevant for them, payment, and accessing/maintaining PrEP use. DiversiPrEP includes five ERIC strategies (Increase Demand, Promote Adaptability, Alter Client Fees, Intervene with Clients to Enhance Uptake and Adherence, and Tailor Strategies).DescriptionPhotovoice was used to conduct five two-part focus groups with LMSM (n = 12) and Non-LMSM (n = 12). In the first session, trainers provided guidance on selecting and contextualizing photos to generate CFIR themes. Then, participants captured photos that embodied their lived experiences accessing PrEP. In the second session, using SHOWeD, participants discussed photos, identifiedhow photos relate to culturally relevant issues. Triangulation approaches compared/contrasted themes between LMSM and Non-LMSM.ResultsFive central themes emerged around barriers and facilitators to PrEP services: 1) the need for normalizing PrEP messages within the MSM community, 2) the need for normalizing PrEP messages outside the MSM community, 3) the need for expanding PrEP knowledge, 4) different motivations for using PrEP, and 5) the presence of structural barriers that limit PrEP access. This study compared similarities and differences of barriers and facilitators to PrEP use between Latino/a and non-Latino/a MSM. Similarities included the built environment (outer setting) as a barrier, the need for normalizing PrEP messaging within and outside of the MSM community, and the need to expand PrEP knowledge. Differences between Latino/a and non-Latino/a MSM were found in assessing the motivation and personal drivers (inner setting) for initiating PrEP associated with how participants viewed their responsibilities to self or others.ConclusionsPhotovoice with focus groups identified CFIR constructs that can guide the large-scale implementation of a client-centered PrEP service model with telehealth for both Latino/a and non-Latino/a MSM. Implementing client-centered accessible PrEP programs is an essential step to promoting sexual-health equity.

Azooxanthellate scleractinian corals, a group of species that lack a symbiotic relationship with dinoflagellates, are influenced by environmental variables at various scales. As the global commitment to sustainably manage ocean ecosystems and resources rises, there is a growing need to describe biodiversity trends in previously unsampled areas. Benthic invertebrate research in South Africa is a developing field, and many taxa in deep water environments remain inadequately characterized. Recently, the South African azooxanthellate scleractinian fauna was taxonomically reviewed, but their distributional correlations with physical parameters have not been studied. Here we aim to understand the biodiversity gradients of the South African azooxanthellate coral fauna by analysing the environmental correlates of museum samples. The associated coordinate data were georeferenced and depth obtained from a national bathymetric dataset, prior to undertaking a multivariate analysis. This analysis encompassed several steps, including the grouping of the longitude and depth data (environmental data), identifying families characteristic of the group variability, and examining the correlation of the associated data with the biological data. Additionally, the analysis involved quantifying diversity patterns along the environmental gradients. Overall, our results confirmed two longitudinal groups (eastern margin [Group A] vs southern and western margin [Group B]) and 11 depth categories represented within two bathymetric zones (shallow [50-200 m] and deep [300-1000 m]). Caryophylliids, flabellids, and dendrophylliids contributed the most towards distinguishing longitudinal and depth gradients. Both abiotic variable (longitudinal and depth) partially explained coral distribution patterns, with depth being highly correlated to the species variation observed. Data limitations within our data set resulted to unexplained variance, however, despite these limitations, the study demonstrates that historical museum samples provide a valuable data source that can fill research sampling gaps and help improve the understanding of biodiversity patterns of the coral fauna in under sampled marine ecosystems.

BackgroundElectrolytes (sodium, potassium, calcium, magnesium, chloride, phosphate) are required in specific amounts for proper functioning of the human body. Although the body has different organ systems, such as the kidneys, that regulate electrolyte levels in the blood, electrolyte abnormalities occur frequently in people with eating disorders. The objective of this review will be to examine the association between electrolyte imbalances and adverse outcomes in people with eating disorders.MethodsA systematic review of studies on eating and electrolyte disorders shall be conducted. Electronic searches shall be done in the Ovid MEDLINE, EMBASE, and PsycINFO databases. Selected studies shall include randomized control trials (RCTs), non-randomized controlled trials, and cross-sectional studies published in English or French. Quality appraisal of studies and a narrative synthesis of extracted data shall be conducted.DiscussionThis review will synthesize existing evidence on electrolyte abnormalities in people with eating disorders. It will identify the type of electrolyte imbalances, their impact, and outcomes in people with eating disorders. We anticipate that information that will be useful to policy makers and clinicians in designing better policies to prevent eating disorders and or manage people with eating disorders shall be elucidated in this study.DisseminationThe final manuscript will be submitted for publication in a journal.Review registrationThis protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO); registration number CRD42023477497.

BackgroundTuberculosis remains a significant global health concern, especially for People Living with HIV, who are at an increased risk of severe TB disease. Despite the availability of TB Preventive Treatment, knowledge gaps persist among People Living with HIV regarding its importance, accessibility, and administration. The study aimed to assess TPT knowledge levels and determinants among People Living with HIV in Tanzania.MethodsA cross-sectional survey was conducted from April to May 2023 in 12 regions of mainland Tanzania. The study included PLHIV aged 18 years and above, receiving HIV care in selected Care and Treatment Centers. Data were collected through face-to-face interviews using a semi-structured questionnaire covering sociodemographic characteristics and Tuberculosis preventive treatment knowledge. Descriptive statistics, chi-square tests, and logistic regression analyses were employed for data analysis.ResultsOut of the 391 People Living with HIV interviewed, 71.4% demonstrated adequate Tuberculosis preventive treatment knowledge. Female participants, those attending urban health facilities, and individuals with longer durations of HIV care exhibited higher Tuberculosis preventive treatment knowledge levels. However, knowledge disparities persisted based on demographic characteristics such as gender and location of health facilities.ConclusionWhile a considerable portion of People Living with HIV demonstrated adequate higher Tuberculosis preventive treatment knowledge, addressing gaps among those with lower understanding is crucial. Targeted education campaigns tailored to the needs of People Living with HIV, especially in rural areas and among male populations, are essential. Collaborative efforts between national health programs and community organizations are vital to integrate Tuberculosis preventive treatment awareness effectively into comprehensive HIV care programs, ultimately reducing the burden of Tuberculosis among People Living with HIV and the general population.

BackgroundIn May 2020, England implemented soft 'opt-out' or 'deemed consent' for deceased donation with the intention of raising consent rates. However, this coincided with the COVID-19 pandemic, making it difficult to assess the early impact of the law change. Wales and Scotland changed their organ donation legislation to implement soft opt-out systems in 2015 and 2021 respectively. This study provides a descriptive analysis of changes in consent and transplant rates for deceased organ donation in England, Scotland and Wales.MethodsLogistic regression and descriptive trend analysis were employed to assess the probability of a patient who died in critical care becoming a donor, and to report consent rates using data, respectively, from the Intensive Care National Audit and Research Centre (ICNARC) in England from 1 April 2014 to 30 September 2021, and from the Potential Donor Audit for England, Scotland and Wales from April 2010 to June 2023.ResultsThe number of eligible donors in April-June 2020 were 56.5%, 59.3% and 57.6% lower in England, Scotland and Wales relative to April-June 2019 (pre-pandemic). By April-June 2023, the number of eligible donors had recovered to 87.4%, 64.2% and 110.3%, respectively, of their levels in 2019. The consent rate in England, Scotland and Wales reduced from 68.3%, 63.0% and 63.6% in April-June 2019 to 63.2%, 60.5% and 56.3% in April-June 2023.ConclusionsWhile the UK organ donation system shows signs of recovery from the COVID-19 pandemic, the number of eligible potential donors and consent rates remain below their pre-pandemic levels.

BackgroundSurgical site infections (SSI) are a significant concern following traumatic brain injury (TBI) surgery and often stem from the skin's microbiota near the surgical site, allowing bacteria to penetrate deeper layers and potentially causing severe infections in the cranial cavity. This study investigated the relationship between scalp skin microbiota composition and the risk of SSI after TBI surgery in sub-Saharan Africa (SSA).MethodsThis was a prospective cohort study, enrolling patients scheduled for TBI surgery. Sterile skin swabs were taken from the surrounding normal skin of the head and stored for analysis at -80°Celcius. Patients were monitored postoperatively for up to three months to detect any occurrences of SSI. 16S rRNA sequencing was used to analyze the skin microbiota composition, identifying different taxonomic microorganisms at the genus level. The analysis compared two groups: those who developed SSI and those who did not.ResultsA total of 57 patients were included, mostly male (89.5%) with a mean age of 26.5 years, predominantly from urban areas in Uganda and victims of assault. Graphical visualization and metagenomic metrics analysis revealed differences in composition, richness, and evenness of skin microbiota within samples (α) or within the community (β), and showed specific taxa (phylum and genera) associated with either the group of SSI or the No SSI.ConclusionsMetagenomic sequencing analysis uncovered several baseline findings and trends regarding the skin microbiome's relationship with SSI risk. There is an association between scalp microbiota composition (abundancy and diversity) and SSI occurrence following TBI surgery in SSA. We hypothesize under reserve that the scalp microbiota dysbiosis could potentially be an independent predictor of the occurrence of SSI; we advocate for further studies with larger cohorts.

BackgroundA common complaint in older adults is trouble with their memory, especially for new information. Current knowledge about normal aging and changes in memory identify a divide between memory tasks that are unaffected by aging and those that are. Among the unaffected are recognition tasks. These memory tasks rely on accessing well-known information, often include environmental support, and tend to be automatic. Negative age effects on memory are often observed at both encoding and during recall. Older adults often have difficulty with recall tasks, particularly those that require effortful self-initiated processing, episodic memory, and retention of information about contextual cues. Research in memory for music in healthy aging suggests a skill-invariance hypothesis: that age effects dominate when general-purpose cognitive mechanisms are needed to perform the musical task at hand, while experience effects dominate when music-specific knowledge is needed to perform the task [1].AimsThe goals of this pair of studies were to investigate the effects of age and familiarity on musical memory in the context of real pieces of music, and to compare a live concert experimental setting with a lab-based experimental setting.MethodParticipants' task was to click a button (or press the spacebar) when they heard the target theme in three pieces of music. One was Mozart's Eine Kleine Nachtmusik and the others were original pieces commissioned for this study, one tonal and one atonal. Participants heard the relevant theme three times before listening to a piece of music. The music was performed by the Newfoundland Symphony Orchestra; participants either attended the concert, or watched a recording of the concert in the lab. Participants also completed two short cognitive tests and filled out a questionnaire collecting demographic information and a hearing abilities self-assessment.ResultsWe find a significant effect of familiarity and setting but not of age or musical training on recognition performance as measured by d'. More specifically, performance is best for the familiar, tonal piece, moderate for the unfamiliar tonal piece and worst for the unfamiliar atonal piece. Performance was better in the live setting than the lab setting.ConclusionsThe absence of an age effect provides encouraging evidence that music's diverse cues may encourage cognitive scaffolding, in turn improving encoding and subsequent recognition. Better performance in an ecological versus lab setting supports the expansion of ecological studies in the field.

IntroductionEach person having access to needed health services, of sufficient quality, and without suffering financial hardship, defined as universal health coverage (UHC) by the World Health Organization, is critical to improve population health, particularly for vulnerable populations. UHC requires multisectoral collaboration and good governance, and this will require buy-in of key stakeholders; but their views are under-documented. The aim of this stakeholder analysis was to explore the awareness and perceptions of UHC by health care workers (HCWs) in Uganda.MethodsA mixed-methods study was conducted based on primary data from HCWs including an online QualtricsXM survey of 274 HCWs (from a database of persons who had received training at an academic institution), 23 key informant semi-structured interviews, and one eight-person focus group discussion. Data was collected from February to April 2022. Microsoft Excel and R Programme were used for quantitative analyses and NVivo version 12 for qualitative analyses.ResultsHCWs attributed a high level of importance to UHC in Uganda. Participants discussed national communication and management practices, organisational roles, health financing and power dynamics, health care demand and the impact of and learnings from COVID-19. Four main themes-each with related sub-themes-emerged from the interview data providing insights into: (1) communication, (2) organisation, (3) power, and (4) trust.ConclusionThere is a critical need for better communication of UHC targets by policymakers to improve understanding at a grassroots level. Results indicated that ensuring trust among the population through transparency in metrics and budgets, strong accountability measures, awareness of local cultural sensitivities, sensitisation of the UHC concept and community inclusion will be essential for a multisectoral roll out of UHC. Further provision of quality health services, a harmonisation of efforts, increased domestic health financing and investment of HCWs through fair remuneration will need to underpin the delivery of UHC.

We analyzed COI barcode sequences from 138 over-a-century old specimens of Calinaga including 36 name-bearing type specimens stored at the Natural History Museum London. These new data, combined with previously available RPS5 sequences, divide the Calinaga samples into four well-supported mitochondrial lineages that together with a novel wing-pattern analysis, support the recognition of six species (lhatso, buddha, brahma, aborica, formosana and davidis), with all other names subsumed either as subspecies or synonyms. One new taxon is described, Calinaga aborica naima Vane-Wright, ssp. n.

BackgroundLine manager (LM) training in mental health is gaining recognition as an effective method for improving the mental health and wellbeing of workers. However, research predominantly focuses on the impacts of training at the employee-level, often neglecting the broader organisational-level outcomes. Most studies derive insights from LMs using self-reported data, with very few studies examining impacts on organisational-level outcomes.AimTo explore the relationship between LM training in mental health and organisational-level outcomes using company-level data from a diverse range of organisations.MethodsThis study is a secondary analysis of anonymised panel survey data from firms in England, with data derived from computer-assisted telephone surveys over four waves (2020, 1899 firms; 2021, 1551; 2022, 1904; and 2023, 1902). The analysis merged the four datasets to control for temporal variations. Probit regression was conducted including controls for age of organisation, sector, size, and wave to isolate specific relationships of interest.ResultsWe found that LM training in mental health is significantly associated with several organisational-level outcomes, including: improved staff recruitment (β = .317, p < .001) and retention (β = .453, p < .001), customer service (β = .453, p < .001), business performance (β = .349, p < .001), and lower long-term sickness absence due to mental ill-health (β = -.132, p < .05).ConclusionThis is the first study to explore the organisational-level outcomes of LM training in mental health in a large sample of organisations of different types, sizes, and sectors. Training LM in mental health is directly related to diverse aspects of an organisations' functioning and, therefore, has strategic business value for organisations. This knowledge has international relevance for policy and practice in workforce health and business performance.

BackgroundThis study evaluates primary care practices' engagement with various features of a quality improvement (QI) intervention for patients with coronary heart disease (CHD) in four Australian states.MethodsTwenty-seven practices participated in the QI intervention from November 2019 -November 2020. A combination of surveys, semi-structured interviews and other materials within the QUality improvement in primary care to prevent hospitalisations and improve Effectiveness and efficiency of care for people Living with heart disease (QUEL) study were used in the process evaluation. Data were summarised using descriptive statistical and thematic analyses for 26 practices.ResultsSixty-four practice team members and Primary Health Networks staff provided feedback, and nine of the 63 participants participated in the interviews. Seventy-eight percent (40/54) were either general practitioners or practice managers. Although 69% of the practices self-reported improvement in their management of heart disease, engagement with the intervention varied. Forty-two percent (11/26) of the practices attended five or more learning workshops, 69% (18/26) used Plan-Do-Study-Act cycles, and the median (Interquartile intervals) visits per practice to the online SharePoint site were 170 (146-252) visits. Qualitative data identified learning workshops and monthly feedback reports as the key features of the intervention.ConclusionPractice engagement in a multi-featured data-driven QI intervention was common, with learning workshops and monthly feedback reports identified as the most useful features. A better understanding of these features will help influence future implementation of similar interventions.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR) number ACTRN12619001790134.

Previous studies on crosslinguistic influence (CLI) on third language (L3) morphosyntactic acquisition have provided support for competing theories about the source(s) of CLI. The present study aimed to test if both L1 and L2 can be the source of CLI, and whether they influence L3 learning in similar or different ways. In particular, we aimed to add to our knowledge of the neural correlates of CLI by conducting an exploratory EEG study to investigate how L1 and L2 CLI affect L3 neural processing. Predictions based on the D/P model, which posited different memory systems sustaining L1 and L2, were tested. The findings confirmed both L1-sourced and L2-sourced facilitation on L3 morphosyntactic acquisition. Specifically, we suggest that L1-similarity showed a consolidating effect on L3 implicit knowledge and neurocognitive internalization, whereas L2-similarity contributed to enhanced L3 metalinguistic knowledge. This preliminary study is the first to investigate the neurocognitive mechanisms underlying CLI in L3 learning by natural language learners.

IntroductionPhysical disability represents a major burden to health and lifespan, particularly as the proportion of older adults within the United States is expected to grow. Prevention efforts for physical disability targets methods and strategies to decrease modifiable risk factors. Potential challenges for health professionals may exist in synthesizing and interpreting this broad spectrum of literature due to the discipline-specific nuance of language used, practice type or specialty, and lack of interdisciplinary resources. This scoping review will map and synthesize the literature across healthcare disciplines to identify modifiable risk factors and the evidence related to their ability to predict physical disability. We will also draw attention to the possibility of modifiable risk factors for physical disability being operationalized as pre-disability in order to strengthen primary and secondary prevention efforts.MethodsA planned search strategy using physical disability terminology will be searched in English across MEDLINE, CINAHL, Health Source, PEDro, and REHABDATA by two reviewers in line with our review objectives and inclusion criteria. Eligibility for inclusion include peer-reviewed primary research published in the English language and have established a relationship between a person-level measurable characteristic that is modifiable by changes in lifestyle behaviors and any of the commonly accepted terms used to categorize or describe physical disability.Expected resultsPresentation of results will be using the PRISMA flowchart, with additional mapping and synthesis of evidence for modifiable risk factors for physical disability to clarify divergent terms used in classifying and measuring these factors and their potential for prediction of physical disability.Expected conclusionIt is anticipated that this scoping review will identify and highlight a variety of modifiable risk factors for physical disability that may aid primary and secondary prevention efforts for health professionals.

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.

[This corrects the article DOI: 10.1371/journal.pone.0244109.].