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Objective: To assess whether women with a genetic predisposition to medical conditions known to increase pre‐eclampsia risk have an increased risk of pre‐eclampsia in pregnancy. Design: Case–control study. Setting and population: Pre‐eclampsia cases (n = 498) and controls (n = 1864) in women of European ancestry from five US sites genotyped on a cardiovascular gene‐centric array. Methods: Significant single‐nucleotide polymorphisms (SNPs) from 21 traits in seven disease categories (cardiovascular, inflammatory/autoimmune, insulin resistance, liver, obesity, renal and thrombophilia) with published genome‐wide association studies (GWAS) were used to create a genetic instrument for each trait. Multivariable logistic regression was used to test the association of each continuous scaled genetic instrument with pre‐eclampsia. Odds of pre‐eclampsia were compared across quartiles of the genetic instrument and evaluated for significance. Main outcome measures: Genetic predisposition to medical conditions and relationship with pre‐eclampsia. Results: An increasing burden of risk alleles for elevated diastolic blood pressure (DBP) and increased body mass index (BMI) were associated with an increased risk of pre‐eclampsia (DBP, overall OR 1.11, 95% CI 1.01–1.21, P = 0.025; BMI, OR 1.10, 95% CI 1.00–1.20, P = 0.042), whereas alleles associated with elevated alkaline phosphatase (ALP) were protective (OR 0.89, 95% CI 0.82–0.97, P = 0.008), driven primarily by pleiotropic effects of variants in the FADS gene region. The effect of DBP genetic loci was even greater in early‐onset pre‐eclampsia cases (at <34 weeks of gestation, OR 1.30, 95% CI 1.08–1.56, P = 0.005). For other traits, there was no evidence of an association. Conclusions: These results suggest that the underlying genetic architecture of pre‐eclampsia may be shared with other disorders, specifically hypertension and obesity. A genetic predisposition to increased diastolic blood pressure and obesity increases the risk of pre‐eclampsia. A genetic predisposition to increased diastolic blood pressure and obesity increases the risk of pre‐eclampsia. [ABSTRACT FROM AUTHOR]

Background: Latinos are a heterogeneous population in terms of demographics, culture, and genetic admixture from three racial groups (white, African, and Native American). This study examines the role of genetic ancestry and environmental risk factors in the risk of hypertensive disorder of pregnancy among Latinas in Los Angeles County.Methods: Gestational hypertension, preeclampsia, eclampsia, or hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome cases (n = 125), plus unaffected controls (n = 161), were recruited from Los Angeles County + University of Southern California Women's and Children's Hospital from 1999 through 2008. Diagnoses were confirmed with extensive chart review. Personal information, demographics, and biospecimens were collected from all participants. Ancestry informative markers were used to estimate genetic ancestry proportions.Results: After adjusting for European ancestry and key risk factors, African ancestry was positively associated with hypertensive disorders of pregnancy risk for the highest vs. the lowest quartiles of African ancestry (odds ratio = 2.6 [95% confidence interval = 1.1-6.1]). This association was stronger among women born in Mexico with parents born in Mexico (4.3 [1.4-13]). The results from generalized additive models showed a positive association between joint European/African ancestry and hypertensive disorders of pregnancy risk and an inverse association between Native American ancestry and risk. These associations were stronger among women of Mexican origin.Conclusion: Our findings suggest that higher Native American ancestry among Latinas may protect against hypertensive disorders of pregnancy. Further studies are needed to determine whether this protective effect is driven by specific alleles present in this population or by other risk factors that correlate with Native American ancestry. [ABSTRACT FROM AUTHOR]

Carbon fibre couch inserts are widely used in external beam radiotherapy to provide rigid and lightweight patient support. Carbon fibre is often perceived to be essentially radiotranslucent implying that it does not interfere with the radiation beam. However, there is evidence in the literature which suggests that this perception may not be appropriate, particularly at oblique angles of incidence. Furthermore, there is evidence indicating that the use of carbon fibre significantly reduces the skin sparing effect. In this study, the radiation attenuation and surface dose enhancement characteristics of the carbon fibre insert for the Varian ExactTM couch have been investigated. It was found that attenuation increased significantly with increasing angle of incidence, resulting in in-phantom dose reductions of up to 6% at 6 MV and 4% at 15 MV. It has been shown that it is possible to model couch attenuation on a commercial treatment planning system (Elekta CMS XiO) by including the carbon fibre insert in the planning computed tomography (CT) dataset. Finally, the carbon fibre insert was found to significantly increase skin dose to the patient. The skin dose was approximately three times as large when the couch insert was added to 6 and 15 MV photon beams. However, even with this substantial increase it is highly unlikely that the skin tolerance dose will be exceeded. [ABSTRACT FROM PUBLISHER]

OBJECTIVES: We compared 3 methods for classifying methicillin-resistant Staphylococcus aureus (MRSA) infections as health care associated or community associated for use in public health surveillance. METHODS: We analyzed data on MRSA infections reported to the Michigan Department of Community Health from October 1, 2004, to December 31, 2005. Patient demographics, risk factors, infection information, and susceptibility were collected for 2151 cases. We classified each case by the health care risk factor, infection-type, and susceptibility pattern methods and compared the results of the 3 methods. RESULTS: Demographic, clinical, and microbiological variables yielded similar health care-associated and community-associated distributions when classified by risk factor and infection type. When 2 methods yielded the same classifications, the overall distribution was similar to classification by 3 methods. No specific combination of 2 methods was superior. CONCLUSIONS: MRSA categorization by 2 methods is more accurate than it is by a single method. The health care risk factor and infection-type methods yield comparable classification results. Accuracy is increased by using more variables; however, further research is needed to identify the optimal combination. [ABSTRACT FROM AUTHOR]

Objective: In previous studies, we have shown a three to four times higher urban incidence of breast cancer and estrogen receptor-positive breast cancers in the Gharbiah Province of Egypt. We investigated the urban-rural incidence differences of gynaecologic malignancies (uterine, ovarian and cervical cancers) to explore if they show the same trend that we found for breast cancer.Design: Cancer registry-based incidence comparison.Setting: Gharbiah population-based cancer registry (GPCR), Tanta, Egypt.Sample: All patients with uterine, ovarian and cervical cancer in GPCR from 1999 to 2002.Methods: We calculated uterine, ovarian and cervical cancer incidence from 1999 to 2002. For each of the three cancers, we calculated the overall and age-specific rates for the province as a whole, and by urban-rural status, as well as for the eight districts of the province.Results: Incidence of all three cancer sites was higher in urban than in rural areas. Uterine cancer showed the highest urban-rural incidence rate ratio (IRR = 6.07, 95% CI = 4.17, 8.85). Uterine cancer also showed the highest urban incidence in the oldest age group (70+ age category, IRR = 14.39, 95% CI = 4.24, 48.87) and in developed districts (Tanta, IRR = 4.14, 95% CI = 0.41, 42.04). Incidence rates by groups of cancer sites showed an increasing gradient of urban incidence for cancers related to hormonal aetiology, mainly of the breast and uterus (IRR = 4.96, 95% CI = 2.86, 8.61).Conclusions: The higher urban incidence of uterine cancer, coupled with our previous findings of higher incidence of breast cancer and estrogen receptor positive breast cancer in urban areas in this region, may be suggestive of possible higher exposure to environmental estrogenic compounds, such as xenoestrogens, in urban areas. [ABSTRACT FROM AUTHOR]

Objective: To identify risk factors for uncomplicated malaria in highland areas of East Africa at higher risk of malaria epidemics, in order to design appropriate interventions.Methods: Prospective, population-based, case-control study in the Nandi Hills, a highland area of western Kenya, to identify environmental, sociodemographic and behavioural factors associated with clinical malaria. Data were collected using field observation, a structured questionnaire, and a global positioning system device.Results: We interviewed 488 cases of slide-confirmed malaria and 980 age-matched controls. Multivariate analyses associated higher malaria risk with living <250 m of a forest [OR = 3.3 (95% CI 1.5, 7.1)], <250 m of a swamp [2.8 (1.3, 5.9)], <200 m of maize fields [2.0 (1.2, 3.4)], in the absence of trees <200 m [1.6 (1.2, 2.2)], on flat land [1.6 (1.2, 2.2)], in houses without ceilings [1.5 (1.1, 2.2)], in houses with a separate kitchen building [1.8 (1.4, 2.3)] and in households where the female household head had no education [1.9 (1.1, 3.1)]. Travelling out of the study site [2.2 (1.2, 4.1)] was also associated with increased risk. CONCLUSIONS; In this East African highland area, risk of developing uncomplicated malaria was multifactorial with a risk factor profile similar to that in endemic regions. Households within close proximity to forest and swamp borders are at higher risk of malaria and should be included in indoor residual spraying campaigns. [ABSTRACT FROM AUTHOR]

The regular seasonality of influenza in temperate countries is recognized, but regional differences in patterns of influenza-related mortality are poorly understood. Identifying patterns could improve epidemic prediction and prevention. The authors analyzed the monthly percentage of deaths attributable to pneumonia and influenza among people aged 65 or more years in the contiguous United States, 1968-1998. The local Moran's I test for spatial autocorrelation and correlograms assessing space-time synchrony within each influenza season were applied to detect and to characterize mortality patterns. Western US regions experienced epidemics of greater magnitude than did eastern regions. Positive spatial autocorrelation (two-sided p = 0.001) revealed the similarity in influenza mortality of neighboring states, with several western states forming a focus of high mortality. In transmission seasons dominated by virus subtype A(H3N2), mortality was correlated at a high and consistent level across the United States (mean correlation = 0.56, standard deviation = 0.134). However, when subtype A(H1N1) or type B dominated, the average synchrony was lower (mean correlation = 0.23, standard deviation = 0.058). These novel analyses suggest that causes of spatial heterogeneity (e.g., large-scale environmental drivers and population movement) have impacted influenza-associated mortality. [ABSTRACT FROM AUTHOR]

Electronic health records (EHRs) are a cost-saving and environmentally friendly means for documenting patient care and improving patient safety, quality, and evidence-based practice. Standardized clinical classification systems and terminologies are essential ingredients of the EHR. Their selection must be driven by a clear understanding of requirements for their use and application. This article describes the principle uses of clinical information and motives for consistency in practice, and provides a distinction between classification systems and reference terminologies for clinical settings. [ABSTRACT FROM AUTHOR]

We present MacKenzie, a HPC-driven multi-cluster workflow system that was used repeatedly to configure and execute fine-grained US national-scale epidemic simulation models during the COVID-19 pandemic. Mackenzie supported federal and Virginia policymakers, in real-time, for a large number of "what-if" scenarios during the COVID-19 pandemic, and continues to be used to answer related questions as COVID-19 transitions to the endemic stage of the disease. MacKenzie is a novel HPC meta-scheduler that can execute US-scale simulation models and associated workflows that typically present significant big data challenges. The meta-scheduler optimizes the total execution time of simulations in the workflow, and helps improve overall human productivity. As an exemplar of the kind of studies that can be conducted using Mackenzie, we present a modeling study to understand the impact of vaccine-acceptance in controlling the spread of COVID-19 in the US. We use a 288 million node synthetic social contact network (digital twin) spanning all 50 US states plus Washington DC, comprised of 3300 counties, with 12 billion daily interactions. The highly-resolved agent-based model used for the epidemic simulations uses realistic information about disease progression, vaccine uptake, production schedules, acceptance trends, prevalence, and social distancing guidelines. Computational experiments show that, for the simulation workload discussed above, MacKenzie is able to scale up well to 10K CPU cores. Our modeling results show that, when compared to faster and accelerating vaccinations, slower vaccination rates due to vaccine hesitancy cause averted infections to drop from 6.7M to 4.5M, and averted total deaths to drop from 39.4K to 28.2K across the US. This occurs despite the fact that the final vaccine coverage is the same in both scenarios. We also find that if vaccine acceptance could be increased by 10% in all states, averted infections could be increased from 4.5M to 4.7M (a 4.4% improvement) and total averted deaths could be increased from 28.2K to 29.9K (a 6% improvement) nationwide., Competing Interests: Parantapa Bhattacharya reports financial support was provided by Centers for Disease Control and Prevention. Parantapa Bhattacharya reports financial support was provided by Virginia Department of Health. Parantapa Bhattacharya reports financial support was provided by National Science Foundation. Parantapa Bhattacharya reports financial support was provided by National Institutes of Health.

Purpose: Hypertensive disorders of pregnancy cause significant neonatal complications. Disease severity is often used to predict neonatal outcomes, however gestational age (GA) at delivery may be a better predictor. We aimed to assess whether disease severity or GA was more predictive of adverse neonatal outcomes., Methods: We included 165 participants with confirmed HELLP syndrome or severe preeclampsia (sPE). Two predictive models were constructed to assess the ability of disease severity compared to GA to predict a composite adverse neonatal outcome. The composite outcome included low birth weight, SGA, IUGR, Apgar score, and neonatal death., Results: Using severity as a predictor of binary neonatal outcome had an AUC of 0.73 (0.65-0.81), with a sensitivity (SE) of 70.3% and a specificity (SP) of 64.4%. For GA, we observed an AUC of 0.82 (0.75-0.89), with a SE of 75.7% and a SP of 76.7%., Conclusion: For the composite neonatal outcome, GA was a better predictor than ACOG diagnosis (severity). This observation underscores the need for further research to validate these findings in larger cohorts and to determine their applicability to maternal outcomes., (© 2024. The Author(s).)

Adolescent suicide is a major public health concern, particularly among adolescents who have endured Adverse Childhood Experiences (ACEs). Adolescents who have been exposed to multiple ACEs are as much as three times more likely to present with suicidality compared to the general adolescent population. Adolescents who have been exposed to multiple ACEs are also more likely to receive behavioral and mental health services in the community. It is therefore important to understand patterns of suicidality among this sub-population of adolescents in order to provide the best clinical care. The present study examined the temporal patterns of suicidality among adolescents who have been exposed to multiple ACEs and are receiving behavioral and mental health services in the community. Using Electronic Health Record (EHR) data from a community-based behavioral and mental health care organization, an exploratory survival analysis was conducted on time to suicidal thoughts and behaviors (STBs) after suicidality risk screen at intake. Average time from suicidality risk screen at intake to STB was 185 days (6.2 months). Youth who screened negative for suicidality risk at intake had a longer survival time than youth who screened positive for suicidality risk, and the survival distributions between the two groups was significant. Predictors of STBs were also examined, with gender being a significant predictor of an STB occurring during the follow-up period. These findings may be used to guide suicidality screening and clinical practice at community-based behavioral and mental health care organizations serving adolescents who have been exposed to multiple ACEs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Context: Postprandial lipemia (PPL) is associated with increased risk of endothelial dysfunction (ED), a precursor of atherosclerotic cardiovascular disease (ASCVD). The effects of low-carbohydrate, high-fat (LCHF) diets on ASCVD risk are uncertain; therefore, gaining a greater understanding of LCHF meals on PPL may provide valuable insights., Objective: The current systematic review investigated the effects of single LCHF meal consumption on PPL and markers of ED., Data Sources: CINAHL Plus, PubMed, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for key terms related to endothelial function, cardiovascular disease, glycemia, lipemia, and the postprandial state with no restriction on date., Data Extraction: Full-text articles were independently screened by 2 reviewers, of which 16 studies were eligible to be included in the current review. All trials reported a minimum analysis of postprandial triglycerides (PPTG) following consumption of an LCHF meal (<26% of energy as carbohydrate). Results were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement., Data Analysis: Single-meal macronutrient composition was found to play a key role in determining postprandial lipid and lipoprotein responses up to 8 hours post-meal. Consumption of LCHF meals increased PPTG and may contribute to ED via reduced flow-mediated dilation and increased oxidative stress; however, energy and macronutrient composition varied considerably between studies., Conclusion: Consumption of an LCHF meal had a negative impact on PPL based on some, but not all, single-meal studies; therefore, the contribution of LCHF meals to cardiometabolic health outcomes remains unclear. Further research is needed on specific categories of LCHF diets to establish a causal relationship between postprandial modulation of lipids/lipoproteins and impaired vascular endothelial function., Systematic Review Registration: PROSPERO registration no. CRD 42023398774., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Life Sciences Institute.)

Objective: To evaluate the impact of screening and treating asymptomatic pregnant women for Chlamydia (C.) trachomatis and Neisseria (N.) gonorrhoeae infections on the frequency of preterm birth or low birthweight infants in Botswana., Design: Non-randomised, cluster-controlled trial., Setting: Four antenatal care clinics in Gaborone, Botswana., Population: Pregnant women aged ≥15 years, attending a first antenatal care visit, ≤27 weeks of gestation and without urogenital symptoms were eligible., Methods: Participants in the intervention clinics received screening (GeneXpert®, Cepheid) during pregnancy and at the postnatal visit. Participants in the standard-of-care clinics received screening at the postnatal visit only. We used multivariable logistic regression and post-estimation predictive margins analysis. Post-hoc analysis was conducted among sub-samples stratified by parity., Main Outcome Measures: Preterm birth (<37 weeks of gestation) and low birthweight (<2500 g)., Results: After controlling for parity, hypertension, antenatal care visits and clinic site, the predicted prevalence of preterm birth or low birthweight was lower in the intervention arm (11%) compared with the standard-of-care arm (16%) (adjusted odds ratio [aOR] 0.59; 95% confidence interval [CI] 0.28-1.24). In post-hoc analysis, the intervention was more effective than the standard-of-care (aOR 0.20; 95% CI 0.07-0.64) among nulliparous participants., Conclusion: A C. trachomatis and N. gonorrhoeae infection screening and treatment intervention among asymptomatic pregnant women may have reduced preterm birth or low birthweight outcomes, but results were not statistically significant. Post-hoc analysis found that the intervention reduced adverse outcomes among nulliparous participants., (© 2024 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Introduction: Mortality due to injuries disproportionately impact low income countries. Knowledge of who is at risk of poor outcomes is critical to guide resource allocation and prioritization of severely injured. Kampala Trauma Score (KTS), developed in 1996 and last modified in 2002 as KTS II, is still widely being used to predict injury outcomes in resource-limited settings with no further revisions in the past two decades, despite ongoing criticism of some of its parameters. The New Trauma Score (NTS), a recent development in 2017, has shown potential in mortality prediction, but a dearth of evidence exist regarding its performance in the African population., Objectives: To compare NTS to the modified Kampala Trauma Score (KTS II) in the prediction of 30-day mortality, and injury severity amongst patients sustaining road traffic crashes in Ugandan low-resource settings., Methods: Multi-center prospective cohort study of patients aged 15 years and above. Of the 194 participants, 85.1% were males with a mean age of 31.7 years. NTS and KTS II were determined for each participant within 30-minutes of admission and followed-up for 30 days to determine their injury outcomes. The sensitivity, specificity, and area under receiver operating characteristics curve (AUC) for predicting mortality were compared between the two trauma scores using SPSS version 22. Ethical clearance: Research and Ethics Committee of Kampala International University Western Campus (Ref No: KIU-2022-125)., Results: The injury severity classifications based on NTS vs. KTS II were mild (55.7% vs. 25.8%), moderate (29.9% vs. 30.4%), and severe (14.4% vs. 43.8%). The mortality rates for each injury severity category based on NTS vs. KTS II were mild (0.9% v 0%), moderate (20.7% vs. 5.1%), and severe (50% vs. 28.2%). The AUC was 0.87 for NTS (95% CI 0.808-0.931) vs. 0.86 (95% CI 0.794-0.919) for KTS II respectively. The sensitivity of NTS vs. KTS II in predicting mortality was 92.6% (95% CI: 88.9-96.3) vs. 70.4% (95% CI: 63.0-77.8) while the specificity was 70.7% (95% CI: 64.2-77.2) vs. 78.4% (95% CI: 72.1-84.7) at cut off points of 17 for NTS and 6 for KTS II respectively., Conclusions: NTS was more sensitive but its specificity for purposes of 30-day mortality prediction was lower compared to KTS II. Thus, in low-resourced trauma environment where time constraints and pulse oximeters are of concern, KTS II remains superior to NTS., (© 2024. The Author(s).)

Accurate and timely interpretation of microcytic anemia can be diagnostically challenging in the primary care setting. We sought to develop a novel model for distinguishing iron-deficiency anemia from thalassemia trait in the modern pediatric population. Demographic history and red blood cell indices were retrospectively characterized for 76 children referred to our pediatric hematology clinic for evaluation of microcytic anemia. Statistically significant variables were sequentially added into a logistic regression model to develop the final model. The final discriminating model incorporates red cell distribution width, mean corpuscular hemoglobin concentration, and red blood cell values. Favorable predictive performance is seen in the initial (sensitivity 89.2%, specificity 92.3%) and external validation cohort (sensitivity 84.4%, specificity 88.9%). This novel tool may aid in determining the cause of hypochromic, microcytic anemia in the primary care setting. Finally, the study cohort reflects an underrepresented group in the development of screening tools, and thus offers generalizability., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Reproductive success relies on proper establishment and maintenance of biological sex. In many animals, including mammals, the primary gonad is initially ovary biased. We previously showed the RNA binding protein (RNAbp), Rbpms2, is required for ovary fate in zebrafish. Here, we identified Rbpms2 targets in oocytes (Rbpms2-bound oocyte RNAs; rboRNAs). We identify Rbpms2 as a translational regulator of rboRNAs, which include testis factors and ribosome biogenesis factors. Further, genetic analyses indicate that Rbpms2 promotes nucleolar amplification via the mTorc1 signaling pathway, specifically through the mTorc1-activating Gap activity towards Rags 2 (Gator2) component, Missing oocyte (Mios). Cumulatively, our findings indicate that early gonocytes are in a dual poised, bipotential state in which Rbpms2 acts as a binary fate-switch. Specifically, Rbpms2 represses testis factors and promotes oocyte factors to promote oocyte progression through an essential Gator2-mediated checkpoint, thereby integrating regulation of sexual differentiation factors and nutritional availability pathways in zebrafish oogenesis., (© 2024. The Author(s).)

Introduction: Treatment of vestibular schwannoma (VS) has been extensively studied, but a gap in knowledge exists demonstrating how racial and socioeconomic status influence VS presentation. Our institution has a unique setting with a public safety net hospital (PSNH) and tertiary academic medical center (TAMC) in the same zip code, which we study to evaluate initial VS presentation disparities in patient populations presenting to these hospital settings., Methods: Retrospective chart review was performed of all adult patients (n = 531) presenting 2010 to 2020 for initial VS evaluation at TAMC (n = 462) and PSNH (n = 69). Ethnicity, insurance, maximum tumor size, audiometry, initial treatment recommendation, treatment received, and follow up were recorded and statistical analysis performed to determine differences., Results: Average age at diagnosis (51.7 ± 13.6 TAMC vs 52.3 ± 12.4 PSNH) and gender (58.4% TAMC vs 52.2% PSNH female) were similar. Patients' insurance (TAMC 75.9% privately insured vs PSNH 82% Medicaid) and racial/ethnic profiles (TAMC 67.7% White and 10.0% Hispanic/Latinx, vs PSNH 4.8% White but 59.7% Hispanic/Latinx) were significantly different. Tumor size was larger at PSNH (20.2 ± 13.3 mm) than TAMC (16.6 ± 10.0 mm). Hearing was more impaired at PSNH than TAMC (mean pure tone average 58.3 dB vs 43.9 dB, word recognition scores 52.3% vs 68.2%, respectively). Initial treatment recommendations and treatment received may include more than 1 modality. TAMC patients were offered 66.7% surgery, 31.2% observation, and 5.2% radiation, while PSNH patients offered 50.7% observation, 49.3% surgery, and 8.7% radiation. TAMC patients received 62.9% surgery, 32.5% observation, and 5.3% radiation, while PSNH patients received 36.2% surgery, 59.4% observation, and 14.5% radiation. Follow up and treatment at the same facility was not significantly different between hospitals., Conclusions: Hearing was worse and tumor size larger in patients presenting to PSNH. Despite worse hearing status and larger tumor size, the majority of PSNH patients were initially offered observation, compared to TAMC where most patients were initially offered surgery., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Scenario-based modeling frameworks have been widely used to support policy-making at state and federal levels in the United States during the COVID-19 response. While custom-built models can be used to support one-off studies, sustained updates to projections under changing pandemic conditions requires a robust, integrated, and adaptive framework. In this paper, we describe one such framework, UVA-adaptive, that was built to support the CDC-aligned Scenario Modeling Hub (SMH) across multiple rounds, as well as weekly/biweekly projections to Virginia Department of Health (VDH) and US Department of Defense during the COVID-19 response. Building upon an existing metapopulation framework, PatchSim, UVA-adaptive uses a calibration mechanism relying on adjustable effective transmissibility as a basis for scenario definition while also incorporating real-time datasets on case incidence, seroprevalence, variant characteristics, and vaccine uptake. Through the pandemic, our framework evolved by incorporating available data sources and was extended to capture complexities of multiple strains and heterogeneous immunity of the population. Here we present the version of the model that was used for the recent projections for SMH and VDH, describe the calibration and projection framework, and demonstrate that the calibrated transmissibility correlates with the evolution of the pathogen as well as associated societal dynamics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Injury is a global health concern, and injury-related mortality disproportionately impacts low- and middle-income countries (LMICs). Compelling evidence from observational studies in high-income countries shows that trauma education programs, such as the Rural Trauma Team Development Course (RTTDC), increase clinician knowledge of injury care. There is a dearth of such evidence from controlled clinical trials to demonstrate the effect of the RTTDC on process and patient outcomes in LMICs., Objective: This multicenter cluster randomized controlled clinical trial aims to examine the impact of the RTTDC on process and patient outcomes associated with motorcycle accident-related injuries in an African low-resource setting., Methods: This is a 2-arm, parallel, multi-period, cluster randomized, controlled, clinical trial in Uganda, where rural trauma team development training is not routinely conducted. We will recruit regional referral hospitals and include patients with motorcycle accident-related injuries, interns, medical trainees, and road traffic law enforcement professionals. The intervention group (RTTDC) and control group (standard care) will include 3 hospitals each. The primary outcomes will be the interval from the accident to hospital admission and the interval from the referral decision to hospital discharge. The secondary outcomes will be all-cause mortality and morbidity associated with neurological and orthopedic injuries at 90 days after injury. All outcomes will be measured as final values. We will compare baseline characteristics and outcomes at both individual and cluster levels between the intervention and control groups. We will use mixed effects regression models to report any absolute or relative differences along with 95% CIs. We will perform subgroup analyses to evaluate and control confounding due to injury mechanisms and injury severity. We will establish a motorcycle trauma outcome (MOTOR) registry in consultation with community traffic police., Results: The trial was approved on August 27, 2019. The actual recruitment of the first patient participant began on September 01, 2019. The last follow-up was on August 27, 2023. Posttrial care, including linkage to clinical, social support, and referral services, is to be completed by November 27, 2023. Data analyses will be performed in Spring 2024, and the results are expected to be published in Autumn 2024., Conclusions: This trial will unveil how a locally contextualized rural trauma team development program impacts organizational efficiency in a continent challenged with limited infrastructure and human resources. Moreover, this trial will uncover how rural trauma team coordination impacts clinical outcomes, such as mortality and morbidity associated with neurological and orthopedic injuries, which are the key targets for strengthening trauma systems in LMICs where prehospital care is in the early stage. Our results could inform the design, implementation, and scalability of future rural trauma teams and trauma education programs in LMICs., Trial Registration: Pan African Clinical Trials Registry (PACTR202308851460352); https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=25763., International Registered Report Identifier (irrid): DERR1-10.2196/55297., (©Herman Lule, Micheal Mugerwa, Robinson Ssebuufu, Patrick Kyamanywa, Till Bärnighausen, Jussi P Posti, Michael Lowery Wilson. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 07.05.2024.)

Researchers investigating the evolution of human aggression look to our closest living relatives, bonobos (Pan paniscus) and chimpanzees (Pan troglodytes), as valuable sources of comparative data. 1 , 2 Males in the two species exhibit contrasting patterns: male chimpanzees sexually coerce females 3 , 4 , 5 , 6 , 7 , 8 and sometimes kill conspecifics, 9 , 10 , 11 , 12 whereas male bonobos exhibit less sexual coercion 13 , 14 and no reported killing. 13 Among the various attempts to explain these species differences, the self-domestication hypothesis proposes negative fitness consequences of male aggression in bonobos. 2 , 15 , 16 Nonetheless, the extent to which these species differ in overall rates of aggression remains unclear due to insufficiently comparable observation methods. 17 , 18 , 19 , 20 , 21 , 22 , 23 We used 14 community-years of focal follow data-the gold standard for observational studies 24 -to compare rates of male aggression in 3 bonobo communities at the Kokolopori Bonobo Reserve, Democratic Republic of Congo, and 2 chimpanzee communities at Gombe National Park, Tanzania. As expected, given that females commonly outrank males, we found that bonobos exhibited lower rates of male-female aggression and higher rates of female-male aggression than chimpanzees. Surprisingly, we found higher rates of male-male aggression among bonobos than chimpanzees even when limiting analyses to contact aggression. In both species, more aggressive males obtained higher mating success. Although our findings indicate that the frequency of male-male aggression does not parallel species difference in its intensity, they support the view that contrary to male chimpanzees, whose reproductive success depends on strong coalitions, male bonobos have more individualistic reproductive strategies. 25 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The metabolic engineering of microbes has broad applications, including biomanufacturing, bioprocessing, and environmental remediation. The introduction of a complex, multistep pathway often imposes a substantial metabolic burden on the host cell, restraining the accumulation of productive biomass and limiting pathway efficiency. One strategy to alleviate metabolic burden is the division of labor (DOL) in which different subpopulations carry out different parts of the pathway and work together to convert a substrate into a final product. However, the maintenance of different engineered subpopulations is challenging due to competition and convoluted interstrain population dynamics. Through modeling, we show that dynamic division of labor (DDOL), which we define as the DOL between indiscrete populations capable of dynamic and reversible interchange, can overcome these limitations and enable the robust maintenance of burdensome, multistep pathways. We propose that DDOL can be mediated by horizontal gene transfer (HGT) and use plasmid genomics to uncover evidence that DDOL is a strategy utilized by natural microbial communities. Our work suggests that bioengineers can harness HGT to stabilize synthetic metabolic pathways in microbial communities, enabling the development of robust engineered systems for deployment in a variety of contexts.