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BackgroundPopulation size estimates (PSEs) for hidden populations at increased risk of HIV, including female sex workers (FSWs), are important to inform public health policy and resource allocation. The service multiplier method (SMM) is commonly used to estimate the sizes of hidden populations. We used this method to obtain PSEs for FSWs at 9 sites in Zimbabwe and explored methods for assessing potential biases that could arise in using this approach. ObjectiveThis study aimed to guide the assessment of biases that arise when estimating the population sizes of hidden populations using the SMM combined with respondent-driven sampling (RDS) surveys. MethodsWe conducted RDS surveys at 9 sites in late 2013, where the Sisters with a Voice program (the program), which collects program visit data of FSWs, was also present. Using the SMM, we obtained PSEs for FSWs at each site by dividing the number of FSWs who attended the program, based on program records, by the RDS-II weighted proportion of FSWs who reported attending this program in the previous 6 months in the RDS surveys. Both the RDS weighting and SMM make a number of assumptions, potentially leading to biases if the assumptions are not met. To test these assumptions, we used convergence and bottleneck plots to assess seed dependence of RDS-II proportion estimates, chi-square tests to assess if there was an association between the characteristics of FSWs and their knowledge of program existence, and logistic regression to compare the characteristics of FSWs attending the program with those recruited to RDS surveys. ResultsThe PSEs ranged from 194 (95% CI 62-325) to 805 (95% CI 456-1142) across 9 sites from May to November 2013. The 95% CIs for the majority of sites were wide. In some sites, the RDS-II proportion of women who reported program use in the RDS surveys may have been influenced by the characteristics of selected seeds, and we also observed bottlenecks in some sites. There was no evidence of association between characteristics of FSWs and knowledge of program existence, and in the majority of sites, there was no evidence that the characteristics of the populations differed between RDS and program data. ConclusionsWe used a series of rigorous methods to explore potential biases in our PSEs. We were able to identify the biases and their potential direction, but we could not determine the ultimate direction of these biases in our PSEs. We have evidence that the PSEs in most sites may be biased and a suggestion that the bias is toward underestimation, and this should be considered if the PSEs are to be used. These tests for bias should be included when undertaking population size estimation using the SMM combined with RDS surveys.

How human genetic variation contributes to vaccine effectiveness in infants is unclear, and data are limited on these relationships in populations with African ancestries. We undertook genetic analyses of vaccine antibody responses in infants from Uganda (n = 1391), Burkina Faso (n = 353) and South Africa (n = 755), identifying associations between human leukocyte antigen (HLA) and antibody response for five of eight tested antigens spanning pertussis, diphtheria and hepatitis B vaccines. In addition, through HLA typing 1,702 individuals from 11 populations of African ancestry derived predominantly from the 1000 Genomes Project, we constructed an imputation resource, fine-mapping class II HLA-DR and DQ associations explaining up to 10% of antibody response variance in our infant cohorts. We observed differences in the genetic architecture of pertussis antibody response between the cohorts with African ancestries and an independent cohort with European ancestry, but found no in silico evidence of differences in HLA peptide binding affinity or breadth. Using immune cell expression quantitative trait loci datasets derived from African-ancestry samples from the 1000 Genomes Project, we found evidence of differential HLA-DRB1 expression correlating with inferred protection from pertussis following vaccination. This work suggests that HLA-DRB1 expression may play a role in vaccine response and should be considered alongside peptide selection to improve vaccine design.

Malaria and iron deficiency (ID) are common and interrelated public health problems in African children. Observational data suggest that interrupting malaria transmission reduces the prevalence of ID1. To test the hypothesis that malaria might cause ID, we used sickle cell trait (HbAS, rs334 ), a genetic variant that confers specific protection against malaria2, as an instrumental variable in Mendelian randomization analyses. HbAS was associated with a 30% reduction in ID among children living in malaria-endemic countries in Africa (n = 7,453), but not among individuals living in malaria-free areas (n = 3,818). Genetically predicted malaria risk was associated with an odds ratio of 2.65 for ID per unit increase in the log incidence rate of malaria. This suggests that an intervention that halves the risk of malaria episodes would reduce the prevalence of ID in African children by 49%.

Student enrollments in online college courses have grown steadily over the past decade, and college administrators expect this trend to continue or accelerate. Despite the growing popularity of online education, one major critique in the sciences is that students are not trained in the hands-on skills they may need for the workforce, graduate school, or professional school. For example, the Association of American Medical Colleges has recommended that medical schools evaluate applicants on their motor skills and observation skills, yet many online biology programs do not offer opportunities for students to develop these skills. In on-campus biology programs, students commonly develop these skills through hands-on animal dissections, but educators have struggled with how to teach dissections in an online environment. We designed a fully online undergraduate biology course that includes at-home, hands-on dissections of eight vertebrate specimens. Over three course offerings, we evaluated changes in four student outcomes: anatomical self-efficacy, confidence in laboratory skills, perceptions of support, and concerns about dissections. Here, we describe how we implemented at-home dissections in the online course and show that students taking the course gained anatomical self-efficacy and confidence in multiple laboratory skills. Based on open-ended responses, the students perceived that their experiences with the at-home dissections facilitated these gains. These results demonstrate that at-home, hands-on laboratories are a viable approach for teaching practical skills to students in fully online courses. We encourage science instructors to introduce at-home laboratories into their online courses, and we provide recommendations for instructors interested in implementing at-home laboratories.

I. INTRODUCTION 343 II. OVERVIEW OF COMMUNITY COLLEGES & THEIR ROLE IN 344 ECONOMIC MOBILITY A. Who Attends Community Colleges--Demographics of 345 Community College Students B. Community College as a [...], Community colleges have the potential to be a powerful force to alleviate poverty in the United States. However, the persistent underfunding of community colleges inhibits their ability to meet the aspiration of economic mobility for all students as they serve students who have more significant needs with fewer resources than public or private four-year institutions of higher education. The challenges faced by community colleges mirror the circumstances faced by many K-12 schools in low-income communities and communities of color in the United States where limited school funding has contributed to inequitable access to opportunity and inhibited student outcomes. However, unlike the community college context, decades of litigation and strategic advocacy have contributed to improvements in K-12 school funding. This Note argues that key lessons from the K-12 school funding litigation can be applied to the community college context to both increase funding available to community colleges and improve the funding pipeline so that it better accounts for the unique needs in the community college context. This would be achieved through a dual-pronged strategy. The first prong centers on litigation advancing the argument that states have a constitutional obligation to adequately fund community colleges. The second prong requires political advocacy at the state and federal levels. By taking a multi-pronged approach advancing both litigation and advocacy efforts, those seeking to achieve more adequate community college funding amplify their power and reach. Community colleges have the ability to promote economic mobility and alleviate poverty. Through collective legal and advocacy efforts, this potential can be realized.

Background: Environmental enteric dysfunction (EED) is an acquired subclinical condition of the small intestine with lasting health implications for nutritional status, linear growth and development among children. EED is characterised by structural and functional changes to the gut barrier. There are no standardised diagnostic criteria, however, a number of biomarkers have been evaluated to capture EED domains. While the causes of EED are not fully understood, risk factors include poor water, sanitation and hygiene conditions and exposure to enteric pathogens. Very few studies have evaluated the impact of schistosomiasis on EED despite repeated intestinal damage from parasite eggs passing across the gut barrier. Methods: In a cohort of 354 preschool‐aged children aged 12–47 months with Schistosoma mansoni infection recruited from the Lake Albert region of Uganda, we assessed exposure to water, sanitation and hygiene conditions and measured markers from each EED domain: intestinal inflammation (faecal calprotectin), epithelial damage (serum intestinal fatty‐acid binding‐protein), increased permeability (urine lactulose to mannitol ratio and faecal alpha‐1 antitrypsin) and microbial translocation (serum endotoxin core antibody). Results: In multivariable linear regression models, we found that children whose drinking water was sourced from Lake Albert had higher concentrations of intestinal fatty‐acid binding‐protein (β = 0.48, 95% CI 0.20–0.76, p < 0.001), and lack of toilet/latrine access was associated with higher concentrations of calprotectin (β = 0.48, 95% CI 0.18–0.78, p < 0.01). Higher schistosomiasis intensity (eggs per gram of stool) was associated with higher calprotectin (β = 0.10, 95% CI 0.02–0.17, p = 0.01), but not with other EED markers. Conclusions: Few studies have investigated schistosomiasis‐related morbidities in very young children infected with schistosomiasis. Our findings from Uganda show that poor water, sanitation and hygiene conditions and heavier schistosomiasis burden are associated with intestinal inflammation and damage, contributing to EED. Improved treatment coverage for preschool‐aged children infected with schistosomiasis may reduce the burden from EED and associated long‐term morbidities. [ABSTRACT FROM AUTHOR]

It is widely regarded that the anti-tumour immune response drives clearance of tumours and leads to prolonged survival in patients. However, tumours are adept at reprogramming the surrounding microenvironment to an immunosuppressive milieu to prevent successful immune directed killing. Adhesion of cells to the extracellular matrix is essential for regulating cellular processes such as survival, proliferation and migration. This adhesion is largely conducted via integrins and their related intracellular signalling networks. Adhesion proteins such as focal adhesion kinase (FAK) are expressed in both tumour cells and cells of the surrounding microenvironment, and are often dysregulated in cancers. Recent work has demonstrated that adhesion proteins are contributing to regulation of the immunosuppressive microenvironment within tumours, and could provide a new avenue to target in combination with immunotherapies. Here, we provide an overview of the effort being made to elucidate the roles adhesion proteins play in modulating anti-tumour responses within a variety of cancer settings. In particular we focus on the multi-faceted role of FAK within the tumour immune microenvironment. Finally, we summarise the data in clinical trials, where targeting FAK is being exploited to prime the tumour microenvironment and create potent responses when combined with immunotherapies. [ABSTRACT FROM AUTHOR]

Global attention on early child development, inclusive of those with disability, has the potential to translate into improved action for the millions of children with developmental disability living in low- and middle-income countries. Nurturing care is crucial for all children, arguably even more so for children with developmental disability. A high proportion of survivors of neonatal conditions such as prematurity and neonatal encephalopathy are affected by early child developmental disability. The first thousand days of life is a critical period for neuroplasticity and an important window of opportunity for interventions, which maximize developmental potential and other outcomes. Since 2010, our group has been examining predictors, outcomes, and experiences of neonatal encephalopathy in Uganda. The need for an early child intervention program to maximize participation and improve the quality of life for children and families became apparent. In response, the "ABAaNA early intervention program," (now re-branding as 'Baby Ubuntu') a group participatory early intervention program for young children with developmental disability and their families, was developed and piloted. Piloting has provided early evidence of feasibility, acceptability, and impact and a feasibility trial is underway. Future research aims to develop programmatic capacity across diverse settings and evaluate its impact at scale.

PURPOSE:Integrated interventional radiology (IR) residencies recently underwent their second year in the match, the first year of which involved only a limited number of programs. Now that students can choose to enter IR directly, student perceptions of IR vs diagnostic radiology (DR) are of paramount importance. METHODS:We surveyed first- through fourth-year medical students and radiology residents regarding interest in IR vs DR. RESULTS:Students considering a radiological career expressed more interest in IR than DR. Conversely, residents expressed more interest in DR. CONCLUSIONS:Medical student advisors and IR programs should continue to anticipate a high number of applications for integrated IR positions.

Rationale and Objectives We aimed to assess the impact of our institution's recently created point-of-care ultrasound (POCUS) course for preclinical medical students by examining its effect on first–year-level medical knowledge, self-reported skill level, and beliefs regarding the importance of ultrasound in future clinical practice. Materials and Methods A total of 18 first-year medical students completed a 5-month near–peer-led training program in POCUS consisting of 3-hour teaching sessions (7), 4-hour clinical sessions (10–12), and an independent study. Students completed pre- and postprogram assessments examining (1) student perceptions about ultrasound and its importance to future careers, (2) students' self-reported skill level with ultrasound, and (3) performance on an anatomy and physiology knowledge quiz. Scores and responses were compared to 20 controls. Results The majority of students believed that ultrasound was useful for learning anatomy and would be important in their future clinical practice. Students who completed our training program tended to perform better than controls on a test of medical knowledge. Despite reporting far fewer hours of formal ultrasound training, control students rated their skill level comparably to POCUS-trained students. Conclusions This study provides evidence that ultrasound is well received by medical students and may be useful for teaching basic anatomy concepts.

Rationale and objectivesRadiology expertise is dependent on the use of efficient search strategies. The aim of this study is to investigate the effect of teaching search strategies on trainee's accuracy in detecting lung nodules at computed tomography.Materials and methodsTwo search strategies, "scanning" and "drilling," were tested with a randomized crossover design. Nineteen junior radiology residents were randomized into two groups. Both groups first completed a baseline lung nodule detection test allowing a free search strategy, followed by a test after scanning instruction and drilling instruction or vice versa. True positive (TP) and false positive (FP) scores and scroll behavior were registered. A mixed-design analysis of variance was applied to compare the three search conditions.ResultsSearch strategy instruction had a significant effect on scroll behavior, F(1.3) = 54.2, P

Introduction: Tight junctions (TJs) serve as permeability filters between the internal and external cellular environment. A large number of proteins have been identified to be localized at the TJs. Due to limitations in tissue collection, TJs in the male genital tract have been understudied. Methods: We analysed the transcriptomics of 132 TJ genes in foreskin tissue of men requesting voluntary medical male circumcision (VMMC) and enrolled in the Combined HIV Adolescent Prevention Study (CHAPS) trial conducted in South Africa and Uganda (NCT03986970). The trial evaluated the dose requirements for event-driven HIV pre-exposure prophylaxis (PrEP) with emtricitabine-tenofovir (FTC-TDF) or emtricitabine-tenofovir alafenamide (FTC-TAF) during insertive sex. A total of 144 participants were randomized to either control arm or one of 8 PrEP arms (n=16/arm), receiving oral FTC-TDF or FTC-TAF over one or two days. Following in vivo oral PrEP dosing and VMMC, the expression level of three important TJ proteins (CLDN-1, OCN and ZO-1) was measured ex vivo in foreskin tissue by Western blot. The expression of cytokine genes implicated in TJ regulation was determined. Non-parametric Kruskal-Wallis tests were used to compare TJ gene expression and protein levels by type of PrEP received, and Spearman's correlation coefficients were calculated to assess whether TJ gene expression levels were related to cytokine gene levels or to PrEP drug concentrations and their active intracellularly phosphorylated metabolites. Results: A high level of expression in foreskin tissue was found for 118 (of 132) TJ genes analysed; this finding contributed to create a map of TJ components within the male genital tract. Importantly, PrEP regimens tested in the CHAPS trial did not affect the expression of TJ genes and the analysed proteins in the foreskin; thus, further supporting the safety of this prevention strategy against HIV-1 transmission during insertive sex. Additionally, we identified the level of several cytokines' genes to be correlated to TJ gene expression: among them, IL-18, IL-33 and VEGF. Discussion: TJs can limit viral entry into target cells; to affect this biological function viruses can reduce the expression of TJ proteins. Our study, on the expression and regulation of TJs in the foreskin, contribute important knowledge for PrEP safety and further design of HIV-1 prophylaxis. [ABSTRACT FROM AUTHOR]

Chikungunya virus (CHIKV) and Mayaro virus (MAYV) are emerging/re‐emerging alphaviruses transmitted by Aedes spp. mosquitoes and responsible for recent disease outbreaks in the Americas. The capacity of these viruses to cause epidemics is frequently associated with increased mosquito transmission, which in turn is governed by virus−host−vector interactions. Although many studies have explored virus−vector interactions, significant gaps remain in understanding how vertebrate host factors influence alphavirus transmission by mosquitoes. We previously showed that obesity, a ubiquitous vertebrate host biological factor, reduces alphavirus transmission potential in mosquitoes. We hypothesized that alphavirus‐infected obese bloodmeals altered immune genes and/or pathways in mosquitoes, thereby inhibiting virus transmission. To test this, we conducted RNA sequencing (RNA‐seq) and reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) on midgut RNA from mosquitoes fed on alphavirus‐infected lean and obese mice. This approach aimed to identify potential antiviral or proviral genes and pathways altered in mosquitoes after consuming infected obese bloodmeals. We found upregulation of the Toll pathway and downregulation of several metabolic and other genes in mosquitoes fed on alphavirus‐infected obese bloodmeals. Through gene knockdown studies, we demonstrated the antiviral role of Toll pathway and proviral roles of AAEL009965 and fatty acid synthase (FASN) in the transmission of alphaviruses by mosquitoes. Therefore, this study utilized obesity to identify factors influencing alphavirus transmission by mosquitoes and this research approach may pave the way for designing broadly effective antiviral measures to combat mosquito‐borne viruses, such as releasing transgenic mosquitoes deficient in the identified genes. [ABSTRACT FROM AUTHOR]

Vaccine efficacy varies globally, often showing reduced immune responses in low‐ and middle‐income countries, possibly due to the immunomodulatory effects of parasitic infections like malaria. This systematic review evaluates the impact of malaria on immune responses to unrelated vaccines in humans and animals. We systematically searched five databases—MEDLINE, Web of Science, Global Health, Scopus and Embase—up to 5th December 2023. Eligible studies compared immune responses to WHO‐approved vaccines between malaria‐infected and uninfected groups, or between antimalarial‐treated and untreated groups. Meta‐analysis was performed using random‐effects models with standardised mean differences (SMDs) as summary statistics. The study is registered with PROSPERO (CRD42022298053). Twenty‐four articles (17 human, 7 animal) met the inclusion criteria, with 13 human articles contributing data for the meta‐analysis. Significant heterogeneity was observed. Vaccine responses were higher in malaria uninfected individuals (SMD 0.34, 95% CI 0.07 to 0.60, I2 = 87.15%) with weaker differences between antimalarial‐treated and untreated groups (SMD 0.07, 95% CI −0.01 to 0.16, I2 = 85.01%). The overall SMD for malaria uninfected/treated vs. infected/untreated was 0.15, 95% CI 0.05–0.26, I2 = 90.91. Narrative analysis suggested malaria's adverse impact on vaccine responses in animals. Malaria infection may impair vaccines responses; with preventive treatment of malaria partially reversing these effects, highlighting the need for targeted public health interventions. [ABSTRACT FROM AUTHOR]

Background: Variations in vaccine responses have been observed between populations. A role for helminth infections has been proposed due to their immunomodulatory properties. In a secondary analysis of data from a randomised trial assessing effects of anthelminthic treatment on vaccine responses, we examined associations between helminth infections at baseline prior to vaccine administration, and vaccine responses among adolescents (9-17 years) in Koome Islands, Lake Victoria, Uganda. Methods: Participants received BCG [week 0], yellow fever (YF-17D), oral typhoid (Ty21a), HPV-prime [week 4], and HPV-boost, tetanus/diphtheria [week 28]. Outcomes were BCG-specific interferon-g ELISpot responses and antibody responses to yellow-fever-, typhoid-, HPV-, tetanus- and diphtheria-specific antigens measured at two time points post vaccination. S. mansoni infection was determined as positive if either the plasma Circulating Anodic Antigen (CAA) assay or stool PCR were positive. Hookworm and Strongyloides were determined by stool PCR. Linear mixed effects regression was used to assess associations. Results: Among 478 adolescents, 70% were Schistosoma mansoni (Sm) infected and 23% hookworm infected at baseline. Sm was associated with lower Salmonella Typhi O:LPS-specific IgG responses (adjusted geometric mean ratio (aGMR) 0.69 (0.57-0.83)), and hookworm with higher diphtheria-specific IgG (aGMR 1.16 (1.02, 1.31)) and lower HPV-16-specific IgG (aGMR 0.70 (0.55, 0.90)) post-vaccination. High Sm intensity was associated with lower BCG-specific interferon-g and S. Typhi O:LPS-specific IgG. Conclusions: We found inverse associations between Sm and responses to two live vaccines, whereas hookworm was positively associated with diphtheriaspecific IgG. These findings support the hypothesis that helminth infections can modulate vaccine responses, while also highlighting potential heterogeneity in the direction of these effects. [ABSTRACT FROM AUTHOR]

BackgroundGames with educational intent offer a possible advantage of being more interactive and increasing learner satisfaction.ObjectiveWe conducted a two-armed experiment to evaluate student satisfaction and content mastery for an introductory pediatric radiology topic, taught by either an interactive digital game or with a traditional didactic lecture.Materials and methodsMedical students participating in a fourth-year radiology elective were invited to participate. Student cohorts were alternatively given a faculty-supervised 1h session playing a simple interactive digital Tic-tac-toe quiz module on pediatric gastrointestinal radiology or a 1h didactic introductory lecture on the same topic. Survey questions assessed the learners' perceived ability to recall the material as well as their satisfaction with the educational experience. Results of an end-of-rotation exam were reviewed to evaluate a quantitative measure of learning between groups. Survey responses were analyzed with a chi-squared test. Exam results for both groups were analyzed with a paired Student's t-test.ResultsStudents in the lecture group had higher test scores compared to students in the game group (4.0/5 versus 3.6/5, P = 0.045). Students in the lecture group reported greater understanding and recall of the material than students in the game group (P