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Abstract Digital decision support and remote patient monitoring may improve outcomes and efficiency, but rarely scale beyond a single institution. Over the last 5 years, the platform Timely Interventions for Diabetes Excellence (TIDE) has been associated with reduced care provider screen time and improved, equitable type 1 diabetes care and outcomes for 268 patients in a heterogeneous population as part of the Teamwork, Targets, Technology, and Tight Control (4T) Study (NCT03968055, NCT04336969). Previous efforts to deploy TIDE at other institutions continue to face delays. In partnership with the diabetes technology non-profit, Tidepool, we developed Tidepool-TIDE, a clinic-agnostic, turnkey solution available to any clinic in the United States. We present how we overcame common technical and operational barriers specific to scaling digital health technology from one site to many. The concepts described are broadly applicable for institutions interested in facilitating broader adoption of digital technology for population-level management of chronic health conditions.

Abstract Background We report the impact of HIV infection within a household on oral Kaposi’s sarcoma-associated herpesvirus (KSHV) shedding. Methods We enrolled 469 individuals from 90 households. Mouthwash rinse samples collected at three monthly visits were analyzed for KSHV DNA using quantitative polymerase chain reaction (qPCR). Generalized linear mixed effects logistic models were applied to analyze factors associated with KSHV ever shedding, and among shedders, always versus intermittent shedding. Linear mixed effects models were applied to models of KSHV viral loads. Intraclass correlation coefficients (ICCs) were calculated to assess the contribution of household-level factors to variations in shedding probabilities. Hotspot analyses of geospatial feature clusters were calculated using Getis-Ord Gi* statistic and visualized using inverse distance weighted interpolation. Results Analyses included 340 KSHV seropositive individuals, aged 3 + years, with qPCR results from 89 households. Forty households had 1 + persons living with HIV (PLWH), while 49 had none. Among participants, 149(44%) were KSHV ever shedders. Of 140 who shed KSHV at two or more visits, 34(24%) were always shedders. Increasing number of KSHV seropositive household members was significantly associated with ever shedding [Odds ratio(OR) (95% Confidence Interval(95%CI)):1.14(1.03,1.26);p = 0.013]. Among KSHV shedders, a statistically significant age-related trend was identified with 10–19 years being more likely to be always shedders (type III test p = 0.039) and to have higher viral loads (type III test p = 0.027). In addition, higher viral loads were significantly associated with increasing number of household members [coefficient(95%CI):0.06(0.01,0.12);p = 0.042], increasing number of KSHV seropositive members [coefficient(95%CI):0.08(0.01,0.15);p = 0.021], and living in households with 1 + PLWH [coefficient(95%CI):0.51(0.04,0.98);p = 0.033]. Always shedders exhibited higher viral loads than intermittent shedders [coefficient(95%CI):1.62(1.19,2.05);p

Abstract Background Describe trends in perpetrator characteristics and firearm use in pediatric homicides across the United States. Methods Multiply-imputed data from the Federal Bureau of Investigation’s 1976–2020 Supplementary Homicide Reports were used to estimate perpetrator characteristics (sex, age, and relationship to victim) and firearm use in pediatric homicides. Descriptive analyses were stratified by victim age group, sex, race, and five-year time periods. Results Family members were the most common perpetrator of infant and toddler (ages 0–4) and child (ages 5–12) homicides, whereas acquaintances accounted for the majority of adolescent (ages 13–19) homicides. Perpetrator characteristics vary across victim sex and race, particularly among adolescents. Despite overall stability, there were changes in perpetrator characteristics from 1976 to 2020. There was a sustained increase in the proportion of homicides committed with a firearm. In 2016–2020, the proportion of firearm-involved homicides was an all-time high for infant and toddler (14.8%), child (53.1%), and adolescent victims (88.5%). Conclusions Policy interventions that improve family stability and well-being may be most effective at preventing infant, toddler, and child homicides, whereas programs that target peer and community relationships, as well as policies that focus on firearm access, may be more crucial for preventing adolescent homicides.

Birmingham City University (BCU) has responded proactively to the evolving landscape of generative artificial intelligence (GenAI) in higher education by creating written guidance and workshops for staff and students. This initiative addresses prevalent concerns surrounding AI in education and is rooted in a sector report assessing the positions of higher education institutions (HEIs) and offering guidance on effective integration of GenAI use in teaching and assessment. Our project carries several impactful aspects, including written guidance and workshops for staff and students, which reflects BCU’s dedication to addressing common concerns surrounding GenAI in education. Furthermore, the multi-agency collaborative approach brings diverse perspectives to the table. The different perspectives enable us to tailor our learner development offer through knowledge of curriculum and assessment in a particular discipline and whether that discipline is more susceptible to GenAI use than others. The insights from learner developers in creating student guidelines ensure the project is attuned to the needs and concerns of the student body, promoting a student-centred approach. This session focused on an institutional take on GenAI through the collaborative development of staff and student guidance at BCU. The presentation outlined the new AI staff and student guidance project and discussed how effective integration of GenAI education has been implemented at BCU. It also noted positive influences of GenAI through our new staff and student workshops which bring together existing and new knowledge around academic integrity and assessment literacy. Finally, it highlighted next steps around AI integration for the Education Development Service at BCU.

This qualitative sub-study investigated household practices affecting orally shed infections using Kaposi’s sarcoma-associated herpesvirus (KSHV) as a focus. Participants enrolled from 50 households in rural south-western Uganda were followed monthly up to three times. At enrolment, in-depth interviews were completed, and venous blood collected. KSHV seropositivity was defined as anti-KSHV antibody detection to any of 25 antigens by multiplex bead-based assay. Mouthwash samples from every visit were tested by qPCR and KSHV shedders defined as individuals with KSHV DNA detected. At least one KSHV seropositive person was in 48/49(98%) households. Among those, 79% had 1+ KSHV shedders including 45% with 1+ always shedders and 92% with 1+ intermittent shedders, not mutually exclusively. All respondents reported feeding infants with pre-masticated hard food/fruits and testing food/tea temperature. Temperature was tested by tasting, pouring tea on their hand, or touching the cup to their cheek. Some cooled food/tea using a utensil or blowing over it. Food sharing amongst children and adults and using the same dish was common practice. To treat colic pain, carers/mothers reported chewing herbs and spitting into the child’s mouth. Feeding and treatment practices did not vary by KSHV status. We identified potential KSHV transmission modes in rural Ugandan households.

This article considers the intersection between two major themes in university policy: the improvement of participation by rural and regional communities and the dimension of graduate employability. It argues that work-integrated learning has the potential to address both themes, but that the development of an apprenticeship model for prestige degrees such as law may deliver additional benefits to rural and regional student engagement. It considers a radical approach to employability by the reintroduction of the apprenticeship approach in disciplines of law and accounting specifically to assist scaffolding of learning for rural and regional students. It considers the modern context of university education and the implications of an expanded university system for delivering employability skills. The expansion of university education has not delivered consistent improvements in participation among rural and regional populations, and it is hypothesised that the visible integration of work-integrated learning has the capacity to address this deficit. However, it is argued that these measures should be supplemented by an innovative program of modern apprenticeships in prestige degrees; such a program could address both participation and employability outcomes. The article contributes to the literature by making explicit the links between the visibility of prestige occupational pathways to rural and regional students, the affective concerns of potential students making the choice to undertake higher education, and the scaffolding of skills and knowledge. It recommends further research in the form of a pilot integration of an apprenticeship model within a university program, but notes the current funding, discipline, and systemic barriers to this process in the current university system in Australia.

Abstract Background Previous studies show increased morbidity in children who are HIV-exposed but uninfected (HEU) compared to children who are HIV-unexposed uninfected (HUU). We sought to evaluate the effects of prenatal HIV exposure on clinical and immunological outcomes in the first 24 months of life. Methods Eighty-five HEU and 168 HUU children from Kenya were followed from birth to 24 months. All mothers living with HIV received combination antiretroviral therapy. Children who were HEU received standard-of-care cotrimoxazole prophylaxis through 18 months. Episodes of acute illness were identified through a combination of active and passive follow up. Trajectories of plasma cytokines, vaccine-specific antibodies, and antimalarial antibodies were examined. Results Children who were HEU and children who were HUU had similar growth curves. Children who were HEU had lower rates of malaria (rate ratio 0.54, 95% CI 0.38, 0.77) and respiratory illness (rate ratio 0.80, 95% CI 0.68, 0.93). Trajectories of plasma cytokines and vaccine-specific antibodies were similar in children who were HEU and HUU. There were subtle differences in antimalarial antibody dynamics, in which children who were HEU had overall lower antibody levels against five of the 14 malaria antigens tested. Conclusions Children who were HEU and born to optimally treated mothers living with HIV had similar growth characteristics and immune profiles compared to children who were HUU. Children who were HEU had reduced risk for malaria and respiratory illness, which may be secondary to cotrimoxazole prophylaxis.

School attendance zone boundary (AZB) data remain relatively underdocumented and understudied within the field of education, despite their critical implications for educational (in)equity. AZBs shape student outcomes and residential sorting patterns both by determining the public schools a student is assigned to and by signaling neighborhood characteristics to prospective homebuyers. The limited access, regulation, and review of AZB data to date has left a gap in the knowledge base, having the potential to leave intact (and exacerbate) patterns of segregation that maintain inequities in educational opportunity. Lack of data also limits our ability to know whether and when AZBs may mitigate segregation. In this brief, we examine a novel data collection effort of current and historical AZB data--the Longitudinal School Attendance Boundary System--to explore the contextual and political factors associated with data access and data quality. We aim to show how factors that hinder access to quality AZB data affect the study of educational equity, and we advocate for more comprehensive, top-down governmental efforts to create, maintain, and collect these data.

AimsIndividuals with lipodystrophies typically suffer from metabolic disease linked to adipose tissue dysfunction including lipoatrophic diabetes. In the most severe forms of lipodystrophy, congenital generalised lipodystrophy, adipose tissue may be almost entirely absent. Better therapies for affected individuals are urgently needed. Here we performed the first detailed investigation of the effects of a glucagon like peptide-1 receptor (GLP-1R) agonist in lipoatrophic diabetes, using mice with generalised lipodystrophy.MethodsLipodystrophic insulin resistant and glucose intolerant seipin knockout mice were treated with the GLP-1R agonist liraglutide either acutely preceding analyses of insulin and glucose tolerance or chronically prior to metabolic phenotyping and ex vivo studies.ResultsAcute liraglutide treatment significantly improved insulin, glucose and pyruvate tolerance. Once daily injection of seipin knockout mice with liraglutide for 14 days led to significant improvements in hepatomegaly associated with steatosis and reduced markers of liver fibrosis. Moreover, liraglutide enhanced insulin secretion in response to glucose challenge with concomitantly improved glucose control.ConclusionsGLP-1R agonist liraglutide significantly improved lipoatrophic diabetes and hepatic steatosis in mice with generalised lipodystrophy. This provides important insights regarding the benefits of GLP-1R agonists for treating lipodystrophy, informing more widespread use to improve the health of individuals with this condition.

BackgroundTo determine the pattern of immune cell subsets across the life span in rural sub-Saharan Africa (SSA), and to set a reference standard for cell subsets amongst Africans, we characterised the major immune cell subsets in peripheral blood including T cells, B cells, monocytes, NK cells, neutrophils and eosinophils, in individuals aged 3 to 89 years from Uganda.MethodsImmune phenotypes were measured using both conventional flow cytometry in 72 individuals, and full spectrum flow cytometry in 80 individuals. Epstein-Barr virus (EBV) IFN-γ T cell responses were quantified in 332 individuals using an ELISpot assay. Full blood counts of all study participants were also obtained.ResultsThe percentages of central memory (TCM) and senescent CD4+ and CD8+ T cell subsets, effector memory (TEM) CD8+ T cells and neutrophils increased with increasing age. On the other hand, the percentages of naïve T (TN) and B (BN) cells, atypical B cells (BA), total lymphocytes, eosinophils and basophils decreased with increasing age. There was no change in CD4+ or CD8+ T effector memory RA (TEMRA) cells, exhausted T cells, NK cells and monocytes with age. Higher eosinophil and basophil percentages were observed in males compared to females. T cell function as measured by IFN-γ responses to EBV increased with increasing age, peaking at 31-55 years.ConclusionThe percentages of cell subsets differ between individuals from SSA compared to those elsewhere, perhaps reflecting a different antigenic milieu. These results serve as a reference for normal values in this population.

Abstract Background Epstein–Barr virus (EBV) infection is ubiquitous and in sub-Saharan Africa, occurs early in life. In a population-based rural African cohort, we leveraged historical samples from the General Population Cohort (GPC) in Uganda to examine the epidemiology of infection with EBV over time, in the era of HIV. Methods We used 9024 serum samples collected from the GPC in 1992, 2000, 2008, from 7576 participants across the age range (0–99 years of age) and tested for anti-EBV immunoglobulin G (IgG) antibodies to EAd, VCA, and EBNA-1 using a multiplex bead-based assay. The related gammaherpesvirus, Kaposi’s sarcoma-associated herpesvirus (KSHV) seropositivity was also determined by detection of anti-KSHV IgG antibodies to K8.1 or ORF73 measured by recombinant protein enzyme-linked immunosorbent assay. Data on sex, age, and HIV serostatus were also collected. EBV seropositivity was modeled with age (excluding those under one year, who may have had maternal antibodies), sex, HIV serostatus, and KSHV serostatus using generalized linear mixed effects models to produce beta estimates. Results More than 93% of children were EBV seropositive by one year of age. EBV seropositivity was significantly associated with KSHV seropositivity. Anti-EBNA-1 antibody levels decreased with increasing age and were lower on average in people living with HIV. In general, anti-EAd antibody levels increased with age, were higher in males and KSHV seropositive persons, but decreased over calendar time. Anti-VCA antibody levels increased with age and with calendar time and were higher in KSHV seropositive persons but lower in males. Conclusions This is the first study to identify factors associated with EBV antibodies across the entire life-course in rural sub-Saharan Africa. Consistent with other studies, EBV was near ubiquitous in the population by age one year. Patterns of antibodies show changes by age, sex and calendar time, but no association with HIV was evident, suggesting no relationship between EBV sero-epidemiology and the spread of HIV in the population over time in Uganda.

Abstract Background Epstein Barr virus (EBV)-associated endemic Burkitt’s Lymphoma pediatric cancer is associated with morbidity and mortality among children resident in holoendemic Plasmodium falciparum regions in western Kenya. P. falciparum exerts strong selection pressure on sickle cell trait (SCT), alpha thalassemia (-α3.7/αα), glucose-6-phosphate dehydrogenase (G6PD), and merozoite surface protein 2 (MSP-2) variants (FC27, 3D7) that confer reduced malarial disease severity. The current study tested the hypothesis that SCT, (-α3.7/αα), G6PD mutation and (MSP-2) variants (FC27, 3D7) are associated with an early age of EBV acquisition. Methods Data on infant EBV infection status ( A)/Chinese (1024 C > T) (OR = 2.614, P = 0.212)] and [Union (1360 C > T)/Kaiping (1388G > A) (OR = 0.321, P = 0.295)]. There was no relationship between EBV acquisition and in-utero exposure to either FC27 (OR = 0.922, P = 0.914) or 3D7 (OR = 0.933, P = 0.921). In addition, EBV acquisition in infants ≥ 6–12 months also showed no association with -α3.7/αα (OR = 0.681, P = 0.442), SCT (OR = 0.513, P = 0.305), G6PD [(Viangchan (871G > A)/Chinese (1024 C > T) (OR = 0.640, P = 0.677)], [Mahidol (487G > A)/Coimbra (592 C > T) (OR = 0.948, P = 0.940)], [(Union (1360 C > T)/Kaiping (1388G > A) (OR = 1.221, P = 0.768)], African A (OR = 0.278, P = 0.257)], or in utero exposure to either FC27 (OR = 0.780, P = 0.662) or 3D7 (OR = 0.549, P = 0.241). Conclusion Although hemoglobinopathies (-α3.7/αα, SCT, and G6PD mutations) and in-utero exposure to MSP-2 were not associated with EBV acquisition in infants 0–12 months, novel G6PD variants were discovered in the population from western Kenya. To establish that the known and novel hemoglobinopathies, and in utero MSP-2 exposure do not confer susceptibility to EBV, future studies with larger sample sizes from multiple sites adopting genome-wide analysis are required.

Abstract We previously found that age, sex and malaria were associated with KSHV in individuals from Uganda. In this study, we have evaluated these same factors in relation to EBV in the same specimens. Overall, 74% (oral fluids) and 46% (PBMCs) had detectable EBV. This was significantly higher than observed for KSHV (24% oral fluids and 11% PBMCs). Individuals with EBV in PBMCs were more likely to have KSHV in PBMCs (P = 0.011). The peak age for detection of EBV in oral fluids was 3–5 years while that of KSHV was 6–12 years. In PBMCs, there was a bimodal peak age for detection of EBV (at 3–5 years and 66 + years) while for KSHV there was a single peak at 3–5 years. Individuals with malaria had higher levels of EBV in PBMCs compared to malaria-negative individuals (P = 0.002). In summary, our results show that younger age and malaria are associated with higher levels of EBV and KSHV in PBMCs suggesting malaria impacts immunity to both gamma-herpesviruses.

AbstractPartner notification (PN) is considered integral to the management of sexually transmitted infections (STI). Patient-referral is a common PN strategy and relies on index cases notifying and encouraging their partners to access treatment; however, it has shown limited efficacy. We conducted a mixed methods study to understand young people’s experiences of PN, particularly the risks and challenges encountered during patient-referral. All young people (16–24 years) attending a community-based sexual and reproductive health service in Zimbabwe who were diagnosed with an STI were counselled and offered PN slips, which enabled their partners to access free treatment at the service. PN slip uptake and partner treatment were recorded. Among 1807 young people (85.0% female) offered PN slips, 745 (41.2%) took up ≥1 PN slip and 103 partners (5.7%) returned for treatment. Most participants described feeling ill-equipped to counsel and persuade their partners to seek treatment. Between June and August 2021, youth researchers conducted in-depth interviews with 41 purposively selected young people diagnosed with an STI to explore their experiences of PN. PN posed considerable social risks, threatening their emotional and physical safety. Except for a minority in long-term, publicly acknowledged relationships, participants did not expect PN would achieve successful outcomes. Public health discourse, which constructs PN as “the right thing to do”, influenced participants to adopt narratives that concealed the difficulties of PN and their unmet needs. Urgent interrogation is needed of whether PN is a suitable or constructive strategy to continue pursuing with young people. To improve the outcomes of preventing reinfection and onward transmission of STIs, we must consider developing alternative strategies that better align with young people’s lived experiences.Plain language summary Partner notification is a public health strategy used to trace the sexual partners of people who have received a sexually transmitted infection (STI) diagnosis. It aims to interrupt the chains of STI transmission and prevent reinfection by treating both the person diagnosed and their sexual partners. The least effective but most common partner notification strategy used in many resource-limited settings is called “patient referral”. This involves a sexual healthcare provider encouraging the person diagnosed to give a “partner notification slip” to their potentially exposed sexual partner/s and persuading them to access treatment. This research sought to better understand young people’s experiences of partner notification, particularly the risks and challenges they faced during patient-referral.All young people (16–24 years) attending a community-based sexual and reproductive health service in Zimbabwe who were diagnosed with an STI were counselled and offered PN slips, which enabled their partners to access free treatment at the service. Young people trained as researchers interviewed 41 young people who had received a STI diagnosis to explore their experiences of partner notification.Only a small number (5.7%) of the partners of those who took a slip attended the service for treatment. Most participants felt they did not have the preparation, skills, or resources to persuade their partners to seek treatment. Many described negative experiences during and after partner notification, including relationship breakdown, reputation damage, and physical violence.These findings suggest that we should reconsider if partner notification is suitable or effective for use with young people. We should explore alternative approaches that do not present risks to young people’s social, emotional, and physical safety and well-being.

IntroductionMost childhood-onset SLE patients (cSLE) develop lupus nephritis (cLN), but only a small proportion achieve complete response to current therapies. The prognosis of children with LN and end-stage renal disease is particularly dire. Mortality rates within the first five years of renal replacement therapy may reach 22%. Thus, there is urgent need to decipher and target immune mechanisms that drive cLN. Despite the clear role of autoantibody production in SLE, targeted B cell therapies such as rituximab (anti-CD20) and belimumab (anti-BAFF) have shown only modest efficacy in cLN. While many studies have linked dysregulation of germinal center formation to SLE pathogenesis, other work supports a role for extrafollicular B cell activation in generation of pathogenic antibody secreting cells. However, whether extrafollicular B cell subsets and their T cell collaborators play a role in specific organ involvement in cLN and/or track with disease activity remains unknown.MethodsWe analyzed high-dimensional mass cytometry and gene expression data from 24 treatment naïve cSLE patients at the time of diagnosis and longitudinally, applying novel computational tools to identify abnormalities associated with clinical manifestations (cLN) and disease activity (SLEDAI).ResultscSLE patients have an extrafollicular B cell expansion signature, with increased frequency of i) DN2, ii) Bnd2, iii) plasmablasts, and iv) peripheral T helper cells. Most importantly, we discovered that this extrafollicular signature correlates with disease activity in cLN, supporting extrafollicular T/B interactions as a mechanism underlying pediatric renal pathogenesis.DiscussionThis study integrates established and emerging themes of extrafollicular B cell involvement in SLE by providing evidence for extrafollicular B and peripheral T helper cell expansion, along with elevated type 1 IFN activation, in a homogeneous cohort of treatment-naïve cSLE patients, a point at which they should display the most extreme state of their immune dysregulation.