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Abstract Metabolic syndrome (MetS), comprising obesity, insulin resistance, hypertension, and dyslipidemia, increases the risk of type II diabetes mellitus and cardiovascular disease. This study aimed to identify the prevalence and determinants of specific clusters of the MetS components and tobacco consumption among older adults in Iran. The current study was conducted in the second stage of the Bushehr Elderly Health (BEH) program in southern Iran—a population-based cohort including 2424 subjects aged ≥ 60 years. Latent class analysis (LCA) was used to identify MetS and tobacco consumption patterns. Multinomial logistic regression was conducted to investigate factors associated with each MetS class, including sociodemographic and behavioral variables. Out of 2424 individuals, the overall percentage of people with one or more components of MetS or current tobacco use was 57.8% and 20.8%, respectively. The mean (SD) age of all participants was 69.3(6.4) years. LCA ascertained the presence of four latent classes: class 1 (“low risk”; with a prevalence of 35.3%), class 2 (“MetS with medication-controlled diabetes”; 11.1%), class 3 (“high risk of MetS and associated medication use”; 27.1%), and class 4 (“central obesity and treated hypertension”; 26.4%). Compared to participants with a body mass index (BMI)

Abstract Melioidosis is an often-fatal neglected tropical disease caused by an environmental bacterium Burkholderia pseudomallei. However, our understanding of the disease-causing bacterial lineages, their dissemination, and adaptive mechanisms remains limited. To address this, we conduct a comprehensive genomic analysis of 1,391 B. pseudomallei isolates collected from nine hospitals in northeast Thailand between 2015 and 2018, and contemporaneous isolates from neighbouring countries, representing the most densely sampled collection to date. Our study identifies three dominant lineages, each with unique gene sets potentially enhancing bacterial fitness in the environment. We find that recombination drives lineage-specific gene flow. Transcriptome analyses of representative clinical isolates from each dominant lineage reveal increased expression of lineage-specific genes under environmental conditions in two out of three lineages. This underscores the potential importance of environmental persistence for these dominant lineages. The study also highlights the influence of environmental factors such as terrain slope, altitude, and river direction on the geographical dispersal of B. pseudomallei. Collectively, our findings suggest that environmental persistence may play a role in facilitating the spread of B. pseudomallei, and as a prerequisite for exposure and infection, thereby providing useful insights for informing melioidosis prevention and control strategies.

Introduction Preterm birth (PTB) is strongly associated with encephalopathy of prematurity (EoP) and neurocognitive impairment. The biological axes linking PTB with atypical brain development are uncertain. We aim to elucidate the roles of neuroendocrine stress activation and immune dysregulation in linking PTB with EoP.Methods and analysis PRENCOG (PREterm birth as a determinant of Neurodevelopment and COGnition in children: mechanisms and causal evidence) is an exposure-based cohort study at the University of Edinburgh. Three hundred mother–infant dyads comprising 200 preterm births (gestational age, GA 37 weeks, non-exposed), will be recruited between January 2023 and December 2027. We will collect parental and infant medical, demographic, socioeconomic characteristics and biological data which include placental tissue, umbilical cord blood, maternal and infant hair, infant saliva, infant dried blood spots, faecal material, and structural and diffusion MRI. Infant biosamples will be collected between birth and 44 weeks GA.EoP will be characterised by MRI using morphometric similarity networks (MSNs), hierarchical complexity (HC) and magnetisation transfer saturation imaging (MTsat). We will conduct: first, multivariable regressions and statistical association assessments to test how PTB-associated risk factors (PTB-RFs) relate to MSNs, HC and or MTsat; second, structural equation modelling to investigate neuroendocrine stress activation and immune dysregulation as mediators of PTB-RFs on features of EoP. PTB-RF selection will be informed by the variables that predict real-world educational outcomes, ascertained by linking the UK National Neonatal Research Database with the National Pupil Database.Ethics and dissemination A favourable ethical opinion has been given by the South East Scotland Research Ethics Committee 02 (23/SS/0067) and NHS Lothian Research and Development (2023/0150). Results will be reported to the Medical Research Council, in scientific media, via stakeholder partners and on a website in accessible language (https://www.ed.ac.uk/centre-reproductive-health/prencog).

In September 2021, a total of 25 patients diagnosed with COVID-19 developed acute melioidosis after (median 7 days) admission to a COVID-19 field hospital in Thailand. Eight nonpotable tap water samples and 6 soil samples were culture-positive for Burkholderia pseudomallei. Genomic analysis suggested contaminated tap water as the likely cause of illness.

Abstract Background The COVID-19 pandemic produced system-level changes within the criminal legal system and community-based substance use disorder (SUD) treatment system with impacts on recovery efforts. This study examines rural and urban clinicians’ perspectives of COVID-19 on SUD treatment delivery for people on community supervision. Methods Virtual qualitative interviews were conducted between April and October 2020 with 25 community supervision clinicians employed by Kentucky’s Department of Corrections (DOC), who conduct assessments and facilitate community-based treatment linkages for individuals on probation or parole. Transcripts were analyzed in NVivo using directed content analysis methods. Results Clinicians were predominantly white (92%) and female (88%) with an average of over 9 years working in the SUD treatment field and 4.6 years in their current job. Four COVID-19 themes were identified by both rural and urban clinicians including: (1) telehealth increases the modes of communication, but (2) also creates paperwork and technological challenges, (3) telehealth requires more effort for inter/intra-agency collaboration, and (4) it limits client information (e.g., no urine drug screens). Two additional rural-specific themes emerged related to COVID-19: (5) increasing telehealth options removes SUD treatment transportation barriers and (6) requires flexibility with programmatic requirements for rural clients. Conclusions Findings indicate the need for community-based SUD treatment providers approved or contracted by DOC to support and train clients to access technology and improve information-sharing with community supervision officers. A positive lesson learned from COVID-19 transitions was a reduction in costly travel for rural clients, allowing for greater engagement and treatment adherence. Telehealth should continue to be included within the SUD continuum of care, especially to promote equitable services for individuals from rural areas.

Abstract Background and objectives Multimorbidity, defined as the presence of two or more long-term health conditions in an individual, is one of the most significant challenges facing health systems worldwide. This study aimed to identify determinants of classes of multimorbidity among older adults in Iran. Research Design and methods In a cross-sectional sample of older adults (aged ≥ 60 years) from the second stage of the Bushehr Elderly Health (BEH) program in southern Iran, latent class analysis (LCA) was used to identify patterns of multimorbidity. Multinomial logistic regression was conducted to investigate factors associated with each multimorbidity class, including age, gender, education, household income, physical activity, smoking status, and polypharmacy. Results In 2,426 study participants (mean age 69 years, 52% female), the overall prevalence of multimorbidity was 80.2%. Among those with multimorbidity, 3 latent classes were identified. These comprised: class 1, individuals with a low burden of multisystem disease (56.9%); class 2, individuals with predominantly cardiovascular-metabolic disorders (25.8%) and class 3, individuals with predominantly cognitive and metabolic disorders (17.1%). Compared with men, women were more likely to belong to class 2 (odds ratio [OR] 1.96, 95% confidence interval [CI] 1.52–2.54) and class 3 (OR 4.52, 95% CI 3.22–6.35). Polypharmacy was associated with membership class 2 (OR 3.52, 95% CI: 2.65–4.68) and class 3 (OR 1.84, 95% CI 1.28–2.63). Smoking was associated with membership in class 3 (OR 1.44, 95% CI 1.01–2.08). Individuals with higher education levels (59%) and higher levels of physical activity (39%) were less likely to belong to class 3 (OR 0.41; 95% CI: 0.28–0.62) and to class 2 (OR 0.61; 95% CI: 0.38–0.97), respectively. Those at older age were less likely to belong to class 2 (OR 0.95). Discussion and implications A large proportion of older adults in Iran have multimorbidity. Female sex, polypharmacy, sedentary lifestyle, and poor education levels were associated with cardiovascular-metabolic multimorbidity and cognitive and metabolic multimorbidity. A greater understanding of the determinants of multimorbidity may lead to strategies to prevent its development.

Objectives: Although the incidence of malaria is increased in women in endemic areas after delivery compared to non-pregnant women, no studies have assessed the benefit of presumptive antimalarial treatment given postpartum. Methods: A randomised controlled trial investigating the efficacy of antimalarial treatment in preventing postpartum malaria was performed in healthy Papua New Guinea mothers immediately following delivery. Participants were randomised 1:1 to no treatment (n = 90) or artemisinin combination therapy (ACT), with further 1:1 ACT randomisation to artemether-lumefantrine (AL; n = 45) or dihydroartemisinin-piperaquine (DP; n = 45). Standardised reviews were conducted monthly for 6 months, including clinical assessment, malaria screening and haemoglobin measurement. The primary endpoint was incidence of slide-positive malaria within 6 months of delivery. Results: Of 183 recruited participants, 151 completed study procedures and were included in per-protocol analyses (no treatment n = 71, AL n = 40, DP, n = 40). Those allocated to ACT were significantly less likely to develop slide-positive malaria during the 6-month follow-up period compared to those who were untreated (n = 17 (21%) vs n = 27 (38%); P = 0.016; hazard ratio 0.49 (95% confidence intervals 0.27-0.90). There was no significant difference in malaria incidence between the two ACT groups. Conclusion: A treatment course of ACT at time of delivery halved the incidence of malaria infection during the first 6-month postpartum.

Multiligament knee reconstruction surgery is technically challenging, requiring careful planning and execution. Accurate placement of bone tunnels is important for graft function and there is an inherent risk of tunnel collision, which can compromise graft integrity. In this proof-of-concept study, we present a technique using computer navigation to help optimize tunnel placement and to avoid collision during multiligament knee reconstruction. A computed tomography (CT)-based navigation system was used to plan and execute femoral tunnel placement on a Sawbones model, for a Schenck KD-IV multiligament knee reconstruction. After CT scanning of the Sawbones model, commercially available software was used to plan tunnel trajectories for reconstruction of the posterolateral corner, medial ligament complex, and both cruciate ligaments. Tunnel entry points and trajectories were based on bony landmarks as identified on CT. The model was successfully registered with an accuracy of

Summary: Background: While individuals who were separated from their biological family and placed into the care of the state during childhood (out-of-home care) are more prone to developing selected adverse health problems in adulthood, their risk of cardiovascular disease is uncertain. Our aim was to explore this association by pooling published and unpublished results from prospective cohort studies. Methods: We used two approaches to identifying relevant data on childhood care and adult cardiovascular disease (PROSPERO registration CRD42021254665). First, to locate published studies, we searched PubMed (Medline) until November 2023. Second, with the objective of identifying unpublished studies with the potential to address the present research question, we scrutinised retrieved reviews on childhood out-of-home care and other adult health outcomes. Included studies were required to satisfy three criteria: a cohort study in which the assessment of care was made prospectively pre-adulthood (in the avoidance of recall bias); data on an unexposed comparator group were available (for the computation of relative risk); and a diagnosis of adult cardiovascular disease events (coronary heart disease, stroke, or their combination) had been made (as opposed to risk factors only). Collaborating investigators provided study-specific estimates which were aggregated using random-effects meta-analysis. The Newcastle-Ottawa Scale was used to assess individual study quality. Findings: Twelve studies (2 published, 10 unpublished) met the inclusion criteria, and investigators from nine provided viable results, including updated analyses of the published studies. Studies comprised 611,601 individuals (301,129 women) from the US, UK, Sweden, Finland, and Australia. Five of the nine studies were judged to be of higher methodological quality. Relative to the unexposed, individuals with a care placement during childhood had a 51% greater risk of cardiovascular disease in adulthood (summary rate ratio after age- and sex-adjustment [95% confidence interval]: 1.51 [1.22, 1.86]; range of study-specific estimates: 1.07 to 2.06; I2 = 69%, p = 0.001). This association was attenuated but persisted after adjustment for socioeconomic status in childhood (8 studies; 1.41 [1.15, 1.72]) and adulthood (9 studies, 1.29 [1.11, 1.51]). Interpretation: Our findings show that individuals with experience of out-of-home care in childhood have a moderately raised risk of cardiovascular disease in adulthood. Funding: Medical Research Council; National Institute on Aging; Wellcome Trust.

Membrane fouling is a major problem encountered in the use of microfiltration (MF) processes to separate the emulsified oil from water. This work involves assessing the efficacy of removing oil-in-water emulsion (O/W emulsion), and evaluating fouling resistance by studying the membrane morphology before and after fouling, and after washing with different cleaning solutions via field emission scanning electron microscopy (FESEM) analysis. Also, the fundamental mechanism involved in the flux drop during crossflow MF has been assessed using models such as the Hermia blocking models and the modified model by Field. The standard and intermediate pore blocking models provided the best prediction for experimental behavior when analyzing the decay in the flux with time for the bio silicon oxide/polyvinylchloride (B-SiO2/PVC) membrane and the stannic oxide/polyvinylchloride (SnO2/PVC) membrane. This research established regression equations of the flux for both membranes in which these equations are highly correlated with R2 of 98.33% for B-SiO2/PVC and R2 of 99.52% for SnO2/PVC using the surface response methodology (RSM). The high flux recovery ratio (FRR) is indicative of the improved antifouling feature of the manufactured membranes where it was 96.8% for B-SiO2/PVC and 94.6% for SnO2/PVC. The results obtained by Hermia and Field were in good agreement with RSM analysis supporting the standard pore-blocking mechanism.

Summary: Background: Physical abuse can lead to severe health consequences that extend beyond immediate harm. We explored the associations of physical abuse experienced during childhood and adulthood with a wide range of adult health conditions requiring hospital treatment. Methods: We utilised data from a sub-cohort of 157,366 UK Biobank participants (46.4% of the baseline population; age range 45–81; 89,101 women) and repeated analyses in an independent population of 85,929 adults from the Finnish Public Sector (FPS) study (age range 17–78; 68,544 women). Participants in both cohorts reported instances of physical and sexual abuse at study baseline. Follow-up included 77 common health conditions ascertained from linkage data to national hospital and mortality registries. Findings: Mean follow-up duration was 4.6 years (SD 0.14) in UK Biobank and 10.6 years (4.3) in FPS. Physical and sexual abuse was associated with 22 mental and physical health conditions. After multivariable adjustments, participants who experienced abuse during both early and later stages of life had a 2.12- (95% confidence interval 1.39–3.23) to 3.37-fold (1.52–7.45) increased risk of mental and behavioural disorders, a 1.46 (1.20–1.79) to 1.83 (1.05–3.20) times increased risk of metabolic, haematologic, and respiratory diseases, and a 1.24 (1.07–1.45) times higher risk of inflammatory diseases compared with non-exposed participants. The absolute risk difference between these groups was greatest for metabolic and haematologic conditions (rate 381 and risk difference 160 per 100,000 person-years). Frailty, comorbidities, and competing risk of death did not modify these associations, but the possibility of bias or residual confounding cannot be excluded. Interpretation: Repeated exposure to physical and sexual abuse amplifies the risk of hospitalisations from mental disorders and physical diseases spanning diverse organ systems. Addressing this issue may necessitate multifaceted strategies, including shifts in societal norms, legal measures, and increased healthcare provision for affected individuals and their families. Funding: Wellcome Trust, UK Medical Research Council, U.S. National Institute on Aging, Academy of Finland.

BackgroundMultiple myeloma is diagnosed in 5,800 people in the United Kingdom (UK) each year with up to 64% having vertebral compression fractures at the time of diagnosis. Painful vertebral compression fractures can be of significant detriment to patients’ quality of life. Percutaneous vertebroplasty aims to provide long-term pain relief and stabilize fractured vertebrae.Methods and materialsData was collected from all cases of percutaneous vertebroplasty performed on patients with multiple myeloma from November 2017 to January 2019. Pain scores were measured using the Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) pre-procedure, 2 months post procedure and 4 years post-procedure. Procedure related complications and analgesia use were also documented.Results22 patients were included with a total of 119 vertebrae treated. Patients reported a significant improvement in overall pain score with a median pre-procedure VAS of 8 and a median post-procedure VAS of 3.5 (p

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

Abstract Despite SARS-CoV-2 vaccines eliciting systemic neutralising antibodies (nAbs), breakthrough infections still regularly occur. Infection helps to generate mucosal immunity, possibly reducing disease transmission. Monitoring mucosal nAbs is predominantly restricted to lab-based assays, which have limited application to the public. In this multi-site study, we used lateral-flow surrogate neutralisation tests to measure mucosal and systemic nAbs in vaccinated and breakthrough infected individuals in Australia and Singapore. Using three lateral flow assays to detect SARS-CoV-2 nAbs, we demonstrated that nasal mucosal nAbs were present in 71.4 (95% CI 56.3–82.9%) to 85.7% (95% CI 71.8–93.7%) of individuals with breakthrough infection (positivity rate was dependent upon the type of test), whereas only 20.7 (95% CI 17.1–49.4%) to 34.5% (95% CI 19.8–52.7%) of vaccinated individuals without breakthrough infection had detectible nasal mucosal nAbs. Of the individuals with breakthrough infection, collective mucosal anti-S antibody detection in confirmatory assays was 92.9% (95% CI 80.3–98.2%) of samples, while 72.4% (95% CI 54.1–85.5%) of the vaccinated individuals who had not experienced a breakthrough infection were positive to anti-S antibody. All breakthrough infected individuals produced systemic anti-N antibodies; however, these antibodies were not detected in the nasal cavity. Mucosal immunity is likely to play a role in limiting the transmission of SARS-CoV-2 and lateral flow neutralisation tests provide a rapid readout of mucosal nAbs at the point-of-care.

OBJECTIVE: This study aimed to compare the utility of risk estimation derived from questionnaires and administrative records in predicting long-term sickness absence among shift workers.METHODS: This prospective cohort study comprised 3197 shift-working hospital employees (mean age 44.5 years, 88.0% women) who responded to a brief 8-item questionnaire on work disability risk factors and were linked to 28 variables on their working hour and workplace characteristics obtained from administrative registries at study baseline. The primary outcome was the first sickness absence lasting ≥90 days during a 4-year follow-up.RESULTS: The C-index of 0.73 [95% confidence interval (CI) 0.70–0.77] for a questionnaire-only based prediction model, 0.71 (95% CI 0.67–0.75) for an administrative records-only model, and 0.79 (95% CI 0.76–0.82) for a model combining variables from both data sources indicated good discriminatory ability. For a 5%-estimated risk as a threshold for positive test results, the detection rates were 76%, 74%, and 75% and the false positive rates were 40%, 45% and 34% for the three models. For a 20%-risk threshold, the corresponding detection rates were 14%, 8%, and 27% and the false positive rates were 2%, 2%, and 4%. To detect one true positive case with these models, the number of false positive cases accompanied varied between 7 and 10 using the 5%-estimated risk, and between 2 and 3 using the 20%-estimated risk cut-off. The pattern of results was similar using 30-day sickness absence as the outcome.CONCLUSIONS: The best predictive performance was reached with a model including both questionnaire responses and administrative records. Prediction was almost as accurate with models using only variables from one of these data sources. Further research is needed to examine the generalizability of these findings.

Objectives: To assess the pharmacokinetics, safety, and tolerability of two high-dose, short-course primaquine (PQ) regimens compared with standard care in children with Plasmodium vivax infections. Methods: We performed an open-label pediatric dose-escalation study in Madang, Papua New Guinea (Clinicaltrials.gov NCT02364583). Children aged 5-10 years with confirmed blood-stage vivax malaria and normal glucose-6-phosphate dehydrogenase activity were allocated to one of three PQ treatment regimens in a stepwise design (group A: 0.5 mg/kg once daily for 14 days, group B: 1 mg/kg once daily for 7 days, and group C: 1 mg/kg twice daily for 3.5-days). The study assessments were completed at each treatment time point and fortnightly for 2 months after PQ administration. Results: Between August 2013 and May 2018, 707 children were screened and 73 met the eligibility criteria (15, 40, and 16 allocated to groups A, B, and C, respectively). All children completed the study procedures. The three regimens were safe and generally well tolerated. The pharmacokinetic analysis indicated that an additional weight adjustment of the conventionally recommended milligram per kilogram PQ doses is not necessary to ensure the therapeutic plasma concentrations in pediatric patients. Conclusions: A novel, ultra-short 3.5-day PQ regimen has potential benefits for improving the treatment outcomes in children with vivax malaria that warrants further investigation in a large-scale clinical trial.

It is shown, with two sets of indicators that separately load on two distinct factors, independent of one another conditional on the past, that if it is the case that at least one of the factors causally affects the other, then, in many settings, the process will converge to a factor model in which a single factor will suffice to capture the covariance structure among the indicators. Factor analysis with one wave of data then cannot distinguish between factor models with a single factor vs those with two factors that are causally related. Therefore, unless causal relations between factors can be ruled out a priori, alleged empirical evidence from one-wave factor analysis for a single factor still leaves open the possibilities of a single factor or of two factors that causally affect one another. The implications for interpreting the factor structure of psychological scales, such as self-report scales for anxiety and depression, or for happiness and purpose, are discussed. The results are further illustrated through simulations to gain insight into the practical implications of the results in more realistic settings prior to the convergence of the processes. Some further generalizations to an arbitrary number of underlying factors are noted. Factor analyses with one wave of data should themselves be interpreted as characterizing associations among indicators that may be present either due to conceptual relations or due to causal relations concerning the underlying construct phenomena.

BackgroundThe occurrence of a range of health outcomes following myocardial infarction (MI) is unknown. Therefore, this study aimed to determine the long-term risk of major health outcomes following MI and generate sociodemographic stratified risk charts in order to inform care recommendations in the post-MI period and underpin shared decision making.Methods and findingsThis nationwide cohort study includes all individuals aged ≥18 years admitted to one of 229 National Health Service (NHS) Trusts in England between 1 January 2008 and 31 January 2017 (final follow-up 27 March 2017). We analysed 11 non-fatal health outcomes (subsequent MI and first hospitalisation for heart failure, atrial fibrillation, cerebrovascular disease, peripheral arterial disease, severe bleeding, renal failure, diabetes mellitus, dementia, depression, and cancer) and all-cause mortality. Of the 55,619,430 population of England, 34,116,257 individuals contributing to 145,912,852 hospitalisations were included (mean age 41.7 years (standard deviation [SD 26.1]); n = 14,747,198 (44.2%) male). There were 433,361 individuals with MI (mean age 67.4 years [SD 14.4)]; n = 283,742 (65.5%) male). Following MI, all-cause mortality was the most frequent event (adjusted cumulative incidence at 9 years 37.8% (95% confidence interval [CI] [37.6,37.9]), followed by heart failure (29.6%; 95% CI [29.4,29.7]), renal failure (27.2%; 95% CI [27.0,27.4]), atrial fibrillation (22.3%; 95% CI [22.2,22.5]), severe bleeding (19.0%; 95% CI [18.8,19.1]), diabetes (17.0%; 95% CI [16.9,17.1]), cancer (13.5%; 95% CI [13.3,13.6]), cerebrovascular disease (12.5%; 95% CI [12.4,12.7]), depression (8.9%; 95% CI [8.7,9.0]), dementia (7.8%; 95% CI [7.7,7.9]), subsequent MI (7.1%; 95% CI [7.0,7.2]), and peripheral arterial disease (6.5%; 95% CI [6.4,6.6]). Compared with a risk-set matched population of 2,001,310 individuals, first hospitalisation of all non-fatal health outcomes were increased after MI, except for dementia (adjusted hazard ratio [aHR] 1.01; 95% CI [0.99,1.02];p = 0.468) and cancer (aHR 0.56; 95% CI [0.56,0.57];p < 0.001). The study includes data from secondary care only-as such diagnoses made outside of secondary care may have been missed leading to the potential underestimation of the total burden of disease following MI.ConclusionsIn this study, up to a third of patients with MI developed heart failure or renal failure, 7% had another MI, and 38% died within 9 years (compared with 35% deaths among matched individuals). The incidence of all health outcomes, except dementia and cancer, was higher than expected during the normal life course without MI following adjustment for age, sex, year, and socioeconomic deprivation. Efforts targeted to prevent or limit the accrual of chronic, multisystem disease states following MI are needed and should be guided by the demographic-specific risk charts derived in this study.

Objectives: We aimed to assess safety, tolerability, and Plasmodium vivax relapse rates of ultra-short course (3.5 days) high-dose (1 mg/kg twice daily) primaquine (PQ) for uncomplicated malaria because of any Plasmodium species in children randomized to early- or delayed treatment. Methods: Children aged 0.5 to 12 years with normal glucose-6-phosphate-dehydrogenase (G6PD) activity were enrolled. After artemether-lumefantrine (AL) treatment, children were randomized to receive PQ immediately after (early) or 21 days later (delayed). Primary and secondary endpoints were the appearance of any P. vivax parasitemia within 42 or 84 days, respectively. A non-inferiority margin of 15% was applied (ACTRN12620000855921). Results: A total of 219 children were recruited, 70% with Plasmodium falciparum and 24% with P. vivax. Abdominal pain (3.7% vs 20.9%, P

Abstract Background Children with disabilities and their families are at higher risk during emergencies and disasters, which is often attributed to the lack of disability inclusion in emergency response as well as disparities in preparedness. This disparity speaks to a need for emergency preparedness that centers children with disabilities and their families. The purpose of this study was to elicit the perspectives of health professionals (nurses, occupational therapists, social workers), disability advocates, and public safety personnel (e.g., fire fighters, police officers, emergency management administrators) on what would enable these types of professionals to support family-centered emergency preparedness for families who care for children with disabilities. One goal of this research is to provide recommendations for practice and policy to improve safety outcomes for children with disabilities and their families in emergency situations. Methods This study consisted of 46 qualitative interviews with nurses, occupational therapists, social workers, public safety personnel, and advocacy organization representatives about their role in emergency preparedness for families of children with disabilities. Qualitative content analysis was used to identify themes from participants’ responses. Results Participants expressed interest in family-centered emergency preparedness, and stated that greater awareness, more education and training, increased networking between professions, and institutional support would enable their involvement. Conclusions These findings have implications for the importance of interprofessional collaboration in supporting family-centered emergency preparedness for families of children with disabilities. Stronger interprofessional networks would help overcome many of the barriers identified by participants, and advocacy groups appear to be well-positioned to bridge the gap between these professionals and their areas of expertise.

Abstract Few risk prediction scores are available to identify people at increased risk of work disability, particularly for those with an existing morbidity. We examined the predictive performance of disability risk scores for employees with chronic disease. We used prospective data from 88,521 employed participants (mean age 43.1) in the Finnish Public Sector Study including people with chronic disorders: musculoskeletal disorder, depression, migraine, respiratory disease, hypertension, cancer, coronary heart disease, diabetes, comorbid depression and cardiometabolic disease. A total of 105 predictors were assessed at baseline. During a mean follow-up of 8.6 years, 6836 (7.7%) participants were granted a disability pension. C-statistics for the 8-item Finnish Institute of Occupational Health (FIOH) risk score, comprising age, self-rated health, number of sickness absences, socioeconomic position, number of chronic illnesses, sleep problems, BMI, and smoking at baseline, exceeded 0.72 for all disease groups and was 0.80 (95% CI 0.80–0.81) for participants with musculoskeletal disorders, 0.83 (0.82–0.84) for those with migraine, and 0.82 (0.81–0.83) for individuals with respiratory disease. Predictive performance was not significantly improved in models with re-estimated coefficients or a new set of predictors. These findings suggest that the 8-item FIOH work disability risk score may serve as a scalable screening tool in identifying individuals with increased risk for work disability.

Abstract The polycentric city model has gained popularity in spatial planning policy, since it is believed to overcome some of the problems often present in monocentric metropolises, ranging from congestion to difficult accessibility to jobs and services. However, the concept ‘polycentric city’ has a fuzzy definition and as a result, the extent to which a city is polycentric cannot be easily determined. Here, we leverage the fine spatio-temporal resolution of smart travel card data to infer urban polycentricity by examining how a city departs from a well-defined monocentric model. In particular, we analyse the human movements that arise as a result of sophisticated forms of urban structure by introducing a novel probabilistic approach which captures the complexity of these human movements. We focus on London (UK) and Seoul (South Korea) as our two case studies, and we specifically find evidence that London displays a higher degree of monocentricity than Seoul, suggesting that Seoul is likely to be more polycentric than London.

Abstract Background Anterior cruciate ligament (ACL) reconstruction aims to restore anteroposterior and rotatory stability to the knee following ACL injury. This requires the graft to withstand the forces applied during the process of ligamentisation and the rehabilitative period. We hypothesise that the use of suture tape augmentation of single bundle ACL reconstruction (ACLR) will reduce residual knee laxity and improve patient-reported outcomes at 2-year follow-up. We will conduct a 1:1 parallel arm single-centre randomised controlled trial comparing suture tape augmented ACLR to standard ACLR technique. Methods The study design will be a parallel arm 1:1 allocation ratio randomised controlled trial. Sixty-six patients aged 18 and over waitlisted for primary ACLR will be randomised. Patients requiring osteotomy and extra-articular tenodesis and who have had previous contralateral ACL rupture or repair of meniscal or cartilage pathology that modifies the post-operative rehabilitation will be excluded. The primary outcome measure will be the side-to-side difference in anterior tibial translation (measured on the GNRB arthrometer) at 24 months post-surgery. GNRB arthrometer measures will also be taken preoperatively, at 3 months and 12 months post-surgery. Secondary outcomes will include patient-reported outcome measures (PROMs) collected online, including quality of life, activity and readiness to return to sport, complication rates (return to theatre, graft failure and rates of sterile effusion), examination findings and return to sport outcomes. Participants will be seen preoperatively, at 6 weeks, 3 months, 12 months and 24 months post-surgery. Participants and those taking arthrometer measures will be blinded to allocation. Discussion This will be the first randomised trial to investigate the effect of suture-tape augmentation of ACLR on either objective or subjective outcome measures. The use of suture-tape augmentation in ACLR has been associated with promising biomechanical and animal-level studies, exhibiting equivalent complication profiles to the standard technique, with initial non-comparative clinical studies establishing possible areas of advantage for the technique. The successful completion of this trial will allow for an improved understanding of the in situ validity of tape augmentation whilst potentially providing a further platform for surgical stabilisation of the ACL graft. Trial registration Australia New Zealand Clinical Trial Registry ACTRN12621001162808. Universal Trial Number (UTN): U1111-1268-1487. Registered prospectively on 27 August 2021

Sildenafil is used to treat pulmonary hypertension in neonatal intensive care unit (NICU) settings. As multiple intravenous (IV) medications are co-administered in NICU settings, we sought to investigate the physicochemical compatibility of sildenafil with a range of IV drugs. Sildenafil 600 mcg/mL or 60 mcg/mL was mixed 1:1 with the secondary drug solution to simulate Y-site co-administration procedures. Physical compatibility was evaluated by visual observation against a black and white background and under polarized light for two hours for changes in colour, precipitation, haze and evolution of gas. Chemical compatibility was determined from sildenafil concentrations, using a validated, stability-indicating high-performance liquid chromatography assay. Sildenafil 600 mcg/mL was physicochemically compatible with 29 of the 45 drugs tested at ‘high-end’ clinical concentrations and physically incompatible with 16 drugs and six ‘2-in-1’ parenteral nutrition solutions. Sildenafil 600 mcg/mL was compatible with lower, clinically relevant concentrations of calcium gluconate, heparin and hydrocortisone. Aciclovir, amoxicillin, ampicillin, ibuprofen lysine, indometacin, phenobarbitone and rifampicin were incompatible with sildenafil 600 mcg/mL, however these IV medications were compatible with sildenafil 60 mcg/mL. Sildenafil 600 mcg/mL and 60 mcg/mL were incompatible with amphotericin, flucloxacillin, furosemide, ibuprofen, meropenem and sodium bicarbonate. Sildenafil compatibility with commonly used syringe filters was also investigated. Sildenafil solution was compatible with nylon syringe filters, however, absorption/adsorption loss occurred with polyethersulfone and cellulose ester filters.

Summary: Background: Knowledge of post-myocardial infarction (MI) disease risk to date is limited—yet the number of survivors of MI has increased dramatically in recent decades. We investigated temporally ordered sequences of all conditions following MI in nationwide electronic health record data through the application of process mining. Methods: We conducted a national retrospective cohort study of all hospitalisations (145,670,448 episodes; 34,083,204 individuals) admitted to NHS hospitals in England (1st January 2008–31st January 2017, final follow-up 27th March 2017). Through process mining, we identified trajectories of all major disease diagnoses following MI and compared their relative risk (RR) and all-cause mortality hazard ratios (HR) to a risk-set matched non-MI control cohort using Cox proportional hazards and flexible parametric survival models. Findings: Among a total of 375,669 MI patients (130,758 females; 34.8%) and 1,878,345 matched non-MI patients (653,790 females; 34.8%), we identified 28,799 unique disease trajectories. The accrual of multiple circulatory diagnoses was more common amongst MI patients (RR 4.32, 95% CI 3.96–4.72) and conferred an increased risk of death (HR 1.32, 1.13–1.53) compared with matched controls. Trajectories featuring neuro-psychiatric diagnoses (including anxiety and depression) following circulatory disorders were markedly more common and had increased mortality post MI (HR ranging from 1.11 to 1.73) compared with non-MI individuals. Interpretation: These results provide an opportunity for early intervention targets for survivors of MI—such as increased focus on the psychological and behavioural pathways—to mitigate ongoing adverse disease trajectories, multimorbidity, and premature mortality. Funding: British Heart Foundation; Alan Turing Institute.

This article asks how educators at tertiary level might attempt to address gender diversity behind the camera in student productions. The 2020 Australian Screen Production Education and Research Association (ASPERA) report Diversity On and Off Screen in Australian Film Schools outlines the results of a national survey measuring levels of gender diversity behind the camera in Australian university capstone (major project-based) screen production units. The survey results reveal that, while close to even numbers of male and female students are completing capstone projects in screen production departments and film schools in Australia, crew roles are highly gendered. A gendered skew is most pronounced in the roles of cinematographer and sound designer (male dominated), and producer and production designer (female dominated). We argue that an investigation of this subject calls for an examination of the specificity of the tertiary screen production environment. The crewing of student projects can be fraught, involving competition for popular roles such as that of director, and choices are made based on student likes and dispositions. In this article, we further drill into quantitative and qualitative data from the ASPERA survey to examine educator attitudes and approaches towards the gendered nature of some student production roles.

Four natural dyes were extracted from different fruits used in the Dye-sensitized solar cell (DSSC). It includes ber, blackberry, black grapes, and blueberry by individual dye or combined with other dyes. The dye solution's absorption spectra were extended to the whole visible region 200–750 nm. FTIR spectroscopy was employed to identify the possible functional group vibrations responsible for the dyes' chemical activity and optical behaviour. The TiO2 powder was coated on the ITO conducting surface to form a thin film. The experimental results showed that the ber dye produces the highest solar cell efficiency (η), ˜13%, among all four extracted anthocyanin studied. It also found that ber combination with other dyes is higher conversion efficiency than blackberry, black grapes, and blueberry with another and vice versa. Ber dye can be helpful in the development of more eco-friendly and cost-effective solar cells with commercially promising DSSC.

Background Although several predictors of COVID-19 vaccine hesitancy have been identified, the role of physical health and, particularly, mental health, is poorly understood. Methods We used individual-level data from a pandemic-focused investigation (COVID Survey), a prospective cohort study nested within the UK Understanding Society (Main Survey) project. In the week immediately following the announcement of successful testing of the first efficacious inoculation (Oxford University/AstraZeneca, November/December 2020), data on vaccine intentionality were collected in 12,035 individuals aged 16–95 years. Pre-pandemic, study members had responded to enquiries about diagnoses of mental and physical health, including the completion of the 12-item General Health Questionnaire for symptoms of psychological distress (anxiety and depression). Peri-pandemic, individuals indicated whether they or someone in their household was shielding; that is, people judged by the UK National Health Service as being particularly clinically vulnerable who were therefore requested to remain at home. Intention to take up vaccination for COVID-19 was also self-reported. Results In an analytical sample of 11,955 people (6741 women), 15.4% indicated that they were vaccine-hesitant. Relative to their disease-free counterparts, shielding was associated with a 24% lower risk of being hesitant (odds ratio; 95% confidence interval: 0.76; 0.59, 0.96), after adjustment for a range of covariates which included age, education, and ethnicity. Corresponding results for cardiometabolic disease were 22% (0.78; 0.64, 0.95), and for respiratory disease were 26% (0.74; 0.59, 0.93). Having a pre-pandemic diagnosis of anxiety or depression, or a high score on the distress symptom scale, were all unrelated to the willingness to vaccine-hesitancy. Conclusions People with a physical condition were more likely to take up the potential offer of a COVID-19 vaccination. These effects were not apparent for indices of mental health.Key messages In understanding predictors of COVID-19 vaccine hesitancy, the role of physical and mental health has not been well-examined despite both groups seemingly experiencing an elevated risk of the disease. In a large UK cohort study, people with a pre-pandemic physical condition were more likely to take up the theoretical offer of vaccination. There were no apparent effects for indices of pre-pandemic mental health.

Recombinant adeno-associated virus (AAV) is an effective platform for therapeutic gene transfer; however, tissue-tropism differences between species are a challenge for successful translation of preclinical results to humans. We evaluated the use of in vitro primary hepatocyte cultures to predict in vivo liver-directed AAV expression in different species. We assessed whether in vitro AAV transduction assays in cultured primary hepatocytes from mice, nonhuman primates (NHPs), and humans could model in vivo liver-directed AAV expression of valoctocogene roxaparvovec (AAV5-hFVIII-SQ), an experimental gene therapy for hemophilia A with a hepatocyte-selective promoter. Relative levels of DNA and RNA in hepatocytes grown in vitro correlated with in vivo liver transduction across species. Expression in NHP hepatocytes more closely reflected expression in human hepatocytes than in mouse hepatocytes. We used this hepatocyte culture model to assess transduction efficacy of a novel liver-directed AAV capsid across species and identified which of 3 different canine factor VIII vectors produced the most transgene expression. Results were confirmed in vivo. Further, we determined mechanisms mediating inhibition of AAV5-hFVIII-SQ expression by concomitant isotretinoin using primary human hepatocytes. These studies support using in vitro primary hepatocyte models to predict species translatability of liver-directed AAV gene therapy and improve mechanistic understanding of drug-drug interactions.

Summary: Background: Former participants in sports characterised by low intensity repetitive head impact appear to have elevated rates of later dementia, but links with other psychological health outcomes such as depression and suicide are uncertain. We quantified the occurrence of these endpoints in former contact sports athletes against general population controls using new data from a cohort study and a meta-analysis. Methods: The cohort study comprised 2004 retired male athletes, who had competed internationally as amateurs for Finland across a range of sports, and 1385 general population controls. All study members were linked to mortality and hospitalisation registries. In the PROSPERO-registered systematic review (CRD42022352780), we searched PubMed and Embase to October 31 2022 for cohort studies that reported standard estimates of association and precision. Study-specific estimates were aggregated in a random-effect meta-analysis. The Newcastle-Ottawa Scale was used to appraise the quality of each study. Findings: In survival analyses of the Finnish cohort data, former boxers (depression: hazard ratio 1.43 [95% CI 0.73, 2.78]; suicide: 1.75 [0.64, 4.38]), Olympic-style wrestlers (depression: 0.94 [0.44, 2.00]; suicide: 1.60 [0.64, 3.99]), and soccer players (depression: 0.62 [0.26, 1.48]; suicide: 0.50 [0.11, 2.16]) did not have statistically higher rates of major depressive disorder or suicide at follow-up relative to controls. In the systematic review, 7 cohort studies met inclusion criteria. After aggregating results with the Finnish cohort, retired soccer players appeared to have a lower risk of depression (summary risk ratio: 0.71 [0.54, 0.93]) relative to general population controls, while the rate of suicide was statistically the same across groups (0.70 [0.40, 1.23]). Past participation in American football seemed to be associated with some protection against suicide (0.58 [0.43, 0.80]) but there were insufficient studies of depression in this sport to facilitate aggregation. The aggregation of results from the soccer and American football studies showed directionally consistent relationships and there was no indication of inter-study heterogeneity (I2 = 0%). Interpretation: Based on a small cluster of studies exclusively comprising men, retired soccer players had a lower rate of later depression and former American football players had a lower risk of suicide relative to comparator groups. Whether these findings are generalisable to women requires testing. Funding: The preparation of this manuscript was unfunded.

Since there are inconsistent data relating to the effect of haemoglobinopathies on disposition of artemisinin antimalarial combination therapy, and none in sickle cell trait (SCT) or sickle cell disease (SCD), the aim of this study was to characterize the pharmacokinetic properties of artemether-lumefantrine (ARM-LUM) in children with SCD/SCT. Thirty-eight Tanzanian children aged 5–10 years with normal (haemoglobin AA; n = 12), heterozygous (haemoglobin AS; n = 14) or homozygous (haemoglobin SS; n = 12) sickle genotypes received six ARM-LUM doses (1.7 mg/kg plus 10 mg/kg, respectively) over 3 days. Sparse venous and mixed-capillary dried blood spot (DBS) samples were taken over 42 days. Plasma and DBS ARM and LUM, and their active metabolites dihydroartemisinin (DHA) and desbutyl-lumefantrine (DBL), were assayed using validated liquid chromatography-mass spectrometry. Multi-compartmental pharmacokinetic models were developed using a population approach. Plasma but not DBS concentrations of ARM/DHA were assessable. The majority (85%) of the 15 measurable values were within 95% prediction intervals from a published population pharmacokinetic ARM/DHA model in Papua New Guinean children of similar age without SCD/SCT who had uncomplicated malaria, and there was no clear sickle genotype clustering. Plasma (n = 38) and corrected DBS (n = 222) LUM concentrations were analysed using a two-compartment model. The median [inter-quartile range] LUM AUC0–∞ was 607,296 [426,480–860,773] μg.h/L, within the range in published studies involving different populations, age-groups and malaria status. DBS and plasma DBL concentrations correlated poorly and were not modelled. These data support use of the conventional ARM-LUM treatment regimen for uncomplicated malaria in children with SCT/SCD.

Intro: In Australia, the main methods to diagnose COVID-19 are through rapid antigen tests (RATs) and through nucleic acid amplification testing (NAAT, including polymerase chain reaction) on healthcare worker (HCW)-collected combined nose/throat swabs. With self-collection widely used by the public for RATs, the aim of this study was to evaluate the performance of self-collected samples using commercial NAAT for SARS-CoV-2. Methods: Consenting participants aged 14 years and older were provided with a self-collection pack containing instructions and either a FLOQSwab (Copan) or a Rhinoswab (Rhinomed). Participants collected their own nasal sample unsupervised prior to having a HCW-collected combined nose and throat swab taken for standard of care NAAT. Paired self-collected and HCW samples were tested on the cobas SARS-CoV-2 assay (Roche) and the Aptima SARS-CoV-2 assay (Hologic). Findings: We demonstrated comparable sensitivity, specificity, and agreement between self-collected nasal and Rhinoswab samples, compared to HCW- collected samples tested using the cobas SARS-CoV-2 and Aptima SARS-CoV-2 assays. In our study the clinical performance of self-collected specimens was comparable to HCW-collected samples, with both self-collect nasal and Rhinoswab samples resulting in 90-95% sensitivity, and in most cases >95% specificity. Discussion: Without the availability of samples for NAAT the ability to perform genomic testing is limited, reducing surveillance and public health investigations. We showed that genomic sequencing from self-collected samples can correctly identify the virus lineage and that the main determination of successful genomic testing is a high viral load rather than collection method. Conclusion: These data support self-collection as an accessible method for community testing for COVID-19 and introduces a novel collection device, the Rhinoswab as an alternative to the standard nasal swab. The testing method of self-collection can be expanded from the widely used RATs to NAAT and genomic testing which may inform the management and public health response to the COVID-19 pandemic.

Intro: Uptake of SARS-CoV-2 rapid antigen tests (RATs) for self-testing has been high following authorisation by the Australian Therapeutic Goods Administration (TGA). However, there are no published Australian data assessing feasibility and compliance with home-based rapid antigen testing. The aim of this study was to determine the acceptability of daily rapid antigen self-testing. Methods: We prospectively recruited a cohort of hospital employees and students from primary and secondary school to perform daily self-testing using RATs in the home over 14 consecutive days. Participants consenting to the study were supplied with 15 Roche SARS-CoV-2 Antigen Nasal Self Tests, 3 saliva swabs for self-collection for RT-PCR and were asked to record results and answer a daily survey using a smartphone application. Findings: 38% (26/68) of the cohort were compliant to 14 consecutive days of testing; this was significantly higher in students (71%) than hospital employees (28%). The median number of tests performed over 14 consecutive days was 11 and time to first missed test was a median 5.5 days. The most common reasons for missing days were “I forgot” (37.5%) and “too busy” (8.9%). Ease of self- nasal swabbing, self-nasal testing. performing the test and using the app were rated as comfortable/very comfortable in over 80% of the cohort. Discussion: Most study participants in this Australian cohort were compliant with frequent home-based RATs. By study end most participants (93.8%) found the testing process acceptable/very acceptable. There is need for further work on the cost-effectiveness and impact of self-tested RATs under a range of specific uses and conditions. Conclusion: This study provided valuable information on acceptability and feasibility of regular home-based testing which could be applied to other diseases. Ongoing community engagement with clear information on RATs including accuracy and use cases is important for decision-making and addressing concerns, particularly for linguistically diverse peoples.

Infection with Extended-spectrum beta-lactamase -producing Enterobacterales (ESBL-E) is common in infants and leads to increased intensive care unit admission and mortality, but the role of maternal transmission in colonization of infants is unclear. Using paired isolates from 50 pairs of mothers and neonates admitted to a Cambodian hospital, we investigated antimicrobial resistance in Escherichia coli and Klebsiella pneumoniae using whole genome sequencing. We detected a wide variety of ESBL-E genes present in this population along with high levels of multidrug resistance. From 21 pairs where the same organism was present in both mother and neonate, we identified eight pairs with identical or near-identical isolates from both individuals suggestive of transmission at or around birth, including a pair with transmission of multiple strains. We found no evidence for transmission of plasmids only from mother to infant. This suggests vertical transmission outside hospitals as a common cause of ESBL-E colonization in neonates.

Background: A major part of the HEALing Communities Study (HCS), launched in 2019 to address the growing opioid epidemic, is evaluating the study’s intervention implementation process through an implementation science (IS) approach. One component of the IS approach involves teams with more than 20 researchers collaborating across four research sites to conduct in-depth qualitative interviews with over 300 participants at four time points. After completion of the first two rounds of data collection, we reflect upon our qualitative data collection and analysis approach. We aim to share our lessons learned about designing and applying qualitative methods within an implementation science framework. Methods: The HCS evaluation is based on the RE-AIM/PRISM framework and incorporates interviews at four timepoints. At each timepoint, the core qualitative team of the Intervention Work Group drafts an interview guide based on the framework and insights from previous round(s) of data collection. Researchers then conduct interviews with key informants and coalition members within their respective states. Data analysis involves drafting, iteratively refining, and finalizing a codebook in a cross-site and within-site consensus processes. Interview transcripts are then individually coded by researchers within their respective states. Results: Successes in the evaluation process include having structured procedures for communication, data collection, and analysis, all of which are critical for ensuring consistent data collection and for achieving consensus during data analysis. Challenges include recognizing and accommodating the diversity of training and knowledge among researchers, as well as establishing reliable ways to securely store, manage, and share the large volumes of data. Conclusion: Qualitative methods using a Team Science approach have been limited in their application in large, multi-site randomized controlled trials of health interventions. Our experience provides practical guidance for future studies with large teams that are experientially and disciplinarily diverse and that are seeking to incorporate qualitative or mixed-methods components for their evaluations.

Currently licensed vaccine adjuvants offer limited mucosal immunity, which is needed to better combat respiratory infections such as influenza. Mast cells (MCs) are emerging as a target for a new class of mucosal vaccine adjuvants. Here, we developed and characterized a nanoparticulate adjuvant composed of an MC activator [mastoparan-7 (M7)] and a TLR ligand (CpG). This novel nanoparticle (NP) adjuvant was co-formulated with a computationally optimized broadly reactive antigen (COBRA) for hemagglutinin (HA), which is broadly reactive against influenza strains. M7 was combined at different ratios with CpG and tested for in vitro immune responses and cytotoxicity. We observed significantly higher cytokine production in dendritic cells and MCs with the lowest cytotoxicity at a charge-neutralizing ratio of nitrogen/phosphate = 1 for M7 and CpG. This combination formed spherical NPs approximately 200 nm in diameter with self-assembling capacity. Mice were vaccinated intranasally with COBRA HA and M7-CpG NPs in a prime–boost–boost schedule. Vaccinated mice had significantly higher antigen-specific antibody responses (IgG and IgA) in serum and mucosa compared with controls. Splenocytes from vaccinated mice had significantly increased cytokine production upon antigen recall and the presence of central and effector memory T cells in draining lymph nodes. Finally, co-immunization with NPs and COBRA HA induced influenza H3N2-specific HA inhibition antibody titers across multiple strains and partially protected mice from a challenge against an H3N2 virus. These results illustrate that the M7-CpG NP adjuvant combination can induce a protective immune response with a broadly reactive influenza antigen via mucosal vaccination.

Introduction Three medications are Food and Drug Administration approved for the treatment of opioid use disorder (OUD); however, these medications are underused within prisons, which elevates the risk of relapse and overdose when persons with opioid use disorder (POUD) are released. Research is scant regarding the multilevel factors associated with POUDs’ willingness to initiate medication treatment for opioid use disorder (MOUD) while in prison and their continued engagement in treatment after release. Furthermore, rural and urban populations have not been compared. The Geographic variation in Addiction Treatment Experiences (GATE) study seeks to identify multilevel factors (ie, individual, personal network, and structural factors) influencing prison-based extended-release injectable naltrexone (XR-NTX) and buprenorphine initiation and will examine predictors of postrelease MOUD use and adverse outcomes (ie, relapse, overdose, recidivism) among both rural and urban POUDs.Methods and analysis This mixed methods study employs a social ecological framework. A prospective observational longitudinal cohort study is being conducted with 450 POUDs using survey and social network data collected in prison, immediately postrelease, 6 months postrelease and 12 months postrelease to identify multilevel rural-urban variation in key outcomes. In-depth qualitative interviews are being conducted with POUDs, prison-based treatment staff and social service clinicians. To maximise rigour and reproducibility, we employ a concurrent triangulation strategy, whereby qualitative and quantitative data contribute equally to the analysis and are used for cross-validation when examining scientific aims.Ethics and dissemination The GATE study was reviewed and approved by the University of Kentucky’s Institutional Review Board prior to implementation. Findings will be disseminated through presentations at scientific and professional association conferences, peer-reviewed journal publications and a summary aggregate report submitted to the Kentucky Department of Corrections.

Abstract The first publication of micro‐ and nanotechnology in medicine was in 1798 with the use of the Cowpox virus by Edward Jenner as an attenuated vaccine against Smallpox. Since then, there has been an explosion of micro‐ and nanotechnologies for medical applications. The breadth of these micro‐ and nanotechnologies is discussed in this piece, presenting the date of their first report and their latest progression (e.g., clinical trials, FDA approval). This includes successes such as the recent severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccines from Pfizer, Moderna, and Janssen (Johnson & Johnson) as well as the most popular nanoparticle therapy, liposomal Doxil. However, the enormity of the success of these platforms has not been without challenges. For example, we discuss why the production of Doxil was halted for several years, and the bankruptcy of BIND therapeutics, which relied on a nanoparticle drug carrier. Overall, the field of micro‐ and nanotechnology has advanced beyond these challenges and continues advancing new and novel platforms that have transformed therapies, vaccines, and imaging. In this review, a wide range of biomedical micro‐ and nanotechnology is discussed to serve as a primer to the field and provide an accessible summary of clinically relevant micro‐ and nanotechnology platforms.

Abstract We report on the electronic and magnetic properties of superconductor-ferromagnet heterostructures fabricated by electron beam evaporation on to unheated thermally oxidised Si substrates. Polycrystalline Nb thin films (5 to 50 nm thick) were shown to possess reliably high superconducting critical temperatures ( $$T_{c}$$ T c ), which correlate well with the residual resistivity ratio (RRR) of the film. These properties improved during ex-situ annealing, resulting in $${\Delta }T_{c}$$ Δ T c and $${\Delta }$$ Δ RRR increases of up 2.2 K ( $$\sim$$ ∼ 40% of the pre-annealed $$T_{c}$$ T c ) and 0.8 ( $$\sim$$ ∼ 60% of the pre-annealed RRR) respectively. Nb/Pt/Co/Pt heterostructures showed substantial perpendicular anisotropy in the ultrathin limit (≤ 2.5 nm), even in the extreme limit of Pt(0.8 nm)/Co(1 nm)/Pt(0.6 nm). These results point to the use of electron beam evaporation as route to line-of-sight deposited, low-thickness, high quality Nb-based superspintronic multilayers.

Abstract Well-defined molecular resistance markers are available for a range of antimalarial drugs, and molecular surveillance is increasingly important for monitoring antimalarial drug resistance. Different genotyping platforms are available, but these have not been compared in detail. We compared Targeted Amplicon Deep sequencing (TADs) using Ion Torrent PGM with Illumina MiSeq for the typing of antimalarial drug resistance genes. We developed and validated protocols to type the molecular resistance markers pfcrt, pfdhfr, pfdhps, pfmdr1, pfkelch, and pfcytochrome b, in Plasmodium falciparum for the Ion Torrent PGM and Illumina MiSeq sequencing platforms. With P. falciparum 3D7 and K1 as reference strains, whole blood samples (N = 20) and blood spots from Rapid Diagnostic Test (RDT) samples (N = 5) from patients with uncomplicated falciparum malaria from Ubon Ratchathani were assessed on both platforms and compared for coverage (average reads per amplicon), sequencing accuracy, variant accuracy, false positive rate, false negative rate, and alternative allele detection, with conventional Sanger sequencing as the reference method for SNP calling. Both whole blood and RDT samples could be successfully sequenced using the Ion Torrent PGM and Illumina MiSeq platforms. Coverage of reads per amplicon was higher with Illumina MiSeq (28,886 reads) than with Ion Torrent PGM (1754 reads). In laboratory generated artificial mixed infections, the two platforms could detect the minor allele down to 1% density at 500X coverage. SNPs calls from both platforms were in complete agreement with conventional Sanger sequencing. The methods can be multiplexed with up to 96 samples per run, which reduces cost by 86% compared to conventional Sanger sequencing. Both platforms, using the developed TAD protocols, provide an accurate method for molecular surveillance of drug resistance markers in P. falciparum, but Illumina MiSeq provides higher coverage than Ion Torrent PGM.

Abstract As cities increase in size, total wages grow superlinearly, meaning that average wages are higher in larger cities. This phenomenon, known as the urban wage premium, supports the notion that urbanization and the growth of cities contribute positively to human well-being. However, it remains unclear how the distribution of wages changes as cities grow. Here we segment the populations of U.S. cities into wage deciles and determine the scaling coefficient of each decile’s aggregate wages versus city size. We find that, while total wages of all deciles grow superlinearly with city size, the effect is uneven, with total wages of the highest wage earners growing faster than all other deciles. We show that this corresponds with the predominance of high-wage jobs in larger cities. Thus, the effects of urbanization are mixed -- it is associated with higher average wages but with increasing inequality, thus inhibiting prospects for long-term sustainability.

Abstract Linear cities where activity is spread out along a transportation line, aim to offer the highest levels of accessibility to their adjacent populations as well as to the countryside. These city forms are popular amongst architects and planners in envisioning ideal cities but they are difficult to implement as they involve strict controls on development which often ignore human behaviour associated with where we locate and how we move. We briefly explore the history of these ideas, noting the latest proposal to build a 170 km city called Neom in north west Saudi Arabia, a plan that has attracted considerable criticism for its apparent ignorance of how actual cities grow and evolve. We use a standard model of human mobility based on gravitational principles to define a set of equilibrium conditions that illustrate how a theoretical city on a line would, without any controls, successively adapt to such a new equilibrium. First, we represent the city on a line, showing how its population moves to an equilibrium along the line, and then we generalise this to a bigger two-dimensional space where the original line cutting across the grid evolves as populations maximise their accessibility over the entire space. In this two-dimensional world, we simulate different forms that reflect a balance of centralising versus decentralising forces, showing the power of such equilibria in destroying any idealised form. This approach informs our thinking about how far idealised future cities can depart from formal plans of the kind that the linear city imposes.