Examination of the shared genetic architecture between multiple sclerosis and systemic lupus erythematosus facilitates discovery of novel lupus risk loci.

Systemic Lupus Erythematosus (SLE) is an autoimmune disease with heterogeneous manifestations, including neurological and psychiatric symptoms. Genetic association studies in SLE have been hampered by insufficient sample size and limited power compared to many other diseases. Multiple Sclerosis (MS) is a chronic relapsing autoimmune disease of the central nervous system (CNS) that also manifests neurological and immunological features. Here, we identify a method of leveraging large-scale genome wide association studies (GWAS) in MS to identify novel genetic risk loci in SLE. Statistical genetic comparison methods including linkage disequilibrium score regression (LDSC) and cross-phenotype association analysis (CPASSOC) to identify genetic overlap in disease pathophysiology, traditional 2-sample and novel PPI-based mendelian randomization to identify causal associations and Bayesian colocalization were applied to association studies conducted in MS to facilitate discovery in the smaller, more limited datasets available for SLE. Pathway analysis using SNP-to-gene mapping identified biological networks composed of molecular pathways with causal implications for CNS disease in SLE specifically, as well as pathways likely causal of both pathologies, providing key insights for therapeutic selection.

Medical student experiences of equality, diversity, and inclusion: content analysis of student feedback using Bronfenbrenner's ecological systems theory.

BACKGROUND: Issues relating to equality, diversity, and inclusion (EDI) significantly impact on medical student achievement and wellbeing. Interventions have been introduced at curricular and organisational levels, yet progress in addressing these issues remains limited. Timely evaluation is needed to assess effectiveness of interventions, and to explore issues and interactions in learning environments impacting on student experience. We introduced an anonymous question concerning students' experiences of EDI into routine online student feedback questionnaires, to scope the nature of ongoing issues and develop greater understanding of students' experiences in our programme environment. Ecological systems theory, which conceptualizes learning as a function of complex social interactions, determined by characteristics of individual learners and their environment, provides a framework for understanding. METHODS: Free-text responses regarding experiences of EDI gathered over 20 months from all programme years (n = 760) were pooled for analysis, providing a holistic overview of experiences in the learning environment. A counting exercise identified broad categories reported by students. Content analysis of the qualitative dataset was undertaken. Bronfenbrenner's ecological systems theory was applied as a framework to demonstrate interdependencies between respondents' experiences and environments, and associated impacts. RESULTS: Three hundred and seventy-six responses were received relating to wide-ranging EDI issues, most frequently gender or ethnicity. Responses mapped onto all areas of the ecological systems model, with frequent links between subsystems, indicating considerable complexity and interdependencies. Interpersonal interactions and associated impacts like exclusion were frequently discussed. Differential experiences of EDI-related issues in medical school compared to clinical settings were reported. Impacts of institutional leadership and wider societal norms were considered by respondents. Respondents discussed their need for awareness of EDI with reference to future professional practice. CONCLUSIONS: Implementation of a regular free-text evaluation question allowed data-gathering across cohorts and throughout several stages of the curriculum, illuminating student experience. Connections established demonstrated intersectionality, and how environment and other factors interact, impacting on student experiences. Students experience EDI-related issues on multiple levels within the educational environment, with consequent impacts on learning. Any successful approach towards tackling issues and promoting equity of opportunity for all requires multi-level actions and widespread culture change. Students can offer fresh and distinct perspectives regarding change needed, to complement and diversify perspectives provided by staff and organisational leadership. Student voice should be enabled to shape change.

Health literacy profiles of final year pre-service teachers in two initial education programs compared with the general population: A cross-sectional study using the Health Literacy Questionnaire.

ISSUE ADDRESSED: Health literacy (HL) can be developed throughout the lifespan starting from the early years highlighting that educational institutions, curriculum and teachers are powerful settings, places and people that can foster HL in youth. Current research shows that Australian teachers need more support to teach health education that promotes students' HL, with limited research focusing on pre-service teachers (PST). This study aims to identify the HL strengths and challenges of PST at one Australian university across two initial teacher education programs (HPE and primary) and compare their health literacy profiles with that of the Australian general population. METHODS: The Health Literacy Questionnaire (HLQ) was administered in March and April, 2022 to measure HL in Australian PST. The research setting was a university in Sydney, Australia, with two of the University's undergraduate initial teacher education (ITE) programs (Health and Physical Education [HPE] and Primary). Of the 24 PST in the HPE cohort, 23 consented. Of the 70 PST in the Primary cohort, 34 consented. The results were compared with Australian Bureau of Statistics data. RESULTS: The participants' median age was 22.3(4.3) years (SD), age ranged from 20 to 54 years, with 36% of participants under the age of 22 years. When comparing the PST data with the general population there were two significant differences: (1) PST scored significantly higher than the general population for Domain 4 (Social support for health, 3.41 vs. 3.19; p < 0.001; d = 0.57); and (2) the PST scored significantly lower for Domain 9 (Understand health information enough to know what to do, 4.02 vs. 4.27; p < 0.01; d = -0.43). In addition, we found that primary PST had significantly lower scores for domains 5-9 (demonstrative of interactive and critical HL), compared with the general Australian population. CONCLUSIONS: Findings show that PST strengths are that they perceive that there they are able to access social support for health, however the PST find it more difficult to analyse and apply health information, compared with the general Australian population. SO WHAT?: Further understanding of health literacy profiles of Australian PST should influence the design of ITE programs and its health education curricular to ensure that PST are able to further develop their HL understandings and capabilities.

Analysis of Trans-Ancestral SLE Risk Loci Identifies Unique Biologic Networks and Drug Targets in African and European Ancestries.

Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disorder with a prominent genetic component. Individuals of African ancestry (AA) experience the disease more severely and with an increased co-morbidity burden compared to European ancestry (EA) populations. We hypothesize that the disparities in disease prevalence, activity, and response to standard medications between AA and EA populations is partially conferred by genomic influences on biological pathways. To address this, we applied a comprehensive approach to identify all genes predicted from SNP-associated risk loci detected with the Immunochip. By combining genes predicted via eQTL analysis, as well as those predicted from base-pair changes in intergenic enhancer sites, coding-region variants, and SNP-gene proximity, we were able to identify 1,731 potential ancestry-specific and trans-ancestry genetic drivers of SLE. Gene associations were linked to upstream and downstream regulators using connectivity mapping, and predicted biological pathways were mined for candidate drug targets. Examination of trans-ancestral pathways reflect the well-defined role for interferons in SLE and revealed pathways associated with tissue repair and remodeling. EA-dominant genetic drivers were more often associated with innate immune and myeloid cell function pathways, whereas AA-dominant pathways mirror clinical findings in AA subjects, suggesting disease progression is driven by aberrant B cell activity accompanied by ER stress and metabolic dysfunction. Finally, potential ancestry-specific and non-specific drug candidates were identified. The integration of all SLE SNP-predicted genes into functional pathways revealed critical molecular pathways representative of each population, underscoring the influence of ancestry on disease mechanism and also providing key insight for therapeutic selection.

E-cigarette use by people who smoke or have recently quit, New South Wales, 2016-2020.

OBJECTIVE: To examine e-cigarette use by adults who smoke or have recently quit, and demographic characteristics associated with their use; to assess reasons for using e-cigarettes. DESIGN: The Cancer Institute NSW Tobacco Tracking Survey (CITTS) is an ongoing, serial, cross-sectional telephone survey study (40 interviews each week). This report is based on interviews during 4 January 2016 - 31 December 2020. SETTING, PARTICIPANTS: Randomly selected New South Wales adults who are current smokers (smoked cigarettes, pipes, or other tobacco products daily, weekly, or less often) or recent quitters (smoked tobacco products in the past twelve months but who no longer smoked). MAIN OUTCOMES: E-cigarette use by age group; reasons for using e-cigarettes. RESULTS: CITTS callers rang 1 494 233 randomly selected numbers; in 203 203 answered calls (13.6%), 11 125 people were eligible for the survey (5.5% of answered calls), of whom 10 004 completed the survey interview, including the question about whether they used e-cigarettes (89.9%). Overall e-cigarette use increased from 6.6% of respondents in 2016 to 13.0% in 2020 (adjusted odds ratio, 1.86; 95% confidence interval [CI], 1.47-2.36). The proportion of respondents aged 18-24 years who reported e-cigarette use increased from 18.4% (95% CI, 12.9-23.9%) in 2018 to 27.2% (95% CI, 20.5-33.9%) in 2020, a larger proportion than for any other age group. The leading reasons offered for e-cigarette use were "to help me quit smoking" (33%; 95% CI, 30-37%) and "to cut down on the number of cigarettes I smoke" (25%; 95% CI, 22-28%). CONCLUSION: The increase between 2016 and 2020 in the proportions of young adults who smoke or have recently quit who use e-cigarettes undermines claims that these products are designed for older smokers who have struggled to quit using other methods.

Twelve tips to foster healthcare student recognition and reporting of unprofessional behaviour or concerns.

Medical trainees and students are required to report concerns where they identify concerning practice or behaviours. While leadership attributes and skills are increasingly expected curricular outcomes, students still struggle to report concerns due to a variety of factors. Changing societal awareness and expectations continue to shine light on poor professionalism and unethical behaviours whose reach extends to medical training and education and that need to be systematically reported and addressed. To prepare graduates for these challenges in professional practice and for exercising skills of reporting concerns, education and training environments must ensure that speaking up is ingrained in the organisational ethos. Supported by evidence from the literature and our experience of revising and enhancing approaches, this paper outlines tips for developing and embedding an infrastructure that facilitates robust concerns reporting and management. Further, we consider mechanisms that support students to develop tendencies and skills for reporting concerns.

Deconvoluting the heterogeneity of SLE: The contribution of ancestry.

Systemic lupus erythematosus (SLE) is a multiorgan autoimmune disorder with a prominent genetic component. Evidence has shown that individuals of non-European ancestry experience the disease more severely, exhibiting an increased incidence of cardiovascular disease, renal involvement, and tissue damage compared with European ancestry populations. Furthermore, there seems to be variability in the response of individuals within different ancestral groups to standard medications, including cyclophosphamide, mycophenolate, rituximab, and belimumab. Although the widespread application of candidate gene, Immunochip, and genome-wide association studies has contributed to our understanding of the link between genetic variation (typically single nucleotide polymorphisms) and SLE, despite decades of research it is still unclear why ancestry remains a key determinant of poorer outcome in non-European-ancestry patients with SLE. Here, we will discuss the impact of ancestry on SLE disease burden in patients from diverse backgrounds and highlight how research efforts using novel bioinformatic and pathway-based approaches have begun to disentangle the complex genetic architecture linking ancestry to SLE susceptibility. Finally, we will illustrate how genomic and gene expression analyses can be combined to help identify novel molecular pathways and drug candidates that might uniquely impact SLE among different ancestral populations.

Hope and sadness: Balancing emotions in tobacco control mass media campaigns aimed at smokers.

ISSUE ADDRESSED: Australia has smoking prevalence of less than 15% among adults, but there are concerns that the rates of decline have stabilised. Sustained mass media campaigns are central to decreasing prevalence, and the emotions evoked by campaigns contribute to their impact. This study investigates the association between potential exposure to campaigns that evoke different emotions on quitting salience (thinking about quitting), quitting intentions and quitting attempts. METHODS: Data on quitting outcomes were obtained from weekly cross-sectional telephone surveys with adult smokers and recent quitters between 2013 and 2018. Campaign activity data were collated, and population-level potential campaign exposure was measured by time and dose. RESULTS: Using multivariate analyses, a positive association between potential exposure to 'hope' campaigns and thinking about quitting and intending to quit was noted, but no association was seen with quit attempts. Potential exposure to 'sadness' evoking campaigns was positively associated with quitting salience and negatively associated with quit attempts, whereas those potentially exposed to campaigns evoking multiple negative emotions (fear, guilt and sadness) were approximately 30% more likely to make a quit attempt. CONCLUSIONS: This study suggests a relationship between the emotional content of campaigns, quitting behaviours. Campaign planners should consider campaigns that evoke negative emotions for population-wide efforts to bring about quitting activity alongside hopeful campaigns that promote quitting salience and quitting intentions. The emotional content of campaigns provides an additional consideration for campaigns targeting smokers and influencing quitting activity. SO WHAT?: This study demonstrates the importance of balancing the emotional content of campaigns to ensure that campaign advertising is given the greatest chance to achieve its objectives. Utilising campaigns that evoke negative emotions appear to be needed to encourage quitting attempts but maintaining hopeful campaigns to promote thinking about quitting and intending to quit is also an important component of the mix of tobacco control campaigns.

Salmonella Typhimurium manipulates macrophage cholesterol homeostasis through the SseJ-mediated suppression of the host cholesterol transport protein ABCA1.

Upon infection of host cells, Salmonella enterica serovar Typhimurium resides in a modified-endosomal compartment referred to as the Salmonella-containing vacuole (SCV). SCV biogenesis is driven by multiple effector proteins translocated through two type III secretion systems (T3SS-1 and T3SS-2). While many host proteins targeted by these effector proteins have been characterised, the role of host lipids in SCV dynamics remains poorly understood. Previous studies have shown that S. Typhimurium infection in macrophages leads to accumulation of intracellular cholesterol, some of which concentrates in and around SCVs; however, the underlying mechanisms remain unknown. Here, we show that S. Typhimurium utilises the T3SS-2 effector SseJ to downregulate expression of the host cholesterol transporter ABCA1 in macrophages, leading to a ~45% increase in cellular cholesterol. Mechanistically, SseJ activates a signalling cascade involving the host kinases FAK and Akt to suppress Abca1 expression. Mutational inactivation of SseJ acyltransferase activity, silencing FAK, or inhibiting Akt prevents Abca1 downregulation and the corresponding accumulation of cholesterol during infection. Importantly, RNAi-mediated silencing of ABCA1 rescued bacterial survival in FAK-deficient macrophages, suggesting that Abca1 downregulation and cholesterol accumulation are important for intracellular survival.

Joint associations of social health and movement behaviours with mortality and cardiovascular disease: an analysis of 497,544 UK biobank participants.

BACKGROUND: Poor physical activity and excessive sedentary behaviour are well-established risk factors for morbidity and mortality. In the presence of emerging social problems, including loneliness and social isolation, these risks may be even greater. We aimed to investigate the joint effects of social health and movement behaviours on mortality and cardiovascular disease (CVD). METHODS: 497,544 UK Biobank participants were followed for an average of 11 years. Loneliness and social isolation were measured via self-report. Physical activity was categorised around current World Health Organisation (WHO) guidelines as low (< 600 metabolic equivalent of task [MET]-mins/week), moderate (600 < 1200) and high (≥ 1200). Sedentary behaviour was classified as low (≤ 3.5 h/day), moderate (3.5 ≤ 5) and high (> 5.5). We derived 24 social health-movement behaviour combinations, accordingly. Mortality and hospitalisations were ascertained to May 2020 for all-cause and CVD mortality, and non-fatal cardiovascular events. RESULTS: Social isolation amplified the risk of both all-cause and CVD death across all physical activity and sedentary levels (hazard ratio, 95% confidence interval [HR, 95% CIs] for all-cause mortality; 1.58 [1.49 to 1.68] for low active-isolated vs. 1.26 [1.22 to 1.30] for low active-not isolated). Loneliness was only found to amplify the risk of death from cardiovascular disease among the high active and low sedentary participants. Loneliness and social isolation did not add to the risk of non-fatal cardiovascular events across most activity levels. CONCLUSION: The detrimental associations of poor physical activity and sedentary behaviour with mortality were consistently amplified by social isolation. Our study supports the need to target the socially isolated as a priority group in preventive public health strategies.

Fair play? Participation equity in organised sport and physical activity among children and adolescents in high income countries: a systematic review and meta-analysis.

BACKGROUND: Physical activity and sport have numerous health benefits and participation is thought to be lower in disadvantaged children and adolescents. However, evidence for the disparity in physical activity is inconsistent, has not been reviewed recently, and for sport has never been synthesised. Our aim was to systematically review, and combine via meta-analyses, evidence of the socioeconomic disparities in physical activity and sport participation in children and adolescents in high income countries. METHODS: We conducted searches of five electronic databases using physical activity, sport, and socioeconomic disparity related terms. Two independent reviewers assessed 21,342 articles for peer-reviewed original research, published in English that assessed socioeconomic disparities in physical activity and sport participation in children and adolescents. We combined evidence from eligible studies using a structural equation modelling approach to multilevel meta-analysis. RESULTS: From the 104 eligible studies, we meta-analysed 163 effect sizes. Overall, children and adolescents living in higher socioeconomic status households were more likely to participate in sport (OR: 1.87, 95% CIs 1.38, 2.36) and participated for a longer duration (d = 0.24, 95% CIs 0.12, 0.35). The socioeconomic disparity in the duration of sport participation was greater in children (d = 0.28, 95% CIs 0.15, 0.41) compared with adolescents (d = 0.13, 95% CIs - 0.03, 0.30). Overall, children and adolescents living in higher socioeconomic status households were more likely to meet physical activity guidelines (OR: 1.21, 95% CIs 1.09, 1.33) and participated for a longer duration (d = 0.08, 95% CIs 0.02, 0.14). The socioeconomic disparity in the duration of total physical activity between low and high socioeconomic status households was greater in children (d = 0.13, 95% CIs 0.04, 0.21) compared with adolescents (d = 0.05, 95% CIs - 0.05, 0.15). There was no significant disparity in leisure time physical activity (d = 0.13, 95% CIs - 0.06, 0.32). CONCLUSIONS: There was evidence of socioeconomic disparities in sport participation and total physical activity participation among children and adolescents. Socioeconomic differences were greater in sport compared to total physical activity and greater in children compared with adolescents. These findings highlight the need importance of targeting sport programs according to socio-economic gradients, to reduce inequities in access and opportunity to organised sport.

Psychometric assessment of scales for measuring loneliness and social isolation: an analysis of the household, income and labour dynamics in Australia (HILDA) survey.

BACKGROUND: Loneliness and social isolation are increasingly recognised as global public health threats, meaning that reliable and valid measures are needed to monitor these conditions at a population level. We aimed to determine if robust and practical scales could be derived for conditions such as loneliness and social isolation using items from a national survey. METHODS: We conducted psychometric analyses of ten items in two waves of the Household, Income and Labour Dynamics in Australia Survey, which included over 15,000 participants. We used the Hull method, exploratory structural equation modelling, and multidimensional item response theory analysis in a calibration sample to determine the number of factors and items within each factor. We cross-validated the factor structure using confirmatory factor analysis in a validation sample. We assessed construct validity by comparing the resulting sub-scales with measures for psychological distress and mental well-being. RESULTS: Calibration and cross-validation consistently revealed a three-factor model, with sub-scales reflecting constructs of loneliness and social isolation. Sub-scales showed high reliability and measurement invariance across waves, gender, and age. Construct validity was supported by significant correlations between the sub-scales and measures of psychological distress and mental health. Individuals who met threshold criteria for loneliness and social isolation had consistently greater odds of being psychologically distressed and having poor mental health than those who did not. CONCLUSIONS: These derived scales provide robust and practical measures of loneliness and social isolation for population-based research.

Improving access to public physical activity events for disadvantaged communities in Australia.

BACKGROUND: Physical activity has numerous health benefits, but participation is lower in disadvantaged communities. 'parkrun' overcomes one of the main barriers for disadvantaged communities, the cost of activities, by providing a free, regular community-based physical activity event for walkers, runners and volunteers. This study assesses equity of access (in terms of distance to the nearest parkrun) stratified by socioeconomic deprivation, and identifies the optimal location for 100 new events to increase equity of access. METHODS: We combined information about population location and socioeconomic deprivation, with information about the location of 403 existing parkrun events, to assess the current level of access by deprivation quintile. We then used a two-step location-allocation analysis (minimising the sum of deprivation-weighted distances) to identify optimal regions, then optimal towns within those regions, as the ideal locations for 100 new parkrun events. RESULTS: Currently, 63.1% of the Australian population lives within 5 km of an event, and the average distance to an event is 14.5 km. A socioeconomic gradient exists, with the most deprived communities having the largest average distance to an event (27.0 km), and the least deprived communities having the best access (living an average 6.6 km from an event). Access improves considerably after the introduction of new event locations with around 68% of the population residing within 5 km of an event, and the average distance to the nearest event approximately 8 km. Most importantly, the improvement in access will be greatest for the most deprived communities (now an average 11 km from an event). CONCLUSIONS: There is a socioeconomic gradient in access to parkrun events. Strategic selection of new parkrun locations will improve equity of access to community physical activity events, and could contribute to enabling greater participation in physical activity by disadvantaged communities.

Is Cohort Representativeness Passé? Poststratified Associations of Lifestyle Risk Factors with Mortality in the UK Biobank.

BACKGROUND: The UK Biobank (UKB) has been used widely to examine associations between lifestyle risk factors and mortality outcomes. It is unknown whether the extremely low UKB response rate (5.5%) and lack of representativeness materially affects the magnitude and direction of effect estimates. METHODS: We used poststratification to match the UKB sample to the target population in terms of sociodemographic characteristics and prevalence of lifestyle risk factors (physical inactivity, alcohol intake, smoking, and poor diet). We compared unweighted and poststratified associations between each lifestyle risk factor and a lifestyle index score with all-cause, cardiovascular disease (CVD), and cancer mortality. We also calculated the unweighted to poststratified ratio of HR (RHR) and 95% confidence interval as a marker of effect-size difference. RESULTS: Of 371,974 UKB participants with no missing data, 302,009 had no history of CVD or cancer, corresponding to 3,298,958 person years of follow-up. Protective associations between alcohol use and CVD mortality observed in the unweighted UKB were substantially altered after poststratification, for example, from a hazard ratio (HR) of 0.63 (0.45-0.87) unweighted to 0.99 (0.65-1.50) poststratified for drinking ≥5 times/week versus never drinking. The magnitude of the poststratified all-cause mortality hazard ratio comparing least healthy with healthiest tertile of lifestyle risk factor index was 9% higher (95% confidence interval: 4%, 14%) than the unweighted estimates. CONCLUSIONS: Lack of representativeness may distort the associations of alcohol with CVD mortality, and may underestimate health hazards among those with cumulatively the least healthy lifestyles.

Effects of the Active Kids voucher program on children and adolescents' physical activity: a natural experiment evaluating a state-wide intervention.

BACKGROUND: There is an urgent need for scaled-up effective interventions which overcome barriers to health-enhancing physical activity for children and adolescents. In New South Wales (NSW), Australia, the state government implemented a universal voucher program, 'Active Kids' to support the cost of structured physical activity registration for school-enrolled children aged 4.5-18 years old. The objective of this study was to understand the effects a financial incentive intervention delivered in a real-world setting has on children and adolescent's physical activity participation. METHOD: In 2018, all children and adolescents registered for an Active Kids voucher provided sociodemographic characteristics, physical activity and research consent. This prospective cohort study used an online survey with validated items to measure physical activity and other personal and social factors in children and adolescents who used an Active Kids voucher. Generalized linear mixed models were used to examine changes from registration to after voucher use at ≤8 weeks, 9-26 weeks and ≥ 6 months. RESULTS: Study participants reported increasing their days achieving physical activity guidelines from 4.0 days per week (95%CI 3.8, 4.2) at registration (n = 37,626 children) to 4.9 days per week (95%CI 4.7, 5.1) after 6 months (n = 14,118 children). Increased physical activity was observed for all sociodemographic population groups. The voucher-specific activity contributed 42.4% (95%CI 39.3, 45.5) to the total time children participated in structured physical activities outside of school. Children and adolescents who increased to, or maintained, high levels of activity were socially supported to be active, had active parent/caregivers, had better concentration and were overall happier than their low-active counterparts. CONCLUSION: The Active Kids program significantly increased children's physical activity levels and these increases continued over a six-month period. The Active Kids voucher program shows promise as a scaled-up intervention to increase children and adolescents' physical activity participation. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry ACTRN12618000897268 , approved May 29th, 2018 - Retrospectively registered.

Qualitative exploration of medical student experiences during the Covid-19 pandemic: implications for medical education.

BACKGROUND: During the Covid-19 pandemic medical students were offered paid roles as medical student healthcare assistants. Anecdotal reports suggested that students found this experience rich for learning. Previous studies have explored alternative models of student service, however this defined medical student support role is novel. METHODS: Individual semi-structured interviews were recorded with 20 medical students at a UK medical school exploring their experiences of placement learning and experiences of working as healthcare assistants. Responses were analysed qualitatively using a framework approach. The framework was developed into a model describing key findings and their relationships. RESULTS: Interviews yielded data that broadly covered aspects of (1) Medical students' experiences of clinical placement learning (2) Medical students' experiences of working as medical student healthcare assistants (3) Learning resulting from working as a healthcare assistant (4) Hierarchies and professional barriers in the clinical environment (5) Influences on professional identity. Participants described barriers and facilitators of clinical learning and how assuming a healthcare assistant role impacted on learning and socialisation within the multidisciplinary team. Students became increasingly socialised within the healthcare team, contributing directly to patient care; the resulting social capital opened new opportunities for learning, team working and enhanced students' interprofessional identity. Students described the impact of these experiences on their aspirations for their future practice. CONCLUSIONS: Changes to work patterns in healthcare and delivery models of medical education have eroded opportunities for students to contribute to healthcare delivery and be embedded within a team. This is impacting negatively on student learning and socialisation and we suggest that medical curricula have much to learn from nursing and allied health professional training. Longitudinal embedment with a multidisciplinary team, where students have a defined role and work directly with patients may not only add value to clinical service, but also overcome current barriers to effective placement learning and interprofessional identity formation for medical students.

Strong support for broad policies to prevent childhood obesity among mothers in New South Wales, Australia.

ISSUE ADDRESSED: Support for broad policies to prevent childhood obesity is not clear. This study aimed to investigate the level of support for state government health promotion policies among mothers with infants and its associated factors. METHODS: This secondary analysis of data from 1155 mothers in NSW assessed approval for six policy options derived from public health approaches to obesity. Descriptive statistics were used to show the extent of policy approval across the cohort. Logistic regression models tested associations between perceived susceptibility and perceived severity of childhood obesity and approval of each policy option. RESULTS: The proportion of mothers who felt these policy options were 'about the right amount' (56%-68%) or 'not going far enough' (24%-36%), collectively represented 89%-95% approval of government intervention. In comparison, 5%-11% felt that these policies were 'going too far'. Factors associated with their levels of support varied between each policy option, based on mothers' characteristics and perceptions of childhood obesity. CONCLUSION: These findings indicate high support for government intervention to prevent obesity among mothers in NSW and support health promotion advocacy in this area. SO WHAT?: Governments should give due consideration to implementing each of the six policy options and prioritise the implementation of restrictions on fast food advertising in publicly owned or controlled areas.

The pathogenesis of systemic lupus erythematosus: Harnessing big data to understand the molecular basis of lupus.

Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease that causes damage to multiple organ systems. Despite decades of research and available murine models that capture some aspects of the human disease, new treatments for SLE lag behind other autoimmune diseases such as Rheumatoid Arthritis and Crohn's disease. Big data genomic assays have transformed our understanding of SLE by providing important insights into the molecular heterogeneity of this multigenic disease. Gene wide association studies have demonstrated more than 100 risk loci, supporting a model of multiple genetic hits increasing SLE risk in a non-linear fashion, and providing evidence of ancestral diversity in susceptibility loci. Epigenetic studies to determine the role of methylation, acetylation and non-coding RNAs have provided new understanding of the modulation of gene expression in SLE patients and identified new drug targets and biomarkers for SLE. Gene expression profiling has led to a greater understanding of the role of myeloid cells in the pathogenesis of SLE, confirmed roles for T and B cells in SLE, promoted clinical trials based on the prominent interferon signature found in SLE patients, and identified candidate biomarkers and cellular signatures to further drug development and drug repurposing. Gene expression studies are advancing our understanding of the underlying molecular heterogeneity in SLE and providing hope that patient stratification will expedite new therapies based on personal molecular signatures. Although big data analyses present unique interpretation challenges, both computationally and biologically, advances in machine learning applications may facilitate the ability to predict changes in SLE disease activity and optimize therapeutic strategies.

A monitoring system to provide feedback on student physical activity during physical education lessons.

School-based physical education (PE) provides opportunities to accumulate moderate-to-vigorous physical activity (MVPA), but many students are insufficiently active during PE lessons. Providing teachers with feedback regarding their students' physical activity may increase the effectiveness of PE for achieving MVPA goals, but existing physical activity monitoring technologies have limitations in class environments. Therefore, the purpose of this study was to develop and validate a system capable of providing feedback on PE lesson MVPA. Equations for translating step counts to %MVPA were derived from measures in 492 students who concurrently wore an ActiGraph GT3X+ (ActiGraph) and Yamax pedometer (Yamax) during a PE lesson. To enhance feedback availability during PE lessons, we then developed a bespoke monitoring system using wireless tri-axial pedometers (HMM) and a smart device app. After developing and testing the monitoring system, we assessed its validity and reliability in 100 students during a PE lesson. There was a strong correlation of 0.896 between step counts and accelerometer-determined %MVPA and quantile regression equations showed good validity for translating step counts to %MVPA with a mean absolute difference of 5.3 (95% CI, 4.4-6.2). The physical activity monitoring system was effective at providing %MVPA during PE lessons with a mean difference of 1.6 ± 7.1 compared with accelerometer-determined %MVPA (7% difference between the two measurement methods). Teachers and students can use a smart device app and wireless pedometers to conveniently obtain feedback during PE lessons. Future studies should determine whether such technologies help teachers to increase physical activity during PE lessons.

An internet-supported school physical activity intervention in low socioeconomic status communities: results from the Activity and Motivation in Physical Education (AMPED) cluster randomised controlled trial.

OBJECTIVE: Quality physical education (PE) is the cornerstone of comprehensive school physical activity (PA) promotion programmes. We tested the efficacy of a teacher professional learning intervention, delivered partially via the internet, designed to maximise opportunities for students to be active during PE lessons and enhance adolescents' motivation towards PE and PA. METHODS: A two-arm cluster randomised controlled trial with teachers and Grade 8 students from secondary schools in low socioeconomic areas of Western Sydney, Australia. The Activity and Motivation in Physical Education (AMPED) intervention for secondary school PE teachers included workshops, online learning, implementation tasks and mentoring sessions. The primary outcome was the proportion of PE lesson time that students spent in moderate-to-vigorous physical activity (MVPA), measured by accelerometers at baseline, postintervention (7-8 months after baseline) and maintenance (14-15 months). Secondary outcomes included observed PE teachers' behaviour during lessons, students' leisure-time PA and students' motivation. RESULTS: Students (n=1421) from 14 schools completed baseline assessments and were included in linear mixed model analyses. The intervention had positive effects on students' MVPA during lessons. At postintervention, the adjusted mean difference in the proportion of lesson time spent in MVPA was 5.58% (p<0.001, approximately 4 min/lesson). During the maintenance phase, this effect was 2.64% (p<0.001, approximately 2 min/lesson). The intervention had positive effects on teachers' behaviour, but did not impact students' motivation. CONCLUSIONS: AMPED produced modest improvements in MVPA and compares favourably with previous interventions delivered exclusively face-to-face. Online teacher training could help facilitate widespread dissemination of professional learning interventions. TRIAL REGISTRATION NUMBER: ACTRN12614000184673.