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(1) Background: More time spent on social media has been linked to increased alcohol use, with exposure to peer alcohol-related content on social media (content exposure) named as a critical factor in this relationship. Little is currently known about whether early content exposure may have lasting effects across adolescent development, or about the capacity of parental monitoring of social media use to interrupt these links. (2) Methods: These gaps were addressed in both cross-sectional and longitudinal contexts among a longitudinal sample of Australian secondary school students (n = 432) across the ages of 13-16. (3) Results: Evidence was found for links between social media use and alcohol use frequency in early development. Social media time at age 13 was significantly associated with concurrent alcohol use frequency. At age 13, alcohol use frequency was significantly higher among those who reported content exposure compared to those who reported no exposure. Longitudinally, the frequency of alcohol use over time increased at a faster rate among participants who reported content exposure at age 13. In terms of parental monitoring, no longitudinal effects were observed. However, parental monitoring at age 13 did significantly reduce the concurrent relationship between alcohol use frequency and content exposure. (4) Conclusion: The impact of social media content exposure on alcohol use in adolescence may be more important than the time spent on social media, and any protective effect of parental monitoring on content exposure may be limited to the time it is being concurrently enacted.

Haematopoiesis in the bone marrow (BM) maintains blood and immune cell production throughout postnatal life. Haematopoiesis first emerges in human BM at 11-12 weeks after conception1,2, yet almost nothing is known about how fetal BM (FBM) evolves to meet the highly specialized needs of the fetus and newborn. Here we detail the development of FBM, including stroma, using multi-omic assessment of mRNA and multiplexed protein epitope expression. We find that the full blood and immune cell repertoire is established in FBM in a short time window of 6-7 weeks early in the second trimester. FBM promotes rapid and extensive diversification of myeloid cells, with granulocytes, eosinophils and dendritic cell subsets emerging for the first time. The substantial expansion of B lymphocytes in FBM contrasts with fetal liver at the same gestational age. Haematopoietic progenitors from fetal liver, FBM and cord blood exhibit transcriptional and functional differences that contribute to tissue-specific identity and cellular diversification. Endothelial cell types form distinct vascular structures that we show are regionally compartmentalized within FBM. Finally, we reveal selective disruption of B lymphocyte, erythroid and myeloid development owing to a cell-intrinsic differentiation bias as well as extrinsic regulation through an altered microenvironment in Down syndrome (trisomy 21).

Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12-87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS-or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research.

Introduction: Risk behaviors commonly co-occur, typically emerge in adolescence, and become entrenched by adulthood. This study investigated the clustering of established (physical inactivity, diet, smoking, and alcohol use) and emerging (sedentary behavior and sleep) chronic disease risk factors among young Australian adults, and examined how clusters relate to mental health. Methods: The sample was derived from the long-term follow-up of a cohort of Australians. Participants were initially recruited at school as part of a cluster randomized controlled trial. A total of 853 participants (Mage = 18.88 years, SD = 0.42) completed an online self-report survey as part of the 5-year follow-up for the RCT. The survey assessed six behaviors (binge drinking and smoking in the past 6 months, moderate-to-vigorous physical activity/week, sitting time/day, fruit and vegetable intake/day, and sleep duration/night). Each behavior was represented by a dichotomous variable reflecting adherence to national guidelines. Exploratory analyses were conducted. Clusters were identified using latent class analysis. Results: Three classes emerged: "moderate risk" (moderately likely to binge drink and not eat enough fruit, high probability of insufficient vegetable intake; Class 1, 52%); "inactive, non-smokers" (high probabilities of not meeting guidelines for physical activity, sitting time and fruit/vegetable consumption, very low probability of smoking; Class 2, 24%), and "smokers and binge drinkers" (high rates of smoking and binge drinking, poor fruit/vegetable intake; Class 3, 24%). There were significant differences between the classes in terms of psychological distress (p = 0.003), depression (p < 0.001), and anxiety (p = 0.003). Specifically, Class 3 ("smokers and binge drinkers") showed higher levels of distress, depression, and anxiety than Class 1 ("moderate risk"), while Class 2 ("inactive, non-smokers") had greater depression than the "moderate risk" group. Discussion: Results

BACKGROUND: The Climate and Preventure (CAP) study was the first trial to assess and demonstrate the effectiveness of a combined universal and selective approach for preventing alcohol use and related harms among adolescents. The current paper reports universal effects from the CAP study on cannabis-related outcomes over three years. METHODS: A cluster randomized controlled trial was conducted with 2190 students from twenty-six Australian high schools (mean age: 13.3 yrs., SD 0.48). Participants were randomised to one of four conditions; universal prevention for all students (Climate); selective prevention for high-risk students (Preventure); combined universal and selective prevention (Climate and Preventure; CAP); or health education as usual (Control). Participants were assessed at baseline, post intervention (6-9 months post baseline), and at 12-, 24- and 36-months, on measures of cannabis use, knowledge and related harms. This paper compares cannabis-related knowledge, harms and cannabis use in the Control, Climate and CAP groups as specified in the protocol, using multilevel mixed linear models to assess outcomes. RESULTS: Compared to Control, the Climate and CAP groups showed significantly greater increases in cannabis-related knowledge initially (p < 0.001), and had higher knowledge at the 6, 12 and 24-month follow-ups. There was no significant difference between the Climate and CAP groups. While no differences were detected between Control and the CAP and Climate groups on cannabis use or cannabis-related harms, the prevalence of these outcomes was lower than anticipated, possibly limiting power to detect intervention effects. Additional Bayesian analyses exploring confidence in accepting the null hypothesis showed there was insufficient evidence to conclude that the interventions had no effect, or to conclude that they had a meaningfully large effect. CONCLUSIONS: Both the universal Climate and the combined CAP programs were effective in increasing cannab

BACKGROUND: Alcohol use and associated harms are among the leading causes of burden of disease among young people, highlighting the need for effective prevention. The Climate and Preventure (CAP) study was the first trial of a combined universal and selective school-based approach to preventing alcohol misuse among adolescents. Initial results indicate that universal, selective and combined prevention were all effective in delaying the uptake of alcohol use and binge drinking for up to 3 years following the interventions. However, little is known about the sustainability of prevention effects across the transition to early adulthood, a period of increased exposure to alcohol and other drug use. This paper describes the protocol for the CAP long-term follow-up study which will determine the effectiveness of universal, selective and combined alcohol misuse prevention up to 7 years post intervention, and across the transition from adolescence into early adulthood. METHODS: A cluster randomized controlled trial was conducted between 2012 and 2015 with 2190 students (mean age: 13.3 yrs) from 26 Australian high schools. Participants were randomized to receive one of four conditions; universal prevention for all students (Climate); selective prevention for high-risk students (Preventure); combined universal and selective prevention (Climate and Preventure; CAP); or health education as usual (Control). The positive effect of the interventions on alcohol use at 12-, 24- and 36-month post baseline have previously been reported. This study will follow up the CAP study cohort approximately 5- and 7-years post baseline. The primary outcome will be alcohol use and related harms. Secondary outcomes will be cannabis use, alcohol and other drug harms including violent behavior, and mental health symptomatology. Analyses will be conducted using multi-level, mixed effects models within an intention-to-treat framework. DISCUSSION: This study will provide the first ever evaluation of th

Background: Mental health and substance use disorders are the leading causes of global disability in children and youth. Both tend to first onset or escalate in adolescence and young adulthood, calling for effective prevention during this time. The Climate Schools Combined (CSC) study was the first trial of a Web-based combined universal approach, delivered through school classes, to prevent both mental health and substance use problems in adolescence. There is also limited evidence for the cost-effectiveness of school-based prevention programs. Objective: The aim of this protocol paper is to describe the CSC follow-up study, which aims to determine the long-term efficacy and cost-effectiveness of the CSC prevention program for depression, anxiety, and substance use (alcohol and cannabis use) up to 7 years post intervention. Methods: A cluster randomized controlled trial (the CSC study) was conducted with 6411 participants aged approximately 13.5 years at baseline from 2014 to 2016. Participating schools were randomized to 1 of 4 conditions: (1) control (health education as usual), (2) Climate Substance Use (universal substance use prevention), (3) Climate Mental Health (universal mental health prevention), or (4) CSC (universal substance use and mental health prevention). It was hypothesized that the CSC program would be more effective than conditions (1) to (3) in reducing alcohol and cannabis use (and related harms), anxiety, and depression symptoms as well as increasing knowledge related to alcohol, cannabis, anxiety, and depression. This long-term study will invite follow-up participants to complete 3 additional Web-based assessments at approximately 5, 6, and 7 years post baseline using multiple sources of locator information already provided to the research team. The primary outcomes include alcohol and cannabis use (and related harms) and mental health symptoms. An economic evaluation of the program will also be conducted using both data linkage as well as s