The PARTNER trial of neoadjuvant olaparib with chemotherapy in triple-negative breast cancer.

PARTNER is a prospective, phase II-III, randomized controlled clinical trial that recruited patients with triple-negative breast cancer1,2, who were germline BRCA1 and BRCA2 wild type3. Here we report the results of the trial. Patients (n = 559) were randomized on a 1:1 basis to receive neoadjuvant carboplatin-paclitaxel with or without 150 mg olaparib twice daily, on days 3 to 14, of each of four cycles (gap schedule olaparib, research arm) followed by three cycles of anthracycline-based chemotherapy before surgery. The primary end point was pathologic complete response (pCR)4, and secondary end points included event-free survival (EFS) and overall survival (OS)5. pCR was achieved in 51% of patients in the research arm and 52% in the control arm (P = 0.753). Estimated EFS at 36 months in the research and control arms was 80% and 79% (log-rank P > 0.9), respectively; OS was 90% and 87.2% (log-rank P = 0.8), respectively. In patients with pCR, estimated EFS at 36 months was 90%, and in those with non-pCR it was 70% (log-rank P < 0.001), and OS was 96% and 83% (log-rank P < 0.001), respectively. Neoadjuvant olaparib did not improve pCR rates, EFS or OS when added to carboplatin-paclitaxel and anthracycline-based chemotherapy in patients with triple-negative breast cancer who were germline BRCA1 and BRCA2 wild type. ClinicalTrials.gov ID: NCT03150576 .

Gut immune maturation depends on colonization with a host-specific microbiota.

Gut microbial induction of host immune maturation exemplifies host-microbe mutualism. We colonized germ-free (GF) mice with mouse microbiota (MMb) or human microbiota (HMb) to determine whether small intestinal immune maturation depends on a coevolved host-specific microbiota. Gut bacterial numbers and phylum abundance were similar in MMb and HMb mice, but bacterial species differed, especially the Firmicutes. HMb mouse intestines had low levels of CD4(+) and CD8(+) T cells, few proliferating T cells, few dendritic cells, and low antimicrobial peptide expression--all characteristics of GF mice. Rat microbiota also failed to fully expand intestinal T cell numbers in mice. Colonizing GF or HMb mice with mouse-segmented filamentous bacteria (SFB) partially restored T cell numbers, suggesting that SFB and other MMb organisms are required for full immune maturation in mice. Importantly, MMb conferred better protection against Salmonella infection than HMb. A host-specific microbiota appears to be critical for a healthy immune system.

Epigenotype-genotype-phenotype correlations in SETD1A and SETD2 chromatin disorders.

Germline pathogenic variants in two genes encoding the lysine-specific histone methyltransferase genes SETD1A and SETD2 are associated with neurodevelopmental disorders (NDDs) characterized by developmental delay and congenital anomalies. The SETD1A and SETD2 gene products play a critical role in chromatin-mediated regulation of gene expression. Specific methylation episignatures have been detected for a range of chromatin gene-related NDDs and have impacted clinical practice by improving the interpretation of variant pathogenicity. To investigate if SETD1A and/or SETD2-related NDDs are associated with a detectable episignature, we undertook targeted genome-wide methylation profiling of > 2 M CpGs using a next-generation sequencing-based assay. A comparison of methylation profiles in patients with SETD1A variants (n = 6) did not reveal evidence of a strong methylation episignature. A review of the clinical and genetic features of the SETD2 patient group revealed that, as reported previously, there were phenotypic differences between patients with truncating mutations (n = 4, Luscan-Lumish syndrome; MIM:616831) and those with missense codon 1740 variants [p.Arg1740Trp (n = 4) and p.Arg1740Gln (n = 2)]. Both SETD2 subgroups demonstrated a methylation episignature, which was characterized by hypomethylation and hypermethylation events, respectively. Within the codon 1740 subgroup, both the methylation changes and clinical phenotype were more severe in those with p.Arg1740Trp variants. We also noted that two of 10 cases with a SETD2-NDD had developed a neoplasm. These findings reveal novel epigenotype-genotype-phenotype correlations in SETD2-NDDs and predict a gain-of-function mechanism for SETD2 codon 1740 pathogenic variants.

Lymphatic Invasion of Plakoglobin-Dependent Tumor Cell Clusters Drives Formation of Polyclonal Lung Metastases in Colon Cancer.

BACKGROUND & AIMS: Patients with colon cancer with liver metastases may be cured with surgery, but the presence of additional lung metastases often precludes curative treatment. Little is known about the processes driving lung metastasis. This study aimed to elucidate the mechanisms governing lung vs liver metastasis formation. METHODS: Patient-derived organoid (PDO) cultures were established from colon tumors with distinct patterns of metastasis. Mouse models recapitulating metastatic organotropism were created by implanting PDOs into the cecum wall. Optical barcoding was applied to trace the origin and clonal composition of liver and lung metastases. RNA sequencing and immunohistochemistry were used to identify candidate determinants of metastatic organotropism. Genetic, pharmacologic, in vitro, and in vivo modeling strategies identified essential steps in lung metastasis formation. Validation was performed by analyzing patient-derived tissues. RESULTS: Cecum transplantation of 3 distinct PDOs yielded models with distinct metastatic organotropism: liver only, lung only, and liver and lung. Liver metastases were seeded by single cells derived from select clones. Lung metastases were seeded by polyclonal clusters of tumor cells entering the lymphatic vasculature with very limited clonal selection. Lung-specific metastasis was associated with high expression of desmosome markers, including plakoglobin. Plakoglobin deletion abrogated tumor cell cluster formation, lymphatic invasion, and lung metastasis formation. Pharmacologic inhibition of lymphangiogenesis attenuated lung metastasis formation. Primary human colon, rectum, esophagus, and stomach tumors with lung metastases had a higher N-stage and more plakoglobin-expressing intra-lymphatic tumor cell clusters than those without lung metastases. CONCLUSIONS: Lung and liver metastasis formation are fundamentally distinct processes with different evolutionary bottlenecks, seeding entities, and anatomic routing. Polyclonal lung metastases originate from plakoglobin-dependent tumor cell clusters entering the lymphatic vasculature at the primary tumor site.

Anti-CCR9 chimeric antigen receptor T cells for T-cell acute lymphoblastic leukemia.

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of immature T lymphocytes, associated with higher rates of induction failure compared with those in B cell acute lymphoblastic leukemia. The potent immunotherapeutic approaches applied in B cell acute lymphoblastic leukemia, which have revolutionized the treatment paradigm, have proven more challenging in T-ALL, largely due to a lack of target antigens expressed on malignant but not healthy T cells. Unlike B cell depletion, T-cell aplasia is highly toxic. Here, we show that the chemokine receptor CCR9 is expressed in >70% of cases of T-ALL, including >85% of relapsed/refractory disease, and only on a small fraction (<5%) of normal T cells. Using cell line models and patient-derived xenografts, we found that chimeric antigen receptor (CAR) T-cells targeting CCR9 are resistant to fratricide and have potent antileukemic activity both in vitro and in vivo, even at low target antigen density. We propose that anti-CCR9 CAR-T cells could be a highly effective treatment strategy for T-ALL, avoiding T cell aplasia and the need for genome engineering that complicate other approaches.

The long-term effectiveness of a personality-targeted substance use prevention program on aggression from adolescence to early adulthood.

BACKGROUND: Addressing aggressive behavior in adolescence is a key step toward preventing violence and associated social and economic costs in adulthood. This study examined the secondary effects of the personality-targeted substance use preventive program Preventure on aggressive behavior from ages 13 to 20. METHODS: In total, 339 young people from nine independent schools (M age = 13.03 years, s.d. = 0.47, range = 12-15) who rated highly on one of the four personality traits associated with increased substance use and other emotional/behavioral symptoms (i.e. impulsivity, anxiety sensitivity, sensation seeking, and negative thinking) were included in the analyses (n = 145 in Preventure, n = 194 in control). Self-report assessments were administered at baseline and follow-up (6 months, 1, 2, 3, 5.5, and 7 years). Overall aggression and subtypes of aggressive behaviors (proactive, reactive) were examined using multilevel mixed-effects analysis accounting for school-level clustering. RESULTS: Across the 7-year follow-up period, the average yearly reduction in the frequency of aggressive behaviors (b = -0.42; 95% confidence interval [CI] -0.64 to -0.20; p < 0.001), reactive aggression (b = -0.22; 95% CI 0.35 to -0.10; p = 0.001), and proactive aggression (b = -0.14; 95% CI -0.23 to -0.05; p = 0.002) was greater for the Preventure group compared to the control group. CONCLUSIONS: The study suggests a brief personality-targeted intervention may have long-term impacts on aggression among young people; however, this interpretation is limited by imbalance of sex ratios between study groups.

Heart disease and stroke statistics 2023 update from the American Heart Association-implications for nephrology.

The annual American Heart Association (AHA) and National Institutes of Health statistical report details the most up to date statistics related to heart disease, stroke and cardiovascular risk factors, primarily within the USA. Although not a formal systematic review or meta-analysis, this 600 page report provides the most comprehensive and best summary of cardiovascular statistics for the year in question. Although data are collated from USA data registries, it serves as a critical resource for clinicians, policymakers, administrators and researchers in the northern and southern hemispheres. In this special report, we have chosen to highlight aspects of the document that are relevant to nephrologists, given the overlap of cardiovascular and renal disease. These include (i) key and emerging cardiovascular data signals in the general and chronic kidney disease (CKD) populations, (ii) ethnic and socio-economic disparity, (iii) environmental and behavioural factors that drive high levels of cardiovascular disease and which are key components of the AHA's eight components of the Life Essential cardiovascular health score, and (iv) the impact of COVID-19 both directly and indirectly on heart health. We provide some commentary and critical analysis of both the data and of the production of such data sets suggesting that similar data on CKD could also be published and linked to the AHA and other datasets.

Age at first drink and its influence on alcohol use behaviours in young adulthood: Evidence from an Australian household-based panel study.

BACKGROUND: Public health guidelines recommend delaying the initiation age for alcohol. However, the causal link between age-at-first-drink (AFD) and future alcohol use in young adulthood is uncertain. This study examined the association between AFD and alcohol-related outcomes at age 20 years using an Australian sample. METHODS: Data were obtained from Waves 1-19 (years 2001-2019) of the Household, Income and Labour Dynamics in Australia Survey on 20-year-olds with responses across ≥3 consecutive waves (n = 2278). The AFD for each respondent (between 15 and 20 years) was analysed relative to Australian legal drinking age (18 years). Inverse probability treatment weighting was used to evaluate associations between AFD and four outcomes at age 20 years: risk of current alcohol use; quantity of weekly alcohol consumption; risk of binge drinking; and frequency of binge drinking. Adjustments were made for confounders (e.g., heavy drinking by parents). Robustness of study findings was evaluated using several diagnostic tests/sensitivity analyses. RESULTS: Among 20-year-olds, those with an AFD of 15-16 years consumed significantly more alcohol per week compared to an AFD of 18 years. Additionally, 20-year-old drinkers with an AFD of 16 years were significantly more likely to binge drink (though this association was likely confounded). An inverse dose-response relationship was observed between AFD and weekly alcohol consumption at 20 years, where a higher AFD led to lower alcohol consumption. CONCLUSION: Study findings indicate an association between a higher AFD and consuming less alcohol in young adulthood, which could potentially support the scale-up of prevention programs to delay AFD among Australian adolescents.

Structure of psychopathology in adolescents and its association with high-risk personality traits.

The present study examined high-risk personality traits and associations with psychopathology across multiple levels of a hierarchical-dimensional model of psychopathology in a large adolescent, general population sample. Confirmatory factor analyses were run using data from two randomized controlled trials of Australian adolescents (N = 8,654, mean age = 13.01 years, 52% female). A higher-order model - comprised of general psychopathology, fear, distress, alcohol use/harms, and conduct/inattention dimensions - was selected based on model fit, reliability, and replicability. Indirect-effects models were estimated to examine the unique associations between high-risk personality traits (anxiety sensitivity, negative thinking, impulsivity, and sensation seeking) and general and specific dimensions and symptoms of psychopathology. All personality traits were positively associated with general psychopathology. After accounting for general psychopathology, anxiety sensitivity was positively associated with fear; negative thinking was positively associated with distress; impulsivity was positively associated with conduct/inattention; and sensation seeking was positively associated with alcohol use/harms and conduct/inattention, and negatively associated with fear. Several significant associations between personality traits and individual symptoms remained after accounting for general and specific psychopathology. These findings contribute to our understanding of the underlying structure of psychopathology among adolescents and have implications for the development of personality-based prevention and early intervention programs.

The Triple E project: a factorial randomised controlled trial to enhance engagement with eHealth approaches to improve health risk behaviours among adolescents.

BACKGROUND: Digital, or eHealth, interventions are highly promising approaches to help adolescents improve their health behaviours and reduce their risk of chronic disease. However, they often have low uptake and retention. There is also a paucity of high-quality research into the predictors of eHealth engagement, and a lack of studies that have systematically evaluated existing engagement strategies in adolescent populations. This paper describes the protocol for a randomised controlled trial which primarily aims to assess the effectiveness of different strategies in increasing engagement with a healthy lifestyles app, Health4Life. Associations between the engagement strategies and improvements in adolescent health behaviours (healthy eating, physical activity, sleep, recreational screen time, smoking, alcohol use) will also be examined, along with potential predictors of adolescents' intentions to use health apps and their use of the Health4Life app. METHODS: The current study will aim to recruit 336 adolescent and parent/guardian dyads (total sample N = 672) primarily through Australia wide online advertising. All adolescent participants will have access to the Health4Life app (a multiple health behaviour change, self-monitoring mobile app). The trial will employ a 24 factorial design, where participants will be randomly allocated to receive 1 of 16 different combinations of the four engagement strategies to be evaluated: text messages, access to a health coach, access to additional gamified app content, and provision of parent/guardian information resources. Adolescents and parents/guardians will both complete consent processes, baseline assessments, and a follow-up assessment after 3 months. All participants will also be invited to complete a qualitative interview shortly after follow-up. The primary outcome, app engagement, will be assessed via an App Engagement Index (Ei) using data collected in the Health4Life app and the Mobile App Rating Scale - User version. DISCUSSION: This research will contribute significantly to building our understanding of the types of strategies that are most effective in increasing adolescents' engagement with health apps and which factors may predict adolescents' use of health apps. TRIAL REGISTRATION: The trial is registered at the Australian New Zealand Clinical Trials Registry (ACTRN12623000399695). Date registered: 19/04/2023.

Mental ill-health and substance use among sexuality diverse adolescents: The critical role of school climate and teacher self-efficacy.

INTRODUCTION: Mental ill-health, substance use and their co-occurrence among sexuality diverse young people during earlier adolescence is relatively understudied. The preventive utility of positive school climate for sexuality diverse adolescents' mental health is also unclear, as well as the role of teachers in conferring this benefit. METHOD: Using Wave 8 'B Cohort' data from the Longitudinal Study of Australian children (N = 3127, Mage = 14.3), prevalence ratios and odds ratios were used to assess prevalence and disparities in mental ill-health and substance use, and multinomial logistic regression for co-occurring outcomes, among sexuality diverse adolescents relative to heterosexual peers. Logistic regression was used to assess associations between school climate and teacher self-efficacy with sexuality diverse adolescents' mental health. RESULTS: Mental ill-health prevalence ranged from 22% (suicidal thoughts/behaviour) to 46% (probable depressive disorders) and substance use between 66% (cigarette use) and 97% (alcohol use). Sexuality diverse participants were significantly more likely to report self-harm and high levels of emotional symptoms in co-occurrence with cigarette, alcohol and/or cannabis use. For each 1-point increase in school climate scores as measured by the Psychological Sense of School Membership scale, there was 10% reduction in sexuality diverse adolescents reporting high levels of emotional symptoms, probable depressive disorder, self-harm thoughts/behaviour and suicidal thoughts/behaviour. For each 1-point increase in lower perceived (worse) teacher self-efficacy scores as measured by four bespoke teacher self-efficacy items, odds of sexuality diverse adolescent-reported suicidal thoughts/behaviour increased by 80%. DISCUSSION: Mental ill-health, substance use and especially their co-occurrence, are highly prevalent and pose significant and inequitable health and well-being risks. Schools represent a potential site for focusing future prevention efforts and educating and training teachers on sexuality diversity is a promising pathway towards optimising these.

A multi-omics approach to lignocellulolytic enzyme discovery reveals a new ligninase activity from Parascedosporium putredinis NO1.

Lignocellulose, the structural component of plant cells, is a major agricultural byproduct and the most abundant terrestrial source of biopolymers on Earth. The complex and insoluble nature of lignocellulose limits its conversion into value-added commodities, and currently, efficient transformation requires expensive pretreatments and high loadings of enzymes. Here, we report on a fungus from the Parascedosporium genus, isolated from a wheat-straw composting community, that secretes a large and diverse array of carbohydrate-active enzymes (CAZymes) when grown on lignocellulosic substrates. We describe an oxidase activity that cleaves the major ß-ether units in lignin, thereby releasing the flavonoid tricin from monocot lignin and enhancing the digestion of lignocellulose by polysaccharidase mixtures. We show that the enzyme, which holds potential for the biorefining industry, is widely distributed among lignocellulose-degrading fungi from the Sordariomycetes phylum.

Potential Mediators of a School-Based Digital Intervention Targeting Six Lifestyle Risk Behaviours in a Cluster Randomised Controlled Trial of Australian Adolescents.

Lifestyle risk behaviours-physical inactivity, poor diet, poor sleep, recreational screen time, and alcohol and tobacco use-collectively known as the "Big 6" emerge during adolescence and significantly contribute to chronic disease development into adulthood. To address this issue, the Health4Life program targeted the Big 6 risk behaviours simultaneously via a co-designed eHealth school-based multiple health behaviour change (MHBC) intervention. This study used multiple causal mediation analysis to investigate some potential mediators of Health4Life's effects on the Big 6 primary outcomes from a cluster randomised controlled trial of Health4Life among Australian school children. Mediators of knowledge, behavioural intentions, self-efficacy, and self-control were assessed. The results revealed a complex pattern of mediation effects across different outcomes. Whilst there was a direct effect of the intervention on reducing moderate-to-vigorous physical activity risk, the impact on sleep duration appeared to occur indirectly through the hypothesised mediators. Conversely, for alcohol and tobacco use, both direct and indirect effects were observed in opposite directions cancelling out the total effect (competitive partial mediation). The intervention's effects on alcohol and tobacco use highlighted complexities, suggesting the involvement of additional undetected mediators. However, little evidence supported mediation for screen time and sugar-sweetened beverage intake risk. These findings emphasise the need for tailored approaches when addressing different risk behaviours and designing effective interventions to target multiple health risk behaviours. The trial was pre-registered with the Australian and New Zealand Clinical Trials Registry: ACTRN12619000431123.

A Systematic Review and Meta-analysis of School-Based Preventive Interventions Targeting E-Cigarette Use Among Adolescents.

This study aimed to examine the efficacy of school-based e-cigarette preventive interventions via a systematic review and meta-analysis. We searched Medline, Embase, PsycINFO, Scopus, CINAHL, Cochrane, and clinical trial registries for studies published between January 2000 and June 2023 using keywords for e-cigarettes, adolescents, and school. Of 1566 double-screened records, 11 met the criteria of targeting adolescents, evaluating an e-cigarette preventive intervention, being conducted in a secondary school, using a randomized controlled trial (RCT), cluster RCT, or quasi-experimental design, and comparing an intervention to a control. Pre-specified data pertaining to the study design, outcomes, and quality were extracted by one reviewer and confirmed by a second, and where necessary, a third reviewer. Meta-analyses found no evidence that school-based interventions prevented e-cigarette use at the longest follow-up, which ranged between 6 and 36 months post-intervention (OR = 0.43, 95% CI = 0.16, 1.12; p = 0.09). However, subgroup analyses identified significant effects at post-test and when studies with < 12-month follow-up were omitted. No effect was found for tobacco use at the longest follow-up (OR = 1.01, 95% CI = 0.65, 1.59, p = 0.95); however, reductions in past 30-day tobacco use (OR = 0.59, 95% CI = 0.39, 0.89, p = 0.01) which encompassed e-cigarettes in some studies were identified. Narrative synthesis supported these mixed results and found some school-based interventions prevented or reduced e-cigarette and/or tobacco use; however, some increased use. School-based interventions were also associated with improved knowledge (SMD = - 0.38, 95% CI = - 0.68, - 0.08, p = 0.01), intentions (SMD = - 0.15, 95% CI = - 0.22, - 0.07, p = 0.0001), and attitudes (SMD = - 0.14, 95% CI = - 0.22, - 0.06; p = 0.0007) in the short term. Overall, the quality of evidence was low-to-moderate. School-based interventions hold the potential for addressing e-cigarette use, however, can have null or iatrogenic effects. More high-quality research is needed to develop efficacious interventions, and schools must be supported to adopt evidence-based programs. This is the first systematic review and meta-analysis to examine the efficacy of school-based preventive interventions for e-cigarette use. It provides crucial new knowledge about the efficacy of such interventions in preventing e-cigarette use and improving other outcomes (e.g., tobacco use, knowledge, intentions, attitudes, and mental health) among adolescents and the key characteristics associated with efficacious interventions. Our findings have important practical implications, highlighting future research directions for the development and evaluation of e-cigarette preventive interventions, along with the need to provide support to schools to help them identify and adopt evidence-based programs.

Freely available, online videos to support neurological physiotherapists and students in task-specific training skill acquisition: a scoping review.

BACKGROUND: Videos to support learning of clinical skills are effective; however, little is known about the scope and educational quality of the content of freely available online videos demonstrating task-specific training (TST). This review aimed to determine the extent, characteristics of freely available online videos, and whether the content is suitable to guide skill acquisition of task-specific training for neurological physiotherapists and students. METHODS: A scoping review was conducted. Google video and YouTube were searched in December 2022. Videos that met our eligibility criteria and were explicitly designed for (TST) skill acquisition were included in the report. RESULTS: Ten videos met the inclusion criteria and were difficult to find amongst the range of videos available. Most were presented by physiotherapists or occupational therapists, originated from the USA, featured stroke as the condition of the person being treated, and involved a range of interventions (upper limb, constraint induced movement therapy, balance, bicycling). Most videos were created by universities or private practices and only two used people with a neurological condition as the participant. When the content of videos and their presentation (instruction and/or demonstration), was assessed against each key component of TST (practice structure, specificity, repetition, modification, progression, feedback), five of the videos were rated very suitable and five moderately suitable to guide skill acquisition. Most videos failed to demonstrate and provide instruction on each key component of TST and were missing at least one component, with feedback most frequently omitted. CONCLUSIONS: There are many freely available online videos which could be described as demonstrating TST; very few are suitable to guide skill acquisition. The development of a standardised and validated assessment tool, that is easy to use and assesses the content of TST videos is required to support learners to critically evaluate the educational quality of video content. Guidelines based on sound teaching theory and practice are required to assist creators of online videos to provide suitable resources that meet the learning needs of neurological physiotherapists and students.

Juvenile sparids (Rhabdosargus holubi) consistently select structurally dense vegetated habitat in nursery seascapes.

Seagrass habitats provide structural complexity in coastal estuarine and marine environments, which offer fish optimal foraging grounds and refuge from predation. However, seagrasses are some of the most threatened ecosystems globally, with anthropogenic activities such as population growth and environmental degradation leading to the fragmentation, thinning, and loss of these habitats. Rhabdosargus holubi is one of only a few vegetation-associated marine fish species in South African estuaries. Although field studies have shown a strong association with seagrass over other aquatic vegetation for the juveniles of this species, habitat choice has never been empirically tested. Here, we used artificial vegetation units to test habitat choice (different structural complexities) for this species. We also tested whether habitat choice is influenced by a predatory threat, with fish preferentially selecting dense habitat in the presence of a predator and whether this effect may be more apparent in smaller individuals. We found that R. holubi significantly prefer greater structural complexity over less complex habitats, in both the absence and presence of a predator and for both small and large juveniles, showing that R. holubi actively choose more complex structures and are attracted to the structure per se irrespective of the threat of predation. This study highlights the importance of dense seagrass as nursery areas for this species and demonstrates how the loss of these habitats could impact the nursery function of estuaries.

Contextualising Experiences of Co-Occurring Mental Ill-Health and Substance Use Among Trans, Non-Binary, and Gender Diverse Young People: Implications for Tailored Harm Reduction Approaches.

Though significant research highlights higher rates of mental ill-health and substance use among trans, non-binary and gender diverse (henceforth 'trans') young people, little research has considered patterns, contextual characteristics, and correlates of co-occurring experiences of mental ill-health and substance use among trans young people. Using data from the Trans Pathways study, we used prevalence ratios and age- and gender-adjusted logistic regression models to examine prevalence and differences of co-occurring substance use (past six-month cigarette use, alcohol use, and other drug use) and contextual characteristics of substance use (past six-month solitary alcohol and/or drug use, substance use for coping) by mental ill-health (depression disorder, anxiety disorder, past 12-month self-harm thoughts and behaviours, suicidal thoughts, planning, and attempt/s). Age- and gender-adjusted models assessed associations between co-occurring depressive and anxiety disorders and recent cigarette, alcohol, and other drug use (six co-occurring items total) and 18 interpersonal stressors. Significantly increased odds of smoking or recent use of cannabis or sedatives was observed among trans young people reporting depressive disorder, anxiety disorder (aORs ranging 1.8-3.1). Trans young people who reported recent smoking or use of cannabis, inhalants, or sedatives, had 40% to 80% reduced odds of past 12-month self-harm thoughts, self-harm behaviours, suicidal thoughts, and suicide attempt/s (aORs ranging 0.2-0.6). On the other hand, solitary alcohol and/or other drug use and substance use for coping was significantly associated with increased odds of all mental ill-health outcomes. Issues with school, secure housing, and intimate partner abuse were the most robust correlates of co-occurring mental ill-health and substance use. Trans young people using substances, especially cigarettes, cannabis, and sedatives, often so do with co-occurring experiences of depression and anxiety though limited substance use in more 'social' contexts may confer benefits for preventing self-harm and suicide thoughts and behaviours. Continued research in partnership with trans young people is warranted to conceptualise more nuanced and precise conceptual parameters of trans-affirming substance use harm reduction approaches.

A tutorial: Analyzing eye and head movements in virtual reality.

This tutorial provides instruction on how to use the eye tracking technology built into virtual reality (VR) headsets, emphasizing the analysis of head and eye movement data when an observer is situated in the center of an omnidirectional environment. We begin with a brief description of how VR eye movement research differs from previous forms of eye movement research, as well as identifying some outstanding gaps in the current literature. We then introduce the basic methodology used to collect VR eye movement data both in general and with regard to the specific data that we collected to illustrate different analytical approaches. We continue with an introduction of the foundational ideas regarding data analysis in VR, including frames of reference, how to map eye and head position, and event detection. In the next part, we introduce core head and eye data analyses focusing on determining where the head and eyes are directed. We then expand on what has been presented, introducing several novel spatial, spatio-temporal, and temporal head-eye data analysis techniques. We conclude with a reflection on what has been presented, and how the techniques introduced in this tutorial provide the scaffolding for extensions to more complex and dynamic VR environments.

Co-design of digital public health substance use resources: A collaboration between young people and experts.

ISSUE ADDRESSED: Substance use and mental illness remain critical issues for young Australians, however, engagement with evidence-based health resources is challenging among this age group. This study aimed to develop engaging, useful digital health resources, underpinned by neuroscience principles, to build awareness of the harms of electronic cigarettes (e-cigarettes) and concurrent alcohol and antidepressant use. METHODS: A mixed-methods approach was adopted to co-design two evidence-based videos resources. The resources were co-designed with the Matilda Centre's Youth Advisory Board Centre's Youth Advisory Board through a series focus groups and individual feedback reviews. Young people residing in New South Wales were then invited to complete a survey to evaluate the usefulness, relatability and impact on perceived harms associated with each substance pre- and post-viewing resources. RESULTS: A total of 100 participants completed the survey (mean age = 21.5 years, SD = 2.77, 42% Female, 2% Non-binary). The animated videos were well received, with the large majority (91% and 87% respectively) of participants rating them 'excellent' or 'very good'. After viewing the videos, there was a significant increase in the perception of harm associated with e-cigarette use, monthly (t(99) = 2.76, p = .003), weekly (t(99) = 4.82, p < .001) and daily (t(99) = 4.92, p < .001), and consuming alcohol whilst taking antidepressants both weekly (t(100) = 2.93, p = .004) and daily (t(100) = 3.13, p = .002). CONCLUSIONS: This study describes a successful co-design process demonstrating how meaningful involvement of young people, alongside traditional research methods, can produce substance use prevention resources that are useful, engaging and increase knowledge of harms among young people. SO WHAT?: To achieve meaningful public health impact researchers, experts and digital creators can work together to co-create substance use educational materials that are engaging, well-liked, while imparting important health knowledge.

Exploring the association between adolescent-perceived parental monitoring on dietary intake.

Parenting practices such as parental monitoring are known to positively impact dietary behaviours in offspring. However, links between adolescent-perceived parental monitoring and dietary outcomes have rarely been examined and never in an Australian context. This study investigated whether adolescent-perceived parental monitoring is associated with more fruit and vegetable, and less sugar-sweetened beverages (SSB) and junk food consumption in Australian adolescents. Cross-sectional data was collected as part of baseline measurement for a randomised controlled trial in 71 Australian schools in 2019. Self-reported fruit, vegetable, SSB and junk food intake, perceived parental monitoring and sociodemographic factors were assessed. Each dietary variable was converted to "not at risk/at risk" based on dietary guidelines, binary logistic regressions examined associations between dietary intake variables and perceived parental monitoring while controlling for gender and socio-economic status. The study was registered in ANZCTR clinical trials. The sample comprised 6053 adolescents (Mage = 12.7, SD = 0.5; 50.6% male-identifying). The mean parental monitoring score was 20.1/24 (SD = 4.76) for males and 21.9/24 (SD = 3.37) for females. Compared to adolescents who perceived lower levels of parental monitoring, adolescents reporting higher parental monitoring had higher odds of insufficient fruit (OR = 1.03; 95% CI = 1.02-1.05) and excessive SSB (OR = 1.07; 95% CI = 1.06-1.09) intake, but lower odds of excessive junk food (OR = 0.96; 95% CI = 0.95-0.98) and insufficient vegetable (OR = 0.97, 95% CI = 0.96-0.99) intake. Adolescent dietary intake is associated with higher perceived parental monitoring; however, these associations for fruit and SSB differ to junk food and vegetable intake. This study may have implications for prevention interventions for parents, identifying how this modifiable parenting factor is related to adolescent diet has highlighted how complex the psychological and environmental factors contributing to dietary intake are.