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Anastasia Suraev,1– 3 Llewellyn Mills,4,5 Sarah V Abelev,1 Thomas R Arkell,6 Nicholas Lintzeris,4,5,* Iain S McGregor1– 3,* 1The University of Sydney, Lambert Initiative for Cannabinoid Therapeutics, Sydney, NSW, Australia; 2The University of Sydney, Faculty of Science, School of Psychology, Sydney, NSW, Australia; 3The University of Sydney, Brain and Mind Centre, Sydney, NSW, Australia; 4Drug and Alcohol Services, South East Sydney Local Health District, Sydney, NSW, Australia; 5Department of Addiction Medicine, Faculty Medicine and Health, University of Sydney, Sydney, NSW, Australia; 6Centre for Human Psychopharmacology, Swinburne University of Technology, Hawthorn, VIC, Australia*These authors contributed equally to this workCorrespondence: Iain S McGregor, The University of Sydney, Lambert Initiative for Cannabinoid Therapeutics, Level 6, Building M02F, 94 Mallett Street Camperdown, Sydney, NSW, 2050, Australia, Tel +612 9351 0883, Email iain.mcgregor@sydney.edu.auIntroduction: Sleep disorders are the third most common indication for the prescription of medical cannabis products in Australia, after pain and anxiety. While the use of cannabis for medical purposes is growing in Australia, underlying consumer behaviours and patterns of use, particularly around sleep disorders, are poorly understood.Methods: We conducted a subanalysis of the cross-sectional “Cannabis as Medicine Survey” 2020– 2021 (CAMS-20) (N = 1600), to explore the characteristics of a sample of Australians who were using prescribed and/or illicit medical cannabis to treat a self-reported sleep disorder.Results: When asked to specify up to seven different conditions they were treating with medical cannabis, a total of 1030 (64%) respondents [mean (SD) 44.9 (13.6) years] selected a sleep disorder, with “insomnia disorder” (85.5%), ‘sleep-related movement disorders’ (26%) and ‘sleep-related breathing disorders’ (11.1%) the most common subtypes. Only 165 (16.8%) respondents selected a self-reported sleep disorder as the main health condition being treated. Relative to other health conditions, use of medical cannabis for a self-reported sleep disorder was associated with younger age, increased likelihood of using both prescribed and illicit forms of medical cannabis, inhaled routes of administration, and THC-dominant products. Most respondents reported a reduction in the use of benzodiazepines and alcohol since starting medical cannabis. Binary logistic regression showed that respondents who predominantly used inhaled routes of administration, and concomitant use of medical cannabis for pain, mental health and/or substance use disorder, or a gastrointestinal disorder, were significantly more likely to also use medical cannabis to treat a self-reported sleep disorder.Conclusion: Overall, these results suggest that self-reported sleep disorders are often being treated with medical cannabis alongside other health conditions (often pain or a mental health disorder) and that use of inhaled methods, THC-dominant products, and illicit sources of medical cannabis are common among people with self-reported sleep disorders in Australia.Keywords: medical cannabis, THC, CBD, cannabinoid, insomnia, sleep disorders, survey

In Australia coeducation dominates government schooling, with single-sex institutions usually being the preserve of selective government schools and private, often elite, institutions. For marginalised young people who 'drop out' or are forced to leave the coeducational mainstream system, flexible and/or non-traditional schools provide alternative pathways. Such schools are primarily coeducational. This paper draws upon data from two flexible/non-traditional schools in Australia that attempted to address the issues of educational disengagement via the provision of single-sex schooling: Fernvale Education Centre and Lorem School. The data are insightful with regard to these two very different gender and education paradigms and to their associated discourses about masculinity and femininity. The paper will identify the ways in which these schools both reproduce and challenge dominant constructions of gender within the context of responding to disenfranchised/disengaged young people.

OBJECTIVES: Precision medicine is data-driven health care tailored to individual patients based on their unique attributes, including biologic profiles, disease expressions, local environments, and socioeconomic conditions. Emergency medicine (EM) has been peripheral to the precision medicine discourse, lacking both a unified definition of precision medicine and a clear research agenda. We convened a national consensus conference to build a shared mental model and develop a research agenda for precision EM. METHODS: We held a conference to (1) define precision EM, (2) develop an evidence-based research agenda, and (3) identify educational gaps for current and future EM clinicians. Nine preconference workgroups (biomedical ethics, data science, health professions education, health care delivery and access, informatics, omics, population health, sex and gender, and technology and digital tools), comprising 84 individuals, garnered expert opinion, reviewed relevant literature, engaged with patients, and developed key research questions. During the conference, each workgroup shared how they defined precision EM within their domain, presented relevant conceptual frameworks, and engaged a broad set of stakeholders to refine precision EM research questions using a multistage consensus-building process. RESULTS: A total of 217 individuals participated in this initiative, of whom 115 were conference-day attendees. Consensus-building activities yielded a definition of precision EM and key research questions that comprised a new 10-year precision EM research agenda. The consensus process revealed three themes: (1) preeminence of data, (2) interconnectedness of research questions across domains, and (3) promises and pitfalls of advances in health technology and data science/artificial intelligence. The Health Professions Education Workgroup identified educational gaps in precision EM and discussed a training roadmap for the specialty. CONCLUSIONS: A research agenda for precision EM, developed with extensive stakeholder input, recognizes the potential and challenges of precision EM. Comprehensive clinician training in this field is essential to advance EM in this domain.

Reproductive phasiRNAs (phased, small interfering RNAs) are broadly present in angiosperms and play crucial roles in sustaining male fertility. While the premeiotic 21-nt (nucleotides) phasiRNAs and meiotic 24-nt phasiRNA pathways have been extensively studied in maize (Zea mays) and rice (Oryza sativa), a third putative category of reproductive phasiRNAs-named premeiotic 24-nt phasiRNAs-have recently been reported in barley (Hordeum vulgare) and wheat (Triticum aestivum). To determine whether premeiotic 24-nt phasiRNAs are also present in maize and related species and begin to characterize their biogenesis and function, we performed a comparative transcriptome and degradome analysis of premeiotic and meiotic anthers from five maize inbred lines and three teosinte species/subspecies. Our data indicate that a substantial subset of the 24-nt phasiRNA loci in maize and teosinte are already highly expressed at the premeiotic phase. The premeiotic 24-nt phasiRNAs are similar to meiotic 24-nt phasiRNAs in genomic origin and dependence on DCL5 (Dicer-like 5) for biogenesis, however, premeiotic 24-nt phasiRNAs are unique in that they are likely i) not triggered by microRNAs, ii) not loaded by AGO18 proteins, and iii) not capable of mediating PHAS precursor cleavage. In addition, we also observed a group of premeiotic 24-nt phasiRNAs in rice using previously published data. Together, our results indicate that the premeiotic 24-nt phasiRNAs constitute a unique class of reproductive phasiRNAs and are present more broadly in the grass family (Poaceae) than previously known.

During HIV infection of CD4+ T cells, ubiquitin pathways are essential to viral replication and host innate immune response; however, the role of specific E3 ubiquitin ligases is not well understood. Proteomics analyses identified 116 single-subunit E3 ubiquitin ligases expressed in activated primary human CD4+ T cells. Using a CRISPR-based arrayed spreading infectivity assay, we systematically knocked out 116 E3s from activated primary CD4+ T cells and infected them with NL4-3 GFP reporter HIV-1. We found 10 E3s significantly positively or negatively affected HIV infection in activated primary CD4+ T cells, including UHRF1 (pro-viral) and TRAF2 (anti-viral). Furthermore, deletion of either TRAF2 or UHRF1 in three JLat models of latency spontaneously increased HIV transcription. To verify this effect, we developed a CRISPR-compatible resting primary human CD4+ T cell model of latency. Using this system, we found that deletion of TRAF2 or UHRF1 initiated latency reactivation and increased virus production from primary human resting CD4+ T cells, suggesting these two E3s represent promising targets for future HIV latency reversal strategies.ImportanceHIV, the virus that causes AIDS, heavily relies on the machinery of human cells to infect and replicate. Our study focuses on the host cell's ubiquitination system which is crucial for numerous cellular processes. Many pathogens, including HIV, exploit this system to enhance their own replication and survival. E3 proteins are part of the ubiquitination pathway that are useful drug targets for host-directed therapies. We interrogated the 116 E3s found in human immune cells known as CD4+ T cells, since these are the target cells infected by HIV. Using CRISPR, a gene-editing tool, we individually removed each of these enzymes and observed the impact on HIV infection in human CD4+ T cells isolated from healthy donors. We discovered that 10 of the E3 enzymes had a significant effect on HIV infection. Two of them, TRAF2 and UHRF1, modulated HIV activity within the cells and triggered an increased release of HIV from previously dormant or "latent" cells in a new primary T cell assay. This finding could guide strategies to perturb hidden HIV reservoirs, a major hurdle to curing HIV. Our study offers insights into HIV-host interactions, identifies new factors that influence HIV infection in immune cells, and introduces a novel methodology for studying HIV infection and latency in human immune cells.

BackgroundSeizure detection is challenging outside the clinical environment due to the lack of comfortable, reliable, and practical long-term neurophysiological monitoring devices. We developed a novel, discreet, unobstructive in-ear sensing system that enables long-term electroencephalography (EEG) recording. This is the first study we are aware of that systematically compares the seizure detection utility of in-ear EEG with that of simultaneously recorded intracranial EEG. In addition, we present a similar comparison between simultaneously recorded in-ear EEG and scalp EEG.MethodsIn this foundational research, we conducted a clinical feasibility study and validated the ability of the ear-EEG system to capture focal-onset seizures against 1255 hrs of simultaneous ear-EEG data along with scalp or intracranial EEG in 20 patients with refractory focal epilepsy (11 with scalp EEG, 8 with intracranial EEG, and 1 with both).ResultsIn a blinded, independent review of the ear-EEG signals, two epileptologists were able to detect 86.4% of the seizures that were subsequently identified using the clinical gold standard EEG modalities, with a false detection rate of 0.1 per day, well below what has been reported for ambulatory monitoring. The few seizures not detected on the ear-EEG signals emanated from deep within the mesial temporal lobe or extra-temporally and remained very focal, without significant propagation. Following multiple sessions of recording for a median continuous wear time of 13 hrs, patients reported a high degree of tolerance for the device, with only minor adverse events reported by the scalp EEG cohort.ConclusionsThese preliminary results demonstrate the potential of using ear-EEG to enable routine collection of complementary, prolonged, and remote neurophysiological evidence, which may permit real-time detection of paroxysmal events such as seizures and epileptiform discharges. This study suggests that the ear-EEG device may assist clinicians in making an epilepsy diagnosis, assessing treatment efficacy, and optimizing medication titration.

Background: Children with phonological impairment present with pattern-based errors in their speech production. While some children have difficulties with speech perception and/or the establishment of robust underlying phonological representations, the nature of phonological impairment in children is still not well understood. Given that phonological and lexical development are closely linked, one way to better understand the nature of the problem in phonological impairment is to examine word learning abilities in children. Aims: To examine word learning and its relationship with speech perception, speech production and vocabulary knowledge in children aged 4-5 years. There were two variables of interest: speech production abilities ranging from phonological impairment to typical speech; and vocabulary abilities ranging from typical to above average ('lexically precocious'). Methods & Procedures: Participants were 49 Australian-English-speaking children aged 48--69 months. Children were each taught four novel non-words (out of a selection of eight) through stories, and word learning was assessed at 1 week post-initial exposure. Word learning was assessed using two measures: confrontation naming and story retell naming. Data were analysed by group using independent-samples t-tests and Mann--Whitney U-tests, and continuously using multiple linear regression. Outcomes & Results: There was no significant difference in word learning ability of children with and without phonological impairment, but regardless of speech group, children with above average vocabulary had significantly better word learning abilities than children with average vocabulary. In multiple linear regression, vocabulary was the only significant predictor of variance in word learning ability. Conclusions & Implications: Children with phonological impairment can be lexically prediction precocious and learn new words like their peers without phonological impairment. Contrary to expectations, vocabulary knowledge rather than expressive phonological ability explained variance in measures of word learning. These findings question an assumption that children with phonological impairment have underspecified phonological representations. They also highlight the heterogeneity among children with phonological impairment and the need to better understand the nature of their difficulty learning the phonological system of the ambient language.

This paper shares findings from a project that examined how schools serving marginalised communities facilitated students' substantive engagement. Through interviews with students, parents, teachers and school leaders, we determined that substantive engagement was supported by formal and informal strategies that enabled access to rich learning opportunities, the provision of welcoming school and classroom climates, and the enactment of pedagogies of care and school-wide programmes focused on substantive engagement. There were four key areas of substantive engagement: engaging curriculum and pedagogy, engaging school climate, engaging with learners, and engaging with communities. Strategies to support engagement included the removal of barriers to learning, such as assistance with breakfast or public transport, nurturing a positive school climate, providing support for ethnic groups and the delivery of alternative or flexible programmes. Drawing on the findings from five case studies, we propose four principles for substantive student engagement in complex contexts, which will be useful for school leaders and teachers who work in schools that serve marginalised communities.

This paper draws together data from two projects on schooling dis/engagement in Australia. One project focused on mainstream schools and the strategies employed to retain and engage young people in learning, whereas the other explored the growing sector of alternative/flexible education for similar solutions. We found interesting parallels. For example, rich, relevant curricula delivered through innovative pedagogies alongside positive staff/student relationships were key elements in schooling engagement across both sectors. Those findings have been published elsewhere. This paper focuses on the contributions to schooling engagement that may be derived from mutually beneficial school/community relationships. Here, we examine one mainstream high school and one flexi secondary school, both situated in remote geolocations, that established bespoke school/community partnerships in response to local needs. The data from each site provide blueprints for other schools that wish to tap into the wealth of human and material support systems in their own local areas.

This paper mobilises the psychoanalytic concepts of desire and enjoyment to better understand how processes of education aimed at extending and defending democratic life might respond to and engage with populist politics. I approach this task by engaging with a particular vector of Mouffe and Laclau's political philosophy, moving from a critique of liberal democracy's rationalist pretensions to their insistence that left populism and its passionate construction of a 'people' is the central task facing radical politics. This attention to the libidinal basis of political identification locates them in a community of Left Lacanian thinkers who reframe the problems of democratic politics in terms of desire and enjoyment rather than miseducation or its lack. Whilst this position might suggest a binary choice between different analytical frames, I inquire into what insights are generated by theorising left populism as an 'education of desire'. The paper is organised into four main parts: the opening discussion clarifies my understanding of education by engaging with the literature on educational agonism. The second section lays the groundwork for a critique of the way in which education is fetishized, in different ways, by liberals and radicals as a panacea for populist politics. The third section reframes democratic crisis as an enjoyment problem in order to better grasp the relationship between the liberal democratic disavowal of its own irrationality and the structure of right-wing populist enjoyment. The fourth section applies these insights to develop a critical analysis of what is at stake when we explicitly consider the left populist construction of a 'people' as an educational task. I conclude by drawing together and summarising the main features and considerations of left populism understood as an education of desire.

Transgender and gender diverse (TGD) adolescents experience mental health challenges at higher rates than cisgender peers due to a combination of minority stress and gender dysphoria. Many TGD youth use video games to cope with stress and access informal networks of support. However, very little is known about the potential positive influence avatar customization has for this group of youth. To address this gap in the literature, in-depth, semi-structured qualitative interviews were conducted with ten TGD adolescents about their experiences with avatar customization. Thematic analysis revealed four primary themes including that: (1) video game avatar customization offers a low stakes environment for gender exploration; (2) avatars offer both internal and external validation of gender identity and transition goals; (3) avatars allow players to enact aspirational appearance goals; and (4) video games and avatars offer immersion and escapism for TGD adolescents. These novel findings underscore the range of positive impacts avatar customization can have for TGD adolescents, particularly for youth with gender dysphoria. Video game avatar customization can be a key part of the gender exploration and affirmation for some TGD adolescents.

To demonstrate how the history classroom could become an important site for addressing climate change, this article describes the piloting of three lessons. Our qualitative case study occurred in an elective environmental education course with teacher candidates who participated in the lessons and were invited to provide feedback. We describe the lessons and their development, and share results from surveys and an interview. Participants identified several educational benefits and expressed feeling better prepared to teach both history and critical thinking in general. Our findings suggest that these lessons may serve as useful examples for developing new resources to support educators in teaching climate change alongside critical and historical thinking.