Primary care in Australia is undergoing significant reform, with a particular focus on cost-effective tailoring of mental health care to individual needs. Link-me is testing whether a patient-completed Decision Support Tool (DST), which predicts future severity of depression and anxiety symptoms and triages individuals into care accordingly, is clinically effective and cost-effective relative to usual care. The trial is set in general practices, with English-speaking patients invited to complete eligibility screening in their general practitioner's waiting room. Eligible and consenting patients will then complete the DST assessment and are randomised and stratified according to predicted symptom severity. Participants allocated to the intervention arm will receive feedback on DST responses, select treatment priorities, assess motivation to change, and receive a severity-matched treatment recommendation (information about and links to low intensity services for those with mild symptoms, or assistance from a specially trained health professional (care navigator) for those with severe symptoms). All patients allocated to the comparison arm will receive usual GP care plus attention control. Primary (psychological distress) and secondary (depression, anxiety, quality of life, days out of role) outcomes will be assessed at 6 and 12 months. Differences in outcome means between trial arms both across and within symptom severity group will be examined using intention-to-treat analyses. Within trial and modelled economic evaluations will be conducted to determine the value for money of credentials of Link-me. Findings will be reported to the Federal Government to inform how mental health services across Australia are funded and delivered in the future.

Mounting evidence suggests that neuronal activity influences myelination, potentially allowing for experience-driven modulation of neural circuitry. The degree to which neuronal activity is capable of regulating myelination at the individual axon level is unclear. Here we demonstrate that stimulation of somatosensory axons in the mouse brain increases proliferation and differentiation of oligodendrocyte progenitor cells (OPCs) within the underlying white matter. Stimulated axons display an increased probability of being myelinated compared to neighboring non-stimulated axons, in addition to being ensheathed with thicker myelin. Conversely, attenuating neuronal firing reduces axonal myelination in a selective activity-dependent manner. Our findings reveal that the process of selecting axons for myelination is strongly influenced by the relative activity of individual axons within a population. These observed cellular changes are consistent with the emerging concept that adaptive myelination is a key mechanism for the fine-tuning of neuronal circuitry in the mammalian CNS.

Background: Aggression is a commonly reported problem following traumatic brain injury (TBI). It may present as verbal insults or outbursts, physical assaults, and/or property destruction. Aggressive behavior can fracture relationships and impede participation in treatment as well as a broad range of vocational and social activities, thereby reducing the individual's quality of life. Pharmacological intervention is frequently used to control aggression following TBI. The aim of this systematic review was to critically evaluate the evidence regarding efficacy of pharmacological interventions for aggression following TBI in adults. Methods: We reviewed studies in English, available before December 2018. MEDLINE, PubMed, CINAHL, EMBASE, PsycINFO, and CENTRAL databases were searched, with additional searching of key journals, clinical trials registries, and international drug regulators. The primary outcomes of interest were reduction in the severity of aggression and occurrence of harms. The secondary outcomes of interest were changes in quality of life, participation, psychological health (e.g., depression, anxiety), and cognitive function. Evidence quality was assessed using the Cochrane Risk of Bias tool and the Joanna Briggs Institute Critical Appraisal Instruments. Results: Ten studies were identified, including five randomized controlled trials (RCTs) and five case series. There were positive, albeit mixed, findings for the RCTs examining the use of amantadine in reducing irritability (n = 2) and aggression (n = 2). There were some positive findings favoring methylphenidate in reducing anger (n = 1). The evidence for propranolol was weak (n = 1). Individual analysis revealed differential drug response across individuals for both methylphenidate and propranolol. The less rigorous studies administered carbamazepine (n = 2), valproic acid (n = 1), quetiapine (n = 1), and sertraline (n = 1), and all reported reductions in aggression. However, given the lack of a control group, it is difficult to discern treatment effects from natural change over time. Conclusions: This review concludes that a recommendation for use of amantadine to treat aggression and irritability in adults following TBI is appropriate. However, there is a need for further well-designed, adequately powered and controlled studies of pharmacological interventions for aggression following TBI.

Parkinson's disease (PD) is a progressive, chronic disease characterized by dyskinesia, rigidity, instability, and tremors. The disease is defined by the presence of Lewy bodies, which primarily consist of aggregated α-synuclein protein, and is accompanied by the loss of monoaminergic neurons. Current therapeutic strategies only give symptomatic relief of motor impairment and do not address the underlying neurodegeneration. Hence, we have identified Cu(II)(atsm) as a potential therapeutic for PD. Drug administration to four different animal models of PD resulted in improved motor and cognition function, rescued nigral cell loss, and improved dopamine metabolism. In vitro, this compound is able to inhibit the effects of peroxynitrite-driven toxicity, including the formation of nitrated α-synuclein oligomers. Our results show that Cu(II)(atsm) is effective in reversing parkinsonian defects in animal models and has the potential to be a successful treatment of PD.

In Australia, Aboriginal and Torres Strait Islander peoples bear a greater burden of disease and have lower life expectancy than their non-Indigenous counterparts. These combined indicators are evidence of an entrenched health crisis in the Indigenous population that is linked to systemic disadvantage over many decades. In an effort to improve life expectancy and lessen the burden of disease, a number of strategies and national frameworks now embed a human rights-based approach to achieving health equality. This paper explores the application of human rights to Indigenous health and examines the inherent tensions that exist in engaging a system of law based on universal assumptions of the Enlightenment to advance Indigenous rights. What becomes apparent through this exploration is that the strategic approach of Indigenous peoples’ use of human rights, despite its genesis in a system of law that

Copy number variations to chromosome 21 (HSA21) cause intellectual disability and Down Syndrome, but our understanding of the HSA21 genetic factors which contribute to fetal brain development remains incomplete. Here, we focussed on the neurodevelopmental functions for EURL (also known as C21ORF91, Refseq Gene ID:54149), a protein-coding gene at the centromeric boundary of the Down Syndrome Critical Region (DSCR) of HSA21. We report that EURL is expressed during human and mouse cerebral cortex development, and we report that alterations to EURL mRNA levels within the human brain underlie Down Syndrome. Our gene perturbation studies in mice demonstrate that disruptions to Eurl impair progenitor proliferation and neuronal differentiation. Also, we find that disruptions to Eurl impair the long-term positioning and dendritic spine densities of cortical projection neurons. We provide evidence that EURL interacts with the coiled-coil domain-containing protein CCDC85B so as to modulate β-catenin levels in cells. Further, we utilised a fluorescent reporter (8xTOPFLASHd2EGFP) to demonstrate that disruptions to Eurl alter β-catenin signalling in vitro as well as in vivo. Together, these studies highlight EURL as an important new player in neuronal development that is likely to impact on the neuropathogenesis of HSA21-related disorders including Down Syndrome.

BACKGROUND: Depression and related disorders represent a significant part of general practitioners (GPs) daily work. Implementing the evidence about what works for depression care into routine practice presents a challenge for researchers and service designers. The emerging consensus is that the transfer of efficacious interventions into routine practice is strongly linked to how well the interventions are based upon theory and take into account the contextual factors of the setting into which they are to be transferred. We set out to develop a conceptual framework to guide change and the implementation of best practice depression care in the primary care setting. METHODS: We used a mixed method, observational approach to gather data about routine depression care in a range of primary care settings via: audit of electronic health records; observation of routine clinical care; and structured, facilitated whole of organisation meetings. Audit data were summarised using simple descriptive statistics. Observational data were collected using field notes. Organisational meetings were audio taped and transcribed. All the data sets were grouped, by organisation, and considered as a whole case. Normalisation Process Theory (NPT) was identified as an analytical theory to guide the conceptual framework development. RESULTS: Five privately owned primary care organisations (general practices) and one community health centre took part over the course of 18 months. We successfully developed a conceptual framework for implementing an effective model of depression care based on the four constructs of NPT: coherence, which proposes that depression work requires the conceptualisation of boundaries of who is depressed and who is not depressed and techniques for dealing with diffuseness; cognitive participation, which proposes that depression work requires engagement with a shared set of techniques that deal with depression as a health problem; collective action, which proposes that agreement is reached about how care is organised; and reflexive monitoring, which proposes that depression work requires agreement about how depression work will be monitored at the patient and practice level. We describe how these constructs can be used to guide the design and implementation of effective depression care in a way that can take account of contextual differences. CONCLUSIONS: Ideas about what is required for an effective model and system of depression care in primary care need to be accompanied by theoretically informed frameworks that consider how these can be implemented. The conceptual framework we have presented can be used to guide organisational and system change to develop common language around each construct between policy makers, service users, professionals, and researchers. This shared understanding across groups is fundamental to the effective implementation of change in primary care for depression.

Identification of mental health risk is important for optimising diabetes care in type 2 diabetes mellitus (T2DM). Personality is linked to diabetes health and may assist detection of individuals with T2DM most at risk of chronic mental health difficulties. This study examined the moderator effect of personality factors on changes in psychological distress and functioning in adults with T2DM and mild-to-moderate depressive symptoms across a 12-month period. Data were obtained from participants in a randomised controlled trial of adults with T2DM.  Participants completed measures of depression (Patient Health Questionnaire-9), anxiety (General Anxiety Disorder-7), general functioning (Work and Social Adjustment Scale), diabetes distress (Diabetes Distress Scale), and diabetes self-management (Self-Management Profile for Type 2 Diabetes) at baseline, 3-, 6- and 12-months. Glycaemic control (HbA1c) was measured at baseline, 6- and 12-months. Two hundred trial completers agreed to complete a personality inventory (Big Five Inventory). Low neuroticism was linked with reduced depression, anxiety, functional impairment and diabetes distress over the year. High extraversion was associated with decreased anxiety and functional impairment. High conscientiousness was linked to increased healthy eating. No personality trait moderated HbA1c levels. Personality screening may help identify mental health risk and guide medical carer approach in T2DM patients.

The Protein Folding Database (PFD) is a publicly accessible repository of thermodynamic and kinetic protein folding data. Here we describe the first major revision of this work, featuring extensive restructuring that conforms to standards set out by the recently formed International Foldeomics Consortium. The database now adopts standards for data acquisition, analysis and reporting proposed by the consortium, which will facilitate the comparison of folding rates, energies and structure across diverse sets of proteins. Data can now be easily deposited using a rich set of deposition tools. Enhanced search tools allow sophisticated searching and graphical data analysis affords simple data analysis online. PFD can be accessed freely at http://www.foldeomics.org/pfd/.

BACKGROUND: Severe malnutrition is a risk factor for pneumonia due to a wide range of pathogens but aetiological data are limited and the role of Mycobacterium tuberculosis is uncertain. METHODS: We prospectively investigated severely malnourished young children (<5 years) with radiological pneumonia admitted over a 15-month period. Investigations included blood culture, sputa for microscopy and mycobacterial culture. Xpert MTB/RIF assay was introduced during the study. Study children were followed for 12 weeks following their discharge from the hospital. RESULTS: 405 eligible children were enrolled, with a median age of 10 months. Bacterial pathogens were isolated from blood culture in 18 (4.4%) children, of which 72% were Gram negatives. Tuberculosis was confirmed microbiologically in 7% (27/396) of children that provided sputum - 10 by culture, 21 by Xpert MTB/RIF assay, and 4 by both tests. The diagnostic yield from induced sputum was 6% compared to 3.5% from gastric aspirate. Sixty (16%) additional children had tuberculosis diagnosed clinically that was not microbiologically confirmed. Most confirmed tuberculosis cases did not have a positive contact history or positive tuberculin test. The sensitivity and specificity of Xpert MTB/RIF assay compared to culture was 67% (95% CI: 24-94) and 92% (95% CI: 87-95) respectively. Overall case-fatality rate was 17% and half of the deaths occurred in home following discharge from the hospital. CONCLUSION AND SIGNIFICANCE: TB was common in severely malnourished Bangladeshi children with pneumonia. X-pert MTB/RIF assay provided higher case detection rate compared to sputum microscopy and culture. The high mortality among the study children underscores the need for further research aimed at improved case detection and management for better outcomes.

Within a city, gender differences in walking for recreation (WfR) vary significantly across neighbourhoods, although the reasons remain unknown. This cross-sectional study investigated the contribution of the social environment (SE) to explaining such variation, using 2009 data from the How Areas in Brisbane Influence healTh and AcTivity (HABITAT) study, including 7866 residents aged 42-67 years within 200 neighbourhoods in Brisbane, Australia (72.6% response rate). The analytical sample comprised 200 neighbourhoods and 6643 participants (mean 33 per neighbourhood, range 8-99, 95% CI 30.6-35.8). Self-reported weekly minutes of WfR were categorised into 0 and 1-840 mins. The SE was conceptualised through neighbourhood-level perceptions of social cohesion, incivilities and safety from crime. Analyses included multilevel binomial logistic regression with gender as main predictor, adjusting for age, socioeconomic position, residential self-selection and neighbourhood disadvantage. On average, women walked more for recreation than men prior to adjustment for covariates. Gender differences in WfR varied significantly across neighbourhoods, and the magnitude of the variation for women was twice that of men. The SE did not explain neighbourhood differences in the gender-WfR relationship, nor the between-neighbourhood variation in WfR for men or women. Neighbourhood-level factors seem to influence the WfR of men and women differently, with women being more sensitive to their environment, although Brisbane's SE did not seem such a factor.

ISSUE ADDRESSED: Men dominate the suicide statistics and are less likely than women to seek help for emotional problems, and this has been linked to aspects of stoic masculinity. Promoting help-seeking and challenging stoic thinking may help to address this problem, but it is unclear what works in engaging men in these topics. METHODS: We developed a multimedia intervention called Man Up - including a documentary and digital campaign. We tested promotional materials and the website by interviewing 17 men from different ages and backgrounds about their perceptions, and asked them whether the materials generated interest in the topics of the documentary. RESULTS: Participants preferred visual materials that were relatable to them and included active and direct language. This helped them to understand and identify with the messages being imparted. Participants had mixed views on talking about masculinity and the use of the term "man up," with some expressing interest and others being deterred by it. Sharing content about mental health and suicide was seen by some as a risk to personal reputation and their relationships with others. CONCLUSIONS: Our findings informed the design of targeted materials for the national Man Up campaign and website which were then used in a multilevel national health promotion intervention in Australia. SO WHAT?: Our study provided valuable insights beyond Man Up for those seeking to design and deliver health promotion interventions targeting Australian men and engage in sensitive and stigmatised male health issues. Using active and empowering language was especially important when addressing men which contrasts with many promotional materials currently available.