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Background: Uveal melanoma is the most common non-cutaneous melanoma and is an intraocular malignancy affecting nearly 7,000 individuals per year worldwide. Of these, approximately 50% will progress to metastatic disease for which there are currently no effective curative therapies. Despite advances in molecular profiling and metastatic stratification of uveal melanoma tumors, little is known regarding their underlying biology of metastasis. Our group has identified a disseminated neoplastic cell population characterized by co-expression of immune and melanoma proteins, circulating hybrid cells (hybrids), in patients with uveal melanoma. Compared to circulating tumor cells, which lack expression of immune proteins, hybrids are detected at an increased prevalence in peripheral blood and can be used as a non-invasive biomarker to predict metastatic progression. Methods: To ascertain mechanisms underlying enhanced hybrid cell dissemination we identified hybrid cells within primary uveal melanoma tumors using single cell RNA sequencing (n = 8) and evaluated their gene expression and predicted ligand-receptor interactions in relation to other melanoma and immune cells within the primary tumor. We then verified expression of upregulated hybrid pathways within patient-matched tumor and peripheral blood hybrids (n = 4) using cyclic immunofluorescence and quantified their protein expression relative to other non-hybrid tumor and disseminated tumor cells. Results: Among the top upregulated genes and pathways in hybrid cells were those involved in enhanced cell motility and cytoskeletal rearrangement, immune evasion, and altered cellular metabolism. In patient-matched tumor and peripheral blood, we verified gene expression by examining concordant protein expression for each pathway category: TMSB10 (cell motility), CD74 (immune evasion) and GPX1 (metabolism). Both TMSB10 and GPX1 were expressed on significantly higher numbers of disseminated hybrid cells compared to circulating tumor cells, and CD74 and GPX1 were expressed on more disseminated hybrids than tumor-resident hybrids. Lastly, we identified that hybrid cells express ligand-receptor signaling pathways implicated in promoting metastasis including GAS6-AXL, CXCL12-CXCR4, LGALS9-P4HB and IGF1-IGFR1. Conclusion: These findings highlight the importance of TMSB10, GPX1 and CD74 for successful hybrid cell dissemination and survival in circulation. Our results contribute to the understanding of uveal melanoma tumor progression and interactions between tumor cells and immune cells in the tumor microenvironment that may promote metastasis. [ABSTRACT FROM AUTHOR]

Introduction: Despite a decline in unintended teenage pregnancy in Australia, rates remain higher amongst justice-involved adolescent girls, who are more likely to be from disadvantaged socio-economic backgrounds, have histories of abuse, substance use and/or mental health issues. Furthermore, exposure to the criminal justice system may alter access to education and employment and opportunities, potentially resulting in distinct risk-factor profiles. We examine factors associated with unintended pregnancy, non-contraceptive use and Long-Acting Reversible Contraception (LARC) in a sample of sexually active, justice-involved adolescent girls from Western Australia and Queensland. Methods: Data from the Mental Health, Sexual Health and Reproductive Health of Young People in Contact with the Criminal Justice System (MeH-JOSH) Study was analysed on 118 sexually active adolescent girls. Participants were aged between 14 and 17 years, purposefully sampled based on justice-system involvement and completed an anonymous telephone survey. We constructed two multivariate models taking reproductive outcomes as the dependent variables. Results: Over one quarter (26%, 30/118) reported a past unintended pregnancy, 54 did not use any contraception at their last sexual encounter, and 17 reported LARC use. Following adjustments in the multivariate analysis, lifetime ecstasy use was associated with both unintended pregnancy (aOR 3.795, p = 0.022) and non-contraception use (aOR 4.562, p = 0.004). A history of physical abuse was also associated with both any contraception (aOR 3.024, p = 0.041) and LARC use (aOR 4.892, p = 0.050). Identifying as Aboriginal & Torres Strait Islander, education/employment status and geographic location appeared to have no association. Conclusion: Our findings suggest that justice-involved adolescent girls have distinct risk factors associated with unplanned pregnancy and contraception use compared to the general population, but more research is required to understand the mechanisms and contexts underlying these risk factors. How exposure to physical violence may encourage contraception and LARC use, in particular, warrants further attention as does the association with ecstasy use. [ABSTRACT FROM AUTHOR]

Introduction: Estimates of the prevalence of intellectual disability or autism spectrum disorder (ASD) may vary depending on the methodology, geographical location, and sources of ascertainment. The National Disability Insurance Scheme (NDIS) in Australia was introduced progressively from 2016 to provide individualized funding for eligible people with a significant and permanent disability. Methods: Its recent inclusion as a source of ascertainment in the populationbased Intellectual Disability Exploring Answers (IDEA) database in Western Australia has allowed comparisons of the prevalence of intellectual disability and ASD before and after its introduction. Results: Prevalence of intellectual disability in 2020 was 22.5 per 1,000 (/1,000) live births compared with previous estimates in 2010 of 17/1,000, and for ASD, the estimate was 20.7/1,000 in 2020 compared with 5.1/1,000 in 2010. Whilst the prevalence of ASD in Aboriginal individuals was about two-thirds that of non-Aboriginals, there was an increased prevalence of ASD in Aboriginal children under 10 years compared with non-Aboriginal children. Discussion: The concurrent relaxation of ASD diagnostic practice standards in Western Australia associated with the administration of access to the NDIS and the release of the National Guidelines empowering single diagnosticians to determine the appropriateness of engaging additional diagnosticians to form a multidisciplinary team on ASD diagnosis, appear to be important factors associated with the increase in ASD diagnoses both with and without intellectual disability. [ABSTRACT FROM AUTHOR]

Background: Traumatic brain injury (TBI) is a major public health problem that may be associated with numerous behavioral problems, including impulsivity, aggression and violence. Rates of self-reported TBI are high within offender populations, but the extent to which TBI is causally implicated in causing illegal behavior is unclear. This study examined the psychological and functional correlates of histories of traumatic brain injury in a sample of impulsive violent offenders. Methods: Study participants, all men, had been recruited to participate in a randomized controlled trial of sertraline to reduce recidivism. Study entry criteria were an age of at least 18 years, a documented history of two or more violent offenses and a score of 70 or above on the Barratt Impulsiveness Scale. An extensive list of standardized questionnaires was administered to obtain information on previous TBI and other neuropsychiatric conditions or symptoms. Results: In the sample of 693 men, 66% were aged between 18 and 35 years old, and 55% gave a history of TBI ("TBI+"). Overall, 55% of study participants reported at least one TBI. High levels of neuropsychiatric symptomatology were reported. In 75% of TBI+ individuals, their most severe TBI (by self-report) was associated with loss of consciousness (LOC) < 30 min. Compared to TBI- (those without history of TBI) participants, TBI+ individuals were more impulsive (Eysenck Impulsivity), irritable, angry, and reported higher levels of assaultive behavior, depressive symptomology, alcohol use disorder, suicidal ideation, suicide attempts, and lower quality of life. Potential "dose effects" of TBI severity and frequency in terms of neuropsychiatric symptomatology were identified. Conclusion: Like other studies of offender populations, single and multiple TBIs were very common. The associations of TBI, TBI severity, and TBI frequency (i.e., TBI "burden") with adverse neuropsychiatric phenomena suggest TBI contributes importantly to offender morbidity but the select nature of the sample and crosssectional study design constrain the interpretation of these findings. [ABSTRACT FROM AUTHOR]

This paper uses first person inquiry and presentational form to argue the case for a sensory approach to understanding professional connection and disconnection with children who may be being abused. The approach is underpinned by an epistemology or theory of knowledge which stems from a participatory world-view where appearances are not permanent or separate from us: the act of perception takes place between the active sensible world and our own bodies, where "otherness" expresses itself directly to our senses. Thus perception, conceived in this way, can lead to right action in the moment; or discounting what is actually being said by a child and disconnection. Buber's notion of the "I-You" is used to explore feelings and the movement to relation when professionals witness children's "stories of suffering" (Buber, 1965; Laub, 1992; Jones, 2008). The paper concludes by arguing the case for practitioners to become researchers of their own practice in rigorously facilitated inquiry groups. It is argued that this form of practitioner-research serves to quality assure frontline practice, and create new knowledge (or practice wisdom) such that feelings can be constructively worked with to improve connection with the lived reality for children.

This paper uses first person inquiry and presentational form to argue the case for a sensory approach to understanding professional connection and disconnection with children who may be being abused. The approach is underpinned by an epistemology or theory of knowledge which stems from a participatory world-view where appearances are not permanent or separate from us: the act of perception takes place between the active sensible world and our own bodies, where ‘otherness’ expresses itself directly to our senses. Thus perception, conceived in this way, can lead to right action in the moment; or discounting what is actually being said by a child and disconnection. Buber’s notion of the ‘I-You’ is used to explore feelings and the movement to relation when professionals witness children’s ‘stories of suffering’ (Buber, 1965; Laub, 1992; Jones, 2008). The paper concludes by arguing the case for practitioners to become researchers of their own practice in rigorously facilitated inquiry groups. It is argued that this form of practitioner-research serves to quality assure frontline practice, and create new knowledge (or practice wisdom) such that feelings can be constructively worked with to improve connection with the lived reality for children.

Hypertension is a common disease that leads to significant cardiovascular morbidity and mortality. Adequate blood pressure control is essential in preventing end organ complications. One of the most popular antihypertensive strategies for the treatment of elevated blood pressure is to attenuate the actions of the renin-angiotensin-aldosterone system. The agents include the angiotensin converting enzyme inhibitors, angiotensin II receptor blockers (ARBs), direct renin inhibitors, and aldosterone antagonists. The ARBs inhibit the action of angiotensin II by binding to the angiotensin II type 1 receptor. The inhibition of angiotensin II results in a dose dependent decrease in peripheral resistance, reduction in vascular smooth muscle contraction, and reduced synthesis of aldosterone in the kidneys. Azilsartan medoxomil is a highly selective ARB. It was approved by the US Food and Drug Administration in February 2011 for the treatment of hypertension in adults. It is the eighth ARB to be added to the market. This article will discuss the pharmacologic and clinical characteristics of azilsartan medoxomil to help differentiate it from other ARBs that are used for the management of hypertension. [ABSTRACT FROM AUTHOR]

Azilsartan medoxomil (Edarbi), the eighth angiotensin II receptor blocker for hypertension. [ABSTRACT FROM AUTHOR]

Background: Aboriginal infants have poorer birth outcomes than non-Aboriginal infants. Harmful use of tobacco, alcohol, and other substances is higher among Aboriginal women, as is violence, due to factors such as intergenerational trauma and poverty. We estimated the proportion of small for gestational age (SGA) births, preterm births, and perinatal deaths that could be attributed to these risks.Methods: Birth, hospital, mental health, and death records for Aboriginal singleton infants born in Western Australia from 1998 to 2010 and their parents were linked. Using logistic regression with a generalized estimating equation approach, associations with birth outcomes and population attributable fractions were estimated after adjusting for demographic factors and maternal health during pregnancy.Results: Of 28,119 births, 16% of infants were SGA, 13% were preterm, and 2% died perinatally. 51% of infants were exposed in utero to at least one of the risk factors and the fractions attributable to them were 37% (SGA), 16% (preterm) and 20% (perinatal death).Conclusions: A large proportion of adverse outcomes were attributable to the modifiable risk factors of substance use and assault. Significant improvements in Aboriginal perinatal health are likely to follow reductions in these risk factors. These results highlight the importance of identifying and implementing risk reduction measures which are effective in, and supported by, Aboriginal women, families, and communities. [ABSTRACT FROM AUTHOR]