Causes and outcomes of at-risk underperforming pharmacy students: implications for policy and practice.

OBJECTIVE: This study aimed to understand the key determinants for poor academic performance of students completing a Bachelor of Pharmacy (BPharm), Bachelor of Pharmacy and Management (BPharmMgmt), or Master of Pharmacy (MPharm) degree. METHODS: Data were collected on pharmacy students who had not met academic progression requirements between 2008 and 2018 at The University of Sydney, Australia. This included: age at the start of pharmacy degree; gender; whether they transferred from another university; whether they were a domestic or international student; Australian Tertiary Admissions Rank upon entry, previous studies in biology, chemistry, or mathematics; show cause triggers (units of study failed); number of show causes; students' written show cause responses; weighted average mark at last show cause or graduation; whether they graduated and were a registered pharmacist; and, the number of years they spent studying the degree. Descriptive studies were used to analyse student characteristics using SPSS software, and student self-reported reasons for poor performance were analysed reflexively using thematic analysis procedures using NVivo. RESULTS: This study included 164 pharmacy students enrolled in a BPharm (79.3%, n = 130), BPharmMgmt (1.2%, n = 2), or MPharm (19.5%, n = 32). Of the students, 54% (n = 88) were men, 81% (n = 133) were domestic students, 15% (n = 24) transferred from another degree program, and 38% (n = 62) graduated from the course. Show cause students were less likely to graduate if they transferred from another degree program (P = 0.0002) or failed more than three units of study (UoS; P < 0.0001). The most commonly failed UoS were related to organic or pharmaceutical chemistry, and the top student self-reported reasons for poor performance was stress/anxiety, physical health, and depression. CONCLUSION: Pharmacy schools should aim to address student foundational knowledge in chemistry, identify at-risk students early using pre-subject testing, and provide better services to address student mental health.

Trajectories of Loneliness Among Older Women and Men: Variation by Sexual Identity?

BACKGROUND AND OBJECTIVES: The aim of this study is to contribute to the literature on variation in later-life outcomes by sexual identity. Drawing on the Iridescent Life Course framework, we examined differences in loneliness trajectories, and tested the roles of social connectedness and support, and socioeconomic and health statuses in explaining any observed disparities. RESEARCH DESIGN AND METHODS: Using growth models, we analyzed 19 years of data (2001-2019) from adults aged 50 years and older from the Household, Income and Labour Dynamics in Australia Survey (n = 5,500 individuals), where a question on sexual identity was asked twice in the study. RESULTS: One percent of our sample reported a change in their sexual identity, which we grouped with individuals who reported as bisexual. Our sample comprised of 45.3% heterosexual men, 52.2% heterosexual women, 0.6% gay men, 0.6% lesbian women, 0.6% bisexual-plus men, and 0.6% bisexual-plus women. We found bisexual-plus men were vulnerable to loneliness as they aged. This group had the highest levels of loneliness at age 50, and differences compared with heterosexual men persisted over time. Loneliness of bisexual-plus men increased steeply from age 70. Socioeconomic and health statuses did not explain the increased loneliness of older bisexual-plus men. Lower social support and connectedness partly accounted for these disparities. DISCUSSION AND IMPLICATIONS: Findings are discussed with regards to existing research and theories on social disadvantage and resilience over the life course. We expand knowledge on factors explaining loneliness and how it varies in women and men by sexual identity.

Life Events and Loneliness Among Older Women of Diverse Sexual Identities: Application of the Stress Process Model.

Loneliness among older adults has been a topic of interest in recent years. We analyse four waves of data from the Australian Longitudinal Study on Women's Health. We estimate growth models to examine differences in loneliness trajectories from age 50 for women who identify as exclusively heterosexual, plurisexual (bisexual, mainly heterosexual, mainly lesbian) and exclusively lesbian. We find no significant differences in levels of loneliness across sexual identity groups at age 50. We find that while loneliness trajectories of exclusively heterosexual women trend down, levels of loneliness increase with age among plurisexual women. Adverse health events and relationship problems increase loneliness to a greater extent among plurisexual women compared to exclusively heterosexual and exclusively lesbian women. Our results suggest older lesbian women may have accumulated social or personal resources or developed coping mechanisms over the courses of their lives, while plurisexual women remain a vulnerable group.

Do extracurricular activities contribute to better adolescent outcomes? A fixed-effects panel data approach.

INTRODUCTION: Extracurricular activity participation is associated with positive academic, health, and behavioral outcomes for adolescents, but these findings may reflect unobserved confounding rather than participation effects. METHOD: Data were drawn from 3885 adolescents aged 12-15 in a nationally representative cohort of Australian adolescents. Effects of participation in three kinds of extracurricular activity (team sport, individual sport, and arts) on an array of outcomes were modeled using fixed-effects regression to account for potential unobserved confounding. RESULTS: Strong bivariate relationships between all forms of activity participation and positive adolescent outcomes were found. These associations were much smaller in the fixed-effects analysis, but beneficial effects of sports for mental health and arts for peer group characteristics remained statistically significant. Minimal effects of extracurricular activity participation for academic achievement were found. CONCLUSION: Extracurricular activity participation has beneficial effects on adolescents' mental health and exposure to peers' delinquent behavior.

Sexual Fluidity and Psychological Distress: What Happens When Young Women's Sexual Identities Change?

The sexual identities of young women today are less binary and more fluid than ever before. Several theoretical perspectives imply that this fluidity could be accompanied by distress. To examine this, we analyzed four waves of data from Australian women born 1989 to 1995 (n = 11,527). We found no evidence of a universal association between sexual identity change and psychological distress. Instead, psychological distress was elevated when women changed their identity away from the heterosexual norm and lowered when they changed their identity toward it. Social stress partly attenuated these associations. In addition, women unsure of their identity at multiple assessment points reported significantly greater psychological distress in the final assessment than women who were never unsure. Our findings suggest that greater support should be offered to women who are questioning their sexual identity or developing a minority identity.

Prevalence and Sociodemographic Correlates of Identifying as Mainly Heterosexual: Stability and Change across Three Cohorts of Australian Women.

In recent decades, the ways in which sexual minorities identify have changed dramatically. In response, social and health surveys have begun offering a greater range of response options within sexual orientation questions-for example, intermediate categories for "mainly heterosexual" and "mainly lesbian/gay" alongside the more common response options of "heterosexual," "bisexual," and "lesbian/gay." Recent studies indicate that women who identify as "mainly heterosexual" report poorer health, greater health-risk behaviors, and higher rates of victimization than women identifying as "exclusively heterosexual." However, we know very little about the demographic profile of women who choose the "mainly heterosexual" identity label compared to the adjacent "exclusively heterosexual" or "bisexual" labels or about changes over time in the prevalence and correlates of "mainly heterosexual" identification. This study addressed these knowledge gaps by modeling unique, high-quality survey data from three national cohorts of Australian women (Australian Longitudinal Study on Women's Health, 2000-2017, n = 76,930 observations). Consistent with the facilitative environments model, we document stark cross-cohort increases in the percentage of Australian women identifying as "mainly heterosexual"-from ∼1% of those born in 1946-1951 to ∼26% of those born in 1989-1995, coinciding with comparable declines in the percentage of women identifying as "exclusively heterosexual." We also found evidence of cohort differences in the associations between key sociodemographic factors-such as age, education, and socioeconomic status-and the likelihood of women identifying as "mainly heterosexual." Finally, our results indicate that same-sex sexual attractions were more strongly associated with "mainly heterosexual" identification than was same-sex sexual behavior.

Changes in Sexual Identity Labels in a Contemporary Cohort of Emerging Adult Women: Patterns, Prevalence and a Typology.

Sexual attraction, behavior and identity are subject to change across the life course for some individuals, and certain developmental periods such as emerging adulthood appear particularly conducive to this. However, the evidence documenting these phenomena comes overwhelmingly from data collected 10-20 years ago. In the brief interlude since, the socio-political context has changed markedly and increasing numbers of women are reporting non-heterosexuality. Drawing on contemporary data from the Australian Longitudinal Study on Women's Health (n = 16,870), we provide up to date evidence on changes in sexual identity labels among emerging adult women. We found that 19% of women changed their sexual identity label from one survey wave to the next, and 30.6% changed their identity label at least once across the four waves. Mostly heterosexual and bisexual labels were both more common and more stable in our sample than in previous studies. We propose a new typology of sexual identity sequences and fit this to our data, providing a blueprint for researchers looking to define sexual minority status longitudinally. Findings suggest that the ways women perceive and label their sexual orientation should be treated as dynamic phenomena situated within the nested temporalities of biographical and historical time.

Sexual Minority Women in Longitudinal Survey Research: Is Attrition a Problem?

As more longitudinal surveys collect information on sexual orientation, evaluating the quality of these data and understanding how sexual minorities engage with the survey process are increasingly important endeavors. This study constitutes the first systematic analysis of sexual orientation as a predictor of attrition from longitudinal surveys. Drawing upon the minority stress model, we developed testable hypotheses about how sexual identity and sexual identity change relate to panel attrition. These hypotheses were subsequently tested using data from two national cohorts of Australian women from the Australian Longitudinal Study on Women's Health (one born 1973-1978, n = 11,262, and one born 1989-1995, n = 16,689). In the older cohort, sexual minority women were more likely to attrit from the survey than exclusively heterosexual women-largely due to noncontact rather than noncooperation. The associations faded once sociodemographic and health-related covariates were included in the models. Further, higher rates of noncontact were observed among women who changed their sexual identity in a more same-sex-oriented direction, compared to women with a stable sexual identity. None of these associations were apparent in the younger cohort. Taken together, our results suggest that sexual minority status may be a risk factor for panel attrition among older but not younger cohorts of women and that improved efforts to locate and contact participants who are generally vulnerable could increase the retention of sexual minorities in longitudinal studies. Effect sizes were nevertheless small, suggesting that existing research on sexual orientation using longitudinal surveys is unlikely to be biased by non-random attrition of non-heterosexual individuals.

Health Disparities Between Sexual Minority and Different-Sex-Attracted Adolescents: Quantifying the Intervening Role of Social Support and School Belonging.

Purpose: An emerging literature documents that sexual minority youth experience significantly and substantially worse health than their heterosexual peers, but few studies have examined the intervening mechanisms linking adolescents' sexual orientation to their health outcomes. This study hypothesized that social support from parents and friends and school belonging would act as important mediators of this relationship and is among the first to test this proposition empirically. Methods: The analyses used rich data from an Australian national probability sample of 14-15-year olds (Longitudinal Study of Australian Children, n = 3204) and regression models to estimate the associations between sexual attraction and four high-quality indicators of adolescent health/well-being capturing health-related quality of life, socio-emotional functioning, depressive symptoms, and life satisfaction. Mediation tests were subsequently performed to quantify the extent to which three scales capturing social support from parents and friends and school belonging mediated the relationships identified. Results: Sexual minority status, social support from parents and friends, and school belonging were significantly related to all health/well-being outcomes. Sexual minority adolescents reported significantly lower levels of support and belonging. Collectively, the support and belonging variables were responsible for 49%-70% of the associations between sexual minority status and the health/well-being outcomes, with school belonging being the most important mediator. Conclusion: These findings have important implications for health equity policy and practice. They suggest that interventions designed to improve the health/well-being of sexual minority adolescents should be directed at eliciting enhanced social support from families and peers and fostering integration at school. School-based interventions may be particularly fruitful.

Mental-health disparities between heterosexual and sexual-minority adolescents: Examining the role of informant discrepancies.

INTRODUCTION: An emerging literature documents substantial mental-health disparities by sexual orientation amongst adolescents, with sexual-minority youth exhibiting poorer mental health than heterosexual youth. This brief report provides the first empirical account of how the association between sexual-minority status and adolescent mental health differs depending on who assesses adolescents' mental health (child/mother/father/teacher), and how informant discrepancies in assessments of adolescent mental health differ by adolescents' sexual orientation. METHODS: Data come from an Australian national sample of 14-/15-year-old adolescents (Longitudinal Study of Australian Children; n~3,000). Adolescent mental health is measured using multiple measures from the Strengths and Difficulties Questionnaire, and modelled using multivariable linear regression models. RESULTS: Mental-health disparities between sexual-minority and heterosexual adolescents emerged irrespective of who assessed the child's mental health. However, their magnitude varied substantially by informant, being largest when mental-health was reported by adolescents (~0.7 standard deviations) and smallest when reported by teachers (~0.2 standard deviations). Discrepancies between mental-health scores collected from the child and other informants were largest for internalising than externalising behaviours, and in child-father than child-mother comparisons. CONCLUSIONS: Understanding informant discrepancies and their meaning is pivotal to designing surveys that generate robust insights into the health of sexual-minority adolescents, as well as appropriate policy interventions.

Sexual Orientation and Adolescent Time Use: How Sexual Minority Youth Spend Their Time.

This study combines minority stress and ecological perspectives to theorize the associations between adolescents' sexual orientation and time use. Hypotheses are tested using data from a national sample of Australian adolescents aged 14-15 years (Longitudinal Study of Australian Children; n = 3,060). Compared to heterosexual adolescents, sexual minority adolescents spent less time with their siblings and fathers, more time alone, less time in active leisure- and school-based activities, and more time in nonactive leisure. There were no differences between sexual minority and heterosexual adolescents in time spent with mothers, peers, and in screen-based leisure. Some associations were gendered. Collectively, the results suggest that sexual minority adolescents may withdraw or be excluded from critical developmental activities and the company of key social partners.

Early roots of sexual-orientation health disparities: associations between sexual attraction, health and well-being in a national sample of Australian adolescents.

BACKGROUND: Research documents substantial adolescent health disparities by sexual orientation, but studies are confined to a small number of countries-chiefly the USA. We provide first-time evidence of associations between sexual orientation and adolescent health/well-being in a new country-Australia. We also add to knowledge by examining health/well-being outcomes not previously analysed in national samples, considering adolescents reporting no sexual attractions, and rank-ordering sexual-orientation health disparities by magnitude. METHODS: Data from an Australian national probability sample of 14/15 years old (Longitudinal Study of Australian Children, n=3318) and regression models adjusted for confounding and for multiple comparisons were used to examine the associations between sexual attraction and 30 outcomes spanning multiple domains of health/well-being-including socio-emotional functioning, health-related quality of life, depressive symptoms, health-related behaviours, social support, self-harm, suicidality, victimisation, self-concept, school belonging and global health/well-being assessments. RESULTS: Lesbian, gay, bisexual and questioning adolescents displayed significantly worse health/well-being than their heterosexual peers in all outcomes (p<0.05). The magnitude of the disparities ranged between 0.13 and 0.75 SD, and was largest in the domains of self-harm, suicidality, peer problems and emotional problems. There were fewer differences between the heterosexual and no-attraction groups. Worse outcomes were observed among both-sex-attracted adolescents compared with same-sex-attracted adolescents, and sexual-minority girls compared with sexual-minority boys. CONCLUSIONS: Consistent with the minority stress model and recent international scholarship, sexual-minority status is an important risk factor for poor adolescent health/well-being across domains in Australia. Interventions aimed at addressing sexual-orientation health disparities within Australian adolescent populations are urgently required.

c-Myc regulates proliferation and Fgf10 expression in airway smooth muscle after airway epithelial injury in mouse.

During lung development, Fibroblast growth factor 10 (Fgf10), which is expressed in the distal mesenchyme and regulated by Wnt signaling, acts on the distal epithelial progenitors to maintain them and prevent them from differentiating into proximal (airway) epithelial cells. Fgf10-expressing cells in the distal mesenchyme are progenitors for parabronchial smooth muscle cells (PSMCs). After naphthalene, ozone or bleomycin-induced airway epithelial injury, surviving epithelial cells secrete Wnt7b which then activates the PSMC niche to induce Fgf10 expression. This Fgf10 secreted by the niche then acts on a subset of Clara stem cells to break quiescence, induce proliferation and initiate epithelial repair. Here we show that conditional deletion of the Wnt target gene c-Myc from the lung mesenchyme during development does not affect proper epithelial or mesenchymal differentiation. However, in the adult lung we show that after naphthalene-mediated airway epithelial injury c-Myc is important for the activation of the PSMC niche and as such induces proliferation and Fgf10 expression in PSMCs. Our data indicate that conditional deletion of c-Myc from PSMCs inhibits airway epithelial repair, whereas c-Myc ablation from Clara cells has no effect on airway epithelial regeneration. These findings may have important implications for understanding the misregulation of lung repair in asthma and COPD.

Localized Fgf10 expression is not required for lung branching morphogenesis but prevents differentiation of epithelial progenitors.

Localized Fgf10 expression in the distal mesenchyme adjacent to sites of lung bud formation has long been thought to drive stereotypic branching morphogenesis even though isolated lung epithelium branches in the presence of non-directional exogenous Fgf10 in Matrigel. Here, we show that lung agenesis in Fgf10 knockout mice can be rescued by ubiquitous overexpression of Fgf10, indicating that precisely localized Fgf10 expression is not required for lung branching morphogenesis in vivo. Fgf10 expression in the mesenchyme itself is regulated by Wnt signaling. Nevertheless, we found that during lung initiation simultaneous overexpression of Fgf10 is not sufficient to rescue the absence of primary lung field specification in embryos overexpressing Dkk1, a secreted inhibitor of Wnt signaling. However, after lung initiation, simultaneous overexpression of Fgf10 in lungs overexpressing Dkk1 is able to rescue defects in branching and proximal-distal differentiation. We also show that Fgf10 prevents the differentiation of distal epithelial progenitors into Sox2-expressing airway epithelial cells in part by activating epithelial ß-catenin signaling, which negatively regulates Sox2 expression. As such, these findings support a model in which the main function of Fgf10 during lung development is to regulate proximal-distal differentiation. As the lung buds grow out, proximal epithelial cells become further and further displaced from the distal source of Fgf10 and differentiate into bronchial epithelial cells. Interestingly, our data presented here show that once epithelial cells are committed to the Sox2-positive airway epithelial cell fate, Fgf10 prevents ciliated cell differentiation and promotes basal cell differentiation.

Parabronchial smooth muscle constitutes an airway epithelial stem cell niche in the mouse lung after injury.

During lung development, parabronchial SMC (PSMC) progenitors in the distal mesenchyme secrete fibroblast growth factor 10 (Fgf10), which acts on distal epithelial progenitors to promote their proliferation. ß-catenin signaling within PSMC progenitors is essential for their maintenance, proliferation, and expression of Fgf10. Here, we report that this Wnt/Fgf10 embryonic signaling cascade is reactivated in mature PSMCs after naphthalene-induced injury to airway epithelium. Furthermore, we found that this paracrine Fgf10 action was essential for activating surviving variant Clara cells (the cells in the airway epithelium from which replacement epithelial cells originate) located at the bronchoalveolar duct junctions and adjacent to neuroendocrine bodies. After naphthalene injury, PSMCs secreted Fgf10 to activate Notch signaling and induce Snai1 expression in surviving variant Clara cells, which subsequently underwent a transient epithelial to mesenchymal transition to initiate the repair process. Epithelial Snai1 expression was important for regeneration after injury. We have therefore identified PSMCs as a stem cell niche for the variant Clara cells in the lung and established that paracrine Fgf10 signaling from the niche is critical for epithelial repair after naphthalene injury. These findings also have implications for understanding the misregulation of lung repair in asthma and cancer.

Specificity in DNA recognition by phage integrases.

The lambda-related (lambdoid) coliphages are related to one another by frequent natural recombination and maintain a high level of functional polymorphism for several activities of the phages. Arguments are presented that the polymorphism of the integration module results from selection (presumably frequency-dependent) for new (not improved) specificities of site recognition. Analysis of phages lambda and HK022 by Weisberg and collaborators previously showed that changes in five noncontiguous amino acids could switch site recognition specificity. Phage 21 and defective element e14, which integrate at the same site, differ in recognition specificity for both core and arm sites. In vitro assays of e14 and 21 insertion and excision confirm this conclusion. Inhibition by ds arm site oligonucleotides defines the sequence specificity more precisely.