Notch and NOXA-related pathways in melanoma cells

Notch receptor-mediated intracellular events represent an ancient cell signaling system, and alterations in Notch expression are associated with various malignancies in which Notch may function as an oncogene or less commonly as a tumor suppressor. Notch signaling regulates cell fate decisions in the epidermis, including influencing stem cell dynamics and growth/differentiation control of cells in skin. Because of increasing evidence that the Notch signaling network is deregulated in human malignancies, Notch receptors have become attractive targets for selective killing of malignant cells. Compared with proliferating normal human melanocytes, melanoma cell lines are characterized by markedly enhanced levels of activated Notch-1 receptor. By using a small molecule gamma-secretase inhibitor (GSI) consisting of a tripeptide aldehyde, N-benzyloxycarbonyl-Leu-Leu-Nle-CHO, which can block processing and activation of all four different Notch receptors, we identified a specific apoptotic vulnerability in melanoma cells. GSI triggers apoptosis in melanoma cells, but only G2/M growth arrest in melanocytes without subsequent cell death. Moreover, GSI treatment induced a pro-apoptotic BH3-only protein, NOXA, in melanoma cells but not in normal melanocytes. The use of GSI to induce NOXA induction overcomes the apoptotic resistance of melanoma cells, which commonly express numerous cell survival proteins such as Mcl-1, Bcl-2, and survivin. Taken together, these results highlight the concept of synthetic lethality in which exposure to GSI, in combination with melanoma cells overexpressing activated Notch receptors, has lethal consequences, producing selective killing of melanoma cells, while sparing normal melanocytes. By identifying signaling pathways that contribute to the transformation of melanoma cells (e.g. Notch signaling), and anti-cancer agents that achieve tumor selectivity (e.g., GSI-induced NOXA), this experimental approach provides a useful framework for future therapeutic strategies in cutaneous oncology.

The Drinking Expectancy Questionnaire for Men who have Sex with Men (DEQ-MSM): A measure of substance-related beliefs

Introduction and Aims. Alcohol expectancies are associated with drinking behaviour and post-drinking use thoughts, feelings and behaviours. The expectancies held by specific cultural or sub-cultural groups have rarely been investigated. This research maps expectancies specific to gay and other men who have sex with men (MSM) and their relationship with substance use. This study describes the specific development of a measure of such beliefs for alcohol, the Drinking Expectancy Questionnaire for Men who have Sex with Men (DEQ-MSM). Design and Methods. Items selected through a focus group and interviews were piloted on 220 self-identified gay or other MSM via an online questionnaire. Results. Factor analysis revealed three distinct substance reinforcement domains ('Cognitive impairment', 'Sexual activity' and 'Social and emotional facilitation'). These factors were associated with consumption patterns of alcohol, and in a crucial test of discriminant validity were not associated with the consumption of cannabis or stimulants. Similarities and differences with existing measures will also be discussed. Discussion and Conclusions. The DEQ-MSM represents a reliable and valid measure of outcome expectancies, related to alcohol use among MSM, and represents an important advance as no known existing alcohol expectancy measure, to date, has been developed and/or normed for use among this group. Future applications of the DEQ-MSM in health promotion, clinical settings and research may contribute to reducing harm associated with alcohol use among MSM, including the development of alcohol use among young gay men.

Knowledge and attitudes of paediatric nurses related to breastfeeding

Introduction: Almost 90% of Australian mothers are exclusively breastfeeding when they discharge from maternity hospitals but by six months of age breastfeeding infants have reduced to 32% nationally and 19% in Queensland, far below the national target of 80%. Many factors influence the choice to breastfeed, including health care provision, therefore the knowledge and attitudes of paediatric nurses have the potential to affect breastfeeding duration. Aims: To assess current breastfeeding knowledge and attitudes of paediatric nurses in metropolitan and regional Queensland settings. Method: The study used a cross-sectional survey design. The tool was developed from several documented health professional questionnaires about breastfeeding, with permission from authors. Survey items relating breastfeeding physiology, factors relating to breastfeeding success, and local, national and international policies were also included. Ethics approval was granted from the appropriate Ethics Committees to conduct the survey through tertiary metropolitan and regional hospital settings. Results: A total of 241 surveys were returned, achieving a response rate of 53%. Nurses acknowledged breastmilk as the best source of nutrition for infants (99%, n=238) and that mothers should be encouraged to breastfeed (92%, n=221). However, many respondents considered infant formula a nutritional equivalent (44%, n=105) and (47%, n=113) were unaware that supplemental formulas interfered with successful breastfeeding. Most nurses recognised that stress (e.g. infant hospitalisation) impacts on the success of breastfeeding (90%, n=216). Knowledge of breastfeeding anatomy and physiology was poor and a substantial number of nurses did not identify correct attachment in response to two diagrammatic representations (76%, n=183 and 45%, n=109). Survey results demonstrated deficiencies in knowledge that would impact on support provided to breastfeeding mothers. Knowledge deficits were also identified relating to local, national and international policies and protocols concerning breastfeeding and breastmilk substitutes. Conclusion: Breastfeeding knowledge and attitudes were exceptional in areas related to general breastfeeding knowledge. However, in areas directly related to nursing practice, considerable deficits in paediatric nurses' knowledge and attitudes were identified. Lack of appropriate skills, knowledge and varying attitudes amongst paediatric nurses has the potential to negatively impact on the education, advice and support provided to breastfeeding mothers and their families whilst their infant is in hospital. These study findings will guide future research and strategies to improve knowledge and policy statements to assist paediatric nurses in fulfilling their role.

The aetiology, impact and management of cancer-related fatigue in patients with advanced cancer

Cancer-related fatigue (CRF) is a distressing symptom frequently experienced by patients with advanced cancer. While there have been some advances in the understanding of the management of fatigue associated with cancer treatment, CRF associated with advanced cancer remains a phenomenon that is not well-managed. The aetiologic factors associated with CRF, the impacts of CRF and the current management of CRF are discussed in this review article in relation to patients with advanced cancer. The paper concludes that while further research is required in the area, there are several potentially effective strategies currently available that can reduce the severity of CRF in patients with advanced cancer.

Teaching tribology and maintenance-related subjects : a hands-on focus

In this paper different aspects of teaching tribology and maintenance-related subjects with a hands-on focus at Queensland University of Technology (QUT) are presented and discussed. As part of the study, a combination of data from core units, such as engineering design units, and elective units, was used, in addition to laboratory experiments, real-life projects, interactive software packages and industry visits. The mechanical engineering curriculum structure used at QUT, consisting of the main specialization (first major) and the second specialization (second major), is also discussed with specific emphasis on the teaching of tribology and maintenance-related subjects. To evaluate students' satisfaction with the novel teaching approaches used, tailored questionnaires were used as well as QUT's online learning experience survey (LEX). Statistical results of these sureveys are presented and discussed. In summary, these showed that students overwhelmingly support the hands-on and practical focus in teaching tribology and maintenance-related subjects and that the teaching approaches used shorten the learning curve and make students better prepared for integration in the workplace.

Caseload management, work-related stress and case manager self-efficacy among Victorian mental health case managers

Objective: In Australia and comparable countries, case management has become the dominant process by which public mental health services provide outpatient clinical services to people with severe mental illness. There is recognition that caseload size impacts on service provision and that management of caseloads is an important dimension of overall service management. There has been little empirical investigation, however, of caseload and its management. The present study was undertaken in the context of an industrial agreement in Victoria, Australia that required services to introduce standardized approaches to caseload management. The aims of the present study were therefore to (i) investigate caseload size and approaches to caseload management in Victoria's mental health services; and (ii) determine whether caseload size and/or approach to caseload management is associated with work-related stress or case manager self-efficacy among community mental health professionals employed in Victoria's mental health services. Method: A total of 188 case managers responded to an online cross-sectional survey with both purpose-developed items investigating methods of case allocation and caseload monitoring, and standard measures of work-related stress and case manager personal efficacy. Results: The mean caseload size was 20 per full-time case manager. Both work-related stress scores and case manager personal efficacy scores were broadly comparable with those reported in previous studies. Higher caseloads were associated with higher levels of work-related stress and lower levels of case manager personal efficacy. Active monitoring of caseload was associated with lower scores for work-related stress and higher scores for case manager personal efficacy, regardless of size of caseload. Although caseloads were most frequently monitored by the case manager, there was evidence that monitoring by a supervisor was more beneficial than self-monitoring. Conclusion: Routine monitoring of caseload, especially by a workplace supervisor, may be effective in reducing work-related stress and enhancing case manager personal efficacy. Keywords: case management, caseload, stress

Work-Related Subjective Experiences, Work-Related Self-Efficacy, and Career Learning Among People with Psychiatric Disabilities

Work-related subjective experiences and work-related self-efficacy were investigated as candidate correlates of career learning among people with schizophrenia and schizoaffective disorder. Work-related self-efficacy was expected to mediate any observed relationship between work-related subjective experiences and employment status, after controlling for demographic, vocational, and clinical covariates. Baseline measures (n 1 = 104) were repeated at six months (n 2 = 94) and 12 months (n 3 = 94). Work-related subjective experiences and work-related self-efficacy were consistently associated with current employment after controlling for covariates. The proposed mediator role of work-related self-efficacy remains a viable hypothesis requiring further investigation. Both work-related subjective experiences and work-related self-efficacy appear promising as components of the social cognitive career learning theory to help explain career development among people with psychiatric disabilities.

Responding to rapid change in higher education : enabling university departments responsible for work related programs through boundary spanning

Boundary spanning links organisations to one another in order to create mutually beneficial relationships; it is a concept developed and used in organisational theory but rarely used to understand organisational structures in higher education (Pruitt & Schwartz, 1999). Yet understanding boundary spanning activity has the capacity to help universities respond to demands for continuous quality improvement, and to increase capacity to react to environmental uncertainty. At a time of rapid change characterised by a fluctuating economic environment, globalisation, increased mobility, and ecological issues, boundary spanning could be viewed as a key element in assisting institutions in effectively understanding and responding to such change. The literature suggests that effective boundary spanning could help universities improve organisational performance, use of infrastructure and resources, intergroup relations, leadership styles, performance and levels of job satisfaction, technology transfer, knowledge creation, and feedback processes, amongst other things. Our research aims to put a face on boundary spanning (Miller, 2008) by contextualising it within organisational systems and structures in university departments responsible for work related programs i.e. Work Integrated Learning (WIL) and Co-operative Education (Co-op). In this paper these approaches are referred to collectively as work related programs. The authors formed a research team in Victoria, British Columbia in 2009 at a sponsored international research forum, Two Days in June. The purpose of the invitation-only forum was to investigate commonalities and differences across programs and to formulate an international research agenda for work related programs over the next five to ten years. Researchers from Queensland University of Technology, University of Cincinnati, Baden-Wuerttemberg Cooperative State University, University of Ottawa,and Dublin City University agreed that further research was needed into the impact stakeholders, organisational systems, structures, policies, and practices have on departments delivering work related programs. This paper illustrates how policy and practice across the five institutions can be better understood through the lens of boundary spanning. It is argued that boundary spanning is an area of theory and practice with great applicability to a better understanding of the activity of these departments. The paper concludes by proposing topics for future research to examine how boundary spanning can be used to better understand practice and change in work related programs.

Work-related self-efficacy among community residents with psychiatric disabilities

A new measure of work-related self-efficacy for people with psychiatric disabilities is reported. The 37-item scale measures self-efficacy in four relevant activity domains: 1) vocational service access and career planning, 2) job acquisition, 3) work-related social skills, and 4) general work skills. The scale was developed in a 12-month longitudinal survey of urban residents diagnosed with schizophrenia or schizoaffective disorder (n = 104). Results indicate validity of both a four-factor structure differentiating four core skill domains, and a single factor representing total work-related self-efficacy. The favorable psychometric properties support further research and trial applications in supported employment and psychiatric vocational rehabilitation.

Work-related subjective experiences among community residents with schizophrenia or schizoaffective disorder

Objective: To develop a self-report scale of subjective experiences of illness perceived to impact on employment functioning, as an alternative to a diagnostic perspective, for anticipating the vocational assistance needs of people with schizophrenia or schizoaffective disorders. Method: A repeated measures pilot study (n1 = 26, n2 = 21) of community residents with schizophrenia identified a set of work-related subjective experiences perceived to impact on employment functioning. Items with the best psychometric properties were applied in a 12 month longitudinal survey of urban residents with schizophrenia or schizoaffective disorder (n1 = 104; n2 = 94; n3 = 94). Results: Construct validity, factor structure, responsiveness, internal consistency, stability, and criterion validity investigations produced favourable results. Work-related subjective experiences provide information about the intersection of the person, the disorder, and expectations of employment functioning, which suggest new opportunities for vocational professionals to explore and discuss individual assistance needs. Conclusion: Further psychometric investigations of test-retest reliability, discriminant and predictive validity, and research applications in supported employment and vocational rehabilitation, are recommended. Subject to adequate psychometric properties, the new measure promises to facilitate exploring: individuals' specific subjective experiences; how each is perceived to contribute to employment restrictions; and the corresponding implications for specialized treatment, vocational interventions and workplace accommodations.

Apoptosis-related genes confer resistance to Fusarium wilt in transgenic ‘Lady Finger’ bananas

Fusarium wilt, caused by Fusarium oxysporum f. sp. cubense (Foc), is one of the most devastating diseases of banana (Musa spp.). Apart from resistant cultivars, there are no effective control measures for the disease. We investigated whether the transgenic expression of apoptosis-inhibition related genes in banana could be used to confer disease resistance. Embryogenic cell suspensions of the banana cultivar, ‘Lady Finger’, were stably transformed with animal genes that negatively regulate apoptosis, namely Bcl-xL, Ced-9 and Bcl-2 3’ UTR, and independently transformed plant lines were regenerated for testing. Following a 12 week exposure to Foc race 1 in small-plant glasshouse bioassays, seven transgenic lines (2 x Bcl-xL, 3 x Ced-9 and 2 x Bcl-2 3’ UTR) showed significantly less internal and external disease symptoms than the wild-type susceptible ‘Lady Finger’ banana plants used as positive controls. Of these, one Bcl-2 3’ UTR line showed resistance that was equivalent to that of wild-type Cavendish bananas that were included as resistant negative controls. Further, the resistance of this line continued for 23 weeks post-inoculation at which time the experiment was terminated. Using TUNEL assays, Foc race 1 was shown to induce apoptosis-like features in the roots of wild-type ‘Lady Finger’ plants consistent with a necrotrophic phase in the lifecycle of this pathogen. This was further supported by the observed reduction of these effects in the roots of the resistant Bcl-2 3’ UTR transgenic line. This is the first report on the generation of transgenic banana plants with resistance to Fusarium wilt.

Cross-cultural comparisons of health-related quality of life in Australian and Japanese midlife women

Objective: The purpose of this study was to address (1) the existence of an association between menopausal status and the health-related quality of life (HRQOL) in Australian and Japanese women and (2) the relative contributions of menopausal status, modifiable lifestyle risk factors, health, and sociodemographic factors on HRQOL. Design: The Australian and Japanese Midlife Women's Health Study (AJMWHS) was a multisite, population-based study conducted in 2001 to 2002. Measures were conducted on data collected from a survey questionnaire used for a sample of women from Australia and Japan. HRQOL was assessed with seven subscales from the Short Form-36. Results: The differences seen in physical functioning, general health, and vitality are significant. The results support an effect of country of residence on physical functioning and general health. The impact of menopausal status on HRQOL was significantly associated with bodily pain and role-emotional. The country of residence did have a modifying effect on the relationship between menopausal status and physical functioning. After control for confounders, there was a significant difference between Australian and Japanese women for HRQOL. Menopausal status was not associated with HRQOL in the areas of general health and physical functioning. Modifiable lifestyle risk factors contributed more highly to HRQOL for the Australian women than for the Japanese women. If the women had a lowered body mass index, undertook physical activity, consumed dietary phytoestrogens, and used alcohol, their physical functioning seemed to be better. Differences were seen in the contributions to HRQOL in these areas, with lower body mass index in the Australian women and physical activity in the Japanese women being the highest predictors. Somatic and psychological symptoms seem to negatively affect both Japanese and Australian women's physical functioning, contributing more than sociodemographic factors, menopausal status, and behavioral determinants combined to general health and physical functioning. Conclusions: It is important that that consideration be given to incorporating the same tool within the cross-cultural design of studies so that comparisons between cultures and patterns of healthy aging can be made. The research suggests that there seems to be variations across Australian and Japanese midlife women in some areas of HRQOL and some factors that contribute to these areas.

Associations between perception of wellness and health-related quality of life, comorbidities, modifiable lifestyle factors and demographics in older Australians

Aim: The associations between perceived wellness and health-related quality of life, comorbidities and modifiable lifestyle factors in older adults were explored. Methods: Self-administered questionnaires including the Perceived Wellness Survey and the 36-Item Short Form of the Medical Outcomes Study version two were distributed to 328 community-living adults aged 65 years and over. Results: Results showed positive associations between perception of wellness and health-related quality of life. General health (r(249) = 0.66, P < 0.01), vitality (r(249) = 0.59, P < 0.01) and mental health (r(249) = 0.52, P < 0.01) had the strongest association; and social functioning (r(249) = 0.3, P < 0.01) and pain (r(249) = 0.36, P < 0.01) the lowest. Perceived wellness was influenced by hearing, mobility, memory, chronic disease, exercise, gambling and single status. Conclusion: The study identified that perceived wellness in older adults is a multidimensional construct.

Chronological age and age-related cognitive deficits are associated with an increase in multiple types of driving errors in late life

Objective: Older driver research has mostly focused on identifying that small proportion of older drivers who are unsafe. Little is known about how normal cognitive changes in aging affect driving in the wider population of adults who drive regularly. We evaluated the association of cognitive function and age, with driving errors. Method: A sample of 266 drivers aged 70 to 88 years were assessed on abilities that decline in normal aging (visual attention, processing speed, inhibition, reaction time, task switching) and the UFOV® which is a validated screening instrument for older drivers. Participants completed an on-road driving test. Generalized linear models were used to estimate the associations of cognitive factor with specific driving errors and number of errors in self-directed and instructor navigated conditions. Results: All errors types increased with chronological age. Reaction time was not associated with driving errors in multivariate analyses. A cognitive factor measuring Speeded Selective Attention and Switching was uniquely associated with the most errors types. The UFOV predicted blindspot errors and errors on dual carriageways. After adjusting for age, education and gender the cognitive factors explained 7% of variance in the total number of errors in the instructor navigated condition and 4% of variance in the self-navigated condition. Conclusion: We conclude that among older drivers errors increase with age and are associated with speeded selective attention particularly when that requires attending to the stimuli in the periphery of the visual field, task switching, errors inhibiting responses and visual discrimination. These abilities should be the target of cognitive training.

Substance-related expectancies among men who have sex with men : development of psychometric tools to predict unprotected sexual activity

Significant research has demonstrated direct and indirect associations between substance use and sexual behaviour. Substance use is related to sexual risk-taking and HIV seroconversion among some substance-using MSM. It remains unclear what factors mediate or underlie this relationship, and which substances are associated with greater harm. Substance-related expectancies are hypothesised as potential mechanisms. A conceptual model based on social-cognitive theory was tested, which explores the role of demographic factors, substance use, substance-related expectancies and novelty-seeking personality characteristics in predicting unprotected anal intercourse (UAI) while under the influence, across four commonly used substance types. Phase 1, a qualitative study (N = 20), explored how MSM perceive the effects of substance use on their thoughts, feelings and behaviours, including sexual behaviours. Information was attained through discussion and interviews, resulting in the establishment of key themes. Results indicated MSM experience a wide range of reinforcing aspects associated with substance use. General and specific effects were evident across substance types, and were associated with sexual behaviour and sexual risk-taking. Phase 2 consisted of developing a comprehensive profile of substance-related expectancies for MSM (SEP-MSM) regarding alcohol, cannabis, amyl nitrite and stimulants that possessed sound psychometric properties and was appropriate for use among this group. A cross-sectional questionnaire with 249 participants recruited through gay community networks was used to validate these measures, and involved online data collection, participants rating expectancy items and subsequent factor analysis. Results indicated expectancies can be reliably assessed, and predicted substance use patterns. Phase 3 examined demographic factors, substance use, substance-related expectancies, and novelty-seeking traits among another community sample of MSM (N = 277) throughout Australia, in predicting UAI while under the influence. Using a cross-sectional design, participants were recruited through gay community networks and completed online questionnaires. The SEP-MSM, and associated substance use, predicted UAI. This research extends social-cognitive theory regarding sexual behaviour, and advances understanding of the role of expectancies associated with substance use and sexual risk-taking. Future applications of the SEP-MSM in health promotion, prevention, clinical interventions and research are likely to contribute to reducing harm associated with substance-using MSM (e.g., HIV transmission).