Application of bioluminescence resonance energy transfer to quantitate cell-surface expression of membrane proteins.

We report a bioluminescence resonance energy transfer (BRET) assay to quantitate the fraction of an engineered membrane protein at the cell surface versus inside the cell. As test cases, we engineered two different G protein-coupled receptors (GPCRs) in which a NanoLuc luciferase (NLuc) and a HaloTag are fused to the extracellular amino-terminal tail of the receptors. We then employed a pulse-chase labeling approach relying on two different fluorescent dyes with distinctive cell permeability properties. The dyes are efficiently excited by luminescence from NLuc, but are spectrally distinct. Measuring BRET from the chemiluminescence of the NLuc to the fluorophores bound to the HaloTag minimizes the limitations of in-cell fluorescence resonance energy transfer (FRET)-based approaches such as photobleaching and autofluorescence. The BRET surface expression assay can quantitatively differentiate between the labeling of receptors at the cell surface and receptors inside of the cell. The assay is shown to be quantitative and robust compared with other approaches to measure cell surface expression of membrane proteins such as enzyme-linked immunosorbent assay or immunoblotting, and significantly increases the throughput because the assay is designed to be carried out in microtiter plate format.

IDTWO: A Protocol for a Randomised Controlled Trial of a Web-Based Mental Health Intervention for Australians with Intellectual Disability.

People with intellectual disability (ID) experience higher rates of mental illness and reduced access to appropriate care and treatment. Tailored electronic mental health (eMH) programs offer opportunities to address these disparities. The aim of this study is to examine whether a fully automated and self-guided eMH program tailored to the needs of people with ID can reduce symptoms of anxiety and depression and improve daily functioning in people with borderline-to-mild ID. Australians with borderline-to-mild ID, aged 16 years and older with mild-to-moderate depression and/or anxiety symptoms will be eligible to participate with the help of a nominated carer, if necessary. A randomised controlled trial with a sample size of 150 participants divided into treatment and waitlist control arms will be conducted. Participants randomised to the intervention group will have full access to the Healthy Mind program for eight weeks. The waitlist control group will gain full access to the program following the eight-week treatment period. Efficacy will be assessed on the Anxiety, Depression, and Mood Scale; Kessler-10; and the World Health Organisation Disability Assessment Schedule 2.0 across three time-points (baseline, eight weeks, and three months). We expect that people who use the intervention will report reduced depression and anxiety, relative to the control group. To our knowledge, this is the first study to examine the effectiveness of a fully automated eMH program for improving mental health in people with ID. We expect our study to render new knowledge on the delivery and effects of internet-based cognitive behaviour therapy (CBT) tools for people with ID.

Investigating the prevalence of intimate partner violence victimisation in women presenting to the emergency department in suicidal crisis.

OBJECTIVE: To investigate the prevalence of intimate partner violence (IPV) and frequency of victimisation questioning by hospital staff in women presenting to EDs for suicide-related complaints and injuries. METHODS: A cross-sectional survey design was used to assess IPV and ED experiences among women with a recent (<18 months) suicide-related presentation to EDs within six Local Health Districts across New South Wales. Women aged 16 years and over, residing in participating health districts were recruited in-person by hospital staff, or via Facebook advertisements. Variables assessed included demographic characteristics, psychosocial assessment coverage and exposure to IPV (Composite Abuse Scale [Revised]-Short-Form). Binary logistic regression was used to test for independent associations between variables on victimisation questioning by hospital staff. RESULTS: A total of 563 women completed questionnaires following presentation to the ED for a suicide attempt (n = 329; 58%) or suicide crisis (n = 234; 42%). Of these, 200 women (36%) reported IPV exposure in the 18 months prior and 141 women (25%) reported earlier lifetime victimisation. Of the 341 women with a history of IPV, 155 women (45%) were asked about victimisation by hospital staff. Younger age and lower socio-economic status were significantly associated with questioning (P = 0.03). CONCLUSION: Findings suggest a large proportion of women seeking support for suicide in the ED are affected by IPV, although few are asked about abuse experiences. Victimisation is associated with complex health issues and heightened mortality risk, which carry important implications for patient-care. Findings support routine ED screening and can be applied to stratify risk within IPV responses.

Study protocol for a mixed methods prospective cohort study to explore experiences of care following a suicidal crisis in the Australian healthcare system.

INTRODUCTION: For individuals presenting to the emergency department (ED) for a suicide attempt, the period after discharge from hospital is marked by heightened vulnerability for further suicide attempts. Effective care following a suicidal crisis has the potential to significantly decrease this risk. The current study aims to examine the impact of the LifeSpan multilevel suicide prevention model on experiences of care following a suicidal crisis. Perspectives from healthcare consumers (individuals who have presented to the ED following a suicidal crisis), carers, and health professionals will be explored. The LifeSpan model is currently being evaluated as a high-fidelity trial in four geographically defined regions in New South Wales, Australia. METHODS AND ANALYSIS: This study will use a mixed methods prospective cohort design. Quantitative data collection includes a structured survey, administered to healthcare consumers from LifeSpan sites and control sites. Two cohorts of healthcare consumers will be recruited 12 months apart with baseline assessment occurring within 18 months of the ED presentation, and follow-up 12 months after the initial assessment. Survey participants will be recruited online and through participating EDs, mental health organisations and aftercare services. Qualitative interview data from healthcare consumers, carers who have accompanied a loved one to the ED following a suicidal crisis and health professionals who provide care to people at risk of suicide will be collected concurrently with the recruitment of the first cohort of survey participants. Purposive and convenience sampling techniques will be used for recruitment of interview participants. The primary outcome for this study will be healthcare consumers' experiences of service provided at the ED. Analysis will be undertaken of the change over time within LifeSpan sites, as well as between LifeSpan sites and control sites, using mixed effects repeated measures models as principal means of data analysis. ETHICS AND DISSEMINATION: This research has been approved by the Hunter New England Human Research Ethics Committee (HREC/17/HNE/144). Results will be disseminated via conferences and peer-reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12617000457347.

Evaluation of telephone genetic counselling to facilitate germline BRCA1/2 testing in women with high-grade serous ovarian cancer.

Systemic healthcare issues and geographical challenges restrict women's access to BRCA1/2 testing to inform the use of tailored treatments for high-grade serous ovarian cancer. Consequently, BRCA1/2 testing in this population is low and improved testing pathways are urgently needed. This study aimed to determine the acceptability and feasibility of telephone genetic counselling (TGC) to facilitate treatment-focused BRCA1/2 testing in Australia for women with high-grade serous ovarian cancer. Women who received TGC were invited to complete a survey examining their experiences of the service. A cost analysis was conducted to compare the service to standard, in-person genetic counselling. One hundred and seven women responded (48% response rate); 8 had a BRCA1/2 variant affecting function. Geographical barriers prevented women from accessing genetic services in the past. All participants had a positive attitude towards testing, and regret following testing was minimal. While the impact of testing was greater for those with a positive test result, overall, genetic testing did not put the additional psychosocial burden on the participants. Participant's evaluations of the telephone interactions with the genetic counsellors were highly satisfactory. The service was also found to be cost-effective. This model of telephone genetic counselling was an acceptable and effective way to reduce barriers to BRCA1/2 testing for women with ovarian cancer.

Men's experiences of recontact about a potential increased risk of prostate cancer due to Lynch Syndrome: "Just another straw on the stack".

The practice of recontacting patients to provide new health information is becoming increasingly common in clinical genetics, despite the limited research to evidence the patient experience. We explored how men with Lynch Syndrome (LS) understand and experience being recontacted about a potential increased risk of prostate cancer. Sixteen men with LS (Meanage 51 years) were recruited from an Australian screening study to undergo a semi-structured interview. A modified grounded theory approach was used to guide data collection and thematic analysis. Qualitative coding was shared by the research team to triangulate analysis. The practice of recontact was viewed by participants as acceptable and was associated with minimal emotional distress. The majority of men understood that they may be above population risk of prostate cancer, although evidence was still emerging. Men reported high engagement with personal and familial health, including regular screening practices and familial risk communication. Findings suggest that men's carrier status and beliefs about the actionability of the new cancer risk information influence their response to recontact. Recontact practices that include the offer of risk management strategies may lead to improved patient outcomes (e.g., reduced cancer worry and increased health engagement), if perceived as valuable by recipients.

A comparison of Australian and French families affected by sarcoma: perceptions of genetics and incidental findings.

AIM: To compare Australian and French perceptions of genetics and preferences regarding the return of incidental findings. METHODS: Participants from the International Sarcoma Kindred Study received a survey at intake to cancer referral units. A total of 1442 Australian and 479 French individuals affected by sarcoma and their unaffected family members responded to four hypothetical scenarios depicting hereditary conditions of varying treatability and severity. RESULTS: Australians' preference for the return of incidental findings was consistently higher than French for all scenarios. Country group differences were significant for two scenarios when individual characteristics were controlled through multivariable analyses. CONCLUSION: Findings support the need for guidelines that are sensitive to sociocultural context and promote autonomous decision-making.

Making Sense of SNPs: Women's Understanding and Experiences of Receiving a Personalized Profile of Their Breast Cancer Risks.

Genome wide association studies have identified a number of common genetic variants - single nucleotide polymorphisms (SNPs) - that combine to increase breast cancer risk. SNP profiling may enhance the accuracy of risk assessment and provides a personalized risk estimate. SNP testing for breast cancer risks may supplement other genetic tests in the future, however, before it can be implemented in the clinic we need to know how it will be perceived and received. Semi-structured qualitative interviews were conducted with 39 women who had previously had a breast cancer diagnosis and undergone BRCA1/2 testing, participated in the Variants in Practice (ViP) study and received personalized risk (SNP) profiles. Interviews explored their understanding and experiences of receiving this SNP information. Women reported feeling positive about receiving their personalized risk profile, because it: provided an explanation for their previous diagnosis of cancer, vindicated previous risk management decisions and clarified their own and other family members' risks. A small group was initially shocked to learn of the increased risk of a second primary breast cancer. This study suggests that the provision of personalized risk information about breast cancer generated by SNP profiling is understood and well received. However, a model of genetic counseling that incorporates monogenic and polygenic genetic information will need to be developed prior to clinical implementation.

Burnout among psychosocial oncologists in Israel: The direct and indirect effects of job demands and job resources.

OBJECTIVE: Psychosocial oncologists may be particularly vulnerable to burnout. This study aimed to assess burnout among Israeli psychosocial oncologists in relation to the Job Demands-Resources model and the coping strategies model. METHOD: Participants included 85 of 128 listed psychosocial oncologists currently working with cancer patients. They completed a questionnaire assessing emotional exhaustion, depersonalization, job demands, job resources, work engagement, overcommitment, and perceived value of work. RESULTS: The mean level of burnout was low, whereas 16.3% experienced high levels of emotional exhaustion and only 2.4% experienced high levels of depersonalization. According to mediation analysis, overcommitment, partially mediated job demands-burnout associations, and work engagement mediated the perceived value-burnout association. Job resources and burnout were not related, either directly or indirectly.Significance of resultsThe study extended the Job Demands-Resources model to include perceived value as an additional resource, and work-engagement and overcommitment as coping strategies. Two distinct patterns of associations were found between work characteristics and burnout: the positive-protective pattern (perceived value and work engagement) and the negative pattern (job demands and overcommitment). These two patterns should be considered for further research and for implementing preventive interventions to reduce burnout in the workplace setting.

Burnout among psychosocial oncologists: an application and extension of the effort-reward imbalance model.

OBJECTIVES: Burnout is a significant problem among healthcare professionals working within the oncology setting. This study aimed to investigate predictors of emotional exhaustion (EE) and depersonalisation (DP) in psychosocial oncologists, through the application of the effort-reward imbalance (ERI) model with an additional focus on the role of meaningful work in the burnout process. METHODS: Psychosocial oncology clinicians (n = 417) in direct patient contact who were proficient in English were recruited from 10 international psychosocial oncology societies. Participants completed an online questionnaire, which included measures of demographic and work characteristics, EE and DP subscales of the Maslach Burnout Inventory-Human Services Survey, the Short Version ERI Questionnaire and the Work and Meaning Inventory. RESULTS: Higher effort and lower reward were both significantly associated with greater EE, although not DP. The interaction of higher effort and lower reward did not predict greater EE or DP. Overcommitment predicted both EE and DP but did not moderate the impact of effort and reward on burnout. Overall, the ERI model accounted for 33% of the variance in EE. Meaningful work significantly predicted both EE and DP but accounted for only 2% more of the variance in EE above and beyond the ERI model. CONCLUSIONS: The ERI was only partially supported as a useful framework for investigating burnout in psychosocial oncology professionals. Meaningful work may be a viable extension of the ERI model. Burnout among health professionals may be reduced by interventions aimed at increasing self-efficacy and changes to the supportive work environment.

An exploration of the prevalence and predictors of work-related well-being among psychosocial oncology professionals: An application of the job demands-resources model.

OBJECTIVE: Burnout is reportedly high among oncology healthcare workers. Psychosocial oncologists may be particularly vulnerable to burnout. However, their work engagement may also be high, counteracting stress in the workplace. This study aimed to document the prevalence of both burnout and work engagement, and the predictors of both, utilizing the job demands-resources (JD-R) model, within a sample of psychosocial oncologists. METHOD: Psychosocial-oncologist (N = 417) clinicians, recruited through 10 international and national psychosocial-oncology societies, completed an online questionnaire. Measures included demographic and work characteristics, burnout (the MBI-HSS Emotional Exhaustion (EE) and Depersonalization (DP) subscales), the Utrecht Work Engagement Scale, and measures of job demands and resources. RESULTS: High EE and DP was reported by 20.2 and 6.6% of participants, respectively, while 95.3% reported average to high work engagement. Lower levels of job resources and higher levels of job demands predicted greater burnout, as predicted by the JD-R model, but the predicted interaction between these characteristics and burnout was not significant. Higher levels of job resources predicted higher levels of work engagement. SIGNIFICANCE OF RESULTS: Burnout was surprisingly low and work engagement high in this sample. Nonetheless, one in five psychosocial oncologists have high EE. Our results suggest that both the positive (resources) and negative (demands) aspects of this work environment have an on impact burnout and engagement, offering opportunities for intervention. Theories such as the JD-R model can be useful in guiding research in this area.