SCRIB expression is deregulated in human prostate cancer, and its deficiency in mice promotes prostate neoplasia

Loss of cellular polarity is a hallmark of epithelial cancers, raising the possibility that regulators of polarity have a role in suppressing tumorigenesis. The Scribble complex is one of at least three interacting protein complexes that have a critical role in establishing and maintaining epithelial polarity. In human colorectal, breast, and endometrial cancers, expression of the Scribble complex member SCRIB is often mislocalized and deregulated. Here, we report that Scrib is indispensable for prostate homeostasis in mice. Scrib heterozygosity initiated prostate hyperplasia, while targeted biallelic Scrib loss predisposed mice to prostate intraepithelial neoplasia. Mechanistically, Scrib was shown to negatively regulate the MAPK cascade to suppress tumorigenesis. Further analysis revealed that prostate-specific loss of Scrib in mice combined with expression of an oncogenic Kras mutation promoted the progression of prostate cancer that recapitulated the human disease. The clinical significance of the work in mice was highlighted by our observation that SCRIB deregulation strongly correlated with poor survival in human prostate cancer. These data suggest that the polarity network could provide a new avenue for therapeutic intervention

Moderating Perceptions of Bother Reports by Individuals Experiencing Lower Urinary Tract Symptoms

We compared reports of symptom bother for the same urinary symptoms to understand why symptom severity and bother do not correspond in a straightforward manner. We used a grounded theory approach to analyze qualitative data from 123 individual interviews and developed a conceptual framework, identifying three symptom perceptions that might “moderate” symptom bother: causal, relative, and uncertainty. Symptom bother was lower for respondents who viewed symptoms causally (symptoms seemed explainable or “normal”) or relatively (urinary symptoms were compared to other symptoms or conditions). Bother tended to be higher for respondents who viewed symptoms with uncertainty (when symptom etiology and course were unknown). A greater portion of respondents in the causal perception group had not sought health care for their symptoms. This conceptual framework is useful for understanding the relationship between reactions to and health care-seeking for other symptoms

Beyond incontinence: The stigma of other urinary symptoms

This paper is a report of a study conducted to characterize the stigma of urinary frequency and urgency and differentiate it from the stigma of incontinence and to describe race/ethnic and gender differences in the experience of stigma among a diverse sample of individuals

Feasibility of a cognitive behavioural group intervention to reduce fear of falling and associated avoidance of activity in community-living older people: a process evaluation

BACKGROUND: Fear of falling and associated avoidance of activity are common among older people and may have negative consequences in terms of functional decline, quality of life and institutionalisation. We evaluated the effects of a cognitive behavioural group intervention to reduce fear of falling and associated avoidance of activity among older persons. This intervention showed favourable effects on fear of falling, avoidance of activity, daily activity, and several secondary outcomes. The aim of the present study is to assess the feasibility of this cognitive behavioural group intervention for participants and facilitators. METHODS: The intervention consisted of eight weekly group sessions lasting two hours each and a booster session after six months. Self-administered questionnaires, registration forms and interviews were used to collect data from participants (n = 168) and facilitators (n = 6) on the extent to which the intervention was performed according to protocol, participant attendance, participant adherence, and participants' and facilitators' opinion of the intervention. Quantitative data from the questionnaires and registration forms were analysed by means of descriptive statistics. Qualitative data were categorised based on matching contents of the answers. RESULTS: Facilitators reported no major protocol deviations. Twenty-six percent of the participants withdrew before the start of the programme. Of the persons who started the programme, 84% actually completed it. The participants reported their adherence as good, but facilitators had a less favourable opinion of this. The majority of participants still reported substantial benefits from the programme after six and twelve months of follow-up (71% and 61% respectively). Both participants and facilitators provided suggestions for improvement of the intervention. CONCLUSION: Results of this study show that the current cognitive behavioural group intervention is feasible for both participants and facilitators and fits in well with regular care. Minor refinement of the intervention, however, is warranted to further improve intervention effectiveness and efficiency. Based on these positive findings, we recommend implementing a refined version of this effective and feasible intervention in regular care. TRIAL REGISTRATION: ISRCTN43792817

Blurred lines: work, eldercare and HRM

peer-reviewedThe full text of this article will not be available in ULIR until the embargo expires on the 27/06/2020Increased levels of female labour market participation have impacted on the ability of families to provide care for elderly relatives in many industrialised societies. While work–family balance has received significant academic attention, less attention has focused specifically on individuals with eldercare responsibility, a cohort which accounts for a growing segment of the labour market internationally. Taking a qualitative research approach this paper uses work/family border theory to the constraints and facilitators to reconciling care and employment for employees working full-time in Ireland. The findings highlight the significant impact that eldercare provision has on employees with regard to day-to-day work commitments. We find that while general work–life balance policies exist within organisations, that the design and functionality of such policies are of limited value to elder caregivers. Furthermore, this paper highlights how the lack of formal HR policies around eldercare within organisations results in a reliance on supervisory discretion. We make some recommendations for organisational level strategies to address the needs of a growing number of caregivers.peer-reviewe

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Attrition and bias in the MRC cognitive function and ageing study: an epidemiological investigation

BACKGROUND: Any hypothesis in longitudinal studies may be affected by attrition and poor response rates. The MRC Cognitive Function and Ageing study (MRC CFAS) is a population based longitudinal study in five centres with identical methodology in England and Wales each recruiting approximately 2,500 individuals. This paper aims to identify potential biases in the two-year follow-up interviews. METHODS: Initial non-response: Those not in the baseline interviews were compared in terms of mortality to those who were in the baseline interviews at the time of the second wave interviews (1993–1996). Longitudinal attrition: Logistic regression analysis was used to examine baseline differences between individuals who took part in the two-year longitudinal wave compared with those who did not. RESULTS: Initial non-response: Individuals who moved away after sampling but before baseline interview were 1.8 times more likely to die by two years (95% Confidence interval(CI) 1.3–2.4) compared to respondents, after adjusting for age. The refusers had a slightly higher, but similar mortality pattern to responders (Odds ratio 1.2, 95%CI 1.1–1.4). Longitudinal attrition: Predictors for drop out due to death were being older, male, having impaired activities of daily living, poor self-perceived health, poor cognitive ability and smoking. Similarly individuals who refused were more likely to have poor cognitive ability, but had less years of full-time education and were more often living in their own home though less likely to be living alone. There was a higher refusal rate in the rural centres. Individuals who moved away or were uncontactable were more likely to be single, smokers, demented or depressed and were less likely to have moved if in warden-controlled accommodation at baseline. CONCLUSIONS: Longitudinal estimation of factors mentioned above could be biased, particularly cognitive ability and estimates of movements from own home to residential homes. However, these differences could also affect other investigations, particularly the estimates of incidence and longitudinal effects of health and psychiatric diseases, where the factors shown here to be associated with attrition are risk factors for the diseases. All longitudinal studies should investigate attrition and this may help with aspects of design and with the analysis of specific hypotheses

Оценка надежности высоконадежных систем с учетом ЗИП

Предложены приближенные верхние и нижние оценки коэффициента готовности высоконадежной восстанавливаемой системы со структурной избыточностью. Полученные расчетные соотношения могут использоваться для оценки надежности высоконадежных систем с учетом различных стратегий пополнения ЗИП