Merkel cell polyomavirus large T antigen disrupts lysosome clustering by translocating human Vam6p from the cytoplasm to the nucleus

Merkel cell polyomavirus (MCV) has been recently described as the cause for most human Merkel cell carcinomas. MCV is similar to simian virus 40 (SV40) and encodes a nuclear large T (LT) oncoprotein that is usually mutated to eliminate viral replication among tumor-derived MCV. We identified the hVam6p cytoplasmic protein involved in lysosomal processing as a novel interactor with MCV LT but not SV40 LT. hVam6p binds through its clathrin heavy chain homology domain to a unique region of MCV LT adjacent to the retinoblastoma binding site. MCV LT translocates hVam6p to the nucleus, sequestering it from involvement in lysosomal trafficking. A naturally occurring, tumor-derived mutant LT (MCV350) lacking a nuclear localization signal binds hVam6p but fails to inhibit hVam6p-induced lysosomal clustering. MCV has evolved a novel mechanism to target hVam6p that may contribute to viral uncoating or egress through lysosomal processing during virus replication

Which doctors and with what problems contact a specialist service for doctors? A cross sectional investigation

Background: In the United Kingdom, specialist treatment and intervention services for doctors are underdeveloped. The MedNet programme, created in 1997 and funded by the London Deanery, aims to fill this gap by providing a self-referral, face-to-face, psychotherapeutic assessment service for doctors in London and South-East England. MedNet was designed to be a low-threshold service, targeting doctors without formal psychiatric problems. The aim of this study was to delineate the characteristics of doctors utilising the service, to describe their psychological morbidity, and to determine if early intervention is achieved. Methods: A cross-sectional study including all consecutive self-referred doctors (n = 121, 50% male) presenting in 2002–2004 was conducted. Measures included standardised and bespoke questionnaires both self-report and clinician completed. The multi-dimensional evaluation included: demographics, CORE (CORE-OM, CORE-Workplace and CORE-A) an instrument designed to evaluate the psychological difficulties of patients referred to outpatient services, Brief Symptom Inventory to quantify caseness and formal psychiatric illness, and Maslach Burnout Inventory. Results: The most prevalent presenting problems included depression, anxiety, interpersonal, self-esteem and work-related issues. However, only 9% of the cohort were identified as severely distressed psychiatrically using this measure. In approximately 50% of the sample, problems first presented in the preceding year. About 25% were on sick leave at the time of consultation, while 50% took little or no leave in the prior 12 months. A total of 42% were considered to be at some risk of suicide, with more than 25% considered to have a moderate to severe risk. There were no significant gender differences in type of morbidity, severity or days off sick. Conclusion: Doctors displayed high levels of distress as reflected in the significant proportion of those who were at some risk of suicide; however, low rates of severe psychiatric illness were detected. These findings suggest that MedNet clients represent both ends of the spectrum of severity, enabling early clinical engagement for a significant proportion of cases that is of importance both in terms of personal health and protecting patient care, and providing a timely intervention for those who are at risk, a group for whom rapid intervention services are in need and an area that requires further investigation in the UK

Ripples in a pond: Do social work students need to learn about terrorism?

In the face of heightened awareness of terrorism, however it is defined, the challenges for social work are legion. Social work roles may include working with the military to ensure the well-being of service-men and women and their families when bereaved or injured, as well as being prepared to support the public within the emergency context of an overt act of terrorism. This paper reviews some of the literature concerning how social work responds to confl ict and terrorism before reporting a smallscale qualitative study examining the views of social work students, on a qualifying programme in the UK, of terrorism and the need for knowledge and understanding as part of their education

Healthcare Staff Wellbeing, Burnout, and Patient Safety: A Systematic Review

Objective To determine whether there is an association between healthcare professionals’ wellbeing and burnout, with patient safety. Design Systematic research review. Data Sources PsychInfo (1806 to July 2015), Medline (1946 to July 2015), Embase (1947 to July 2015) and Scopus (1823 to July 2015) were searched, along with reference lists of eligible articles. Eligibility Criteria for Selecting Studies Quantitative, empirical studies that included i) either a measure of wellbeing or burnout, and ii) patient safety, in healthcare staff populations. Results Forty-six studies were identified. Sixteen out of the 27 studies that measured wellbeing found a significant correlation between poor wellbeing and worse patient safety, with six additional studies finding an association with some but not all scales used, and one study finding a significant association but in the opposite direction to the majority of studies. Twenty-one out of the 30 studies that measured burnout found a significant association between burnout and patient safety, whilst a further four studies found an association between one or more (but not all) subscales of the burnout measures employed, and patient safety. Conclusions Poor wellbeing and moderate to high levels of burnout are associated, in the majority of studies reviewed, with poor patient safety outcomes such as medical errors, however the lack of prospective studies reduces the ability to determine causality. Further prospective studies, research in primary care, conducted within the UK, and a clearer definition of healthcare staff wellbeing are needed. Implications This review illustrates the need for healthcare organisations to consider improving employees’ mental health as well as creating safer work environments when planning interventions to improve patient safety

Light Hydrocarbon Geochemistry of Oils in the Alpine Foreland Basin: Impact of Geothermal Fluids on the Petroleum System

Oil is produced in the Austrian sector of the Alpine Foreland Basin from Eocene and Cenomanian reservoirs. Apart from petroleum, the basin hosts a significant geothermal potential, which is based on the regional flow of meteoric water through Malmian (Upper Jurassic) carbonate rocks. Oils are predominantly composed of n-alkanes, while some samples are progressively depleted in light aromatic components. The depletion in aromatic components relative to abundant n-alkanes is an effect of water washing. Waters coproduced with oils that are affected by water washing show a progressive reduction in salinity and depletion in 2H and 18O isotopes, indicating that the degree of water washing is mainly controlled by the inflow of meteoric water from the Malmian aquifer. In some fields with Cenomanian reservoir rocks, a hydraulic connectivity with the Malmian aquifer is evident. However, water washing is also recognized in Eocene reservoirs and in areas where the Malmian aquifer is missing. This shows that existing flow models for the regional Malmian aquifer have to be modified. Therefore, the results emphasize the importance of combining data from the petroleum and geothermal industry, which are often handled separately

Using the net benefit regression framework to construct cost-effectiveness acceptability curves: an example using data from a trial of external loop recorders versus Holter monitoring for ambulatory monitoring of "community acquired" syncope

BACKGROUND: Cost-effectiveness acceptability curves (CEACs) describe the probability that a new treatment or intervention is cost-effective. The net benefit regression framework (NBRF) allows cost-effectiveness analysis to be done in a simple regression framework. The objective of the paper is to illustrate how net benefit regression can be used to construct a CEAC. METHODS: One hundred patients referred for ambulatory monitoring with syncope or presyncope were randomized to a one-month external loop recorder (n = 49) or 48-hour Holter monitor (n = 51). The primary endpoint was symptom-rhythm correlation during monitoring. Direct costs were calculated based on the 2003 Ontario Health Insurance Plan (OHIP) fee schedule combined with hospital case costing of labour, materials, service and overhead costs for diagnostic testing and related equipment. RESULTS: In the loop recorder group, 63.27% of patients (31/49) had symptom recurrence and successful activation, compared to 23.53% in the Holter group (12/51). The cost in US dollars for loop recording was $648.50 and$212.92 for Holter monitoring. The incremental cost-effectiveness ratio (ICER) of the loop recorder was $1,096 per extra successful diagnosis. The probability that the loop recorder was cost-effective compared to the Holter monitor was estimated using net benefit regression and plotted on a CEAC. In a sensitivity analysis, bootstrapping was used to examine the effect of distributional assumptions. CONCLUSION: The NBRF is straightforward to use and interpret. The resulting uncertainty surrounding the regression coefficient relates to the CEAC. When the link from the regression's p-value to the probability of cost-effectiveness is tentative, bootstrapping may be used

Medical school faculty discontent: prevalence and predictors of intent to leave academic careers

<p>Abstract</p> <p>Background</p> <p>Medical school faculty are less enthusiastic about their academic careers than ever before. In this study, we measured the prevalence and determinants of intent to leave academic medicine.</p> <p>Methods</p> <p>A 75-question survey was administered to faculty at a School of Medicine. Questions addressed quality of life, faculty responsibilities, support for teaching, clinical work and scholarship, mentoring and participation in governance.</p> <p>Results</p> <p>Of 1,408 eligible faculty members, 532 (38%) participated. Among respondents, 224 (40%; CI95: 0.35, 0.44) reported that their careers were not progressing satisfactorily; 236 (42%; CI95: 0.38, 0.46) were "seriously considering leaving academic medicine in the next five years." Members of clinical departments (OR = 1.71; CI95: 1.01, 2.91) were more likely to consider leaving; members of inter-disciplinary centers were less likely (OR = 0.68; CI95: 0.47, 0.98). The predictors of "serious intent to leave" included: Difficulties balancing work and family (OR = 3.52; CI95: 2.34, 5.30); inability to comment on performance of institutional leaders (OR = 3.08; CI95: 2.07, 4.72); absence of faculty development programs (OR = 3.03; CI95: 2.00, 4.60); lack of recognition of clinical work (OR = 2.73; CI95: 1.60, 4.68) and teaching (OR = 2.47; CI95: 1.59, 3.83) in promotion evaluations; absence of "academic community" (OR = 2.67; CI95: 1.86, 3.83); and failure of chairs to evaluate academic progress regularly (OR = 2.60; CI95: 1.80, 3.74).</p> <p>Conclusion</p> <p>Faculty are a medical school's key resource, but 42 percent are seriously considering leaving. Medical schools should refocus faculty retention efforts on professional development programs, regular performance feedback, balancing career and family, tangible recognition of teaching and clinical service and meaningful faculty participation in institutional governance.</p

Evaluation of job satisfaction of practice staff and general practitioners: an exploratory study

Contains fulltext : 95875.pdf (publisher's version ) (Open Access

Specialty Care Use in US Patients with Chronic Diseases

Despite efforts to eliminate health disparities, racial, ethnic, and geographic groups continue lag behind their counterparts in health outcomes in the United States. The purpose of this study is to determine variation in specialty care utilization by chronic disease status. Data were extracted from the Commonwealth Fund 2006 Health Care Quality Survey (n = 2475). A stratified minority sample design was employed to ensure a representative sample. Logistic regression was used in analyses to predict specialty care utilization in the sample. Poor perceived health, minority status, and lack of insurance was associated with reduced specialty care use and chronic disease diagnosis