Regulation of transient receptor potential melastatin 8 (TRPM8) channel activity by its short isoforms.

One important mechanism of membrane ion channels regulation involves their non-functional isoforms generated by alternative splicing. However, knowledge of such isoforms for the members of transient receptor potential (TRP) superfamily of ion channels remains quite limited. This study focuses on TRPM member, TRPM8, which functions as a cold receptor in sensory neurons, but is also expressed in tissues not exposed to ambient temperatures, as well as in cancer tissues. We report the cloning from prostate cancer cells of new short-splice variants of TRPM8, termed short TRPM8a (sM8a) and short TRPM8ß (sM8ß). Our results show that both variants are in a closed configuration with the C-terminal tail of the full-size TRPM8 chan-nel, resulting in stabilization of its closed state and thus reducing both its cold sensitivity and its activity. Our findings, therefore, uncover a new mode of the regulation of TRPM8 channel by its splice variants.

General Practice after the Introduction of the QOF

While the Quality and Outcomes Framework (QOF) is reported to improve performance, its impact on some aspects of organisations need to be explored given the increased reliance on such schemes. Organisational culture can be seen as providing a sense of common values, belief, and norms, which may act as guidelines for behaviour in organisational settings. This research employs a competing value framework depictures different types of culture based on specific focuses and processes. The study is based on interviews with 2 GP practices in the north of England involving 19 participants. Healthcare professionals were aware that there is a dominant value held and shared strongly among members of the organisations-to provide high quality patient-centred services. This study found that while clan culture is still strong in both practices, changes occured in respondents' culture after the implementation of the QOF.

Managing Cultural Diversity in Healthcare Partnerships: The Case of LIFT

Purpose: The National Health Service (NHS) Local Improvement Finance Trust (LIFT) programme was launched in 2001 as an innovative public-private partnership to address the historical under-investment in local primary care facilities in England. The organisations from the public and private sector that comprise a local LIFT partnership each have their own distinctive norms of behaviour and acceptable working practices - ultimately different organisational cultures. The purpose of this article is to assess the role of organisational culture in facilitating (or impeding) LIFT partnerships and to contribute to an understanding of how cultural diversity in public-private partnerships is managed at the local level. Design/methodology/approach: The approach taken was qualitative case studies, with data gathering comprising interviews and a review of background documentation in three LIFT companies purposefully sampled to represent a range of background factors. Elite interviews were also conducted with senior policy makers responsible for implementing LIFT policy at the national level. Findings: Interpreting the data against a conceptual framework designed to assess approaches to managing strategic alliances, the authors identified a number of key differences in the values, working practices and cultures in public and private organisations that influenced the quality of joint working. On the whole, however, partners in the three LIFT companies appeared to be working well together, with neither side dominating the development of strategy. Differences in culture were being managed and accommodated as partnerships matured. Research limitations/implications: As LIFT develops and becomes the primary source of investment for managing, developing and channelling funding into regenerating the primary care infrastructure, further longitudinal work might examine how ongoing partnerships are working, and how changes in the cultures of public and private partners impact upon wider relationships within local health economies and shape the delivery of patient care. Originality/value: To the authors' knowledge this is the first study of the role of culture in mediating LIFT partnerships and the findings add to the evidence on public-private partnerships in the NHS

Breast Cancer Risk in Relation to Occupations with Exposure to Carcinogens and Endocrine Disruptors:a Canadian Case-Control Study

Background

Endocrine disrupting chemicals and carcinogens, some of which may not yet have been classified as such, are present in many occupational environments and could increase breast cancer risk. Prior research has identified associations with breast cancer and work in agricultural and industrial settings. The purpose of this study was to further characterize possible links between breast cancer risk and occupation, particularly in farming and manufacturing, as well as to examine the impacts of early agricultural exposures, and exposure effects that are specific to the endocrine receptor status of tumours.

Methods

1005 breast cancer cases referred by a regional cancer center and 1147 randomly-selected community controls provided detailed data including occupational and reproductive histories. All reported jobs were industry- and occupation-coded for the construction of cumulative exposure metrics representing likely exposure to carcinogens and endocrine disruptors. In a frequency-matched case?control design, exposure effects were estimated using conditional logistic regression.

Results

Across all sectors, women in jobs with potentially high exposures to carcinogens and endocrine disruptors had elevated breast cancer risk (OR = 1.42; 95% CI, 1.18-1.73, for 10 years exposure duration). Specific sectors with elevated risk included: agriculture (OR = 1.36; 95% CI, 1.01-1.82); bars-gambling (OR = 2.28; 95% CI, 0.94-5.53); automotive plastics manufacturing (OR = 2.68; 95% CI, 1.47-4.88), food canning (OR = 2.35; 95% CI, 1.00-5.53), and metalworking (OR = 1.73; 95% CI, 1.02-2.92). Estrogen receptor status of tumors with elevated risk differed by occupational grouping. Premenopausal breast cancer risk was highest for automotive plastics (OR = 4.76; 95% CI, 1.58-14.4) and food canning (OR = 5.70; 95% CI, 1.03-31.5).

Conclusions

These observations support hypotheses linking breast cancer risk and exposures likely to include carcinogens and endocrine disruptors, and demonstrate the value of detailed work histories in environmental and occupational epidemiology.

The Bright Side of Manufacturing–Remanufacturing Conflict in a Decentralised Closed-Loop Supply Chain

Researchers and managers broadly agree that original equipment manufacturers (OEMs), which have opportunities to produce both new and remanufactured products, are better off by centrally controlling their manufacturing and remanufacturing activities. Thus, OEMs should not remanufacture used products until the remanufacturing cost is sufficiently low to overcome the negative impact of new product cannibalisation. In this paper, we present a contrasting view of the manufacturing–remanufacturing conflict: OEMs sometimes benefit from the decentralised control mode under which they ignore the internal cannibalisation rather than the remanufacturing option. We consider a decentralised closed-loop supply chain in which one OEM can purchase new components from one supplier to produce new products and collect used products from consumers to produce remanufactured products. The key feature of our model is that the OEM can select a centralised or decentralised control mode to manage its manufacturing and remanufacturing activities before the supplier prices the new component. In a steady state period setting, we analyse the players’ optimal decisions and compare the OEM's profits under centralised and decentralised control modes. Our analytic results reveal that the decentralised control within the OEM can outperform the centralised control when the cost structure of producing new and remanufactured products satisfies certain conditions. Finally, the key findings are distilled in a conceptual framework and its managerial implications are discussed.

Chemical Exposures of Women Workers in the Plastics Industry with Particular Reference to Breast Cancer and Reproductive Hazards.

Despite concern about the harmful effects of substances contained in various
plastic consumer products, little attention has focused on the more heavily
exposed women working in the plastics industry. Through a review of the
toxicology, industrial hygiene, and epidemiology literatures in conjunction
with qualitative research, this article explores occupational exposures in producing
plastics and health risks to workers, particularly women, who make up
a large part of the workforce. The review demonstrates that workers are
exposed to chemicals that have been identified as mammary carcinogens and
endocrine disrupting chemicals, and that the work environment is heavily
contaminated with dust and fumes. Consequently, plastics workers have a
body burden that far exceeds that found in the general public.

Improving Patient Safety Through Formal and Informal Learning Networks

This paper explores a novel perspective on patient safety improvements, which draws on
contemporary social network and learning theories. A case study was conducted at a Portuguese
acute university hospital. Data collection followed a staged approach, whereby 46 interviews
were conducted involving 49 respondents from a broad array of departments and professional
backgrounds. This case study highlights the importance of two major interlinked factors in
contributing to patient safety improvements. The first of these is the crucial role of formal and
informal, internal and external social networks. The second is the importance and the possible
advantage of combining formal and informal learning. The analysis suggests that initiatives
rooted in formal learning approaches alone do not necessarily lead to the creation of long-term
grounded internal safety networks, and that patient safety improvements can crucially depend on
bottom-up initiatives of communities of practice and informal learning. Traditional research on
patient safety places a strong emphasis on top-down and managerialist approaches and is often
based on the assumption that „safety? learning is primarily formal and context-independent. This
paper suggests that bottom-up initiatives and a combination of formal and informal learning can
make a major contribute to patient safety improvements.

An exploration of the relationship between social support and depressive symptoms in schizophrenia

Objective: Depressive symptoms in schizophrenia have previously been associated with a perceived lack of social support. The aim of this study was to explore the relationship between perceived social support and depressive symptoms in schizophrenia; to assess the psychological wellbeing of their carers; and to examine the quality of the relationship between the patients and their carers. Method: Individuals with schizophrenia (n = 17) were assessed on the Beck Depression Inventory (BDI), the Beck Hopelessness Scale (BHS), a measure of perceived social support, the Significant Others Scale (SOS) and the Quality of Relationship Inventory (QRI). Results: The mean score on the BDI for patients fell within the moderate-severe range and the mean range on the BHS fell within the moderate range. Family and friends were perceived as supportive resources by patients. There was no significant relationship between patient epressive symptoms or hopelessness and perceived social support. Carers of patients did not report high rates of depressive symptoms or hopelessness. Conclusions: These findings do not support the previous finding of an association between depressive symptoms and a perceived lack of social support in schizophrenia.

Selection and Treatment of Data for Radiocarbon Calibration: An Update to the International Calibration (IntCal) Criteria

High-quality data from appropriate archives are needed for the continuing improvement of radiocarbon calibration curves. We discuss here the basic assumptions behind 14C dating that necessitate calibration and the relative strengths and weaknesses of archives from which calibration data are obtained. We also highlight the procedures, problems and uncertainties involved in determining atmospheric and surface ocean 14C/12C in these archives, including a discussion of the various methods used to derive an independent absolute timescale and uncertainty. The types of data required for the current IntCal database and calibration curve model are tabulated with examples.

IntCal13 and Marine13 Radiocarbon Age Calibration Curves 0-50,000 Years Cal BP

The IntCal09 and Marine09 radiocarbon calibration curves have been revised utilizing newly available and updated data sets from C measurements on tree rings, plant macrofossils, speleothems, corals, and foraminifera. The calibration curves were derived from the data using the random walk model (RWM) used to generate IntCal09 and Marine09, which has been revised to account for additional uncertainties and error structures. The new curves were ratified at the 21st International Radiocarbon conference in July 2012 and are available as Supplemental Material at www.radiocarbon.org. The database can be accessed at http://intcal.qub.ac.uk/intcal13/.