Membrane traffic research: Challenges for the next decade

The study of membrane traffic is now a well-established area of research, and one that has resulted in several Nobel prizes including ones awarded to Albert Claude, George Palade, and Christian DeDuve in 1974, Michael Brown and Joseph Goldstein in 1985, Gunter Blobel in 1999, and most recently James Rothman, Randy Schekman, and Thomas Südhof in 2013. As a result of their studies and other research, we now have fundamental insights into the organization and routes of transport between the cells' membranous organelles. Moreover, we have defined the basic "cellular machinery" that governs protein and lipid synthesis, that ensures selective recognition of proteins and lipids, and that promotes vesicle fission, transport, and fusion. In addition, we have a large number of insights into the regulatory molecules that control these processes including the Rab GTPases and their effectors. While the challenges for the future are many, this essay is focused on areas of investigation that we see as moving forward at a rapid pace, which speak to how membrane traffic contributes to overall cell and tissue function, and which are likely to provide important avenues of funding for both established and new investigators. These challenges include how membrane traffic is regulated in response to metabolic needs, how molecules are transferred between organelles, how membrane traffic is regulated and functions during processes such as development, and how membrane traffic is used by highly differentiated cells to perform specialized cell functions

Overweight and obesity as major, modifiable risk factors for urinary incontinence in young to mid-aged women: a systematic review and meta-analysis

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.The purpose of this review and meta-analysis was to evaluate overweight and obesity as risk factors for urinary incontinence in young to mid-aged women. Understanding these relationships during this life stage is important as early onset increases the risk for developing severe and persistent incontinence. A systematic search resulted in 497 citations, 14 of which were retained for review. Data were analysed by overweight and obesity and by subtype of urinary incontinence – stress, urge, mixed and severe. When compared with ‘normal’ body mass index, overweight was associated with a one-third increase in risk of urinary incontinence (relative risk = 1.35, 95% confidence interval = 1.20–1.53), while the risk was doubled in women with obesity (relative risk = 1.95, 95% confidence interval = 1.58–2.42). When estimates were pooled according to urinary incontinence subtype, there was no statistical difference in risk. Overweight and obesity are strong predictors of urinary incontinence, with a significantly greater risk observed for obesity. Clinical advice to young women at risk of, or presenting with, obesity should not be limited to metabolic health only but should emphasize the role of excess weight on pelvic floor weakening and subsequent risk of incontinence

Interdisciplinary (retail) research: The business of geography and the geography of business

NoAt the 2005 British Academy of Management conference several well-known economic geographers, including Neil Wrigley, Gordon Clark, and Susan Christopherson, called for management researchers to engage with economic geographers on interrelated geographical and managerial issues in the study of (retail) firms. In this commentary we reflect upon the present geography -management interface.We begin by considering the term `interdisciplinary research' and its relationship to any management - geography interface. This is followed by a context-specific discussion of international retailing and the role of research on the retail transnational corporation (TNC) in developing an interdisciplinary agenda. This commentary represents an initial more business and management focused response to the call from geography academics for more/better interdisciplinary research at the geography - management interface

Shift work and the risk of cardiovascular disease. A systematic review and meta-analysis including dose–response relationship

This is the final version. Available from Nordic Association of Occupational Safety and Health (NOROSH) via the DOI in this record.Objectives The aim of this review was to assess the risk of cardiovascular disease (CVD) events associated with shift work and determine if there is a dose–response relationship in this association. Method Electronic databases (PubMed, Scopus, and Web of Science) were searched for cohort or case–control control study designs in any population, reporting exposure to shift work as the main contributing factor to estimate CVD risk. For each study, adjusted relative risk (RR) ratios and 95% confidence intervals (CI) were extracted, and used to calculate the pooled RR using random-effect models. Meta-regression analysis was conducted to explore potential heterogeneity sources. Potential non-linear dose–response relationships were examined using fractional polynomial models. Results We included 21 studies with a total of 173 010 unique participants. The majority of the studies were ranked low-to-moderate risk of bias. The risk of any CVD event was 17% higher among shift workers than day workers. The risk of coronary heart disease (CHD) morbidity was 26% higher (1.26, 95% CI 1.10–1.43, I2= 48.0%). Sub-group analysis showed an almost 20% higher risk of CVD and CHD mortality among shift workers than those who did not work shifts (1.22, 95% CI 1.09–1.37, I2= 0% and 1.18, 95% CI 1.06–1.32 I2=0%; respectively). After the first five years of shift work, there was a 7.1% increase in risk of CVD events for every additional five years of exposure (95% CI 1.05–1.10). Heterogeneity of the pooled effect size (ES) estimates was high (I2=67%), and meta-regression analysis showed that sample size explained 7.7% of this. Conclusions The association between shift work and CVD risk is non-linear and seems to appear only after the first five years of exposure. As shift work remains crucial for meeting production and service demands across many industries, policies and initiatives are needed to reduce shift workers’ CVD risk

Who does not gain weight? Prevalence and predictors of weight maintenance in young women

OBJECTIVE: To investigate the prevalence and predictors of weight maintenance over time in a large sample of young Australian women. DESIGN: This population study examined baseline and 4 y follow-up data from the cohort of young women participating in the Australian Longitudinal Study on Women\u27s Health. SUBJECTS: A total of 8726 young women aged 18-23 y at baseline. MEASURES: Height, weight and body mass index (BMI); physical activity; time spent sitting; selected eating behaviours (eg dieting, disordered eating, takeaway food consumption); cigarette smoking, alcohol consumption; parity; and sociodemographic characteristics. RESULTS: Only 44% of the women reported their BMI at follow-up to be within 5% of their baseline BMI (maintainers); 41% had gained weight and 15% had lost weight. Weight maintainers were more likely to be in managerial or professional occupations; to have never married; to be currently studying; and not to be mothers. Controlling for sociodemographic factors, weight maintainers were more likely to be in a healthy weight range at baseline, and to report that they spent less time sitting, and consumed less takeaway food, than women who gained weight. CONCLUSIONS: Fewer than half the young women in this community sample maintained their weight over this 4 y period in their early twenties. Findings of widespread weight gain, particularly among those already overweight, suggest that early adulthood, which is a time of significant life changes for many women, may be an important time for implementing strategies to promote maintenance of healthy weight. Strategies which encourage decreased sitting time and less takeaway food consumption may be effective for encouraging weight maintenance at this life stage.<br /

Resource use data by patient report or hospital records: Do they agree?

Background: Economic evaluations alongside clinical trials are becoming increasingly common. Cost data are often collected through the use of postal questionnaires; however, the accuracy of this method is uncertain. We compared postal questionnaires with hospital records for collecting data on physiotherapy service use. Methods: As part of a randomised trial of orthopaedic medicine compared with orthopaedic surgery we collected physiotherapy use data on a group of patients from retrospective postal questionnaires and from hospital records. Results: 315 patients were referred for physiotherapy. Hospital data on attendances was available for 30% (n = 96), compared with 48% (n = 150) of patients completing questionnaire data (95% Cl for difference = 10% to 24%); 19% (n = 59) had data available from both sources. The two methods produced an intraclass correlation coefficient of 0.54 (95% Cl 0.31 to 0.70). However, the two methods produced significantly different estimates of resource use with patient self report recalling a mean of 1.3 extra visits (95% Cl 0.4 to 2.2) compared with hospital records. Conclusions: Using questionnaires in this study produced data on a greater number of patients compared with examination of hospital records. However, the two data sources did differ in the quantity of physiotherapy used and this should be taken into account in any analysi

A multilevel study of neighborhood disadvantage, individual socioeconomic position, and body mass index: Exploring cross-level interaction effects

This study examined associations between neighborhood disadvantage and body mass index (BMI), and tested whether this differed by level of individual socioeconomic position (SEP). Data were from 9953 residents living in 200 neighborhoods in Brisbane, Australia in 2007. Multilevel linear regression analyses were undertaken by gender to determine associations between neighborhood disadvantage, individual SEP (education, occupation and household income) and BMI (from self-reported height and weight); with cross-level interactions testing whether the relationship between neighborhood disadvantage and BMI differed by level of individual SEP. Both men (Quintile 4, where Quintile 5 is the most disadvantaged β = 0.66 95%CI 0.20, 1.12) and women (Quintile 5 β = 1.32 95%CI 0.76, 1.87) from more disadvantaged neighborhoods had a higher BMI. BMI was significantly higher for those with lower educational attainment (men β = 0.71 95%CI 0.36, 1.07 and women β = 1.66 95%CI 0.78, 1.54), and significantly lower for those in blue collar occupations (men β = −0.67 95%CI −1.09, −0.25 and women β = −0.71 95%CI −1.40, −0.01). Among men, those with a lower income had a significantly lower BMI, while the opposite was found among women. None of the interaction models had a significantly better fit than the random intercept models. The relationship between neighborhood disadvantage and BMI did not differ by level of education, occupation, or household income. This suggests that individual SEP is unlikely to be an effector modifier of the relationship between neighborhood disadvantage and BMI. Further research is required to assist policy-makers to make more informed decisions about where to intervene to counteract BMI-inequalities

Integrin-mediated interactions with extracellular matrix proteins for nucleus pulposus cells of the human intervertebral disc.

The extracellular matrix (ECM) of the human intervertebral disc is rich in molecules that interact with cells through integrin-mediated attachments. Porcine nucleus pulposus (NP) cells have been shown to interact with laminin (LM) isoforms LM-111 and LM-511 through select integrins that regulate biosynthesis and cell attachment. Since human NP cells lose many phenotypic characteristics with age, attachment and interaction with the ECM may be altered. Expression of LM-binding integrins was quantified for human NP cells using flow cytometry. The cell-ECM attachment mechanism was determined by quantifying cell attachment to LM-111, LM-511, or type II collagen after functionally blocking specific integrin subunits. Human NP cells express integrins β1, α3, and α5, with over 70% of cells positive for each subunit. Blocking subunit β1 inhibited NP cell attachment to all substrates. Blocking subunits α1, α2, α3, and α5 simultaneously, but not individually, inhibits NP cell attachment to laminins. While integrin α6β1 mediated porcine NP cell attachment to LM-111, we found integrins α3, α5, and β1 instead contributed to human NP cell attachment. These findings identify integrin subunits that may mediate interactions with the ECM for human NP cells and could be used to promote cell attachment, survival, and biosynthesis in cell-based therapeutics