Genetic variants influencing human aging from late-onset Alzheimer's disease (LOAD) genome-wide association studies (GWAS)

Genetics plays a crucial role in human aging with up to 30% of those living to the mid-80s being determined by genetic variation. Survival to older ages likely entails an even greater genetic contribution. There is increasing evidence that genes implicated in age-related diseases, such as cancer and neuronal disease, play a role in affecting human life span. We have selected the 10 most promising late-onset Alzheimer's disease (LOAD) susceptibility genes identified through several recent large genome-wide association studies (GWAS). These 10 LOAD genes (APOE, CLU, PICALM, CR1, BIN1, ABCA7, MS4A6A, CD33, CD2AP, and EPHA1) have been tested for association with human aging in our dataset (1385 samples with documented age at death [AAD], age range: 58-108 years; mean age at death: 80.2) using the most significant single nucleotide polymorphisms (SNPs) found in the previous studies. Apart from the APOE locus (rs2075650) which showed compelling evidence of association with risk on human life span (p = 5.27 × 10(-4)), none of the other LOAD gene loci demonstrated significant evidence of association. In addition to examining the known LOAD genes, we carried out analyses using age at death as a quantitative trait. No genome-wide significant SNPs were discovered. Increasing sample size and statistical power will be imperative to detect genuine aging-associated variants in the future. In this report, we also discuss issues relating to the analysis of genome-wide association studies data from different centers and the bioinformatic approach required to distinguish spurious genome-wide significant signals from real SNP associations.

International Projects and Cross-Cultural Adjustment of British Expatriates in Middle East: A Qualitative Investigation of Influencing Factors

Increased globalisation within the British AEC (Architectural, Engineering and Construction) sector has increased the need for companies to transfer staff to manage their overseas operations. To be able to perform abroad, expatriates must harmonise themselves to the conditions prevailing in the host country. These include getting accustomed to living, working and interacting with the host country nationals. The process is commonly referred to as 'cross-cultural adjustment'. Various factors influence the process of adjustment. In order to identify these issues, a qualitative study was undertaken, which mainly comprised of comprehensive literature review, individual interviews and focus group discussion with British expatriates working on international AEC assignments in Middle Eastern countries. Through interpretative approach, the current study aims to understand the concept of cross-cultural adjustment of British Expatriates based in Middle East and their influencing factors.

The findings suggest that success of expatriation does not entirely rest on an expatriate's ability but also on organisational support and assistance that expatriates receive prior to and during the assignment. Organisational factors such as selection mechanisms, job design, training, logistical and social support, mentoring, etc., influence various facets of expatriate adjustment. Striking cultural contrasts between British and Arab culture both in work and non work situations also dictate the level of support required by the expatriate, suggesting that relocation to less developed, remote or politically unstable regions, demands additional support and consideration by the parent company. This study is relevant to the AEC companies employing British expatriates, who need to be cognisant of the issues highlighted above to make rational and informed decisions when handling international assignments in the Middle East.

'Lipoproteins, glycoxidation and diabetic angiopathy'

The chronic vascular complications of diabetes (nephropathy, retinopathy and accelerated atherosclerosis) are a major cause of morbidity and premature mortality. In spite of the more widespread availability of intensive diabetes management, approximately one in three people with diabetes develop aggressive complications and over 70% die of atherosclerosis-related diseases. Genetic and acquired factors are likely to be contributory. Potential mediators of vascular damage may include the interrelated processes of lipoprotein abnormalities, glycation, oxidation and endothelial dysfunction. Lipoprotein abnormalities encompass alterations in lipid concentrations, lipoprotein composition and subclass distribution and lipoprotein-related enzymes. Nonenzymatic glycation and oxidative damage to lipoproteins, other proteins and to vascular structures may also be deleterious. As atherosclerosis is a chronic condition commencing in youth, and because clinical events may be silent in diabetes, surrogate measures of vascular disease are important for early identification of diabetic patients with or at high risk of vascular damage, and for monitoring efficacy of interventions. The increasing array of biochemical assays for markers and mediators of vascular damage, noninvasive measures of vascular health, and therapeutic options should enable a reduction in the excessive personal and economic burden of vascular disease in type 1 and type 2 diabetes.

Quantification of N-(glucitol)ethanolamine and N-(carboxymethyl)serine:two products of nonenzymatic modification of aminophospholipids formed in vivo

Chemical, nonenzymatic modification of protein and lipids by reducing sugars, such as glucose, is thought to contribute to age-related deterioration in tissue protein and cellular membranes and to the pathogenesis of diabetic complications. This report describes the synthesis and quantification of N-(glucitol)ethanolamine (GE) and N-(carboxymethyl)serine (CMS), two products of nonenzymatic modification of aminophospholipids. GE is the product of reduction and hydrolysis of glycated phosphatidylethanolamine (PE), while CMS is formed through reaction of phosphatidylserine (PS) with products of oxidation of either carbohydrate (glycoxidation) or lipids (lipoxidation). Gas chromatography/mass spectrometry procedures for quantification of the N,O-acetyl methyl ester derivatives of the modified head groups were developed. GE and CMS were quantified in samples of PE and PS, respectively, following incubation with glucose in vitro; CMS formation was dependent on the presence of oxygen during the incubation. Both GE and CMS were detected and quantified in lipid extracts of human red blood cell membranes. The content of GE, but not CMS, was increased in the lipids from diabetic compared to nondiabetic subjects. Measurement of these modified lipids should prove useful for assessing the role of carbonyl-amine reactions of aminophospholipids in aging and age-related diseases.

Effect of interleukin-6 polymorphisms on human longevity:a systematic review and meta-analysis

Several studies have assessed changes in frequency of -174 interleukin (IL)-6 single nucleotide polymorphism (SNP) with age. If IL-6 tracks with disability and age-related diseases, then there should be reduction, in the oldest old, of the frequency of homozygous GG subjects, who produce higher IL-6 levels. However, discordant results have been obtained. To explore the relationship between this polymorphism and longevity, we analyzed individual data on long-living subjects and controls from eight case-control studies conducted in Europeans, using meta-analysis. There was no significant difference in the IL-6 genotype between the oldest old and controls (Odds Ratio [OR]=0.96; 95% C.I.: 0.77-1.20; p=0.71), but there was significant between-study heterogeneity (I2=55.5%). In a subgroup analyses when male centenarians from the three Italian studies were included, the frequency of the IL-6 -174 GG genotype was significantly lower than the other genotypes (OR=0.49; 95% C.I.: 0.31-0.80; p=0.004), with no evidence of heterogeneity (I2=0%). Our data supports a negative association between the GG genotype of IL-6 SNP and longevity in Italian centenarians, with males who carry the genotype being two times less likely to reach extreme old age compared with subjects carrying CC or CG genotypes. These findings were not replicated in other European groups suggesting a possible interaction between genetics, sex and environment in reaching longevity.

The prospective effects of workplace violence on physicians' job satisfaction and turnover intentions: the buffering effect of job control

Background: Health care professionals, including physicians, are at high risk of encountering workplace violence. At the same time physician turnover is an increasing problem that threatens the functioning of the health care sector worldwide. The present study examined the prospective associations of work-related physical violence and bullying with physicians’ turnover intentions and job satisfaction. In addition, we tested whether job control would modify these associations.

Methods: The present study was a 4-year longitudinal survey study, with data gathered in 2006 and 2010.The present sample included 1515 (61% women) Finnish physicians aged 25–63 years at baseline. Analyses of covariance (ANCOVA) were conducted while adjusting for gender, age, baseline levels, specialisation status, and employment sector.

Results: The results of covariance analyses showed that physical violence led to increased physician turnover intentions and that both bullying and physical violence led to reduced physician job satisfaction even after adjustments. We also found that opportunities for job control were able to alleviate the increase in turnover intentions resulting from bullying.

Conclusions: Our results suggest that workplace violence is an extensive problem in the health care sector and may lead to increased turnover and job dissatisfaction. Thus, health care organisations should approach this problem through different means, for example, by giving health care employees more opportunities to control their own work.

Association of physical activity with future mental health in older, mid-life and younger women

Background: Mental ill-health, particularly depression and anxiety, is a leading and increasing cause of disability worldwide, especially for women.

Methods: We examined the prospective association between physical activity and symptoms of mental ill-health in younger, mid-life and older working women. Participants were 26 913 women from the ongoing cohort Finnish Public Sector Study with complete data at two phases, excluding those who screened positive for mental ill-health at baseline. Mental health was assessed using the 12-item General Health Questionnaire. Self-reported physical activity was expressed in metabolic equivalent task (MET) hours per week. Logistic regression models were used to analyse associations between physical activity levels and subsequent mental health.

Results: There was an inverse dose–response relationship between physical activity and future symptoms of mental ill-health. This association is consistent with a protective effect of physical activity and remained after adjustments for socio-demographic, work-related and lifestyle factors, health and body mass index. Furthermore, those mid-life and older women who reported increased physical activity by more than 2 MET hours per week demonstrated a reduced risk of later mental ill-health in comparison with those who did not increase physical activity. This protective effect of increased physical activity did not hold for younger women.

Conclusions: This study adds to the evidence for the protective effect of physical activity for later mental health in women. It also suggests that increasing physical activity levels may be beneficial in terms of mental health among mid-life and older women. The alleviation of menopausal symptoms may partly explain age effects but further research is required.

Respiratory syncytial virus infections enhance cigarette smoke induced COPD in mice

Respiratory syncytial viral (RSV) infections are a frequent cause of chronic obstructive pulmonary disease (COPD) exacerbations, which are a major factor in disease progression and mortality. RSV is able to evade antiviral defenses to persist in the lungs of COPD patients. Though RSV infection has been identified in COPD, its contribution to cigarette smoke-induced airway inflammation and lung tissue destruction has not been established. Here we examine the long-term effects of cigarette smoke exposure, in combination with monthly RSV infections, on pulmonary inflammation, protease production and remodeling in mice. RSV exposures enhanced the influx of macrophages, neutrophils and lymphocytes to the airways of cigarette smoke exposed C57BL/6J mice. This infiltration of cells was most pronounced around the vasculature and bronchial airways. By itself, RSV caused significant airspace enlargement and fibrosis in mice and these effects were accentuated with concomitant smoke exposure. Combined stimulation with both smoke and RSV synergistically induced cytokine (IL-1a, IL-17, IFN-c, KC, IL-13, CXCL9, RANTES, MIF and GM-CSF) and protease (MMP-2, -8, -12, -13, -16 and cathepsins E, S, W and Z) expression. In addition, RSV exposure caused marked apoptosis within the airways of infected mice, which was augmented by cigarette smoke exposure. RSV and smoke exposure also reduced protein phosphatase 2A (PP2A) and protein tyrosine phosphates (PTP1B) expression and activity. This is significant as these phosphatases counter smoke-induced inflammation and protease expression. Together, these findings show for the first time that recurrent RSV infection markedly enhances inflammation, apoptosis and tissue destruction in smoke-exposed mice. Indeed, these results indicate that preventing RSV transmission and infection has the potential to significantly impact on COPD severity and progression.

Job strain and the risk of severe asthma exacerbations: A meta-analysis of individual-participant data from 100 000 European men and women

Background: Many patients and healthcare professionals believe that work-related psychosocial stress, such as job strain, can make asthma worse, but this is not corroborated by empirical evidence. We investigated the associations between job strain and the incidence of severe asthma exacerbations in working-age European men and women. Methods: We analysed individual-level data, collected between 1985 and 2010, from 102 175 working-age men and women in 11 prospective European studies. Job strain (a combination of high demands and low control at work) was self-reported at baseline. Incident severe asthma exacerbations were ascertained from national hospitalization and death registries. Associations between job strain and asthma exacerbations were modelled using Cox regression and the study-specific findings combined using random-effects meta-analyses. Results: During a median follow-up of 10 years, 1 109 individuals experienced a severe asthma exacerbation (430 with asthma as the primary diagnostic code). In the age- and sex-adjusted analyses, job strain was associated with an increased risk of severe asthma exacerbations defined using the primary diagnostic code (hazard ratio, HR: 1.27, 95% confidence interval, CI: 1.00, 1.61). This association attenuated towards the null after adjustment for potential confounders (HR: 1.22, 95% CI: 0.96, 1.55). No association was observed in the analyses with asthma defined using any diagnostic code (HR: 1.01, 95% CI: 0.86, 1.19). Conclusions: Our findings suggest that job strain is probably not an important risk factor for severe asthma exacerbations leading to hospitalization or death.

Evaluation of the effect of wheat aleurone-rich foods on markers of antioxidant status, inflammation and endothelial function in apparently healthy men and women

Observational data show an inverse association between the consumption of whole-grain foods, and inflammation and related diseases. Although the underlying mechanisms are unclear, whole grains, and in particular the aleurone layer, contain a wide range of components with putative antioxidant and anti-inflammatory effects. We evaluated the effects of a diet high in wheat aleurone on plasma antioxidants status, markers of inflammation and endothelial function. In this parallel, participant-blinded intervention, seventy-nine healthy, older, overweight participants (45-65 years, BMI>25 kg/m²) incorporated either aleurone-rich cereal products (27 g aleurone/d), or control products balanced for fibre and macronutrients, into their habitual diets for 4 weeks. Fasting blood samples were taken at baseline and on day 29. Results showed that, compared to control, consumption of aleurone-rich products provided substantial amounts of micronutrients and phytochemicals which may function as antioxidants. Additionally, incorporating these products into a habitual diet resulted in significantly lower plasma concentrations of the inflammatory marker, C-reactive protein (P = 0·035), which is an independent risk factor for CVD. However, no changes were observed in other markers of inflammation, antioxidant status or endothelial function. These results provide a possible mechanism underlying the beneficial effects of longer-term whole-grain intake. However, it is unclear whether this effect is owing to a specific component, or a combination of components in wheat aleurone.

The Outcomes of Cross-Cultural Adjustment: A Case of British Expatriates Working on International Architectural, Engineering and Construction Assignments

The main aim of this study is to investigate the consequences of cross-cultural adjustment in an under researched sample of British expatriates working on International Architectural, Engineering and Construction (AEC) assignments. Adjustment is the primary outcome of an expatriate assignment. According to Bhaskar-Srinivas et al., (2005), Harrison et al., (2004) it is viewed to affect other work related outcomes which could eventually predict expatriate success. To address the scarcity of literature on expatriate management in the AEC sector, an exploratory design was adopted. Phase one is characterised by extensive review of extant literature, whereas phase two was qualitative exploration from British expatriates’ perspective; here seven unstructured interviews were carried out. Further, cognitive mapping analysis through Banaxia decision explorer software was conducted to develop a theoretical framework and propose various hypotheses. The findings imply that British AEC firms could sustain their already established competitive advantage in the global marketplace by acknowledging the complexity of international assignments, prioritising expatriate management and offering a well-rounded support to facilitate expatriate adjustment and ultimately achieve critical outcomes like performance, assignment completion and job satisfaction.

The outcomes of cross-cultural adjustment: A case of British expatriates working on international architectural, engineering and construction assignments

The main aim of this study is to investigate the consequences of cross-cultural adjustment in an under researched sample of British expatriates working on International Architectural, Engineering and Construction (AEC) assignments. Adjustment is the primary outcome of an expatriate assignment. According to Bhaskar-Srinivas et al., (2005), Harrison et al., (2004) it is viewed to affect other work related outcomes which could eventually predict expatriate success. To address the scarcity of literature on expatriate management in the AEC sector, an exploratory design was adopted. Phase one is characterised by extensive review of extant literature, whereas phase two was qualitative exploration from British expatriatesÕ perspective; here seven unstructured interviews were carried out. Further, cognitive mapping analysis through Banaxia decision explorer software was conducted to develop a theoretical framework and propose various hypotheses. The findings imply that British AEC firms could sustain their already established competitive advantage in the global marketplace by acknowledging the complexity of international assignments, prioritising expatriate management and offering a well-rounded support to facilitate expatriate adjustment and ultimately achieve critical outcomes like performance, assignment completion and job satisfaction.

Does vicarious traumatisation affect oncology nurses?:A literature review

It is widely documented that nurses experience work-related stress [Quine, L., 1998. Effects of stress in an NHS trust: a study. Nursing Standard 13 (3), 36-41; Charnley, E., 1999. Occupational stress in the newly qualified staff nurse. Nursing Standard 13 (29), 32-37; McGrath, A., Reid, N., Boore, J., 2003. Occupational stress in nursing. International Journal of Nursing Studies 40, 555-565; McVicar, A., 2003. Workplace stress in nursing: a literature review. Journal of Advanced Nursing 44 (6), 633-642; Bruneau, B., Ellison, G., 2004. Palliative care stress in a UK community hospital: evaluation of a stress-reduction programme. International Journal of Palliative Nursing 10 (6), 296-304; Jenkins, R., Elliott, P., 2004. Stressors, burnout and social support: nurses in acute mental health settings. Journal of Advanced Nursing 48 (6), 622-631], with cancer nursing being identified as a particularly stressful occupation [Hinds, P.S., Sanders, C.B., Srivastava, D.K., Hickey, S., Jayawardene, D., Milligan, M., Olsen, M.S., Puckett, P., Quargnenti, A., Randall, E.A., Tyc, V., 1998. Testing the stress-response sequence model in paediatric oncology nursing. Journal of Advanced Nursing 28 (5), 1146-1157; Barnard, D., Street, A., Love, A.W., 2006. Relationships between stressors, work supports and burnout among cancer nurses. Cancer Nursing 29 (4), 338-345]. Terminologies used to capture this stress are burnout [Pines, A.M., and Aronson, E., 1988. Career Burnout: Causes and Cures. Free Press, New York], compassion stress [Figley, C.R., 1995. Compassion Fatigue. Brunner/Mazel, New York], emotional contagion [Miller, K.I., Stiff, J.B., Ellis, B.H., 1988. Communication and empathy as precursors to burnout among human service workers. Communication Monographs 55 (9), 336-341] or simply the cost of caring (Figley, 1995). However, in the mental health field such as psychology and counselling, there is terminology used to captivate this impact, vicarious traumatisation. Vicarious traumatisation is a process through which the therapist's inner experience is negatively transformed through empathic engagement with client's traumatic material [Pearlman, L.A., Saakvitne, K.W., 1995a. Treating therapists with vicarious traumatization and secondary traumatic stress disorders. In: Figley, C.R. (Ed.), Compassion Fatigue: Coping with Secondary Traumatic Stress Disorder in Those Who Treat the Traumatized. Brunner/Mazel, New York, pp. 150-177]. Trauma not only affects individuals who are primarily present, but also those with whom they discuss their experience. If an individual has been traumatised as a result of a cancer diagnosis and shares this impact with oncology nurses, there could be a risk of vicarious traumatisation in this population. However, although Thompson [2003. Vicarious traumatisation: do we adequately support traumatised staff? The Journal of Cognitive Rehabilitation 24-25] suggests that vicarious traumatisation is a broad term used for workers from any profession, it has not yet been empirically determined if oncology nurses experience vicarious traumatisation. This purpose of this paper is to introduce the concept of vicarious traumatisation and argue that it should be explored in oncology nursing. The review will highlight that empirical research in vicarious traumatisation is largely limited to the mental health professions, with a strong recommendation for the need to empirically determine whether this concept exists in oncology nursing.

New FMO Type to Flag ROI in H264/AVC

This paper presents a new type of Flexible Macroblock Ordering (FMO) type for the H.264 Advanced Video Coding (AVC) standard, which can more efficiently flag the position and shape of regions of interest (ROIs) in each frame. In H.264/AVC, 7 types of FMO have been defined, all of which are designed for error resilience. Most previous work related to ROI processing has adopted Type-2 (foreground & background), or Type-6 (explicit), to flag the position and shape of the ROI. However, only rectangular shapes are allowed in Type-2 and for non-rectangular shapes, the non-ROI macroblocks may be wrongly flagged as being within the ROI, which could seriously affect subsequent processing of the ROI. In Type-6, each macroblock in a frame uses fixed-length bits to indicate to its slice group. In general, each ROI is assigned to one slice group identity. Although this FMO type can more accurately flag the position and shape of the ROI, it incurs a significant bitrate overhead. The proposed new FMO type uses the smallest rectangle that covers the ROI to indicate its position and a spiral binary mask is employed within the rectangle to indicate the shape of the ROI. This technique can accurately flag the ROI and provide significantly savings in the bitrate overhead. Compared with Type-6, an 80% to 90% reduction in the bitrate overhead can be obtained while achieving the same accuracy.

Higher effort-reward imbalance and lower job control predict exit from the labour market at the age of 61 years or younger: Evidence from the English Longitudinal Study of Ageing

Background: We examined whether higher effort-reward imbalance (ERI) and lower job control are associated with exit from the labour market. 

Methods: There were 1263 participants aged 50-74 years from the English Longitudinal Study on Ageing with data on working status and work-related psychosocial factors at baseline (wave 2; 2004-2005), and working status at follow-up (wave 5; 2010-2011). Psychosocial factors at work were assessed using a short validated version of ERI and job control. An allostatic load index was formed using 13 biological parameters. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale. Exit from the labour market was defined as not working in the labour market when 61 years old or younger in 2010-2011. 

Results: Higher ERI OR=1.62 (95% CI 1.01 to 2.61, p=0.048) predicted exit from the labour market independent of age, sex, education, occupational class, allostatic load and depression. Job control OR=0.60 (95% CI 0.42 to 0.85, p=0.004) was associated with exit from the labour market independent of age, sex, education, occupation and depression. The association of higher effort OR=1.32 (95% CI 1.01 to 1.73, p=0.045) with exit from the labour market was independent of age, sex and depression but attenuated to non-significance when additionally controlling for socioeconomic measures. Reward was not related to exit from the labour market. 

Conclusions: Stressful work conditions can be a risk for exiting the labour market before the age of 61 years. Neither socioeconomic position nor allostatic load and depressive symptoms seem to explain this association.