Neighbourhood greenspace is associated with a slower decline in physical activity in older adults: A prospective cohort study

Maintaining physical activity in later life is important for maintaining health and function. Activity outdoors, such as walking, jogging and cycling, may provide an accessible, sociable and practical solution, but maintaining outdoor mobility may be a challenge in later life. Providing green environments which are supportive of physical activity may facilitate this, yet research into how greenspace could be best used is inconclusive. This study evaluates the role of greenspace in protecting against decline in physical activity over time in older adults. Data from the European Prospective Investigation of Cancer Norfolk, UK, cohort 1993–2009 (N=15,672) was used. Linear regression modelling was used to examine the association between exposure to greenspace in the home neighbourhood and change in overall, recreational and outdoor physical activity measured in terms of metabolic equivalent cost (MET) in hours/week. Mediation analysis was conducted to assess if dog walking explained the relationship between greenspace and physical activity change. Models were adjusted for known and hypothesised confounders. People living in greener neighbourhoods experienced less of a decline in physical activity than those living in less green areas. Comparing change for those living in the greenest versus least green quartiles, participants showed a difference in overall physical activity of 4.21 MET hours/week (trend P=0.001), adjusted for baseline physical activity, age, sex, BMI, social class and marital status. This difference was 4.03 MET hours/week for recreational physical activity (trend P<0.001) and 1.28 MET hours/week for outdoor physical activity (trend P=0.007). Dog walking partially mediated the association between greenspace and physical activity change, by 22.6% for overall, 28.1% for recreational and 50.0% for outdoor physical activity (all P<0.001). Greenspace in the home neighbourhood may be protective against decline in physical activity among older people as they age. Dog walking is a potential mechanism in this relationship, and warrants further investigation as a way of maintaining physical activity in later life.This work was supported by the Centre for Diet and Activity Research (CEDAR), a UKCRC Public Health Research Centre of Excellence. Funding from Cancer Research UK, the British Heart Foundation, the Economic and Social Research Council, the Medical Research Council, the National Institute for Health Research, and the Wellcome Trust, under the auspices of the UK Clinical Research Collaboration, is gratefully acknowledged. The corresponding author was supported by the Medical Research Council, grant number MR/K025147/1. The study was also supported by the Medical Research Council, grant numbers MC_UU_12015/1 and MC_UU_12015/4

The role of host cell factors in the lytic reactivation of Kaposi’s sarcoma-associated herpesvirus from latency

Kaposi’s Sarcoma-Associated Herpesvirus (KSHV) has two stages to its life cycle; latency and lytic replication. KSHV latent infection is associated with the B-cell tumour, Primary Effusion Lymphoma (PEL). During latency the viral episome is maintained, few viral genes are expressed and no infectious virions are produced. The switch between phases is controlled by the viral transcription factor, RTA encoded by ORF50. Lytic replication, which results in the production of progeny virions, can be triggered by a variety of causes suggesting KSHV has the ability to reactivate in response to a multitude of scenarios. However, many of the stimuli described, to date, have no clear physiological relevance. This thesis investigates how cellular transcription factors can induce the KSHV lytic cycle. Firstly, a model system for monitoring KSHV lytic replication is developed and characterised. This system is then employed to demonstrate how the cellular transcription factor XBP-1s is able to induce KSHV reactivation. XBP-1 is responsible for the terminal differentiation of B-cells into plasma cells (PCs) and is a major regulator of the unfolded protein response (UPR). PEL do not express the transcription factor X-box binding protein-1 (XBP-1). When spliced active XBP-1s is supplied, PEL cells differentiate towards a PC and induce KSHV lytic replication. B-cell terminal differentiation is therefore a physiological trigger of KSHV lytic reactivation. To understand the role of host cell factors in this interaction further, the gene expression changes that occur when XBP-1s is supplied to PEL are also examined. Finally, we investigate the specific roles of XBP-1s and HIF-1α in the KSHV reactivation seen in response to hypoxia. We conclude that both B-cell differentiation and hypoxia are physiologically relevant triggers for KSHV lytic cycle induction, highlighting some of the many complex interactions between the virus and its host

Six Sigma vs. Performance Solutions by Milliken

Continuous improvement plays a huge role in managing processes and developing best practices. It covers a wide range of methods and is practiced by companies all over the world, both in manufacturing and service sectors. The two types or methodologies that will be examined here are Six Sigma and, perhaps the less well known, Performance Solutions by Milliken. Especially in today’s environment of thin profit margins on end products and physical assets, traditional manufacturers have evolved into service organizations and must remain competitive. This paper focuses on these methodologies, and on the dual use of them, by a world-class manufacture

Managerial risk incentives and investment related agency costs

AbstractWe assess the impact of compensation based incentives together with monitoring mechanisms on investment related agency costs. The results indicate that well structured compensation based incentives significantly reduce agency costs. Managerial firm based wealth delta has a significant, negative effect on agency costs for firms in all size categories. The significance of managerial firm based wealth vega in reducing agency costs is concentrated in small firms, suggesting that vega exposure is more effective where risk is higher. The significance of cash compensation in reducing agency costs is concentrated in the large firms. This result implies that higher cash compensation reduces agency costs by allowing risk-averse managers the opportunity to diversify outside the firm

Detection of Novel QTLs for Late Blight Resistance Derived from the Wild Potato Species Solanum microdontum and Solanum pampasense

peer-reviewedWild potato species continue to be a rich source of genes for resistance to late blight in potato breeding. Whilst many dominant resistance genes from such sources have been characterised and used in breeding, quantitative resistance also offers potential for breeding when the loci underlying the resistance can be identified and tagged using molecular markers. In this study, F1 populations were created from crosses between blight susceptible parents and lines exhibiting strong partial resistance to late blight derived from the South American wild species Solanum microdontum and Solanum pampasense. Both populations exhibited continuous variation for resistance to late blight over multiple field-testing seasons. High density genetic maps were created using single nucleotide polymorphism (SNP) markers, enabling mapping of quantitative trait loci (QTLs) for late blight resistance that were consistently expressed over multiple years in both populations. In the population created with the S. microdontum source, QTLs for resistance consistently expressed over three years and explaining a large portion (21–47%) of the phenotypic variation were found on chromosomes 5 and 6, and a further resistance QTL on chromosome 10, apparently related to foliar development, was discovered in 2016 only. In the population created with the S. pampasense source, QTLs for resistance were found in over two years on chromosomes 11 and 12. For all loci detected consistently across years, the QTLs span known R gene clusters and so they likely represent novel late blight resistance genes. Simple genetic models following the effect of the presence or absence of SNPs associated with consistently effective loci in both populations demonstrated that marker assisted selection (MAS) strategies to introgress and pyramid these loci have potential in resistance breeding strategies.Department of Agriculture, Food and the Marine, Irelan

Residential neighbourhood greenspace is associated with reduced risk of incident diabetes in older people: a prospective cohort study

Abstract Background Three cross sectional studies suggest that neighbourhood greenspace may protect against incident diabetes. This study uses data from a longitudinal study with a large sample size to investigate the association between greenspace and the occurrence of incident diabetes over time. Methods Data was from the European Prospective Investigation of Cancer Norfolk, UK, cohort, recruitment 1993–2007 (N = 23,865). Neighbourhoods were defined as 800 m circular buffers around participants’ home locations, according to their home postcode (zip code). Greenspace exposure was defined as the percentage of the home neighbourhood that was woodland, grassland, arable land, mountain, heath and bog, according to the UK Land Cover Map. Cox proportional hazards regression examined the association between neighbourhood greenspace exposure and incident diabetes. The population attributable fraction assessed the proportion of diabetes cases attributable to exposure to least green neighbourhoods. Mediation analysis assessed if physical activity explained associations between greenspace and diabetes. Interaction analysis was used to test for the modifying effect of rurality and socio-economic status on the relationship between greenspace and diabetes. Models were adjusted for known and hypothesised confounders. Results The mean age of participants was 59 years at baseline and 55.1% were female. The mean follow-up time was 11.3 years. Individuals living in the greenest neighbourhood quartile had a 19% lower relative hazard of developing diabetes (HR 0.81; 95% CI 0.67, 0.99; p = 0.035; linear trend p = 0.010). The hazard ratio remained similar (HR 0.81; 95% CI 0.65, 0.99; p = 0.042) after adjusting for age, sex, BMI, whether a parent had been diagnosed with diabetes and socio-economic status at the individual and neighbourhood level. A HR of 0.97 was attributed to the pathway through physical activity in a fully adjusted model, although this was non-significant (95% CI 0.88, 1.08; p = 0.603). The incidence of diabetes in the least green neighbourhoods (with 20% greenspace on average) would fall by 10.7% (95% CI −2.1%, 25.2%; p = 0.106) if they were as green as the average neighbourhood observed across the whole cohort (59% greenspace on average). There were no significant interactions between rurality or socio-economic status and level of greenspace. Conclusions Greener home neighbourhoods may protect against risk of diabetes in older adults, although this study does not support a mediation role for physical activity. Causal mechanisms underlying the associations require further investigation

Olfactory receptor accessory proteins play crucial roles in receptor function and gene choice

Each of the olfactory sensory neurons (OSNs) chooses to express a single G protein-coupled olfactory receptor (OR) from a pool of hundreds. Here, we show the receptor transporting protein (RTP) family members play a dual role in both normal OR trafficking and determining OR gene choice probabilities. Rtp1 and Rtp2 double knockout mice (RTP1,2DKO) show OR trafficking defects and decreased OSN activation. Surprisingly, we discovered a small subset of the ORs are expressed in larger numbers of OSNs despite the presence of fewer total OSNs in RTP1,2DKO. Unlike typical ORs, some overrepresented ORs show robust cell surface expression in heterologous cells without the co-expression of RTPs. We present a model in which developing OSNs exhibit unstable OR expression until they choose to express an OR that exits the ER or undergo cell death. Our study sheds light on the new link between OR protein trafficking and OR transcriptional regulation.R01 DC012095 - NIDCD NIH HHS; R01 DC014423 - NIDCD NIH HH

Racial/Ethnic Differences in Perceived Smoking Prevalence: Evidence from a National Survey of Teens

Prior studies show that perceived smoking prevalence is a significant predictor of smoking initiation. In this study, we examine racial/ethnic differences in perceived smoking prevalence and racial/ethnic differences in exposure to contextual factors associated with perceived smoking prevalence. We used cross-sectional time series data from the Legacy Media Tracking Surveys (LMTS), a national sample of 35,000 12- to 17-year-olds in the United States. Perceived smoking prevalence was the primary outcome variable, measured using an LMTS question: “Out of every 10 people your age, how many do you think smoke?” Multivariable models were estimated to assess the association between perceived smoking prevalence; race/ethnicity; and exposure to social contextual factors. Findings indicate that African American, Hispanic, and American Indian youth exhibit the highest rates of perceived smoking prevalence, while white and Asian youth exhibit the lowest. Minority youth are also disproportionately exposed to social contextual factors that are correlated with high perceived smoking prevalence. These findings suggest that disproportionate exposure to social contextual factors may partially explain why minority youth exhibit such high levels of perceived smoking prevalence