Priorities, policies and (time)scales : the delivery of emissions reductions in the UK transport sector

Peer reviewedPreprin

Simian Immunodeficiency Virus Infection of Chimpanzees (Pan troglodytes) Shares Features of Both Pathogenic and Non-pathogenic Lentiviral Infections.

The virus-host relationship in simian immunodeficiency virus (SIV) infected chimpanzees is thought to be different from that found in other SIV infected African primates. However, studies of captive SIVcpz infected chimpanzees are limited. Previously, the natural SIVcpz infection of one chimpanzee, and the experimental infection of six chimpanzees was reported, with limited follow-up. Here, we present a long-term study of these seven animals, with a retrospective re-examination of the early stages of infection. The only clinical signs consistent with AIDS or AIDS associated disease was thrombocytopenia in two cases, associated with the development of anti-platelet antibodies. However, compared to uninfected and HIV-1 infected animals, SIVcpz infected animals had significantly lower levels of peripheral blood CD4+ T-cells. Despite this, levels of T-cell activation in chronic infection were not significantly elevated. In addition, while plasma levels of β2 microglobulin, neopterin and soluble TNF-related apoptosis inducing ligand (sTRAIL) were elevated in acute infection, these markers returned to near-normal levels in chronic infection, reminiscent of immune activation patterns in 'natural host' species. Furthermore, plasma soluble CD14 was not elevated in chronic infection. However, examination of the secondary lymphoid environment revealed persistent changes to the lymphoid structure, including follicular hyperplasia in SIVcpz infected animals. In addition, both SIV and HIV-1 infected chimpanzees showed increased levels of deposition of collagen and increased levels of Mx1 expression in the T-cell zones of the lymph node. The outcome of SIVcpz infection of captive chimpanzees therefore shares features of both non-pathogenic and pathogenic lentivirus infections.This work was supported by the Biotechnology and Biological Sciences Research Council and by the Wellcome Trust.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.ppat.100514

Impact of quality-led design on real estate value: a spatiotemporal analysis of city centre apartments

This paper estimates the impact of quality design attributes on real estate value through empirical investigation of the owner-occupied multifamily residential sector. The methodological design is based on spatiotemporal modelling using a unique data-set of 424 Belfast City Centre apartments sold during the period 2000–2008. The key findings indicate that urban scale aspects of quality such as connectivity and vitality associated with building density add to real estate value. At the building level, quality features highly valued by home buyers are namely appropriateness of material quality, fenestration and massing to the surroundings. These key criteria are considered to have a significant visual perception compared to more complex concepts such as identity, material choice and overall condition. The contribution to knowledge involves extending the hedonic model to incorporate a wider selection of design quality variables; and improving estimation through the use of spatiotemporal modelling.</p

The occurrence of DSP toxicity in Ireland

The geographical and temporal variations in the occurrence of DSP in Ireland are presented and the implications of the resulting closures on aquaculture operations and fisheries are discussed. Prior to 1992 DSP toxicity had been confined to the southwest and south coasts but in 1992 a protracted occurrence of DSP was recorded in Killary Harbour on the west coast

A primate model of severe malarial anaemia: a comparative pathogenesis study.

Severe malarial anaemia (SMA) is the most common life-threatening complication of Plasmodium falciparum infection in African children. SMA is characterised by haemolysis and inadequate erythropoiesis, and is associated with dysregulated inflammatory responses and reduced complement regulatory protein levels (including CD35). However, a deeper mechanistic understanding of the pathogenesis requires improved animal models. In this comparative study of two closely related macaque species, we interrogated potential causal factors for their differential and temporal relationships to onset of SMA. We found that rhesus macaques inoculated with blood-stage Plasmodium coatneyi developed SMA within 2 weeks, with no other severe outcomes, whereas infected cynomolgus macaques experienced only mild/ moderate anaemia. The abrupt drop in haematocrit in rhesus was accompanied by consumption of haptoglobin (haemolysis) and poor reticulocyte production. Rhesus developed a greater inflammatory response than cynomolgus macaques, and had lower baseline levels of CD35 on red blood cells (RBCs) leading to a significant reduction in the proportion of CD35+ RBCs during infection. Overall, severe anaemia in rhesus macaques infected with P. coatneyi has similar features to SMA in children. Our comparisons are consistent with an association of low baseline CD35 levels on RBCs and of early inflammatory responses with the pathogenesis of SMA

Kyphosis and paraspinal muscle composition in older men: a cross-sectional study for the osteoporotic fractures in men (MrOS) research group

BACKGROUND: The prevalence of hyperkyphosis is increased in older men; however, risk factors other than age and vertebral fractures are not well established. We previously reported that poor paraspinal muscle composition contributes to more severe kyphosis in a cohort of both older men and women. METHODS: To specifically evaluate this association in older men, we conducted a cross-sectional study to evaluate the association of paraspinal muscle composition and degree of thoracic kyphosis in an analytic cohort of 475 randomly selected participants from the Osteoporotic Fractures in Men (MrOS) study with baseline abdominal quantitative computed tomography (QCT) scans and plain thoracic radiographs. Baseline abdominal QCT scans were used to obtain abdominal body composition measurements of paraspinal muscle and adipose tissue distribution. Supine lateral spine radiographs were used to measure Cobb angle of kyphosis. We examined the linear association of muscle volume, fat volume and kyphosis using loess plots. Multivariate linear models were used to investigate the association between muscle and kyphosis using total muscle volume, as well as individual components of the total muscle volume, including adipose and muscle compartments alone, controlling for age, height, vertebral fractures, and total hip bone mineral density (BMD). We examined these associations among those with no prevalent vertebral fracture and those with BMI < 30 kg/m(2). RESULTS: Among men in the analytic cohort, means (SD) were 74 (SD = 5.9) years for age, and 37.5 (SD = 11.9) degrees for Cobb angle of kyphosis. Men in the lowest tertile of total paraspinal muscle volume had greater mean Cobb angle than men in the highest tertile, although test of linear trend across tertiles did not reach statistical significance. Neither lower paraspinal skeletal muscle volume (p-trend = 0.08), or IMAT (p-trend = 0.96) was associated with greater kyphosis. Results were similar among those with no prevalent vertebral fractures. However, among men with BMI < 30 kg/m(2), those in the lowest tertile of paraspinal muscle volume had greater adjusted mean kyphosis (40.0, 95% CI: 37.8 – 42.1) compared to the highest tertile (36.3, 95% CI: 34.2 – 38.4). CONCLUSIONS: These results suggest that differences in body composition may potentially influence kyphosis

Power training and postmenopausal hormone therapy affect transcriptional control of specific co-regulated gene clusters in skeletal muscle

At the moment, there is no clear molecular explanation for the steeper decline in muscle performance after menopause or the mechanisms of counteractive treatments. The goal of this genome-wide study was to identify the genes and gene clusters through which power training (PT) comprising jumping activities or estrogen containing hormone replacement therapy (HRT) may affect skeletal muscle properties after menopause. We used musculus vastus lateralis samples from early stage postmenopausal (50–57 years old) women participating in a yearlong randomized double-blind placebo-controlled trial with PT and HRT interventions. Using microarray platform with over 24,000 probes, we identified 665 differentially expressed genes. The hierarchical clustering method was used to assort the genes. Additionally, enrichment analysis of gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was carried out to clarify whether assorted gene clusters are enriched with particular functional categories. The analysis revealed transcriptional regulation of 49 GO/KEGG categories. PT upregulated transcription in “response to contraction”—category revealing novel candidate genes for contraction-related regulation of muscle function while HRT upregulated gene expression related to functionality of mitochondria. Moreover, several functional categories tightly related to muscle energy metabolism, development, and function were affected regardless of the treatment. Our results emphasize that during the early stages of the postmenopause, muscle properties are under transcriptional modulation, which both PT and HRT partially counteract leading to preservation of muscle power and potentially reducing the risk for aging-related muscle weakness. More specifically, PT and HRT may function through improving energy metabolism, response to contraction as well as by preserving functionality of the mitochondria

Strategies and challenges associated with recruiting retirement village communities and residents into a group exercise intervention

Background: Randomized controlled trials (RCTs) provide the highest level of scientific evidence, but successful participant recruitment is critical to ensure the external and internal validity of results. This study describes the strategies associated with recruiting older adults at increased falls risk residing in retirement villages into an 18-month cluster RCT designed to evaluate the effects of a dual-task exercise program on falls and physical and cognitive function. Methods: Recruitment of adults aged ≥65 at increased falls risk residing within retirement villages (size 60–350 residents) was initially designed to occur over 12 months using two distinct cohorts (C). Recruitment occurred via a three-stage approach that included liaising with: 1) village operators, 2) independent village managers, and 3) residents. To recruit residents, a variety of different approaches were used, including distribution of information pack, on-site presentations, free muscle and functional testing, and posters displayed in common areas. Results: Due to challenges with recruitment, three cohorts were established between February 2014 and April 2015 (14 months). Sixty retirement villages were initially invited, of which 32 declined or did not respond, leaving 28 villages that expressed interest. A total of 3947 individual letters of invitation were subsequently distributed to residents of these villages, from which 517 (13.1%) expressions of interest (EOI) were received. Across three cohorts with different recruitment strategies adopted there were only modest differences in the number of EOI received (10.5 to 15.3%), which suggests that no particular recruitment approach was most effective. Following the initial screening of these residents, 398 (77.0%) participants were deemed eligible to participate, but a final sample of 300 (58.0% of the 517 EOI) consented and was randomized; 7.6% of the 3947 residents invited. Principal reasons for not participating, despite being eligible, were poor health, lack of time and no GP approval. Conclusion: This study highlights that there are significant challenges associated with recruiting sufficient numbers of older adults from independent living retirement villages into an exercise intervention designed to improve health and well-being. Trial registration: Australian New Zealand Clinical Trials Registry: ACTRN12613001 161718. Date registered 23rd October 2013

Exercise and inflammation in female survivors of breast cancer: systematic review and meta-analysis with secondary mediation analysis on body composition

oai:repository.mdx.ac.uk:2qyx02Purpose Inflammation plays a key role in breast cancer recurrence and mortality by promoting tumor progression. Exercise significantly reduces pro-inflammatory markers such as IL-6, TNF-α, and CRP, potentially reducing mortality risk. However, it is yet to be determined whether exercise-induced changes in body composition can modulate inflammatory biomarker responses in the breast cancer setting. Methods We conducted a secondary mediation analysis based on the findings from our previously published systematic review with meta-analysis. Randomized controlled trials examining the effects of exercise on IL-1β, IL-6, IL-8, IL-10, TNF-α, and CRP and body composition and anthropometry measures such as lean mass (LM), fat mass (FM), body weight and body mass index (BMI) were included. Random-effect meta-regression models were undertaken. Results Sixteen studies were included in the secondary analysis (n = 752). Increases in LM were significantly associated with reductions in IL-6 (p = 0.03) and there was a trend toward decreases in IL-8 (p = 0.05). In addition, there were non-significant trends suggesting that reductions in FM may be associated with decreases in IL-6 (p = 0.08) and TNF-α (p = 0.06), and that decreases in BMI may be linked to changes in IL-8 (p = 0.06). Conclusions Changes in body composition following exercise were not consistently associated with inflammatory biomarker responses in breast cancer survivors with only LM significantly associated with IL-6 while a trend in LM and FM existed for some other inflammatory markers. Although these findings do not provide conclusive evidence, they highlight a possible role of exercise-induced body composition changes in mediating inflammation. Further research is needed to clarify whether targeted exercise interventions that improve body composition can contribute to reducing inflammation and, ultimately, impact breast cancer progression, recurrence, and mortality

Moderators of exercise effects on self-reported cognitive functioning in cancer survivors:an individual participant data meta-analysis

PURPOSE: This individual participant data meta-analysis (IPD-MA) assesses exercise effects on self-reported cognitive functioning (CF) and investigates whether effects differ by patient-, intervention-, and exercise-related characteristics.METHODS: IPD from 16 exercise RCTs, including 1987 patients across multiple types of non-metastatic cancer, was pooled. A one-stage IPD-MA using linear mixed-effect models was performed to assess exercise effects on self-reported CF (z-score) and to identify whether the effect was moderated by sociodemographic, clinical, intervention- and exercise-related characteristics, or fatigue, depression, anxiety, and self-reported CF levels at start of the intervention (i.e., baseline). Models were adjusted for baseline CF and included a random intercept at study level to account for clustering of patients within studies. A sensitivity analysis was performed in patients who reported cognitive problems at baseline.RESULTS: Minimal significant beneficial exercise effects on self-reported CF (β=-0.09 [-0.16; -0.02]) were observed, with slightly larger effects when the intervention was delivered post-treatment (n=745, β=-0.13 [-0.24; -0.02]), and no significant effect during cancer treatment (n=1,162, β=-0.08 [-0.18; 0.02]). Larger effects were observed in interventions of 12 weeks or shorter (β=-0.14 [-0.25; -0.04]) or 24 weeks or longer (β=-0.18 [-0.32; -0.02]), whereas no effects were observed in interventions of 12-24 weeks (β=0.01 [-0.13; 0.15]). Exercise interventions were most beneficial when provided to patients without anxiety symptoms (β=-0.10 [-0.19; -0.02]) or after completion of treatment in patients with cognitive problems (β=-0.19 [-0.31; -0.06]). No other significant moderators were identified.CONCLUSIONS: This cross-cancer IPD meta-analysis observed small beneficial exercise effects on self-reported CF when the intervention was delivered post-treatment, especially in patients who reported cognitive problems at baseline.IMPLICATIONS FOR CANCER SURVIVORS: This study provides some evidence to support the prescription of exercise to improve cognitive functioning. Sufficiently powered trials are warranted to make more definitive recommendations and include these in the exercise guidelines for cancer survivors.</p