ORCID Profile
0000-0002-0850-3177
Current Organisation
University of Veterinary Medicine Vienna
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Publisher: Elsevier BV
Date: 12-2011
Publisher: Elsevier BV
Date: 07-2011
Publisher: JCFCorp SG PTE LTD
Date: 05-2016
DOI: 10.5993/AJHB.40.3.8
Publisher: BMJ
Date: 19-07-2017
DOI: 10.1136/BJSPORTS-2016-097210
Abstract: Sedentary time (ST) is an important risk factor for a variety of health outcomes in older adults. Consensus is needed on future research directions so that collaborative and timely efforts can be made globally to address this modifiable risk factor. In this review, we examined current literature to identify gaps and inform future research priorities on ST and healthy ageing. We reviewed three primary topics:(1) the validity/reliability of self-report measurement tools, (2) the consequences of prolonged ST on geriatric-relevant health outcomes (physical function, cognitive function, mental health, incontinence and quality of life) and(3) the effectiveness of interventions to reduce ST in older adults. A trained librarian created a search strategy that was peer reviewed for completeness. Self-report assessment of the context and type of ST is important but the tools tend to underestimate total ST. There appears to be an association between ST and geriatric-relevant health outcomes, although there is insufficient longitudinal evidence to determine a dose-response relationship or a threshold for clinically relevant risk. The type of ST may also affect health some cognitively engaging sedentary behaviours appear to benefit health, while time spent in more passive activities may be detrimental. Short-term feasibility studies of in idual-level ST interventions have been conducted however, few studies have appropriately assessed the impact of these interventions on geriatric-relevant health outcomes, nor have they addressed organisation or environment level changes. Research is specifically needed to inform evidence-based interventions that help maintain functional autonomy among older adults.This consensus statement has been endorsed by the following societies: Academy of Geriatric Physical Therapy, Exercise & Sports Science Australia, Canadian Centre for Activity and Aging, Society of Behavioral Medicine, and the National Centre for Sport and Exercise Medicine.
Publisher: Frontiers Media SA
Date: 22-02-2016
Publisher: BMJ
Date: 25-11-2020
DOI: 10.1136/BJSPORTS-2020-103270
Abstract: To examine the joint associations of accelerometer-measured physical activity and sedentary time with all-cause mortality. We conducted a harmonised meta-analysis including nine prospective cohort studies from four countries. 44 370 men and women were followed for 4.0 to 14.5 years during which 3451 participants died (7.8% mortality rate). Associations between different combinations of moderate-to-vigorous intensity physical activity (MVPA) and sedentary time were analysed at study level using Cox proportional hazards regression analysis and summarised using random effects meta-analysis. Across cohorts, the average time spent sedentary ranged from 8.5 hours/day to 10.5 hours/day and 8 min/day to 35 min/day for MVPA. Compared with the referent group (highest physical activity/lowest sedentary time), the risk of death increased with lower levels of MVPA and greater amounts of sedentary time. Among those in the highest third of MVPA, the risk of death was not statistically different from the referent for those in the middle (16% 95% CI 0.87% to 1.54%) and highest (40% 95% CI 0.87% to 2.26%) thirds of sedentary time. Those in the lowest third of MVPA had a greater risk of death in all combinations with sedentary time 65% (95% CI 1.25% to 2.19%), 65% (95% CI 1.24% to 2.21%) and 263% (95% CI 1.93% to 3.57%), respectively. Higher sedentary time is associated with higher mortality in less active in iduals when measured by accelerometry. About 30–40 min of MVPA per day attenuate the association between sedentary time and risk of death, which is lower than previous estimates from self-reported data.
Publisher: BMJ
Date: 19-07-2017
Publisher: Springer Science and Business Media LLC
Date: 12-2015
Publisher: Elsevier BV
Date: 04-2016
Publisher: Public Library of Science (PLoS)
Date: 09-06-2016
Publisher: Springer Science and Business Media LLC
Date: 13-07-2016
DOI: 10.1038/NCOMMS12258
Abstract: The JAK/STAT pathway is an attractive target for breast cancer therapy due to its frequent activation, and clinical trials evaluating JAK inhibitors (JAKi) in advanced breast cancer are ongoing. Using patient biopsies and preclinical models of breast cancer, we demonstrate that the JAK/STAT pathway is active in metastasis. Unexpectedly, blocking the pathway with JAKi enhances the metastatic burden in experimental and orthotopic models of breast cancer metastasis. We demonstrate that this prometastatic effect is due to the immunosuppressive activity of JAKi with ensuing impairment of NK-cell-mediated anti-tumour immunity. Furthermore, we show that immunostimulation with IL-15 overcomes the enhancing effect of JAKi on metastasis formation. Our findings highlight the importance of evaluating the effect of targeted therapy on the tumour environment. The impact of JAKi on NK cells and the potential value of immunostimulators to overcome the weakened tumour immunosurveillance, are worthwhile considering in the clinical setting of breast cancer.
Publisher: Oxford University Press (OUP)
Date: 30-01-2021
DOI: 10.1093/HMG/DDAB023
Abstract: Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) in iduals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (Pcombined = 1.8 × 10−11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (Pcombined = 1.5 × 10−10) in the combined meta-analyses of all s les. We also replicated the IL6R rs4537545 locus on Chr1q21 (Pcombined = 1.2 × 10−122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.
Publisher: BMJ
Date: 07-12-2021
DOI: 10.1136/BJSPORTS-2021-104827
Abstract: The joint associations of total and intensity-specific physical activity with obesity in relation to all-cause mortality risk are unclear. We included 34 492 adults (72% women, median age 62.1 years, 2034 deaths during follow-up) in a harmonised meta-analysis of eight population-based prospective cohort studies with mean follow-up ranging from 6.0 to 14.5 years. Standard body mass index categories were cross-classified with s le tertiles of device-measured total, light-to-vigorous and moderate-to-vigorous physical activity and sedentary time. In five cohorts with waist circumference available, high and low waist circumference was combined with tertiles of moderate-to-vigorous physical activity. There was an inverse dose–response relationship between higher levels of total and intensity-specific physical activity and mortality risk in those who were normal weight and overweight. In in iduals with obesity, the inverse dose–response relationship was only observed for total physical activity. Similarly, lower levels of sedentary time were associated with lower mortality risk in normal weight and overweight in iduals but there was no association between sedentary time and risk of mortality in those who were obese. Compared with the obese-low total physical activity reference, the HRs were 0.59 (95% CI 0.44 to 0.79) for normal weight-high total activity and 0.67 (95% CI 0.48 to 0.94) for obese-high total activity. In contrast, normal weight-low total physical activity was associated with a higher risk of mortality compared with the obese-low total physical activity reference (1.28 95% CI 0.99 to 1.67). Higher levels of physical activity were associated with lower risk of mortality irrespective of weight status. Compared with obesity-low physical activity, there was no survival benefit of being normal weight if physical activity levels were low.
Publisher: Springer Science and Business Media LLC
Date: 24-06-2016
DOI: 10.1038/SREP28514
Abstract: Impaired kidney function, as measured by reduced estimated glomerular filtration rate (eGFR), has been associated with increased risk of coronary heart disease (CHD) in observational studies, but it is unclear whether this association is causal or the result of confounding or reverse causation. In this study we applied Mendelian randomisation analysis using 17 genetic variants previously associated with eGFR to investigate the causal role of kidney function on CHD. We used 13,145 participants from the UCL-LSHTM-Edinburgh-Bristol (UCLEB) Consortium and 194,427 participants from the Coronary ARtery DIsease Genome-wide Replication and Meta-analysis plus Coronary Artery Disease (CARDIoGRAMplusC4D) consortium. We observed significant association of an unweighted gene score with CHD risk (odds ratio = 0.983 per additional eGFR-increasing allele, 95% CI = 0.970–0.996, p = 0.008). However, using weights calculated from UCLEB, the gene score was not associated with disease risk (p = 0.11). These conflicting results could be explained by a single SNP, rs653178, which was not associated with eGFR in the UCLEB s le, but has known pleiotropic effects that prevent us from drawing a causal conclusion. The observational association between low eGFR and increased CHD risk was not explained by potential confounders and there was no evidence of reverse causation, therefore leaving the remaining unexplained association as an open question.
Location: United States of America
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Barbara Jefferis.