188 research outputs found
Near-threshold electron injection in the laser-plasma wakefield accelerator leading to femtosecond bunches
We gratefully acknowledge the support of the UK EPSRC (grant no. EP/J018171/1), the EU FP7 programmes: the Extreme Light Infrastructure (ELI) project, the Laserlab-Europe (no. 284464), and the EUCARD-2 project (no. 312453).The laser-plasma wakefield accelerator is a compact source of high brightness, ultra-short duration electron bunches. Self-injection occurs when electrons from the background plasma gain sufficient momentum at the back of the bubble-shaped accelerating structure to experience sustained acceleration. The shortest duration and highest brightness electron bunches result from self-injection close to the threshold for injection. Here we show that in this case injection is due to the localized charge density build-up in the sheath crossing region at the rear of the bubble, which has the effect of increasing the accelerating potential to above a critical value. Bunch duration is determined by the dwell time above this critical value, which explains why single or multiple ultra-short electron bunches with little dark current are formed in the first bubble. We confirm experimentally, using coherent optical transition radiation measurements, that single or multiple bunches with femtosecond duration and peak currents of several kiloAmpere, and femtosecond intervals between bunches, emerge from the accelerator.Publisher PDFPeer reviewe
Association between active commuting and incident cardiovascular disease, cancer, and mortality: prospective cohort study
Objective:Â To investigate the association between active commuting and incident cardiovascular disease (CVD), cancer, and all cause mortality.
Design:Â Prospective population based study.
Setting:Â UK Biobank.
Participants: 263 450 participants (106 674 (52%) women; mean age 52.6), recruited from 22 sites across the UK. The exposure variable was the mode of transport used (walking, cycling, mixed mode v non-active (car or public transport)) to commute to and from work on a typical day.
Main outcome measures:Â Incident (fatal and non-fatal) CVD and cancer, and deaths from CVD, cancer, or any causes.
Results:Â 2430 participants died (496 were related to CVD and 1126 to cancer) over a median of 5.0 years (interquartile range 4.3-5.5) follow-up. There were 3748 cancer and 1110 CVD events. In maximally adjusted models, commuting by cycle and by mixed mode including cycling were associated with lower risk of all cause mortality (cycling hazard ratio 0.59, 95% confidence interval 0.42 to 0.83, P=0.002; mixed mode cycling 0.76, 0.58 to 1.00, P<0.05), cancer incidence (cycling 0.55, 0.44 to 0.69, P<0.001; mixed mode cycling 0.64, 0.45 to 0.91, P=0.01), and cancer mortality (cycling 0.60, 0.40 to 0.90, P=0.01; mixed mode cycling 0.68, 0.57 to 0.81, P<0.001). Commuting by cycling and walking were associated with a lower risk of CVD incidence (cycling 0.54, 0.33 to 0.88, P=0.01; walking 0.73, 0.54 to 0.99, P=0.04) and CVD mortality (cycling 0.48, 0.25 to 0.92, P=0.03; walking 0.64, 0.45 to 0.91, P=0.01). No statistically significant associations were observed for walking commuting and all cause mortality or cancer outcomes. Mixed mode commuting including walking was not noticeably associated with any of the measured outcomes.
Conclusions:Â Cycle commuting was associated with a lower risk of CVD, cancer, and all cause mortality. Walking commuting was associated with a lower risk of CVD independent of major measured confounding factors. Initiatives to encourage and support active commuting could reduce risk of death and the burden of important chronic conditions
The impact of confounding on the associations of different adiposity measures with the incidence of cardiovascular disease: a cohort study of 296 535 adults of white European descent
Aims:
The data regarding the associations of body mass index (BMI) with cardiovascular (CVD) risk, especially for those at the low categories of BMI, are conflicting. The aim of our study was to examine the associations of body composition (assessed by five different measures) with incident CVD outcomes in healthy individuals.
Methods and results:
A total of 296 535 participants (57.8% women) of white European descent without CVD at baseline from the UK biobank were included. Exposures were five different measures of adiposity. Fatal and non-fatal CVD events were the primary outcome. Low BMI (≤18.5 kg m−2) was associated with higher incidence of CVD and the lowest CVD risk was exhibited at BMI of 22–23 kg m−2 beyond, which the risk of CVD increased. This J-shaped association attenuated substantially in subgroup analyses, when we excluded participants with comorbidities. In contrast, the associations for the remaining adiposity measures were more linear; 1 SD increase in waist circumference was associated with a hazard ratio of 1.16 [95% confidence interval (CI) 1.13–1.19] for women and 1.10 (95% CI 1.08–1.13) for men with similar magnitude of associations for 1 SD increase in waist-to-hip ratio, waist-to-height ratio, and percentage body fat mass.
Conclusion:
Increasing adiposity has a detrimental association with CVD health in middle-aged men and women. The association of BMI with CVD appears more susceptible to confounding due to pre-existing comorbidities when compared with other adiposity measures. Any public misconception of a potential ‘protective’ effect of fat on CVD risk should be challenged
Dietary fat and total energy intake modifies the association of genetic profile risk score on obesity: evidence from 48 170 UK Biobank participants
Background: Obesity is a multifactorial condition influenced by both genetics and lifestyle. The aim of this study was to investigate whether the association between a validated genetic profile risk score for obesity (GPRS-obesity) and body mass index (BMI) or waist circumference (WC) was modified by macronutrient intake in a large general population study.
Methods: This study included cross-sectional data from 48 170 white European adults, aged 37–73 years, participating on the UK Biobank. Interactions between GPRS-obesity, and macronutrient intake (including total energy, protein, fat, carbohydrate and dietary fibre intake) and its effects on BMI and WC were investigated.
Results: The 93-SNPs genetic profile risk score was associated with a higher BMI (β:0.57 kg.m−2 per standard deviation (s.d.) increase in GPRS, [95%CI:0.53–0.60]; P=1.9 × 10−183) independent of major confounding factors. There was a significant interaction between GPRS and total fat intake (P[interaction]=0.007). Among high fat intake individuals, BMI was higher by 0.60 [0.52, 0.67] kg.m−2 per s.d. increase in GPRS-obesity; the change in BMI with GPRS was lower among low fat intake individuals (β:0.50 [0.44, 0.57] kg.m-2). Significant interactions with similar patterns were observed for saturated fat intake (High β:0.66 [0.59, 0.73] versus Low β:0.49 [0.42, 0.55] kg.m-2, P-interaction=2 × 10-4), and total energy intake (High β:0.58 [0.51, 0.64] versus Low β:0.49 [0.42, 0.56] kg.m−2, P-interaction=0.019), but not for protein intake, carbohydrate intake and fiber intake (P-interaction >0.05). The findings were broadly similar using WC as the outcome.
Conclusions: These data suggest that the benefits of reducing the intake of fats and total energy intake, may be more important in individuals with high genetic risk for obesity
Associations between diabetes and both cardiovascular disease and all-cause mortality are modified by grip strength: evidence from UK Biobank, a prospective population-based cohort study
OBJECTIVE Grip strength and diabetes are predictors of mortality and cardiovascular disease (CVD), but whether these risk factors interact to predispose to adverse health outcomes is unknown. This study determined the interactions between diabetes and grip strength and their association with health outcomes.
RESEARCH DESIGN AND METHODS We undertook a prospective, general population cohort study by using UK Biobank. Cox proportional hazards models were used to explore the associations between both grip strength and diabetes and the outcomes of all-cause mortality and CVD incidence/mortality as well as to test for interactions between diabetes and grip strength.
RESULTS 347,130 UK Biobank participants with full data available (mean age 55.9 years, BMI 27.2 kg/m2, 54.2% women) were included in the analysis, of which 13,373 (4.0%) had diabetes. Over a median follow-up of 4.9 years (range 3.3–7.8 years), 6,209 died (594 as a result of CVD), and 4,301 developed CVD. Participants with diabetes were at higher risk of all-cause and CVD mortality and CVD incidence. Significant interactions (P < 0.05) existed whereby the risk of CVD mortality was higher in participants with diabetes with low (hazard ratio [HR] 4.05 [95% CI 2.72, 5.80]) versus high (HR 1.46 [0.87, 2.46]) grip strength. Similar results were observed for all-cause mortality and CVD incidence.
CONCLUSIONS Risk of adverse health outcomes among people with diabetes is lower in those with high grip strength. Low grip strength may be useful to identify a higher-risk subgroup of patients with diabetes. Intervention studies are required to determine whether resistance exercise can reduce risk
Association of injury related hospital admissions with commuting by bicycle in the UK: prospective population based study
Objective: To determine whether bicycle commuting is associated with risk of injury.
Design: Prospective population based study.
Setting: UK Biobank.
Participants: 230 390 commuters (52.1% women; mean age 52.4 years) recruited from 22 sites across the UK compared by mode of transport used (walking, cycling, mixed mode versus non-active (car or public transport)) to commute to and from work on a typical day.
Main outcome measure: First incident admission to hospital for injury.
Results: 5704 (2.5%) participants reported cycling as their main form of commuter transport. Median follow-up was 8.9 years (interquartile range 8.2-9.5 years), and overall 10 241 (4.4%) participants experienced an injury. Injuries occurred in 397 (7.0%) of the commuters who cycled and 7698 (4.3%) of the commuters who used a non-active mode of transport. After adjustment for major confounding sociodemographic, health, and lifestyle factors, cycling to work was associated with a higher risk of injury compared with commuting by a non-active mode (hazard ratio 1.45, 95% confidence interval 1.30 to 1.61). Similar trends were observed for commuters who used mixed mode cycling. Walking to work was not associated with a higher risk of injury. Longer cycling distances during commuting were associated with a higher risk of injury, but commute distance was not associated with injury in non-active commuters. Cycle commuting was also associated with a higher number of injuries when the external cause was a transport related incident (incident rate ratio 3.42, 95% confidence interval 3.00 to 3.90). Commuters who cycled to work had a lower risk of cardiovascular disease, cancer, and death than those who did not. If the associations are causal, an estimated 1000 participants changing their mode of commuting to include cycling for 10 years would result in 26 additional admissions to hospital for a first injury (of which three would require a hospital stay of a week or longer), 15 fewer first cancer diagnoses, four fewer cardiovascular disease events, and three fewer deaths.
Conclusion: Compared with non-active commuting to work, commuting by cycling was associated with a higher risk of hospital admission for a first injury and higher risk of transport related incidents specifically. These risks should be viewed in context of the health benefits of active commuting and underscore the need for a safer infrastructure for cycling in the UK
Associations of grip strength with cardiovascular, respiratory, and cancer outcomes and all cause mortality: prospective cohort study of half a million UK Biobank participants
Objective: To investigate the association of grip strength with disease specific incidence and mortality and whether grip strength enhances the prediction ability of an established office based risk score.
Design: Prospective population based study.
Setting: UK Biobank.
Participants: 502 293 participants (54% women) aged 40-69 years.
Main outcome measures: All cause mortality as well as incidence of and mortality from cardiovascular disease, respiratory disease, chronic obstructive pulmonary disease, and cancer (all cancer, colorectal, lung, breast, and prostate).
Results: Of the participants included in analyses, 13 322 (2.7%) died over a mean of 7.1 (range 5.3-9.9) years’ follow-up. In women and men, respectively, hazard ratios per 5 kg lower grip strength were higher (all at P<0.05) for all cause mortality (1.20, 95% confidence interval 1.17 to 1.23, and 1.16, 1.15 to 1.17) and cause specific mortality from cardiovascular disease (1.19, 1.13 to 1.25, and 1.22, 1.18 to 1.26), all respiratory disease (1.31, 1.22 to 1.40, and 1.24, 1.20 to 1.28), chronic obstructive pulmonary disease (1.24, 1.05 to 1.47, and 1.19, 1.09 to 1.30), all cancer (1.17, 1.13 to 1.21, 1.10, 1.07 to 1.13), colorectal cancer (1.17, 1.04 to 1.32, and 1.18, 1.09 to 1.27), lung cancer (1.17, 1.07 to 1.27, and 1.08, 1.03 to 1.13), and breast cancer (1.24, 1.10 to 1.39) but not prostate cancer (1.05, 0.96 to 1.15). Several of these relations had higher hazard ratios in the younger age group. Muscle weakness (defined as grip strength <26 kg for men and <16 kg for women) was associated with a higher hazard for all health outcomes, except colon cancer in women and prostate cancer and lung cancer in both men and women. The addition of handgrip strength improved the prediction ability, based on C index change, of an office based risk score (age, sex, diabetes diagnosed, body mass index, systolic blood pressure, and smoking) for all cause (0.013) and cardiovascular mortality (0.012) and incidence of cardiovascular disease (0.009).
Conclusion: Higher grip strength was associated with a range of health outcomes and improved prediction of an office based risk score. Further work on the use of grip strength in risk scores or risk screening is needed to establish its potential clinical utility
Association of total and differential leukocyte counts with cardiovascular disease and mortality in the UK Biobank
Objective—Elevated white blood cell count is associated with a higher risk of cardiovascular disease (CVD). We aimed to investigate whether specific leukocyte subpopulations, which may more closely indicate a specific inflammatory pathway, are specifically associated with CVD.
Approach and Results—Participants (478 259) from UK Biobank with data for white blood cell count were included. Death because of CVD (n=1377) and non-CVD causes (n=8987) occurred during median follow-up time of 7.0 years (interquartile range, 6.3–7.6). In Cox models, deciles of leukocyte counts (lymphocytes, monocytes, neutrophils, eosinophils, and basophils) were examined using the fifth decile as the referent group. Models were stratified by sex and adjusted for a range of classical risk factors. A sensitivity analysis excluded participants with baseline comorbidites and the first 2 years of follow-up. Men (hazard ratio [HR], 1.59; 95% confidence interval, 1.22–2.08) and women (HR, 2.15; 95% confidence interval, 1.38–3.35) in the highest decile of neutrophil count were at higher risk of CVD mortality and nonfatal CVD (men HR, 1.28; 95% confidence interval, 1.16–1.42 and women HR, 1.21; 95% confidence interval, 1.06–1.38). In the sensitivity analysis, the power to investigate CVD mortality was limited, but for both sexes combined, the linear HRs for a 1×109/L cell count increase in white blood cell count and neutrophils, respectively, was 1.05 (1.03–1.07) and 1.07 (1.04–1.11).
Conclusions—Among circulating leukocyte subpopulations, neutrophil count in men was most consistently associated with fatal and nonfatal CVD. Further studies of interventions that lower circulating neutrophils, such as canakinumab, are required to investigate causality
Glomerular filtration rate by differing measures, albuminuria and prediction of cardiovascular disease, mortality and end-stage kidney disease
Chronic kidney disease is common in the general population and associated with excess cardiovascular disease (CVD), but kidney function does not feature in current CVD risk-prediction models. We tested three formulae for estimated glomerular filtration rate (eGFR) to determine which was the most clinically informative for predicting CVD and mortality. Using data from 440,526 participants from UK Biobank, eGFR was calculated using serum creatinine, cystatin C (eGFRcys) and creatinine-cystatin C. Associations of each eGFR with CVD outcome and mortality were compared using Cox models and adjusting for atherosclerotic risk factors (per relevant risk scores), and the predictive utility was determined by the C-statistic and categorical net reclassification index. We show that eGFRcys is most strongly associated with CVD and mortality, and, along with albuminuria, adds predictive discrimination to current CVD risk scores, whilst traditional creatinine-based measures are weakly associated with risk. Clinicians should consider measuring eGFRcys as part of cardiovascular risk assessment
Comparison of conventional lipoprotein tests and apolipoproteins in the prediction of cardiovascular disease: data from UK Biobank
Background:
Total cholesterol and high-density lipoprotein cholesterol (HDL-C) measurements are central to cardiovascular disease (CVD) risk assessment, but there is continuing debate around the utility of other lipids for risk prediction.
Methods:
Participants from UK Biobank without baseline CVD and not taking statins, with relevant lipid measurements (n=346 686), were included in the primary analysis. An incident fatal or nonfatal CVD event occurred in 6216 participants (1656 fatal) over a median of 8.9 years. Associations of nonfasting lipid measurements (total cholesterol, HDL-C, non–HDL-C, direct and calculated low-density lipoprotein cholesterol [LDL-C], and apolipoproteins [Apo] A1 and B) with CVD were compared using Cox models adjusting for classical risk factors, and predictive utility was determined by the C-index and net reclassification index. Prediction was also tested in 68 649 participants taking a statin with or without baseline CVD (3515 CVD events).
Results:
ApoB, LDL-C, and non–HDL-C were highly correlated (r>0.90), while HDL-C was strongly correlated with ApoA1 (r=0.92). After adjustment for classical risk factors, 1 SD increase in ApoB, direct LDL-C, and non–HDL-C had similar associations with composite fatal/nonfatal CVD events (hazard ratio, 1.23, 1.20, 1.21, respectively). Associations for 1 SD increase in HDL-C and ApoA1 were also similar (hazard ratios, 0.81 [both]). Adding either total cholesterol and HDL-C, or ApoB and ApoA, to a CVD risk prediction model (C-index, 0.7378) yielded similar improvement in discrimination (C-index change, 0.0084; 95% CI, 0.0065, 0.0104, and 0.0089; 95% CI, 0.0069, 0.0109, respectively). Once total and HDL-C were in the model, no further substantive improvement was achieved with the addition of ApoB (C-index change, 0.0004; 95% CI, 0.0000, 0.0008) or any measure of LDL-C. Results for predictive utility were similar for a fatal CVD outcome, and in a discordance analysis. In participants taking a statin, classical risk factors (C-index, 0.7118) were improved by non–HDL-C (C-index change, 0.0030; 95% CI, 0.0012, 0.0048) or ApoB (C-index change, 0.0030; 95% CI, 0.0011, 0.0048). However, adding ApoB or LDL-C to a model already containing non–HDL-C did not further improve discrimination.
Conclusions:
Measurement of total cholesterol and HDL-C in the nonfasted state is sufficient to capture the lipid-associated risk in CVD prediction, with no meaningful improvement from addition of apolipoproteins, direct or calculated LDL-C
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