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1.  Assessing Risk Prediction Models Using Individual Participant Data From Multiple Studies 
Pennells, Lisa | Kaptoge, Stephen | White, Ian R. | Thompson, Simon G. | Wood, Angela M. | Tipping, Robert W. | Folsom, Aaron R. | Couper, David J. | Ballantyne, Christie M. | Coresh, Josef | Goya Wannamethee, S. | Morris, Richard W. | Kiechl, Stefan | Willeit, Johann | Willeit, Peter | Schett, Georg | Ebrahim, Shah | Lawlor, Debbie A. | Yarnell, John W. | Gallacher, John | Cushman, Mary | Psaty, Bruce M. | Tracy, Russ | Tybjærg-Hansen, Anne | Price, Jackie F. | Lee, Amanda J. | McLachlan, Stela | Khaw, Kay-Tee | Wareham, Nicholas J. | Brenner, Hermann | Schöttker, Ben | Müller, Heiko | Jansson, Jan-Håkan | Wennberg, Patrik | Salomaa, Veikko | Harald, Kennet | Jousilahti, Pekka | Vartiainen, Erkki | Woodward, Mark | D'Agostino, Ralph B. | Bladbjerg, Else-Marie | Jørgensen, Torben | Kiyohara, Yutaka | Arima, Hisatomi | Doi, Yasufumi | Ninomiya, Toshiharu | Dekker, Jacqueline M. | Nijpels, Giel | Stehouwer, Coen D. A. | Kauhanen, Jussi | Salonen, Jukka T. | Meade, Tom W. | Cooper, Jackie A. | Cushman, Mary | Folsom, Aaron R. | Psaty, Bruce M. | Shea, Steven | Döring, Angela | Kuller, Lewis H. | Grandits, Greg | Gillum, Richard F. | Mussolino, Michael | Rimm, Eric B. | Hankinson, Sue E. | Manson, JoAnn E. | Pai, Jennifer K. | Kirkland, Susan | Shaffer, Jonathan A. | Shimbo, Daichi | Bakker, Stephan J. L. | Gansevoort, Ron T. | Hillege, Hans L. | Amouyel, Philippe | Arveiler, Dominique | Evans, Alun | Ferrières, Jean | Sattar, Naveed | Westendorp, Rudi G. | Buckley, Brendan M. | Cantin, Bernard | Lamarche, Benoît | Barrett-Connor, Elizabeth | Wingard, Deborah L. | Bettencourt, Richele | Gudnason, Vilmundur | Aspelund, Thor | Sigurdsson, Gunnar | Thorsson, Bolli | Kavousi, Maryam | Witteman, Jacqueline C. | Hofman, Albert | Franco, Oscar H. | Howard, Barbara V. | Zhang, Ying | Best, Lyle | Umans, Jason G. | Onat, Altan | Sundström, Johan | Michael Gaziano, J. | Stampfer, Meir | Ridker, Paul M. | Michael Gaziano, J. | Ridker, Paul M. | Marmot, Michael | Clarke, Robert | Collins, Rory | Fletcher, Astrid | Brunner, Eric | Shipley, Martin | Kivimäki, Mika | Ridker, Paul M. | Buring, Julie | Cook, Nancy | Ford, Ian | Shepherd, James | Cobbe, Stuart M. | Robertson, Michele | Walker, Matthew | Watson, Sarah | Alexander, Myriam | Butterworth, Adam S. | Angelantonio, Emanuele Di | Gao, Pei | Haycock, Philip | Kaptoge, Stephen | Pennells, Lisa | Thompson, Simon G. | Walker, Matthew | Watson, Sarah | White, Ian R. | Wood, Angela M. | Wormser, David | Danesh, John
American Journal of Epidemiology  2013;179(5):621-632.
Individual participant time-to-event data from multiple prospective epidemiologic studies enable detailed investigation into the predictive ability of risk models. Here we address the challenges in appropriately combining such information across studies. Methods are exemplified by analyses of log C-reactive protein and conventional risk factors for coronary heart disease in the Emerging Risk Factors Collaboration, a collation of individual data from multiple prospective studies with an average follow-up duration of 9.8 years (dates varied). We derive risk prediction models using Cox proportional hazards regression analysis stratified by study and obtain estimates of risk discrimination, Harrell's concordance index, and Royston's discrimination measure within each study; we then combine the estimates across studies using a weighted meta-analysis. Various weighting approaches are compared and lead us to recommend using the number of events in each study. We also discuss the calculation of measures of reclassification for multiple studies. We further show that comparison of differences in predictive ability across subgroups should be based only on within-study information and that combining measures of risk discrimination from case-control studies and prospective studies is problematic. The concordance index and discrimination measure gave qualitatively similar results throughout. While the concordance index was very heterogeneous between studies, principally because of differing age ranges, the increments in the concordance index from adding log C-reactive protein to conventional risk factors were more homogeneous.
doi:10.1093/aje/kwt298
PMCID: PMC3927974  PMID: 24366051
C index; coronary heart disease; D measure; individual participant data; inverse variance; meta-analysis; risk prediction; weighting
2.  Healthy Lifestyles Reduce the Incidence of Chronic Diseases and Dementia: Evidence from the Caerphilly Cohort Study 
PLoS ONE  2013;8(12):e81877.
Background
Healthy lifestyles based on non-smoking, an acceptable BMI, a high fruit and vegetable intake, regular physical activity, and low/moderate alcohol intake, are associated with reductions in the incidence of certain chronic diseases, but to date there is limited evidence on cognitive function and dementia.
Methods
In 1979 healthy behaviours were recorded on 2,235 men aged 45–59 years in Caerphilly, UK. During the following 30 years incident diabetes, vascular disease, cancer and death were recorded, and in 2004 cognitive state was determined.
Findings
Men who followed four or five of the behaviours had an odds ratio (OR) and confidence intervals (CI) for diabetes, corrected for age and social class, of 0.50 (95% CI: 0.19, 1.31; P for trend with increasing numbers of healthy behaviours <0.0005). For vascular disease the OR was 0.50 (95% CI: 0.30, 0.84; P for trend <0.0005), and there was a delay in vascular disease events of up to 12 years. Cancer incidence was not significantly related to lifestyle although there was a reduction associated with non-smoking (OR: 0.65; 95% CI: 0.54, 0.79). All-cause mortality was reduced in men following four or five behaviours (OR 0.40; 95% CI: 0.24, 0.67; P for trend <0.005).
After further adjustment for NART, the OR for men following four or five healthy behaviours was 0.36 (95% CI: 0.12, 1.09; P for trend <0.001) for cognitive impairment, and 0.36 (95% CI: 0.07, 1.99; P for trend <0.02) for dementia.
The adoption of a healthy lifestyle by men was low and appears not to have changed during the subsequent 30 years, with under 1% of men following all five of the behaviours and 5% reporting four or more in 1979 and in 2009.
Interpretation
A healthy lifestyle is associated with increased disease-free survival and reduced cognitive impairment but the uptake remains low.
doi:10.1371/journal.pone.0081877
PMCID: PMC3857242  PMID: 24349147
3.  Prevalence and Characteristics of Probable Major Depression and Bipolar Disorder within UK Biobank: Cross-Sectional Study of 172,751 Participants 
PLoS ONE  2013;8(11):e75362.
Objectives
UK Biobank is a landmark cohort of over 500,000 participants which will be used to investigate genetic and non-genetic risk factors for a wide range of adverse health outcomes. This is the first study to systematically assess the prevalence and validity of proposed criteria for probable mood disorders within the cohort (major depression and bipolar disorder).
Methods
This was a descriptive epidemiological study of 172,751 individuals assessed for a lifetime history of mood disorder in relation to a range of demographic, social, lifestyle, personality and health-related factors. The main outcomes were prevalence of a probable lifetime (single) episode of major depression, probable recurrent major depressive disorder (moderate), probable recurrent major depressive disorder (severe), probable bipolar disorder and no history of mood disorder (comparison group). Outcomes were compared on age, gender, ethnicity, socioeconomic status, educational attainment, functioning, self-reported health status, current depressive symptoms, neuroticism score, smoking status and alcohol use.
Results
Prevalence rates for probable single lifetime episode of major depression (6.4%), probable recurrent major depression (moderate) (12.2%), probable recurrent major depression (severe) (7.2%) and probable bipolar disorder (1.3%) were comparable to those found in other population studies. The proposed diagnostic criteria have promising validity, with a gradient in evidence from no mood disorder through major depression and probable bipolar disorder in terms of gender distribution, socioeconomic status, self-reported health rating, current depressive symptoms and smoking.
Significance
The validity of our proposed criteria for probable major depression and probable bipolar disorder within this cohort are supported by these cross-sectional analyses. Our findings are likely to prove useful as a framework for a wide range of future genetic and non-genetic studies.
doi:10.1371/journal.pone.0075362
PMCID: PMC3839907  PMID: 24282498
4.  Childhood milk consumption is associated with better physical performance in old age 
Age and Ageing  2012;41(6):776-784.
Background: studies have shown that milk and dairy consumption in adulthood have beneficial effects on health.
Methods: we examined the impact of childhood and adult diet on physical performance at age 63–86 years. The Boyd Orr cohort (n = 405) is a 65-year prospective study of children who took part in a 1930's survey; the Caerphilly Prospective Study (CaPS; n = 1,195) provides data from mid-life to old age. We hypothesised that higher intakes of childhood and adult milk, calcium, protein, fat and energy would be associated with a better performance.
Results: in fully adjusted models, a standard deviation (SD) increase in natural log-transformed childhood milk intake was associated with 5% faster walking times from the get-up and go test in Boyd Orr (95% CI: 1 to 9) and 25% lower odds of poor balance (OR: 0.75; 0.55 to 1.02). Childhood calcium intake was positively associated with walking times (4% faster per SD; 0 to 8) and a higher protein intake was associated with lower odds of poor balance (OR: 0.71; 0.54 to 0.92). In adulthood, protein intake was positively associated with walking times (2% faster per SD; 1 to 3; Boyd Orr and CaPS pooled data).
Conclusion: this is the first study to show positive associations of childhood milk intake with physical performance in old age.
doi:10.1093/ageing/afs052
PMCID: PMC3476828  PMID: 22542496
diet; physical performance; walking speed; standing balance; older people
5.  Participant Profiles According to Recruitment Source in a Large Web-Based Prospective Study: Experience From the Nutrinet-Santé Study 
Background
Interest in Internet-based epidemiologic research is growing given the logistic and cost advantages. Cohort recruitment to maximally diversify the sociodemographic profiles of participants, however, remains a contentious issue.
Objective
The aim of the study was to characterize the sociodemographic profiles according to the recruitment mode of adult volunteers enrolled in a Web-based cohort.
Methods
The French NutriNet-Santé Web-based cohort was launched in 2009. Recruitment is ongoing and largely relies on recurrent multimedia campaigns. One month after enrollment, participants are asked how they learned about the study (eg, general newscast or a health program on television, radio newscast, newspaper articles, Internet, personal advice, leaflet/flyers) The sociodemographic profiles of participants recruited through operative communication channels (radio, print media, Internet, advice) were compared with the profiles of those informed through television by using polytomous logistic regression.
Results
Among the 88,238 participants enrolled through the end of 2011, 30,401 (34.45%), 16,751 (18.98%), and 14,309 (16.22%) learned about the study from television, Internet, and radio newscasts, respectively. Sociodemographic profiles were various, with 14,541 (16.5%) aged ≥60 years, 20,166 (22.9%) aged <30 years, 27,766 (32.1%) without postsecondary education, 15,397 (19.7%) with household income <€1200/month, and 8258 (10.6%) with household income €3700/month. Compared to employed individuals, unemployed and retired participants were less likely to be informed about the study through other sources than through television (adjusted ORs 0.56-0.83, P<.001). Participants reporting up to secondary education were also less likely to have learned about the study through radio newscasts, newspaper articles, Internet, and advice than through television (adjusted ORs 0.60-0.77, P<.001).
Conclusions
Television broadcasts appear to permit the recruitment of e-cohort participants with diverse sociodemographic backgrounds, including socioeconomically disadvantaged individuals who are usually difficult to reach and retain in long-term epidemiologic studies. These findings could inform future Web-based studies regarding the development of promising targeted or general population recruitment strategies.
doi:10.2196/jmir.2488
PMCID: PMC3785981  PMID: 24036068
cohort study; Internet; selection bias; population characteristics
6.  Urban built environment configuration and psychological distress in older men: Results from the Caerphilly study 
BMC Public Health  2013;13:695.
Background
Few studies have examined the impact of the built environment configuration upon mental health. The study examines the impact of objectively assessed land use and street network configuration upon psychological distress and whether this association is moderated by the natural environment and area-level deprivation.
Methods
In a community sample of 687 older men from the Caerphilly Prospective Study, built environment morphological metrics (morphometrics) were related to differences in psychological distress as measured by the General Health Questionnaire. Cross-sectional data were taken from the most recent (5th) phase. A multi-level analysis with individuals nested within census-defined neighbourhoods was conducted. Environmental measures comprised GIS-constructed land use and street network metrics, slope variability and a satellite derived measure of greenness.
Results
Reduced psychological distress was associated with residing in a terraced dwelling (OR = 0.48, p = 0.03), higher degrees of land-use mix (OR = 0.42, p = 0.03 for the high tertile) and having higher local-level street-network accessibility (‘movement potential’) (OR = 0.54, p = 0.03). Hillier topography with higher slope variability was associated with increased risks of psychological distress (OR = 1.38, p = 0.05).
Conclusions
The findings support our hypothesis that built environment configuration is independently associated with psychological distress. The study underscores the need for effective intervention in the planning and design of residential built environment to achieve the goal of health-sustaining communities.
doi:10.1186/1471-2458-13-695
PMCID: PMC3735426  PMID: 23898839
Psychological distress; GHQ; Older adults; Built environment configuration; Space syntax; Random effects; Runmlwin
7.  Telomere Length and Physical Performance at Older Ages: An Individual Participant Meta-Analysis 
PLoS ONE  2013;8(7):e69526.
Background
Telomeres are involved in cellular ageing and shorten with increasing age. If telomere length is a valuable biomarker of ageing, then telomere shortening should be associated with worse physical performance, an ageing trait, but evidence for such an association is lacking. The purpose of this study was to examine whether change in telomere length is associated with physical performance.
Methods
Using data from four UK adult cohorts (ages 53–80 years at baseline), we undertook cross-sectional and longitudinal analyses. We analysed each study separately and then used meta-analytic methods to pool the results. Physical performance was measured using walking and chair rise speed, standing balance time and grip strength. Telomere length was measured by quantitative real-time polymerase chain reaction (PCR) in whole blood at baseline and follow-up (time 1, time 2).
Results
Total sample sizes in meta-analyses ranged from 1,217 to 3,707. There was little evidence that telomere length was associated with walking speed, balance or grip strength, though weak associations were seen with chair rise speed and grip strength at baseline (p = 0.02 and 0.01 respectively). Faster chair rise speed at follow-up, was associated with a smaller decline in telomere length between time 1 and time 2 (standardised coefficient per SD increase 0.061, 95% CI 0.006, 0.115, p = 0.03) but this was consistent with chance (p = 0.08) after further adjustment.
Conclusions
Whereas shortening of leukocyte telomeres might be an important measure of cellular ageing, there is little evidence that it is a strong biomarker for physical performance.
doi:10.1371/journal.pone.0069526
PMCID: PMC3724915  PMID: 23922731
8.  Physical capability and subsequent positive mental wellbeing in older people: findings from five HALCyon cohorts 
Age  2013;36(1):445-456.
Objective measures of physical capability are being used in a growing number of studies as biomarkers of healthy ageing. However, very little research has been done to assess the impact of physical capability on subsequent positive mental wellbeing, the maintenance of which is widely considered to be an essential component of healthy ageing. We aimed to test the associations of grip strength and walking, timed get up and go and chair rise speeds (assessed at ages 53 to 82 years) with positive mental wellbeing assessed using the Warwick–Edinburgh Mental Wellbeing Scale (WEMWBS) 5 to 10 years later. Data were drawn from five British cohorts participating in the Healthy Ageing across the Life Course research collaboration. Data from each study were analysed separately and then combined using random-effects meta-analyses. Higher levels of physical capability were consistently associated with higher subsequent levels of wellbeing; for example, a 1SD increase in grip strength was associated with an age and sex-adjusted mean difference in WEMWBS score of 0.81 (0.25, 1.37), equivalent to 10 % of a standard deviation (three studies, N = 3,096). When adjusted for body size, health status, living alone, socioeconomic position and neuroticism the associations remained albeit attenuated. The finding of these consistent modest associations across five studies, spanning early and later old age, highlights the importance of maintaining physical capability in later life and provides additional justification for using objective measures of physical capability as markers of healthy ageing.
Electronic supplementary material
The online version of this article (doi:10.1007/s11357-013-9553-8) contains supplementary material, which is available to authorized users.
doi:10.1007/s11357-013-9553-8
PMCID: PMC3818137  PMID: 23818103
Physical capability; Positive mental wellbeing; Grip strength; Walking speed; Chair rise time
9.  Body Mass Index, Muscle Strength and Physical Performance in Older Adults from Eight Cohort Studies: The HALCyon Programme 
PLoS ONE  2013;8(2):e56483.
Objective
To investigate the associations of body mass index (BMI) and grip strength with objective measures of physical performance (chair rise time, walking speed and balance) including an assessment of sex differences and non-linearity.
Methods
Cross-sectional data from eight UK cohort studies (total N = 16 444) participating in the Healthy Ageing across the Life Course (HALCyon) research programme, ranging in age from 50 to 90+ years at the time of physical capability assessment, were used. Regression models were fitted within each study and meta-analysis methods used to pool regression coefficients across studies and to assess the extent of heterogeneity between studies.
Results
Higher BMI was associated with poorer performance on chair rise (N = 10 773), walking speed (N = 9 761) and standing balance (N = 13 921) tests. Higher BMI was associated with stronger grip strength in men only. Stronger grip strength was associated with better performance on all tests with a tendency for the associations to be stronger in women than men; for example, walking speed was higher by 0.43 cm/s (0.14, 0.71) more per kg in women than men. Both BMI and grip strength remained independently related with performance after mutual adjustment, but there was no evidence of effect modification. Both BMI and grip strength exhibited non-linear relations with performance; those in the lowest fifth of grip strength and highest fifth of BMI having particularly poor performance. Findings were similar when waist circumference was examined in place of BMI.
Conclusion
Older men and women with weak muscle strength and high BMI have considerably poorer performance than others and associations were observed even in the youngest cohort (age 53). Although causality cannot be inferred from observational cross-sectional studies, our findings suggest the likely benefit of early assessment and interventions to reduce fat mass and improve muscle strength in the prevention of future functional limitations.
doi:10.1371/journal.pone.0056483
PMCID: PMC3577921  PMID: 23437142
10.  A Platform for the Remote Conduct of Gene-Environment Interaction Studies 
PLoS ONE  2013;8(1):e54331.
Background
Gene-environment interaction studies offer the prospect of robust causal inference through both gene identification and instrumental variable approaches. As such they are a major and much needed development. However, conducting these studies using traditional methods, which require direct participant contact, is resource intensive. The ability to conduct gene-environment interaction studies remotely would reduce costs and increase capacity.
Aim
To develop a platform for the remote conduct of gene-environment interaction studies.
Methods
A random sample of 15,000 men and women aged 50+ years and living in Cardiff, South Wales, of whom 6,012 were estimated to have internet connectivity, were mailed inviting them to visit a web-site to join a study of successful ageing. Online consent was obtained for questionnaire completion, cognitive testing, re-contact, record linkage and genotyping. Cognitive testing was conducted using the Cardiff Cognitive Battery. Bio-sampling was randomised to blood spot, buccal cell or no request.
Results
A heterogeneous sample of 663 (4.5% of mailed sample and 11% of internet connected sample) men and women (47% female) aged 50–87 years (median = 61 yrs) from diverse backgrounds (representing the full range of deprivation scores) was recruited. Bio-samples were donated by 70% of those agreeing to do so. Self report questionnaires and cognitive tests showed comparable distributions to those collected using face-to-face methods. Record linkage was achieved for 99.9% of participants.
Conclusion
This study has demonstrated that remote methods are suitable for the conduct of gene-environment interaction studies. Up-scaling these methods provides the opportunity to increase capacity for large-scale gene-environment interaction studies.
doi:10.1371/journal.pone.0054331
PMCID: PMC3548886  PMID: 23349852
11.  Dysregulation of the hypothalamic pituitary adrenal (HPA) axis and physical performance at older ages: An individual participant meta-analysis 
Psychoneuroendocrinology  2013;38(1):40-49.
Summary
The association between functioning of the hypothalamic pituitary adrenal (HPA) axis and physical performance at older ages remains poorly understood. We carried out meta-analyses to test the hypothesis that dysregulation of the HPA axis, as indexed by patterns of diurnal cortisol release, is associated with worse physical performance. Data from six adult cohorts (ages 50–92 years) were included in a two stage meta-analysis of individual participant data. We analysed each study separately using linear and logistic regression models and then used meta-analytic methods to pool the results. Physical performance outcome measures were walking speed, balance time, chair rise time and grip strength. Exposure measures were morning (serum and salivary) and evening (salivary) cortisol. Total sample sizes in meta-analyses ranged from n = 2146 for associations between morning Cortisol Awakening Response and balance to n = 8448 for associations between morning cortisol and walking speed. A larger diurnal drop was associated with faster walking speed (standardised coefficient per SD increase 0.052, 95% confidence interval (CI) 0.029, 0.076, p < 0.001; age and gender adjusted) and a quicker chair rise time (standardised coefficient per SD increase −0.075, 95% CI −0.116, −0.034, p < 0.001; age and gender adjusted). There was little evidence of associations with balance or grip strength. Greater diurnal decline of the HPA axis is associated with better physical performance in later life. This may reflect a causal effect of the HPA axis on performance or that other ageing-related factors are associated with both reduced HPA reactivity and performance.
doi:10.1016/j.psyneuen.2012.04.016
PMCID: PMC3533133  PMID: 22658392
HPA axis; Physical capability; Healthy ageing
12.  Socioeconomic disadvantage from childhood to adulthood and locomotor function in old age: a lifecourse analysis of the Boyd Orr and Caerphilly prospective studies 
Background
Socioeconomic influences over a lifetime impact on health and may contribute to poor physical functioning in old age.
Methods
We examined the impact of both childhood and adulthood socioeconomic factors on locomotor function at 63-86 years (measured with the get up and go timed walk and flamingo balance test), in the UK-based Boyd Orr (n=405) and Caerphilly (n=1,196) prospective cohorts.
Results
There was a marked reduction in walking speed and balance time with increasing age. Each year of age was associated with a 1.7% slower walk time and a 14% increased odds of poor balance. Participants who moved from a low socioeconomic position in childhood to a high socioeconomic position in adulthood had walking times 3% slower (95% CI: -2%, 8%) than people with high socioeconomic position in both periods. Participants who moved from a high socioeconomic position in childhood to a low adulthood socioeconomic position had walking times 5% slower (95% CI: -2%, 12%). Participants with a low socioeconomic position in both periods had walking times 10% slower (95% CI: 5%, 16%; P for trend <0.001).
In Boyd Orr, low socioeconomic position in childhood was associated with poor balance in old age (OR per worsening category = 1.26; 95% CI 1.01, 1.57; P=0.043), as was socioeconomic position in adulthood (OR = 1.71; 95% CI 1.20, 2.45; P=0.003). Similar associations were not observed in Caerphilly.
Conclusion
Accumulating socioeconomic disadvantage from childhood to adulthood is associated with slower walking time in old age, with mixed results for balance ability.
doi:10.1136/jech.2009.103648
PMCID: PMC3381706  PMID: 20644236
Aged; Gait; Physical performance; Social Class; Socioeconomic Factors
13.  ‘Sifting the significance from the data’ - the impact of high-throughput genomic technologies on human genetics and health care 
Human Genomics  2012;6(1):11.
This report is of a round-table discussion held in Cardiff in September 2009 for Cesagen, a research centre within the Genomics Network of the UK’s Economic and Social Research Council. The meeting was arranged to explore ideas as to the likely future course of human genomics. The achievements of genomics research were reviewed, and the likely constraints on the pace of future progress were explored. New knowledge is transforming biology and our understanding of evolution and human disease. The difficulties we face now concern the interpretation rather than the generation of new sequence data. Our understanding of gene-environment interaction is held back by our current primitive tools for measuring environmental factors, and in addition, there may be fundamental constraints on what can be known about these complex interactions.
doi:10.1186/1479-7364-6-11
PMCID: PMC3500243  PMID: 23244462
14.  Generating Large-Scale Longitudinal Data Resources for Aging Research 
Objectives.
The need for large studies and the types of large-scale data resources (LSDRs) are discussed along with their general scientific utility, role in aging research, and affordability. The diversification of approaches to large-scale data resourcing is described in order to facilitate their use in aging research.
Methods.
The need for LSDRs is discussed in terms of (a) large sample size; (b) longitudinal design; (c) as platforms for additional investigator-initiated research projects; and (d) broad-based access to core genetic, biological, and phenotypic data.
Discussion.
It is concluded that a “lite-touch, lo-tech, lo-cost” approach to LSDRs is a viable strategy for the development of LSDRs and would enhance the likelihood of LSDRs being established which are dedicated to the wide range of important aging-related issues.
doi:10.1093/geronb/gbr047
PMCID: PMC3165456  PMID: 21743049
15.  Associations of Insulin and Insulin-Like Growth Factors with Physical Performance in Old Age in the Boyd Orr and Caerphilly Studies 
PLoS ONE  2012;7(1):e30096.
Objective
Insulin and the insulin-like growth factor (IGF) system regulate growth and are involved in determining muscle mass, strength and body composition. We hypothesised that IGF-I and IGF-II are associated with improved, and insulin with worse, physical performance in old age.
Methods
Physical performance was measured using the get-up and go timed walk and flamingo balance test at 63–86 years. We examined prospective associations of insulin, IGF-I, IGF-II and IGFBP-3 with physical performance in the UK-based Caerphilly Prospective Study (CaPS; n = 739 men); and cross-sectional insulin, IGF-I, IGF-II, IGFBP-2 and IGFBP-3 in the Boyd Orr cohort (n = 182 men, 223 women).
Results
In confounder-adjusted models, there was some evidence in CaPS that a standard deviation (SD) increase in IGF-I was associated with 1.5% faster get-up and go test times (95% CI: −0.2%, 3.2%; p = 0.08), but little association with poor balance, 19 years later. Coefficients in Boyd Orr were in the same direction as CaPS, but consistent with chance. Higher levels of insulin were weakly associated with worse physical performance (CaPS and Boyd Orr combined: get-up and go time = 1.3% slower per SD log-transformed insulin; 95% CI: 0.0%, 2.7%; p = 0.07; OR poor balance 1.13; 95% CI; 0.98, 1.29; p = 0.08), although associations were attenuated after controlling for body mass index (BMI) and co-morbidities. In Boyd Orr, a one SD increase in IGFBP-2 was associated with 2.6% slower get-up and go times (95% CI: 0.4%, 4.8% slower; p = 0.02), but this was only seen when controlling for BMI and co-morbidities. There was no consistent evidence of associations of IGF-II, or IGFBP-3 with physical performance.
Conclusions
There was some evidence that high IGF-I and low insulin levels in middle-age were associated with improved physical performance in old age, but estimates were imprecise. Larger cohorts are required to confirm or refute the findings.
doi:10.1371/journal.pone.0030096
PMCID: PMC3254635  PMID: 22253890
16.  Age and Gender Differences in Physical Capability Levels from Mid-Life Onwards: The Harmonisation and Meta-Analysis of Data from Eight UK Cohort Studies 
PLoS ONE  2011;6(11):e27899.
Using data from eight UK cohorts participating in the Healthy Ageing across the Life Course (HALCyon) research programme, with ages at physical capability assessment ranging from 50 to 90+ years, we harmonised data on objective measures of physical capability (i.e. grip strength, chair rising ability, walking speed, timed get up and go, and standing balance performance) and investigated the cross-sectional age and gender differences in these measures. Levels of physical capability were generally lower in study participants of older ages, and men performed better than women (for example, results from meta-analyses (N = 14,213 (5 studies)), found that men had 12.62 kg (11.34, 13.90) higher grip strength than women after adjustment for age and body size), although for walking speed, this gender difference was attenuated after adjustment for body size. There was also evidence that the gender difference in grip strength diminished with increasing age,whereas the gender difference in walking speed widened (p<0.01 for interactions between age and gender in both cases). This study highlights not only the presence of age and gender differences in objective measures of physical capability but provides a demonstration that harmonisation of data from several large cohort studies is possible. These harmonised data are now being used within HALCyon to understand the lifetime social and biological determinants of physical capability and its changes with age.
doi:10.1371/journal.pone.0027899
PMCID: PMC3218057  PMID: 22114723
17.  Diurnal cortisol patterns are associated with physical performance in the Caerphilly Prospective Study 
Background Cross-sectional studies have suggested that elevated cortisol is associated with worse physical performance, a surrogate of ageing. We examined the relationship between repeat cortisol measures over 20 years and physical performance in later life.
Methods Middle-aged men (45–59 years) were recruited between 1979 and 1983 (Phase 1) from the Caerphilly Prospective Study (CaPS) and re-examined 20 years later at 65–83 years of age (Phase 5). Participants included 750 and 898 subjects with either Phase 1 and/or Phase 5 data on exposure and outcomes. Outcome measures were walking speed and balance time and exposures included morning fasting serum cortisol (Phase 1) and four salivary samples on 2 consecutive days (Phase 5).
Results Faster walking speed was associated with higher morning cortisol at Phase 1 [coefficient per standard deviation (SD) increase 0.68, 95% confidence interval (95% CI) 0.09–1.27; P = 0.02] though this was attenuated after adjustment for covariates (coefficient per SD increase 0.45; 95% CI –0.16 to 1.07; P = 0.15). Higher night-time cortisol at Phase 5 was associated with slower speed (coefficient per SD increase –1.06; 95% CI –1.60 to –0.52; P < 0.001) and poorer balance (odds ratio of top tertile vs bottom 2.49; 95% CI 1.63–3.81; P < 0.001). Worst performance was seen for men with a poor morning response (Phase 1) and less nocturnal decline (Phase 5).
Conclusions Dysregulation of the hypothalamic pituitary adrenal (HPA) axis is associated with worse physical performance in later life. This may reflect a causal effect of the HPA axis on ageing or that ageing itself is associated with reduced HPA reactivity.
doi:10.1093/ije/dyr113
PMCID: PMC3235020  PMID: 21764771
HPA axis; physical capability; healthy ageing
18.  Psychosocial impact of the summer 2007 floods in England 
BMC Public Health  2011;11:145.
Background
The summer of 2007 was the wettest in the UK since records began in 1914 and resulted in severe flooding in several regions. We carried out a health impact assessment using population-based surveys to assess the prevalence of and risk factors for the psychosocial consequences of this flooding in the United Kingdom.
Methods
Surveys were conducted in two regions using postal, online, telephone questionnaires and face-to-face interviews. Exposure variables included the presence of flood water in the home, evacuation and disruption to essential services (incident management variables), perceived impact of the floods on finances, house values and perceived health concerns. Validated tools were used to assess psychosocial outcome (mental health symptoms): psychological distress (GHQ-12), anxiety (GAD-7), depression (PHQ-9) and probable post-traumatic stress disorder (PTSD checklist-shortform). Multivariable logistic regression was used to describe the association between water level in the home, psychological exposure variables and incident management variables, and each mental health symptom, adjusted for age, sex, presence of an existing medical condition, employment status, area and data collection method.
Results
The prevalence of all mental health symptoms was two to five-fold higher among individuals affected by flood water in the home. People who perceived negative impact on finances were more likely to report psychological distress (OR 2.5, 1.8-3.4), probable anxiety (OR 1.8, 1.3-2.7) probable depression (OR 2.0, 1.3-2.9) and probable PTSD (OR 3.2, 2.0-5.2). Disruption to essential services increased adverse psychological outcomes by two to three-fold. Evacuation was associated with some increase in psychological distress but not significantly for the other three measures.
Conclusion
The psychosocial and mental health impact of flooding is a growing public health concern and improved strategies for minimising disruption to essential services and financial worries need to be built in to emergency preparedness and response systems. Public Health Agencies should address the underlying predictors of adverse psychosocial and mental health when providing information and advice to people who are or are likely to be affected by flooding.
doi:10.1186/1471-2458-11-145
PMCID: PMC3062606  PMID: 21371296
19.  Childhood Socioeconomic Position and Objectively Measured Physical Capability Levels in Adulthood: A Systematic Review and Meta-Analysis 
PLoS ONE  2011;6(1):e15564.
Background
Grip strength, walking speed, chair rising and standing balance time are objective measures of physical capability that characterise current health and predict survival in older populations. Socioeconomic position (SEP) in childhood may influence the peak level of physical capability achieved in early adulthood, thereby affecting levels in later adulthood. We have undertaken a systematic review with meta-analyses to test the hypothesis that adverse childhood SEP is associated with lower levels of objectively measured physical capability in adulthood.
Methods and Findings
Relevant studies published by May 2010 were identified through literature searches using EMBASE and MEDLINE. Unpublished results were obtained from study investigators. Results were provided by all study investigators in a standard format and pooled using random-effects meta-analyses. 19 studies were included in the review. Total sample sizes in meta-analyses ranged from N = 17,215 for chair rise time to N = 1,061,855 for grip strength. Although heterogeneity was detected, there was consistent evidence in age adjusted models that lower childhood SEP was associated with modest reductions in physical capability levels in adulthood: comparing the lowest with the highest childhood SEP there was a reduction in grip strength of 0.13 standard deviations (95% CI: 0.06, 0.21), a reduction in mean walking speed of 0.07 m/s (0.05, 0.10), an increase in mean chair rise time of 6% (4%, 8%) and an odds ratio of an inability to balance for 5s of 1.26 (1.02, 1.55). Adjustment for the potential mediating factors, adult SEP and body size attenuated associations greatly. However, despite this attenuation, for walking speed and chair rise time, there was still evidence of moderate associations.
Conclusions
Policies targeting socioeconomic inequalities in childhood may have additional benefits in promoting the maintenance of independence in later life.
doi:10.1371/journal.pone.0015564
PMCID: PMC3027621  PMID: 21297868
20.  Interleukin-18 Polymorphism and Physical Functioning in Older People: A Replication Study and Meta-Analysis 
Background
Levels of the proinflammatory cytokine interleukin-18 (IL-18) are raised in old age and are associated with reduced physical functioning. Previous studies have indicated that the C allele of the rs5744256 polymorphism in the IL-18 gene is strongly associated with reduced circulating IL-18 levels. This variant has previously been associated with improved locomotor performance in old age, but the finding requires independent replication.
Methods
We examined the association between the IL-18 polymorphism rs5744256 and physical functioning in three cohorts with a total of 4,107 participants aged 60–85 years: the English Longitudinal Study of Ageing, Caerphilly, and Boyd Orr. We meta-analyzed (N = 6,141) the results with data from the original paper reporting this association: Iowa-Established Populations for Epidemiological Study of the Elderly and InCHIANTI cohorts. Physical functioning was assessed by timed walks or the get up and go test. As locomotor performance tests differed between the cohorts and the distributions of times to complete the test (in seconds) were positively skewed, we used the reciprocal transformation and computed study-specific z scores.
Results
Based on the three new studies, the estimated linear regression coefficient per C allele was 0.011 (95% confidence interval [95% CI]: −0.04 to 0.06). A meta-analysis that pooled the data from all studies showed weak evidence of an effect, with a regression coefficient of 0.047 (95% CI: 0.010 to 0.083).
Conclusions
We did not replicate an association between the IL-18 rs5744256 polymorphism and the physical function in people aged 60–85 years. However, pooling data from all studies suggested a weak association of the C allele of the rs5744256 single nucleotide polymorphism on improving walking times in old age.
doi:10.1093/gerona/glp092
PMCID: PMC2981454  PMID: 19633236
Interleukin-18 polymorphism; IL-18; Ageing; Physical function; Gait speed; Walk time
21.  Quality, quantity and harmony: the DataSHaPER approach to integrating data across bioclinical studies 
Background Vast sample sizes are often essential in the quest to disentangle the complex interplay of the genetic, lifestyle, environmental and social factors that determine the aetiology and progression of chronic diseases. The pooling of information between studies is therefore of central importance to contemporary bioscience. However, there are many technical, ethico-legal and scientific challenges to be overcome if an effective, valid, pooled analysis is to be achieved. Perhaps most critically, any data that are to be analysed in this way must be adequately ‘harmonized’. This implies that the collection and recording of information and data must be done in a manner that is sufficiently similar in the different studies to allow valid synthesis to take place.
Methods This conceptual article describes the origins, purpose and scientific foundations of the DataSHaPER (DataSchema and Harmonization Platform for Epidemiological Research; http://www.datashaper.org), which has been created by a multidisciplinary consortium of experts that was pulled together and coordinated by three international organizations: P3G (Public Population Project in Genomics), PHOEBE (Promoting Harmonization of Epidemiological Biobanks in Europe) and CPT (Canadian Partnership for Tomorrow Project).
Results The DataSHaPER provides a flexible, structured approach to the harmonization and pooling of information between studies. Its two primary components, the ‘DataSchema’ and ‘Harmonization Platforms’, together support the preparation of effective data-collection protocols and provide a central reference to facilitate harmonization. The DataSHaPER supports both ‘prospective’ and ‘retrospective’ harmonization.
Conclusion It is hoped that this article will encourage readers to investigate the project further: the more the research groups and studies are actively involved, the more effective the DataSHaPER programme will ultimately be.
doi:10.1093/ije/dyq139
PMCID: PMC2972444  PMID: 20813861
Data synthesis; data quality; data pooling; harmonization; meta-analysis; DataSHaPER; prospective harmonization; retrospective harmonization
22.  The effect of different cardiovascular risk presentation formats on intentions, understanding and emotional affect: a randomised controlled trial using a web-based risk formatter (protocol) 
Background
The future risk of heart disease can be predicted with increasing precision. However, more research is needed into how this risk is conveyed and presented. The aim of this study is to compare the effects of presenting cardiovascular risk in different formats on individuals' intention to change behaviour to reduce risk, understanding of risk information and emotional affect.
Methods/design
A randomised controlled trial comprising four arms, with a between subjects design will be performed. There will be two intervention groups and two control groups. The first control comprises a pre-intervention questionnaire and presents risk in a bar graph format. The second control presents risk in a bar graph format without pre-intervention questionnaire. These two control groups are to account for the potential Hawthorne effect of thinking about cardiovascular risk before viewing actual risk. The two intervention groups comprise presenting risk in either a pictogram or metonym format (image depicting seriousness of having a myocardial infarction). 800 individuals' aged between 45 and 64 years, who have not been previously diagnosed with heart disease and have access to a computer with internet, will be given a link to a website comprising a risk calculator and electronic questionnaires. 10-year risk of having a coronary heart disease event will be assessed and presented in one of the three formats. A post-intervention questionnaire will be completed after viewing the risk format. Main outcome measures are (i) intention to change behaviour, (ii) understanding of risk information, (iii) emotional affect and (iv) worry about future heart disease. Secondary outcomes are the sub-components of the theory of planned behaviour: attitudes, perceived behavioural control and subjective norms.
Discussion
Having reviewed the literature, we are not aware of any other studies which have used the assessment of actual risk, in a trial to compare different graphical cardiovascular risk presentation formats. This trial will provide data about which graphical cardiovascular risk presentation format is most effective in encouraging behaviour change to reduce cardiovascular risk.
Trial registration
Current Controlled Trials ISRCTN91319318
doi:10.1186/1472-6947-10-41
PMCID: PMC2922081  PMID: 20673347
23.  Symptomatology attributable to psychological exposure to a chemical incident: a natural experiment 
Background
Exposure to a complex emergency has a substantial psychological component, which is rarely assessed. This study compares the health impact of physically and psychologically mediated exposure to a complex emergency.
Setting
The Sea Empress oil tanker spill.
Design
A cross‐sectional analysis of self‐report questionnaire responses collected from inhabitants of 6 different coastal towns—4 of them physically exposed to the oil spill, 2 unexposed—was undertaken. The towns were known to be psychologically homogeneous before the incident. Perceived risk was used as a measure of psychological exposure. Anxiety, depression and symptom reporting were used as measures of health impact.
Participants
1089 (69%) men and women aged 18–65 years responded.
Main results
Perceived risk was associated with raised anxiety and non‐toxicologically related symptom reporting, whereas physical exposure to oil was only associated with toxicologically related symptom reporting. The impact of raised perceived risk on the population was greater than that of physical oil exposure, involving more persons over a wider area.
Conclusions
Psychological exposure was shown to be quantifiable, and to be a substantially more sensitive measure of health impact than physical exposure in relation to psychological outcomes. This type of analysis has important implications for emergency response planning, and for the interpretation of a complex emergency by the general public.
doi:10.1136/jech.2006.046987
PMCID: PMC2465723  PMID: 17496259
24.  The Consumption of Milk and Dairy Foods and the Incidence of Vascular Disease and Diabetes: An Overview of the Evidence 
Lipids  2010;45(10):925-939.
The health effects of milk and dairy food consumption would best be determined in randomised controlled trials. No adequately powered trial has been reported and none is likely because of the numbers required. The best evidence comes, therefore, from prospective cohort studies with disease events and death as outcomes. Medline was searched for prospective studies of dairy food consumption and incident vascular disease and Type 2 diabetes, based on representative population samples. Reports in which evaluation was in incident disease or death were selected. Meta-analyses of the adjusted estimates of relative risk for disease outcomes in these reports were conducted. Relevant case–control retrospective studies were also identified and the results are summarised in this article. Meta-analyses suggest a reduction in risk in the subjects with the highest dairy consumption relative to those with the lowest intake: 0.87 (0.77, 0.98) for all-cause deaths, 0.92 (0.80, 0.99) for ischaemic heart disease, 0.79 (0.68, 0.91) for stroke and 0.85 (0.75, 0.96) for incident diabetes. The number of cohort studies which give evidence on individual dairy food items is very small, but, again, there is no convincing evidence of harm from consumption of the separate food items. In conclusion, there appears to be an enormous mis-match between the evidence from long-term prospective studies and perceptions of harm from the consumption of dairy food items.
doi:10.1007/s11745-010-3412-5
PMCID: PMC2950929  PMID: 20397059
Dairy; Milk; Butter; Cheese; Heart disease; Stroke; Diabetes; Cohort studies

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