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OBJECTIVE To evaluate the association of Jewish cultural and religious identity and denominational affiliation with interest in, intention to undertake and uptake of population-based BRCA (Breast Cancer Gene)-testing. DESIGN Cohort-study set within recruitment to GCaPPS-trial (ISRCTN73338115). SETTING London Ashkenazi-Jewish (AJ) population. POPULATION OR SAMPLE AJ men and women, >18 years. METHODS Participants were self-referred, and attended recruitment clinics (clusters) for pre-test counselling. Subsequently consenting individuals underwent BRCA testing. Participants self-identified to one Jewish denomination: Conservative/Liberal/Reform/Traditional/Orthodox/Unaffiliated. Validated scales measured Jewish Cultural-Identity (JI) and Jewish Religious-identity (JR). Four-item Likert-scales analysed initial 'interest' and 'intention to test' pre-counselling. Item-Response-Theory and graded-response models, modelled responses to JI and JR scales. Ordered/multinomial logistic regression modelling evaluated association of JI-scale, JR-scale and Jewish Denominational affiliation on interest, intention and uptake of BRCA testing. MAIN OUTCOME MEASURES Interest, intention, uptake of BRCA testing. RESULTS In all, 935 AJ women/men of mean age = 53.8 (S.D = 15.02) years, received pre-test education and counselling through 256 recruitment clinic clusters (median cluster size = 3). Denominational affiliations included Conservative/Masorti = 91 (10.2%); Liberal = 82 (9.2%), Reform = 135 (15.1%), Traditional = 212 (23.7%), Orthodox = 239 (26.7%); and Unaffiliated/Non-practising = 135 (15.1%). Overall BRCA testing uptake was 88%. Pre-counselling, 96% expressed interest and 60% intention to test. JI and JR scores were highest for Orthodox, followed by Conservative/Masorti, Traditional, Reform, Liberal and Unaffiliated Jewish denominations. Regression modelling showed no significant association between overall Jewish Cultural or Religious Identity with either interest, intention or uptake of BRCA testing. Interest, intention and uptake of BRCA testing was not significantly associated with denominational affiliation. CONCLUSIONS Jewish religious/cultural identity and denominational affiliation do not appear to influence interest, intention or uptake of population-based BRCA testing. BRCA testing was robust across all Jewish denominations. TWEETABLE ABSTRACT Jewish cultural/religious factors do not affect BRCA testing, with robust uptake seen across all denominational affiliations.

Ovarian cancer is the fifth most common cancer in UK women, and the leading cause of gynaecological cancer death. Five-year survival rates, of around 40%, have shown little improvement despite recent advances in cancer treatment. Mutations in the cancer susceptibility genes BRCA1 and BRCA2 confer lifetime risks of breast and ovarian cancer of up to 80% and 40% respectively. The traditional approach of using cancer family history to select patients for genetic testing is being challenged; up to 44% of BRCA mutation carriers do not have a significant family history. Recent research has shown that offering BRCA testing to all women with high grade non-mucinous ovarian cancer is an effective approach to identifying more BRCA carriers. Furthermore, there is an opportunity to prevent ovarian cancer if women at increased risk can be identified before developing the disease. This article is protected by copyright. All rights reserved.

BackgroundThe UK guideline recommends 3-yearly surveillance for patients with intermediate-risk (IR) adenomas. No study has examined whether or not this group has heterogeneity in surveillance needs.ObjectivesTo examine the effect of surveillance on colorectal cancer (CRC) incidence; assess heterogeneity in risk; and identify the optimum frequency of surveillance, the psychological impact of surveillance, and the cost-effectiveness of alternative follow-up strategies.DesignRetrospective multicentre cohort study.SettingRoutine endoscopy and pathology data from 17 UK hospitals (n = 11,944), and a screening data set comprising three pooled cohorts (n = 2352), followed up using cancer registries.SubjectsPatients with IR adenoma(s) (three or four small adenomas or one or two large adenomas).Primary outcomesAdvanced adenoma (AA) and CRC detected at follow-up visits, and CRC incidence after baseline and first follow-up.MethodsThe effects of surveillance on long-term CRC incidence and of interval length on findings at follow-up were examined using proportional hazards and logistic regression, adjusting for patient, procedural and polyp characteristics. Lower-intermediate-risk (LIR) subgroups and higher-intermediate-risk (HIR) subgroups were defined, based on predictors of CRC risk. A model-based cost–utility analysis compared 13 surveillance strategies. Between-group analyses of variance were used to test for differences in bowel cancer worry between screening outcome groups (n = 35,700). A limitation of using routine hospital data is the potential for missed examinations and underestimation of the effect of interval and surveillance.ResultsIn the hospital data set, 168 CRCs occurred during 81,442 person-years (pys) of follow-up [206 per 100,000 pys, 95% confidence interval (CI) 177 to 240 pys]. One surveillance significantly lowered CRC incidence, both overall [hazard ratio (HR) 0.51, 95% CI 0.34 to 0.77] and in the HIR subgroup (n = 9265; HR 0.50, 95% CI 0.34 to 0.76). In the LIR subgroup (n = 2679) the benefit of surveillance was less clear (HR 0.62, 95% CI 0.16 to 2.43). Additional surveillance lowered CRC risk in the HIR subgroup by a further 15% (HR 0.36, 95% CI 0.20 to 0.62). The odds of detecting AA and CRC at first follow-up (FUV1) increased by 18% [odds ratio (OR) 1.18, 95% CI 1.12 to 1.24] and 32% (OR 1.32, 95% CI 1.20 to 1.46) per year increase in interval, respectively, and the odds of advanced neoplasia at second follow-up increased by 22% (OR 1.22, 95% CI 1.09 to 1.36), after adjustment. Detection rates of AA and CRC remained below 10% and 1%, respectively, with intervals to 3 years. In the screening data set, 32 CRCs occurred during 25,745 pys of follow-up (124 per 100,000 pys, 95% CI 88 to 176 pys). One follow-up conferred a significant 73% reduction in CRC incidence (HR 0.27, 95% CI 0.10 to 0.71). Owing to the small number of end points in this data set, no other outcome was significant. Although post-screening bowel cancer worry was higher in people who were offered surveillance, worry was due to polyp detection rather than surveillance. The economic evaluation, using data from the hospital data set, suggested that 3-yearly colonoscopic surveillance without an age cut-off would produce the greatest health gain.ConclusionsA single surveillance benefited all IR patients by lowering their CRC risk. We identified a higher-risk subgroup that benefited from further surveillance, and a lower-risk subgroup that may require only one follow-up. A surveillance interval of 3 years seems suitable for most IR patients. These findings should be validated in other studies to confirm whether or not one surveillance visit provides adequate protection for the lower-risk subgroup of intermediate-risk patients.Study registrationCurrent Controlled Trials ISRCTN15213649.FundingThe National Institute for Health Research Health Technology Assessment programme.

BackgroundBowel cancer screening reduces cancer-specific mortality. There is a socioeconomic gradient in the uptake of the English NHS Bowel Cancer Screening Programme (BCSP), which may lead to inequalities in cancer outcomes.ObjectiveTo reduce socioeconomic inequalities in uptake of the NHS BCSP’s guaiac faecal occult blood test (gFOBt) without compromising uptake in any socioeconomic group.DesignWorkstream 1 explored psychosocial determinants of non-uptake of gFOBt in focus groups and interviews. Workstream 2 developed and tested four theoretically based interventions: (1) ‘gist’ information, (2) a ‘narrative’ leaflet, (3) ‘general practice endorsement’ (GPE) and (4) an ‘enhanced reminder’ (ER). Workstream 3 comprised four national cluster randomised controlled trials (RCTs) of the cost-effectiveness of each intervention.MethodsInterventions were co-designed with user panels, user tested using interviews and focus groups, and piloted with postal questionnaires. RCTs compared ‘usual care’ (existing NHS BCSP invitations) with usual care plus each intervention. The four trials tested: (1) ‘gist’ leaflet (n = 163,525), (2) ‘narrative’ leaflet (n = 150,417), (3) GPE on the invitation letter (n = 265,434) and (4) ER (n = 168,480). Randomisation was based on day of mailing of the screening invitation. The Index of Multiple Deprivation (IMD) score associated with each individual’s home address was used as the marker of socioeconomic circumstances (SECs). Change in the socioeconomic gradient in uptake (interaction between treatment group and IMD quintile) was the primary outcome. Screening uptake was defined as the return of a gFOBt kit within 18 weeks of the invitation that led to a ‘definitive’ test result of either ‘normal’ (i.e. no further investigation required) or ‘abnormal’ (i.e. requiring referral for further testing). Difference in overall uptake was the secondary outcome.ResultsThe gist and narrative trials showed no effect on the SECs gradient or overall uptake (57.6% and 56.7%, respectively, compared with 57.3% and 58.5%, respectively, for usual care; allp-values > 0.05). GPE showed no effect on the gradient (p = 0.5) but increased overall uptake [58.2% vs. 57.5% in usual care, odds ratio (OR) = 1.07, 95% confidence interval (CI) 1.04 to 1.10;p p = 0.005), with a stronger effect in the most deprived IMD quintile (14.1% vs. 13.3% in usual care, OR = 1.11, 95% CI 1.04 to 1.20;p = 0.003) than the least deprived (34.7% vs. 34.9% in usual care OR = 1.00, 95% CI 0.94 to 1.06;p = 0.98), and higher overall uptake (25.8% vs. 25.1% in usual care, OR = 1.07, 95% CI 1.03 to 1.11;p = 0.001). All interventions were inexpensive to provide.LimitationsIn line with NHS policy, the gist and narrative leaflets supplemented rather than replaced existing NHS BCSP information. This may have undermined their effect.ConclusionsEnhanced reminder reduced the gradient and modestly increased overall uptake, whereas GPE increased overall uptake but did not reduce the gradient. Therefore, given their effectiveness and very low cost, the findings suggest that implementation of both by the NHS BCSP would be beneficial. The gist and narrative results highlight the challenge of achieving equitable delivery of the screening offer when all communication is written; the format is universal and informed decision-making mandates extensive medical information.Future workSocioculturally tailored research to promote communication about screening with family and friends should be developed and evaluated.Trial registrationCurrent Controlled Trials ISRCTN74121020.FundingThis project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full inProgramme Grants for Applied Research; Vol. 5, No. 8. See the NIHR Journals Library website for further project information.

Objectives:Randomised controlled trials are required to address causality in the reported associations between maternal influences and offspring adiposity. The aim of this study was to determine whether an antenatal lifestyle intervention, associated with improvements in maternal diet and reduced gestational weight gain (GWG) in obese pregnant women leads to a reduction in infant adiposity and sustained improvements in maternal lifestyle behaviours at 6 months postpartum.Subjects and methods:We conducted a planned postnatal follow-up of a randomised controlled trial (UK Pregnancies Better Eating and Activity Trial (UPBEAT)) of a complex behavioural intervention targeting maternal diet (glycaemic load (GL) and saturated fat intake) and physical activity in 1555 obese pregnant women. The main outcome measure was infant adiposity, assessed by subscapular and triceps skinfold thicknesses. Maternal diet and physical activity, indices of the familial lifestyle environment, were assessed by questionnaire.Results:A total of 698 (45.9%) infants (342 intervention and 356 standard antenatal care) were followed up at a mean age of 5.92 months. There was no difference in triceps skinfold thickness z-scores between the intervention vs standard care arms (difference −0.14 s.d., 95% confidence interval −0.38 to 0.10, P=0.246), but subscapular skinfold thickness z-score was 0.26 s.d. (−0.49 to −0.02; P=0.03) lower in the intervention arm. Maternal dietary GL (−35.34; −48.0 to −22.67; P

Rationale: Low uptake of low-dose computed tomography (LDCT) lung cancer screening, particularly by current smokers of a low socioeconomic position, compromises effectiveness and equity. Objectives: To compare the effect of a targeted, low-burden, and stepped invitation strategy versus control on uptake of hospital-based Lung Health Check appointments offering LDCT screening. Methods: In a two-arm, blinded, between-subjects, randomized controlled trial, 2,012 participants were selected from 16 primary care practices using these criteria: 1) aged 60 to 75 years, 2) recorded as a current smoker within the last 7 years, and 3) no prespecified exclusion criteria contraindicating LDCT screening. Both groups received a stepped sequence of preinvitation, invitation, and reminder letters from their primary care practitioner offering prescheduled appointments. The key manipulation was the accompanying leaflet. The intervention group’s leaflet targeted psychological barriers and provided low-burden information, mimicking the concept of the U.K. Ministry of Transport’s annual vehicle test (“M.O.T. For Your Lungs”). Measurements and Main Results: Uptake was 52.6%, with no difference between intervention (52.3%) and control (52.9%) groups in unadjusted (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.82–1.16) or adjusted (OR, 0.98; 95% CI, 0.82–1.17) analyses. Current smokers were less likely to attend (adjusted OR, 0.70; 95% CI, 0.56–0.86) than former smokers. Socioeconomic deprivation was significantly associated with lower uptake for the control group only (P

Background Cancer screening is a behavior that represents investment in future health. Such investment may depend on how much ‘future’ a person expects. Purpose The purpose of this study was to investigate the prospective association between perceived personal life expectancy and participation in fecal occult blood test screening for colorectal cancer (CRC) in a national program. Methods Data were from interviews with 3975 men and women in the English Longitudinal Study of Ageing (ELSA) within the eligible age range for the national screening program (60 to 74 years). Perceived life expectancy was indexed as the individual’s estimate of their chance of living another 10–15 years (exact time varied by age), assessed in 2008/2009. Participation in CRC screening from 2010 to 2012/2013 was assessed in 2012/2013. Logistic regression was used to estimate the association between perceived life expectancy and screening participation, adjusted for numeracy and known mortality risk factors. Results Overall, 71% of respondents (2817/3975) reported completing at least one fecal occult blood test (FOBt) during the follow-up. Screening uptake was 76% (1272/1683) among those who estimated their 10–15-year life expectancy as 75–100%, compared with 52% (126/243) among those who estimated theirs as 0–25% (adjusted OR 1.74, 95% CI 1.29–2.34). Conclusions A longer perceived life expectancy is associated with greater likelihood of participating in CRC screening in England. However, half of people with a low perceived life expectancy still participated in screening. Given that CRC screening is recommended for adults with a remaining life expectancy of ≥10 years, future research should investigate how to communicate the aims of screening more effectively.

It is important that teenage and young adult (TYA) cancer survivors adopt a healthy lifestyle, since health vulnerabilities associated with their diagnosis and treatment may be exacerbated by poor health behaviors. This review aims to synthesize the current literature on health behavior change interventions created specifically for TYA-aged cancer survivors.MEDLINE, EMBASE, PsycINFO, and CINAHL databases were searched for studies investigating interventions targeting one or more health behaviors, including: physical activity, diet, smoking cessation, and alcohol consumption. Studies were eligible for review if the study population were defined as TYA cancer survivors and the mean age of the sample was younger than 30 years of age.Twelve studies were identified, of which nine were randomized controlled trials. Physical activity was the most commonly targeted health behavior. Six of the 12 interventions included within this review were successful in changing health behavior. Due to the heterogeneity of intervention characteristics, the relationship between intervention efficacy or outcome and intervention content, delivery mode, or theoretical framework was not discernible. Nevertheless, trends emerged relating to the delivery and content of health behavior interventions designed specifically for TYA cancer survivors.More research is required to identify the most effective means of promoting health behavior change among the TYA cancer survivor population. Specifically, future research should focus on providing evidence of the efficiency and feasibility of interventions that use online technologies to facilitate remote intervention delivery and peer support.

BACKGROUND: Physical activity reduces the risk of morbidity and high sedentary time may be associated with negative health outcomes. The workplace offers an arena to promote physical activity and reduce sedentary time, but existing workplace-based interventions have typically yielded small effects. AIMS: To collate the literature on correlates of occupational physical activity and sedentary behaviour and to inform future novel approaches to workplace-based intervention or policy. METHODS: Systematic literature searches were conducted in December 2014 using multiple databases. Identified papers were screened against an inclusion criterion. Papers were deemed eligible for this review if they included occupational physical activity and sedentary behaviour as an outcome, were quantitative observational studies and included an adult working population. Identified correlates of occupational physical activity and sedentary behaviour were organized into levels of the socioecological model. RESULTS: Forty studies met the inclusion criterion. A higher number of studies included only occupational physical activity, not sedentary time, as an outcome and were carried out in the USA and Australia. The review identified that white-collar workers are at greater risk of low occupational physical activity and high sedentary time. The majority of correlates found to be associated with occupational physical activity and sedentary time were intrapersonal and non-modifiable. CONCLUSIONS: Intervention efforts to increase occupational physical activity and reduce sedentary time may be most effective when targeted at white-collar workers. Research is needed to identify additional modifiable correlates of occupational physical activity and sedentary behaviour, in white-collar workers.

Chemoprevention is a risk reduction option for women who have increased risk of breast cancer. Selective Estrogen Receptor Modulators (SERMs) have been extensively tested, and alternative agents are being evaluated. Long-term adherence to chemoprevention is critical to obtaining the drug's full benefit. We systematically reviewed articles reporting uptake rates and adherence among healthy adult women, who were prescribed medication to prevent primary breast cancer. We also extracted data on the clinical, socio-demographic and psychological predictors of uptake and adherence. Searches were performed in PubMed, CINAHL, EMBASE, and PsychInfo, yielding 3851 unique articles. Title, abstract and full text screening left 53 articles that met inclusion criteria, and a further 4 studies were identified from reference lists, giving a total of 57. The mean quality score using the Mixed Methods Appraisal Tool was 3 out of 4. Thirty-one articles reported uptake, of which 14 tested predictors, and 23 reported adherence of which 11 tested predictors. Seven studies reported qualitative data. Most studies (50) involved SERMs, but 5 tested Aromatase Inhibitors, 1 tested Aspirin, 1 tested a statin. Twenty studies included data from a clinical setting, 35 reported trial data, and 2 reported both. Twenty-four studies reporting 26 instances of uptake in 21,423 women were included in a meta-analysis. The pooled uptake estimate was 16.3% (95% CI, 13.6-19.0), with high heterogeneity (I^2=98.9%, p Chemoprevention uptake for the prevention of breast cancer is low, and long-term adherence is often insufficient for the full preventive effect. Uptake rates were higher in trials than in clinical settings, suggesting further work should focus on implementing chemoprevention within routine patient care. Further research is warranted to identify factors amenable to modification and to improve informed decision-making surrounding chemoprevention. Citation Format: Smith SG, Sestak I, Forster A, Partridge A, Side L, Horne R, Wardle J, Cuzick J. Factors affecting uptake and adherence to breast cancer chemoprevention: A systematic review and meta-analysis. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD1-08.

Objective To evaluate demographic and clinical variables as predictors of nasal high-flow treatment success in newborn infants with respiratory distress cared for in Australian nontertiary special care nurseries. Study design A secondary analysis of the HUNTER trial, a multicenter, randomized controlled trial evaluating nasal high-flow as primary respiratory support for newborn infants with respiratory distress who were born ≥31 weeks of gestation and with birth weight ≥1200 g, and cared for in Australian nontertiary special care nurseries. Treatment success within 72 hours after randomization to nasal high-flow was determined using objective criteria. Univariable screening and multivariable analysis was used to determine predictors of nasal high-flow treatment success. Results Infants (n = 363) randomized to nasal high-flow in HUNTER were included in the analysis; the mean gestational age was 36.9 ± 2.7 weeks and birth weight 2928 ± 782 g. Of these infants, 290 (80%) experienced nasal high-flow treatment success. On multivariable analysis, nasal high-flow treatment success was predicted by higher gestational age and lower fraction of inspired oxygen immediately before randomization, but not strongly. The final model was found to have an area under the curve of 0.65, which after adjustment for optimism was found to be 0.63 (95% CI, 0.57-0.70). Conclusions Gestational age and supplemental oxygen requirement may be used to guide decisions regarding the most appropriate initial respiratory support for newborn infants in nontertiary special care nurseries. Further prospective research is required to better identify which infants are most likely to be successfully treated with nasal high-flow. Trial registration ACTRN12614001203640.

BACKGROUND: Behavioural interventions might improve clinical outcomes in pregnant women who are obese. We aimed to investigate whether a complex intervention addressing diet and physical activity could reduce the incidence of gestational diabetes and large-for-gestational-age infants.METHODS: The UK Pregnancies Better Eating and Activity Trial (UPBEAT) is a randomised controlled trial done at antenatal clinics in eight hospitals in multi-ethnic, inner-city locations in the UK. We recruited pregnant women (15-18 weeks plus 6 days of gestation) older than 16 years who were obese (BMI ≥30 kg/m(2)). We randomly assigned participants to either a behavioural intervention or standard antenatal care with an internet-based, computer-generated, randomisation procedure, minimising by age, ethnic origin, centre, BMI, and parity. The intervention was delivered once a week through eight health trainer-led sessions. Primary outcomes were gestational diabetes (diagnosed with an oral glucose tolerance test and by criteria from the International Association of Diabetes in Pregnancy Study Groups) and large-for-gestational-age infants (≥90th customised birthweight centile). Analysis was by intention to treat. This trial is registered with Current Controlled Trials, ISCRTN89971375. Recruitment and pregnancy outcomes are complete but childhood follow-up is ongoing.FINDINGS: Between March 31, 2009, and June 2, 2014, we assessed 8820 women for eligibility and recruited 1555, with a mean BMI of 36·3 kg/m(2) (SD 4·8). 772 were randomly assigned to standard antenatal care and 783 were allocated the behavioural intervention, of which 651 and 629 women, respectively, completed an oral glucose tolerance test. Gestational diabetes was reported in 172 (26%) women in the standard care group compared with 160 (25%) in the intervention group (risk ratio 0·96, 95% CI 0·79-1·16; p=0·68). 61 (8%) of 751 babies in the standard care group were large for gestational age compared with 71 (9%) of 761 in the intervention group (1·15, 0·83-1·59; p=0·40). Thus, the primary outcomes did not differ between groups, despite improvements in some maternal secondary outcomes in the intervention group, including reduced dietary glycaemic load, gestational weight gain, and maternal sum-of-skinfold thicknesses, and increased physical activity. Adverse events included neonatal death (two in the standard care group and three in the intervention group) and fetal death in utero (ten in the standard care group and six in the intervention group). No maternal deaths were reported. Incidence of miscarriage (2% in the standard care group vs 2% in the intervention group), major obstetric haemorrhage (1% vs 3%), and small-for-gestational-age infants (≤5th customised birthweight centile; 6% vs 5%) did not differ between groups.INTERPRETATION: A behavioural intervention addressing diet and physical activity in women with obesity during pregnancy is not adequate to prevent gestational diabetes, or to reduce the incidence of large-for-gestational-age infants.FUNDING: National Institute for Health Research, Guys and St Thomas' Charity, Chief Scientist Office Scotland, Tommy's Charity.

Objective To compare self-reported with objectively recorded participation in Faecal Occult Blood testing (FOBt) colorectal cancer (CRC) screening in a national programme. Methods Survey respondents living in England who were eligible for screening were asked in face-to-face interviews if they had ever been invited to do a CRC screening test, how many times they had been invited, and how many times they had participated. National Health Service (NHS) Bowel Cancer Screening Programme (BCSP) records were consulted for respondents who had consented to a record check. The outcome measures were ‘ever uptake’ (responded to ≥1 invitation), ‘repeat uptake’ (responded to ≥2 invitations), and ‘consistent uptake’ (responded to all invitations). Results In the verified group, self-reported ever uptake was highly consistent with recorded ever uptake (87.0% vs. 87.8%). Among those who indicated that they had been invited more than once, self-reported repeat uptake was 89.8% compared with 84.8% recorded repeat uptake. Among those with more than one recorded invitation, self-reported repeat uptake was 72.7% compared with 77.2% recorded repeat uptake, and self-reported consistent uptake was 81.6% compared with 65.6% recorded consistent uptake. Conclusion Our results suggest that people can accurately report whether they have ever taken part in CRC screening. The vast majority of those whose records were verified could also accurately report whether they had taken part in screening at least twice. They were somewhat less accurate in reporting whether they had responded to all screening invitations.

Objective To examine uptake in the first six pilot centres of the English Bowel Scope Screening (BSS) programme, which began in early 2013 and invites adults aged 55 for a one off Flexible Sigmoidoscopy. Methods Between March 2013 and May 2014 the six pilot centres sent 21,187 invitations. Using multivariate logistic regression analysis, we examined variation in uptake by gender, socioeconomic deprivation (using the Index of Multiple Deprivation), area-based ethnic diversity (proportion of non-white residents), screening centre, and appointment time (routine: daytime vs out-of-hours: evening/weekend). Results Uptake was 43.1%. Men were more likely to attend than women (45% vs 42%; OR 1.136, 95% CI 1.076, 1.199, p Conclusion Early indications of uptake are encouraging. Future efforts should focus on increasing public awareness of the programme and reducing socioeconomic inequalities.

Objective: To qualitatively explore associations between emotional responses to experience of cancer 'alarm' symptoms and help-seeking in a community sample of adults. Method: Interviewees (n=62) were recruited from a community sample (n=2042) of adults aged ≥50 years, who had completed a health survey that included a list of cancer alarm symptoms. Participants who had reported an alarm symptom both at baseline and 3-month follow-up (n=271), and who had consented to contact (n=215), constituted the pool for invitations to interview. Results: Over a third of participants (37%) described an emotional response to their symptom experience. In all these cases, there was evidence of awareness of the risk of cancer. Emotional responses were usually either classified as mild ('worry') or severe ('fear'). Worry was often described in the context of a desire to seek medical help, either to rule out cancer or to minimise patient delay. In contrast, the 'fear' group described associations with death, the perceived incurability of cancer, and the consequence of a cancer diagnosis. Where the emotional reaction was fear, medical contact was seen as something to be avoided either because it had no value or because it was preferable not to be told a diagnosis. Conclusion: In this community sample, worry about the possibility of cancer was associated with help-seeking, either for reassurance or as part of a 'sensible' strategy to deal with the risk. In contrast, fear was associated with avoiding help-seeking or even thinking about cancer, which could lead to prolonged help-seeking intervals.

Objective Health policy in the UK is committed to tackling inequalities in cancer screening participation. We examined whether socioeconomic inequalities in breast and cervical cancer screening participation in England have reduced over five years. Methods Cross-sectional analyses compared cervical and breast screening coverage between 2007/8 and 2012/13 in Primary Care Trusts (PCTs) in England in relation to area-level income deprivation. Results At the start and the end of this five year period, there were socioeconomic inequalities in screening coverage for breast and cervical screening. Inequalities were highest for breast screening. Over time, the coverage gap between the highest and lowest quintiles of income deprivation significantly reduced for breast screening (from 12.3 to 8.3 percentage points), but not for cervical screening (5.3 to 4.9 percentage points). Conclusions Efforts to reduce screening inequalities appear to have resulted in a significant improvement in equitable delivery of breast screening, although not of cervical screening. More work is needed to understand the differences, and see whether broader lessons can be learned from the reduction of inequalities in breast screening participation.

The nature of cancer control is changing, with an increasing emphasis, fuelled by public and political demand, on prevention, early diagnosis, and patient experience during and after treatment. At the same time, primary care is increasingly promoted, by governments and health funders worldwide, as the preferred setting for most health care for reasons of increasing need, to stabilise health-care costs, and to accommodate patient preference for care close to home. It is timely, then, to consider how this expanding role for primary care can work for cancer control, which has long been dominated by highly technical interventions centred on treatment, and in which the contribution of primary care has been largely perceived as marginal. In this Commission, expert opinion from primary care and public health professionals with academic and clinical cancer expertise-from epidemiologists, psychologists, policy makers, and cancer specialists-has contributed to a detailed consideration of the evidence for cancer control provided in primary care and community care settings. Ranging from primary prevention to end-of-life care, the scope for new models of care is explored, and the actions needed to effect change are outlined. The strengths of primary care-its continuous, coordinated, and comprehensive care for individuals and families-are particularly evident in prevention and diagnosis, in shared follow-up and survivorship care, and in end-of-life care. A strong theme of integration of care runs throughout, and its elements (clinical, vertical, and functional) and the tools needed for integrated working are described in detail. All of this change, as it evolves, will need to be underpinned by new research and by continuing and shared multiprofessional development.

The double burden of under- and overnutrition profoundly affects human health globally. According to the World Health Organization, obesity and diabetes rates have almost doubled worldwide since 1980, and, in 2011, more than 40 million children under 5 years of age were overweight. Ecologic factors, parental genetics and fitness, and the intrauterine environment significantly influence the likelihood of offspring developing the dysmetabolic diathesis of obesity. This report examines the effects of these factors, including preconception, intrauterine and postnatal energy balance affecting programming of transgenerational transmission, and development of chronic diseases later in life-in particular, diabesity and its comorbidities.

Summary Prevention of obesity requires policies that work. In this Series paper, we propose a new way to understand how food policies could be made to work more effectively for obesity prevention. Our approach draws on evidence from a range of disciplines (psychology, economics, and public health nutrition) to develop a theory of change to understand how food policies work. We focus on one of the key determinants of obesity: diet. The evidence we review suggests that the interaction between human food preferences and the environment in which those preferences are learned, expressed, and reassessed has a central role. We identify four mechanisms through which food policies can affect diet: providing an enabling environment for learning of healthy preferences, overcoming barriers to the expression of healthy preferences, encouraging people to reassess existing unhealthy preferences at the point-of-purchase, and stimulating a food-systems response. We explore how actions in three specific policy areas (school settings, economic instruments, and nutrition labelling) work through these mechanisms, and draw implications for more effective policy design. We find that effective food-policy actions are those that lead to positive changes to food, social, and information environments and the systems that underpin them. Effective food-policy actions are tailored to the preference, behavioural, socioeconomic, and demographic characteristics of the people they seek to support, are designed to work through the mechanisms through which they have greatest effect, and are implemented as part of a combination of mutually reinforcing actions. Moving forward, priorities should include comprehensive policy actions that create an enabling environment for infants and children to learn healthy food preferences and targeted actions that enable disadvantaged populations to overcome barriers to meeting healthy preferences. Policy assessments should be carefully designed on the basis of a theory of change, using indicators of progress along the various pathways towards the long-term goal of reducing obesity rates.

Background: Screening using fecal occult blood testing (FOBt) reduces colorectal cancer mortality, but the test has low sensitivity. A “missed” cancer may cause psychologic harms in the screened population that partially counteract the benefits of early detection. Methods: Three hundred and eleven people diagnosed with colorectal cancer (i) after a negative FOBt result (interval cancer), (ii) a positive result (screen-detected cancer), or (iii) in regions where screening was not offered, completed questions on quality of life (FACT-C), depression (CES-D), perceived diagnostic delay, and trust in the results of FOBt screening. Fifteen withheld consent to data matching with medical records, leaving a sample size of 296. Results: Controlling for demographic and clinical variables, patients with an interval cancer reported poorer quality of life (difference in means = 6.16, P = 0.03) and more diagnostic delay (OR, 0.37; P = 0.02) than patients with screen-detected disease, with no differences in depression. No differences were observed between the interval cancer group and the group not offered screening on these measures. Patients with an interval cancer reported the lowest levels of trust in FOBt. Conclusions: An interval cancer has adverse effects on trust in FOBt, but does not result in worse psychologic outcomes compared with people diagnosed in areas with no screening program. People with an interval cancer report poorer quality of life than people with screen-detected disease. Impact: Improvements in test sensitivity could improve quality of life among people who complete an FOB test over and above any benefits already conferred by earlier detection. Cancer Epidemiol Biomarkers Prev; 24(7); 1–7. ©2015 AACR .

Background: Fatalistic beliefs may be implicated in longer help-seeking intervals, and consequently, greater risk of advanced stage at cancer diagnosis. Methods: We examined associations between fatalism and stage at diagnosis in a population-based cohort of 4,319 U.S. patients with newly diagnosed lung or colorectal cancer participating in the Cancer Care Outcomes and Research Surveillance (CanCORS) study. Fatalistic beliefs were assessed with an established measure. A fatalism score (range, 4–16) was created by summing Likert scale responses to four items. Cancer stage at diagnosis was abstracted from medical records by trained staff. Logistic regression was used to assess the association between fatalism score and advanced stage at diagnosis (IV vs. I–III), adjusting for sociodemographic and clinical characteristics. Results: Overall, 917 (21%) patients had stage IV cancers (lung: 28%, colorectal: 16%). The mean fatalism score was 10.7 (median = 11; interquartile range, 9–12). In adjusted analyses, a higher fatalism score was associated with greater odds of stage IV diagnosis (OR per unit increase in fatalism = 1.05; 95% confidence interval 1.02–1.08; P = 0.003). Patients with the highest fatalism score had an adjusted 8.9% higher frequency of stage IV diagnosis compared with patients with the lowest score (25.4% vs. 16.5%). Discussion: In this large and socioeconomically, geographically, and ethnically diverse population of patients with lung and colorectal cancer, fatalistic beliefs were associated with higher risk of advanced stage at diagnosis. Longitudinal studies are needed to confirm causation. Impact: These findings support the value of incorporating information about the curability of early-stage cancers in public education campaigns. Cancer Epidemiol Biomarkers Prev; 24(4); 720–6. ©2015 AACR.

Background: Cancer fear has been associated with higher and lower screening uptake across different studies, possibly because different aspects of cancer fear have different effects on intentions versus behavior. The present study examined associations of three aspects of cancer fear with intention and uptake of endoscopic screening for colorectal cancer. Methods: A subsample of UK Flexible Sigmoidoscopy (FS) Trial participants received a baseline questionnaire that included three cancer fear items from a standard measure asking if: (i) cancer was feared more than other diseases, (ii) cancer worry was experienced frequently, and (iii) thoughts about cancer caused discomfort. Screening intention was assessed by asking participants whether, if invited, they would accept an invitation for FS screening. Positive responders were randomized to be invited or not in a 1:2 ratio. The behavioral outcome was clinic-recorded uptake. Control variables were age, gender, ethnicity, education, and marital status. Results: The questionnaire return rate was 60% (7,971/13,351). The majority (82%) intended to attend screening; 1,920 were randomized to receive an invitation, and 71% attended. Fearing cancer more than other diseases (OR = 2.32, P < 0.01) and worrying a lot about cancer (OR = 2.34, P < 0.01) increased intentions to attend screening, but not uptake. Finding thoughts about cancer uncomfortable did not influence intention, but predicted lower uptake (OR = 0.72, P < 0.01). Conclusions: Different aspects of cancer fear have different effects on the decision and action processes leading to screening participation. Impact: Knowledge of the different behavioral effects of cancer fear may aid the design of effective public health messages. Cancer Epidemiol Biomarkers Prev; 24(2); 400–5. ©2015 AACR.

Kaprio, Jaakko/0000-0002-3716-2455; Knafo-Noam, Ariel/0000-0003-0613-1960; de Freitas, Duarte Luis/0000-0001-6642-3370; Haworth, Claire/0000-0002-8608-289X; Siribaddana, Sisira/0000-0001-5821-2557; Kyvik, Kirsten O/0000-0003-2981-0245; Aliev, Fazil/0000-0001-8357-4699; Craig, Jeffrey M/0000-0003-3979-7849; Ordonana, Juan R./0000-0001-7779-6017; Sund, Reijo/0000-0002-6268-8117; Bartels, Meike/0000-0002-9667-7555; Kandler, Christian/0000-0002-9175-235X; Fagnani, Corrado/0000-0001-5771-7772; Huibregtse, Brooke M./0000-0003-0977-7249; Montgomery, Grant W/0000-0002-4140-8139; Colodro-Conde, Lucia/0000-0002-9004-364X; Loos, Ruth J F/0000-0002-8532-5087; Busjahn, Andreas/0000-0001-9650-6919; ONCEL, Sevgi YURT/0000-0002-0990-292X; Christensen, Kaare/0000-0002-5429-5292; Martin, Nicholas/0000-0003-4069-8020; Tan, Qihua/0000-0003-3194-0030; ROMERA, JUAN FRANCISCO SANCHEZ/0000-0002-5405-6216; D'Ippolito, Cristina/0000-0001-7902-9380; Skytthe, Axel E/0000-0002-8629-4913; Tan, Qihua/0000-0003-3194-0030; Heikkila, Kauko/0000-0002-9256-8028; Duncan, Glen/0000-0001-6909-1869; Jelenkovic, Aline/0000-0002-6191-8371; Magnusson, Patrik/0000-0002-7315-7899; mangino, massimo/0000-0002-2167-7470; Medland, Sarah E/0000-0003-1382-380X; Saffery, Richard/0000-0002-9510-4181; Plomin, Robert/0000-0002-0756-3629; Harden, Kathryn/0000-0002-1557-6737; Hotopf, Matthew/0000-0002-3980-4466; McAdams, Tom/0000-0002-6825-3499; Aaltonen, Sari/0000-0002-2873-4263; Kremen, William/0000-0002-8629-5609; Pahlen, Shandell/0000-0003-0753-4155; Llewellyn, Clare/0000-0002-0066-2827; Franz, Carol/0000-0002-8987-1755; Derom, Catherine/0000-0001-5574-796X; Willemsen, Gonneke/0000-0003-3755-0236; Rasmussen, Finn/0000-0001-7915-7809; Rebato, Esther/0000-0003-1221-8501; lee, kayoung/0000-0002-2816-554X; Sodemann, Morten/0000-0001-8992-2500; Gatz, Margaret/0000-0002-1071-9970; Boivin, Michel/0000-0001-8621-9844; Silventoinen, Karri/0000-0003-1759-3079 WOS: 000358874400002 PubMed: 26014041 For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m(2)) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes. National Institute of Mental HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [R01 MH58354]; National Institute on AgingUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [1RO1-AG13662-01A2]; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R21 AG039572]; WT Grant Foundation; University of London Central Research fund; Medical Research CouncilMedical Research Council UK (MRC) [G81/343, G120/635]; Economic and Social Research CouncilEconomic & Social Research Council (ESRC) [RES-000-22-2206]; Institute of Social Psychiatry [06/07-11]; Leverhulme Research FellowshipLeverhulme Trust [RF/2/RFG/2008/0145]; Goldsmiths; University of London; National Research Foundation of KoreaNational Research Foundation of Korea [NRF-371-2011-1B00047]; Danish Agency for Science, Technology and Innovation; Research Council for Health and Disease; Velux Foundation; US National Institute of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [P01 AG08761]; Fund of Scientific Research, FlandersFWO; Twins, a non-profit Association for Scientific Research in Multiple Births (Belgium); Global Research Network Program of the National Research Foundation [NRF 2011-220-E00006]; NIDAUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Drug Abuse (NIDA) [DA011015]; Longitudinal Twin Study [HD10333]; National Institute of Health grantsUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [NIA R01 AG018384, R01 AG018386, R01 AG022381, R01 AG022982]; Cooperative Studies Program of the Office of Research AMP; Development of the United States Department of Veterans Affairs; Centre of Research Excellence from the National Health and Medical Research CouncilNational Health and Medical Research Council of Australia [1079102]; Michigan State University from the National Institute of Mental Health (NIMH) [R01-MH081813, R01-MH0820-54, R01-MH092377-02, R21-MH070542-01, R03-MH63851-01]; Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD) [R01-HD066040]; MSU Foundation [11-SPG-2518]; California Tobacco-Related Disease Research ProgramUniversity of California System [7RT-0134H, 8RT-0107H, 6RT-0354H]; The National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [1R01ESO15150-01]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81125007]; Australian National Health and Medical Research CouncilNational Health and Medical Research Council of Australia [437015, 607358]; Bonnie Babes Foundation [BBF20704]; Financial Markets Foundation for Children [032-2007]; Victorian Government's Operational Infrastructure Support Program; ENGAGE-European Network for Genetic and Genomic Epidemiology [201413]; National Institute of Alcohol Abuse and AlcoholismUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) [AA-12502, AA-00145, AA-09203]; Academy of Finland Center of Excellence in Complex Disease GeneticsAcademy of Finland [213506, 129680]; Academy of FinlandAcademy of Finland [100499, 205585, 118555, 141054, 265240, 263278, 264146]; Osaka University's International Joint Research Promotion Program; Kirikkale University Research Grant: KKUKirikkale University; TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [114C117]; European Research Council (ERC)European Research Council (ERC) [240994]; European Union's Seventh Framework Programmes ENGAGE ConsortiumEuropean Union (EU) [HEALTH-F4-2007-201413]; BioSHaRE EU [HEALTH-F4-2010-261433]; Seneca FoundationFundacion Seneca; Regional Agency for Science and Technology, Murcia, Spain [08633/PHCS/08, 15302/PHCS/10]; Ministry of Science and Innovation, SpainSpanish Government [PSI11560-2009]; UK Medical Research CouncilMedical Research Council UK (MRC) [G0901245]; UK Biotechnology and Biological Sciences Research CouncilBiotechnology and Biological Sciences Research Council (BBSRC) [31/D19086]; Portuguese agency for research (The Foundation for Science and Technology) [POCI/DES/56834/2004]; National Institutes of Health.United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 HD068435, R01 MH062375]; Wellcome TrustWellcome Trust; European Community's Seventh Framework ProgrammeEuropean Union (EU); National Institute for Health Research (NIHR) BioResource Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London; Netherlands Organization for Scientific Research (NWO)Netherlands Organization for Scientific Research (NWO); MagW/ZonMW [904-61-090, 985-10-002, 912-10-020, 904-61-193, 480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464-14192]; VU University's Institute for Health and Care Research (EMGO+); European Research CouncilEuropean Research Council (ERC) [ERC-230374]; Avera Institute, Sioux Falls, South Dakota (USA); Cancer Research UKCancer Research UK [C1418/A7974]; [5T32DA017637-10]; [NIH RC2 HL103416]; Cancer Research UKCancer Research UK [14133]; Medical Research CouncilMedical Research Council UK (MRC) [G0901245, MC_UU_12013/1]; NNF Center for Basic Metabolic ResearchNovo Nordisk Foundation [Metabolic Genetics]; Novo Nordisk FondenNovo NordiskNovo Nordisk Foundation [NNF10CC1016515] This study was conducted within the CODATwins project (Academy of Finland #266592). Support for participating twin projects: the University of Southern California Twin Study is funded by a grant from the National Institute of Mental Health (R01 MH58354). The Carolina African American Twin Study of Aging (CAATSA) was funded by a grant from the National Institute on Aging (grant 1RO1-AG13662-01A2) to K. E. Whitfield. The NAS-NRC Twin Registry acknowledges financial support from the National Institutes of Health grant number R21 AG039572. Waves 1-3 of Genesis 12-19 were funded by the WT Grant Foundation, the University of London Central Research fund and a Medical Research Council Training Fellowship (G81/343) and Career Development Award (G120/635) to Thalia C. Eley. Wave 4 was supported by grants from the Economic and Social Research Council (RES-000-22-2206) and the Institute of Social Psychiatry (06/07-11) to Alice M. Gregory who was also supported at that time by a Leverhulme Research Fellowship (RF/2/RFG/2008/0145). Wave 5 was supported by funding to Alice M. Gregory from Goldsmiths, University of London. Anthropometric measurements of the Hungarian twins were supported by Medexpert Ltd., Budapest, Hungary. South Korea Twin Registry is supported by National Research Foundation of Korea (NRF-371-2011-1B00047). The Danish Twin Registry is supported by the National Program for Research Infrastructure 2007 from the Danish Agency for Science, Technology and Innovation, The Research Council for Health and Disease, the Velux Foundation and the US National Institute of Health (P01 AG08761). Since its origin, the East Flanders Prospective Survey has been partly supported by grants from the Fund of Scientific Research, Flanders and Twins, a non-profit Association for Scientific Research in Multiple Births (Belgium). Korean Twin-Family Register was supported by the Global Research Network Program of the National Research Foundation (NRF 2011-220-E00006). The Colorado Twin Registry is funded by NIDA funded center grant DA011015 and Longitudinal Twin Study HD10333; Author Huibregtse is supported by 5T32DA017637-10. The Vietnam Era Twin Study of Aging was supported by National Institute of Health grants NIA R01 AG018384, R01 AG018386, R01 AG022381, and R01 AG022982, and, in part, with resources of the VA San Diego Center of Excellence for Stress and Mental Health. The Cooperative Studies Program of the Office of Research & Development of the United States Department of Veterans Affairs has provided financial support for the development and maintenance of the Vietnam Era Twin (VET) Registry. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIA/NIH, or the VA. The Australian Twin Registry is supported by a Centre of Research Excellence (grant ID 1079102) from the National Health and Medical Research Council administered by the University of Melbourne. The Michigan State University Twin Registry has been supported by Michigan State University, as well as grants R01-MH081813, R01-MH0820-54, R01-MH092377-02, R21-MH070542-01, R03-MH63851-01 from the National Institute of Mental Health (NIMH), R01-HD066040 from the Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD), and 11-SPG-2518 from the MSU Foundation. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIMH, the NICHD, or the National Institutes of Health.; r The California Twin Program was supported by The California Tobacco-Related Disease Research Program (7RT-0134H, 8RT-0107H, 6RT-0354H) and the National Institutes of Health (1R01ESO15150-01). The Guangzhou Twin Eye Study is supported by National Natural Science Foundation of China (grant #81125007). PETS was supported by grants from the Australian National Health and Medical Research Council (grant numbers 437015 and 607358 to JC, and RS), the Bonnie Babes Foundation (grant number BBF20704 to JMC), the Financial Markets Foundation for Children (grant no. 032-2007 to JMC), and by the Victorian Government's Operational Infrastructure Support Program. Data collection and analyses in Finnish twin cohorts have been supported by ENGAGE-European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007, grant agreement number 201413, National Institute of Alcohol Abuse and Alcoholism (grants AA-12502, AA-00145, and AA-09203 to R. J. Rose, the Academy of Finland Center of Excellence in Complex Disease Genetics (grant numbers: 213506, 129680), and the Academy of Finland (grants 100499, 205585, 118555, 141054, 265240, 263278 and 264146 to J. Kaprio). K. Silventoinen is supported by Osaka University's International Joint Research Promotion Program. S. Y. Oncel and F. Aliev are supported by Kirikkale University Research Grant: KKU, 2009/43 and TUBITAK grant 114C117. The Longitudinal Israeli Study of Twins was funded by the Starting Grant no. 240994 from the European Research Council (ERC) to Ariel Knafo. Data collection and research stemming from the Norwegian Twin Registry is supported, in part, from the European Union's Seventh Framework Programmes ENGAGE Consortium (grant agreement HEALTH-F4-2007-201413, and BioSHaRE EU (grant agreement HEALTH-F4-2010-261433). The Murcia Twin Registry is supported by the Seneca Foundation, Regional Agency for Science and Technology, Murcia, Spain (08633/PHCS/08 & 15302/PHCS/10) and Ministry of Science and Innovation, Spain (PSI11560-2009). The Twins Early Development Study (TEDS) is supported by a program grant (G0901245) from the UK Medical Research Council and the work on obesity in TEDS is supported in part by a grant from the UK Biotechnology and Biological Sciences Research Council (31/D19086). The Madeira data comes from the following project: genetic and environmental influences on physical activity, fitness, and health: the Madeira family study Project reference: POCI/DES/56834/2004 founded by the Portuguese agency for research (The Foundation for Science and Technology). The Boston University Twin Project is funded by grants (#R01 HD068435 #R01 MH062375) from the National Institutes of Health to K. Saudino. TwinsUK was funded by the Wellcome Trust; European Community's Seventh Framework Programme (FP7/2007-2013). The study also receives support from the National Institute for Health Research (NIHR) BioResource Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. The University of Washington Twin Registry is supported by the grant NIH RC2 HL103416 (D. Buchwald, PI). The Netherlands Twin Register acknowledges the Netherlands Organization for Scientific Research (NWO) and MagW/ZonMW grants 904-61-090, 985-10-002, 912-10-020, 904-61-193,480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464-14192; VU University's Institute for Health and Care Research (EMGO+); the European Research Council (ERC-230374), the Avera Institute, Sioux Falls, South Dakota (USA).; r Gemini was supported by a grant from Cancer Research UK (C1418/A7974).

Background: Sociodemographic, health- and work-related factors have been found to influence return to work in cancer survivors. It is feasible though that behavioural factors, such as expectation of being at work, could also affect work-related outcomes. Therefore, the effect of earlier identified factors and expectation of being at work on future employment status in cancer survivors was explored. To assess the degree to which these factors specifically concern cancer survivors, a comparison with heart attack survivors was made. Methods: Data from the English Longitudinal Study of Ageing were used. Cancer and heart attack survivors of working age in the UK were included and followed up for 2 years. Baseline characteristics of both cancer and heart attack survivors were compared regarding employment status. Univariate and multivariate regression analyses were performed in survivors at work, and the interaction between independent variables and diagnose group was assessed. Results: In cancer survivors at work (N = 159), alcohol consumption, participating in moderate or vigorous sport activities, general health and participation were univariate associated with employment status at two-year follow-up. Only fair general health (compared to very good general health) remained statistically significant in the multivariate model (OR 0.31; 95% CI 0.13-0.76; p = 0.010). In heart attack survivors at work (N = 78), gender, general health and expectation of being at work were univariate associated with employment status at follow-up. Female gender (OR 0.03; 95% CI 0.00-0.57; p = 0.018) and high expectation of being at work (OR 10.68; 95% CI 1.23-93.92; p = 0.033) remained significant in the multivariate model. The influence of gender (p = 0.066) and general health (p = 0.020) regarding employment status was found to differ significantly between cancer and heart attack survivors. Conclusions: When predicting future employment status in cancer survivors in the UK, general health is the most relevant factor to consider. While expectation of being at work did not show any significant influence in cancer survivors, in heart attack survivors, it should not be disregarded though, when developing interventions to affect their employment status. Future research should focus on more specific measures for expectation, and additional behavioural factors, such as self-efficacy, and their effect on employment status.

Objective The aim of this study was to explore the potential effects of diet-induced weight loss on molecular biomarkers of colorectal cancer risk in serum and colorectal tissue. Methods This single-arm exploratory study included 20 adults with BMI ≥ 30 kg/m2 completing an 8-week, complete, low-energy liquid diet. Pre- and postintervention anthropometric measurements, fasting blood draws, and endoscopic examinations to procure colorectal biopsies were performed. Fasting insulin, glucose, insulinlike growth factor 1 (IGF-1), C-reactive protein (CRP), and blood lipids were measured in serum, and tissue markers of apoptosis (M30), colonocyte proliferation (Ki-67), and insulin signaling (phospho-mTOR) were assessed using immunohistochemical staining. Results Participants achieved substantial weight loss (mean = 13.56%). Mean concentrations of insulin, glucose, and cholesterol were significantly reduced (P

BackgroundObesity in pregnancy is associated with insulin resistance, which underpins many common complications including gestational diabetes mellitus (GDM) and fetal macrosomia.ObjectivesTo assess the effect of a complex behavioural intervention based on diet and physical activity (PA) on the risk of GDM and delivery of a large-for-gestational age (LGA) infant.DesignThree phases: (1) the development phase, (2) the pilot study and (3) a multicentre randomised controlled trial (RCT) comparing a behavioural intervention to improve glycaemic control with standard antenatal care in obese pregnant women. A cost–utility analysis was undertaken to estimate the cost-effectiveness of the health training (intervention) over and above standard care (control).SettingPilot study: antenatal clinics in four inner-city UK hospitals. RCT: eight antenatal clinics in eight UK inner-city hospitals.ParticipantsWomen were eligible for inclusion if they had a body mass index of ≥ 30 kg/m2, were pregnant with a single fetus and at 15+0to 18+6weeks’ gestation, were able to give written informed consent and were without predefined disorders.InterventionThe intervention comprised an initial session with a health trainer, followed by eight weekly sessions. Dietary advice recommended foods with a low dietary glycaemic index, avoidance of sugar-sweetened beverages and reduced saturated fats. Women were encouraged to increase daily PA.Main outcome measuresDevelopment phase: intervention development, acceptability and optimal approach for delivery. Pilot study: change in dietary and PA behaviours at 28 weeks’ gestation. RCT: the primary outcome of the RCT was, for the mother, GDM [as measured by the International Association of the Diabetes and Pregnancy Study Groups (IADPSG)’s diagnostic criteria] and, for the infant, LGA delivery (i.e. customised birthweight ≥ 90th centile for gestational age).ResultsDevelopment phase: following a literature meta-analysis, a study of dietary intention questionnaires and semistructured interviews, an intervention based on behavioural science was developed that incorporated optimal and acceptable methods for delivery. Pilot study: the pilot study demonstrated improvement in dietary behaviours in the intervention compared with the standard care arm but no increase in objectively measured PA. Process evaluation demonstrated feasibility and general acceptability. RCT: the RCT showed no effect of the intervention on GDM in obese pregnant women or the number of deliveries of LGA infants. There was a reduction in dietary glycaemic load (GL) and reduced saturated fat intake, an increase in PA and a modest reduction in gestational weight gain, all secondary outcomes. Lower than expected was the number of LGA infant deliveries in all women, which suggested that universal screening for GDM with IADPSG’s diagnostic criteria, and subsequent treatment, may reduce the number of deliveries of LGA infants. According to the cost–utility analysis, the estimated probability that the UK Pregnancies Better Eating and Activity Trial (UPBEAT) behavioural intervention is cost-effective at the £30,000/quality-adjusted life-year willingness-to-pay threshold was 1%.LimitationsIncluded the high refusal rate for participation and self-reported assessment of diet and PA.ConclusionsThe UPBEAT intervention, an intense theoretically based intervention in obese pregnant women, did not reduce the risk of GDM in women or the number of LGA infant deliveries, despite successfully reducing the dietary GL. Based on total cost to the NHS provider and health gains, the UPBEAT intervention provided no supporting evidence to suggest that the intervention represents value for money based on the National Institute for Health and Care Excellence benchmarks for cost-effectiveness.Future workAlternative strategies for reducing the risk of GDM in obese pregnant women and the number of LGA infant deliveries should be considered, including development of clinically effective interventions to prevent obesity in women of reproductive age, of clinically effective interventions to reduce weight retention following pregnancy and of risk stratification tools in early pregnancy.Trial registrationCurrent Controlled Trials ISRCTN89971375 and UK Clinical Research Network Portfolio 5035.FundingThis project was funded by the NIHR Programme Grant for Applied Research programme and will be published in full inProgramme Grants for Applied Research, Vol. 5, No. 10. See the NIHR journals library website for further project information. Contributions to funding were also provided by the Chief Scientist Office CZB/4/680, Scottish Government Health Directorates, Edinburgh; Guys and St Thomas’ Charity, Tommy’s Charity (Lucilla Poston, Annette L Briley, Paul T Seed) and the NIHR Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, UK and the Academy of Finland, Finland. Keith M Godfrey was supported by the National Institute for Health Research through the NIHR Southampton Biomedical Research Centre. Lucilla Poston and Keith M Godfrey were supported by the European Union’s Seventh Framework Programme (FP7/2007-2013), project EarlyNutrition under grant agreement number 289346.

Background Health literacy skills tend to decline during ageing, which is often attributed to age-related cognitive decline. Whether health literacy skills may be influenced by technological and social factors during ageing is unknown. Methods We investigated whether internet use and social engagement protect against health literacy decline during ageing, independent of cognitive decline. We used prospective data from 4368 men and women aged ≥52 years in the English Longitudinal Study of Ageing from 2004 to 2011. Health literacy was measured at baseline (2004–2005) and at follow-up (2010–2011) using a reading comprehension test of a fictitious medicine label. The influences of consistent internet use and engagement in each of the civic, leisure and cultural activities on health literacy decline over the follow-up were estimated. Results After adjusting for cognitive decline and other covariates, consistent internet use (1379/4368; 32%) was protectively associated with health literacy decline (OR=0.77; 95% CI 0.60 to 0.99), as was consistent engagement in cultural activities (1715/4368; 39%; OR=0.73; 95% CI 0.56 to 0.93). As the number of activities engaged in increased, the likelihood of health literacy decline steadily decreased (ptrend

Among the key characteristics of the Western obesogenic food environment is a highly palatable and varied food supply. Laboratory investigations of eating behavior in both humans and animals established key roles for palatability and variety in stimulating appetite, delaying satiety, and promoting excessive energy intake. There is a robust effect of food palatability and variety on short-term food intake, and increased variety and palatability also cause weight gain in animal models. However, laboratory paradigms do not replicate the complexities of eating in a natural setting, and there is a shortage of evidence to estimate the magnitude of effects on weight in humans. There are substantial individual differences in susceptibility to the palatability effect and this may be a key determinant in individual vulnerability to weight gain. The understanding of pathways through which palatability and variety can affect eating is advancing, and epidemiologic and intervention studies are needed to translate laboratory findings into applications in public health or clinical domains, and to establish whether there is a role for greater regulation of the food environment in tackling increases in obesity.

Objectives: Most types of population-based cancer screening require repeat participation to be effective. This study investigated predictors of repeat participation in the NHS Bowel Cancer Screening Programme (BCSP). Methods: The BCSP in England offers biennial colorectal cancer screening using a guaiac fecal occult blood test (gFOBt) from age 60–74 years. This analysis included 62 081 individuals aged 60–64 years at the time of the first invitation (R1). The main outcome was repeat participation at their second (R2) or third (R3) invitation. Behavioural measures derived from screening records included late return of the gFOBt kit, compliance with follow-up investigations and previous screening participation. Other potential predictors of repeat participation included results of individual test kit analysis (normal, weak positive, strong positive, spoilt) and the definitive result of the gFOBt screening episode (normal or abnormal). Age, sex and socioeconomic deprivation were also recorded. Results: Overall repeat uptake was 86.6% in R2 and 88.6% in R3. Late return of the test kit was consistently associated with lower uptake (R2: 82.3% vs 88.6%, P

Background Repeated taste exposure, in combination with small rewards, has been shown to increase children's acceptance of disliked foods. However, previous studies have used direct contact with researchers or professionals for the implementation of the repeated exposure procedure. If mailed taste exposure instructions to parents produced comparable outcomes, this could be a cost-effective and easily disseminable strategy to promote healthier diets in children. Objective Our randomized controlled study aimed to test the efficacy and acceptability of mailed materials giving instructions on taste exposure as a means of increasing acceptance of vegetables in preschool-aged children. Design Participants were families of 3-year-old twins from the Gemini cohort who took part between March 2011 and April 2012. Families were randomized to a mailed intervention or a no treatment control condition. The intervention involved offering each child 14 daily tastes of a disliked (target) vegetable with a small reward (a sticker) if the child complied. Main outcome measures Outcomes were the child's intake of the target vegetable (number of pieces) and parent reports of the child's liking at two baseline (T1 and T2) and one postintervention (T3) behavior assessment. Results Record sheets with intake and liking data from T1, T2, and T3 were returned for 472 children, of which 442 were complete (94%). Over the intervention period (T2 to T3) intake and liking of the target vegetable increased significantly more in the intervention group than in the control group (intake: odds ratio 12.05, 95% CI 8.05 to 18.03, P

Objective Earlier diagnosis of cancer has become a policy priority. There is evidence that minority ethnic groups are more likely to delay help-seeking for cancer symptoms, but few studies have explored reasons for delay in these groups. The present study explored facilitators and barriers to help-seeking for breast and cervical cancer in an ethnically diverse sample of women. Methods Semi-structured interviews were carried out with 54 healthy women from a range of ethnic backgrounds; Indian, Pakistani, Bangladeshi, Caribbean, African, Black British, Black other, White British and White other. Framework analysis was used to identify themes. Results Appraising a symptom as possibly due to cancer was an important facilitator of help-seeking, although for some the prospect of a cancer diagnosis was a deterrent. Women believed that earlier diagnosis improved the chance of survival, and this facilitated prompt help-seeking. A sympathetic GP facilitated help-seeking, and an unsympathetic GP was a deterrent. Some ethnic minority women described the use of alternative medicine and prayer as a first-line strategy that might delay help-seeking. Language barriers, racism and a tendency to ‘soldier on’ were also mentioned by these women. Conclusions Models of delay in presentation for early cancer symptoms are likely to transfer across different ethnic groups. Encouraging open discussion about cancer among minority communities could help raise awareness about the importance of early detection and promote help-seeking as a priority response to a possible cancer symptom. © 2013 The Authors. Psycho-Oncology published by John Wiley & Sons, Ltd.

Background: Gynaecological cancers account for ∼12% of female cancer incidence in the United Kingdom. Encouraging prompt help-seeking for potential symptoms could help improve outcomes. However, before developing help-seeking interventions, it is important to estimate the number of women with symptoms potentially indicative of a gynaecological cancer to help estimate the impact of such interventions on primary care. Methods: As part of a face-to-face, population-based survey, women aged ⩾16 (n=911) were shown a list of symptoms potentially indicative of a gynaecological cancer and were asked to indicate any experienced in the last 3 months. Those who reported symptoms were asked about their responses to one randomly selected index symptom. Results: Just under half (44%) of the respondents reported a symptom, with 35% reporting a frequent and/or severe symptom. Younger (P

A wide range of screening technologies is available for colorectal cancer screening. There is demand to discover public preferences for these tests on the rationale that tailoring screening to preferences may improve uptake. This review describes a type of study (conjoint analysis) used to assess people's preferences for colorectal cancer screening tests and critically evaluates research quality using a recently published set of guidelines. Most primary studies assessed preferences for colonoscopy and fecal occult blood testing but newer technologies (e.g., capsule endoscopy) have not yet been evaluated. Although studies often adhered to guidelines, there was limited correspondence between stated preferences and actual screening behavior. Future research should investigate how studies can go beyond the guidelines in order to improve this and also explore how test preferences may differ by important population subgroups.

Objective Uptake of cancer screening tends to be lower for colorectal cancer (CRC) than cervical or breast cancer. Dislike of the test itself has often been identified as a barrier to CRC screening with the Faecal Occult Blood (FOB) test, but there have been no head-to-head comparisons of the three tests. Methods Women aged 50–80 ( n = 890) were recruited in spring 2012 as part of a population-based TNS Research International survey in Great Britain. Those in the eligible age range were asked if they had ever participated in breast, cervical or CRC screening. For each screening test, women who had never participated were asked for their ‘main reason’ using a checklist of barriers. Results Among eligible women, 67%, 83% and 90% reported ever having been screened for CRC, cervical and breast cancer respectively. More socioeconomically deprived women were less likely to report any screening, and single women were less likely to report CRC or breast screening than married women. Age was not associated with participation. Overall there were few differences between tests in the reported barriers, but dislike of the test was endorsed more often for CRC screening. Conclusion This was the first study to compare barriers to participation in organised screening programmes for CRC, breast and cervical cancer. Cancer screening tests share many barriers, but dislike of the test appears to be a stronger barrier to CRC screening. Women who are non-participants in more than one programme may have more global barriers to screening, such as cancer fatalism. The findings suggest that uptake of CRC screening could be improved by targeting the unpleasantness of stool sampling.

Objective To identify family and infant characteristics associated with timing of introduction of two food types: core foods (nutrient-dense) and non-core foods (nutrient-poor) in a population-based sample of mothers and infants. Method Participants were 1861 mothers and infants from the Gemini twin birth cohort (one child per family). Family and infant characteristics were assessed when the infants were around 8 months old. Timing of introducing core and non-core foods was assessed at 8 and 15 months. As the distributions of timing were skewed, three similar-sized groups were created for each food type: earlier (core: 1–4 months; non-core: 3–8 months), average (core: 5 months; non-core: 9–10 months), and later introduction (core: 6–12 months; non-core: 11–18 months). Ordinal logistic regression was used to examine predictors of core and non-core food introduction, with bootstrapping to test for differences between the core and non-core models. Results Younger maternal age, lower education level, and higher maternal BMI were associated with earlier core and non-core food introduction. Not breastfeeding for at least 3 months and higher birth weight were specifically associated with earlier introduction of core foods. Having older children was specifically associated with earlier introduction of non-core foods. Conclusion There are similarities and differences in the characteristics associated with earlier introduction of core and non-core foods. Successful interventions may require a combination of approaches to target both food types.

Background: Survival for many cancers is improved by healthier lifestyles, but giving lifestyle advice to cancer patients may seem insensitive. We investigated attitudes of members of cancer patients' social networks towards doctors giving lifestyle advice. Methods: We identified social network members through a population survey of UK adults (n=2024, age ⩾50) by asking respondents whether anyone close to them had ever had cancer (n=1273). Individuals with a cancer diagnosis themselves (n=222) were termed cancer survivors. Attitudes towards doctors giving advice to cancer patients on physical activity, diet and weight were each assessed with eight items. Results: Most social network members (88–93%) and survivors (87–93%) agreed that advice on diet, activity and weight would be ‘beneficial', ‘helpful' and ‘encouraging', and 84–87% thought it was ‘the doctor's duty' to provide it. Few network members (10–18%) or survivors (10–24%) believed it was ‘unnecessary', ‘interfering', ‘insensitive' or implied ‘blame'. Adjusted analyses using composite scores showed that attitudes did not differ between the groups. Conclusion: Few cancer survivors or members of social networks of individuals with cancer thought lifestyle advice would be insensitive, and most thought it would be beneficial. These results help counter doubts about the acceptability of lifestyle advice in the cancer context.

Aim: After dramatic rises in paediatric obesity, the critical period for obesity onset may now be pre-adolescence. Methods: We monitored adiposity over 4 years in 400 children aged 7-9 years recruited from schools in London. Weight, height, waist circumference (WC) and fat mass were measured annually. Weight status was defined using International Obesity Task Force (IOTF) criteria, and standardised scores and percentiles used British 1990 reference data. Results: BMI, WC and fat mass index all tracked strongly over time (average correlation for BMI = 0.95). Emergence of obesity was relatively uncommon: only 2% of the total sample increased from overweight to obese over the 4-year period, and this was nearly matched by the 1.3% that reduced from obese to overweight. However, more children (6%) moved from healthy weight to overweight than the reverse direction (2%). There were greater absolute gains in adiposity in children with higher baseline weight status, but this was disguised in analyses using standardised scores. Obesity was not an emergent trait in middle childhood, but rates were already high and, in absolute terms, adiposity increased more in overweight and obese than healthy weight children. Conclusion: These results highlight the need for active management of obesity in middle childhood.

Limited literature exists on attitudes towards, knowledge of and where cancer survivors seek information on physical activity. This study aimed to address these gaps in the literature. Interviews were conducted with 19 UK-based adult cancer survivors. Interviews covered participants’ knowledge of the relationship between physical activity\ud and cancer, sources of information and attitudes towards physical activity following their cancer treatment. Data were analysed using Thematic Analysis. Key themes included “physical activity is good for you,” “desire to be more physically active,” “limited guidance on participation in physical activity,” “multi-dimensional barriers and facilitators of physical activity.” Participants thought physical activity was good for them, and felt they should be more physically active. Participants reported receiving little information from oncology health professionals, as well as a desire for more guidance. Tiredness/fatigue was an important reported barrier to physical activity participation, as were situational constraints. Social support and structured exercise programmes were reported to facilitate physical activity. Health professionals should be encouraged to direct patients to appropriate sources for guidelines on physical activity for cancer survivors. Multi-component interventions to increase physical activity behaviour that consider tiredness/fatigue and incorporate components of social support could be explored.

Background Understanding dietary patterns in obese pregnant women will inform future intervention strategies to improve pregnancy outcomes and the health of the child. The aim of this study was to investigate the effect of a behavioral intervention of diet and physical activity advice on dietary patterns in obese pregnant woman participating in the UPBEAT study, and to explore associations of dietary patterns with pregnancy outcomes. Methods In the UPBEAT randomized controlled trial, pregnant obese women from eight UK multi-ethnic, inner-city populations were randomly assigned to receive a diet/physical activity intervention or standard antenatal care. The dietary intervention aimed to reduce glycemic load and saturated fat intake. Diet was assessed using a food frequency questionnaire (FFQ) at baseline (15+0-18+6 weeks’ gestation), post intervention (27+0-28+6 weeks) and in late pregnancy (34+0-36+0 weeks). Dietary patterns were characterized using factor analysis of the baseline FFQ data, and changes compared in the control and intervention arms. Patterns were related to pregnancy outcomes in the combined control/intervention cohort (n = 1023). Results Four distinct baseline dietary patterns were defined; Fruit and vegetables, African/Caribbean, Processed, and Snacks, which were differently associated with social and demographic factors. The UPBEAT intervention significantly reduced the Processed (−0.14; 95% CI −0.19, −0.08, P

Background: The NHS Bowel Cancer Screening Programme in England offers biennial guaiac faecal occult blood testing (gFOBt). There is a socioeconomic gradient in participation and socioeconomically disadvantaged groups have worse colorectal cancer survival than more advantaged groups. We compared the effectiveness and cost of an enhanced reminder letter with the usual reminder letter on overall uptake of gFOBt and the socioeconomic gradient in uptake. Methods: We enhanced the usual reminder by including a heading ‘A reminder to you’ and a short paragraph restating the offer of screening in simple language. We undertook a cluster-randomised trial of all 168 480 individuals who were due to receive a reminder over 20 days in 2013. Randomisation was based on the day of invitation. Blinding of individuals was not possible, but the possibility of bias was minimal owing to the lack of direct contact with participants. The enhanced reminder was sent to 78 067 individuals and 90 413 received the usual reminder. The primary outcome was the proportion of people adequately screened and its variation by quintile of Index of Multiple Deprivation. Data were analysed by logistic regression with conservative variance estimates to take account of cluster randomisation. Results: There was a small but statistically significant ( P ¼ 0.001) increase in participation with the enhanced reminder (25.8% vs 25.1%). There was significant ( P ¼ 0.005) heterogeneity of the effect by socioeconomic status with an 11% increase in the odds of participation in the most deprived quintile (from 13.3 to 14.1%) and no increase in the least deprived. We estimated that implementing the enhanced reminder nationally could result in up to 80 more people with high or intermediate risk colorectal adenomas and up to 30 more cancers detected each year if it were implemented nationally. The intervention incurred a small one- off cost of d 78 000 to modify the reminder letter. Conclusions: The enhanced reminder increases overall uptake and reduces the socioeconomic gradient in bowel cancer screening participation at little additional cost.

Objective: To evaluate the effects on mood of a substantial and prolonged reduction in total cholesterol concentration. Design: Randomised placebo controlled comparison of patients who had been allocated to receive simvastatin 20 mg or 40 mg daily versus those allocated matching placebo in a ratio of 2:1. Follow up at an average of 152 weeks after randomisation. Subjects: Men and women aged between 40 and 75 years at entry with blood total cholesterol of 3.5 mmol/l or greater, who were considered to be at higher than average risk of coronary heart disease based on medical history. Main outcome measures: The shortened profile of mood states questionnaire, reported use of psychotropic medication, and symptoms possibly related to mood. Results: Simvastatin reduced total cholesterol by 1.9 mmol/l (26.7%) at the time of follow up. Among all 621 patients randomised to simvastatin (414 patients) or placebo (207 patients) there were no significant differences in the use of psychotropic medication or in reports of symptoms possibly related to mood. Of these patients, 491 (334 simvastatin, 157 placebo) completed the mood questionnaire, and there were no significant differences between the treatment groups in total or subscale scores, even when patients with low baseline cholesterol concentrations or elderly subjects were considered separately. Conclusion: These results do not support the hypothesis that treatment to lower cholesterol concentration causes mood disturbance. Key messages A randomised placebo controlled trial of simvas- tatin (a drug that lowers cholesterol concentration substantially) showed no associated mood distur- bance over a period of nearly three years in subjects with cardiovascular disease and no pre-existing psychiatric conditions No effects on mood were seen in individuals with low baseline cholesterol concentrations or in older individuals, and there were no differences in use of psychotropic drugs between the treatment groups These results give little support to the idea that reducing cholesterol concentration has adverse effects on mood

Loos, Ruth J F/0000-0002-8532-5087; Huibregtse, Brooke M./0000-0003-0977-7249; Busjahn, Andreas/0000-0001-9650-6919; Skytthe, Axel E/0000-0002-8629-4913; Heikkila, Kauko/0000-0002-9256-8028; Haworth, Claire/0000-0002-8608-289X; Hjelmborg, Jacob/0000-0001-9630-9149; Sund, Reijo/0000-0002-6268-8117; Aliev, Fazil/0000-0001-8357-4699; Fagnani, Corrado/0000-0001-5771-7772; Kaprio, Jaakko/0000-0002-3716-2455; Knafo-Noam, Ariel/0000-0003-0613-1960; Montgomery, Grant W/0000-0002-4140-8139; Moller, Soren/0000-0003-0858-4269; ONCEL, Sevgi YURT/0000-0002-0990-292X; Duncan, Glen/0000-0001-6909-1869; Medland, Sarah E/0000-0003-1382-380X; Kandler, Christian/0000-0002-9175-235X; Christensen, Kaare/0000-0002-5429-5292; Magnusson, Patrik/0000-0002-7315-7899; mangino, massimo/0000-0002-2167-7470; Bartels, Meike/0000-0002-9667-7555; de Freitas, Duarte Luis/0000-0001-6642-3370; Harden, Kathryn/0000-0002-1557-6737; Derom, Catherine/0000-0001-5574-796X; Plomin, Robert/0000-0002-0756-3629; Silventoinen, Karri/0000-0003-1759-3079; Rasmussen, Finn/0000-0001-7915-7809; Boivin, Michel/0000-0001-8621-9844; Saffery, Richard/0000-0002-9510-4181; Pahlen, Shandell/0000-0003-0753-4155; van Beijsterveldt, Toos/0000-0002-6617-4201; Rebato, Esther/0000-0003-1221-8501; Pedersen, Nancy/0000-0001-8057-3543; Aaltonen, Sari/0000-0002-2873-4263; Llewellyn, Clare/0000-0002-0066-2827; Kyvik, Kirsten Ohm/0000-0003-2981-0245; Sodemann, Morten/0000-0001-8992-2500; Willemsen, Gonneke/0000-0003-3755-0236; D'Ippolito, Cristina/0000-0001-7902-9380; McAdams, Tom/0000-0002-6825-3499 WOS: 000378317900001 PubMed: 27333805 Height variation is known to be determined by both genetic and environmental factors, but a systematic description of how their influences differ by sex, age and global regions is lacking. We conducted an individual-based pooled analysis of 45 twin cohorts from 20 countries, including 180,520 paired measurements at ages 1-19 years. The proportion of height variation explained by shared environmental factors was greatest in early childhood, but these effects remained present until early adulthood. Accordingly, the relative genetic contribution increased with age and was greatest in adolescence (up to 0.83 in boys and 0.76 in girls). Comparing geographic-cultural regions (Europe, North-America and Australia, and East-Asia), genetic variance was greatest in North-America and Australia and lowest in East-Asia, but the relative proportion of genetic variation was roughly similar across these regions. Our findings provide further insights into height variation during childhood and adolescence in populations representing different ethnicities and exposed to different environments. Academy of FinlandAcademy of Finland [266592, 100499, 205585, 118555, 141054, 265240, 263278, 264146]; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 HD068435, R01 MH062375, 1R01ESO15150-01, AA023322, HD081437, R21 AG039572]; California Tobacco-Related Disease Research ProgramUniversity of California System [7RT-0134H, 8RT-0107H, 6RT-0354H]; Special Fund for Health Scientific Research in the Public Welfare, China [201502006]; NIDAUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Drug Abuse (NIDA) [DA011015, HD10333]; National Program for Research Infrastructure from the Danish Agency for Science, Technology and Innovation; Research Council for Health and Disease; Velux Foundation; US National Institute of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [P01 AG08761]; Fund of Scientific Research, Flanders and Twins; NGAGE-European Network for Genetic and Genomic Epidemiology [FP7-HEALTH-F4-2007, 201413]; National Institute of Alcohol Abuse and AlcoholismUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) [AA-12502, AA-00145, AA-09203]; Academy of Finland Center of Excellence in Complex Disease GeneticsAcademy of Finland [213506, 129680]; Osaka University's International Joint Research Promotion Program; Cancer Research UKCancer Research UK [C1418/A7974]; WT Grant Foundation; University of London Central Research fund; Medical Research Council Training FellowshipMedical Research Council UK (MRC) [G81/343, G120/635]; Economic and Social Research CouncilEconomic & Social Research Council (ESRC) [RES-000-22-2206]; Institute of Social Psychiatry [06/07-11]; Leverhulme Research FellowshipLeverhulme Trust [RF/2/RFG/2008/0145]; Goldsmiths, University of London; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81125007]; Medexpert Ltd., Budapest, Hungary; European Research Council (ERC)European Research Council (ERC) [240994]; Michigan State University; National Institute of Mental Health (NIMH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [R01-MH081813, R01-MH0820-54, R01-MH092377-02, R21-MH070542-01, R03-MH63851-01]; Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD) [R01-HD066040]; MSU Foundation [11-SPG-2518]; Netherlands Organization for Scientific Research (NWO)Netherlands Organization for Scientific Research (NWO); MagW/ZonMW [904-61-090, 985-10-002, 912-10-020, 904-61-193, 480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464-14192]; VU University's Institute for Health and Care Research (EMGO+); European Research CouncilEuropean Research Council (ERC) [ERC-230374]; Avera Institute, Sioux Falls, South Dakota (USA); Australian National Health and Medical Research CouncilNational Health and Medical Research Council of Australia [437015, 607358]; Bonnie Babes Foundation [BBF20704]; Financial Markets Foundation for Children [032-2007]; Victorian Government's Operational Infrastructure Support Program; Portuguese agency for research (The Foundation for Science and Technology [FCT]) [POCI/DES/56834/2004]; Fonds Quebecois de la Recherche sur la Societe et la CultureFQRNT; Fonds de la Recherche en Sante du QuebecFonds de la Recherche en Sante du Quebec; Social Science and Humanities Research Council of Canada; National Health Research Development Program; Canadian Institutes for Health ResearchCanadian Institutes of Health Research (CIHR); Sainte-Justine Hospital's Research Center; Canada Research Chair ProgramCanada Research Chairs; National Research Foundation of KoreaNational Research Foundation of Korea [NRF-371-2011-1 B00047]; UK Medical Research CouncilMedical Research Council UK (MRC) [G0901245]; UK Biotechnology and Biological Sciences Research CouncilBiotechnology and Biological Sciences Research Council (BBSRC) [31/D19086]; Kirikkale University Research Grant: KKUKirikkale University [2009/43]; TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [114C117]; Wellcome TrustWellcome Trust; European Community's Seventh Framework Programme (FP7)European Union (EU); National Institute for Health Research (NIHR) BioResource Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London; National Institute of Mental HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [R01 MH58354]; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [RC2 HL103416]; Japan Society for the Promotion of ScienceMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of Science [15H05105]; [5T32DA017637-11]; Medical Research CouncilMedical Research Council UK (MRC) [G19/2, MR/M021475/1, G120/635, G0500079, G0901245]; NNF Center for Basic Metabolic ResearchNovo Nordisk Foundation [Metabolic Genetics]; Novo Nordisk FondenNovo NordiskNovo Nordisk Foundation [NNF10CC1016515] This study was conducted within the CODATwins project (Academy of Finland #266592). Support for participating twin projects: The Boston University Twin Project is funded by grants (#R01 HD068435 #R01 MH062375) from the National Institutes of Health to K. Saudino. California Twin Program was supported by The California Tobacco-Related Disease Research Program (7RT-0134H, 8RT-0107H, 6RT-0354H) and the National Institutes of Health (1R01ESO15150-01). Chinese National Twin Registry is funded by Special Fund for Health Scientific Research in the Public Welfare (Project No: 201502006), China. Colorado Twin Registry is funded by NIDA funded center grant DA011015, & Longitudinal Twin Study HD10333; Author Huibregtse is supported by to 5T32DA017637-11. Danish Twin Registry is supported by the National Program for Research Infrastructure 2007 from the Danish Agency for Science, Technology and Innovation, The Research Council for Health and Disease, the Velux Foundation and the US National Institute of Health (P01 AG08761). Since its origin the East Flanders Prospective Survey has been partly supported by grants from the Fund of Scientific Research, Flanders and Twins, a non-profit Association for Scientific Research in Multiple Births (Belgium). Data collection and analyses in Finnish twin cohorts have been supported by ENGAGE-European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007, grant agreement number 201413, National Institute of Alcohol Abuse and Alcoholism (grants AA-12502, AA-00145, and AA-09203 to RJ Rose, the Academy of Finland Center of Excellence in Complex Disease Genetics (grant numbers: 213506, 129680), and the Academy of Finland (grants 100499, 205585, 118555, 141054, 265240, 263278 and 264146 to J. Kaprio). K. Silventoinen is supported by Osaka University's International Joint Research Promotion Program. Gemini was supported by a grant from Cancer Research UK (C1418/A7974). Waves 1-3 of Genesis 12-19 were funded by the WT Grant Foundation, the University of London Central Research fund and a Medical Research Council Training Fellowship (G81/343) and Career Development Award (G120/635) to Thalia C. Eley. Wave 4 was supported by grants from the Economic and Social Research Council (RES-000-22-2206) and the Institute of Social Psychiatry (06/07-11) to Alice M. Gregory who was also supported at that time by a Leverhulme Research Fellowship (RF/2/RFG/2008/0145). Wave 5 was supported by funding to Alice M. Gregory from Goldsmiths, University of London. Guangzhou Twin Eye Study is supported by National Natural Science Foundation of China (grant #81125007). Anthropometric measurements of the Hungarian twins were supported by Medexpert Ltd., Budapest, Hungary. Longitudinal Israeli Study of Twins was funded by the Starting Grant no. 240994 from the European Research Council (ERC) to Ariel Knafo. The Michigan State University Twin Registry has been supported by Michigan State University, as well as grants R01-MH081813, R01-MH0820-54, R01-MH092377-02, R21-MH070542-01, R03-MH63851-01 from the National Institute of Mental Health (NIMH), R01-HD066040 from the Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD), and 11-SPG-2518 from the MSU Foundation. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIMH, the NICHD, or the National Institutes of Health. The NAS-NRC Twin Registry acknowledges financial support from the National Institutes of Health grant number R21 AG039572.; Netherlands Twin Register acknowledges the Netherlands Organization for Scientific Research (NWO) and MagW/ZonMW grants 904-61-090, 985-10-002, 912-10-020, 904-61-193,480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464-14192; VU University's Institute for Health and Care Research (EMGO+); the European Research Council (ERC-230374), the Avera Institute, Sioux Falls, South Dakota (USA). PETS was supported by grants from the Australian National Health and Medical Research Council (grant numbers 437015 and 607358 to J. C. and R.S.), the Bonnie Babes Foundation (grant number BBF20704 to J. M. C.), the Financial Markets Foundation for Children (grant no. 032-2007 to J. M. C.), and by the Victorian Government's Operational Infrastructure Support Program. Madeira data comes from the following project: Genetic and environmental influences on physical activity, fitness and health: the Madeira family study Project reference: POCI/DES/56834/2004 Founded by the Portuguese agency for research (The Foundation for Science and Technology [FCT]). The Quebec Newborn Twin Study acknowledges financial support from the Fonds Quebecois de la Recherche sur la Societe et la Culture, the Fonds de la Recherche en Sante du Quebec, the Social Science and Humanities Research Council of Canada, the National Health Research Development Program, the Canadian Institutes for Health Research, Sainte-Justine Hospital's Research Center, and the Canada Research Chair Program (Michel Boivin). South Korea Twin Registry is supported by National Research Foundation of Korea (NRF-371-2011-1 B00047). The Texas Twin Project is currently funded by grants AA023322 and HD081437 from the National Institutes of Health. The Twins Early Development Study (TEDS) is supported by a program grant (G0901245) from the UK Medical Research Council and the work on obesity in TEDS is supported in part by a grant from the UK Biotechnology and Biological Sciences Research Council (31/D19086). S.Y. Oncel and F. Aliev are supported by Kirikkale University Research Grant: KKU, 2009/43 and TUBITAK grant 114C117. TwinsUK was funded by the Wellcome Trust; European Community's Seventh Framework Programme (FP7/2007-2013). The study also receives support from the National Institute for Health Research (NIHR) BioResource Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. The University of Southern California Twin Study is funded by a grant from the National Institute of Mental Health (R01 MH58354). Washington State Twin Registry (formerly the University of Washington Twin Registry) was supported in part by grant NIH RC2 HL103416 (D. Buchwald, PI). The West Japan Twins and Higher Order Multiple Births Registry was supported by Grant-in-Aid for Scientific Research (B) (grant number 15H05105) from the Japan Society for the Promotion of Science.

Importance Genome-wide association studies have identified genetic risks for obesity. These genetic risks influence development of obesity partly by accelerating weight gain in childhood. Research is needed to identify mechanisms to inform intervention. Cross-sectional studies suggest appetite traits as a candidate mechanism. Longitudinal studies are needed to test whether appetite traits mediate genetic influences on children’s weight gain. Objective To test whether genetic risk for obesity predicts accelerated weight gain in middle childhood (ages 4-8 years) and whether genetic association with accelerated weight gain is mediated by appetite traits. Design, Setting, and Participants Longitudinal study of a representative birth cohort at the Trondheim Early Secure Study, Trondheim, Norway, enrolled at age 4 years during 2007 to 2008, with follow-ups at ages 6 and 8 years. Participants were sampled from all children born in 2003 or 2004 who attended regular community health checkups for 4-year-olds (97.2% attendance; 82.0% consent rate, n = 2475). Nine hundred ninety-five children participated at age 4 years, 795 at age 6 years, and 699 at age 8 years. Analyses included 652 children with genotype, adiposity, and appetite data. Main Outcomes and Measures Outcomes were body mass index and body-fat phenotypes measured from anthropometry (ages 4, 6, and 8 years) and bioelectrical impedance (ages 6 and 8 years). Genetic risk for obesity was measured using a genetic risk score composed of 32 single-nucleotide polymorphisms previously discovered in genome-wide association studies of adult body mass index. Appetite traits were measured at age 6 years with the Children’s Eating Behavior Questionnaire. Results Of the 652 genotyped child participants, 323 (49.5%) were female, 58 (8.9%) were overweight, and 1 (0.2%) was obese. Children at higher genetic risk for obesity had higher baseline body mass index and fat mass compared with lower genetic risk peers, and they gained weight and fat mass more rapidly during follow-up. Each SD increase in genetic risk score was associated with a 0.22-point increase in BMI at age-4 baseline (for the intercept, unstandardized path coefficient B = 0.22 [95% CI, 0.06-0.38]; P = .008. Children with higher genetic risk scores also gained BMI points more rapidly from ages 4 to 6 years ( B = 0.11 [95% CI, 0.03-0.20]; P = .01 ; β = 0.12) and from 6 to 8 years ( B = 0.09 [95% CI, 0.00-0.19]; P = .05; β = 0.10), compared with their lower genetic risk peers. Children at higher genetic risk had higher levels of alleged obesogenic appetite traits than peers with lower genetic risk at age 6 years, but appetite traits did not mediate genetic associations with weight gain. The sum of the 5 indirect effects was B = −0.001 (95% CI, −0.02 -0.01); P = .86; β = 0.00. Conclusions and Relevance Genetic risk for obesity is associated with accelerated childhood weight gain. Interventions targeting childhood weight gain may provide one path to mitigating genetic risk. However, middle childhood appetite traits may not be a promising target for such interventions. Studies of early-childhood samples are needed to test whether appetite traits explain how genetic risks accelerate growth earlier in development.

BACKGROUND: Encouraging prompt help-seeking for cancer symptoms can help shorten the patient interval and improve timely diagnosis. We explored factors associated with help-seeking in a primary care sample reporting 'alarm' symptoms. METHODS: A questionnaire was mailed to 9771 adults (⩾50 years of age and no cancer diagnosis) and 3766 (39%) returned it. Our sample included 1732 adults reporting at least one cancer 'alarm' symptom; with a total of 2726 symptoms. Respondents completed questions relating to help-seeking, demographic and symptom characteristics (e.g., type, knowledge, concern, interference and attribution). RESULTS: Over a third of people who reported a cancer 'alarm' symptom in the past 3 months had not sought help from a doctor. An unexplained lump (odds ratio (OR) 2.46, 1.42-4.26) and persistent unexplained pain (OR 1.79, 1.19-2.69) were associated with increased likelihood of help-seeking. Symptom concern (OR 3.10, 2.19-4.39) and interference (OR 3.06, 2.15-4.36) were associated with an increased likelihood of seeking help independently of symptom type. People who were not working (OR 1.41, 1.09-1.83), were married/cohabiting rather than single (OR 1.38, 1.10-1.74) and were older (60-69 years) rather than younger (50-59 years; OR 1.33, 1.02-1.75) were more likely to have sought help. CONCLUSIONS: Our findings highlighted symptom type and symptom characteristics as key drivers of help-seeking. We also found that there may be specific demographic groups where encouraging help-seeking might be warranted.British Journal of Cancer (2015) advance online publication 21 January 2016; doi:10.1038/bjc.2015.445 www.bjcancer.com.

We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.

Objectives Flexible sigmoidoscopy (FS) screening for colorectal cancer will be introduced into the National Cancer Screening Programmes in England in 2013. Patient-reported outcome measures (PROMs) from trial participants indicate high acceptability and no adverse physical or psychological consequences, but this may not generalize to routine screening in the community. This study examined PROMs in a community-based FS screening programme. Methods Eligible adults aged 58–59 ( n = 2016) registered at 34 London general practices were mailed a National Health Service-endorsed invitation to attend FS screening. Pain and side-effects were assessed in a ‘morning-after’ questionnaire, and satisfaction was assessed in a three-month follow-up questionnaire. Anxiety, self-rated health and colorectal symptoms were assessed at prescreening and follow-up. Results In total, 1020 people attended screening and were included in the current analyses, of whom 913 (90%) returned the morning-after questionnaire, and 674 (66%) the follow-up questionnaire. The prescreening questionnaire had been completed by 751 (74%) of those who attended. The majority (87%) of respondents reported no pain or mild pain, and the most frequent side-effect (wind) was only experienced more than mildly by 16%. Satisfaction was extremely high, with 98% glad they had the test; 97% would encourage a friend to have it. From prescreening to follow-up there were no changes in anxiety or self-rated health, and the number of colorectal symptoms declined. Satisfaction and changes in wellbeing were not moderated by gender, deprivation, ethnicity or screening outcome. Conclusions PROMs indicate high acceptability of FS screening in 58–59 year olds, with no adverse effects on colorectal symptoms, health status or psychological wellbeing.

Summary Objective To explore awareness of cancer risk factors in ethnic minority men and women living in England. Study design Cross-sectional survey. Methods Men and women were recruited from the six largest ethnic minority groups in the UK proportional to the population distribution: Indian ( n = 467); Pakistani ( n = 333); Bangladeshi ( n = 126); Caribbean ( n = 252); African ( n = 216); and Chinese ( n = 106). Participants responded to an open-ended question about cancer risk factors. Analyses were adjusted for age, gender, socio-economic class and language. Results The most commonly cited cancer risk factors were smoking (55%), diet (20%), genetics (20%), drinking alcohol (19%) and lifestyle (17%). On average, participants who were able to name cancer risk factors (91% of respondents) cited 2.13 factors. There were some differences between broad ethnic groups (Asian, Black and Chinese), but fewer differences within them (e.g. between Indian, Pakistani and Bangladeshi, or African and Caribbean). Conclusions Awareness of risk factors (particularly diet and exercise) was lower in this sample than in previous population representative samples in the UK. Interventions aimed at raising awareness of cancer risk factors are likely to be beneficial across the whole ethnic minority population. Any ethnically targeted interventions should consider risk factor awareness levels as well as cancer risk.

Objective To examine whether HPV vaccination influences sexual behaviour in adolescent girls, either by giving them a ‘green light’ to have sex, or because perceived protection afforded by the vaccine permits compensatory risky sexual behaviour. Design Cross-sectional and longitudinal surveys. Setting Seven English schools. Main outcome measures Self-reported sexual behaviour. Participants The cross-sectional survey included 1053 girls (mean age 17.1 years) who had ( n = 433 recruited in March 2010) or had not ( n = 620 recruited in March 2009) been offered the HPV vaccine. The longitudinal survey included 407 girls (mean age 17.5 years) who had been offered HPV vaccination and had either received at least one dose ( n = 148) or had not received any doses ( n = 259). Results In the cross-sectional survey, the group of girls who had been offered the HPV vaccine were no more likely to be sexually active than the group of girls who had not been offered the HPV vaccine. In the longitudinal survey, the vaccinated group were no more likely to have changed their condom use or increased their total number of sexual partners than the unvaccinated group. Conclusions Neither being offered the HPV vaccine nor receiving it affected sexual behaviour.