Quantitative Trait Loci Associated with the Tocochromanol (Vitamin E) Pathway in Barley.

The Genome-Wide Association Studies approach was used to detect Quantitative Trait Loci associated with tocochromanol concentrations using a panel of 1,466 barley accessions. All major tocochromanol types- α-, ß-, δ-, γ-tocopherol and tocotrienol- were assayed. We found 13 single nucleotide polymorphisms associated with the concentration of one or more of these tocochromanol forms in barley, seven of which were within 2 cM of sequences homologous to cloned genes associated with tocochromanol production in barley and/or other plants. These associations confirmed a prior report based on bi-parental QTL mapping. This knowledge will aid future efforts to better understand the role of tocochromanols in barley, with specific reference to abiotic stress resistance. It will also be useful in developing barley varieties with higher tocochromanol concentrations, although at current recommended daily consumption amounts, barley would not be an effective sole source of vitamin E. However, it could be an important contributor in the context of whole grains in a balanced diet.

Engaging patients, clinicians and health funders in weight management: the Counterweight Programme.

BACKGROUND: The Counterweight Programme provides an evidence based and effective approach for weight management in routine primary care. Uptake of the programme has been variable for practices and patients. Aim. To explore key barriers and facilitators of practice and patient engagement in the Counterweight Programme and to describe key strategies used to address barriers in the wider implementation of this weight management programme in UK primary care. METHODS: All seven weight management advisers participated in a focus group. In-depth interviews were conducted with purposeful samples of GPs (n = 7) and practice nurses (n = 15) from 11 practices out of the 65 participating in the programme. A total of 37 patients participated through a mixture of in-depth interviews (n = 18) and three focus groups. Interviews and focus groups were analysed for key themes that emerged. RESULTS: Engagement of practice staff was influenced by clinicians' beliefs and attitudes, factors relating to the way the programme was initiated and implemented, the programme content and organizational/contextual factors. Patient engagement was influenced by practice endorsement of the programme, clear understanding of programme goals, structured proactive follow-up and perception of positive outcomes. CONCLUSIONS: Having a clear understanding of programme goals and expectations, enhancing self-efficacy in weight management and providing proactive follow-up is important for engaging both practices and patients. The widespread integration of weight management programmes into routine primary care is likely to require supportive public policy.

Changes in the incidence of cutaneous melanoma in the west of Scotland and Queensland, Australia: hope for health promotion?

We compared trends in melanoma incidence by body site in two populations exposed to different levels of sunlight and different approaches to melanoma prevention. We analysed site-specific melanoma incidence during the period 1982-2001 in Queensland, Australia (n=28 862 invasive melanomas; 2536 lentigo maligna melanomas) and the west of Scotland (n=4278 invasive melanomas; 525 lentigo maligna melanomas). Analyses were stratified by sex and age group (<40 years, 40-59 years, >/=60 years). We estimated annual percentage change (APC) in melanoma incidence by regressing the logarithms of the rates and exponentiating the coefficients. Among men, overall melanoma incidence increased log-linearly in both settings, but significantly more rapidly in the west of Scotland (APC 2.8%) than Queensland (APC 1.4%). Rates of increase among Scottish men were higher for every body site and all ages than among Queensland men. Among women, overall melanoma incidence increased more rapidly among Scottish (APC 1.8%) than Queensland women (APC 0.7%). Most discrepant were trends in upper limb melanomas, which underwent large annual increases among Scottish women, but declined among younger Queensland women. Melanoma incidence continues to rise rapidly in all age groups in Scotland and among older people in Queensland. Rates of melanoma in younger people in Queensland are stabilizing, as might be expected if primary prevention campaigns were effective in reducing solar exposure. Variations in rates of change at different body sites warrant further monitoring.

Body mass index in middle life and future risk of hospital admission for psychoses or depression: findings from the Renfrew/Paisley study.

BACKGROUND: There is evidence that greater body mass index (BMI) protects against depression, schizophrenia and suicide. However, there is a need for prospective studies. METHOD: We examined the association of BMI with future hospital admissions for psychoses or depression/anxiety disorders in a large prospective study of 7036 men and 8327 women. Weight and height were measured at baseline (1972-76) when participants were aged 45-64. Follow-up was for a median of 29 years. RESULTS: Greater BMI and obesity were associated with a reduced risk of hospital admission for psychoses and depression/anxiety in both genders, with the magnitude of these associations being the same for males and females. With adjustment for age, sex, smoking and social class, a 1 standard deviation (s.d.) greater BMI at baseline was associated with a rate ratio of 0.91 [95% confidence interval (CI) 0.82-1.01] for psychoses and 0.87 (95% CI 0.77-0.98) for depression/anxiety. Further adjustment for baseline psychological distress and total cholesterol did not alter these associations. CONCLUSIONS: Our findings add to the growing body of evidence that suggests that greater BMI is associated with a reduced risk of major psychiatric outcomes. Long-term follow-up of participants in randomized controlled trials of interventions that effectively result in weight loss and the use of genetic variants that are functionally related to obesity as instrumental variables could help to elucidate whether these associations are causal.

Effect of conjugal bereavement on mortality of the bereaved spouse in participants of the Renfrew/Paisley Study.

OBJECTIVES: To investigate how loss of a spouse affects mortality risk in the bereaved partner. DESIGN AND SETTING: Prospective cohort study in Renfrew and Paisley in Scotland. PARTICIPANTS: 4395 married couples aged 45-64 years when the study was carried out between 1972 and 1976. METHODS: The date of bereavement for the bereaved spouse was the date of death of his or her spouse. Bereavement could occur at any time during the follow-up period, so it was considered as a time-dependent exposure variable and the Cox proportional hazards model for time-dependent variables was used. The relative rate (RR) of mortality was calculated for bereaved versus non-bereaved spouses and adjusted for confounding variables. MAIN OUTCOME MEASURES: Causes of death to 31 March 2004. RESULTS: Bereaved participants were at higher risk than non-bereaved participants of dying from any cause (RR 1.27; 95% CI 1.2 to 1.35). These risks remained but were attenuated after adjustment for confounding variables. There were raised RRs for bereaved participants dying of cardiovascular disease, coronary heart disease, stroke, all cancer, lung cancer, smoking-related cancer, and accidents or violence. After adjustment for confounding variables, RRs remained higher for bereaved participants for all these causes except for mortality from lung cancer. There was no strong statistical evidence that the increased risks of death associated with bereavement changed with time after bereavement. CONCLUSIONS: Conjugal bereavement, in addition to existing risk factors, is related to mortality risk for major causes of death.

Breast cancer incidence trends in deprived and affluent Scottish women.

OBJECTIVE: Breast cancer is commoner in the affluent and breast cancer rates in many countries are rising; it remains unclear whether this incidence rise is consistent across the different socio-economic groups. The rising incidence of breast cancer may be related to changes in population risk factor profiles. This study aimed to determine breast cancer incidence trends in women of different socio-economic categories and whether these trends were related to breast cancer risk factor trends. DESIGN: Data on breast cancer incidence rates by deprivation quintile in Scotland 1991-2000 were analysed using linear regression. Data on first births at late maternal age, BMI trends (based on the Scottish Health Surveys) and breast screening uptake trends in the different categories were also analysed and their relation to breast cancer incidence trends explored. POPULATION AND SETTING: Breast cancer incidence data was based on all women in Scotland. BMI data was based on representative cross-sectional survey data from the Scottish Health Surveys-women in the 1995, 1998 and 2003 surveys were 16-64, 16-74 and aged 16 and over, respectively. First birth data was based on all women aged 35-39 in Scotland. Breast screening uptake data was studied in women of screening age, that is, aged 50-64. RESULTS: Breast cancer incidence rates in Scottish women are rising in parallel across all socio-economic categories and the incidence gap between deprived and affluent still remains. Since the late 1980s, numbers of first birth in Scottish women aged 35-39 have risen dramatically, especially in the affluent, but numbers were stable before this. The prevalence of obesity and mean BMI has increased over time in all socio-economic classes but BMI continues to be higher in the deprived. Uptake of screening invitations has increased in all socio-economic groups. CONCLUSIONS: Breast cancer is rising in women of all socio-economic status in Scotland and the deprived-affluent gap remains. Trends in late age at first pregnancy, prevalence of obesity and screening uptake do not fully explain the observed trends.

Reverse causality and confounding and the associations of overweight and obesity with mortality.

OBJECTIVE: To examine the effect of reverse causality and confounding on the association of BMI with all-cause and cause-specific mortality. RESEARCH METHODS AND PROCEDURES: Data from two large prospective studies were used. One (a community-based cohort) included 8327 women and 7017 men who resided in two Scottish towns at the time of the baseline assessment in 1972-1976; the other (an occupational cohort) included 4016 men working in the central belt of Scotland at the time of the baseline assessment in 1970-1973. Participants in both cohorts were ages 45 to 64 years at baseline; the follow-up period was 28 to 34 years. RESULTS: In age-adjusted analyses that did not take account of reverse causality or smoking, there was no association between being overweight (BMI 25 to <30 kg/m(2)) and mortality, and weak to modest associations between obesity (BMI > or =30 kg/m(2)) and mortality. There was a strong association between smoking and lower BMI in women and men in both cohorts (all p < 0.0001). Among never-smokers and with the first 5 years of deaths removed, overweight was associated with an increase in all-cause mortality (relative risk ranging from 1.12 to 1.38), and obesity was associated with a doubling of risk in men in both cohorts (relative risk, 2.10 and 1.96, respectively) and a 60% increase in women (relative risk, 1.56). In both never-smokers and current smokers, being overweight or obese was associated with important increases in the risk of cardiovascular disease. DISCUSSION: These findings demonstrate that with appropriate control for smoking and reverse causality, both overweight and obesity are associated with important increases in all-cause and cause-specific mortality, and in particular with cardiovascular disease mortality.

Meat consumption reduces the risk of nutritional rickets and osteomalacia.

Endogenous vitamin D deficiency (low serum 25(OH)D3) is a necessary but insufficient requirement for the genesis of vitamin D-deficiency rickets and osteomalacia. The magnitude of the independent contributions of dietary factors to rachitic and osteomalacic risk remains uncertain. We reanalysed two weighed dietary surveys of sixty-two cases of rickets and osteomalacia and 113 normal women and children. The independent associations of four dietary variables (vitamin D, Ca, fibre and meat intakes) and daylight outdoor exposure with rachitic and osteomalacic relative risk were estimated by multivariate logistic regression. Meat and fibre intakes showed significant negative and positive associations respectively with rachitic and osteomalacic relative risk (RR; zero meat intake: RR 29.8 (95 % CI 4.96, 181), P<0.001; fibre intake: RR 1.53 (95 % CI 1.01, 2.32), P=0.043). The negative association of meat intakes with rachitic and osteomalacic relative risk was curvilinear; relative risk did not fall further at meat intakes above 60 g daily. Daylight outdoor exposure showed a significant negative association with combined relative risk (RR 0.33 (95 % CI 0.17, 0.66), P<0.001). Operation of the meat and fibre risk factors was related to sex, age and dietary pattern (omnivore/lactovegetarian), mainly determined by religious affiliation. The mechanism by which meat reduces rachitic and osteomalacic risk is uncertain and appears independent of revised estimates of meat vitamin D content. The meat content of the omnivore Western diet may explain its high degree of protection against nutritional rickets and osteomalacia from infancy to old age in the presence of endogenous vitamin D deficiency.

Childhood IQ and social factors on smoking behaviour, lung function and smoking-related outcomes in adulthood: linking the Scottish Mental Survey 1932 and the Midspan studies.

OBJECTIVE: To investigate the associations of childhood IQ and adult social factors, and smoking behaviour, lung function (forced expiratory volume in one second; FEV(1)), and smoking-related outcomes in adulthood. DESIGN: Retrospective cohort study. METHOD: Participants were from the Midspan prospective studies conducted on Scottish adults in the 1970s. The sample consisted of 938 Midspan participants born in 1921 who were successfully matched with their cognitive ability test results on the Scottish Mental Survey 1932. RESULTS: Structural equation modelling showed that age 11 IQ was not directly associated with smoking consumption, but that IQ and adult social class had indirect effects on smoking consumption via deprivation category. The influence of IQ on FEV(1) was partly indirect via social class. Gender influenced smoking consumption and also IQ and social class. There was a 21% higher risk of having a smoking-related hospital admission, cancer, or death during 25 years of follow-up for each standard deviation disadvantage in IQ. Adjustment for adult social class, deprivation category, and smoking reduced the association to 10%. CONCLUSION: Childhood IQ was associated with social factors which influenced lung function in adulthood, but was not associated directly with smoking consumption. In future studies, it is important to consider other pathways which may account for variance in the link between childhood IQ and health in later life.

Does knowledge of cancer diagnosis affect quality of life? A methodological challenge.

BACKGROUND: As part of an assessment of quality of life in lung cancer patients an investigation was carried out to examine whether the knowledge of their diagnosis affected their quality of life. METHODS: Every patient in a defined geographical area with a potential diagnosis of lung cancer was interviewed at first consultation and after a definitive treatment has been given. Quality of life was assessed using three standard measures: the Nottingham Health Profile (NHP), the EORTC quality of life questionnaire (QLQ-C30) and its lung cancer supplementary questionnaire (QLQ-LC13). Comparison was made in quality of life scores between patients who knew their cancer diagnosis and those who did not. RESULTS: In all, 129 lung cancer patients were interviewed. Of these, 30 patients (23%) knew and 99 (78%) did not know their cancer diagnosis at the time of baseline assessment. The patient groups were similar in their characteristics except for age (P = 0.04) and cell type (P < 0.0001). Overall, there were no significant differences between these two groups with regard to their scores on the three instruments used. A major finding was that both group scored almost the same on emotional reactions (P = 0.8) and social isolation (P = 1.0) as measured by the NHP, and emotional (P = 0.7) and social functioning (P = 1.0) as measured by the EORTC QLQ-C30. In addition there were no significant differences in patients' symptom scores between those who knew their diagnosis and those who did not, nor did any consistent pattern emerge. The only significant difference was for sleep difficulties (P = 0.02). CONCLUSION: The findings suggest that the knowledge of cancer diagnosis does not affect the way in which patients respond to quality of life questionnaires.

Childhood mental ability and blood pressure at midlife: linking the Scottish Mental Survey 1932 and the Midspan studies.

OBJECTIVES: To establish the relationship between childhood mental ability and adult hypertension. DESIGN: Retrospective cohort study. SETTING: Community. PARTICIPANTS: Non-clinical sample of people born in 1921 who participated in both the Scottish Mental Survey 1932 and the Midspan studies. Nine hundred and thirty-eight people were participants in both studies. MAIN OUTCOME MEASURES: Mid-life systolic and diastolic blood pressure, intelligence quotient (IQ) at age 11 years, sex, social class, height and weight. RESULTS: After adjustment for age, sex, social class, body mass index, height, cholesterol level and smoking, there remained a 3.15 mmHg decrease in systolic blood pressure and a 1.5 mmHg decrease in diastolic blood pressure for each standard deviation increase in childhood IQ. CONCLUSIONS: The association between hypertension and lower cognitive function in adulthood is partly accounted for by individual differences in childhood IQ.

Childhood IQ, social class, deprivation, and their relationships with mortality and morbidity risk in later life: prospective observational study linking the Scottish Mental Survey 1932 and the Midspan studies.

OBJECTIVE: To investigate how childhood mental ability (IQ) is related to mortality and morbidity risk, when socioeconomic factors are also considered. METHODS: Participants were from the Midspan studies conducted on adults in the 1970s; 938 Midspan participants were successfully matched with the Scottish Mental Survey 1932 in which children born in 1921 and attending Scottish schools on June 1, 1932, took a cognitive ability test. Mortality, hospital admissions, and cancer incidence in the 25 years after the Midspan screening were investigated in relation to childhood IQ, social class, and deprivation. RESULTS: The risk of dying in 25 years was 17% higher for each standard deviation disadvantage in childhood IQ. Adjustment for social class and deprivation category accounted for some, but not all, of this higher risk, reducing it to 12%. Analysis by IQ quartile showed a substantial increased risk of death for the lowest-scoring quarter only. Structural equation modeling indicated that the effect of childhood IQ on mortality was partly indirectly influenced by social factors. Cause-specific mortality or hospital admission showed that lower IQ was associated with higher risks for all cardiovascular disease and coronary heart disease. Cause-specific mortality or cancer incidence risk was higher with decreasing IQ for lung cancer. CONCLUSIONS: Lower childhood IQ was related to higher mortality risk and some specific causes of death or morbidity. Childhood IQ may be considered as a marker for risk of death or illness in later life in similar and complementary ways to social class or deprivation category.

Quality of life in lung cancer patients: does socioeconomic status matter?

BACKGROUND: As part of a prospective study on quality of life in newly diagnosed lung cancer patients an investigation was carried out to examine whether there were differences among patients' quality of life scores and their socioeconomic status. METHODS: Quality of life was measured at two points in time (baseline and three months after initial treatment) using three standard instruments; the Nottingham Health Profile (NHP), the European Organization for Research and Cancer Treatment Quality of Life Questionnaire (EORTC QLQ-C30) and its lung cancer supplement (QLQ-LC13). Socioeconomic status for each individual patient was derived using Carstairs and Morris Deprivation Category ranging from 1 (least deprived) to 7 (most deprived) on the basis of the postcode sector of their address. RESULTS: In all, 129 lung cancer patients entered into the study. Of these data for 82 patients were complete (at baseline and follow-up). 57% of patients were of lower socioeconomic status and they had more health problems, less functioning, and more symptoms as compared to affluent patients. Of these, physical mobility (P = 0.05), energy (P = 0.01), role functioning (P = 0.04), physical functioning (P = 0.03), and breathlessness (P = 0.02) were significant at baseline. However, at follow-up assessment there was no significant difference between patient groups nor did any consistent pattern emerge. CONCLUSION: At baseline assessment patients of lower socioeconomic status showed lower health related quality of life. Since there was no clear trend at follow-up assessment this suggests that patients from different socioeconomic status responded to treatment similarly. In general, the findings suggest that quality of life is not only the outcome of the disease and its treatment, but is also highly dependent on each patients' socioeconomic characteristics.

Outcome following surgery for colorectal cancer.

There is evidence to suggest that survival following surgery for colorectal cancer is improving. Audits undertaken in a single institution between 1974-1979 and 1991-1994 provide the opportunity to evaluate the extent to which earlier diagnosis and better surgery contribute to the improvement in survival. There was little evidence that patients were presenting at an earlier stage during the latter period. In contrast, more patients had a potentially curative resection. This analysis confirmed that, over this period, there has been a substantial improvement in survival following surgery for colorectal cancer; this improvement was largely due to better surgery rather than earlier presentation.

A population-based study of the long-term risks associated with atrial fibrillation: 20-year follow-up of the Renfrew/Paisley study.

PURPOSE: To describe the effect of atrial fibrillation on long-term morbidity and mortality. SUBJECTS AND METHODS: The Renfrew/Paisley Study surveyed 7052 men and 8354 women aged 45-64 years between 1972 and 1976. All hospitalizations and deaths occurring during the subsequent 20 years were analyzed by the presence or absence of atrial fibrillation at baseline. Lone atrial fibrillation was defined in the absence of other cardiovascular signs or symptoms. Cox proportional hazards models were used to adjust for age and cardiovascular conditions. RESULTS: After 20 years, 42 (89%) of the 47 women with atrial fibrillation had a cardiovascular event (death or hospitalization), compared with 2276 (27%) of the 8307 women without this arrhythmia. Among men, 35 (66%) of 53 with atrial fibrillation had an event, compared with 3151 (45%) of 6999 without atrial fibrillation. In women, atrial fibrillation was an independent predictor of cardiovascular events (rate ratio [RR] = 3.0; 95% confidence interval [CI]: 2.1-4.2), fatal or nonfatal strokes (RR = 3.2; 95% CI: 1.0-5.0), and heart failure (RR = 3.4; 95% CI: 1.9-6.2). The rate ratios among men were 1.8 (95% CI: 1.3-2.5) for cardiovascular events, 2.5 (95% CI: 1.3-4.8) for strokes, and 3.4 (95% CI: 1.7-6.8) for heart failure. Atrial fibrillation was an independent predictor of all-cause mortality in women (RR = 2.2; 95% CI: 1.5-3.2) and men (RR = 1.5; 95% CI: 1.2-2.2). However, lone atrial fibrillation (which occurred in 15 subjects) was not associated with a statistically significant increase in either cardiovascular events (RR = 1.5; 95% CI: 0.6-3.6) or mortality (RR = 1.8; 95% CI: 0.9-3.8). CONCLUSIONS: Atrial fibrillation is associated with an increased long-term risk of stroke, heart failure, and all-cause mortality, especially in women.

Incidence of and survival from malignant melanoma in Scotland: an epidemiological study.

BACKGROUND: We aimed to assess the incidence and survival for all patients with invasive primary cutaneous malignant melanoma diagnosed in Scotland, UK, during 1979-98. METHODS: The Scottish Melanoma Group obtained data for 8830 patients (3301 male and 5529 female) first diagnosed with invasive cutaneous malignant melanoma. FINDINGS: Age-standardised incidence rose from 3.5 in 1979 to 10.6 per 10(5) population in 1998 for men, and from 7.0 to 13.1 for women, a rise of 303% and 187%, respectively. After 1995, the rate of increase levelled in women younger than 65 years at diagnosis. Melanoma incidence increased most in men on the trunk, head, and neck and in women on the leg. 5-year survival rose from 58% to 80% for men diagnosed in 1979 and 1993, respectively, and from 74% to 85% for women; improvements of 38% (p<0.001) and 15% (p<0.001), respectively. Most improvement was attributable to a higher proportion of thinner tumours. Male mortality from melanoma was 1.9/10(5) population per year at the start and end of the study, whereas mortality for men younger than 65 years at diagnosis rose from 1.2 to 1.35 (p=0.24). For all women, mortality fell slightly from 1.9 to 1.85/10(5) population per year (p=0.61), whereas for women younger than 65 years at diagnosis, mortality fell from 1.3 to 1.15 (p=0.62). INTERPRETATION: Interventions aimed at both primary and secondary prevention of melanoma are justified. Specialist tumour registers for entire countries can be used to plan and monitor public health interventions.