Showing papers by "George Davey Smith published in 2002"

Data dredging, bias, or confounding.

Abstract: On 4 October 2002, women who were moderate drinkers received good news: their risk of breast cancer was not raised, according to a report in the Lancet that was widely covered by the British media.1 The bad news was that smoking at an early age was now implicated as a risk factor for breast cancer. However, after they had enjoyed guilt-free drinks (without cigarettes) for only a few days, on 13 November the message was reversed: alcohol did increase the risk of breast cancer after all, but smoking was declared innocent.2 The press release proclaimed “Alcohol, tobacco and breast cancer: the definitive answer.” A reader was driven to complain in the letters page of the Guardian (14 November 2002): “So let me get this right—alcohol's no good anymore, and if you smoked within five years of getting your periods, that's bad news too. Oh no, that was a couple of weeks ago; smoking's okay now … Do things stop being bad for us if we just forget about them for a bit, do you think?” This is a familiar story—so much so that in Bristol we set our medical students the exercise of examining the “health scare of the week” that appears each Friday, generally from a study reported in the BMJ or Lancet .w1 The widespread perception that epidemiological studies generate conflicting and often meaningless findingsw2 has received support from recent randomised controlled trials, which have failed to confirm even apparently robust findings from observational epidemiological studies. The most topical of these relates to hormone replacement therapy. In 1991 a meta-analysis of epidemiological results relating the use of hormone replacement therapy to the risk of coronary heart disease concluded that it halved the risk, and that the evidence was statistically robust (relative risk 0.50; 95% …

Systematic review of long term effects of advice to reduce dietary salt in adults

Abstract: Objective: To assess the long term effects of advice to restrict dietary sodium in adults with and without hypertension. Design: Systematic review and meta-analysis of randomised controlled trials. Data sources: Cochrane library, Medline, Embase, and bibliographies. Study selection: Unconfounded randomised trials that aimed to reduce sodium intake in healthy adults over at least 6 months. Inclusion decisions, validity and data extraction were duplicated. Random effects meta-analysis, subgrouping, sensitivity analysis, and meta-regression were performed. Outcomes: Mortality, cardiovascular events, blood pressure, urinary sodium excretion, quality of life, and use of antihypertensive drugs. Results: Three trials in normotensive people (n=2326), five trials in those with untreated hypertension (n=387), and three trials in people being treated for hypertension (n=801) were included, with follow up from six months to seven years. The large high quality (and therefore most informative) studies used intensive behavioural interventions. Deaths and cardiovascular events were inconsistently defined and reported. There were 17 deaths, equally distributed between intervention and control groups. Systolic and diastolic blood pressures were reduced (systolic by 1.1 mm Hg, 95% confidence interval 1.8 to 0.4 mm Hg; diastolic by 0.6 mm Hg, 1.5 to 0.3 mm Hg) at 13 to 60 months, as was urinary 24 hour sodium excretion (by 35.5 mmol/24 hours, 47.2 to 23.9). Degree of reduction in sodium intake and change in blood pressure were not related. Conclusions: Intensive interventions, unsuited to primary care or population prevention programmes, provide only small reductions in blood pressure and sodium excretion, and effects on deaths and cardiovascular events are unclear. Advice to reduce sodium intake may help people on antihypertensive drugs to stop their medication while maintaining good blood pressure control.

Psychological stress and cardiovascular disease: empirical demonstration of bias in a prospective observational study of Scottish men.

Abstract: Objectives: To examine the association between self perceived psychological stress and cardiovascular disease in a population where stress was not associated with social disadvantage. Design: Prospective observational study with follow up of 21 years and repeat screening of half the cohort 5 years from baseline. Measures included perceived psychological stress, coronary risk factors, self reported angina, and ischaemia detected by electrocardiography. Setting: 27 workplaces in Scotland. Participants: 5606 men (mean age 48 years) at first screening and 2623 men at second screening with complete data on all measures Main outcome measures: Prevalence of angina and ischaemia at baseline, odds ratio for incident angina and ischaemia at second screening, rate ratios for cause specific hospital admission, and hazard ratios for cause specific mortality. Results: Both prevalence and incidence of angina increased with increasing perceived stress (fully adjusted odds ratio for incident angina, high versus low stress 2.66, 95% confidence interval 1.61 to 4.41; P for trend Conclusions: The relation between higher stress, angina, and some categories of hospital admissions probably resulted from the tendency of participants reporting higher stress to also report more symptoms. The lack of a corresponding relation with objective indices of heart disease suggests that these symptoms did not reflect physical disease. The data suggest that associations between psychosocial measures and disease outcomes reported from some other studies may be spurious. What is already known on this topic Higher psychological stress has predicted coronary heart disease in several observational studies Exposure to stress and heart disease outcomes were often based on self report so that a general tendency to negative perceptions may have generated a spurious association between higher perceived stress and heart disease symptoms What this study adds Perceived stress was strongly related to subjective symptoms of heart disease, including those leading to hospital admission However, stress showed a weakly inverse relation to all objective indices of heart disease: socially advantaged men perceived themselves to be most stressed, and the “protective” effect of stress was probably attributable to residual confounding Suggestions that psychological stress is an important determinant of heart disease may be premature

Admissions for myocardial infarction and World Cup football: database survey.

Abstract: Objectives: To examine hospital admissions for a range of diagnoses on days surrounding England9s 1998 World Cup football matches. Design: Analysis of hospital admissions obtained from English hospital episode statistics. Setting: England. Participants: Population aged 15-64 years. Main outcome measures: Ratio of number of admissions for acute myocardial infarction, stroke, deliberate self harm, and road traffic injuries on the day of and five days after England9s World Cup matches, compared with admissions at the same time in previous and following years and in the month preceding the tournament. Results: Risk of admission for acute myocardial infarction increased by 25% on 30 June 1998 (the day England lost to Argentina in a penalty shoot-out) and the following two days. No excess admissions occurred for other diagnoses or on the days of the other England matches. The effect was the same when only the two days after the match were treated as the exposed condition. Individual analyses of the day of and the two days after the Argentina match showed 55 extra admissions for myocardial infarctions compared with the number expected. Conclusion: The increase in admissions suggests that myocardial infarction can be triggered by emotional upset, such as watching your football team lose an important match. What is already known on this topic Physical and emotional triggers, such as environmental disasters and vigorous physical exercise, can precipitate acute myocardial infarction An increase in cardiovascular mortality among Dutch men was associated with the 1996 European championship match between the Netherlands and France What this study adds Admissions for myocardial infarction increased on the day England was eliminated from the 1998 World Cup by Argentina in a penalty shoot-out and on the two subsequent days No effect was seen on admissions for other diagnoses or after other matches These data support the hypothesis that intense emotional reactions can trigger myocardial infarction

Socioeconomic position in childhood and adulthood and insulin resistance: cross sectional survey using data from British women's heart and health study

Abstract: Objective: To assess the associations between childhood and adulthood social class and insulin resistance. Design: Cross sectional survey. Setting: 23 towns across England, Scotland, and Wales. Participants: 4286 women aged 60-79years. Main outcome measures: Insulin resistance and other cardiovascular disease risk factors. Results: Belonging to manual social classes in childhood and in adulthood was independently associated with increased insulin resistance, dyslipidaemia, and general obesity. The association between childhood social class and insulin resistance was stronger than that for adult social class. The effect, on insulin resistance and other risk factors, of belonging to a manual social class at either stage in the life course was cumulative, with no evidence of an interaction between childhood and adult social class. Women who were in manual social classes in childhood remained at increased risk of insulin resistance, dyslipidaemia, and obesity—even if they moved into non-manual social classes in adulthood—compared with women who were in non-manual social classes at both stages. Conclusions: Adverse social circumstances in childhood, as well as adulthood, are strongly and independently associated with increased risk of insulin resistance and other metabolic risk factors.

Does psychological distress predict the risk of ischemic stroke and transient ischemic attack? The Caerphilly Study.

Abstract: Background and Purpose — Psychological distress is common after stroke, but little is known about its etiologic importance, although the general public often ascribes stroke to the experience of stress. Therefore, we examined whether psychological distress leads to an increased risk of ischemic stroke and transient ischemic attack (TIA). Methods — The association between the 30-item General Health Questionnaire (GHQ), a measure of psychological distress, and the incidence of nonfatal and fatal ischemic stroke and TIA was measured by Cox regression modeling in a prospective observational study of 2201 men aged 45 to 59 years in phase II of the Caerphilly cohort. Hazard ratios comparing those with high (≥5) and normal GHQ scores were calculated with adjustment for age and other covariates. Results — Twenty-two percent of men suffered from psychological distress, indicated by a score of ≥5 on the GHQ. There were 130 incident strokes recorded, of which 17 were fatal and 113 nonfatal. The relative risk of incident ischemic stroke was 1.45 (95% CI, 0.98 to 2.14) for those who showed symptoms of psychological distress compared with those who did not. For fatal stroke the relative risk was 3.36 (95% CI, 1.29 to 8.71) and for nonfatal stroke 1.25 (95% CI, 0.82 to 1.92). The relative risk of TIA for the distressed group was 0.63 (95% CI, 0.26 to 1.53). The results were unchanged after adjustment for body mass index, systolic blood pressure, smoking, heavy drinking, social class, and marital status. However, additionally controlling for previously diagnosed ischemic heart disease, diabetes, respiratory disease, and retirement due to ill health attenuated the relative risks, but not markedly. For fatal strokes the relative risk decreased to 2.56 (95% CI, 0.97 to 6.75) when all confounding variables were included in the model. There was a graded association between degree of psychological distress and risk of fatal ischemic stroke. Conclusions — Psychological distress is a predictor of fatal ischemic stroke but not of nonfatal ischemic stroke or TIA. Further work examining the mechanisms of this association is required.

A putative functional polymorphism in the IGF-I gene: association studies with type 2 diabetes, adult height, glucose tolerance, and fetal growth in U.K. populations.

Abstract: IGF-I has a critical role in growth and metabolism. A microsatellite polymorphism 1 kb upstream to the IGF-I gene has recently been associated with several adult phenotypes. In a large Dutch cohort, the absence of the commonest allele (Z) was associated with reduced serum IGF-I levels, reduced height, and an increased risk of type 2 diabetes and myocardial infarction. This result has not been replicated, and the role of this polymorphism in these traits in U.K. subjects is not known. We sought further evidence for the involvement of this variant in type 2 diabetes using a case-control study and IGF-I and diabetes-related traits in a population cohort of 640 U.K. individuals aged 25 years. Absence of the common allele was not associated with type 2 diabetes (odds ratio 0.70, 95% CI 0.47-1.04 for X/X versus Z/Z genotype, chi(2) test for trend across genotypes, P = 0.018). In the population cohort, the common allele (Z) was associated with decreased IGF-I levels (P = 0.01), contrary to the Dutch study, but not with adult height (P = 0.23), glucose tolerance (P = 0.84), oral glucose tolerance test-derived values of beta-cell function (P = 0.90), or insulin resistance (P = 0.66). There was no association with measures of fetal growth, including birth weight (P = 0.17). Our results do not support the previous associations and suggest that the promoter microsatellite is unlikely to be functionally important.

Where now for meta-analysis?

Abstract: In the short time since its introduction, meta-analysis, the statistical pooling of the results from independent but ‘combinable’ studies, has established itself as an influential branch of clinical epidemiology and health services research, with hundreds of meta-analyses published in the medical literature each year. 1 This issue of the International Journal of Epidemiology contains several papers 2‐9 that address methodological issues in metaanalytic research, a review article on where we stand with systematic reviews in observational epidemiology 10 and three meta-analyses of observational studies. 11‐13 Publication of a themed issue on meta-analysis by an epidemiological journal begs several questions: Where does meta-analysis come from? Does it deserve the attention it is currently getting? And where should it be going next? The statistical basis of meta-analysis reaches back to the 17th century when, in astronomy, intuition and experience suggested that combinations of data might be better than attempts

The long-term effect of dietary advice in men with coronary disease: follow-up of the Diet and Reinfarction trial (DART)

Abstract: Objective: To assess the long-term effect of dietary advice on diet and mortality after a randomised trial of men with a recent history of myocardial infarction. Design: Questionnaire survey and mortality follow-up after a trial of dietary advice. Setting: Twenty-one hospitals in south Wales and south-west England. Subjects: Former participants in the Diet and Reinfarction Trial. Main outcome measures: Current fish intake and cereal fibre intake. All-cause mortality, stroke mortality and coronary mortality. Results: By February 2000, after 21147 person years of follow-up, 1083 (53%) of the men had died. Completed questionnaires were obtained from 879 (85%) of the 1030 men alive at the beginning of 1999. Relative increases in fish and fibre intake were still present at 10 y but were much smaller. The early reduction in all-cause mortality observed in those given fish advice (unadjusted hazard 0.70 (95% CI 0.54, 0.92)) was followed by an increased risk over the next 3 y (unadjusted hazard 1.31 (95% CI 1.01, 1.70). Fat and fibre advice had no clear effect on coronary or all-cause mortality. The risk of stroke death was increased in the fat advice group¾the overall unadjusted hazard was 2.03 (95% CI 1.14, 3.63). Conclusions: In this follow-up of a trial of intensive dietary advice following myocardial infarction we did not observe any substantial long-term survival benefit. Further trials of fish and fibre advice are feasible and necessary to clarify the role of these foods in coronary disease.

Life-Course Socioeconomic and Behavioral Influences on Cardiovascular Disease Mortality: The Collaborative Study

Abstract: Objectives. This study sought to demonstrate life-course influences on cardiovascular disease (CVD). Methods. Data were derived from a prospective observational study in which the main outcome measure was death resulting from CVD. Results. Combining 4 socioeconomic and behavioral risk indicators into a measure of life-course exposure produced 5 groups whose relative risks of CVD mortality ranged from 1.00 (the group with the most favorable life-course exposures) to 4.55 (the group with the least favorable life-course exposures). If the entire study population had had the CVD mortality risk of the subsample with the most favorable risk factor profile, approximately two thirds of cardiovascular deaths would not have occurred. Conclusions. CVD risk is influenced in a cumulative fashion by socioeconomic and behavioral factors acting throughout the life course.

Height in Young Adulthood and Risk of Death from Cardiorespiratory Disease: A Prospective Study of Male Former Students of Glasgow University, Scotland

Abstract: To investigate the association between height in young, socially homogeneous males and cause-specific mortality, the authors conducted a prospective study of 8,361 male former students who underwent medical examinations while attending Glasgow University, Scotland, from 1948 to 1968 The mean age at examination was 205 (range, 161-300) years The median follow-up time was 413 years There were 863 deaths In Cox proportional hazards modeling, there was no association between height and all-cause mortality with age-adjusted hazard ratios per 10-cm increase in height (hazard ratio = 092, 95% confidence interval: 083, 102) Height was inversely associated with all cardiovascular disease and coronary heart disease mortality, with hazard ratios per 10-cm increase in height of 078 (95% confidence interval: 066, 093) and 076 (95% confidence interval: 062, 093), respectively Sizeable inverse associations with stroke and respiratory disease were also found, although these did not reach conventional levels of significance There was no association with cancer or noncardiorespiratory disease mortality There was a positive, although nonsignificant, association between height and mortality from aortic aneurysm Controlling for confounding variables had little effect on these results The findings suggest that factors operating in early life, and which influence height, also influence future cardiovascular health in men

Commentary: Behind the Broad Street pump: aetiology, epidemiology and prevention of cholera in mid-19th century Britain

Abstract: Introductory epidemiology text books and courses generally contain little epidemiological history, but an exception is made for the story of John Snow, the water-born transmission of cholera, and the handle of the Broad Street pump.1–5 Snow’s 1855 book, On The Mode Of Communication Of Cholera,6 is indeed a beautiful demonstration of ‘the epidemiological imagination’7 in action, and continues to provide example and inspiration to people entering the discipline. However, it appeared amidst a veritable spate of speculation, experiment, investigation and recommendations regarding cholera, and some of these less celebrated (at least now) contributions remain instructive. Therefore, in the current issue of the International Journal of Epidemiology we reprint a section of Dr John Sutherland’s report for the General Board of Health on the 1848–1849 British cholera epidemic (Figure 1), together with a series of commentaries.8–10 The extracts from Sutherland’s report include his investigation of the effect of water source on cholera risk in Salford, Manchester, which was briefly referred to by Snow6 and has occasionally been recognized as a seminal investigation.11,12 The discussion by Sutherland of the implications of his finding are clearly at variance with those of Snow, who more strongly emphasized the necessary transmissible element in generating cholera (and thus in triggering epidemics), but Sutherland’s utilization of quantitative data is striking. As with (virtually) all scientific advances, Snow’s work did not emerge from a vacuum, and this background has been explored from various perspectives.13–23 The proto-epidemiological approaches to cholera in the mid-19th century have continuing implications for epidemiological theory and practice, and this does not only apply to the investigations now seen to have contributed to us reaching the correct conclusions. The efforts of many of Snow’s predecessors and contemporaries were seen, at the time, as of at least (and often greater) importance than those of Snow.13,14,24,25 The contributions of those who are now excluded from potted histories of epidemiology are certainly worth revisiting.

Birth weight of offspring and insulin resistance in late adulthood: cross sectional survey

Abstract: Objective: To investigate the association between birth weight of offspring and mothers9 insulin resistance in late adulthood. Design: Cross sectional survey. Setting: General practitioner9s surgeries in 23 towns in Great Britain. Participants: 4286 women aged 60-79 years Main outcome measures: Maternal insulin resistance Results: Birth weight of offspring was inversely related to maternal insulin resistance in late adulthood. For each 1 kg higher birth weight of offspring, women had a 15% reduction in the odds of being in the fourth with highest insulin resistance, compared to other fourths (odds ratio 0.85; 95% confidence interval 0.71 to 1.00). This increased to 27% (0.73; 0.60 to 0.90) after adjusting data for potential confounders. A U shaped relation between birth weight of offspring and diabetes in older age was found; women with the lightest and heaviest offspring had the highest prevalence of diabetes Conclusions: Birth weight of offspring is inversely related to the mother9s insulin resistance in late adulthood, despite the association of glucose intolerance during pregnancy with heavier offspring at birth. Common genetic factors contribute to the relation between birth weight and risk of cardiovascular disease and diabetes in adults

Is There a Sex Difference in the Association between Birth Weight and Systolic Blood Pressure in Later Life? Findings from a Meta-Regression Analysis

Abstract: The aim of this study was to determine whether a sex difference exists in the association between birth weight and systolic blood pressure. A meta-analysis of all observational studies (n = 57) in which the study population contained both males and females and the association between birth weight and blood pressure was presented as a linear regression coefficient was undertaken. There were no differences in the pooled regression coefficients between males and females combining all studies; the regression of blood pressure on birth weight for males was -1.27 (95% confidence interval: -1.77, -0.77) mmHg/kg and for females was -1.24 (95% confidence interval: -1.90, -0.58) mmHg/kg. When studies in which blood pressure had been measured in childhood were considered separately from those in which it was measured in adulthood, there were no sex differences in either age group. The pooled regression coefficient tended to be weaker in studies reporting sex-specific results than in those reporting combined results. These findings suggest that reports of sex differences in the association between birth weight and blood pressure are chance findings.

Does the opioid‐sparing effect of rectal diclofenac following total abdominal hysterectomy benefit the patient?

Abstract: Background The aim of this prospective, double-blind, randomized, placebo-controlled clinical trial was to investigate the opioid-sparing effects of rectal diclofenac following total abdominal hysterectomy. Methods Forty ASA I–II patients, aged 20–60 yr, were randomized to receive identical-looking suppositories of either diclofenac 75 mg or placebo, twice daily. All patients were given a standardized anaesthetic, with intravenous morphine via a patient-controlled analgesia device and either diclofenac or placebo for postoperative analgesia. Results The median 24 h morphine consumption (interquartile range) was significantly higher (P=0.02) in the placebo group [59 (45–85) mg] than in the diclofenac group [31 (14–65) mg]. In comparison with the placebo group, there were significant reductions in total pain score in the diclofenac group at rest (P=0.04) and on movement (P sd ) sedation score was significantly lower (P=0.04) in the diclofenac group [90 (73) mm] than in the placebo group [148 (89) mm]. Total (interquartile range) nausea score was significantly lower (P Conclusions Rectal diclofenac reduces morphine consumption, improves postoperative analgesia, and reduces the incidence of adverse effects such as sedation and nausea.

I: Intraperitoneal administration of analgesia: is this practice of any utility?

Abstract: Intraperitoneal administration of analgesia: is this practice of any utility? Local anaesthetic techniques are part of the multimodal approach to postoperative pain management. 1 This involves the use of opioids, non-steroidal anti-in¯ammatory drugs (NSAIDs) 2 , paracetamol 3 and local anaesthetics. 4 The purpose of this editorial is to review whether or not instillation of local anaesthetics into the peritoneal cavity is a worthwhile modality in routine clinical practice during some intra-abdominal procedures. Data from a nationwide survey in the UK of anaesthesia for gynaecological laparoscopy revealed that local anaesthetic solutions are administered commonly, particularly into the wound and the peritoneal cavity. 5 For this type of ambulatory surgery and anaesthesia, the main advantage of using local anaesthetics is that they do not have the adverse effects of opioids, which may delay recovery and discharge from hospital. These effects include postoperative nausea, sedation, 2 impairment of return of gastrointestinal motility, and pruritis. In addition, time to return of bowel function in the postoperative period may be reduced when the use of opioids is obviated by administering local anaesthetics. 6 Although NSAIDs provide morphine-sparing effects 2 , they do not appear, on their own, to provide suf®ciently reliable postoperative analgesia for minimally invasive laparoscopic surgery. 7 In addition, they have the disadvantage that they may cause gastric irritation in addition to impairing platelet and renal function. In the perioperative period, many patients are at risk of these problems because of enforced starvation, dehydration and tissue trauma. Additional methods of analgesia are thus necessary. Local anaesthetics have been administered into the peritoneal cavity during minimally invasive procedures, such as laparoscopic cholecystectomy and gynaecological laparoscopy for sterilization and diagnosis, 8 in addition to open abdominal procedures, such as total abdominal hysterectomy. The rationale for this route of administration is that the peritoneum is exposed to block of visceral nociceptive conduction, thereby providing an additional mechanism of analgesia. However, absorption from the large peritoneal surface may also occur, and this may be a further mechanism of analgesia. It has been shown after radical retropubic prostatectomy that i.v. lidocaine 1.5 mg kg ±1 bolus and 2±3 mg min ±1 infusion reduced morphine consumption and total pain scores signi®cantly compared with placebo. 6 These data are supported by a clinical trial in which i.v. lidocaine produced a concentration-dependent reduction in pain scores when the plasma concentration exceeded 1.5 mg ml ±1. 11 In addition, it has …

Characterisation of the non-peptide nociceptin receptor agonist, Ro64-6198 in Chinese hamster ovary cells expressing recombinant human nociceptin receptors.

Abstract: Nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand for the opioid receptor-like receptor or nociceptin receptor (NOP). We have compared a novel non–peptide NOP agonist Ro64-6198 with N/OFQ in a series of GTPγ35S binding and inhibition of forskolin stimulated cAMP formation assays. GTPγ35S binding assays were performed in membranes prepared from Chinese hamster ovary cells expressing the recombinant human NOP (CHOhNOP). cAMP inhibition studies were performed in whole CHOhNOP cells. Both Ro64-6198 and N/OFQ stimulated GTPγ35S binding with pEC50 values(95%CL) of 7.61(0.18) and 8.58(0.21) respectively. Both Ro64-6198 and N/OFQ inhibited cAMP formation with pEC50 values of 8.45(0.09) and 9.28(0.28) respectively. In each assay Ro64-6198 and N/OFQ were full agonists. Ro64-6198 stimulation of GTPγ35S binding and inhibition of cAMP formation was competitively antagonised by the NOP antagonists [Nphe1]NC(1–13)NH2 (10μM), J-113397 (100nM) and III-BTD (1μM) with pKB values of 7.04(0.34) and 6.29(0.10), 8.65(0.34) and 7.90(0.30) and 7.59(0.22) and 7.60(0.22) respectively. Despite the slightly reduced potency of Ro64-6198 compared with N/OFQ, by virtue of high selectivity and relative metabolic stability this molecule will be of considerable use in studies of the actions of the NOP.

Zena Stein, Mervyn Susser and epidemiology: observation, causation and action

Abstract: highlight the contributions of two pioneering self-taught epidemiologists, Zena Stein and Mervyn Susser. Their joint paper ‘Civilization and Peptic Ulcer‘, originally published in the Lancet in 1962, appears as one of our series of reprints of important epidemiological papers, along with several commentaries. These include a reflection, 40 years on, by the original authors. A companion series of papers originated in an international symposium held by the Mailman School of Public Health of Columbia University, New York, to mark the 80th years of both Zena and Mervyn. The event ended in a manner perhaps unusual for such an occasion: it was closed by Ahmed Kathrada, a friend of Zena and Mervyn, who was incarcerated with Nelson Mandela on Robben Island during the struggle against apartheid in South Africa. He read out a letter from Nelson Mandela to mark the occasion (Box 1). The interlocked careers of Zena and Mervyn have been described elsewhere,1 as well as in the present collection.2 The range of their work in epidemiology and public health can be appreciated from the bibliographies which we have made available on the web (http://www.ije.oupjournals.org). Therefore here we will just give a brief account of their continuing contributions to epidemiology and public health. For both Zena and Mervyn their work in epidemiology and public health started in South Africa and has continued to have a strong attachment to that country. Their initial driving motivation was to contribute to the health and medical care of ‘non-whites’ in apartheid South Africa in the early 1950s. This majority population was virtually ignored in medical curricula at the time, so the task meant striking out with a small group of colleagues to direct a ‘township’ clinic, in Alexandra, Johannesburg. Although they began with no knowledge of epidemiology, the effort naturally led them to carry out one of the first studies of community health in the developing world, published in the Lancet in 1955 as ‘Medical Care in an African Township’.3 It was during this period that they developed ties with Ahmed Kathrada, Walter Sisulu, Joe Slovo and Nelson Mandela, among many others, in the anti-apartheid movement. The efforts made by them and others such as Sidney Kark4 (a mentor) to address the health of the community as a whole is of more than historic importance; if anything, it may be even more germane today than it was then. Even as the AIDS epidemic brings catastrophe to South Africa—as outlined in the present collection5—medical training in that country still fails to give any centrality to the care and prevention of HIV/AIDS. Zena and Mervyn are once again in the centre of the melee, supporting those in South Africa who want to bring about change. Due to political difficulties in South Africa in 1955, they settled in England for the next decade. Taking positions at Manchester University, they took up research on what are now called developmental disabilities. Their many early contributions to this field are exemplified by studies showing the influence © International Epidemiological Association 2002 Printed in Great Britain

Role of endogenous oestrogen in aetiology of coronary heart disease: analysis of age related trends in coronary heart disease and breast cancer in England and Wales and Japan.

Abstract: The sex difference in mortality from coronary heart disease decreases with increasing age, suggesting a protective effect of oestrogen in premenopausal women. This decrease is, however, the result of a deceleration in death rates in men, with no change in rates in women around the age of menopause.1 The age specific rate of breast cancer—a condition associated with endogenous oestrogen—does show a change around the age of menopause among women in the United States.2 The relatively low rates of coronary heart disease in premenopausal women may make it difficult to detect an effect of the menopause.3 Rates of breast cancer among Japanese women are low. If low rates of coronary heart disease around the time of the menopause explain the lack of an effect of the menopause on age related …

Thermal stability of electrodeposited nanocrystalline nickel

Abstract: The effect of annealing electrodeposited nanocrystalline nickel at 250°C was studied by microhardness testing, XRD, TEM and three-dimensional atom probe (3DAP) analysis. TEM micrographs revealed that the type of growth is abnormal, i.e. a composite structure is formed with some large (>1 μm) grains embedded in a matrix of nanometre sized grains. 3DAP studies showed no grain boundary segregation in as deposited materials and only low levels in material annealed for 1 h. Upon annealing, a 10% increase in hardness was observed within the first five minutes, after which the hardness was maintained for long times, despite the high volume fraction of large grains. Only after extensive annealing, when the majority of the material was made up of large grains, did the hardness decrease rapidly. The results demonstrate that the hardness is not determined by a law of mixtures but by percolation of the large grains.

Conflicting results on variation in the IGFI gene highlight methodological considerations in the design of genetic association studies

Abstract: Conflicting results on variation in the IGFI gene highlight methodological considerations in the design of genetic association studies We have analysed the same IGFI gene polymorphism in UK subjects and we did not observe any of the associations seen in the Dutch study (all trends seen were in the opposite direction). This highlights important methodological issues regarding the design of genetic association studies. We have analysed the IGFI gene polymorphism in 611 subjects from the UK Barry-Caerphilly cohort (BCG), and 348 patients with Type II diabetes [4] and a further 169 subjects from the Exeter Family study of childhood growth (EFS). All subjects gave informed consent with approval from the local research ethics committee in accordance with the declaration of Helsinki. We did not find that the absence of the common allele was associated with Type II diabetes or with any diabetic intermediate traits such as insulin resistance or beta-cell dysfunction. In addition, there was no association with birth weight (Table 1). The following factors could have caused differences in results: (i) the microsatellite might be in linkage disequilibrium (LD) with the functional variant and patterns of LD might differ between the two populations; (ii) the environmental exposures experienced by the study populations, which differ greatly in age – may lead to genotype influencing outcomes in different ways; (iii) the initial study is possibly a false positive result, since the many plausible candidate genes and polymorphisms that could be involved in fetal growth and or Type II diabetes means that the a priori odds of finding a genuine association will be low; (iv) our results could be a false negative, particularly because larger sample sizes are needed to replicate initial genetic associations that are real, given the finding that initial reports tend to overstate the effect size [5]. Diabetologia (2002) 45:1605–1606 DOI 10.1007/s00125-002-0951-1