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Background: This study describes heat- and cold-related mortality in 12 urban populations in low- and middle-income countries, thereby extending knowledge of how diverse populations, in non-OECD countries, respond to temperature extremes., Methods: The cities were: Delhi, Monterrey, Mexico City, Chiang Mai, Bangkok, Salvador, São Paulo, Santiago, Cape Town, Ljubljana, Bucharest and Sofia. For each city, daily mortality was examined in relation to ambient temperature using autoregressive Poisson models (2- to 5-year series) adjusted for season, relative humidity, air pollution, day of week and public holidays., Results: Most cities showed a U-shaped temperature-mortality relationship, with clear evidence of increasing death rates at colder temperatures in all cities except Ljubljana, Salvador and Delhi and with increasing heat in all cities except Chiang Mai and Cape Town. Estimates of the temperature threshold below which cold-related mortality began to increase ranged from 15 degrees C to 29 degrees C; the threshold for heat-related deaths ranged from 16 degrees C to 31 degrees C. Heat thresholds were generally higher in cities with warmer climates, while cold thresholds were unrelated to climate., Conclusions: Urban populations, in diverse geographic settings, experience increases in mortality due to both high and low temperatures. The effects of heat and cold vary depending on climate and non-climate factors such as the population disease profile and age structure. Although such populations will undergo some adaptation to increasing temperatures, many are likely to have substantial vulnerability to climate change. Additional research is needed to elucidate vulnerability within populations.

Background: Living in a damp or mouldy home reportedly damages children's respiratory health, yet mould appears not to be a prominent risk factor in the public's perception. Analyses of data on over 58,000 children from the Pollution and the Young (PATY) study are presented. In this collaboration, researchers from 12 cross-sectional studies pooled their data to assess the effects of air quality on a spectrum of children's respiratory disorders., Method: Original studies were conducted in Russia, North America and 10 countries in Eastern and Western Europe. Pooled analyses were restricted to children aged 6-12 years. Associations between visible mould reported in the household and a spectrum of eight respiratory and allergic symptoms were estimated within each study. Logistic regressions were used, controlling for individual risk factors and for study area. Heterogeneity between study-specific results and mean effects (allowing for heterogeneity) were estimated using meta-analysis., Results: Visible mould was reported by 13.9% of respondents in Russia, increasing to 39.1% in North America. Positive associations between exposure to mould and children's respiratory health were seen with considerable consistency across studies and across outcomes. Confounder-adjusted combined ORs ranged from 1.30 (95% CI 1.22 to 1.39) for "nocturnal cough" to 1.50 (1.31 to 1.73) for "morning cough". Evidence of stronger effects in more crowded households was statistically significant for only asthma and sensitivity to inhaled allergens. No consistent interactions between mould and age, sex or parental smoking were found., Conclusion: Indoor mould exposure was consistently associated with adverse respiratory health outcomes in children living in these diverse countries.

Aims: This paper describes prevalences, time-trends and characteristics of self-reported never-drinkers, during the period 1994-2003, focussing particularly on white adults aged 18-54., Methods: Data on 122,809 adults (18 + ) were obtained from the Health Survey for England (HSfE). Logistic regressions were used to estimate time trends in self-reported never-drinking, and associations between never-drinking and living alone, and educational qualification. Analyses were stratified by gender, age group and period., Results: The overall proportion of white, female never-drinkers was 5.5%, rising monotonically with age. Proportions among men were much lower, with the lowest proportion (1.1%) in the 30-54 age group. Odds of never-drinking increased by 3% per year in those aged 30-54, a trend not explained by any covariates. Smaller increases were seen among those aged 18-29. Never-drinking was strongly associated with living with another adult and with lower qualification. The association with qualification increased over time among young women, and the association with living with another adult increased among men aged 30-54., Conclusions: Never-drinkers are a significant minority in England, whose prevalence rose, between 1994 and 2003, among adults aged under 55 years. The prevalence varies considerably by age, sex, and social characteristics, and the social discrepancies in never-drinking appear to be widening.

Background: Environmental pollution as a cause of congenital anomalies is sometimes suspected because of clustering of anomalies in areas of higher exposure. This highlights questions around spatial heterogeneity (clustering) in congenital anomaly rates. If spatial variation is endemic, then any one specific cluster is less remarkable, though the presence of uncontrolled geographically clustered risk factors is suggested. If rates are relatively homogeneous across space other than around specific hazards, then evidence for these hazards causing the clusters is strengthened. We sought to estimate the extent of spatial heterogeneity in congenital anomaly rates in the United Kingdom., Methods: The study population covered about one million births from five registers in Britain from 1991-1999. We estimated heterogeneity across four geographical levels: register area, hospital catchment, electoral ward, and enumeration district, using a negative binomial regression model. We also sought clusters using a circular scan statistic., Results: Congenital anomaly rates clearly varied across register areas and hospital catchments (p < 0.001), but not below this level (p > 0.2). Adjusting for socioeconomic deprivation and maternal age made little difference to the extent of geographical variation for most congenital anomaly subtypes. The two most significant circular clusters (of four ano-rectal atresias and six congenital heart diseases) contained two or more siblings., Conclusion: The variation in rates between registers and hospital catchment area may have resulted in part from differences in case ascertainment, and this should be taken into account in geographical epidemiological studies of environmental exposures. The absence of evidence for variation below this level should be interpreted cautiously in view of the low power of general heterogeneity tests. Nevertheless, the data suggest that strong localised clusters in congenital anomalies are uncommon, so clusters around specific putative environmental hazards are remarkable when observed. Negative binomial models applied at successive hierarchical levels provide an approach of intermediate complexity to characterising geographical heterogeneity.

Objectives: NO2)is a major urban air pollutant. Previously reported associations between ambient NO2)and children's respiratory health have been inconsistent, and independent effects of correlated pollutants hard to assess. The authors examined effects of NO2 on a spectrum of 11 respiratory symptoms, controlling for PM10 and SO2, using a large pooled dataset., Methods: Cross sectional studies were conducted in Russia, Austria, Italy, Switzerland, and the Netherlands, during 1993-99, contributing in total 23 955 children. Study-specific odds ratios for associations with ambient NO2 are estimated using logistic regressions with area-level random effects. Heterogeneity between study-specific results, and mean estimates (allowing for heterogeneity) are calculated., Results: Long term average NO2 concentrations were unrelated to prevalences of bronchitis or asthma. Associations were found for sensitivity to inhaled allergens and allergy to pets, with mean odds ratios around 1.14 per 10 microg/m3 NO2. SO2 had little confounding effect, but an initial association between NO2 and morning cough was reduced after controlling for PM10. Associations with reported allergy were not reduced by adjustment for the other pollutants. Odds ratios for allergic symptoms tended to be higher for the 9-12 year old children compared with the 6-8 year old children., Conclusions: Evidence for associations between NO2 and respiratory symptoms was robust only for inhalation allergies. NO2 most likely is acting as an indicator of traffic related air pollutants, though its direct effect cannot be ruled out. This remains important, as policies to reduce traffic related air pollution will not result in rapid reductions.

Objectives: Adverse effects have been reported of prenatal and/or postnatal passive exposure to smoking on children's health. Uncertainties remain about the relative importance of smoking at different periods in the child's life. We investigate this in a pooled analysis, on 53,879 children from 12 cross-sectional studies--components of the PATY study (Pollution And The Young)., Methods: Effects were estimated, within each study, of three exposures: mother smoked during pregnancy, parental smoking in the first two years, current parental smoking. Outcomes were: wheeze, asthma, "woken by wheeze", bronchitis, nocturnal cough, morning cough, "sensitivity to inhaled allergens" and hay fever. Logistic regressions were used, controlling for individual risk factors and study area. Heterogeneity between study-specific results, and mean effects (allowing for heterogeneity) were estimated using meta-analytical tools., Results: There was strong evidence linking parental smoking to wheeze, asthma, bronchitis and nocturnal cough, with mean odds ratios all around 1.15, with independent effects of prenatal and postnatal exposures for most associations., Conclusions: Adverse effects of both pre- and postnatal parental smoking on children's respiratory health were confirmed. Asthma was most strongly associated with maternal smoking during pregnancy, but postnatal exposure showed independent associations with a range of other respiratory symptoms. All tobacco smoke exposure has serious consequences for children's respiratory health and needs to be reduced urgently.

Rationale: Both prenatal and postnatal passive smoking have been linked with respiratory symptoms and asthma in childhood. Their differential contributions to lung function growth in the general children's population are less clear., Objective: To study the relative impact of pre- and postnatal exposure on respiratory functions of primary school children in a wide range of geographic settings, we analyzed flow and volume data of more than 20,000 children (aged 6-12 yr) from nine countries in Europe and North America., Methods: Exposure information had been obtained by comparable questionnaires, and spirometry followed a protocol of the American Thoracic Society/European Respiratory Society. Linear and logistic regressions were used, controlling for individual risk factors and study area. Heterogeneity between study-specific results and mean effects were estimated using meta-analytic tools., Main Results: Smoking during pregnancy was associated with decreases in lung function parameters between -1% (FEV1) and -6% maximal expiratory flow at 25% of vital capacity left (MEF25). A 4% lower maximal midexpiratory flow (MMEF) corresponded to a 40% increase in the risk of poor lung function (MMEF < 75% of expected). Associations with current passive smoking were weaker though still measurable, with effects ranging from -0.5% (FEV1) to -2% maximal expiratory flow (MEF50)., Conclusions: Considering the high number of children exposed to maternal smoking in utero and the even higher number exposed to passive smoking after birth, this risk factor for reduced lung function growth remains a serious pediatric and public health issue.

Inequalities in health between socio-economic groups are a major public health concern. The current authors studied associations between parental socio-economic status (SES) and children's respiratory and allergic symptoms in 13 diverse countries, including the Russian Federation, North America (Canada and the USA), and countries across Eastern and Western Europe. Data of 57,000 children aged 6-12 yrs, originating from eight cross-sectional studies, were analysed. SES was defined by parental education. Respiratory and allergic symptoms were defined by parental questionnaire reports. Multiple logistic regressions showed that low parental education was associated with a decreased risk of inhalant allergy and itchy rash in school children. Furthermore, low parental education was associated with an increased prevalence of wheeze and nocturnal dry cough. No clear association was found between parental education and prevalence of doctor-diagnosed asthma and bronchitis. Part of the difference between socio-economic groups with regard to their children's symptoms was explained by established risk factors, such as parental allergy, smoking during pregnancy, pet ownership, crowding, mould/moisture in the home, use of gas for cooking, and air pollution (particulate matter with a diameter of <10 microm). However, differences remained after adjusting for these variables. Children's health was associated with parental education. The association could not fully be explained by established risk factors.

Aims: To describe trends in total and live birth prevalence, regional differences in prevalence, and outcome of pregnancy of selected congenital anomalies., Methods: Population based registry study of 839,521 births to mothers resident in five geographical areas of Britain during 1991-99. Main outcome measures were: total and live birth prevalence; pregnancy outcome; proportion of stillbirths due to congenital anomalies; and secular trends., Results: The sample consisted of 10,844 congenital anomalies, giving a total prevalence of 129 per 10,000 registered births (95% CI 127 to 132). Live birth prevalence was 82.2 per 10,000 births (95% CI 80.3 to 84.2) and declined significantly with time. The proportion of all stillbirths with a congenital anomaly was 10.5% (453 stillbirths). The proportion of pregnancies resulting in a termination increased from 27% (289 cases) in 1991 to 34.7% (384 cases) in 1999, whereas the proportion of live births declined from 68.2% (730 cases) to 58.5% (648 cases). Although similar rates of congenital anomaly groups were notified to the registers, variation in rates by register was present. There was a secular decline in the total prevalence of non-chromosomal and an increase in chromosomal anomalies., Conclusions: Regional variation exists in the prevalence of specific congenital anomalies. For some anomalies this can be partially explained by ascertainment variation. For others (neural tube defects, diaphragmatic hernia, gastroschisis), higher prevalence rates in the northern regions (Glasgow and Northern) were true differences. Live birth prevalence declined over the study due to an increase in terminations of pregnancy.

Background: Congenital anomaly registers collect data on antenatally and postnatally detected anomalies for surveillance, research, and public health purposes. Each anomaly is coded using the International Statistical Classification of Diseases and Related Health Problems (ICD-9/ICD-10) based on body systems, allowing accurate comparisons between registers for individual anomalies. When commencing an environmental, epidemiological study, it became clear to us that there is no standard classification that takes aetiology into account. This paper describes a new classification for use in studies addressing aetiology., Method: A classification system was evolved and piloted using cases in a study of geographical variation in congenital anomaly prevalence.1 Cases that were difficult to categorise were noted, and after discussion with a team of experts, the classification was adjusted accordingly., Results and Conclusion: A robust, hierarchical method of classifying birth defects into eight categories has been produced, for use at source of data registration in conjunction with, but independent of, ICD coding.

Objective: Firstly, to assess the completeness of ascertainment in the National Congenital Anomaly System (NCAS), the basis for congenital anomaly surveillance in England and Wales, and its variation by defect, geographical area, and socioeconomic deprivation. Secondly, to assess the impact of the lack of data on pregnancies terminated because of fetal anomaly., Design: Comparison of the NCAS with four local congenital anomaly registers in England., Setting: Four regions in England covering some 109,000 annual births., Participants: Cases of congenital anomalies registered in the NCAS (live births and stillbirths) and independently registered in the four local registers (live births, stillbirths, fetal losses from 20 weeks' gestation, and pregnancies terminated after prenatal diagnosis of fetal anomaly)., Main Outcome Measure: The ratio of cases identified by the national register to those in local registry files, calculated for different specified anomalies, for whole registry areas, and for hospital catchment areas within registry boundaries., Results: Ascertainment by the NCAS (compared with data from local registers, from which terminations of pregnancy were removed) was 40% (34% for chromosomal anomalies and 42% for non-chromosomal anomalies) and varied markedly by defect, by local register, and by hospital catchment area, but not by area deprivation. When terminations of pregnancy were included in the register data, ascertainment by NCAS was 27% (19% for chromosomal anomalies and 31% for non-chromosomal anomalies), and the geographical variation was of a similar magnitude., Conclusion: The surveillance of congenital anomalies in England is currently inadequate because ascertainment to the national register is low and non-uniform and because no data exist on termination of pregnancy resulting from prenatal diagnosis of fetal anomaly.

Objective: To examine the determinants of vulnerability to winter mortality in elderly British people., Design: Population based cohort study (119,389 person years of follow up)., Setting: 106 general practices from the Medical Research Council trial of assessment and management of older people in Britain., Participants: People aged > or = 75 years., Main Outcome Measures: Mortality (10,123 deaths) determined by follow up through the Office for National Statistics., Results: Month to month variation accounted for 17% of annual all cause mortality, but only 7.8% after adjustment for temperature. The overall winter:non-winter rate ratio was 1.31 (95% confidence interval 1.26 to 1.36). There was little evidence that this ratio varied by geographical region, age, or any of the personal, socioeconomic, or clinical factors examined, with two exceptions: after adjustment for all major covariates the winter:non-winter ratio in women compared with men was 1.11 (1.00 to 1.23), and those with a self reported history of respiratory illness had a winter:non-winter ratio of 1.20 (1.08 to 1.34) times that of people without a history of respiratory illness. There was no evidence that socioeconomic deprivation or self reported financial worries were predictive of winter death., Conclusion: Except for female sex and pre-existing respiratory illness, there was little evidence for vulnerability to winter death associated with factors thought to lead to vulnerability. The lack of socioeconomic gradient suggests that policies aimed at relief of fuel poverty may need to be supplemented by additional measures to tackle the burden of excess winter deaths in elderly people.

Objective: To estimate the protection against death provided by vaccination against influenza., Design: Prospective cohort follow up supplemented by weekly national counts of influenza confirmed in the community., Setting: Primary care., Participants: 24,535 patients aged over 75 years from 73 general practices in Great Britain., Main Outcome Measure: Death., Results: In unvaccinated members of the cohort daily all cause mortality was strongly associated with an index of influenza circulating in the population (mortality ratio 1.16, 95% confidence interval 1.04 to 1.29 at 90th centile of circulating influenza). The association was strongest for respiratory deaths but was also present for cardiovascular deaths. In contrast, in vaccinated people mortality from any cause was not associated with circulating influenza. The difference in patterns between vaccinated and unvaccinated people could not easily be due to chance (P = 0.02, all causes)., Conclusions: This study, using a novel and robust approach to control for confounding, provides robust evidence of a protective effect on mortality of vaccination against influenza.

Background: The aim of this study was to determine whether the risk of congenital anomalies in a population resident close to a waste combustion plant located at Byker in the city of Newcastle upon Tyne, United Kingdom, was higher than in a population resident further away., Methods: A geographical study was carried out on the prevalence of congenital anomalies in residents living within 3 km (inner zone) of the Byker combustion plant compared with those living 3-7 km (outer zone) from the plant. There were 81255 live births (1985-1999) and 1508 cases with chromosomal and non-chromosomal congenital anomalies. The cases were identified from the Northern Region Congenital Abnormality Survey., Results: After the site commenced operation the estimated rate ratio (inner versus outer zone) was 1.11 (95 per cent confidence interval (CI) 0.96-1.28) adjusted for socio-economic deprivation. There was significant heterogeneity across years and an increasing trend, of marginal significance (p = 0.07), in the rate ratio. The inner zone rate approached or became significantly higher than that in the outer zone in some of the later years., Conclusions: No significant overall association between the number of congenital anomalies and proximity of residence to the Byker waste combustion plant has been found in this study. Significantly increased rates near the site during the later years may suggest a possible risk but are difficult to interpret. More comprehensive, multi-site investigations around other waste combustion plants are indicated.

Study Objective: Heat and cold have been associated with increased mortality, independently of seasonal trends, but details are little known. This study explores associations between mortality and temperature in two European capitals-Sofia and London-using four years of daily deaths, air pollution, and weather data., Design: Generalised additive models were used to permit non-linear modelling of confounders such as season and humidity, and to show the shape of mortality-temperature relations-using both two day and two week average temperatures separately. Models with linear terms for heat and cold were used to estimate lags of effect, linear effects, and attributable fractions., Participants: 44701 all age all cause deaths in Sofia (1996-1999) and 256464 in London (1993-1996)., Main Results: In London, for each degree of extreme cold (below the 10th centile of the two week mean temperature), mortality increased by 4.2% (95% CI 3.4 to 5.1), and in Sofia by 1.8% (0.6 to 3.9). For each degree rise above the 95th centile of the two day mean, mortality increased by 1.9% (1.4 to 2.4) in London, and 3.5% (2.2 to 4.8) in Sofia. Cold effects appeared after lags of around three days and lasted-particularly in London-at least two weeks. Main heat effects occurred more promptly. There were inverse associations at later lags for heat and cold in Sofia., Conclusions: Average temperatures over short periods do not adequately model cold, and may be inadequate for heat if they ignore harvesting effects. Cold temperatures in London, particularly, seem to harm the general population and the effects are not concentrated among persons close to death.

Background: The results of studies on the effect of nutrition on respiratory diseases are inconsistent. The role of nutrition in children's respiratory health was therefore analysed within the cross sectional Central European Study on Air Pollution and Respiratory Health (CESAR)., Method: A total of 20 271 children aged 7-11 were surveyed in six European countries. Respiratory health and food intake were assessed using questionnaires. Associations between four symptoms and nutritional factors were evaluated using logistic regression, controlling for area plus other potential confounders., Results: All symptoms showed initial associations with nutritional factors. Low consumption of fish and of summer and winter fruit were the most consistent predictors. In a fully adjusted model low fish intake remained a significant independent predictor of persistent cough (OR=1.18; 95% CI 1.04 to 1.34), wheeze ever (OR=1.14; 95% CI 1.03 to 1.25) and current wheeze (OR=1.21; 95% CI 1.06 to 1.39) and a weaker predictor of winter cough (OR=1.10; 95% CI 0.99 to 1.23). Low summer fruit intake was a predictor of winter cough (OR=1.40; 95% CI 1.10 to 1.79) and persistent cough (OR=1.35; 95% CI 1.01 to 1.82). Low winter fruit intake was associated with winter cough (OR=1.28; 95% CI 1.09 to 1.51). Associations between symptoms and vegetable intake were inconsistent. Low summer intake was significantly associated with winter cough (OR=1.23; 95% CI 1.03 to 1.47) but, overall, winter intake had inverse associations with both coughs. Associations between winter vegetable intake and wheeze varied considerably between countries., Conclusion: A number of associations were found between respiratory symptoms and low intake of fish, fruit and vegetables in children. Low fish intake was the most consistent predictor of poor respiratory health. Fruit and vegetable intake showed stronger associations with cough than with wheeze.

There is currently little and conflicting evidence concerning the existence of socio-economic inequalities in cerebral palsy prevalence, or the extent to which this is influenced by socio-economic inequalities in low birthweight, a strong risk factor for cerebral palsy. The study is based on 753 children registered with cerebral palsy, resident in the former Oxford Regional Health Authority area and born in the years 1984-90. Two population definitions were used: 1. Children with cerebral palsy resident at birth in the area, with resident births as denominator, 2. Children with cerebral palsy resident at age 5 in the area, with children of ages 1-7 resident in the area in the 1991 census as denominator. Children with cerebral palsy and all births/children were classified according to the Carstairs area deprivation index (grouped into quintiles) of their ward of residence. The prevalence among residents at birth varied from 2.08 per 1000 births in the most affluent quintile to 3.33 in the most deprived quintile (trend P < 0.001). Although there was a tendency for children to move to more affluent areas during early childhood, the socio-economic gradient was similar at age 5. A greater proportion of births in the more deprived quintiles were of low or very low birthweight, the proportion rising from 5.6% in the most affluent quintile to 8.2% in the most deprived. Within the normal birthweight category there was a trend for higher prevalence of cerebral palsy in more deprived quintiles, from 1.29 per 1000 in the most affluent quintile to 2.42 in the most deprived quintile (trend P < 0.001). Within the low birthweight and very low birthweight groups, separately or combined, there was no evidence of any relationship between cerebral palsy prevalence and deprivation. We estimate that up to 17% of cerebral palsy cases might be "preventable" in terms of the reduction to be expected if the whole population had the rate of cerebral palsy of the most affluent quintile. Although the strong socio-economic gradient for cerebral palsy was restricted to the normal birthweight category, we estimate that two-thirds of the excess cases in the population associated with greater socio-economic deprivation were normal birthweight cases, and one-third were low birthweight cases owing to the greater prevalence of low birthweight in more deprived populations. The pattern of socio-economic inequalities should be further explored in other regions, and should be taken into account in aetiological research, and in the effective delivery and evaluation of services.

This paper describes the method of compilation of the Northern Ireland Cerebral Palsy Register (NICPR) and outlines the epidemiology of cerebral palsy (CP) in Northern Ireland in 1981--93 based on an analysis of 784 cases. Multiple and overlapping sources of notification were used to compile the NICPR. Each case was followed up with a standardised assessment completed at age 5 years and validated by a paediatrician. Over 70% of cases were multiply notified, and paediatricians were the most important source of notification. Cases of CP most likely to be under-ascertained included those very mildly affected, cases who died before the register began (death certificates were searched but found to be unreliable) and cases who moved out of the area before their diagnosis was confirmed. The prevalence of CP for the birth period 1981--93 was 2.24 per 1000 livebirths [95% CI 2.08, 2.40]. There were no statistically significant temporal or geographic variations in the rate of CP. Almost half the cases of CP were of low birthweight (<2500 g), and this proportion increased during 1987--89, but decreased (P < 0.01) more recently (1990--93). The proportion of cases weighing <1000 g trebled from 3% in 1981--83 to 10% in 1990--93 (P < 0.01). The most common CP subtype was bilateral spastic cerebral palsy (55%). Just over a quarter (29%) of cases were unable to walk (with/without aids), and one-fifth (22%) had no useful hand/arm function. Almost half (49%) the cases had at least one other impairment (intellectual, sensory impairment or active seizures) in association with their CP. Prevalence rates and the pattern of disability in populations of people with CP can only be evaluated on the basis of the methods of case definition and ascertainment. We have demonstrated the methods necessary to ensure valid, standard and detailed information on CP for the purposes of surveillance, service planning and research.

Objectives: Many studies of air pollution and health are carried out over several geographical areas, and sometimes over several countries. This paper explores three approaches to analysis in such studies: a non hierarchical model, a two-stage analysis, and multilevel modelling. Illustrations are given using a preliminary subset of data from the CESAR study., Design: The Central European Study on Air pollution and Respiratory Health (CESAR) was conducted in 25 areas within six Central European countries, enrolling 20,271 schoolchildren. Pollution averages were calculated for each area. Associations between pollution and health outcomes were estimated under different models., Main Results: A regression analysis of log FVC (forced vital capacity) on PM10, ignoring the geographical hierarchy, estimated a significant mean drop in FVC (adjusted for confounders) of 2.2% (95% CI 0.5% to 1.3%), p=0.007, from the area with the lowest PM10 to that with the highest. A multilevel model (mlm), using data for all children, but with random effects at area and country level, estimated a drop of 2.8% (-0.6% to 6.1%), p=0.110. A two-stage analysis (mean log FVC, adjusted for confounders, was estimated for each area using regression, and these means then regressed on PM10) estimated a drop of 2.6% (-0.5% to 5.5%), p=0.101. Simulation exercises showed the non hierarchical method to be very inadequate in the context of the CESAR study, with only half of all 95% confidence intervals for the estimated PM10 slope containing the true value (i.e., that used to create the simulated data). The two-stage and multilevel modelling methods gave results which were substantially better, though both underperformed slightly. All three methods appeared to give unbiased slope estimates., Conclusions: Acknowledgement of hierarchical structures is essential in statistical inference--standard errors can be substantially incorrect when they are ignored. Multilevel, random-effects models correctly address hierarchical structures, though having few units at higher levels can cause problems in convergence, especially where complex modelling is required. Two-stage analyses, acknowledging hierarchy, provide simple alternatives to random-effects models.

With growing evidence of the adverse health effects of air pollution--especially fine particulates--investigators must concentrate on the fetus, neonate, and infant as potentially vulnerable groups. Cokeworks are a major source of smoke and sulfur dioxide. In the current study, the authors investigated whether populations residing near cokeworks had a higher risk of adverse perinatal and infant outcomes. Zones of 7.5-km radius around 22 cokeworks in Great Britain were studied, within which the authors assumed that exposure declined from highest levels within 2 km to background levels. Routinely recorded birth and death data for Great Britain during the period 1981-1992 were analyzed. Each individual record had a postcode that referred to a small geographical area of typically 15-17 addresses. The authors calculated expected numbers on the basis of regional rates, stratified by year, sex, and a small-area socioeconomic deprivation score. For all cokeworks combined, the observed/expected ratio (95% confidence intervals within parentheses) within 2 km of cokeworks was 1.00 (0.95, 1.06) for low-birth-weight (i.e., < 2,500 g) infants; 0.94 (0.78, 1.12) for still births; 0.95 (0.83, 1.09) for infant mortality; 0.86 (0.72, 1.03) for neonatal mortality; 1.10 (0.90, 1.33) for postneonatal mortality; 0.79 (0.30, 1.46) for respiratory postneonatal mortality; and 1.07 (0.77, 1.43) for postneonatal Sudden Infant Death Syndrome. Respiratory postneonatal mortality was low throughout the entire 0-7.5-km study area (observed/expected = 0.74 [0.61, 0.88]). There was no statistically significant decline in risk with distance from cokeworks for any of the outcomes studied. The authors concluded that there was no evidence of an increased risk of low birth weight, stillbirths, and/or neonatal mortality near cokeworks, and there was no strong evidence for any association between residence near cokeworks and postneonatal mortality. One must remember, however, the limited statistical power of the study to detect small risks.

pRB is required for IFN-gamma-induction of MHC class II in human tumor cell lines, providing a potential link between tumor suppressors and the immune system. However, other genes, such as cyclin D1, show pRB-dependency only in tumor cells, so by analogy, pRB may not be necessary for cII-regulation in normal cells. Here, we demonstrate that induction of the mouse MHC class II I-A heterodimer is normal in RB+/+ mouse embryonic fibroblasts (MEFs), but deficient in RB-/- MEFs. Inducibility is restored in RB-/- MEFs stably transfected with wild type RB cDNA or infected with an adenovirus expressing pRB. Thus, involvement of pRB in MHC class II expression is conserved in the mouse and is not an aberrant feature of tumorigenic, aneuploid, human tumor cells. Although cII genes are generally induced in a coordinate fashion, suggesting a common mechanism, we found that pRB was specifically required for induction of the Abeta, but not Aalpha or other MHC cII genes including Ebeta, Ii and H2-Malpha. Finally, IFN-gamma-induction of class II transactivator (CIITA), was pRB-independent, suggesting that pRB works downstream of this master-regulator of MHC class II expression.

Objective: To describe the extent of socioeconomic inequalities in low birth weight. To assess the relative benefits of measuring socioeconomic status by individual occupation, socioeconomic deprivation status of area of residence, or both, for describing inequalities and targeting resources., Design: Analysis of birth registrations by registration status: joint compared with sole registrants ("lone mothers"), routinely recorded parental occupation (father's for joint registrants), and census derived enumeration district (ED) deprivation., Setting: England and Wales, 1986-92., Subjects: 471,411 births with coded parental occupation (random 10% sample) and birth weight., Main Outcome Measures: Proportion of low birth weight (< 2500 g), Results: 34% of births to joint registrants in social classes IV and V, and 45% of births to sole registrants, were in the quintile of most deprived EDs. It was found that 6.8% of births were of low birth weight. Sole registrants were at higher risk (9.3% overall) than joint registrants, across all deprivation quintiles. For joint registrants, the socioeconomic risk gradient was similar by social class or area deprivation, but a greater gradient from 4.7% to 8.7% was found with combined classification., Conclusions: Up to 30% of low birth weight can be seen as being associated with levels of socioeconomic deprivation below that of the most affluent group, as measured in this study. Caution is needed when targeting interventions to high risk groups when using single indicators. For example, the majority of births to lone mothers and to joint registrants in social classes IV and V would be missed by targeting the most deprived quintile. There is a high degree of inequality in low birth weight according to social class, area deprivation and lone mother status. When using routinely recorded birth and census data, all three factors are important to show the true extent of inequalities.

Objectives: To examine the incidence and mortality of cancer near the Pan Britannica Industries factory, Waltham Abbey, after reports of a possible cluster of all cancers and brain cancer in the vicinity., Method: Small area study of cancer incidence 1977-89, and mortality 1981-92, within a 7.5 km radius of the factory site. Postcoded cancer registrations and deaths in the study area were extracted from national data sets held by the Small Area Health Statistics Unit and compared with expected numbers computed by applying national rates stratified for age, sex, and deprivation to the local population (1981 and 1991 censuses). Observed/ expected (O/E) ratios were examined from 0-1 km and 0-7.5 km of the plant, and tests applied for a decline in relative risk with distance up to 7.5 km., Results: There were 12,859 incidence cancers (1977-89) from 0-7.5 km (O/E ratio 1.04; 95% confidence interval (95% CI) 1.02 to 1.06) and 385 from 0-1 km (O/E 1.10; 1.00 to 1.22). There was an excess of skin melanoma from 0-1 km based on 11 cases (O/E 2.13; 1.06 to 3.80), and an excess from 0-7.5 km of cancer of the lung, stomach and pancreas combined, and prostate (O/Es ranged from 1.09 to 1.13). Only the findings from lung cancer were suggestive of a decline in risk with distance, especially in the later period (1982-9). There were 9196 cancer deaths (1981-92) from 0-7.5 km (O/E 1.04; 95% CI 1.02 to 1.06) and 308 from 0-1 km (O/E 1.24; 1.11 to 1.39); and 25507 non-cancer deaths (O/E 1.02; 1.01 to 1.04) from 0-7.5 km and 745 (O/E 1.14; 1.06 to 1.22) from 0-1 km. There was evidence of a decline in mortality with distance for all cancers combined, lung cancer (P = 0.001 for each), and colorectal cancer (P < 0.05), and also for non-cancers (P = 0.001). Proportional mortality analyses suggested a decline in risk with distance for lung cancer (P = 0.003) but not for all cancers or the site specific cancers examined. There was no evidence of an excess in the incidence or mortality from brain cancer. For cancer mortality in the inner-most wards, the findings were, for the most part, well within the range of variation across the region as a whole., Conclusions: The study provides limited and inconsistent evidence for a localised excess of cancer in the vicinity of the PBI plant. At present, further investigation does not seem warranted other than continued surveillance of mortality and cancer incidence in the locality.

Objectives: To study incidence and mortality of leukaemias, cancer of the larynx, and other cancers near the petrochemical plant at Baglan Bay, in response to local concerns of an alleged cluster of cancers in the vicinity., Methods: This is a small area study of cancer incidence, 1974-84 and of mortality, 1981-91 based on the national postcoded data held by the Small Area Health Statistics Unit and with population and socioeconomic data from the 1981 census. The study is centred on BP Chemicals Ltd, Baglan Bay, Port Talbot, West Glamorgan, South Wales and includes a general population sample of 115,721 people (1981 census) living within 7.5 km of the plant. Cancer incidence and mortality for all cancers, leukaemias, and cancer of the larynx were examined within 7.5 km and 3 km of the plant, and tests for decline in risk of these cancers with distance from the plant were carried out. Mortality from several other cancers possibly associated with the petrochemical industry was also studied., Results: There were 5417 incident cancer cases and 2458 cancer deaths within 7.5 km of the plant during the periods of study. There was an 8% excess incidence of all cancers within 7.5 km, and a 24% excess of cancer of the larynx, consistent with a general excess of these cancers in West Glamorgan, but no apparent decline in incidence with distance from the plant, nor excess mortality. There was also no evidence of decline in leukaemia incidence or mortality with distance, at all ages or in children. Among the other causes included in the mortality study, there was an excess of multiple myeloma within 7.5 km, especially among women, and a significant decline in mortality from non-Hodgkin's lymphomas although there was no excess overall within 7.5 km., Conclusions: The apparent excess incidence of all cancers and cancer of the larynx within 7.5 km of the BP Chemical Ltd works was consistent with an excess more generally in West Glamorgan, possibly related, at least to some extent, to cancer registration in Wales. There was no excess mortality from these cancers. The results for multiple myeloma and especially non-Hodgkin's lymphomas may have been chance findings in view of the multiple tests of significance carried out in the study. A study of lymphatic and haematopoietic cancers near oil refineries in Great Britain is to be undertaken that will help put the findings of the present study in wider context.

The Small Area Health Statistics Unit (SAHSU) is a new independent facility for the investigation of disease near industrial installations in the UK. SAHSU analysed the incidence of cancers of the larynx and lung near the incinerator of waste solvents and oils at Charnock Richard, Coppull, Lancashire (which operated between 1972 and 1980) and nine other similar incinerators in Great Britain, after reports of a cluster of cases of cancer of the larynx near the Charnock Richard site. Postcoded cancer registration data were available for 1974-84 in England and Wales and 1975-87 in Scotland. Lag periods of 5 and 10 years were used between start-up (or first registration) of the incinerators and cancer incidence. Standardised observed/expected (O/E) ratios were assessed within 3 km and 3-10 km of each site and then aggregated over all sites. Expected values were based on national rates (regionally adjusted) with and without stratification by Carstairs' index, a measure of the socioeconomic profile of areas that uses census data for enumeration districts. Data were also assessed over a range of circles up to 10 km to test for trend in O/E ratios with distance. For Charnock Richard, none of the O/E ratios within 3 km or from 3-10 km differed significantly from unity, for either cancer or lag period. In the analysis of all sites with stratification by Carstairs' index, none of these O/E ratios differed significantly from unity for the two cancers. There was no evidence of decreasing risk with distance from the sites of either cancer. We conclude that the apparent cluster of cases of cancer of the larynx reported near Charnock Richard was unlikely to be due to its former incinerator.