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G R Law

Publications and source records attributed to G R Law.

At least 19 recordsLinked to original sources
PubMed2002

The importance of full participation: lessons from a national case-control study.

Differential participation between cases and controls can lead to biased estimates of risk. However, the effects of participation are often ignored. We report a detailed analysis of locations of residence for participants and non-participants in a large, national case-control study of childhood cancer in Great Britain, using the 1991 census. The initial selection of 7669 controls, taken from lists of those registered with a General Practitioner, was representative of the British population in respect to an areal-based index of material deprivation. However, parents of controls agreeing to participate were living in more affluent areas than initially selected controls and their matched 3838 cases. The three components of the deprivation index, persons unemployed, households not owning a car or their home were similarly associated with participation. Other census characteristics, such as proportion of flat dwellers and centrally heated households were also associated with control participation. Population density of the local area was not different between participating controls and their matched cases. However, initially selected controls lived in more urban areas than their cases. Such differences are not unique to this study, as they are an inevitable consequence of incomplete participation. The implications of these differences are discussed, in relation to the difficulty this imposes in the interpretation of studies of disease aetiology.

Adolescent↗
PubMed2002

Population mixing, childhood leukaemia, CNS tumours and other childhood cancers in Yorkshire.

We tested the hypothesis that variation in population mixing attributable to the diversity of migrants moving to an area is associated with the incidence of childhood leukaemia and other childhood cancers. An ecological analysis was performed on 954 children (<15 years) diagnosed with a malignancy between 1986 and 1996 in 532 electoral wards in Yorkshire, UK. Incidence rate ratios (IRR) were calculated for all childhood leukaemias (n=325), acute lymphoblastic leukaemia (ALL) (n=248), central nervous system (CNS) tumours (n=236) and other solid tumours (n=393) Incidence of all childhood leukaemias was significantly lower in areas of high (top decile) population mixing (IRR 0.72, 95% Confidence Interval (CI) 0.54-0.97) and higher in areas of low (bottom decile) population mixing (IRR 1.56, 95% CI 0.73-3.34), but similar patterns of incidence were not observed for central nervous system or other solid tumours. Population mixing may be a proxy for the range of infections circulating in a community and these results are consistent with the hypothesis that greater exposure to infections reduces the risk of developing childhood leukaemia by conferring efficient modulation of the immune system.

Adolescent↗
PubMed2002

Leukaemia incidence near coastal features.

BACKGROUND: The aim of the study was to independently test the hypothesis that leukaemia incidence is higher in proximity to estuaries. METHODS: Electoral wards were classified as to whether they included estuarine, coastal or only inland features. Rates of different adult and childhood leukaemias were computed for each ward category; that is, acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), chronic myeloid leukaemia (CML) aged 0-79 and for all childhood leukaemias combined (aged 0-14). RESULTS: Poisson regression analysis controlling for the effects of sex, age, and socioeconomic and urban-rural status, showed no statistically significant differences in incidence between wards with different levels of estuarine classification. CONCLUSION: The hypothesis created from an earlier dataset that a link exists between leukaemia and residence near estuaries is not upheld.

Adolescent↗
PubMed2001

Large tables.

The traditional exploration of large contingency tables leads to multiple comparisons with the inherent generation of chance associations. To allow for this, a simple empirical Bayesian approach is used here to derive estimates of association 'shrunk' towards a global mean. Estimates are displayed on ordered normal plots, to allow visual detection of outliers, with the addition of 'guide rails', derived from simulation, to facilitate their detection. The methods, and the interpretation of results, are illustrated using a large table of occupations for cancer registrations in England and Wales for 1971-90.

Journal Article↗
PubMed2001

Population mixing and childhood diabetes.

BACKGROUND: Exposure to infections, particularly in early life, may modify the risk of developing childhood diabetes. Population mixing, based on the number and diversity of incoming migrants to an area can be used as a proxy measure for exposure to infections. We tested the hypothesis that incidence of childhood Type 1 diabetes is higher in areas of low population mixing. METHODS: Children (<15 years) diagnosed with diabetes between 1986--1994 in Yorkshire, UK (n = 994) were analysed with demographic data and denominator populations from the 1991 UK Census. Population mixing was estimated separately for 'any age' (>1 year) and children (1--15 years) for each area, using the proportion of migrants and an index of diversity based on numbers and origins of migrants. Regression models calculated the effect of 'any age' and childhood population mixing on the incidence of diabetes, controlling for population density, ethnicity and proportion of migrants. RESULTS: Areas with low levels of population mixing of children (bottom decile), were significantly associated with higher incidence of childhood diabetes for 0-14 years (incidence rate ratio [IRR] = 1.46, 95% CI : 1.01--2.11). When stratified by age different effects were observed for childhood population mixing with raised IRR for ages 5-9 (2.23, 95% CI : 1.20--4.11) and 10-14 (1.47, 95% CI : 0.89--2.42), and decreased IRR for 0--4-year-olds (0.56, 95% CI : 0.17--1.82). CONCLUSION: The incidence of childhood diabetes is highest in areas where limited childhood population mixing occurs and the diversity of origins of incoming children is low; those over 4 years are at greatest risk. This is consistent with an infectious hypothesis where absence of stimulation to the developing immune system increases vulnerability to late infectious exposure, which may precipitate diabetes.

Adolescent↗
PubMed2000

Residential radon exposure and adult acute leukaemia.

Exposure to radioactive radon gas in homes, from natural sources, is an important public-health issue for many countries. We found no association between household exposure to radon and leukaemia in adults in the UK.

Acute Disease↗
PubMed2000

Early social mixing and childhood Type 1 diabetes mellitus: a case-control study in Yorkshire, UK.

AIMS: Evidence from animal models shows an increased risk of Type 1 diabetes mellitus associated with the absence of early life exposure to pathogens. To test this 'hygiene hypothesis', patterns of social mixing and infections in the first year of life and the risk of developing autoimmune diabetes in childhood were examined. METHODS: Personal interviews were conducted with the mothers of 220 children with Type 1 diabetes (0-15 years) and 433 age/sex matched controls from a population-based case control study in Yorkshire, UK. Social mixing including attendance at daycare, and infections occurring under 1 year of age were measures of exposure. Adjusted odds ratios (OR) were derived using conditional logistic regression. RESULTS: Frequency of attendance at daycare during the 1st year of life was inversely associated with childhood diabetes (OR 0.71, 95% confidence interval 0.51-1.00, P = 0.05), a finding not explained by mother's age, level of education or maternal diabetes. Increasing numbers of children in the daycare setting and numbers of sessions attended were significantly associated with increasing protection from diabetes. The strongest effect was observed in children with diabetes diagnosed aged 0-4 years. CONCLUSIONS: Social mixing through attendance at daycare in early infancy appears to confer protection against the development of childhood diabetes. This may be mediated through exposure to infectious agent(s) as a significant dose-response effect was evident with increasing numbers of child 'contacts'. These findings suggest early infectious exposure may play a role in the development of immunoregulatory mechanisms which protect against diabetes and further work is warranted.

Adolescent↗
PubMed1999

Perinatal and neonatal determinants of childhood type 1 diabetes. A case-control study in Yorkshire, U.K.

OBJECTIVE: To identify environmental factors that exert their effect in the perinatal and neonatal period and influence the subsequent onset of insulin dependent (type 1) diabetes during childhood. RESEARCH DESIGN AND METHODS: A population-based case-control study of data abstracted from the hospital obstetric and neonatal records of 196 children with type 1 diabetes and 325 age- and sex-matched control subjects. Analysis of matched sets by conditional logistic regression was conducted for a range of perinatal and neonatal factors. RESULTS: A significantly raised risk was observed for illnesses in the neonatal period (OR 1.61, 95% CI 1.06-2.44), the majority of which were infections and respiratory difficulties. Exclusive breast feeding as the initial feeding method was significantly protective (OR 0.65, 95% CI 0.45-0.94). There were no significant associations with high- or low-birth weight, being firstborn or small-for-dates. All factors significant (5% level) for the entire dataset, that is, maternal age, type 1 diabetes in mothers, preeclampsia, delivery by cesarean section, neonatal illnesses, and initial breast feeding were modeled and the OR remained significant for all variables other than cesarean section. CONCLUSIONS: The findings are based on medical record data that cannot be subject to biased recall of mothers. Neonatal illnesses increased and initial breast feeding decreased the risk of childhood type 1 diabetes. Further determinants of risk are mothers with type 1 diabetes, older mothers, and preeclampsia during pregnancy.

Adolescent↗
PubMed1998

Nitrate in drinking water and the incidence of gastric, esophageal, and brain cancer in Yorkshire, England.

OBJECTIVES: This small-area ecologic study in Yorkshire, northern England, examines the hypothesis that exposure to higher levels of nitrate in drinking water increases the risk of stomach, esophageal, or brain cancer in adults. METHODS: Nitrate levels over the period 1990-95 and numbers of incident cancers from 1975-94 were available for 148 water supply zones, geographically defined areas each supplying water of homogeneous chemical composition to an average population of around 20,000. RESULTS: No relationship was found between nitrate concentrations and the incidence of stomach or esophageal cancers. The incidence of cancer of the brain and central nervous system was found to be higher in areas with higher nitrate levels, with a relative risk of 1.18 (95 percent confidence interval = 1.08-1.30) in the quartile of the population with the highest average levels (mean 29.8 mg/l) compared with the lowest quartile (mean 2.4 mg/l). The increase in risk remained statistically significant (P < 0.01) after allowing for other covariates and for extra-Poisson variation in a regression model. CONCLUSIONS: This study does not support the hypothesis of an increased risk of stomach or esophageal cancer associated with higher nitrate levels in drinking water. The observed relationship with brain cancer requires confirmation in other studies, including those involving data on individuals.

Adolescent↗
PubMed1998

Mortality and diabetes from a population based register in Yorkshire 1978-93.

OBJECTIVE: To investigate mortality of children diagnosed with insulin dependent diabetes mellitus (IDDM) and to identify common factors before death. DESIGN: Follow up of a population based cohort of children diagnosed with IDDM to ascertain deaths. SETTING: Children were diagnosed in Yorkshire but followed up throughout the United Kingdom. SUBJECTS: From the Yorkshire Children's Diabetes Register details of 1854 children aged 0-16 years (1978-93) were submitted to the NHS Central Register. MAIN OUTCOME MEASURE: Notification and causes of death. RESULTS: 98.3% of cases were traced and 26 deaths identified. Follow up ranged from 1-18 years (median 9.3 years), providing 17,350 person-years of IDDM. Fifteen deaths (58%) were attributed to diabetes or its complications; 11 (42%) were unrelated and included one suicide. For mortality from all causes, the standardised mortality ratio (SMR) of 247 (95% confidence interval (CI) 163 to 362) was significantly increased for those under 34 years. The largest number of deaths (n = 10) occurred in the 15-19 year age range, with an SMR of 442 (95% CI 209 to 802). Case note examination showed a clear tendency towards poor diabetic control, and worries over control were expressed before death by health care professionals. CONCLUSIONS: Despite advances in treatment, IDDM still carries an increased mortality for young people, particularly in the "transition" age range.

Adolescent↗
PubMed1997

Incidence of childhood diabetes mellitus in Yorkshire, northern England, is associated with nitrate in drinking water: an ecological analysis.

The relationship between the incidence of childhood-onset insulin-dependent diabetes mellitus and levels of nitrate in drinking water in the former Yorkshire Regional Health Authority was investigated by means of an ecological analysis. A population-based register contributed 1797 0-16-year-olds diagnosed with diabetes between 1978 and 1994. Nitrate data were based on 9330 samples of drinking water tested between 1990 and 1995 in 148 water supply zones, for which 1991 census small area statistics were taken on population density, ethnicity and socio-economic status. Diabetes incidence was positively associated with raised mean nitrate levels with a standardised incidence ratio of 115 in zones with greater than 14.85 mg.1-1 (chi2 = 26.81, 1 df, p < 0.001). Significant negative trends were found between standardised incidence ratios and proportion of non-whites in the population (chi2 = 33.57, 1 df, p < 0.001), childhood population density (chi2 = 30.81, 1 df, p < 0.001) and the Townsend deprivation score (chi2 = 33.89, 1 df, p < 0.001). Poisson regression modelling, adjusting for the other factors, showed a significant increase in relative incidence rate ratio from a baseline of 1 at nitrate levels below 3.22 mg.1-1 to 1.27 (95% confidence interval 1.09, 1.48) for mean nitrate levels above 14.85 mg.1-1. An association between higher nitrate levels in domestic drinking water and incidence of childhood diabetes has been demonstrated. This was not explained by the ethnic composition of the population, population density or socioeconomic status. Nitrate in drinking water may be a precursor of chemicals which are toxic to the pancreas.

Adolescent↗
PubMed1997

Small area variation in the incidence of childhood insulin-dependent diabetes mellitus in Yorkshire, UK: links with overcrowding and population density.

BACKGROUND: The incidence of insulin-dependent diabetes mellitus (IDDM) incidence varies between and within countries. The origins of this variation are disputed, but they involve both genetic and non-genetic influences. To explore the role of environmental factors in the aetiology of IDDM we have examined the incidence in small geographical areas and related it to variables derived from national censuses. METHODS: This is an ecological analysis of incidence data from a register of children with IDDM covering the counties of West Yorkshire, North Yorkshire and Humberside in the north of England. All children aged < or = 16, diagnosed with IDDM between 1978 and 1990 were eligible for inclusion. Spatial variation in incidence between electoral wards was investigated using Poisson regression, in relation to socioeconomic status, population density, urban-rural status and measures of geographical isolation. Ward child populations varied in size from 84 to 7197 (mean = 1545). RESULTS: Rates were significantly lower in wards of high population density and with many overcrowded houses. The rate ratio for areas in the upper half of the childhood density distribution was 0.88 (95% confidence interval (CI): 0.78-0.99) and for the two upper tertiles of household overcrowding the rate ratios were 0.84 (95% CI: 0.74-0.95) and 0.68 (95% CI: 0.58-0.79) respectively. CONCLUSIONS: The incidence of childhood IDDM was associated with environmental factors including population density and overcrowded homes. A possible inference from these data is that patterns of infection are involved in the occurrence of IDDM. Analytical epidemiological studies will be needed to investigate these ideas further.

Adolescent↗
PubMed1997

Clustering of childhood IDDM. Links with age and place of residence.

OBJECTIVE: To improve understanding of the etiology of IDDM by analyzing spatial and space-time distribution of the incidence in children. RESEARCH DESIGN AND METHODS: Statistical tests to detect clustering were applied to a population-based register of 1,490 children (aged 0-16 years) with IDDM in Yorkshire, northern England. The Knox test analyzed clustering in space and time, and the Potthoff-Whittinghill test quantified spatial differences in incidence between small-area census units (electoral wards). The Potthoff-Whittinghill test was conditioned for childhood population density and deprivation (Townsend index). RESULTS: Both tests demonstrated clustering of IDDM in Yorkshire children. Space-time and spatial clustering is strongest in the younger children (0-4 and 5-9 years of age), even after conditioning for known associations. Clustering was more common in the county of Humberside during the years 1982-1985 and in wards of low population density (< 0.26 0- to 16 year-old subjects per hectare). CONCLUSIONS: The study revealed a nonrandom space-time distribution of IDDM in children not accounted for by known covarying demographic factors. The Potthoff-Whittinghill test has not previously been applied to childhood IDDM. The new finding of strong clustering in young children is consistent with early exposure, possibly in utero, to infectious agents or localized environmental sources.

Adolescent↗
PubMed1996

Geographical mapping of childhood diabetes in the northern English county of Yorkshire.

This study aimed to highlight geographical differences in childhood Type 1 (insulin dependent) diabetes mellitus (IDDM) by mapping incidence at 3 different geographical scales, within the northern English county of Yorkshire. Mapping techniques are applied to incident cases from a population-based regional register of childhood IDDM. The Yorkshire Children's Diabetes Register (YCDR) comprises 1310 children (0-14 years) diagnosed with IDDM from 1978-1990. Age standardized incidence rates (cases/100000/year) are given for administrative county, standardized incidence ratios (SIRs) are mapped by local government district and electoral ward. Heterogeneity between areas was assessed by a chi 2 test. At county level, incidence is 25% higher in Humberside (16.82 per 100000 per year) compared to West Yorkshire (12.21 per 100000 per year) (p < 0.001). SIRs for the 22 districts display significant heterogeneity (p < 0.001) with deficits in the urban areas of Kirklees (70 95% CI 57-85) and Bradford (81 95% CI 68-95) and significant excesses in the rural districts of Ryedale (147 95% CI 106-198), Beverley (149 95% CI 113-193), Holderness (166 95% CI 112-237) and Boothferry (186 95% CI 134-250). At the smallest scale, variation between wards is significant (p < 0.001) and low incidence in urban areas is notable. Geographical variation in the incidence of childhood IDDM may provide strong clues to its aetiology. Within Yorkshire, geographical distribution shows significant heterogeneity at three different scales. The magnitude of the variation is not explained by ethnic or genetic differences in the population and underlines the important influence of environmental factors in disease aetiology.

Adolescent↗
PubMed1978

Maternal vitamin E alters passively acquired immunity of chicks.

Passively transferred antibody levels were significantly increased in plasma of two- and seven-day-old chicks when the dams were fed 150 and 450 p.p.m. vitamin E prior to immunization with Brucella abortus. However, if the hens were fed 90, 300 and 900 p.p.m. vitamin E before immunization, the chicks evidenced no increase in antibody titers relative to controls. This nonlinear antibody response by the reticulo-endothelial system to vitamin E confirms in Gallus domesticus similar results reported for other species.

Animals↗