Denis Hémon

Modifying the t test for assessing the correlation between two spatial processes

Clifford, Richardson, and Hm they require the estimation of an effective sample size that takes into account the spatial structure of both processes. Clifford et al. developed their method on the basis of an approximation of the variance of the sample correlation coefficient and assessed it by Monte Carlo simulations for lattice and non-lattice networks of moderate to large size. In the present paper, the variance of the sample covariance is computed for a finite number of locations, under the multinormality assumption, and the mathematical derivation of the definition of effective sample size is given. The theoretically expected number of degrees of freedom for the modified t test with renewed modifications is compared with that computed on the basis of equation (2.9) of Clifford et al. (1989). The largest differences are observed for small numbers of locations and high autocorrelation, in particular when the latter is present with opposite sign in the two processes. Basic references that were missing in Clifford et al. (1989) are given and inherent ambiguities are discussed.

Assessing the significance of the correlation between two spatial processes.

Modified tests of association based on the correlation coefficient or the covariance between two spatially autocorrelated processes are presented. These tests can be used both for lattice and nonlattice data. They are based on the evaluation of an effective sample size that takes into account the spatial structure. For positively autocorrelated processes, the effective sample size is reduced. A method for evaluating this reduction via an approximation of the variance of the correlation coefficient is developed. The performance of the tests is assessed by Monte Carlo simulations. The method is illustrated by examples from geographical epidemiology.

Household exposure to pesticides and risk of childhood acute leukaemia

Objectives: To investigate the relation between childhood acute leukaemia and household exposure to pesticides. Methods: The study included 280 incident cases of acute leukaemia and 288 controls frequency matched on gender, age, hospital, and ethnic origin. The data were obtained from standardised face to face interviews of the mothers with detailed questions on parental occupational history, home and garden insecticide use, and insecticidal treatment of pediculosis. Odds ratios were estimated using unconditional regression models including the stratification variables parental socioeconomic status and housing characteristics. Results: Acute leukaemia was observed to be significantly associated with maternal home insecticide use during pregnancy (OR = 1.8, 95% CI 1.2 to 2.8) and during childhood (OR = 1.7, 95% CI 1.1 to 2.4), with garden insecticide use (OR = 2.4, 95% CI 1.3 to 4.3), and fungicide use (OR = 2.5, 95% CI 1.0 to 6.2) during childhood. Insecticidal shampoo treatment of pediculosis was also associated with childhood acute leukaemia (OR = 1.9, 95% CI 1.2 to 3.3). Conclusion: The results reported herein support the hypothesis that various types of insecticide exposure may be a risk factor for childhood acute leukaemia. The observed association with insecticidal shampoo treatment of pediculosis, which has never been investigated before, requires further study.

Age, blood pressure and smoking effects on chronic renal failure in primary glomerular nephropathies.

BACKGROUND Smoking is a known risk factor for renal damage in diabetic patients, but its relationship to other renal diseases is less clear. To assess its effect in primary glomerular nephropathy (GN), we used data from a case control study designed to assess several environmental risk factors. METHODS This study included 295 biopsy-proven GN cases, 80 membranous nephropathy, 116 IgA nephropathy, and 99 nephrotic syndrome with either minimal change nephropathy or focal segmental hyalinosis, and 242 matched hospital controls, with diseases unrelated to smoking. Subjects were interviewed about their smoking history. Chronic renal failure (CRF), defined by serum creatinine> 150 micromol/L, was present in 74 cases (57 men and 17 women). Logistic regression was used to estimate odds ratios (ORs) adjusted for age and social class. RESULTS In men, the percentage of ever-smokers did not differ between GN cases (60%) and controls [65%, OR = 0.9 (95% Confidence Interval 0.6-1.4)], but was significantly higher among cases with CRF (75%) than those without [55%, OR = 2.4 (1.2-4.5)]. Dose-effect relationships were observed with both the daily and cumulative dose; this relationship was stronger in the comparison of cases with CRF and those without CRF than in the comparison of cases with CRF with controls: OR = 1.9 versus 1.3 (</=20 cigarettes/day) and OR = 5.2 versus 3.0 (>20 cigarettes/day); OR = 1.9 versus 1.4 (</=15 pack years) and OR = 3.9 vs. 2.0 (>15 pack years). Interactions between age, hypertension, and smoking were observed in the risk of CRF: smoking was significantly related to CRF among cases who were older than 40 years and/or hypertensive, but not among those cases younger than 40 or normotensive. The results did not significantly differ among the three histologic types. No relationship was shown between smoking and CRF in women. CONCLUSION This study provides additional support for the hypothesis that smoking is related to GN severity, particularly in the at-risk groups of men older than 40 and/or hypertensive patients. These findings should be corroborated by further observations in other populations.

Childhood leukaemia, polymorphisms of metabolism enzyme genes, and interactions with maternal tobacco, coffee and alcohol consumption during pregnancy.

Metabolic polymorphisms may influence the risk of childhood leukaemia related to maternal tobacco, coffee or alcohol consumption. The data were extracted from a case-control study including 280 cases of acute leukaemia and 288 controls. Blood sampling was obtained for a representative subset of 219 cases and 105 controls. Gene–environment interactions were estimated using both case–control and case-only analyses. The polymorphisms of CYP1A1, GSTM1, GSTP1, GSTT1 and NQO1 were not associated with the risk of leukaemia. The slow EPHX1 allele was negatively associated with childhood leukaemia while an inverse non-significant association was observed with the fast EPHX1 allele. Maternal smoking during pregnancy was not related to leukaemia, but an interaction was observed in the case-only analysis with CYP1A1*2A variant allele (odds ratio (OR) 2.2 [1.0–4.9]) and with GSTM1 deletion (OR 2.3 [1.2–4.4]). Conversely, coffee drinking interacted negatively with NQO1 polymorphism in the case-only analysis (OR 0.6 [0.3–1.2] and 0.4 [0.1–1.0] for light and heavy coffee consumptions, respectively). This study suggests that maternal smoking may be a risk factor for leukaemia in children who carry CYP1A1 or GSTM1 genotypes, which might increase reactive metabolites of polycyclic aromatic hydrocarbons.

Childhood Acute Leukemia, Early Common Infections, and Allergy: The ESCALE Study

This study investigated the role of factors considered related to early stimulation of the immune system in the etiology of childhood acute leukemia. The national registry-based case-control study ESCALE was carried out in France in 2003-2004. Population controls were frequency matched to cases on age and gender. Data were obtained from structured telephone questionnaires administered to mothers. Odds ratios were estimated using unconditional regression models adjusted for potential confounders. Included were 634 acute lymphoblastic leukemia cases, 86 acute myeloblastic leukemia cases, and 1,494 controls aged ≥1 year. Negative associations were observed between acute lymphoblastic leukemia and birth order (P for trend < 0.0001), attendance at a day-care center before age 1 year (odds ratio (OR) = 0.8, 95% confidence interval (CI): 0.6, 1.1), prolonged breastfeeding (OR = 0.7, 95% CI: 0.5, 1.0), repeated early common infections (OR = 0.7, 95% CI: 0.6, 0.9), regular contact with farm animals (OR = 0.6, 95% CI: 0.5, 0.8), frequent farm visits in early life (OR = 0.4, 95% CI: 0.3, 0.6), and history of asthma (OR = 0.7, 95% CI: 0.4, 1.0) or eczema (OR = 0.7, 95% CI: 0.6, 0.9). Results support the hypothesis that repeated early infections and asthma may play a role against childhood acute leukemia.

Household Exposure to Pesticides and Risk of Childhood Hematopoietic Malignancies: The ESCALE Study (SFCE)

Objectives We investigated the role of household exposure to pesticides in the etiology of childhood hematopoietic malignancies. Methods The national registry-based case–control study ESCALE (Etude sur les cancers de l’enfant) was carried out in France over the period 2003–2004. Population controls were frequency matched with the cases on age and sex. Maternal household use of pesticides during pregnancy and paternal use during pregnancy or childhood were reported by the mothers in a structured telephone questionnaire. Insecticides (used at home, on pets, or for garden crops), herbicides, and fungicides were distinguished. We estimated odds ratios (ORs) using unconditional regression models closely adjusting for age, sex, degree of urbanization, and type of housing (flat or house). Results We included a total of 764 cases of acute leukemia (AL), 130 of Hodgkin lymphoma (HL), 166 of non-Hodgkin lymphoma (NHL), and 1,681 controls. Insecticide use during pregnancy was significantly associated with childhood AL [OR = 2.1; 95% confidence interval (CI), 1.7–2.5], both lymphoblastic and myeloblastic, NHL (OR = 1.8; 95% CI, 1.3–2.6), mainly for Burkitt lymphoma (OR = 2.7; 95% CI, 1.6–4.5), and mixed-cell HL (OR = 4.1; 95% CI, 1.4–11.8), but not nodular sclerosis HL (OR = 1.1; 95% CI, 0.6–1.9). Paternal household use of pesticides was also related to AL (OR = 1.5; 95% CI, 1.2–1.8) and NHL (OR = 1.7; 95% CI, 1.2–2.6); but for AL the relationships did not remain after adjustment for maternal pesticide use during pregnancy. Conclusion The study findings strengthen the hypothesis that domestic use of pesticides may play a role in the etiology of childhood hematopoietic malignancies. The consistency of the findings with those of previous studies on AL raises the question of the advisability of preventing pesticide use by pregnant women.

Childhood leukemia around French nuclear power plants—The geocap study, 2002–2007

The aim of this work is to study the risk of childhood acute leukemia (AL) around French nuclear power plants (NPPs). The nationwide Geocap case–control study included the 2,753 cases diagnosed in mainland France over 2002–2007 and 30,000 contemporaneous population controls. The last addresses were geocoded and located around the 19 NPPs. The study used distance to NPPs and a dose‐based geographic zoning (DBGZ), based on the estimated dose to bone marrow related to NPP gaseous discharges. An odds ratio (OR) of 1.9 [1.0–3.3], based on 14 cases, was evidenced for children living within 5 km of NPPs compared to those living 20 km or further away, and a very similar association was observed in the concomitant incidence study (standardized incidence ratio (SIR) = 1.9 [1.0–3.2]). These results were similar for all the 5‐year‐age groups. They persisted after stratification for several contextual characteristics of the municipalities of residence. Conversely, using the DBGZ resulted in OR and SIR close to one in all of the dose categories. There was no increase in AL incidence over 1990–2001 and over the entire 1990–2007 period. The results suggest a possible excess risk of AL in the close vicinity of French NPPs in 2002–2007. The absence of any association with the DBGZ may indicate that the association is not explained by NPP gaseous discharges. Overall, the findings call for investigation for potential risk factors related to the vicinity of NPP and collaborative analysis of multisite studies conducted in various countries.

Heat exposure and socio-economic vulnerability as synergistic factors in heat-wave-related mortality

Heat waves may become a serious threat to the health and safety of people who currently live in temperate climates. It was therefore of interest to investigate whether more deprived populations are more vulnerable to heat waves. In order to address the question on a fine geographical scale, the spatial heterogeneity of the excess mortality in France associated with the European heat wave of August 2003 was analysed. A deprivation index and a heat exposure index were used jointly to describe the heterogeneity on the Canton scale (3,706 spatial units). During the heat wave period, the heat exposure index explained 68% of the extra-Poisson spatial variability of the heat wave mortality ratios. The heat exposure index was greater in the most urbanized areas. For the three upper quintiles of heat exposure in the densely populated Paris area, excess mortality rates were twofold higher in the most deprived Cantons (about 20 excess deaths/100,000 people/day) than in the least deprived Cantons (about 10 excess deaths/100,000 people/day). No such interaction was observed for the rest of France, which was less exposed to heat and less heterogeneous in terms of deprivation. Although a marked increase in mortality was associated with heat wave exposure for all degrees of deprivation, deprivation appears to be a vulnerability factor with respect to heat-wave-associated mortality.

Structural relationship between the nucleolus and the nuclear envelope.

A quantitative ultrastructural analysis of the relationship between the invaginations formed by the inner and outer membrane of the nuclear envelope and the nucleoli was performed in a variety of established cell lines and in a human primary line grown in vitro. This study provides statistical evidence that such invaginations are significantly associated with nucleoli. This anatomical relationship reflects the existence of a junction with a remarkably stable ultrastructure between the nucleolus and the nuclear envelope. Functionally, this association may be related to nucleolocytoplasmic exchanges and/or may represent the mode of mechanical attachment of the nucleolus. The usefulness and limits of such a quantitative analysis to investigate relationships of this sort between two organelles are discussed.