Data Representativeness: Issues and Solutions

In its control programmes on maximum residue level compliance and exposure assessments, EFSA requires the participating countries to submit results, from specific numbers of food item samples, analyzed in the countries. These data are used to obtain estimates such as the proportion of samples exceeding the maximum residue limits, and the mean and maximum residue concentration per food item to assess exposure. An important consideration is the design and analysis of the programmes. In this report, we combine elements of survey sampling methodology, and statistical modeling, as a benchmark framework for the programmes, starting from the translation of research questions into statistical problems, to the statistical analysis and interpretation. Particular focus is placed on the issues that could affect the representativeness of the data, and remedial procedures are proposed. For example, in the absence of information on the sampling design, a sensitivity analysis, across a range of designs, is proposed. On the other hand, weighted generalized linear mixed models, and generalized linear mixed models combining both conjugate and normal random effects, are proposed, to address selection bias. Likelihood-based analysis methods are also proposed to address missing and censored data problems. Suggestions for improvements in the design and analysis of the programmes are also identified and discussed. For instance, incorporation of stratified sampling methodology, in determining both the total number, and the allocation of samples to the participating countries, is proposed. All through the report, statistical analysis models which properly take into account the hierarchical (and thus correlated) structure in which the data are collected are proposed

PFAS levels and determinants of variability in exposure in European teenagers - Results from the HBM4EU aligned studies (2014-2021)

Background: Perfluoroalkyl substances (PFAS) are man-made fluorinated chemicals, widely used in various types of consumer products, resulting in their omnipresence in human populations. The aim of this study was to describe current PFAS levels in European teenagers and to investigate the determinants of serum/plasma concentrations in this specific age group. Methods: PFAS concentrations were determined in serum or plasma samples from 1957 teenagers (12-18 years) from 9 European countries as part of the HBM4EU aligned studies (2014-2021). Questionnaire data were post-harmonized by each study and quality checked centrally. Only PFAS with an overall quantification frequency of at least 60% (PFOS, PFOA, PFHxS and PFNA) were included in the analyses. Sociodemographic and lifestyle factors were analysed together with food consumption frequencies to identify determinants of PFAS exposure. The variables study, sex and the highest educational level of household were included as fixed factors in the multivariable linear regression models for all PFAS and each dietary variable was added to the fixed model one by one and for each PFAS separately. Results: The European exposure values for PFAS were reported as geometric means with 95% confidence intervals (CI): PFOS [2.13 μg/L (1.63-2.78)], PFOA ([0.97 μg/L (0.75-1.26)]), PFNA [0.30 μg/L (0.19-0.45)] and PFHxS [0.41 μg/L (0.33-0.52)]. The estimated geometric mean exposure levels were significantly higher in the North and West versus the South and East of Europe. Boys had significantly higher concentrations of the four PFAS compared to girls and significantly higher PFASs concentrations were found in teenagers from households with a higher education level. Consumption of seafood and fish at least 2 times per week was significantly associated with 21% (95% CI: 12-31%) increase in PFOS concentrations and 20% (95% CI: 10-31%) increase in PFNA concentrations as compared to less frequent consumption of seafood and fish. The same trend was observed for PFOA and PFHxS but not statistically significant. Consumption of eggs at least 2 times per week was associated with 11% (95% CI: 2-22%) and 14% (95% CI: 2-27%) increase in PFOS and PFNA concentrations, respectively, as compared to less frequent consumption of eggs. Significantly higher PFOS concentrations were observed for participants consuming offal (14% (95% CI: 3-26%)), the same trend was observed for the other PFAS but not statistically significant. Local food consumption at least 2 times per week was associated with 40% (95% CI: 19-64%) increase in PFOS levels as compared to those consuming local food less frequently. Conclusion: This work provides information about current levels of PFAS in European teenagers and potential dietary sources of exposure to PFAS in European teenagers. These results can be of use for targeted monitoring of PFAS in food.This work was supported by the European Union’s Horizon 2020 research and innovation programme under Grant agreement No 733032 HBM4EU (www.HBM4EU.eu), and received co-funding from the authors’ organizations: Riksmaten Adolescents: Riksmaten Adolescents was performed by the Swedish Food Agency with financial support from the Swedish Environmental Protection Agency and the Swedish Civil Contingencies Agency. NEB II: The Norwegian Institute of Public Health (NIPH) has contributed to funding of the Norwegian Environmental Biobank (NEB). The laboratory measurements have partly been funded by the Research Council of Norway through research projects (275903 and 268465) PCB cohort follow-up: PCB cohort follow-up received additional funding from the Ministry of Health of the Slovak Republic, program 07B0103. BEA: BEA study was funded by the Spanish Ministry of Agriculture, Fisheries and Food and the Instituto de Salud Carlos III (SEG 1321/15) SLO-CRP: The Slovenian SLO-CRP study was co-financed by the Jozef Stefan Institute program P1- 0143, and a national project “Exposure of children and adolescents to selected chemicals through their habitat environment” (grant agreement No. C2715-16-634802). CROME: CROME study was co-funded by the European Commission research funds of Horizon 2020. ESTEBAN: ESTEBAN study was funded by Santé Publique France and the French ministries of Health and the Environment. GerES V-sub: The funding of the German Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection is gratefully acknowledged. FLEHS IV: The Flemish Center of Expertise on Environment and Health is funded by the Government of Flanders, Department of Environment & Spatial Development.S

Pollutant effects on genotoxic parameters and tumor-associated protein levels in adults: a cross sectional study

<p>Abstract</p> <p>Background</p> <p>This study intended to investigate whether residence in areas polluted by heavy industry, waste incineration, a high density of traffic and housing or intensive use of pesticides, could contribute to the high incidence of cancer observed in Flanders.</p> <p>Methods</p> <p>Subjects were 1583 residents aged 50–65 from 9 areas with different types of pollution. Cadmium, lead, p,p'-DDE, hexachlorobenzene, PCBs and dioxin-like activity (Calux test) were measured in blood, and cadmium, t,t'-muconic acid and 1-hydroxypyrene in urine. Effect biomarkers were prostate specific antigen, carcinoembryonic antigen and p53 protein serum levels, number of micronuclei per 1000 binucleated peripheral blood cells, DNA damage (comet assay) in peripheral blood cells and 8-hydroxy-deoxyguanosine in urine. Confounding factors were taken into account.</p> <p>Results</p> <p>Overall significant differences between areas were found for carcinoembryonic antigen, micronuclei, 8-hydroxy-deoxyguanosine and DNA damage. Compared to a rural area with mainly fruit production, effect biomarkers were often significantly elevated around waste incinerators, in the cities of Antwerp and Ghent, in industrial areas and also in other rural areas. Within an industrial area DNA strand break levels were almost three times higher close to industrial installations than 5 kilometres upwind of the main industrial installations (p < 0.0001). Positive exposure-effect relationships were found for carcinoembryonic antigen (urinary cadmium, t,t'-muconic acid, 1-hydroxypyrene and blood lead), micronuclei (PCB118), DNA damage (PCB118) and 8-hydroxy-deoxyguanosine (t,t'-muconic acid, 1-hydroxypyrene). Also, we found significant associations between values of PSA above the p90 and higher values of urinary cadmium, between values of p53 above the p90 and higher serum levels of p,p'-DDE, hexachlorobenzene and marker PCBs (PCB 138, 153 and 180) and between serum levels of p,p'-DDE above the p90 and higher serum values of carcinoembryonic antigen. Significant associations were also found between effect biomarkers and occupational or lifestyle parameters.</p> <p>Conclusion</p> <p>Levels of internal exposure, and residence near waste incinerators, in cities, or close to important industries, but not in areas with intensive use of pesticides, showed positive correlations with biomarkers associated with carcinogenesis and thus probably contribute to risk of cancer. In some rural areas, the levels of these biomarkers were not lower than in the rest of Flanders.</p

Clustering multiply imputed multivariate high-dimensional longitudinal profiles

In this paper, we propose a method to cluster multivariate functional data with missing observations. Analysis of functional data often encompasses dimension reduction techniques such as principal component analysis (PCA). These techniques require complete data matrices. In this paper, the data are completed by means of multiple imputation, and subsequently each imputed data set is submitted to a cluster procedure. The final partition of the data, summarizing the partitions obtained for the imputed data sets, is obtained by means of ensemble clustering. The uncertainty in cluster membership, due to missing data, is characterized by means of the agreement between the members of the ensemble and fuzziness of the consensus clustering. The potential of the method was brought out on the heart failure (HF) data. Daily measurement for four biomarkers (heart rate, diastolic, and systolic blood pressure, weight) were used to cluster the patients. To normalize the distributions of the longitudinal outcomes, the data were transformed with a natural logarithm function. A cubic spline base with 69 basis functions was employed to smooth the profiles. The proposed algorithm indicates the existence of a latent structure and divides the HF patients into two clusters, showing a different evolution in blood pressure values and weight. In general, cluster results are sensitive to choices made. Likewise for the proposed approach, alternative choices for the distance measure, procedure to optimize the objective function, choice of the scree-test threshold, or the number of principal components, to be used in the approximation of the surrogate density, could all influence the final partition. For the HF data set, the final partition depends on the number of principal components used in the procedure.status: publishe

Characterizing persistent disturbing behavior using longitudinal and multivariate techniques

Persistent disturbing behavior (PDB) refers to a chronic condition in therapy-resistant psychiatric patients. Since these patients are highly unstable and difficult to maintain in their natural living environment and even in hospital wards, it is important to properly characterize this group. Previous studies in the Belgian province of Limburg indicated that the size of this group was larger than anticipated. Here, using a score calculated from longitudinal psychiatric registration data in 611 patients, we characterize the difference between PDB patients and a set of control patients. These differences are studied both at a given point in time, using discriminant analysis, as well as in terms of the evolution of the score over time, using longitudinal data analysis methods. Further, using clustering techniques, the group of PDB patients is split into two subgroups, characterized in terms of a number of ordinal scores. Such findings are useful from a scientific as well as from an organizational point of view. © 2010 Taylor & Francis.status: publishe