From eyeballing to statistical modelling : methods for assessment of occupational exposure

In this thesis methods for assessment of occupational exposure are evaluated and developed. These methods range from subjective methods (qualitative and semiquantitative) to more objective quantitative methods based on actual measurement of personal exposure to chemical and physical agents.In chapter 2, data from a general population cohort of 878 men from the town of Zutphen, the Netherlands, were used to evaluate the performance of two general job- exposure matrices. Exposures, generated by the job-exposure matrices on the basis of job histories, were compared. The validity of those exposures was measured against exposures reported by the participants in 1977/1978. The performance of the different exposure measures was assessed in proportional hazards analyses of lung cancer morbidity incidence. The two general job-exposure matrices generally disagreed with regard to exposure classification because of differences in exposure assessment and the level of detail of the job axis. When compared with self-reported exposures, the sensitivity of both job-exposure matrices was low (on average, below 0.51), while the specificity was generally high (on average, above 0.90). Self-reported exposures to asbestos, pesticides, and welding fumes showed elevated risk ratios for lung cancer, which were absent for exposures generated by the two job- exposure matrices. A population-specific jobexposure matrix was proposed as an alternative to general job-exposure matrices developed elsewhere. Such a matrix can be constructed from the results of indepth interviews of a job-stratified sample of cohort members. Sound validation and documentation of exposure assessment methods used in job-exposure matrices were recommended.In chapter 3 a study is described in which a method for semi-quantitative estimation of the exposure at task level was used and validated with actual measurements in five small factories. The results showed that occupational hygienists were in general the most successful raters. Plant supervisors and workers handled the estimation method less successfully because of more misclassification of the tasks. The method resulted, in general, in a classification of tasks in four exposure categories ranging from no exposure to high exposure. The exposure categories correlated positively with mean concentrations, but showed overlapping exposure distributions. This resulted in misclassification of the exposure for individual workers when a relatively large inter-individual variability in exposure levels within an exposure category was present. The results showed that this method can be used for workplace exposure zoning, but that the usefulness of the estimates for epidemiological purposes was not clear-cut and depended strongly on the actual exposure characteristics within a workplace. A combination of the semiquantitative exposure estimation method together with assessment of the exposure levels by measurements makes a rearrangement of tasks or individual workers possible and could improve the validity of this method for epidemiological purposes.In chapter 4 the performance is studied of nine occupational hygienists, who semiquantitatively estimated the exposure to methylene chloride and styrene in a small polyester factory. They ranked the jobs from low to high exposure, and subsequently classified them into three exposure categories (0-½TLV, ½TLV-TLV, and>TLV). The influence of quantitative exposure data on the results of the estimations was studied. Therefore, three estimations were performed. The first estimation was made after a visit to the workplace; the second and third were made after limited exposure data were presented. The ranking of styrene exposure was, in general, poor compared to the ranking of methylene chloride exposure. Physical properties, such as perception of smell, application in the process, and level of exposure might be the reasons for this striking difference. Classification of exposure into quantitative exposure categories was poor without knowledge of actual exposure data. No differences in the performance of the occupational hygienists between the two solvents were present. The results suggested that the success of an exposure estimation method depends on the type of exposure (kind of chemical, use, appearance), the available information on jobs and process, and the kind of estimate (ranking or classification). Semiquantitative classification of exposure by occupational hygienists appears to be better if they have a limited set of air sampling data at their disposal. Ranking of jobs can be performed successfully without exposure data, but a detailed description of the workplace and tasks is needed. More insight is needed concerning the influence of the chemical type, exposure pattern(s), and raters' experience on the results of semiquantitative ranking methods.Chapter 5 describes an exposure survey in 10 rubber-manufacturing plants. Personal exposures to airborne particulates, rubber fumes and solvents, and also dermal contamination, were measured. To identify factors affecting exposure the personal exposure levels and information on tasks performed, ventilation characteristics, and production variables were used in multiple linear regression models. The exposure was generally very variable. The specific circumstances in each department of each plant determined the actual levels of exposure to a large extent. The factors affecting exposure turned out to be different for each of the types of exposure considered. The model for exposure to airborne particulates explained 40% of the total variability and incorporating the actual time spent on a task only slightly improved the model ( R2=0.42) . The handling of chemicals in powder form was the main factor affecting exposure, forced ventilation having a negligible effect. The model for exposure to curing fumes (measured as the cyclohexane-soluble fraction of the particulate matter) explained 50% of the variability. Both curing temperature and pressure determined the level of rubber fumes. Local exhaust ventilation showed a significant exposure reducing effect. The effect of curing different elastomers was not statistically significant. Dermal exposure to cyclohexane- soluble matter could only be explained to a limited extent ( R2=0.22) . Tasks with frequent contact with (warm) compound and maintenance tasks in the engineering services departments resulted in high dermal exposure. Tasks in which solvents were directly used explained 56% of the variation in solvent exposures. Exposure data together with information on tasks, methods of work, ventilation and production throughout a branch of industry, can be used to derive empirical statistical models which occupational hygienists can apply to study factors affecting exposure. These determining factors are of crucial importance, whenever hazard control or epidemiologic research is the ultimate goal. In chapter 6 the implications of exposure variability are examined for the design of occupational epidemiology studies in the rubber industry. The efficiency of different grouping schemes for exposure to particulates, dermal exposure to cyclohexane-soluble contaminants, and exposure to solvents was assessed. Statistical parameters for contrast in average exposure and precision of average exposure were developed to enable comparison of different grouping schemes. Groupings based on job title, plant, factors affecting exposure, published classifications, and the ISCO-ILO classification were compared. Grouping of exposure to particulates and dermal exposure appeared to be less efficient than grouping of exposure to solvents. Grouping of solvent exposure using either occupational title groups, existing classification schemes, and schemes based on factors affecting exposure showed comparable high resolution in exposure levels. Even the most detailed grouping schemes based on the combination of plant and occupational title group showed relative modest resolution in particulate and dermal exposure levels. Groupings based on factors affecting exposure showed for these exposures similar resolution, but were more efficient because of a higher precision due to a smaller number of groups. It was concluded, that application of optimal exposure grouping strategies will benefit new research on cancer among rubber workers. Eventually, this might resolve the unwanted situation in which a complete industry was included on the list of proven human carcinogens.Chapter 7 focuses on within- and between-worker exposure variability. A database of approximately 20,000 chemical exposures was constructed in close co-operation between the School of Public Health of the University of North Carolina at Chapel Hill and the Department of Air Pollution of the Wageningen Agricultural University. A special feature of this database was that only multiple measurements of exposure from the same workers were included. This enabled estimation of within- and between-worker variance components of occupational exposure to chemical agents throughout industry. Most of the groups were not uniformly exposed as is generally assumed by occupational hygienists. In fact only 42 out of a total of 165 groups (25%), based on job title and factory, had 95% of individual mean exposures within a two-fold range. On the contrary, about 30% of the groups had 95% of individual mean exposures in a range which was greater than 10-fold. Environmental and production factors were shown to have distinct influences on the within-worker (day-to-day) variability, but not on the between-worker variability. Groups working outdoors and those working without local exhaust ventilation showed more day-to-day variability than groups working indoors and those working with local exhaust ventilation. Groups consisting of mobile workers, those working with an intermittent process and those where the source of contamination was either local or mobile also showed great day-to-day variability. In a multivariate regression model, environment (indoors- outdoors) and type of process (continuous-intermittent) explained 41 % of the variability in the within-worker component of variance. Another model, in which only type of process (continuous-intermittent) had a significant effect, explained only 13% of the variability in the between-worker component of variance.In chapter 8 the results are reported of a large survey of occupational exposure to 60 Hz magnetic fields conducted among randomly selected workers in five electric power companies. The design of the study facilitated the examination of exposure variability and provided the base for a job-exposure matrix (JEM) for linking health outcomes and occupational magnetic field exposures in the epidemiological study of employees of these companies. Almost 3.000 successful measurement attempts indicated average exposures ranging from 0.11 μT for 'Senior Managers' to 1.50 μT for 'Cable Splicers'. The differences among the five companies were relatively small with the more urban companies showing somewhat higher average exposures. The day-to-day component of variance exceeded the within- and between- group components of variance. The final JEM consisted of five groups with average exposure levels of 0.12, 0.21, 0.39, 0.62, and 1.27 μT, respectively. Given the variance in exposure, even this optimal grouping showed considerable overlap in exposure between adjacent groups. Nevertheless, the JEM incorporated the differences in exposure level within occupational categories between companies in the most efficient way and provides an objective and statistically based method for estimation of cumulative magnetic field exposure.Finally, in chapter 9 a general discussion and conclusions are given. Through validation and methodological studies, as described in the thesis, some light has been shed on the science of occupational exposure assessment. Although improvement of subjective methods is feasible to some extent, the inherent pitfalls can lead to exposures estimates not accurate enough to be used in epidemiological exposure-response relationships. Statistical models, as developed in this thesis, to unravel factors affecting exposure and to estimate variance components will contribute to more accurate ways of exposure assessment. Application of the developed statistical methods to optimize the grouping of exposure will result in less misclassification and bias and therefore in better exposure-response relationships. Consequently, this will lead to more protective occupational exposure limits. Hopefully, more randomly collected quantitative exposure data will become available to make use of the developed tools. Only then, the widely criticized art of retrospective guessing of occupational exposures will become obsolete

Relationship between environmental exposure to pesticides and anthropometric outcomes of boys in the rural Western Cape, South Africa

BACKGROUND: Rural residents in the Western Cape (WC), South Africa (SA) are highly exposed to agricultural pesticides that could impact their reproductive development. However, epidemiological evidence of the effect of pesticides on pubertal growth is contradictory. OBJECTIVE: To investigate the effect of pesticide exposure measured using indices of environmental exposure to pesticides on the pubertal growth of boys in rural WC, SA. METHODS: A cross-sectional study of 269 boys (177 of whom gave a history of residing on farms) was conducted. A questionnaire was administered, height and weight were measured and body mass index was calculated. A proximity index (PI) and spraying index (SI) was developed, measuring the lifetime average home distance from pesticide spraying and average frequency of spraying pesticides on a farm, respectively. RESULTS: Median age of boys was 12.4 years (interquartile range 9.5 - 13.3). More than 60% boys had height and weight <50th percentile for age. After adjusting for confounders, PI was significantly associated with shorter stature and lower weight (-1.7 cm/10-fold decrease, p=0.02 and -1.24 kg/10-fold decrease, p=0.04; respectively) and SI was non-significantly associated (-1.4 cm/10-fold increase, p=0.05 and -1.1 cm/10-fold increase, p=0.06; respectively). Associations were stronger for boys aged <11 years and were weaker when excluding non- farm boys. There were no other associations between outcome and exposure. CONCLUSIONS: The use of quantitative exposure indices showed that lower heights and weights might be associated with pesticide exposure in farm boys v. non-farm boys, but not among farm boys. Lower anthropometric measurements among farm boys v. non-farm boys appear stronger at a younger age. The indices of environmental exposure to pesticides require further development

Подавление синхронной помехи в ЯКР с модуляцией Зеемана

Рассмотрены принципы частотной модуляции и модуляции Зеемана в ядерном квадрупольном резонансе и показаны преимущества последней. Предложен метод устранения синхронной помехи, вызываемой переключением магнитного поля. Приведены результаты наблюдения резонансной линии ¹⁴N с достоверной формой в образце гексаметилентетрамине массой 2 г.Розглянуто принципи частотної модуляції та модуляції Зеемана в ядерному квадрупольному резонансі та показано переваги останньої. Запропоновано метод усунення синхронної завади, спричиненої перемиканням магнітного поля. Наведено результат спостереження резонансної лінії ¹⁴N з достовірною формою у зразку гексаметилентетраміну масою 2 г.The principles of frequency and Zeeman modulation in nuclear quadrupole resonance were considered, and the advantages of the latter were shown. The authors propose a method to eliminate the synchronous noise caused by switching of the magnetic field. Results of observations of the resonance line with ¹⁴N in the hexamethylenetetramine sample weighing 2 g were given

An international prospective general population-based study of respiratory work disability

Background: Previous cross-sectional studies have shown that job change due to breathing problems at the workplace (respiratory work disability) is common among adults of working age. That research indicated that occupational exposure to gases, dust and fumes was associated with job change due to breathing problems, although causal inferences have been tempered by the cross-sectional nature of previously available data. There is a need for general population-based prospective studies to assess the incidence of respiratory work disability and to delineate better the roles of potential predictors of respiratory work disability.Methods: A prospective general population cohort study was performed in 25 centres in 11 European countries and one centre in the USA. A longitudinal analysis was undertaken of the European Community Respiratory Health Survey including all participants employed at any point since the baseline survey, 6659 subjects randomly sampled and 779 subjects comprising all subjects reporting physician-diagnosed asthma. The main outcome measure was new-onset respiratory work disability, defined as a reported job change during follow-up attributed to breathing problems. Exposure to dusts (biological or mineral), gases or fumes during follow-up was recorded using a job-exposure matrix. Cox proportional hazard regression modelling was used to analyse such exposure as a predictor of time until job change due to breathing problems.Results: The incidence rate of respiratory work disability was 1.2/1000 person-years of observation in the random sample (95% CI 1.0 to 1.5) and 5.7/1000 person-years in the asthma cohort (95% CI 4.1 to 7.8). In the random population sample, as well as in the asthma cohort, high occupational exposure to biological dust, mineral dust or gases or fumes predicted increased risk of respiratory work disability. In the random sample, sex was not associated with increased risk of work disability while, in the asthma cohort, female sex was associated with an increased disability risk (hazard ratio 2.8, 95% CI 1.3 to 5.9).Conclusions: Respiratory work disability is common overall. It is associated with workplace exposures that could be controlled through preventive measures

Nutrition beyond the first 1000 days:diet quality and 7-year change in BMI and overweight in 3-year old children from the Dutch GECKO Drenthe birth cohort

The identification of early-life determinants of overweight is crucial to start early prevention. As weight gain accelerates between 2 and 6 years, we studied the association between diet quality in children aged 3 years and the change in BMI and overweight incidence in the following 7 years. From the Dutch GECKO Drenthe birth cohort, 1001 children born in 2006 or 2007 with complete data on diet (food frequency questionnaire at the age of 3 years) and growth at the age of 3 and 10 years were included. Diet quality was estimated with the evidence-based Lifelines Diet Score (LLDS). Measured height and weight at the age of 3 and 10 years were used to calculate BMI z-scores standardized for age and sex. The associations of the LLDS (in quintiles) with BMI-z change and overweight incidence were studied with linear and logistic regression analyses. Overweight prevalence in the total study population increased from 8.3% at the age of 3 years to 16.7% at the age of 10 years. The increase in overweight prevalence ranged from 14.7% in Q1 to 3.5% in Q5. Children with a better diet quality (higher quintiles of LLDS) increased significantly less in BMI-z (confounder adjusted βLLDS = -0.064 (-0.101; -0.026)). Children with a poor diet quality at the age of 3 years had a considerably higher risk for overweight at the age of 10 years (confounder adjusted OR for Q1 vs. Q5 was 2.86 (95% CI 1.34-6.13). These results show the importance of diet in healthy development in the early life following the first 1000 days when new habits for a mature diet composed of food groups with lifelong importance are developed, providing a relevant window for overweight prevention early in life

Airborne occupational exposures and the risk of developing respiratory symptoms and airway obstruction in the Lifelines Cohort Study

OBJECTIVES: To date, only a few studies have investigated the associations between occupational exposures and respiratory outcomes longitudinally in the general population. We investigated the associations between occupational exposures and the development of respiratory symptoms and airway obstruction in the Lifelines Cohort Study. METHODS: We included 35 739 occupationally active subjects with data on chronic cough, chronic phlegm, chronic bronchitis or airway obstruction at baseline and approximately 4.5 years follow-up. Exposures to biological dust, mineral dust, gases/fumes, pesticides, solvents and metals in the current job at baseline were estimated with the ALOHA+job-exposure matrix (JEM). Airway obstruction was defined as FEV1/FVC below the lower limit of normal. Logistic regression analysis adjusted for baseline covariates was used to investigate the associations. RESULTS: At follow-up, 1888 (6.0%), 1495 (4.7%), 710 (2.5%) and 508 (4.5%) subjects had developed chronic cough, chronic phlegm, chronic bronchitis and airway obstruction, respectively. High exposure to biological dust was associated with a higher odds to develop chronic cough and chronic bronchitis. High exposure to pesticides was associated with a higher odds for the development of all respiratory symptoms and airway obstruction. In the multiple exposures analyses, only the association between pesticides exposure and respiratory symptoms remained. CONCLUSIONS: Subjects exposed to high pesticides had a higher odds to develop respiratory symptoms on average 4.5 years later. Control measures should be taken to reduce pesticides exposure among the working population to prevent respiratory symptoms and airway obstruction

Papillomavirus Infection of the Anogenital Region: Correlation Between Histology, Clinical Picture, and Virus Type. Proposal of a New Nomenclature

The clinical and histologic picture of 84 anogenital condylomatous and condyloma-like lesions of both sexes were analyzed in an effort to establish a correlation to the different papillomavirus (PV) types. The presence of human papillomavirus (HPV)-specific DNA sequences was confirmed through molecular hybridization and the presence of PV structure antigens was verified in thin sections by means of a group-specific anti-PV-antiserum using the peroxidase-antiperoxidase (PAP) technique. Three distinct clinical forms harboring distinct HPV types were distinguished: (1) Condylomata acuminata in which HPV-6 DNA was present in 37 of 59 samples and HPV-11 DNA in only 13 of 59 samples. HPV-16 DNA was not detected at all and 9 condylomatous lesions remained unclassified. (2) Flat condyloma-like lesions, where HPV-6 and HPV- 11 were associated with lesions of low epidermal atypia in 8 and in 2 of 18 cases, respectively, and where HPV-16 was associated exclusively with 6 of 18 such lesions with severe atypia, called bowenoid papulosis. (3) Pigmented papules where HPV16 was detected twice in lesions of bowenoid papulosis and HPV-11 in 2 of the benign pigmented lesions. The fourth clinical manifestation of genital papillomavirus infections—the so-called condylomata plana—was not available for virologic analysis. Histologically 5 different koilocytotic features were determined which could not be correlated either with one of the clinical pictures or with a specific PV type. HPV-16, however, was found frequently in non-koilocytotic lesions exhibiting the features of severe epithelial atypia known in bowenoid papulosis. The existence of PV structure antigens in these lesions could not be verified using the indirect immunoperoxidase—PAPtechnique—in contrast to the koilocytotic lesions where clear evidence of the presence of HPV was proved in 36 of 56 (64.3%) of the cases

Occupational exposures and small airways obstruction in the UK Biobank Cohort

Background Small airways obstruction (SAO) is a key feature of both Chronic Obstructive Pulmonary Disease and asthma, which have been associated with workplace exposures. Whether SAO, which may occur early in the development of obstructive lung disease and without symptoms, also associates with occupational exposures is unknown. Methods Using UK Biobank data, we derived measurements of SAO from the 65,145 participants with high quality spirometry and lifetime occupational histories. The ALOHA+ Job Exposure Matrix was used to assign lifetime occupational exposures to each participant. The association between SAO and lifetime occupational exposures was evaluated using a logistic regression model adjusted for potential confounders. A second logistic regression model was run to also account for potential co-exposures. Results SAO was present in varying proportions of the population depending on definition used: 5.6% (FEF25–75<LLN)and 21.4% (FEV3/FEV6<LLN). After adjustment for confounders and co-exposures, people in the highest category of exposure to pesticides were significantly more likely to have SAO (FEV3/FEV6<LLN: OR 1.24, 95%CI 1.06–1.44). The association between pesticides and SAO showed an exposure-response pattern. SAO was also less likely among people in the highest exposure categories of aromatic solvents (FEV3/FEV6<LLN: OR 0.85, 95%CI 0.73–0.99) and metals (FEV3/FEV6<LLN: OR 0.77, 95%CI 0.62–0.94). Conclusion Our findings suggest that occupational exposure to pesticides play a role in the SAO. However, further work is needed to determine causality, and identify the specific component(s) responsible and the underlying mechanisms involved

Теоретичні засади дослідження виборчих технологій в електоральному процесі України та проблеми їх ефективності

Здійснено політологічний аналіз ефективності виборчих технологій та проаналізо­вано їх вплив на електоральні процеси в Україні.Осуществлен политологический анализ эффективности избирательных технологий и проанализировано их влияние на электоральные процессы в Украине.Political analysis of electoral technologies effectiveness and analyzes of their impact on the electoral process in Ukraine are made