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Partisan polarization spreads through more and more of American society over time. Republicans and Democrats held different opinions toward partisan-valenced institutions like the presidency and a few economic institutions (e.g. big business) in the 1970s, but today almost all societal institutions – whether governmental or ostensibly apolitical – are understood by many Americans as liberal or conservative, made up mostly of one partisan group or the other. As a result many partisans trust only institutions they believe are made up of people who are similar to them ideologically.This dissertation uses attempts to answer these questions: When did this polarization of trust emerge in each institution? Why did this polarization occur? What effect does it have on regular Americans?Chapter 1 documents trust in institutions using 50 years of existing public opinion data and original public opinion measurement. Chapter 2 uses campaign donation data and machine learning to establish a possible cause of polarization of trust: the real composition of institutions. Chapter 3 demonstrates one reason this polarization is important: if it is provided, Americans will use partisan information about doctors to make decisions about health care. There is already evidence of individual-level partisan differences in trust in doctors, as well as aggregate-level evidence of differential outcomes between Republicans and Democrats.

Childhood obesity in the United States has doubled over the last three decades and currently affects 17% of children and adolescents. While much research has focused on individual behaviors impacting obesity, little research has emphasized the complex interactions of numerous chemical and non-chemical stressors found in a child’s environment and how these interactions affect a child’s health and well-being. The objectives of this systematic scoping review were to (1) identify potential chemical stressors in the context of non-chemical stressors that impact childhood obesity; and, (2) summarize our observations for chemical and non-chemical stressors in regards to child-specific environments within a community setting. A review was conducted to identify chemical and non-chemical stressors related to childhood obesity for the childhood life stages ranging from prenatal to adolescence. Stressors were identified and grouped into domains: individual behaviors, family/household behaviors, community stressors, and chemical exposures. Stressors were related to the child and the child’s everyday environments and used to characterize child health and well-being. This review suggests that the interactions of chemical and non-chemical stressors are important for understanding a child’s overall health and well-being. By considering these relationships, the exposure science research community can better design and implement strategies to reduce childhood obesity.

Background: Results of our recently published phase III randomized clinical trial of ultrasound-enhanced thrombolysis (sonothrombolysis) using an operator-independent, high frequency ultrasound device revealed heterogeneity of patient recruitment among centers. Methods: We performed a post hoc analysis after excluding subjects that were recruited at centers reporting a decline in the balance of randomization between sonothrombolysis and concurrent endovascular trials. Results: From a total of 676 participants randomized in the CLOTBUST-ER trial we identified 52 patients from 7 centers with perceived equipoise shift in favor of endovascular treatment. Post hoc sensitivity analysis in the intention-to-treat population adjusted for age, National Institutes of Health Scale score at baseline, time from stroke onset to tPA bolus and baseline serum glucose showed a significant (p Conclusion: Our experience in CLOTBUST-ER indicates that increasing implementation of endovascular therapies across major academic stroke centers raises significant challenges for clinical trials aiming to test noninterventional or adjuvant reperfusion strategies.

Background/Aim: Children are exposed to diverse chemical and non-chemical stressors in their built, natural, and social environments; and these are thought to contribute to their health and well-be...

Agricultural exposures including pesticides, endotoxin, and allergens have been associated with risk of various cancers and other chronic diseases, although the biological mechanisms underlying these associations are generally unclear. To facilitate future molecular epidemiologic investigations, in 2010 the study of Biomarkers of Exposure and Effect in Agriculture (BEEA) was initiated within the Agricultural Health Study, a large prospective cohort in Iowa and North Carolina. Here the design and methodology of BEEA are described and preliminary frequencies for participant characteristics and current agricultural exposures are reported. At least 1,600 male farmers over 50 years of age will be enrolled in the BEEA study. During a home visit, participants are asked to complete a detailed interview about recent agricultural exposures and provide samples of blood, urine, and (since 2013) house dust. As of mid-September 2014, in total, 1,233 participants have enrolled. Most of these participants (83%) were still farming at the time of interview. Among those still farming, the most commonly reported crops were corn (81%) and soybeans (74%), and the most frequently noted animals were beef cattle (35%) and hogs (13%). There were 861 (70%) participants who reported occupational pesticide use in the 12 months prior to interview; among these participants, the most frequently noted herbicides were glyphosate (83%) and 2,4-D (72%), and most commonly reported insecticides were malathion (21%), cyfluthrin (13%), and permethrin (12%). Molecular epidemiologic investigations within BEEA have the potential to yield important new insights into the biological mechanisms through which these or other agricultural exposures influence disease risk.

Prospective cohorts have played a major role in understanding the contribution of diet, physical activity, medical conditions, and genes to the development of many diseases, but have not been widely used for occupational exposures. Studies in agriculture are an exception. We draw upon our experience using this design to study agricultural workers to identify conditions that might foster use of prospective cohorts to study other occupational settings. Prospective cohort studies are perceived by many as the strongest epidemiologic design. It allows updating of information on exposure and other factors, collection of biologic samples before disease diagnosis for biomarker studies, assessment of effect modification by genes, lifestyle, and other occupational exposures, and evaluation of a wide range of health outcomes. Increased use of prospective cohorts would be beneficial in identifying hazardous exposures in the workplace. Occupational epidemiologists should seek opportunities to initiate prospective cohorts to investigate high priority, occupational exposures.

Organophosphorous insecticides (OPs) are the most commonly used insecticides in US agriculture, but little information is available regarding specific OP use by individual farmers. We describe OP use for licensed private pesticide applicators from Iowa and North Carolina in the Agricultural Health Study (AHS) using lifetime pesticide use data from 701 randomly selected male participants collected at three time periods. Of 27 OPs studied, 20 were used by >1%. Overall, 95% had ever applied at least one OP. The median number of different OPs used was 4 (maximum=13). Malathion was the most commonly used OP (74%) followed by chlorpyrifos (54%). OP use declined over time. At the first interview (1993–1997), 68% of participants had applied OPs in the past year; by the last interview (2005–2007), only 42% had. Similarly, median annual application days of OPs declined from 13.5 to 6 days. Although OP use was common, the specific OPs used varied by state, time period, and individual. Much of the variability in OP use was associated with the choice of OP, rather than the frequency or duration of application. Information on farmers’ OP use enhances our ability to characterize and understand the potential health effects of multiple OP exposures.

The Agricultural Health Study (AHS), a large prospective cohort, was designed to elucidate associations between pesticide use and other agricultural exposures and health outcomes. The cohort includes 57,310 pesticide applicators who were enrolled between 1993 and 1997 in Iowa and North Carolina. A follow-up questionnaire administered 5 years later was completed by 36,342 (63%) of the original participants. Missing pesticide use information from participants who did not complete the second questionnaire impedes both long-term pesticide exposure estimation and statistical inference of risk for health outcomes. Logistic regression and stratified sampling were used to impute key variables related to the use of specific pesticides for 20,968 applicators who did not complete the second questionnaire. To assess the imputation procedure, a 20% random sample of participants was withheld for comparison. The observed and imputed prevalence of any pesticide use in the holdout dataset were 85.7% and 85.3%, respectively. The distribution of prevalence and days/year of use for specific pesticides were similar across observed and imputed in the holdout sample. When appropriately implemented, multiple imputation can reduce bias and increase precision and can be more valid than other missing data approaches.

Comparing agricultural cohorts with the general population is challenging because the general healthiness of farmers may mask potential adverse health effects of farming. Using data from the Agricultural Health Study, a cohort of 89,656 pesticide applicators and their spouses (N = 89, 656) in North Carolina and Iowa, the authors computed standardized mortality ratios (SMRs) comparing deaths from time of the enrollment (1993-1997) through 2007 to state-specific rates. To compensate for the cohort's overall healthiness, relative SMRs were estimated by calculating the SMR for each cause relative to the SMR for all other causes. In 1,198,129 person-years of follow-up, 6,419 deaths were observed. The all-cause mortality rate was less than expected (SMR(applicators) = 0.54, 95% confidence interval (CI): 0.52, 0.55; SMR(spouses) = 0.52, 95% CI: 0.50, 0.55). SMRs for all cancers, heart disease, and diabetes were significantly below 1.0. In contrast, applicators experienced elevated numbers of machine-related deaths (SMR = 4.15, 95% CI: 3.18, 5.31), motor vehicle nontraffic accidents (SMR = 2.80, 95% CI: 1.81, 4.14), and collisions with objects (SMR = 2.12, 95% CI: 1.25, 3.34). In the relative SMR analysis for applicators, the relative mortality ratio was elevated for lymphohematopoietic cancers, melanoma, and digestive system, prostate, kidney, and brain cancers. Among spouses, relative SMRs exceeded 1.0 for lymphohematopoietic cancers and malignancies of the digestive system, brain, breast, and ovary. Unintentional fatal injuries remain an important risk for farmers; mortality ratios from several cancers were elevated relative to other causes.

The science of exposure assessment is relatively new and evolving rapidly with the advancement of sophisticated methods for specific measurements at the picogram per gram level or lower in a variety of environmental and biologic matrices. Without this measurement capability, environmental health studies rely on questionnaires or other indirect means as the primary method to assess individual exposures. Although we use indirect methods, they are seldom used as stand-alone tools. Analyses of environmental and biologic samples have allowed us to get more precise data on exposure pathways, from sources to concentrations, to routes, to exposure, to doses. They also often allow a better estimation of the absorbed dose and its relation to potential adverse health outcomes in individuals and in populations. Here, we make note of various environmental agents and how best to assess exposure to them in the National Children's Study--a longitudinal epidemiologic study of children's health. Criteria for the analytical method of choice are discussed with particular emphasis on the need for long-term quality control and quality assurance measures.

PURPOSE: This analysis of the Agricultural Health Study cohort assesses the mortality experience of licensed pesticide applicators and their spouses. METHODS: This report is based on 52,393 private applicators (who are mostly farmers) and 32,345 spouses of farmers in Iowa and North Carolina. At enrollment, each pesticide applicator completed a 21-page enrollment questionnaire. Mortality assessment from enrollment (1994-1997) through 2000 provided an average follow-up of about 5.3 years, 447,154 person-years, and 2055 deaths. RESULTS: Compared with the general population in the two states, the cohort experienced a very low mortality rate. Standardized mortality ratios (SMRs) for total mortality, cardiovascular disease, diabetes, COPD, total cancer, and cancers of the esophagus, stomach, and lung were 0.6 or lower for both farmers and spouses. These deficits varied little by farm size, type of crops or livestock on the farm, years of handling pesticides, holding a non-farm job, or length of follow up. SMRs among ever smokers were not as low as among never smokers, but were still less than 1.0 for all smoking-related causes of death. No statistically significant excesses occurred, but slightly elevated SMRs, or those near 1.0, were noted for diseases that have been associated with farming in previous studies. CONCLUSIONS: Several factors may contribute to the low mortality observed in this population, including the healthy worker effect typically seen in cohorts of working populations (which may decline in future years), a short follow-up interval, and a healthier lifestyle manifested through lower cigarette use and an occupation that has traditionally required high levels of physical activity.

The authors examined the relation between 45 common agricultural pesticides and prostate cancer incidence in a prospective cohort study of 55,332 male pesticide applicators from Iowa and North Carolina with no prior history of prostate cancer. Data were collected by means of self-administered questionnaires completed at enrollment (1993-1997). Cancer incidence was determined through population-based cancer registries from enrollment through December 31, 1999. A prostate cancer standardized incidence ratio was computed for the cohort. Odds ratios were computed for individual pesticides and for pesticide use patterns identified by means of factor analysis. A prostate cancer standardized incidence ratio of 1.14 (95% confidence interval: 1.05, 1.24) was observed for the Agricultural Health Study cohort. Use of chlorinated pesticides among applicators over 50 years of age and methyl bromide use were significantly associated with prostate cancer risk. Several other pesticides showed a significantly increased risk of prostate cancer among study subjects with a family history of prostate cancer but not among those with no family history. Important family history-pesticide interactions were observed.

A National Human Exposure Assessment Survey (NHEXAS) field study was performed in U.S. Environmental Protection Agency (EPA) Region V, providing population-based exposure distribution data for selected elements in several personal, environmental, and biological media. Population distributions are reported for the 11 elements that were measured in water and dietary samples. Dietary intakes and home tap water concentrations of lead, arsenic, and cadmium were further examined for intermedia associations, for differences between dietary exposure for adults and children, and to estimate the proportion of the population above health-based reference values (dietary) or regulatory action levels or maximum contaminant levels (water). Water lead and arsenic concentrations were significantly associated with dietary intake. Intake of all elements was higher from solid foods than from liquid foods (including drinking water). Dietary intakes of Pb, As, and Cd were greater than those calculated for intake from home tap water or inhalation on a microg/day basis. Median dietary intakes for the Region V population for Pb, As, and Cd were 0.10, 0.13, and 0.19 microg/kg bw/day, respectively. While Pb, As, and Cd concentrations in the foods consumed by 0 to 6-year-old children were similar to or lower than those for adults, dietary intakes calculated on a body weight basis were 1.5 to 2.5 times higher for young children. Intrapersonal intake differences accounted for most of the variance in short-term (daily) dietary intakes for Pb and As, while interpersonal differences accounted for more of the intake variance for Cd. Only small percentages of the population exceeded health-based intake reference values or concentrations equal to regulatory levels in water for Pb, As, and Cd.

Farming and pesticide use have previously been linked to non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). We evaluated agricultural use of specific insecticides, fungicides, and fumigants and risk of NHL and NHL-subtypes (including CLL and MM) in a U.S.-based prospective cohort of farmers and commercial pesticide applicators. A total of 523 cases occurred among 54,306 pesticide applicators from enrollment (1993–97) through December 31, 2011 in Iowa, and December 31, 2010 in North Carolina. Information on pesticide use, other agricultural exposures and other factors was obtained from questionnaires at enrollment and at follow-up approximately five years later (1999–2005). Information from questionnaires, monitoring, and the literature were used to create lifetime-days and intensity-weighted lifetime days of pesticide use, taking into account exposure-modifying factors. Poisson and polytomous models were used to calculate relative risks (RR) and 95% confidence intervals (CI) to evaluate associations between 26 pesticides and NHL and five NHL-subtypes, while adjusting for potential confounding factors. For total NHL, statistically significant positive exposure-response trends were seen with lindane and DDT. Terbufos was associated with total NHL in ever/never comparisons only. In subtype analyses, terbufos and DDT were associated with small cell lymphoma/chronic lymphocytic leukemia/marginal cell lymphoma, lindane and diazinon with follicular lymphoma, and permethrin with MM. However, tests of homogeneity did not show significant differences in exposure-response among NHL-subtypes for any pesticide. Because 26 pesticides were evaluated for their association with NHL and its subtypes, some chance finding could have occurred. Our results showed pesticides from different chemical and functional classes were associated with an excess risk of NHL and NHL subtypes, but not all members of any single class of pesticides were associated with an elevated risk of NHL or NHL subtypes. These findings are among the first to suggest links between DDT, lindane, permethrin, diazinon and terbufos with NHL subtypes.

The Lower Rio Grande Valley Environmental Study (LRGVES) was designed to evaluate multiple forms of exposure to Valley residents because of community concerns of possible adverse health effects from environmental conditions. This is the second of two papers that describe the dietary components of the LRGVES scoping study, conducted in the spring and summer of 1993 in nine Valley residences. Drinking water and household water samples were collected along with food and beverage samples to determine potential dietary exposures of the participants. Water samples were analyzed for various organic compounds, including volatile organic compounds, polycyclic aromatic hydrocarbons, pesticides, haloacetic acids, chlorinated acids, and benzidines. Samples were also analyzed for trace elements, selected anions, and microbial quality. Sources of water available in the residences for drinking and other household purposes were public treatment facilities, vended water machines, and a private well. In general, organic and inorganic chemicals found in commercial sources of drinking water did not exceed federal criteria. However, products of the disinfection process (total trihalomethanes) exceeded the federal regulatory level in one sample. In addition, tap water samples from public water supplies were high in chloride and sulfate anions, often related to poor odor, color, or taste, resulting in residents of the Valley purchasing water for drinking at local vending machines and storing it in their homes in a variety of containers. Microbiological contamination of these containers was found to be a potential health problem. Coliform levels exceeding federal criteria for public water supplies were found in the water of several participants who did not regularly disinfect the containers in which they stored their drinking water. Water from a private well, which was designated for purposes other than drinking, was also unsuitable for drinking because of microbial contamination. Water sampling in the LRGVES pilot study identified the need for intervention and educational programs to eliminate exposures of Valley residents.

The accuracy of the exposure assessment is a critical factor in epidemiological investigations of pesticide exposures and health in agricultural populations. However, few studies have been conducted to evaluate questionnaire-based exposure metrics. The Agricultural Health Study (AHS) is a prospective cohort study of pesticide applicators who provided detailed questionnaire information on their use of specific pesticides. A field study was performed for a subset of the applicators enrolled in the AHS to assess a pesticide exposure algorithm through comparison of algorithm intensity scores with measured exposures. Pre- and post-application urinary biomarker measurements were made for 2,4-D (n = 69) and chlorpyrifos (n = 17) applicators. Dermal patch, hand wipe, and personal air samples were also collected. Intensity scores were calculated using information from technician observations and an interviewer-administered questionnaire. Correlations between observer and questionnaire intensity scores were high (Spearman r = 0.92 and 0.84 for 2,4-D and chlorpyrifos, respectively). Intensity scores from questionnaires for individual applications were significantly correlated with post-application urinary concentrations for both 2,4-D (r = 0.42, p < 0.001) and chlorpyrifos (r = 0.53, p = 0.035) applicators. Significant correlations were also found between intensity scores and estimated hand loading, estimated body loading, and air concentrations for 2,4-D applicators (r-values 0.28–0.50, p-values

In this study, we investigated the 2,4-dichlorophenoxyacetic acid (2,4-D) herbicide exposures of 135 preschool-aged children and their adult caregivers at 135 homes in North Carolina (NC) and Ohio (OH). Participants were randomly recruited from six NC and six OH counties. Monitoring was performed over a 48-h period at the participants' homes. Environmental samples included soil, outdoor air, indoor air, and carpet dust. Personal samples collected by the adult caregivers concerning themselves and their children consisted of solid food, liquid food, hand wipe, and spot urine samples. All samples were analyzed for 2,4-D (free acid form) by gas chromatography/mass spectrometry. 2,4-D was detected in all types of environmental samples but most often in carpet dust samples, with detection frequencies of 83% and 98% in NC and OH, respectively. The median level of 2,4-D in the carpet dust samples was about three times higher in OH homes compared to NC homes (156 vs. 47.5 ng/g, P0.0002). For personal samples, 2,4-D was more frequently detected in the hand wipe samples from OH participants (48%) than from NC participants (9%). Hand wipe levels at the 95th percentile were about five times higher for OH children (0.1 ng/cm(2)) and adults (0.03 ng/cm(2)) than for the NC children (0.02 ng/cm(2)) and adults (0.005 ng/cm(2)). 2,4-D was detected in more than 85% of the child and adult urine samples in both states. The median urinary 2,4-D concentration was more than twice as high for OH children compared to NC children (1.2 vs. 0.5 ng/ml, P0.0001); however, the median concentration was identical at 0.7 ng/ml for both NC and OH adults. The intraclass correlation coefficient of reliability for an individual's urinary 2,4-D measurements, estimated from the unadjusted (0.31-0.62) and specific gravity-adjusted (0.37-0.73) values, were somewhat low for each group in this study. The variability in urinary 2,4-D measurements over the 48-h period for both children and adults in NC and OH suggests that several spot samples were needed to adequately assess these participants' exposures to 2,4-D in residential settings. Results from this study showed that children and their adult caregivers in NC and OH were likely exposed to 2,4-D through several pathways at their homes. In addition, our findings suggest that the OH children might have been exposed to higher levels of 2,4-D through the dermal and nondietary routes of exposure than the NC children and the NC and OH adults.

This report describes the development of a portable spirometer capable of collecting primarily alveolar breath into 1.8-L canisters for subsequent gas chromatographic/mass spectrometric (GC/MS) analysis. Based on CO2 measurements, greater than 97% of the breath collected is alveolar in origin. Sample collection takes place in approximately two minutes. Clean air for inhalation is provided by two organic vapor respirator cartridges. Studies of the breakthrough volume of test compounds at both the 5- and 50-micrograms/m3 levels indicate that each cartridge filter can be used to sample over 300 L of air and that this volume is not altered by intermittent use and storage of the filter for up to five days. In experiments designed to mimic human breathing, recoveries of test compounds through the device at the 5-mu/m3 level ranged from 87 to 112%. Essentially no volatile organic compound (VOC) memory (i.e., adsorption carryover by the device) was measured at the 50-micrograms/m3 level. The data suggest that the device can be used successfully for organic compounds with volatilities greater than that of p-dichlorobenzene.

The Agricultural Health Study (www.aghealth.org) is a cohort of 89,658 pesticide applicators and their spouses from Iowa and North Carolina assembled between 1993 and 1997 to evaluate risk factors for disease in rural farm populations. This prospective study is just now reaching sufficient maturity for analysis of many disease endpoints. Nonetheless, several analyses have already provided interesting and important leads regarding disease patterns in agricultural populations and etiologic clues for the general population. Compared to the mortality experience of the general population in the two states (adjusted for race, gender, age and calendar time), the cohort experienced a very low mortality rate overall and for many specific causes and a low rate of overall cancer incidence. A few cancers, however, appear elevated, including multiple myeloma and cancers of the lip, gallbladder, ovary, prostate, and thyroid, but numbers are small for many cancers. A study of prostate cancer found associations with exposure to several pesticides, particularly among individuals with a family history of prostate cancer. Links to pesticides and other agricultural factors have been found for injuries, retinal degeneration, and respiratory wheeze. Methodological studies have determined that information collected by interview is unbiased and reliable. A third round of interviews scheduled to begin in 2005 will collect additional information on agricultural exposures and health outcomes. The study can provide data to address many health issues in the agricultural community. The study investigators welcome collaboration with interested scientists.

An enzyme-linked immunosorbent assay (ELISA) method was developed to quantitatively measure 2,4-dichlorophenoxyacetic acid (2,4-D) in human urine. Samples were diluted (1:5) with phosphate-buffered saline containing 0.05% Tween and 0.02% sodium azide, with analysis by a 96-microwell plate immunoassay format. No clean up was required as dilution step minimized sample interferences. Fifty urine samples were received without identifiers from a subset of pesticide applicators and their spouses in an EPA pesticide exposure study (PES) and analyzed by the ELISA method and a conventional gas chromatography/mass spectrometry (GC/MS) procedure. For the GC/MS analysis, urine samples were extracted with acidic dichloromethane (DCM); methylated by diazomethane and fractionated by a Florisil solid phase extraction (SPE) column prior to GC/MS detection. The percent relative standard deviation (%R.S.D.) of the 96-microwell plate triplicate assays ranged from 1.2 to 22% for the urine samples. Day-to-day variation of the assay results was within ±20%. Quantitative recoveries (>70%) of 2,4-D were obtained for the spiked urine samples by the ELISA method. Quantitative recoveries (>80%) of 2,4-D were also obtained for these samples by the GC/MS procedure. The overall method precision of these samples was within ±20% for both the ELISA and GC/MS methods. The estimated quantification limit for 2,4-D in urine was 30 ng/mL by ELISA and 0.2 ng/mL by GC/MS. A higher quantification limit for the ELISA method is partly due to the requirement of a 1:5 dilution to remove the urine sample matrix effect. The GC/MS method can accommodate a 10:1 concentration factor (10 mL of urine converted into 1 mL organic solvent for analysis) but requires extraction, methylation and clean up on a solid phase column. The immunoassay and GC/MS data were highly correlated, with a correlation coefficient of 0.94 and a slope of 1.00. Favorable results between the two methods were achieved despite the vast differences in sample preparation. Results indicated that the ELISA method could be used as a high throughput, quantitative monitoring tool for human urine samples to identify individuals with exposure to 2,4-D above the typical background levels.

The authors examined the relation between 50 widely used agricultural pesticides and lung cancer incidence in the Agricultural Health Study, a prospective cohort study of 57,284 pesticide applicators and 32,333 spouses of farmer applicators with no prior history of lung cancer. Self-administered questionnaires were completed at enrollment (1993-1997). Cancer incidence was determined through population-based cancer registries from enrollment through December 31, 2001. A lung cancer standardized incidence ratio of 0.44 (95% confidence interval: 0.39, 0.49) was observed overall, due in large part to a low cigarette smoking prevalence. Two widely used herbicides, metolachlor and pendimethalin (for low-exposed groups to four higher exposure categories: odds ratio (OR) = 1.0, 1.6, 1.2, 5.0; p(trend) = 0.0002; and OR = 1.0, 1.6, 2.1, 4.4; p(trend) = 0.003, respectively), and two widely used insecticides, chlorpyrifos and diazinon (OR = 1.0, 1.1, 1.7, 1.9; p(trend) = 0.03; and OR = 1.0, 1.6, 2.7, 3.7; p(trend) = 0.04, respectively), showed some evidence of exposure response for lung cancer. These excesses could not be explained by previously identified lung cancer risk factors. The usage levels in this cohort are considerably higher than those typically experienced by the general population. An excess risk among spouses directly exposed to pesticides could not be evaluated at this time.

Objectives Farming and exposure to pesticides have been linked to non-Hodgkin lymphoma (NHL), and multiple myeloma (MM) in previous studies. We evaluated use of insecticides, fungicides and fumigants and risk of NHL, including MM and other NHL sub-types in the Agricultural Health Study, a US-based prospective cohort study. Method A total of 527 cases occurred among 55 875 pesticide applicators from enrollment (1993–1997) through 2011 in Iowa and 2010 in North Carolina. Information on pesticide use, other agricultural exposures and other factors was obtained from questionnaires at enrollment and follow-up approximately five years later (1999–2005). Information from these questionnaires was used to create lifetime-days and intensity-weighted lifetime-days of pesticide use. Poisson regression and polytomous logit models were used to calculate relative risks (RR) and 95% confidence intervals (CI) to evaluate associations between 26 pesticides and NHL and five NHL-subtypes including multiple myeloma, while adjusting for potential confounding factors. Results Statistically significant positive exposure-response trends occurred between overall NHL risk and lindane (p-trend = 0.004) and DDT (p-trend = 0.02). In addition, ever use of terbufos was associated with NHL overall (RR=1.2; CI=1.0–1.5), but with no exposure-response trend. In sub-type analyses, terbufos and DDT were associated with small cell lymphoma/chronic lymphocytic leukaemia/marginal cell lymphoma. In addition, lindane and diazinon were associated with follicular lymphoma and permethrin with MM although tests of homogeneity did not show significant differences in exposure-response among NHL-subtypes for any chemical. Conclusions These findings are among the first to suggest links between DDT, lindane, permethrin, diazinon and terbufos and specific NHL subtypes.

In implementing the Food Quality Protection Act (FQPA) the U.S. Environmental Protection Agency (USEPA) has adopted a policy that the exposure factors and models used to assess and predict exposure to pesticides should generally be conservative. Some elements of exposure assessments for FQPA are screening level — they are both uncertain and conservative. If more realistic assessments are to be conducted, then research is required to reduce uncertainty associated with the factors and models used in the exposure assessments. To develop the strategy for conducting this research, critical exposure pathways and factors were identified, and the quality and quantity of data associated with default assumptions for exposure factors were evaluated. Then, based on our current understanding of the pathways that are potentially most important and most uncertain, significant research requirements were identified and prioritized to improve the data available and assumptions used to assess children's aggregate exposure to pesticides. Based on the results of these efforts, four priority research areas were identified: (1) pesticide use patterns in microenvironments where children spend time, (2) temporal and spatial distribution of pesticides following application in a residential setting, (3) dermal and nondietary ingestion exposure assessment methods and exposure factors, (4) dietary exposure assessment methods and exposure factors for infants and young children. The National Exposure Research Laboratory (NERL) research strategy in support of FQPA is designed to address these priority research needs.

Mage et al. criticize our article (Barr et al. 2006), stressing six “… factual and conceptual errors that need to be called to the readers’ attention.” We appreciate their careful reading of our work, and they raise several important points regarding survey design. However, we take issue with some of their statements. Many investigations are designed to generalize the results of the research performed within a sample population to a larger population. In these types of investigations, enrollment of a representative sample is a necessary condition for making inferences to the larger population through known selection probabilities that are then used for applying sampling weights to study results. However, in order to generalize the results, these studies must have an adequate sample size, high response rate, and, importantly, a preliminary assessment of whether the factors for probability selection and weighting will be relevant to the condition being measured. Although representative samples are desirable and have been achieved in many studies, some studies in rare or difficult-to-reach populations cannot practically meet the criteria mentioned above. Farmworkers are often not the ones applying pesticides (i.e., they are not applicators); quite often these farmworkers are unaware of the actual pesticides being applied or when they are applied. The potential for undue exposure may be more likely if farmworkers are not properly informed of the application or reentry times or if they do not understand the potential exposure scenarios. Research investigations involving farmworker exposures can present particular difficulties in selecting a representative sample of the population. Data for developing relevant sampling frames and selection probabilities are often limited by demographic and work factors. Obtaining high response rates for farmworkers can also be challenging because of problems associated with access, high mobility, geographic dispersion, trust, and cultural practices (Arcury et al. 2006). However, these populations remain important and potentially vulnerable populations that should be included in research investigations, even if the conditions for using a probability sample cannot always practically be met. In any particular situation, the decision to use probability sampling will depend on the hypothesis. However, important and relevant research questions can be investigated without selecting a representative sample of the population, as noted by Mage et al. regarding particle exposure studies in high-risk subpopulations. Nonprobability samples can provide useful information on particular hard-to-reach populations, for intensive examination of conditions and factors related to exposures, or for hypothesis generation. By forcing all studies to conform to the same design, we may not be able to answer specific research questions. The studies cited by Mage et al. were designed as probability samples, but each had differential drop-out rates during selection and sampling. Potential drop-out non-representativeness can be accounted for if the effect on exposure or the outcome variable is known. However, in some populations, the details of the accounting are not easily accomplished. Mage et al. cited the National Health and Nutrition Examination Survey (NHANES) as “another excellent example of proper probability-based sample selection.” However, even NHANES III (1988–1994) used a nonprobability sample for the environmental subset (Hill et al. 1995). These data provided an invaluable first look at U.S. population exposures and served as a basis to add statistical sampling for environmental chemicals to the current NHANES series. These data have also been used to estimate doses in the U.S. population for comparison to the U.S. Environmental Protection Agency’s reference doses (Mage et al. 2004). In fact, it is often difficult to design a population-based study without preliminary data. We have participated in the design and implementation of studies using both probability and nonprobability sampling that have added invaluable information on various population exposures. We recognize the practical difficulties and challenges for meeting the criteria for representative sampling in farmworker populations and also the important information that such studies can provide. Although we agree that without a probability sample, the results should only apply to individuals in studies and should not be generalized to a population, we disagree with the contention made by Mage et al. that no useful information can come from studies using samples that do not fulfill their criteria.

PURPOSE: In the Agricultural Health Study we evaluated the mortality experience of 52,395 farmers and 32,347 of their spouses in Iowa and North Carolina obtain information on cancer and other chronic disease risks from agricultural exposures and other factors associated with rural lifestyle. METHODS: Standardized mortality ratios (SMRs) adjusted for race, gender, age, and calendar time were computed for the prospective cohort, using the general population in each state as the referent. RESULTS: After an average follow-up of 3.7 years, the SMRs for most causes of death were significantly less than 1.0. Significant deficits were observed for all causes (SMR = 0.5), all cancers combined (SMR = 0.5), and for cancers of the lung (SMR = 0.3), female genital organs (SMR = 0.4), prostate (SMR = 0.6) and bladder (SMR = 0.6), as well as diabetes (SMR = 0.3), cardiovascular disease (SMR = 0.5), and chronic obstructive pulmonary disease (SMR = 0.2). Non-significant excesses involving at least 3 deaths occurred for liver cancer (SMR = 2.1), multiple myeloma (SMR = 1.6), leukemia (SMR = 1.4), and Parkinson's disease among spouses (SMR = 2.7. Among farmers elevated SMRs were noted for Hodgkin's disease (SMR = 2.9) and cancer of the thyroid gland (SMR = 2.9), and non-motor vehicle accidents (SMR = 1.1). Soft tissue sarcoma (SMR = 1.1 for spouses; SMR = 1.6 for applicators) was elevated in both groups. NHL had an SMR of 1.0 among applicators and spouses. Stratification by presence of livestock or corn on the farm, farm size, and duration of handling pesticides revealed no obvious mortality differences. CONCLUSION: Despite a very low initial mortality experience compared to the general population, Agricultural Health Study farmers and their spouses appear to have rates for some cancers and chronic diseases that deserve continued monitoring and further scrutiny.

Thoracic drainage systems are currently marketed in many varieties, resulting in significant cost and complicating patient management. Realistic needs have been identified from a survey of thoracic surgeons. These are: (1) clear plastic chest catheters with multiple drainage holes in sizes 28, 32, and 36F for adults and 16, 20, and 24F for infants and children; (2) serrated plastic connectors that can be sized at operation; (3) connecting tubes of clear plastic 6 feet long with a diameter of 1/2 inch; (4) a single graduated volume-collecting bottle of 1- to 2-liter capacity that can be emptied and marked, with a separate waterseal component and an associated manometer; and (5) a highflow vacuum source. A drainage system with these characteristics should be safe, effective, simple, and less costly.