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1.  Carbon Nanotube and Nanofiber Exposure Assessments: An Analysis of 14 Site Visits 
Annals of Occupational Hygiene  2015;59(6):705-723.
Recent evidence has suggested the potential for wide-ranging health effects that could result from exposure to carbon nanotubes (CNT) and carbon nanofibers (CNF). In response, the National Institute for Occupational Safety and Health (NIOSH) set a recommended exposure limit (REL) for CNT and CNF: 1 µg m−3 as an 8-h time weighted average (TWA) of elemental carbon (EC) for the respirable size fraction. The purpose of this study was to conduct an industrywide exposure assessment among US CNT and CNF manufacturers and users. Fourteen total sites were visited to assess exposures to CNT (13 sites) and CNF (1 site). Personal breathing zone (PBZ) and area samples were collected for both the inhalable and respirable mass concentration of EC, using NIOSH Method 5040. Inhalable PBZ samples were collected at nine sites while at the remaining five sites both respirable and inhalable PBZ samples were collected side-by-side. Transmission electron microscopy (TEM) PBZ and area samples were also collected at the inhalable size fraction and analyzed to quantify and size CNT and CNF agglomerate and fibrous exposures. Respirable EC PBZ concentrations ranged from 0.02 to 2.94 µg m−3 with a geometric mean (GM) of 0.34 µg m−3 and an 8-h TWA of 0.16 µg m−3. PBZ samples at the inhalable size fraction for EC ranged from 0.01 to 79.57 µg m−3 with a GM of 1.21 µg m−3. PBZ samples analyzed by TEM showed concentrations ranging from 0.0001 to 1.613 CNT or CNF-structures per cm3 with a GM of 0.008 and an 8-h TWA concentration of 0.003. The most common CNT structure sizes were found to be larger agglomerates in the 2–5 µm range as well as agglomerates >5 µm. A statistically significant correlation was observed between the inhalable samples for the mass of EC and structure counts by TEM (Spearman ρ = 0.39, P < 0.0001). Overall, EC PBZ and area TWA samples were below the NIOSH REL (96% were <1 μg m−3 at the respirable size fraction), while 30% of the inhalable PBZ EC samples were found to be >1 μg m−3. Until more information is known about health effects associated with larger agglomerates, it seems prudent to assess worker exposure to airborne CNT and CNF materials by monitoring EC at both the respirable and inhalable size fractions. Concurrent TEM samples should be collected to confirm the presence of CNT and CNF.
doi:10.1093/annhyg/mev020
PMCID: PMC4507369  PMID: 25851309
carbon nanofibers; carbon nanotubes; exposure assessment; nanomaterials
2.  Carbon Nanotube and Nanofiber Exposure Assessments: An Analysis of 14 Site Visits 
Recent evidence has suggested the potential for wide-ranging health effects that could result from exposure to carbon nanotubes (CNT) and carbon nanofibers (CNF). In response, the National Institute for Occupational Safety and Health (NIOSH) set a recommended exposure limit (REL) for CNT and CNF: 1 μg m−3 as an 8-h time weighted average (TWA) of elemental carbon (EC) for the respirable size fraction. The purpose of this study was to conduct an industrywide exposure assessment among US CNT and CNF manufacturers and users. Fourteen total sites were visited to assess exposures to CNT (13 sites) and CNF (1 site). Personal breathing zone (PBZ) and area samples were collected for both the inhalable and respirable mass concentration of EC, using NIOSH Method 5040. Inhalable PBZ samples were collected at nine sites while at the remaining five sites both respirable and inhalable PBZ samples were collected side-by-side. Transmission electron microscopy (TEM) PBZ and area samples were also collected at the inhalable size fraction and analyzed to quantify and size CNT and CNF agglomerate and fibrous exposures. Respirable EC PBZ concentrations ranged from 0.02 to 2.94 μg m−3 with a geometric mean (GM) of 0.34 μg m−3 and an 8-h TWA of 0.16 μg m−3. PBZ samples at the inhalable size fraction for EC ranged from 0.01 to 79.57 μg m−3 with a GM of 1.21 μg m−3. PBZ samples analyzed by TEM showed concentrations ranging from 0.0001 to 1.613 CNT or CNF-structures per cm3 with a GM of 0.008 and an 8-h TWA concentration of 0.003. The most common CNT structure sizes were found to be larger agglomerates in the 2–5 μm range as well as agglomerates >5 μm. A statistically significant correlation was observed between the inhalable samples for the mass of EC and structure counts by TEM (Spearman ρ = 0.39, P < 0.0001). Overall, EC PBZ and area TWA samples were below the NIOSH REL (96% were <1 μg m−3 at the respirable size fraction), while 30% of the inhalable PBZ EC samples were found to be >1 μg m−3. Until more information is known about health effects associated with larger agglomerates, it seems prudent to assess worker exposure to airborne CNT and CNF materials by monitoring EC at both the respirable and inhalable size fractions. Concurrent TEM samples should be collected to confirm the presence of CNT and CNF.
doi:10.1093/annhyg/mev020
PMCID: PMC4507369  PMID: 25851309
carbon nanofibers; carbon nanotubes; exposure assessment; nanomaterials
3.  Trends in Worker Hearing Loss by Industry Sector, 1981–2010 
Background
The purpose of this study was to estimate the incidence and prevalence of hearing loss for noise-exposed U.S. workers by industry sector and 5-year time period, covering 30 years.
Methods
Audiograms for 1.8 million workers from 1981–2010 were examined. Incidence and prevalence were estimated by industry sector and time period. The adjusted risk of incident hearing loss within each time period and industry sector as compared with a reference time period was also estimated.
Results
The adjusted risk for incident hearing loss decreased over time when all industry sectors were combined. However, the risk remained high for workers in Healthcare and Social Assistance, and the prevalence was consistently high for Mining and Construction workers.
Conclusions
While progress has been made in reducing the risk of incident hearing loss within most industry sectors, additional efforts are needed within Mining, Construction and Healthcare and Social Assistance.
doi:10.1002/ajim.22429
PMCID: PMC4557728  PMID: 25690583
occupational hearing loss; material hearing impairment; hazardous noise; noise-induced hearing loss; surveillance; trends; prevalence; incidence
4.  A Simulation Study of Relative Efficiency and Bias in the Nested Case–Control Study Design 
Epidemiologic methods  2013;2(1):85-93.
Purpose
The nested case–control study design, in which a fixed number of controls are matched to each case, is often used to analyze exposure–response associations within a cohort. It has become common practice to sample four or five controls per case; however, previous research has shown that in certain instances, significant gains in relative efficiency can be realized when more controls are matched to each case. This study expanded upon this and investigated the effect of (i) the number of cases, (ii) the strength of the exposure–response, and (iii) the skewness of the exposure distribution on the bias and relative efficiency of the conditional likelihood estimator from a nested case–control study.
Methods
Cohorts were simulated and analyzed using conditional logistic regression.
Results
The relative efficiency decreased and bias away from the null increased, as the true exposure–response parameter increased and the skewness of the exposure distribution of the risk-sets increased. This became more pronounced when the number of cases in the cohort was small.
Conclusions
Gains in relative efficiency and a reduction in bias can be realized by sampling more than four or five controls per case generally used, especially when there are few cases, a strong exposure–response relation, and a skewed exposure variable.
doi:10.1515/em-2013-0007
PMCID: PMC4558410  PMID: 26345580
nested case–control studies; simulation; efficiency; bias; matched case–control studies
5.  Occupational Exposure Assessment in Carbon Nanotube and Nanofiber Primary and Secondary Manufacturers: Mobile Direct-Reading Sampling 
Research Significance
Toxicological evidence suggests the potential for a wide range of health effects from exposure to carbon nanotubes (CNTs) and carbon nanofibers (CNFs). To date, there has been much focus on the use of direct-reading instruments (DRIs) to assess multiple airborne exposure metrics for potential exposures to CNTs and CNFs due to their ease of use and ability to provide instantaneous results. Still, uncertainty exists in the usefulness and interpretation of the data. To address this gap, air-monitoring was conducted at six sites identified as CNT and CNF manufacturers or users and results were compared with filter-based metrics.
Methods
Particle number, respirable mass, and active surface area concentrations were monitored with a condensation particle counter, a photometer, and a diffusion charger, respectively. The instruments were placed on a mobile cart and used as area monitors in parallel with filter-based elemental carbon (EC) and electron microscopy samples. Repeat samples were collected on consecutive days, when possible, during the same processes. All instruments in this study are portable and routinely used for industrial hygiene sampling.
Results
Differences were not observed among the various sampled processes compared with concurrent indoor or outdoor background samples while examining the different DRI exposure metrics. Such data were also inconsistent with results for filter-based samples collected concurrently at the same sites [Dahm MM, Evans DE, Schubauer-Berigan MK et al. (2012) Occupational exposure assessment in CNT and nanofiber primary and secondary manufacturers. Ann Occup Hyg; 56: 542–56]. Significant variability was seen between these processes as well as the indoor and outdoor backgrounds. However, no clear pattern emerged linking the DRI results to the EC or the microscopy data (CNT and CNF structure counts).
Conclusions
Overall, no consistent trends were seen among similar processes at the various sites. The DRI instruments employed were limited in their usefulness in assessing and quantifying potential exposures at the sampled sites but were helpful for hypothesis generation, control technology evaluations, and other air quality issues. The DRIs employed are nonspecific, aerosol monitors, and, therefore, subject to interferences. As such, it is necessary to collect samples for analysis by more selective, time-integrated, laboratory-based methods to confirm and quantify exposures.
doi:10.1093/annhyg/mes079
PMCID: PMC4557693  PMID: 23100605
carbon nanofibers; carbon nanotubes; exposure assessment; nanomaterials; nanoparticles
6.  A prospective study of carpal tunnel syndrome: workplace and individual risk factors 
Objectives
To quantify the risk for carpal tunnel syndrome (CTS) from workplace physical factors, particularly hand activity level and forceful exertion, while taking into account individual factors including age, gender, body mass index (BMI), and pre-existing medical conditions.
Methods
Three healthcare and manufacturing workplaces were selected for inclusion on the basis of range of exposure to hand activity level and forceful exertion represented by their jobs. Each study participants job tasks were observed and evaluated ’ onsite and videotaped for further analysis, including frequency and duration of exertion and postural deviation. Individual health assessment entailed electrodiagnostic testing of median and ulnar nerves, physical examination and questionnaires at baseline with annual follow-up for 2 years.
Results
The incidence of dominant hand CTS during the study was 5.11 per 100 person-years (29 cases). Adjusted HRs for dominant hand CTS were as follows: working with forceful exertion ≥20% but <60% of the time: 2.83 (1.18, 6.79) and ≥60% of the time vs <20%: 19.57 (5.96, 64.24), BMI ≥30 kg/m2 (obesity): 3.19 (1.28, 7.98). The American Conference for Governmental Industrial Hygienists (ACGIH) Threshold Limit Value (TLV) for hand activity level also predicted CTS, HR=1.40 (1.11, 1.78) for each unit increase in the TLV ratio, controlling for obesity and job strain.
Conclusions
Workplace and individual risk factors both contribute to the risk for CTS. Time spent in forceful exertion can be a greater risk for CTS than obesity if the job exposure is high. Preventive workplace efforts should target forceful exertions.
doi:10.1136/oemed-2012-101287
PMCID: PMC4552318  PMID: 23788614
7.  Prevalence of Workers with Shifts in Hearing by Industry: A Comparison of OSHA and NIOSH Hearing Shift Criteria 
Objective
The purpose of this study was to compare the prevalence of workers with National Institute for Occupational Safety and Health significant threshold shifts (NSTS), Occupational Safety and Health Administration standard threshold shifts (OSTS), and with OSTS with age correction (OSTS-A), by industry using North American Industry Classification System codes.
Methods
2001-2010 worker audiograms were examined. Prevalence and adjusted prevalence ratios for NSTS were estimated by industry. NSTS, OSTS and OSTS-A prevalences were compared by industry.
Results
20% of workers had an NSTS, 14% had an OSTS and 6% had an OSTS-A. For most industries, the OSTS and OSTS-A criteria identified 28-36% and 66-74% fewer workers than the NSTS criteria, respectively.
Conclusions
Use of NSTS criteria allowing for earlier detection of shifts in hearing is recommended for improved prevention of occupational hearing loss.
doi:10.1097/JOM.0000000000000124
PMCID: PMC4535326  PMID: 24662953
8.  Mortality Among a Cohort of U.S. Commercial Airline Cockpit Crew 
Background
We evaluated mortality among 5,964 former U.S. commercial cockpit crew (pilots and flight engineers). The outcomes of a priori interest were non-chronic lymphocytic leukemia, central nervous system (CNS) cancer (including brain), and malignant melanoma.
Methods
Vital status was ascertained through 2008. Life table and Cox regression analyses were conducted. Cumulative exposure to cosmic radiation was estimated from work history data.
Results
Compared to the U.S. general population, mortality from all causes, all cancer, and cardiovascular diseases was decreased, but mortality from aircraft accidents was highly elevated. Mortality was elevated for malignant melanoma but not for non-chronic lymphocytic leukemia. CNS cancer mortality increased with an increase in cumulative radiation dose.
Conclusions
Cockpit crew had a low all-cause, all-cancer, and cardiovascular disease mortality but elevated aircraft accident mortality. Further studies are needed to clarify the risk of CNS and other radiation-associated cancers in relation to cosmic radiation and other workplace exposures.
doi:10.1002/ajim.22318
PMCID: PMC4511278  PMID: 24700478
cancer; cockpit crew; cohort study; cosmic radiation; mortality; occupation; pilots
9.  Use of and Occupational Exposure to Indium in the United States 
Indium use has increased greatly in the past decade in parallel with the growth of flat-panel displays, touchscreens, optoelectronic devices, and photovoltaic cells. Much of this growth has been in the use of indium tin oxide (ITO). This increased use has resulted in more frequent and intense exposure of workers to indium. Starting with case reports and followed by epidemiological studies, exposure to ITO has been linked to serious and sometimes fatal lung disease in workers. Much of this research was conducted in facilities that process sintered ITO, including manufacture, grinding, and indium reclamation from waste material. Little has been known about indium exposure to workers in downstream applications. In 2009–2011, the National Institute for Occupational Safety and Health (NIOSH) contacted 89 potential indium-using companies; 65 (73%) responded, and 43 of the 65 responders used an indium material. Our objective was to identify current workplace applications of indium materials, tasks with potential indium exposure, and exposure controls being used. Air sampling for indium was either conducted by NIOSH or companies provided their data for a total of 63 air samples (41 personal, 22 area) across 10 companies. Indium exposure exceeded the NIOSH recommended exposure limit (REL) of 0.1 mg/m3 for certain methods of resurfacing ITO sputter targets, cleaning sputter chamber interiors, and in manufacturing some inorganic indium compounds. Indium air concentrations were low in sputter target bonding with indium solder, backside thinning and polishing of fabricated indium phosphide-based semiconductor devices, metal alloy production, and in making indium-based solder pastes. Exposure controls such as containment, local exhaust ventilation (LEV), and tool-mounted LEV can be effective at reducing exposure. In conclusion, occupational hygienists should be aware that the manufacture and use of indium materials can result in indium air concentrations that exceed the NIOSH REL. Given recent findings of adverse health effects in workers, research is needed to determine if the current REL sufficiently protects workers against indium-related diseases.
doi:10.1080/15459624.2013.836279
PMCID: PMC4476525  PMID: 24195539
thin films; photovoltaics; semiconductor; indium tin oxide; copper indium gallium diselenide; indium phosphide
10.  Carbon nanotube dosimetry: from workplace exposure assessment to inhalation toxicology 
Background
Dosimetry for toxicology studies involving carbon nanotubes (CNT) is challenging because of a lack of detailed occupational exposure assessments. Therefore, exposure assessment findings, measuring the mass concentration of elemental carbon from personal breathing zone (PBZ) samples, from 8 U.S.-based multi-walled CNT (MWCNT) manufacturers and users were extrapolated to results of an inhalation study in mice.
Results
Upon analysis, an inhalable elemental carbon mass concentration arithmetic mean of 10.6 μg/m3 (geometric mean 4.21 μg/m3) was found among workers exposed to MWCNT. The concentration equates to a deposited dose of approximately 4.07 μg/d in a human, equivalent to 2 ng/d in the mouse. For MWCNT inhalation, mice were exposed for 19 d with daily depositions of 1970 ng (equivalent to 1000 d of a human exposure; cumulative 76 yr), 197 ng (100 d; 7.6 yr), and 19.7 ng (10 d; 0.76 yr) and harvested at 0, 3, 28, and 84 d post-exposure to assess pulmonary toxicity. The high dose showed cytotoxicity and inflammation that persisted through 84 d after exposure. The middle dose had no polymorphonuclear cell influx with transient cytotoxicity. The low dose was associated with a low grade inflammatory response measured by changes in mRNA expression. Increased inflammatory proteins were present in the lavage fluid at the high and middle dose through 28 d post-exposure. Pathology, including epithelial hyperplasia and peribronchiolar inflammation, was only noted at the high dose.
Conclusion
These findings showed a limited pulmonary inflammatory potential of MWCNT at levels corresponding to the average inhalable elemental carbon concentrations observed in U.S.-based CNT facilities and estimates suggest considerable years of exposure are necessary for significant pathology to occur at that level.
doi:10.1186/1743-8977-10-53
PMCID: PMC4015290  PMID: 24144386
Workplace exposure assessment; Inhalation exposure; Mouse model; MWCNT Dose response and time dependence; Protein; Gene expression
11.  Determinants of Captan Air and Dermal Exposures among Orchard Pesticide Applicators in the Agricultural Health Study 
Annals of Occupational Hygiene  2011;55(6):620-633.
Objectives: To identify and quantify determinants of captan exposure among 74 private orchard pesticide applicators in the Agricultural Health Study (AHS). To adjust an algorithm used for estimating pesticide exposure intensity in the AHS based on these determinants and to compare the correlation of the adjusted and unadjusted algorithms with urinary captan metabolite levels.
Methods: External exposure metrics included personal air, hand rinse, and dermal patch samples collected from each applicator on 2 days in 2002–2003. A 24-h urine sample was also collected. Exposure determinants were identified for each external metric using multiple linear regression models via the NLMIXED procedure in SAS. The AHS algorithm was adjusted, consistent with the identified determinants. Mixed-effect models were used to evaluate the correlation between the adjusted and unadjusted algorithm and urinary captan metabolite levels.
Results: Consistent determinants of captan exposure were a measure of application size (kilogram of captan sprayed or application method), wearing chemical-resistant (CR) gloves and/or a coverall/suit, repairing spray equipment, and product formulation. Application by airblast was associated with a 4- to 5-fold increase in exposure as compared to hand spray. Exposure reduction to the hands, right thigh, and left forearm from wearing CR gloves averaged ∼80%, to the right and left thighs and right forearm from wearing a coverall/suit by ∼70%. Applicators using wettable powder formulations had significantly higher air, thigh, and forearm exposures than those using liquid formulations. Application method weights in the AHS algorithm were adjusted to nine for airblast and two for hand spray; protective equipment reduction factors were adjusted to 0.2 (CR gloves), 0.3 (coverall/suit), and 0.1 (both).
Conclusions: Adjustment of application method, CR glove, and coverall weights in the AHS algorithm based on our exposure determinant findings substantially improved the correlation between the AHS algorithm and urinary metabolite levels.
doi:10.1093/annhyg/mer008
PMCID: PMC3131503  PMID: 21427168
agriculture; captan; dermal exposure—pesticides, determinants of exposure; exposure assessment—mixed models; orchards; pesticide exposure; variance components
12.  Thyroxine and Free Thyroxine Levels in Workers Occupationally Exposed to Inorganic Lead 
Background:
The effects of lead exposure on thyroid function are unclear.
Methods:
Serum thyroxine (T4) was evaluated among 137 lead-exposed workers and 83 non-exposed workers. Free thyroxine (FT4) was evaluated among a subset of these workers. Exposure metrics included blood lead level (BLL), which reflects recent exposure, zinc protoporphyrin (ZPP), a marker of intermediate-duration lead exposure, exposure duration, and estimated cumulative exposure. Multiple linear regression results were adjusted for age, race, and current smoking status.
Results:
Mean BLLs were 38.9 μg/dL in lead exposed workers and 2.1 μg/dL in non-exposed workers. The adjusted mean T4 and FT4 concentrations among exposed and non-exposed workers were similar. While T4 was not significantly related to any of the exposure metrics, FT4 was inversely related to the logged values of both exposure duration and cumulative exposure, but not to ZPP or BLL.
Conclusions:
The findings suggest that FT4 levels may be related to long-term lead exposure.
doi:10.4137/EHI.S7193
PMCID: PMC3140278  PMID: 21792313
thyroxine; free thyroxine; lead; occupational exposure
13.  Maternal exposure to polychlorinated biphenyls and the secondary sex ratio: an occupational cohort study 
Environmental Health  2011;10:20.
Background
Though commercial production of polychlorinated biphenyls was banned in the United States in 1977, exposure continues due to their environmental persistence. Several studies have examined the association between environmental polychlorinated biphenyl exposure and modulations of the secondary sex ratio, with conflicting results.
Objective
Our objective was to evaluate the association between maternal preconceptional occupational polychlorinated biphenyl exposure and the secondary sex ratio.
Methods
We examined primipara singleton births of 2595 women, who worked in three capacitor plants at least one year during the period polychlorinated biphenyls were used. Cumulative estimated maternal occupational polychlorinated biphenyl exposure at the time of the infant's conception was calculated from plant-specific job-exposure matrices. A logistic regression analysis was used to evaluate the association between maternal polychlorinated biphenyl exposure and male sex at birth (yes/no).
Results
Maternal body mass index at age 20, smoking status, and race did not vary between those occupationally exposed and those unexposed before the child's conception. Polychlorinated biphenyl-exposed mothers were, however, more likely to have used oral contraceptives and to have been older at the birth of their first child than non-occupationally exposed women. Among 1506 infants liveborn to polychlorinated biphenyl-exposed primiparous women, 49.8% were male; compared to 49.9% among those not exposed (n = 1089). Multivariate analyses controlling for mother's age and year of birth found no significant association between the odds of a male birth and mother's cumulative estimated polychlorinated biphenyl exposure to time of conception.
Conclusions
Based on these data, we find no evidence of altered sex ratio among children born to primiparous polychlorinated biphenyl-exposed female workers.
doi:10.1186/1476-069X-10-20
PMCID: PMC3070618  PMID: 21418576
14.  Occupational Exposure to Polychlorinated Biphenyls and Risk of Breast Cancer 
Environmental Health Perspectives  2008;117(2):276-282.
Background
Despite the endocrine system activity exhibited by polychlorinated biphenyls (PCBs), recent studies have shown little association between PCB exposure and breast cancer mortality.
Objectives
To further evaluate the relation between PCB exposure and breast cancer risk, we studied incidence, a more sensitive end point than mortality, in an occupational cohort.
Methods
We followed 5,752 women employed for at least 1 year in one of three capacitor manufacturing facilities, identifying cases from questionnaires, cancer registries, and death certificates through 1998. We collected lifestyle and reproductive information via questionnaire from participants or next of kin and used semiquantitative job-exposure matrices for inhalation and dermal exposures combined. We generated standardized incidence ratios (SIRs) and standardized rate ratios and used Cox proportional hazards regression models to evaluate potential confounders and effect modifiers.
Results
Overall, the breast cancer SIR was 0.81 (95% confidence interval, 0.72–0.92; n = 257), and regression modeling showed little effect of employment duration or cumulative exposure. However, for the 362 women of questionnaire-identified races other than white, we observed positive, statistically significant associations with employment duration and cumulative exposure; only smoking, birth cohort, and self- or proxy questionnaire completion had statistically significant explanatory power when added to models with exposure metrics.
Conclusions
We found no overall elevation in breast cancer risk after occupational exposure to PCBs. However, the exposure-related risk elevations seen among nonwhite workers, although of limited interpretability given the small number of cases, warrant further investigation, because the usual reproductive risk factors accounted for little of the increased risk.
doi:10.1289/ehp.11774
PMCID: PMC2649231  PMID: 19270799
breast cancer; incidence; occupational epidemiology; polychlorinated biphenyls
15.  A comparison of two methods for estimating prevalence ratios 
Background
It is usually preferable to model and estimate prevalence ratios instead of odds ratios in cross-sectional studies when diseases or injuries are not rare. Problems with existing methods of modeling prevalence ratios include lack of convergence, overestimated standard errors, and extrapolation of simple univariate formulas to multivariable models. We compare two of the newer methods using simulated data and real data from SAS online examples.
Methods
The Robust Poisson method, which uses the Poisson distribution and a sandwich variance estimator, is compared to the log-binomial method, which uses the binomial distribution to obtain maximum likelihood estimates, using computer simulations and real data.
Results
For very high prevalences and moderate sample size, the Robust Poisson method yields less biased estimates of the prevalence ratios than the log-binomial method. However, for moderate prevalences and moderate sample size, the log-binomial method yields slightly less biased estimates than the Robust Poisson method. In nearly all cases, the log-binomial method yielded slightly higher power and smaller standard errors than the Robust Poisson method.
Conclusion
Although the Robust Poisson often gives reasonable estimates of the prevalence ratio and is very easy to use, the log-binomial method results in less bias in most common situations, and because it fits the correct model and obtains maximum likelihood estimates, it generally results in slightly higher power, smaller standard errors, and, unlike the Robust Poisson, it always yields estimated prevalences between zero and one.
doi:10.1186/1471-2288-8-9
PMCID: PMC2292207  PMID: 18307814
16.  Maternal and Paternal Risk Factors for Cryptorchidism and Hypospadias: A Case–Control Study in Newborn Boys 
Environmental Health Perspectives  2004;112(15):1570-1576.
Little is known on environmental risk factors for cryptorchidism and hypospadias, which are among the most frequent congenital abnormalities. The aim of our study was to identify risk factors for cryptorchidism and hypospadias, with a focus on potential endocrine disruptors in parental diet and occupation. In a case–control study nested within a cohort of 8,698 male births, we compared 78 cryptorchidism cases and 56 hypospadias cases with 313 controls. The participation rate was 85% for cases and 68% for controls. Through interviews, information was collected on pregnancy aspects and personal characteristics, lifestyle, occupation, and dietary phytoestrogen intake of both parents. Occupational exposure to potential endocrine disruptors was classified based on self-reported exposure and ratings of occupational hygienists based on job descriptions. Our findings indicate that paternal pesticide exposure was associated with cryptorchidism [odds ratio (OR) = 3.8; 95% confidence interval (95% CI), 1.1–13.4]. Smoking of the father was associated with hypospadias (OR = 3.8; 95% CI, 1.8–8.2). Maternal occupational, dietary, and lifestyle exposures were not associated with either abnormality. Both abnormalities were associated with suboptimal maternal health, a lower maternal education, and a Turkish origin of the parents. Being small for gestational age was a risk factor for hypospadias, and preterm birth was a risk factor for cryptorchidism. Because paternal pesticide exposure was significantly associated with cryptorchidism and paternal smoking was associated with hypospadias in male offspring, paternal exposure should be included in further studies on cryptorchidism and hypospadias risk factors.
doi:10.1289/ehp.7243
PMCID: PMC1247623  PMID: 15531444
children; cryptorchidism; endocrine disruptor; environment; epidemiology; hypospadias; nutrition; occupational exposure; testis
17.  Paternal Occupational Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin and Birth Outcomes of Offspring: Birth Weight, Preterm Delivery, and Birth Defects 
Environmental Health Perspectives  2004;112(14):1403-1408.
Agent Orange is a phenoxy herbicide that was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We studied pregnancy outcomes among wives of male chemical workers who were highly exposed to chemicals contaminated with TCDD and among wives of nonexposed neighborhood referents. For exposed pregnancies, we estimated serum TCDD concentration at the time of conception using a pharmacokinetic model. The mean TCDD concentration for workers’ births was 254 pg/g lipid (range, 3–16,340 pg/g). The mean referent concentration of 6 pg/g was assigned to pregnancies fathered by workers before exposure. A total of 1,117 live singleton births of 217 referent wives and 176 worker wives were included. Only full-term births were included in the birth weight analysis (≥37 weeks of gestation). Mean birth weight among full-term babies was similar among referents’ babies (n = 604), preexposure workers’ babies (n = 221), and exposed workers’ babies (n = 292) (3,420, 3,347, and 3,442 g, respectively). Neither continuous nor categorical TCDD concentration had an effect on birth weight for term infants after adjustment for infant sex, mother’s education, parity, prenatal cigarette smoking, and gestation length. An analysis to estimate potential direct exposure of the wives during periods of workers’ exposure yielded a nonstatistically significant increase in infant birth weight of 130 g in the highest exposure group (TCDD concentration > 254 pg/g) compared with referents (p = 0.09). Mothers’ reports of preterm delivery showed a somewhat protective association with paternal TCDD (log) concentration (odds ratio = 0.8; 95% confidence interval, 0.6–1.1). We also include descriptive information on reported birth defects. Because the estimated TCDD concentrations in this population were much higher than in other studies, the results indicate that TCDD is unlikely to increase the risk of low birth weight or preterm delivery through a paternal mechanism.
doi:10.1289/ehp.7051
PMCID: PMC1247568  PMID: 15471733
birth defects; birth weight; congenital anomalies; dioxin; occupation; paternal exposure; preterm birth; TCDD
18.  A 2-year dose-response study of lesion sequences during hepatocellular carcinogenesis in the male B6C3F(1) mouse given the drinking water chemical dichloroacetic acid. 
Dichloroacetic acid (DCA) is carcinogenic to the B6C3F(1) mouse and the F344 rat. Given the carcinogenic potential of DCA in rodent liver and the known concentrations of this compound in drinking water, reliable biologically based models to reduce the uncertainty of risk assessment for human exposure to DCA are needed. Development of such models requires identification and quantification of premalignant hepatic lesions, identification of the doses at which these lesions occur, and determination of the likelihood that these lesions will progress to cancer. In this study we determined the dose response of histopathologic changes occurring in the livers of mice exposed to DCA (0.05-3.5 g/L) for 26-100 weeks. Lesions were classified as foci of cellular alteration smaller than one liver lobule (altered hepatic foci; AHF), foci of cellular alteration larger than one liver lobule (large foci of cellular alteration; LFCA), adenomas (ADs), or carcinomas (CAs). Histopathologic analysis of 598 premalignant lesions revealed that (a)) each lesion class had a predominant phenotype; (b)) AHF, LFCA, and AD demonstrated neoplastic progression with time; and (c)) independent of DCA dose and length of exposure effects, some toxic/adaptive changes in non-involved liver were related to this neoplastic progression. A lesion sequence for carcinogenesis in male B6C3F(1) mouse liver has been proposed that will enable development of a biologically based mathematical model for DCA. Because all classes of premalignant lesions and CAs were found at both lower and higher doses, these data are consistent with the conclusion that nongenotoxic mechanisms, such as negative selection, are relevant to DCA carcinogenesis at lower doses where DCA genotoxicity has not been observed.
PMCID: PMC1241306  PMID: 12515679
19.  Outcome Evaluation of an Intensive Residential Treatment Program for Bulimia 
A 1-month intensive treatment program for bulimic women (ITP) was evaluated. Patients followed up after 1 year had reduced the frequency of purging by 86%, and 38% were symptom free. Patients reported improvements in important relationships and in progress toward life goals. They rated the program highly. Results from the Eating Disorders Inventory, Symptom Checklist 90-R, Eating Attitudes Test, Zung Depression and Anxiety, Body-Cathexis, MMPI, and Color-A-Person Body Dissatisfaction measures indicated highly significant improvement. Patients not followed up had improved similarly but were more impaired. Dropout rate was 1.5%. Results compare well with those of other established eating disorder programs and suggest that the ITP is an effective alternative to hospitalization.
PMCID: PMC3330336  PMID: 22700149

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