Robert L. Herrick

Onset of Breast Development in a Longitudinal Cohort

BACKGROUND AND OBJECTIVES: There is growing evidence of pubertal maturation occurring at earlier ages, with many studies based on cross-sectional observations. This study examined age at onset of breast development (thelarche), and the impact of BMI and race/ethnicity, in the 3 puberty study sites of the Breast Cancer and the Environment Research Program, a prospective cohort of >1200 girls. METHODS: Girls, 6 to 8 years at enrollment, were followed longitudinally at regular intervals from 2004 to 2011 in 3 geographic areas: the San Francisco Bay Area, Greater Cincinnati, and New York City. Sexual maturity assessment using Tanner staging was conducted by using standardized observation and palpation methods by trained and certified staff. Kaplan-Meier analyses were used to describe age at onset of breast maturation by covariates. RESULTS: The age at onset of breast stage 2 varied by race/ethnicity, BMI at baseline, and site. Median age at onset of breast stage 2 was 8.8, 9.3, 9.7, and 9.7 years for African American, Hispanic, white non-Hispanic, and Asian participants, respectively. Girls with greater BMI reached breast stage 2 at younger ages. Age-specific and standardized prevalence of breast maturation was contrasted to observations in 2 large cross-sectional studies conducted 10 to 20 years earlier (Pediatric Research in Office Settings and National Health and Nutrition Examination Survey III) and found to have occurred earlier among white, non-Hispanic, but not African American girls. CONCLUSIONS: We observed the onset of thelarche at younger ages than previously documented, with important differences associated with race/ethnicity and BMI, confirming and extending patterns seen previously. These findings are consistent with temporal changes in BMI.

Serum Biomarkers of Polyfluoroalkyl Compound Exposure in Young Girls in Greater Cincinnati and the San Francisco Bay Area, USA

PFC serum concentrations were measured in 6-8 year-old girls in Greater Cincinnati (GC) (N = 353) and the San Francisco Bay Area (SFBA) (N = 351). PFOA median concentration was lower in the SFBA than GC (5.8 vs. 7.3 ng/mL). In GC, 48/51 girls living in one area had PFOA concentrations above the NHANES 95th percentile for children 12-19 years (8.4 ng/mL), median 22.0 ng/mL. The duration of being breast fed was associated with higher serum PFOA at both sites and with higher PFOS, PFHxS and Me-PFOSA-AcOH concentrations in GC. Correlations of the PFC analytes with each other suggest that a source upriver from GC may have contributed to exposures through drinking water, and water treatment with granular activated carbon filtration resulted in less exposure for SWO girls compared to those in NKY. PFOA has been characterized as a drinking water contaminant, and water treatment systems effective in removing PFCs will reduce body burdens.

Headache Disorders May Be a Risk Factor for the Development of New Onset Hypothyroidism.

To determine whether headache disorders are a risk factor for the development of new onset hypothyroidism.

Polyfluoroalkyl substance exposure in the Mid-Ohio River Valley, 1991–2012

BACKGROUNDnIndustrial discharges of perfluorooctanoic acid (PFOA) to the Ohio River, contaminating water systems near Parkersburg, WV, were previously associated with nearby residents serum PFOA concentrations above US general population medians. Ohio River PFOA concentrations downstream are elevated, suggesting Mid-Ohio River Valley residents are exposed through drinking water.nnnOBJECTIVESnQuantify PFOA and 10 other per- and polyfluoroalkyl substances (PFAS) in Mid-Ohio River Valley resident sera collected between 1991 and 2013 and determine whether the Ohio River and Ohio River Aquifer are exposure sources.nnnMETHODSnWe measured eleven PFAS in 1608 sera from 931 participants. Serum PFOA concentration and water source associations were assessed using linear mixed-effects models. We estimated between-sample serum PFOA using one-compartment pharmacokinetics for participants with multiple samples.nnnRESULTSnIn serum samples collected as early as 1991, PFOA (medianxa0=xa07.6xa0ng/mL) was detected in 99.9% of sera; 47% had concentrations greater than US population 95th percentiles. Five other PFAS were detected in greater than 82% of samples; median other PFAS concentrations were similar to the US general population. Serum PFOA was significantly associated with water source, sampling year, age at sampling, tap water consumption, pregnancy, gravidity and breastfeeding. Serum PFOA was 40-60% lower with granular activated carbon (GAC) use. Repeated measurements and pharmacokinetics suggest serum PFOA peaked 2000-2006 for participants using water without GAC treatment; where GAC was used, serum PFOA concentrations decreased from 1991 to 2012.nnnCONCLUSIONSnMid-Ohio River Valley residents appear to have PFOA, but not other PFAS, serum concentrations above US population levels. Drinking water from the Ohio River and Ohio River Aquifer, primarily contaminated by industrial discharges 209-666xa0km upstream, is likely the primary exposure source. GAC treatment of drinking water mitigates, but does not eliminate, PFOA exposure.

Hypercholesterolemia with consumption of PFOA-laced Western diets is dependent on strain and sex of mice.

Perfluorooctanoic acid (PFOA) is a man-made surfactant with a number of industrial applications. It has a long half-life environmentally and biologically. Past studies suggest a direct relationship between plasma cholesterol and PFOA serum concentrations in humans and an inverse one in rodents fed standard rodent chow, making it difficult to examine mechanisms responsible for the potential PFOA-induced hypercholesterolemia and altered sterol metabolism. To examine dietary modification of PFOA-induced effects, C57BL/6 and BALB/c mice were fed PFOA in a fat- and cholesterol-containing diet. When fed these high fat diets, PFOA ingestion resulted in marked hypercholesterolemia in male and female C57BL/6 mice and less robust hypercholesterolemia in male BALB/c mice. The PFOA-induced hypercholesterolemia appeared to be the result of increased liver masses and altered expression of genes associated with hepatic sterol output, specifically bile acid production. mRNA levels of genes associated with sterol input were reduced only in C57BL/6 females, the mice with the greatest increase in plasma cholesterol levels. Strain-specific PFOA-induced changes in cholesterol concentrations in mammary tissues and ovaries paralleled changes in plasma cholesterol levels. mRNA levels of sterol-related genes were reduced in ovaries of C57BL/6 but not in BALB/c mice and not in mammary tissues. Our data suggest that PFOA ingestion leads to hypercholesterolemia in mice fed fat and cholesterol and effects are dependent upon the genetic background and gender of the mice with C57BL/6 female mice being most responsive to PFOA.

A MARKOV MODEL TO ESTIMATE SALMONELLA MORBIDITY, MORTALITY, ILLNESS DURATION, AND COST

Approximately 690000-1790000 Salmonella cases, 20000 hospitalizations, and 400 deaths occur in the USA annually, costing approximately

Comprehension and perceptions of study participants upon receiving perfluoroalkyl substance exposure biomarker results

2.6bn. Existing models estimate morbidity, mortality, and cost solely from incidence. They do not estimate illness duration or use time as an independent cost predictor. Existing models may underestimate physician visits, hospitalizations, deaths, and associated costs. We developed a Markov chain Monte Carlo model to estimate illness duration, physician/emergency room visits, inpatient hospitalizations, mortality, and resultant costs for a given Salmonella incidence. Interested parties include society, third-party payers, health providers, federal, state and local governments, businesses, and individual patients and their families. The marginal approach estimates individual disease behavior for every patient, explicitly estimates disease duration and calculates separate time-dependent costs. The aggregate approach is a Markov equivalent of the existing models; it assumes average disease behavior and cost for a given morbidity/mortality. Transition probabilities were drawn from a meta-analysis of 53 Salmonella studies. Both approaches were tested using the 1993 Salmonella typhimurium outbreak in Gideon, Missouri. This protocol can be applied to estimate morbidity, mortality and cost of specific outbreaks, provide better national Salmonella burden estimates, and estimate the benefits of reducing Salmonella risk.

ESTIMATING THE ECONOMIC LOSSES OR DAMAGES FROM A WATERBORNE DISEASE OUTBREAK: DEVELOPMENT OF A SIMULATION MODEL

BACKGROUNDnMeasurement of environmental biomarkers in biomedia is increasingly used as a method of exposure characterization in human population studies. Reporting the results of biomarker measurements back to study participants has been controversial, including questions of ethics and whether the study participants would want to receive and would understand the results.nnnMETHODSnRecently we mailed individual measurements of two serum biomarkers, perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) to participants in three exposure studies of persons living in the Ohio River Valley, of whom 60 were parents of children who had been sampled. Many had serum concentrations of PFOA above the US population 95th percentile value. Reporting forms used in the three studies were somewhat different (either tables or charts for comparison to US population values) and varied in complexity. With all reports, we included information about concentrations of PFOA and PFOS in the general population, and a survey designed to ascertain the opinions of the study participants about the information they received.nnnRESULTSnApproximately 33% (273/821) returned the survey, and of those, 96% reported that they were pleased that we had sent them the report. Most (86%) responded that the results were easy to understand and the enclosed fact sheet was helpful in answering questions (87%). Regarding the amount of information, most felt that we provided the right amount (78%) but some too much (7%) and some too little (15%). The majority (53%) were surprised at their serum concentrations. Of those with serum valuesu202f>u202f13.0u202fng/mL, 74% responded that they thought their serum concentration was high, but only 22% of those with serum concentrations ≤5.6 responded that their concentration was low. Surprisingly, many talked to no one about their levels; those who did were most likely to discuss the report with family members.nnnCONCLUSIONSnReporting back individual environmental biomarker results is generally well received by study participants, and those with high concentrations perceived them to be high. Questions remain as to why study participants did not discuss their results with others.

Using Markov Chain Monte Carlo Models to Estimate the Severity, Duration and Cost of a Salmonellosis Outbreak of Known Size

Consumption of potable water is essential/or human survival. However, water distribution systems are vulnerable to a wide variety of contaminants which may enter a system accidentally or even by deliberate injection. Ingestion of this contaminated water can result in the risk of illness on the part of affected consumers and result in a waterborne outbreak. The outbreak will result in economic losses from disease-related mortality and morbidity; these losses consist of medical costs, lost productivity, and lost lives. These costs will vary with the characteristics of the outbreak, including the etiological agent involved, the number of people affected, including any sensitive subpopulations involved and the spatial and temporal extent of the outbreak. A simple method to calculate these economic costs is presented in this paper and used to estimate the medical costs of the Salmonella typhimurium outbreak in Gideon, Missouri, in 1993. This paper was presented at the 8th Annual Water Distribution Systems Analysis Symposium which was held with the generous support of Awwa Research Foundation (AwwaRF).