In vitro and in vivo approaches to assess atherosclerosis following exposure to low-dose mixtures of arsenic and cadmium.

Worldwide, millions of people are co-exposed to arsenic and cadmium. Environmental exposure to both metals is linked with a higher risk of atherosclerosis. While studies have characterized the pro-atherosclerotic effects of arsenic and cadmium as single agents, little is known about the potential effects of metal mixtures, particularly at low doses. Here, we used a combination of in vitro and in vivo models to assess the effects of low-dose metals individually and as mixtures on early events and plaque development associated with atherosclerosis. In vitro, we investigated early pro-atherogenic changes in macrophages and endothelial cells with metal treatments. The combined cytotoxic effects of both metals at low concentrations were dose interactive, specifically, synergistic in macrophages, but antagonistic in endothelial cells. Despite this differential behavior across cell types, the mixtures did not initiate early pro-atherogenic events: neither reactive oxygen species generation in macrophages nor adhesion molecule expression on endothelial cells. In vivo, we utilized the well-characterized hyperlipidemic apolipoprotein E knock-out (ApoE-/-) mouse model. Previously, we have shown that low concentrations of arsenic (down to 10 ppb) enhance atherosclerosis in ApoE-/- mice. This model has also been used with cadmium to demonstrate pro-atherogenic effects, although at concentrations above human-relevant exposures. In both sexes, there are some small increases in atherosclerotic lesion size, but very few changes in plaque constituents in the ApoE-/- mouse model. Together, these results suggests that low-dose metal mixtures are not significantly more pro-atherogenic than either metal alone.

Urinary Cadmium and Incident Heart Failure: A Case-Cohort Analysis Among Never-Smokers in Denmark.

BACKGROUND: Epidemiologic studies suggest cadmium exposure is associated with cardiovascular disease risk, including heart failure. However, prior findings may be influenced by tobacco smoking, a dominant source of cadmium exposure and risk factor for heart failure. The present study leverages up to 20 years of follow-up in the Danish Diet, Cancer and Health cohort to examine the relationship between urinary cadmium and incident heart failure among people who never smoked. METHODS: Between 1993 and 1997, 19,394 never-smoking participants (ages 50-64 years) enrolled and provided a urine sample. From this sample, we randomly selected a subcohort of 600 men and 600 women and identified 958 incident heart failure cases occurring between baseline and 2015. Using a case-cohort approach, we estimated adjusted hazard ratios (aHR) for heart failure in Cox proportional hazards models with age as the time scale. RESULTS: Participants had relatively low concentrations of urinary cadmium, as expected for never smokers (median = 0.20; 25th, 75th = 0.13, 0.32 µg cadmium/g creatinine). In adjusted models, we found that higher urinary cadmium was associated with a higher rate of incident heart failure overall (aHR = 1.1 per interquartile range difference [95% CI = 1.0, 1.2). In sex-stratified analyses, the association seemed restricted to men (aHR = 1.5 [95% CI = 1.2, 1.9]). CONCLUSIONS: In this cohort of people who never smoked tobacco, environmental cadmium was positively associated with incident heart failure, especially among men.

Domestic violence calls for police service in five US cities during the COVID-19 pandemic of 2020.

BACKGROUND: When COVID-19 stay-at-home orders were instituted, there were concerns that isolation may lead to increases in domestic violence (DV). Reports of increased rates of DV during the stay-at-home period have been suggestive of this but inconsistent across different locations. We sought to complement the existing studies by characterizing changes in DV trends in US cities of Chicago, Los Angeles (LA), New York City (NYC), Philadelphia, and Phoenix using police call volume data from January 1st, 2018, through Dec 31st, 2020. METHODS: The stay-at-home orders were generally instituted for most US states in the second half of March 2020. We used the call volume for the pre-COVID-19 period (Jan. 2018 to Feb. 2020) to model a forecast against the stay-at-home order period (Mar. - May 2020) and the period after lifting the order (June - Dec. 2020) using the interrupted autoregressive integrated moving average (ARIMA) time series model. RESULTS: During the stay-at-home order, increases in mean DV calls relative to pre-COVID-19 were observed in Chicago (47.8%), Phoenix (18.4%), NYC (3.5%), and LA (3.4%), but a decrease in Philadelphia (-4.9%). After lifting the stay-at-home order, changes in mean calls relative to pre-COVID-19 remained elevated in Chicago, slightly elevated in Phoenix, and returned to baseline in NYC and LA. CONCLUSION: Results suggest that the stay-at-home orders may have contributed to an increase in DV calls in some cities (Phoenix, and to a smaller extent LA, NYC), but the increase seen in Chicago (and to some extent Phoenix) persisted beyond the stay-at-home order and therefore may not be attributable to the stay-at-home orders. Additional studies are needed to help explain why the association between stay-at-home orders and DV police call volume seems to only appear in some locations.

A wind speed threshold for increased outdoor transmission of coronavirus: an ecological study.

BACKGROUND: To examine whether outdoor transmission may contribute to the COVID-19 epidemic, we hypothesized that slower outdoor wind speed is associated with increased risk of transmission when individuals socialize outside. METHODS: Daily COVID-19 incidence reported in Suffolk County, NY, between March 16th and December 31st, 2020, was the outcome. Average wind speed and maximal daily temperature were collated by the National Oceanic and Atmospheric Administration. Negative binomial regression was used to model incidence rates while adjusting for susceptible population size. RESULTS: Cases were very high in the initial wave but diminished once lockdown procedures were enacted. Most days between May 1st, 2020, and October 24th, 2020, had temperatures 16-28 °C and wind speed diminished slowly over the year and began to increase again in December 2020. Unadjusted and multivariable-adjusted analyses revealed that days with temperatures ranging between 16 and 28 °C where wind speed was < 8.85 km per hour (KPH) had increased COVID-19 incidence (aIRR = 1.45, 95% C.I. = [1.28-1.64], P < 0.001) as compared to days with average wind speed ≥ 8.85 KPH. CONCLUSION: Throughout the U.S. epidemic, the role of outdoor shared spaces such as parks and beaches has been a topic of considerable interest. This study suggests that outdoor transmission of COVID-19 may occur by noting that the risk of transmission of COVID-19 in the summer was higher on days with low wind speed. Outdoor use of increased physical distance between individuals, improved air circulation, and use of masks may be helpful in some outdoor environments where airflow is limited.

Urinary cadmium and stroke - a case-cohort study in Danish never-smokers.

BACKGROUND: and Purpose: Cadmium has been associated with risk of cardiovascular events, including stroke. Human cadmium exposure occurs primarily through diet and tobacco smoke. Recent cohort studies have found an association with stroke, but residual confounding from smoking, could not be ruled out. We therefore conducted a case-cohort study to evaluate whether cadmium is associated with stroke in never-smokers. METHODS: The Danish Diet Cancer and Health cohort consists of Danes 50-64 years old, recruited in 1993-1997. From never-smoking cohort members without previous cancer or stroke we sampled a sub-cohort of 1200 persons. We also identified all (n = 534) cases in the cohort with a validated stroke diagnosis between baseline and 2009. We quantified cadmium and creatinine concentrations from baseline urine samples and used cadmium per creatinine as our main exposure metric. We used Cox proportional hazards models to estimate hazard ratios (HRs) with age as time scale and adjusting for BMI, education and urinary cotinine with and without stratification by sex. RESULTS: The median urinary cadmium concentration was 0.21 µg cadmium/g creatinine in cases and 0.19 µg/g in the sub-cohort. The majority (83%) of stroke cases were diagnosed with ischemic stroke. The HR for stroke in the highest quartile of exposure (median 0.44 µg/g creatinine) was 1.11 (95% CI: 0.79-1.54) compared with the lowest quartile (median 0.10 µg/g creatinine). The HR per inter quartile range (IQR, 0.19 µg/g creatinine) was 1.02 (95% CI: 0.92-1.12). Among men, the HR per IQR higher levels of cadmium (0.16 µg/g creatinine) was 1.18 (95% CI: 0.92-1.52), and 1.00 (95% CI: 0.89-1.12) among women. Adjusting for creatinine or using osmolality instead of creatinine standardization generally attenuated observed relationships. CONCLUSIONS: Our results do not support that low levels of cadmium exposure among never-smokers are strongly associated with risk of stroke, although results varied somewhat by sex and method of accounting for urinary dilution.

Incidence of brain and spinal cord cancer and county-level radon levels in New Jersey, Wisconsin, Minnesota, Pennsylvania, and Iowa, USA.

Ionizing radiation at diagnostic and therapeutic doses is a known contributor to the development of brain and spinal cord (CNS) cancer. However, little is known about risk from exposure to radon, a natural radiation source which the general population is exposed to residentially and environmentally. This study investigated correlations between mean county radon levels and CNS cancer incidence in five highly populated and radon-enriched US states (Minnesota, mean radon level 4.6 pCi/L; Wisconsin, 5.7 pCi/L; Pennsylvania, 8.6 pCi/L; Iowa, 6.1 pCi/L; and New Jersey, 4.4 pCi/L). Mean radon levels per county were accessed through AirChek, which provides publicly available radon data measured in residences and workplaces. CNS cancer incidence data were accessed through the states' health department websites and span differing amounts of time due to the publicly accessible nature of the data, though all time spans were over 10 years. Negative binomial regressions were run to assess correlations between mean radon and CNS cancer incidence per county. Quantile maps were constructed and Moran's I was calculated to assess spatial autocorrelation in residuals; no spatial autocorrelation was evident. Iowa was the only state with a significant positive association between radon and CNS incidence; no associations were detected in other states, and a negative association was observed in the 5 states combined. This study does not provide evidence that radon is a risk factor for CNS cancer; however, the possibility of an association cannot be ruled out due to limitations of the study, principally its ecologic nature and lack of individual-level exposure data.

Urinary concentrations of phthalate biomarkers and weight change among postmenopausal women: a prospective cohort study.

BACKGROUND: Some phthalates are endocrine disrupting chemicals used as plasticizers in consumer products, and have been associated with obesity in cross-sectional studies, yet prospective evaluations of weight change are lacking. Our objective was to evaluate associations between phthalate biomarker concentrations and weight and weight change among postmenopausal women. METHODS: We performed cross-sectional (N = 997) and longitudinal analyses (N = 660) among postmenopausal Women's Health Initiative participants. We measured 13 phthalate metabolites and creatinine in spot urine samples provided at baseline. Participants' weight and height measured at in-person clinic visits at baseline, year 3, and year 6 were used to calculate body mass index (BMI). We fit multivariable multinomial logistic regression models to explore cross-sectional associations between each phthalate biomarker and baseline BMI category. We evaluated longitudinal associations between each biomarker and weight change using mixed effects linear regression models. RESULTS: In cross-sectional analyses, urinary concentrations of some biomarkers were positively associated with obesity prevalence (e.g. sum of di (2-ethylhexyl) phthalate metabolites [ΣDEHP] 4th vs 1st quartile OR = 3.29, 95% CI 1.80-6.03 [p trend< 0.001] vs normal). In longitudinal analyses, positive trends with weight gain between baseline and year 3 were observed for mono-(2-ethyl-5-oxohexyl) phthalate, monoethyl phthalate (MEP), mono-hydroxybutyl phthalate, and mono-hydroxyisobutyl phthalate (e.g. + 2.32 kg [95% CI 0.93-3.72] for 4th vs 1st quartile of MEP; p trend < 0.001). No statistically significant associations were observed between biomarkers and weight gain over 6 years. CONCLUSIONS: Certain phthalates may contribute to short-term weight gain among postmenopausal women.

Fluoridation and county-level secondary bone cancer among cancer patients 18 years or older in New York State.

The decision whether to fluoridate drinking water continues to be controversial in some communities. Dental and skeletal fluorosis in response to chronic fluoride overexposure are cited as reasons to avoid community water fluoridation in spite of evidence of the oral and skeletal health benefits fluoridation confers. Community fluoridation of ~ 1 mg/L fluoride has not been found to be associated with primary bone cancer but is associated with improved bone strength. No studies have examined fluoride exposure and secondary bone cancer, a common metastasis with significant morbidity. We hypothesize that fluoridation could diminish the likelihood of secondary bone cancer due to its role in bone fortification. We examined the association between community water fluoridation category and prevalence of secondary bone cancer from 2008 to 2010 among cancer patients of 18 years of age or older in counties in New York State. Relative to counties with less than 25% of the water supply fluoridated, we report no association between secondary bone cancer among cancer patients in counties with 25-75% of the water supply fluoridated (ß = 0.02, p = 0.96) and among those in counties with > 75% fluoridated (ß = 0.02, p = 0.97). We found no evidence of an association between community water fluoridation category and secondary bone cancer from 2008 to 2010 at the county level in New York State.

Low levels of lead and glutathione markers of redox status in human blood.

Exposure to lead (Pb) is implicated in a plethora of health threats in both adults and children. Increased exposure levels are associated with oxidative stress in the blood of workers exposed at occupational levels. However, it is not known whether lower Pb exposure levels are related to a shift toward a more oxidized state. To assess the association between blood lead level (BLL) and glutathione (GSH) redox biomarkers in a population of healthy adults, BLL and four GSH markers (GSH, GSSG, GSH/GSSG ratio and redox potential E h ) were measured in the blood of a cross-sectional cohort of 282 avid seafood-eating healthy adults living on Long Island (NY). Additionally, blood levels of two other metals known to affect GSH redox status, selenium (Se) and mercury (Hg), and omega-3 index were tested for effect modification. Regression models were further adjusted for demographic and smoking status. Increasing exposure to Pb, measured in blood, was not associated with GSSG, but was associated with lower levels of GSH/GSSG ratio and more positive GSH redox potential E h , driven by its association with GSH. No effect modification was observed in analyses stratified by Hg, Se, omega-3 index, sex, age, or smoking. Blood Pb is associated with lower levels of GSH and the GSH/GSSG ratio in this cross-sectional study of healthy adults.

Mercury exposure, serum antinuclear antibodies, and serum cytokine levels in the Long Island Study of Seafood Consumption: A cross-sectional study in NY, USA.

Mercury (Hg) is a well-known neurotoxin, and has been more recently studied specifically as an immunotoxin. In experimental and a few epidemiologic studies, Hg has been associated with distinct cytokine profiles and antinuclear antibody (ANA) positivity, though patterns at lower levels of exposure, typical of seafood consumers with a western diet, are not well characterized. Seafood consumers (n=287) recruited on Long Island, NY completed food frequency and health questionnaires and provided blood for analysis of Hg, poly-unsaturated fatty acids (omega-3 and omega-6 fatty acids), selenium (Se), ANA, and several cytokines (IL-1ß, IL-4, IL-10, TNF-α, IL-17, IFN-γ, and IL-1ra). Logistic and linear regression analyses were conducted to evaluate associations between serum Hg and cytokines and ANA. Adjusted models accounted for gender, age, ethnicity, income, education, smoking, BMI, selenium, omega-3 fatty acids, omega-6 fatty acids, omega-6/omega-3 ratio, and fish intake. Sex-stratified models were also generated with the expectation that immune profiles would differ between women and men. Median blood Hg was 4.58µg/L with 90th %ile =19.8µg/L. Nine individuals displayed ANA positivity at serum titers above 1:80; many of the cytokines were below detection limits, and the ability to detect was used in the logistic regression analyses. In linear and logistic regression analyses, Hg was not significantly associated with any of the seven investigated cytokines or with ANA-positivity. Therefore, Hg was not associated with altered immune profiles in this population of seafood consumers.

Seafood intake, polyunsaturated fatty acids, blood mercury, and serum C-reactive protein in US National Health and Nutrition Examination Survey (2005-2006).

We examined the association between seafood consumption, mercury concentration, polyunsaturated fatty acids, selenium, and Vitamin D in relation to C-reactive protein using the cross-sectional US National Health and Nutrition Examination Survey 2005-2006. We hypothesized that seafood consumption and fatty acids will be negatively associated, and mercury will be positively associated with C-reactive protein, and that statistical adjustment for these factors will alleviate confounding thereby making these associations more apparent. The study sample included 1217 participants (706 males, 511 females) aged 16-49. Sex-stratified sample weighted multiple linear regression models revealed no associations of mercury, polyunsaturated fatty acids, fish intake, selenium, or vitamin D with serum C-reactive protein. However, when all variables were included together in one model, fish intake was associated with lower levels of CRP in females suggesting confounding in models that do not mutually adjust for seafood contaminants and nutrients. Prospective studies are needed to confirm these findings.

Urinary Cadmium and Risk of Invasive Breast Cancer in the Women's Health Initiative.

Cadmium is a widespread heavy metal pollutant that may act as an exogenous estrogenic hormone. Environmental cadmium exposure has been associated with risk of breast cancer in retrospective studies. We prospectively assessed the relationship between cadmium exposure, evaluated by creatinine-normalized urinary cadmium concentration, and invasive breast cancer among 12,701 postmenopausal women aged ≥50 years in a Women's Health Initiative study of bone mineral density. After a median of 13.2 years of follow-up (1993-2010), 508 cases of invasive breast cancer and 1,050 comparison women were identified for a case-cohort analysis. Multivariable Cox regression was used to calculate hazard ratios and 95% confidence intervals. Risk of breast cancer was not associated with urinary cadmium parameterized either in quartiles (comparing highest quartile with lowest, hazard ratio = 0.80, 95% confidence interval: 0.56, 1.14; P for trend = 0.20) or as a log-transformed continuous variable (per 2-fold higher urinary cadmium concentration, hazard ratio = 0.94, 95% confidence interval: 0.86, 1.03). We did not observe an association between urinary cadmium and breast cancer risk in any subgroup examined, including never smokers and women with body mass index (weight (kg)/height (m)(2)) less than 25. Results were consistent in both estrogen receptor-positive and estrogen receptor-negative tumors. Our results do not support the hypothesis that environmental cadmium exposure is associated with risk of postmenopausal breast cancer.

Low-level mercury, omega-3 index and neurobehavioral outcomes in an adult US coastal population.

BACKGROUND: Neurodevelopmental effects of omega-3 fatty acids and mercury from fish consumption have been characterized in children. In contrast, neurobehavioral outcomes associated with fish are not well studied in adults. OBJECTIVE: This study of avid seafood consumers on Long Island (NY, USA) sought to define associations between mercury, seafood consumption, omega-3 fatty acids and neurobehavioral outcomes. METHODS: A computer-based test system was used to assess neurobehavioral function. Blood total Hg (Hg) and omega-3 index were measured in 199 adult avid seafood eaters, who also completed the neurobehavioral assessment and an extensive food and fish frequency and demographic questionnaire. RESULTS: For most of the outcomes considered, neither Hg nor omega-3 index was associated with neurobehavioral outcomes after adjustment for key confounding variables. Fish consumption, however, was associated with decreased odds of both self-reported fatigue (OR 0.85; 95 % CI 0.72, 1.01) and a constellation of neurologic symptoms (OR 0.79; 95 % CI 0.66, 0.96). CONCLUSIONS: Results from our study provide little evidence that omega-3 fatty acids or Hg is associated with cognitive function in adult avid seafood consumers. Larger studies are needed to confirm our finding of associations between fish consumption and decreased self-reported fatigue and neurologic impairment.

Mercury exposure and a shift toward oxidative stress in avid seafood consumers.

Mechanisms of mercury (Hg) toxicity at low doses from seafood consumption, the most common exposure route, are not well understood. We tested the hypothesis that seafood Hg exposure is related to a shift in redox status, indicated by a decrease in the ratio of reduced to oxidized glutathione (GSH:GSSG) in blood, or increase in redox potential (Eh). We also examined whether key seafood nutrients (selenium (Se), omega-3 fatty acids) confound or modify this shift. We measured blood concentrations of total Hg, Se, GSH, GSSG, and the Omega-3 Index (% omega-3s of total fatty acids in red blood cell membranes) in seafood consumers in Long Island, NY. We examined relationships between Hg, GSH:GSSG ratio and Eh. Elevated blood Hg (>5.8µgL(-1)) was associated with lower GSH:GSSG (ß=-116.73, p=0.01), with no evidence of confounding by Se or Omega-3 Index. However, in models stratified by Omega-3 Index levels, Hg-GSH:GSSG associations were weakened among those with high Omega-3 Index levels (>6% of fatty acids, ß=-63.46, p=0.28), and heightened among those with low Omega-3 Index (ß=-182.53, p<0.01). We observed comparable patterns for Eh in relation to Hg. These results support the hypothesis that Hg exposure from seafood is linked to a shift in redox status toward oxidative stress, modified by omega-3 fatty acids in this population. Further work should examine the role of different seafood nutrients and Hg-induced shifts in redox status in the diverse health effects associated with elevated Hg exposure.

Demographic Profiles, Mercury, Selenium, and Omega-3 Fatty Acids in Avid Seafood Consumers on Long Island, NY.

Seafood consumption is known to confer nutritional benefits and risks from contaminant exposure. Avid seafood consumers are neither well-characterized with regard to their demographic profile nor their underlying risk-benefit profile. Contaminants [e.g., mercury (Hg)] and nutrients [e.g., selenium (Se), omega-3 fatty acids] are prevalent in some seafood. Participants (N = 285) recruited on Long Island, NY, completed food frequency and health questionnaires and received blood draws analyzed for Hg, omega-3s, and Se. Participants were categorized based on frequency and type of seafood consumption. Logistic regression analyses evaluated relationships between seafood consumption and demographics, and were age- and sex-adjusted. t tests assessed relationships between seafood consumption patterns and biomarkers Hg, omega-3s, and Se. Consumption of both tuna and salmon was associated with older age: those aged 55-75 and over 75 years old were more likely than participants aged 18-34 to eat tuna and salmon (OR 2.27; 95% CI 1.05, 4.89 and OR 3.67; 95% CI 1.20, 11.20, respectively). Males were less likely than females to eat fish other than tuna or salmon (OR 0.58; 95% CI 0.34, 0.97). Caucasians were more likely to consume tuna (OR 0.31; 95% CI 0.10, 0.96) or salmon and tuna (OR 0.34; 95% CI 0.12, 0.91), while non-Caucasians were more likely to consume other fish types (OR 2.73; 95% CI 1.45, 5.12). Total blood Hg was associated with weekly consumption of any type of fish (p = 0.01) and with salmon and tuna consumption (p = 0.01). Salmon was associated with plasma omega-3s (p = 0.01). Se was not associated with fish intake categories. Risk communicators can use these findings to influence seafood preferences of different demographic groups.

Dietary cadmium intake and risk of prostate cancer: a Danish prospective cohort study.

BACKGROUND: Cadmium is classified as a human lung carcinogen based on evidence from high-exposure occupational settings. Though cadmium has no physiological role, increasing evidence suggests cadmium may mimic steroid hormones. This dual ability of being carcinogenic and hormone-like makes cadmium a concern for hormone-related cancers. Causes of prostate cancer are not clear, but steroid hormones, particularly androgens and probably estrogens, may be involved. Cadmium has been positively associated with prostate cancer in occupationally exposed men. In non-occupationally exposed populations, diet and smoking are the main sources of cadmium exposure. The aim of this study was to investigate the association between dietary cadmium intake and prostate cancer risk in Danish men. METHODS: Dietary cadmium intake was estimated in the Danish Diet, Cancer and Health cohort at baseline 1993-97. The estimates were based on a 192 item semi-quantitative food frequency questionnaire and cadmium contents in all food items. Among 26,778 men we identified 1,567 prostate cancer cases from baseline through December 31, 2010 using the Danish Cancer Registry. The association between dietary cadmium intake and prostate cancer risk was analysed using Cox regression models. RESULTS: We did not find an association between dietary cadmium intake and prostate cancer risk (adjusted incidence rate ratio per 10 µg day(-1) = 0.98 (95% CI = 0.88-1.10)). The association did not differ according to aggressiveness of prostate cancer. Educational level, smoking status, BMI, zinc or iron intake did not modify the association. CONCLUSIONS: In our study, we did not find an association between dietary cadmium intake and prostate cancer risk in a cohort of Danish men.

Investigation of spatio-temporal cancer clusters using residential histories in a case-control study of non-Hodgkin lymphoma in the United States.

BACKGROUND: Non-Hodgkin lymphoma (NHL) is an enigmatic disease with few known risk factors. Spatio-temporal epidemiologic analyses have the potential to reveal patterns that may give clues to new risk factors worthy of investigation. We sought to investigate clusters of NHL through space and time based on life course residential histories. METHODS: We used residential histories from a population-based NHL case-control study of 1300 cases and 1044 controls with recruitment centers in Iowa, Detroit, Seattle, and Los Angeles, and diagnosed in 1998-2000. Novel methods for cluster detection allowing for residential mobility, called Q-statistics, were used to quantify nearest neighbor relationships through space and time over the life course to identify cancer clusters. Analyses were performed on all cases together and on two subgroups of NHL: Diffuse large B-cell lymphoma and follicular lymphoma. These more homogenous subgroups of cases might have a more common etiology that could potentially be detected in cluster analysis. Based on simulation studies designed to help account for multiple testing across space and through time, we required at least four significant cases nearby one another to declare a region a potential cluster, along with confirmatory analyses using spatial-only scanning windows (SaTScan). RESULTS: Evidence of a small cluster in southeastern Oakland County, MI was suggested using residences 10-18 years prior to diagnosis, and confirmed by SaTScan in a time-slice analysis 20 years prior to diagnosis, when all cases were included in the analysis. Consistent evidence of clusters was not seen in the two histologic subgroups. CONCLUSIONS: Suggestive evidence of a small space-time cluster in southeastern Oakland County, MI was detected in this NHL case-control study in the USA.

Space-time clusters of breast cancer using residential histories: a Danish case-control study.

BACKGROUND: A large proportion of breast cancer cases are thought related to environmental factors. Identification of specific geographical areas with high risk (clusters) may give clues to potential environmental risk factors. The aim of this study was to investigate whether clusters of breast cancer existed in space and time in Denmark, using 33 years of residential histories. METHODS: We conducted a population-based case-control study of 3138 female cases from the Danish Cancer Registry, diagnosed with breast cancer in 2003 and two independent control groups of 3138 women each, randomly selected from the Civil Registration System. Residential addresses of cases and controls from 1971 to 2003 were collected from the Civil Registration System and geo-coded. Q-statistics were used to identify space-time clusters of breast cancer. All analyses were carried out with both control groups, and for 66% of the study population we also conducted analyses adjusted for individual reproductive factors and area-level socioeconomic indicators. RESULTS: In the crude analyses a cluster in the northern suburbs of Copenhagen was consistently found throughout the study period (1971-2003) with both control groups. When analyses were adjusted for individual reproductive factors and area-level socioeconomic indicators, the cluster area became smaller and less evident. CONCLUSIONS: The breast cancer cluster area that persisted after adjustment might be explained by factors that were not accounted for such as alcohol consumption and use of hormone replacement therapy. However, we cannot exclude environmental pollutants as a contributing cause, but no pollutants specific to this area seem obvious.

Predicting arsenic concentrations in groundwater of San Luis Valley, Colorado: implications for individual-level lifetime exposure assessment.

Consumption of inorganic arsenic in drinking water at high levels has been associated with chronic diseases. Risk is less clear at lower levels of arsenic, in part due to difficulties in estimating exposure. Herein we characterize spatial and temporal variability of arsenic concentrations and develop models for predicting aquifer arsenic concentrations in the San Luis Valley, Colorado, an area of moderately elevated arsenic in groundwater. This study included historical water samples with total arsenic concentrations from 595 unique well locations. A longitudinal analysis established temporal stability in arsenic levels in individual wells. The mean arsenic levels for a random sample of 535 wells were incorporated into five kriging models to predict groundwater arsenic concentrations at any point in time. A separate validation dataset (n = 60 wells) was used to identify the model with strongest predictability. Findings indicate that arsenic concentrations are temporally stable (r = 0.88; 95 % CI 0.83-0.92 for samples collected from the same well 15-25 years apart) and the spatial model created using ordinary kriging best predicted arsenic concentrations (ρ = 0.72 between predicted and observed validation data). These findings illustrate the value of geostatistical modeling of arsenic and suggest the San Luis Valley is a good region for conducting epidemiologic studies of groundwater metals because of the ability to accurately predict variation in groundwater arsenic concentrations.

A protocol for the prospective study of urinary cadmium with risk of fracture, bone loss, and muscle loss.

Cadmium (Cd) is a heavy metal and natural element found in soil and crops with increasing concentrations linked to phosphate fertilizers and sewage sludge applied to crop lands. A large fraction of older US men and woman have documented Cd exposure. Cd exposure has proven health concerns such as risk of lung cancer from inhalation and impaired renal function; however, growing evidence suggests it also influences bone and muscle health. Given that low levels of Cd could affect bone and muscle, we have designed prospective studies using the two largest and most detailed US studies of bone health in older men and women: the Osteoporotic Fractures in Men Study and the Study of Osteoporotic Fractures. We are investigating the association of urinary cadmium (U-Cd), as a surrogate for long-term Cd exposure, with bone and muscle health. Building off suggestive evidence from mechanistic and cross-sectional studies, this will be the first well-powered prospective study of incident fracture outcomes, bone loss, and muscle loss in relation to U-Cd, an established biomarker of long-term Cd exposure. The following is a proposed protocol for the intended study; if successful, the proposed studies could be influential in directing future US policy to decrease Cd exposure in the US population similar to recent policies adopted by the European Union to limit Cd in fertilizers.