Person: Weisskopf, Marc
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Weisskopf
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Weisskopf, Marc
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Publication Spinal Cord Injury and Migraine Headache: A Population-Based Study(Public Library of Science, 2015) Warner, Freda M.; Cragg, Jacquelyn J.; Weisskopf, Marc; Kramer, John K.Migraine headaches are a common neurological condition, negatively impacting health and quality of life. Among potential risk factors for migraine headache, risk of migraine headaches was elevated in individuals with spinal cord injury (SCI). The association between migraines and SCI is intriguing to consider from the perspective that migraine headaches may be acquired in response to damage in the spinal cord. The primary objective of this study was to further examine the association between SCI and migraine headache, controlling for potential confounding variables. A secondary objective was to determine the impact of migraine headaches on self-perceived health. Data from a sample of 61,047 participants were obtained from the cross-sectional Canadian Community Health Survey. Multivariable logistic regression was used to explore the association between SCI and migraine headache using probability weights and adjusting for confounders. The multivariable age- and sex-adjusted model revealed a strong association between SCI and migraine headache, with an adjusted odds ratio for migraine of 4.82 (95% confidence interval [3.02, 7.67]) among those with SCI compared to those without SCI. Further, individuals who experienced both SCI and migraine tended to report poorer perceived general health compared with the other groups (i.e., SCI and no migraine). In conclusion, this study established a strong association between SCI and migraine headache. Further research is needed to explore the possible mechanisms underlying this relationship. Improvements in clinical practice to minimize this issue could result in significant improvements in quality of life.Publication Autism Spectrum Disorder and Particulate Matter Air Pollution before, during, and after Pregnancy: A Nested Case–Control Analysis within the Nurses’ Health Study II Cohort(NLM-Export, 2014) Raz, Raanan; Roberts, Andrea L.; Lyall, Kristen; Hart, Jaime; Just, Allan C.; Laden, Francine; Weisskopf, MarcBackground: Autism spectrum disorder (ASD) is a developmental disorder with increasing prevalence worldwide, yet has unclear etiology. Objective: We explored the association between maternal exposure to particulate matter (PM) air pollution and odds of ASD in her child. Methods: We conducted a nested case–control study of participants in the Nurses’ Health Study II (NHS II), a prospective cohort of 116,430 U.S. female nurses recruited in 1989, followed by biennial mailed questionnaires. Subjects were NHS II participants’ children born 1990–2002 with ASD (n = 245), and children without ASD (n = 1,522) randomly selected using frequency matching for birth years. Diagnosis of ASD was based on maternal report, which was validated against the Autism Diagnostic Interview-Revised in a subset. Monthly averages of PM with diameters ≤ 2.5 μm (PM2.5) and 2.5–10 μm (PM10–2.5) were predicted from a spatiotemporal model for the continental United States and linked to residential addresses. Results: PM2.5 exposure during pregnancy was associated with increased odds of ASD, with an adjusted odds ratio (OR) for ASD per interquartile range (IQR) higher PM2.5 (4.42 μg/m3) of 1.57 (95% CI: 1.22, 2.03) among women with the same address before and after pregnancy (160 cases, 986 controls). Associations with PM2.5 exposure 9 months before or after the pregnancy were weaker in independent models and null when all three time periods were included, whereas the association with the 9 months of pregnancy remained (OR = 1.63; 95% CI: 1.08, 2.47). The association between ASD and PM2.5 was stronger for exposure during the third trimester (OR = 1.42 per IQR increase in PM2.5; 95% CI: 1.09, 1.86) than during the first two trimesters (ORs = 1.06 and 1.00) when mutually adjusted. There was little association between PM10–2.5 and ASD. Conclusions: Higher maternal exposure to PM2.5 during pregnancy, particularly the third trimester, was associated with greater odds of a child having ASD. Citation Raz R, Roberts AL, Lyall K, Hart JE, Just AC, Laden F, Weisskopf MG. 2015. Autism spectrum disorder and particulate matter air pollution before, during, and after pregnancy: a nested case–control analysis within the Nurses’ Health Study II cohort. Environ Health Perspect 123:264–270; http://dx.doi.org/10.1289/ehp.1408133Publication Application of linear mixed-effects model with LASSO to identify metal components associated with cardiac autonomic responses among welders: a repeated measures study(BMJ Publishing Group, 2017) Zhang, Jinming; Cavallari, Jennifer M; Fang, Shona C; Weisskopf, Marc; Lin, Xihong; Mittleman, Murray; Christiani, DavidBackground: Environmental and occupational exposure to metals is ubiquitous worldwide, and understanding the hazardous metal components in this complex mixture is essential for environmental and occupational regulations. Objective: To identify hazardous components from metal mixtures that are associated with alterations in cardiac autonomic responses. Methods: Urinary concentrations of 16 types of metals were examined and ‘acceleration capacity’ (AC) and ‘deceleration capacity’ (DC), indicators of cardiac autonomic effects, were quantified from ECG recordings among 54 welders. We fitted linear mixed-effects models with least absolute shrinkage and selection operator (LASSO) to identify metal components that are associated with AC and DC. The Bayesian Information Criterion was used as the criterion for model selection procedures. Results: Mercury and chromium were selected for DC analysis, whereas mercury, chromium and manganese were selected for AC analysis through the LASSO approach. When we fitted the linear mixed-effects models with ‘selected’ metal components only, the effect of mercury remained significant. Every 1 µg/L increase in urinary mercury was associated with −0.58 ms (−1.03, –0.13) changes in DC and 0.67 ms (0.25, 1.10) changes in AC. Conclusion: Our study suggests that exposure to several metals is associated with impaired cardiac autonomic functions. Our findings should be replicated in future studies with larger sample sizes.Publication The relation between past exposure to fine particulate air pollution and prevalent anxiety: observational cohort study(BMJ Publishing Group Ltd., 2015) Power, Melinda C; Kioumourtzoglou, Marianthi-Anna; Hart, Jaime; Okereke, Olivia; Laden, Francine; Weisskopf, MarcObjective: To determine whether higher past exposure to particulate air pollution is associated with prevalent high symptoms of anxiety. Design: Observational cohort study. Setting: Nurses’ Health Study. Participants: 71 271 women enrolled in the Nurses’ Health Study residing throughout the contiguous United States who had valid estimates on exposure to particulate matter for at least one exposure period of interest and data on anxiety symptoms. Main outcome measures Meaningfully high symptoms of anxiety, defined as a score of 6 points or greater on the phobic anxiety subscale of the Crown-Crisp index, administered in 2004. Results: The 71 271 eligible women were aged between 57 and 85 years (mean 70 years) at the time of assessment of anxiety symptoms, with a prevalence of high anxiety symptoms of 15%. Exposure to particulate matter was characterized using estimated average exposure to particulate matter <2.5 μm in diameter (PM2.5) and 2.5 to 10 μm in diameter (PM2.5-10) in the one month, three months, six months, one year, and 15 years prior to assessment of anxiety symptoms, and residential distance to the nearest major road two years prior to assessment. Significantly increased odds of high anxiety symptoms were observed with higher exposure to PM2.5 for multiple averaging periods (for example, odds ratio per 10 µg/m3 increase in prior one month average PM2.5: 1.12, 95% confidence interval 1.06 to 1.19; in prior 12 month average PM2.5: 1.15, 1.06 to 1.26). Models including multiple exposure windows suggested short term averaging periods were more relevant than long term averaging periods. There was no association between anxiety and exposure to PM2.5-10. Residential proximity to major roads was not related to anxiety symptoms in a dose dependent manner. Conclusions: Exposure to fine particulate matter (PM2.5) was associated with high symptoms of anxiety, with more recent exposures potentially more relevant than more distant exposures. Research evaluating whether reductions in exposure to ambient PM2.5 would reduce the population level burden of clinically relevant symptoms of anxiety is warranted.Publication Within-person reproducibility of red blood cell mercury over a 10- to 15-year period among women in the Nurses’ Health Study II(Springer Nature, 2014) Kioumourtzoglou, Marianthi-Anna; Roberts, Andrea L; Nielsen, Flemming; Tworoger, Shelley; Grandjean, Philippe; Weisskopf, MarcBackground Most epidemiologic studies of methylmercury (MeHg) health effects rely on a single measurement of a MeHg biomarker to assess long-term exposures. Long-term reproducibility data are, therefore, needed to assess the reliability of a single measure to reflect long-term exposures. In this study we assessed within-person reproducibility of red blood cell (RBC) mercury (Hg), a marker of methyl-mercury, over 10–15-years in a sample of 57 women. Methods Fifty-seven women from the Nurses’ Health Study II provided two blood samples 10–15-years apart (median:12 years), which were analyzed for mercury levels in the red blood cells (B-Hg*). To characterize within-person reproducibility we estimated correlation and intraclass correlation coefficients (r and ICC) across the two samples. Further, we compared different prediction models, including variables on fish and seafood consumption, for B-Hg* at the first sample using leave-one-out cross-validation to assess predictive ability. Results Overall, we observed strong correlations over 10–15 years (r=0.69), as well as a high ICC (0.67; 95%CI: 0.49, 0.79). Fish and seafood consumption reported concurrently with the first B-Hg* sample accounted for 26.8% of the variability in that B-Hg*, giving a correlation of r=0.52. Conclusions Despite decreasing B-Hg* levels over time, we observed strong correlations and high ICC estimates across B-Hg* measured 10–15 years apart, suggesting good relative within-person stability over time. Our results indicate that a single measurement of B-Hg* likely is adequate to represent long-term exposures.Publication Mitochondrial haplogroups modify the effect of black carbon on age-related cognitive impairment(BioMed Central, 2014) Colicino, Elena; Power, Melinda C; Cox, David G; Weisskopf, Marc; Hou, Lifang; Alexeeff, Stacy E; Sanchez-Guerra, Marco; Vokonas, Pantel; Spiro III, Avron; Schwartz, Joel; Baccarelli, AndreaBackground: Traffic-related air pollution has been linked with impaired cognition in older adults, possibly due to effects of oxidative stress on the brain. Mitochondria are the main source of cellular oxidation. Haplogroups in mitochondrial DNA (mtDNA) mark individual differences in oxidative potential and are possible determinants of neurodegeneration. The aim of this study was to investigate whether mtDNA haplogroups determined differential susceptibility to cognitive effects of long-term exposure to black carbon (BC), a marker of traffic-related air pollution. Methods: We investigated 582 older men (72 ± 7 years) in the VA Normative Aging Study cohort with ≤4 visits per participant (1.8 in average) between 1995–2007. Low (≤25) Mini Mental State Examination (MMSE) was used to assess impaired cognition in multiple domains. We fitted repeated-measure logistic regression using validated-LUR BC estimated in the year before their first visit at the participant’s address. Results: Mitochondrial haplotyping identified nine haplogroups phylogenetically categorized in four clusters. BC showed larger effect on MMSE in Cluster 4 carriers, including I, W and X haplogroups, [OR = 2.7; 95% CI (1.3-5.6)], moderate effect in Cluster 1, including J and T haplogroups [OR = 1.6; 95% CI: (0.9-2.9)], and no effect in Cluster 2 (H and V haplogroups) [OR = 1.1; 95% CI: (0.8-1.5)] or Cluster 3 (K and U haplogroups) [OR = 1.0; 95% CI: (0.6-1.6)]. BC effect varied only moderately across the I, X, and W haplogroups or across the J and T haplogroups. Conclusions: The association of BC with impaired cognition was worsened in carriers of phylogenetically-related mtDNA haplogroups in Cluster 4. No BC effects were detected in Cluster 2 and 3 carriers. MtDNA haplotypes may modify individual susceptibility to the particle cognitive effects.Publication Human exposure to nitro musks and the evaluation of their potential toxicity: an overview(BioMed Central, 2014) Taylor, Kathryn; Weisskopf, Marc; Shine, James P.Synthetic nitro musks are fragrant chemicals found in household and personal care products. The use of these products leads to direct exposures via dermal absorption, as well as inhalation of contaminated dust and volatilized fragrances. Evidence also suggests that humans are exposed to low doses of these chemicals through oral absorption of contaminated liquids and foods. As these compounds are lipophilic, they and their metabolites, have been found not only in blood, but also breast milk and adipose tissue. After personal use, these environmentally persistent pollutants then pass through sewage treatment plants through their effluent into the environment. Little is known about the biological effects in humans after such a prolonged low dose exposure to these chemicals. While epidemiologic studies evaluating the effects of nitro musk exposures are lacking, there is limited evidence that suggest blood levels of nitro musks are inversely related to luteal hormone levels. This is supported by animal models and laboratory studies that have shown that nitro musks are weakly estrogenic. Nitro musks exposure has been associated with an increased risk of tumor formation in mice. The evidence suggests that while nitro musks by themselves are not genotoxic, they may increase the genotoxicity of other chemicals. However, animal models for nitro musk exposure have proven to be problematic since certain outcomes are species specific. This may explain why evidence for developmental effects in animals is conflicting and inconclusive. Given that animal models and cell-line experiments are suggestive of adverse outcomes, further epidemiologic studies are warranted.Publication Association between Blood Lead and Walking Speed in the National Health and Nutrition Examination Survey (NHANES 1999–2002)(National Institute of Environmental Health Sciences, 2013) Ji, John S.; Elbaz, Alexis; Weisskopf, MarcBackground: Walking speed is a simple and reliable measure of motor function that is negatively associated with adverse health events in older people, including falls, disability, hospital admissions, and mortality. Lead has adverse affects on human health, particularly on the vascular and neurological systems. Objective: We explored the hypothesis that lead is associated with slower walking speed. Methods: We used U.S. National Health and Nutrition Examination Survey (NHANES) cross-sectional data from 1999–2002. The time to walk 20 ft (walking speed) was measured among 1,795 men and 1,798 women ≥ 50 years of age. The association between walking speed and quintiles of blood lead concentration was estimated separately in men and women using linear regression models adjusted for age, education, ethnicity, alcohol use, smoking status, height, and waist circumference. Results: Mean blood lead concentrations and walking speeds were 2.17 μg/dL and 3.31 ft/sec in women, and 3.18 μg/dL and 3.47 ft/sec in men, respectively. Among women, walking speed decreased with increasing quintiles of blood lead, resulting in an estimated mean value that was 0.11 ft/sec slower (95% CI: –0.19, –0.04; p-trend = 0.005) for women with blood lead concentrations in the highest versus lowest quintile. In contrast, lead was not associated with walking speed in men. Conclusion: Blood lead concentration was associated with decreased walking speed in women, but not in men. Our results contribute to the growing evidence that lead exposure, even at low levels, is detrimental to public health.Publication Portable XRF Technology to Quantify Pb in Bone In Vivo(Hindawi Publishing Corporation, 2014) Specht, Aaron James; Weisskopf, Marc; Nie, Linda HuilingLead is a ubiquitous toxicant. Bone lead has been established as an important biomarker for cumulative lead exposures and has been correlated with adverse health effects on many systems in the body. K-shell X-ray fluorescence (KXRF) is the standard method for measuring bone lead, but this approach has many difficulties that have limited the widespread use of this exposure assessment method. With recent advancements in X-ray fluorescence (XRF) technology, we have developed a portable system that can quantify lead in bone in vivo within 3 minutes. Our study investigated improvements to the system, four calibration methods, and system validation for in vivo measurements. Our main results show that the detection limit of the system is 2.9 ppm with 2 mm soft tissue thickness, the best calibration method for in vivo measurement is background subtraction, and there is strong correlation between KXRF and portable LXRF bone lead results. Our results indicate that the technology is ready to be used in large human population studies to investigate adverse health effects of lead exposure. The portability of the system and fast measurement time should allow for this technology to greatly advance the research on lead exposure and public/environmental health.Publication Particulate matter and risk of parkinson disease in a large prospective study of women(BioMed Central, 2014) Palacios, Natalia; Fitzgerald, Kathryn C.; Hart, Jaime; Weisskopf, Marc; Schwarzschild, Michael; Ascherio, Alberto; Laden, FrancineBackground: Exposure to air pollution has been implicated in a number of adverse health outcomes and the effect of particulate matter (PM) on the brain is beginning to be recognized. Yet, no prospective study has examined the association between PM and risk of Parkinson Disease. Thus, our goal was assess if exposure to particulate matter air pollution is related to risk of Parkinson’s disease (PD) in the Nurses’ Health Study (NHS), a large prospective cohort of women. Methods: Cumulative average exposure to different size fractions of PM up to 2 years before the onset of PD, was estimated using a spatio-temporal model by linking each individual’s places of residence throughout the study with location-specific air pollution levels. We prospectively followed 115,767 women in the NHS, identified 508 incident PD cases and used multivariable Cox proportional hazards models to estimate the risk of PD associated with each size fraction of PM independently. Results: In models adjusted for age in months, smoking, region, population density, caffeine and ibuprofen intake, we observed no statistically significant associations between exposure to air pollution and PD risk. The relative risk (RR) comparing the top quartile to the bottom quartile of PM exposure was 0.99 (95% Confidence Intervals (CI): 0.84,1.16) for PM10 (≤10 microns in diameter), 1.08 (95% CI: 0.81, 1.45) for PM2.5 (≤2.5 microns in diameter), and 0.92 (95% CI: 0.71, 1.19) for PM10–2.5 (2.5 to 10 microns in diameter). Conclusions: In this study, we found no evidence that exposure to air pollution is a risk factor for PD.