1,720,994 research outputs found
Chemical exposures among reproductive age women and health outcomes for women and offspring
Get PDFIncreasing evidence suggests that ubiquitous exposure to multiple chemical classes, including elements (e.g. metals) and phthalates, can adversely affect maternal and fetal health. The objective of our research was to evaluate the relationship between chemical exposures for reproductive-aged women and fetal and reproductive health outcomes for these women and their children. Specifically, we aimed to investigate associations between maternal exposure to elements and child neurobehavioral outcomes in a prospective pre-birth cohort of women from Massachusetts (Project Viva), and associations between phthalate exposures and uterine leiomyomata (UL or fibroids) incidence in a prospective cohort of premenopausal black women aged 23-35 residing in Detroit, Michigan (Study of the Environment, Lifestyle, and Fibroids, SELF). Three study aims were developed to examine these associations. In the first aim, we identified associations between maternal lead (Pb) exposure during pregnancy and neurobehavioral outcomes in childhood within Project Viva. We utilized 2nd trimester maternal erythrocyte blood samples to characterize prenatal exposure to Pb and estimated associations with parent- and teacher-rated executive function-related behavior and behavioral difficulties at mid-childhood (median 7.7 years) using multivariable linear regression models adjusted for maternal, paternal, and child characteristics as well as element co-exposures. While effect estimates were modest, trends suggested that higher average prenatal erythrocyte Pb levels predicted poorer childhood executive function related behavior and worse behavioral difficulties, as rated by parents responding to the Behavior Rating Inventory of Executive Function (BRIEF) and the Strengths and Difficulties Questionnaire (SDQ) assessments. Results were similar but attenuated for teacher-rated scales. The second aim investigated associations between prenatal exposure to a mixture of multiple elements, including Pb, and neurobehavioral outcomes in mid-childhood. We built on analysis in the first aim within Project Viva and assessed the interactive and joint effects of element mixtures, including essential and non-essential elements (lead, manganese, mercury and selenium) on neurobehavioral outcomes. We conducted Bayesian Kernel Machine regression (BKMR), multivariable linear regression (MLR) and Weighted Quantile Sum (WQS) regression, adjusting for maternal, paternal and child characteristics. Although associations included the null, the BKMR model suggested marginal joint effects of the mixture of Pb, manganese (Mn), mercury (Hg) and selenium (Se) per higher quantile of each element, with higher parent-rated scores indicating worse neurobehavioral performance. Pb and Se were major contributors to the association across all models. Results were attenuated for teacher-rated scales. The third aim evaluated the association between phthalates and UL incidence in SELF. We conducted a case-cohort study of reproductive-age women to examine incidence of UL as detected by vaginal ultrasound. Overall, most individual phthalate metabolites showed weak to moderate inverse associations with UL incidence among obese women, while the associations were null or weakly positive among women with BMI <30. Taken together, the influence of exposure to elements and phthalates on fetal and reproductive health outcomes varied across toxicants. Results suggest that prenatal Pb exposure can adversely affect child behavior, even at levels relevant to the current population concentration, with marginal evidence of adverse effects of the mixture of essential and non-essential elements. Observed findings for phthalates and UL differed across metabolites and among obese women, suggesting mostly null and inverse effects of phthalates on UL that may be influenced by the hormone activity of each phthalate.2022-01-28T00:00:00
Early life exposure to metals and adolescent neurodevelopment
No full textBACKGROUND: Children, especially those living near industry sites, are commonly exposed to multiple metals including lead and manganese. These metals are associated with adverse neurodevelopmental outcomes, with evidence of non-linear associations for essential metals. Metals target brain regions involved in cognition and motor function. However, there is a paucity of epidemiological studies focused on early-life exposure to metals, especially in association with less commonly studied neurodevelopmental domains like motor function.
OBJECTIVE: To characterize exposure to multiple metals in early life, estimate associations with neurodevelopmental outcomes in adolescence, and examine susceptibility factors including exposure timing, co-exposures, and biological sex.
METHODS: Research aims were addressed using data from the Assessing Children’s Environmental Exposures (ACHIEVE) study and the Public Health Impact of Metals Exposure (PHIME) study. The ACHIEVE study included 30 mother-child pairs from the town of Holliston, Massachusetts where naturally shed baby teeth were collected from children ages 5–13 years. In the first aim, we used multivariable linear mixed models to explore sociodemographic, dietary, and behavioral correlates of tooth metal concentrations for children in the ACHIEVE study (N=28). We estimated weekly prenatal and postnatal (up to one year of age) exposure to 12 metals. Tooth metal concentrations were quantified using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). For the second and third aims, we analyzed data from the PHIME study, comprised of 721 Italian adolescents living in proximity to steel production sites. Blood and hair samples were collected at the time of enrollment and analyzed for metals concentrations (manganese, lead, copper, and chromium) using ICP-MS. Teeth were collected for a subset of PHIME participants (N=195) and analyzed for manganese using LA-ICP-MS. A battery of neuropsychological assessments was administered to PHIME participants at enrollment by one of two trained neuropsychologists. In the second aim, we evaluated associations of prenatal, postnatal and childhood manganese levels in teeth with scores of adolescent verbal learning and memory, assessed using an Italian translation of the California Verbal Learning Test for Children (CVLT-C) (N=140). Associations were estimated using multivariable linear and logistic regression, generalized estimating equations and multiple informant models. In the third aim, we estimated associations of a metal mixture (lead, manganese, copper, and chromium) with multiple assessments of motor function (N=612). Statistical methods included generalized additive models, multivariable linear regression, quantile g-computation and Bayesian kernel machine regression. In the second and third aims, we also stratified analysis by sex to examine effect measure modification.
Results: In the first aim, we found that temporal trends of tooth metal levels differed by metals and correlates of tooth metal levels included biological sex and primary source of milk during infancy. In the second aim, we estimated manganese-cognition associations that differed by exposure time window: prenatal manganese and childhood manganese for boys was beneficial but postnatal manganese associations were null. In the third aim, we observed sex-specific associations between a metal mixture with motor function scores. The metal mixture was associated with improved motor function scores among females (driven by copper and chromium) whereas the metal mixture was associated with worse motor function scores among males (driven by manganese and copper).
CONCLUSION: The association between metal exposure in early life with neurodevelopment is dynamic and complex: associations between metals and neurodevelopment depend on exposure timing, biological sex, and co-exposures. This body of research can be used to inform future research by contributing to the understanding of metal neurotoxicity in critical windows of development and in relation to less studied neurodevelopmental domains, like motor function.2025-01-20T00:00:00
Novel techniques for assessing manganese exposure and children's neurodevelopment
Get PDFBACKGROUND: While manganese (Mn) is essential for growth and development, evidence for Mn as a developmental neurotoxicant is mounting. However, inconsistencies in exposure metrics, susceptibility factors and neurobehavioral outcomes muddle the understanding of Mn effects on the developing nervous system.
OBJECTIVE: To estimate Mn-neurobehavioral associations in varied neurobehavioral tasks and evaluate susceptibility factors (sex differences, co-exposures, exposure timing).
METHODS: Research aims were conducted using the Public Health Impact of Mixed element Exposure (PHIME) study, including 720 Italian adolescents living near ferro-manganese industry. Blood, hair, nails, urine and saliva were collected in adolescence and metals [Mn, lead (Pb), copper (Cu), chromium (Cr)] were measured using ICP-MS. Mn was measured in deciduous teeth in a subset of participants (n=195) using LA ICP-MS to represent prenatal, postnatal and childhood exposure periods. Trained neuropsychologists administered a neurobehavioral battery to adolescents. In the first aim, we estimated associations of early-life Mn levels measured in deciduous teeth with visuospatial learning and memory, assessed using the Virtual Radial Arm Maze (VRAM), a novel animal-human translational neurobehavioral task. The second aim estimated associations of prenatal, early postnatal (0-1 year) and childhood (1~6 years) Mn measured in deciduous teeth with IQ scores and subtests measured by the Wechsler Intelligence Scale for Children (WISC-III). The third aim evaluated the association of a mixture of metals (Mn, Pb, Cu, Cr) measured in multiple biomarkers (hair, blood, urine, nails, saliva) and IQ. Data analysis included generalized additive models, linear regression, zero-inflated Poisson regression (for VRAM count outcomes), and Bayesian kernel machine regression (BKMR).
RESULTS: In the first aim we observed U-shaped associations between prenatal Mn and VRAM outcomes among girls only, suggesting that low and high prenatal Mn levels may be harmful to visuospatial learning and memory. In the second aim, several associations were found with specific subtests that assess visuospatial ability, working memory, problem solving and attention, wherein estimates from the prenatal period suggested beneficial Mn associations, unlike the early postnatal and childhood periods. For the third aim we found inverse associations of adolescent Mn, measured either in hair or saliva, with verbal IQ (VIQ) scores, and an inverted U-shaped association for hair Cu. Strongest associations for the overall metals mixture were estimated with VIQ, where the joint increase in metals concentrations was associated with lower VIQ scores.2022-09-25T00:00:00
Metal mixtures and the role of iron status in early adolescent cognition
Get PDFChildren are commonly exposed to metals in the environment, particularly those living in proximity to steel-producing ferroalloy industry. Exposure to metals, including lead (Pb), manganese (Mn), chromium (Cr) and copper (Cu), impacts neurodevelopment, but less attention has been given to examining associations of metal mixtures with cognitive function in children. Further, recent epidemiological studies have identified iron (Fe) status as a modifier of metals-induced neurotoxicity, such that adverse associations of metals (e.g., Mn or Pb) tend to be stronger among children with Fe deficiency. However, no study to date has quantified the modifying or mediating role of Fe status on a complex metal mixture in relation to any neurodevelopmental outcome. We used data from the Public Health Impact of Metals Exposure Study (PHIME), a cohort of 720 Italian adolescents (10–14 years) to quantify the association of an industry-relevant metal mixture (Pb, Mn, Cr, Cu) with neurodevelopment, and examine the role of Fe status as a modifier or mediator of these associations. Metals were measured in blood (Pb) or hair (Mn, Cr, Cu) using inductively-coupled plasma mass spectrometry, and Fe status was assessed using three clinically relevant biomarkers (ferritin, hemoglobin, transferrin) measured in whole blood or serum using luminescent or immunoassays. Of note, there was no indication of Fe deficiency in the study population. In Chapter 2, we identified associations of the metal mixture with verbal learning and memory, measured using the California Verbal Learning Test for Children (CVLT-C), using Bayesian Kernel Machine Regression (BKMR). In adjusted models, we found that the mixture was jointly associated with higher scores for the recall trials: compared to the 50th percentile, the 90th percentile of the mixture was associated with a 0.12 standard deviation increase (95% credible interval [CI]= -0.27, 0.50) in the number of words recalled on trial 5 recall, indicating better cognitive performance. This association was driven primarily by Cu, which was further modified by Fe status: the beneficial association of Cu with recall was stronger at increasing percentiles of ferritin. In Chapter 3, we found that the metal mixture was jointly associated with self-reported attention-related behaviors measured on the Conners Rating Scales. For example, the 90th percentile of the mixture, compared to the 50th percentile, was associated with a 4.1% increase (β= 0.04; 95% CI= 0.00, 0.08) in self-reported inattention T-scores in BKMR models, reflecting worse cognitive performance. These associations were driven primarily by Mn, though there was no indication of modification by Fe status. Lastly, in Chapter 4, we quantified the mediating role of Fe status on the association between the metal mixture and CVLT-C scores using the newly developed BKMR Causal Mediation Analysis (BKMR-CMA). Though the metal mixture was associated with aspects of Fe status (e.g., ferritin), there was no evidence that Fe status mediated the association between the metal mixture and CVLT-C scores. Overall, the findings from this dissertation suggest that an industry-relevant metal mixture can impact aspects of neurodevelopment, including learning, memory and attention-related behaviors, and that Fe status may be a modifier of these associations. These findings have significant implications for potential public health interventions aimed at improving cognitive development in adolescents. However, the generalizability of our findings in a Fe-replete population of healthy adolescents may be limited, and further research in Fe-deficient populations is warranted. 2025-04-26T00:00:00
A prospective ultrasound study of whole blood metals and incidence of uterine leiomyomata
Get PDFBackground: Uterine leiomyomata (UL), hormone-dependent neoplasms, are a major source of gynecologic morbidity. Metals are hypothesized to influence UL risk through endocrine disruption, and their effects may vary by vitamin D status. Objective: We estimated associations of a metal mixture with incident UL, overall and by vitamin D status. Methods: We analyzed data from the Study of Environment, Lifestyle and Fibroids, a Detroit-area prospective cohort study of 1,693 Black women aged 23-35 years. We measured concentrations of 17 metals/metalloids in whole blood and 25-hydroxyvitamin D (25[OH]D) in serum collected at baseline (2010-2012). Participants underwent ultrasonography at baseline and after 20 months to detect UL. We used Bayesian Kernel Machine Regression to estimate adjusted associations (β) of the metal mixture with probit of incident UL. We also ran Cox regression models with interaction terms to estimate incidence rate ratios (IRR) by vitamin D status. Results: Among 1,132 UL-free participants at baseline, 832 (73%) had vitamin D deficiency (25[OH]D<20 ng/mL) and 117 (10%) developed UL within 20 months. Increasing all metals from their 50th to 75th percentiles was weakly positively associated with UL overall (β=0.06, 95% credible interval [CrI]: -0.03, 0.16) and among vitamin D-deficient participants (β=0.13, 95% CrI: 0.01, 0.24), driven by cadmium (overall and vitamin D-deficient) and mercury (vitamin D-deficient only). Increasing cadmium from its 25th to 75th percentile was positively associated with UL overall (β=0.03, 95% CrI: -0.05, 0.11) and among vitamin D-deficient participants (β=0.13, 95% CrI: 0.02, 0.24). In Cox models, cadmium (IRR=1.55, 95% confidence interval [CI]: 1.07, 2.24, per 1-unit increase in standardized concentration) and mercury (IRR=1.38, 95% CI: 0.99, 1.92) were positively associated with UL among vitamin D-deficient participants. Discussion: The metal mixture was positively associated with incident UL, but the association was weak and imprecise. We observed a stronger association among vitamin D-deficient participants that was driven by cadmium and mercury. https://doi.org/10.1289/EHP15218
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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