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Joel Schwartz

Publications and source records attributed to Joel Schwartz.

At least 19 recordsLinked to original sources
PubMed2024

Causal Mediation Analysis for Integrating Exposure, Genomic, and Phenotype Data.

Causal mediation analysis provides an attractive framework for integrating diverse types of exposure, genomic, and phenotype data. Recently, this field has seen a surge of interest, largely driven by the increasing need for causal mediation analyses in health and social sciences. This article aims to provide a review of recent developments in mediation analysis, encompassing mediation analysis of a single mediator and a large number of mediators, as well as mediation analysis with multiple exposures and mediators. Our review focuses on the recent advancements in statistical inference for causal mediation analysis, especially in the context of high-dimensional mediation analysis. We delve into the complexities of testing mediation effects, especially addressing the challenge of testing a large number of composite null hypotheses. Through extensive simulation studies, we compare the existing methods across a range of scenarios. We also include an analysis of data from the Normative Aging Study, which examines DNA methylation CpG sites as potential mediators of the effect of smoking status on lung function. We discuss the pros and cons of these methods and future research directions.

causal inference↗
PubMed2003

Apolipoprotein E genotype predicts 24-month bayley scales infant development score.

Apolipoprotein E (APOE) regulates cholesterol and fatty acid metabolism, and may mediate synaptogenesis during neurodevelopment. To our knowledge, the effects of APOE4 isoforms on infant development have not been studied. This study was nested within a cohort of mother-infant pairs living in and around Mexico City. A multiple linear regression model was constructed using the 24-mo Mental Development Index (MDI) of the Bayley Scale as the primary outcome and infant APOE genotype as the primary risk factor of interest. Regression models stratified on APOE genotype were constructed to explore effect modification. Of 311 subjects, 53 (17%) carried at least one copy of the APOE4 allele. Mean (SD) MDI scores among carriers with at least one copy of APOE4 were 94.1 (14.3) and among E3/E2 carriers were 91.2 (14.0). After adjustment for covariates, APOE4 carrier status was associated with a 4.4 point (95% confidence interval: 0.1-8.7; p = 0.04) higher 24-mo MDI. In the stratified regression models, the negative effects for umbilical cord blood lead level on 24-mo MDI score was approximately 4-fold greater among APOE3/APOE2 carriers than among APOE4 carriers. These results suggest that subjects with the E4 isoform of APOE may have advantages over those with the E2 or E3 isoforms with respect to early life neuronal/brain development.

Apolipoprotein E2↗
PubMed2003

Elucidation of molecular targets of mammary cancer chemoprevention in the rat by organoselenium compounds using cDNA microarray.

We employed cDNA microarray analysis to identify, in mammary adenocarcinomas induced by 7,12-dimethylbenz[a] anthracene (DMBA) in the rat, target genes as potential biomarkers for cancer chemoprevention by 1,4-phenylenebis(methylene)selenocyanate (p-XSC). Confirmation of selected genes was conducted by reverse transcription polymerase chain reactions (RT-PCR). The glutathione conjugate, p-XSeSG, a putative metabolite of p-XSC was also employed to test our hypothesis that p-XSeSG is a more effective cancer chemopreventive agent in the mammary cancer model than p-XSC. Mammary adenocarcinomas were induced by a single oral administration of 5 mg DMBA in 0.2 ml olive oil per rat at 50-55 days of age. Consistent with our previous reports, dietary p-XSC at a non-toxic dose (10 p.p.m. as selenium) significantly inhibited adenocarcinoma development, independent of feeding duration. Moreover, p-XSeSG appears to be just as effective as p-XSC when fed after DMBA administration, but was significantly less effective than p-XSC in inhibiting the induction of mammary adenocarcinomas when it was fed before DMBA and continued until termination. To delineate the molecular basis for cancer chemoprevention by organoselenium compounds, we focused our analysis on differential expression of genes known to be involved in DMBA metabolism, as well as those related to cell cycle, cell proliferation and apoptosis. p-XSC and p-XSeSG were significantly and equally effective in inhibiting levels of expression of genes associated with cytochrome P450 isoforms, but the former was more active than the latter in up-regulating the expression of those related to certain phase II enzymes. p-XSC and p-XSeSG were significantly more effective in the up-regulation of pro-apoptotic genes, such as p21CIP1/WAF1, p27KIP1, APO-1 and Caspase-3, while down-regulating cell growth regulatory genes, such as c-myc, cyclin D1, cyclin D2 and proliferating cell nuclear antigen (PCNA). To our knowledge, this is the first report that provides insights into the effects of p-XSC and p-XSeSG at the molecular level that may account for mammary cancer chemoprevention in vivo in the rat.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2003

Modifiers of the temperature and mortality association in seven US cities.

This paper examines effect modification of heat- and cold-related mortality in seven US cities in 1986-1993. City-specific Poisson regression analyses of daily noninjury mortality were fit with predictors of mean daily apparent temperature (a construct reflecting physiologic effects of temperature and humidity), time, barometric pressure, day of the week, and particulate matter less than 10 micro m in aerodynamic diameter. Percentage change in mortality was calculated at 29 degrees C apparent temperature (lag 0) and at -5 degrees C (mean of lags 1, 2, and 3) relative to 15 degrees C. Separate models were fit to death counts stratified by age, race, gender, education, and place of death. Effect estimates were combined across cities, treating city as a random effect. Deaths among Blacks compared with Whites, deaths among the less educated, and deaths outside a hospital were more strongly associated with hot and cold temperatures, but gender made no difference. Stronger cold associations were found for those less than age 65 years, but heat effects did not vary by age. The strongest effect modifier was place of death for heat, with out-of-hospital effects more than five times greater than in-hospital deaths, supporting the biologic plausibility of the associations. Place of death, race, and educational attainment indicate vulnerability to temperature-related mortality, reflecting inequities in health impacts related to climate change.

Atmospheric Pressure↗
PubMed2003

The association of daily sulfur dioxide air pollution levels with hospital admissions for cardiovascular diseases in Europe (The Aphea-II study).

The objective of this study is to assess the short-term effect of sulfur dioxide (SO(2)) air pollution levels on hospital admissions for cardiovascular diseases. Daily mean hospital admissions for cardiovascular diseases, ischemic heart diseases (IHDs), and stroke in seven European areas (the cities of Birmingham, London, Milan, Paris, Rome, and Stockholm, and in The Netherlands) participating in the multicenter European study of air pollution (Aphea-II), were measured. Time series analysis of daily hospital admission counts was performed using poison autoregressive models. A summary regression coefficient for all cities was provided. Daily numbers of all cardiovascular admissions except stroke, and particularly IHDs, rose significantly with an increase of daily SO(2)levels of the same day and day before. After adjusting for PM(10)(i.e. particles with size <10 microm), the association of SO(2)with IHD admissions remained significant (i.e. an increase of 0.7%; 95% confidence interval=0.1-1.3, per each 10 microg/m(3)increase of SO(2)) among subjects younger than 65 years, but not among subjects older than 65. In the older group the increase was only significant for particles (1.3%; CI 0.7-1.8, per each increase in 10 microg/m(3)of PM(10)). This study provides new evidence for the effects of urban air pollution on cardiac diseases in Europe, and suggests that SO(2)pollution may play an independent role in triggering ischemic cardiac events. From a Public Health perspective these results suggest that reduction in SO(2)levels in European cities could imply a reduction of admissions for IHDs.

Adult↗
PubMed2003

Association between iron deficiency and blood lead level in a longitudinal analysis of children followed in an urban primary care clinic.

OBJECTIVE: To determine if iron deficiency (ID) is longitudinally associated with lead poisoning. STUDY DESIGN: Blood lead levels, hemoglobin, mean corpuscular volume (MCV), red cell distribution width (RDW), insurance status, and age were determined for 1,275 children. ID was defined as MCV <70 fl and RDW >14.5 if age was <2 years and MCV <73 fl and RDW >14.5 if age was >/=2 years. Logistic regression models were constructed by using the second-visit blood lead levels dichotomized at >/=0.48 microm/L (10 microg/dL) as the outcome. RESULTS: The odds ratio (OR) for baseline ID predicting lead poisoning at the second visit was 4.12 (95% CI, 1.96-8.65). In the second model, using children who were iron-replete at both visits as the referent group, for children with ID at both visits, the OR for predicting lead poisoning at the second visit was 5.54 (95% CI, 2.25-13.62). For children with ID at the first visit and iron-replete at the second visit, the OR was 2.73 (95% CI, 0.90-8.27), and for children iron-replete at the first visit and ID at the second visit, the OR was 0.81 (95% CI, 0.10-6.30). CONCLUSIONS: ID is associated with subsequent lead poisoning. These data are consistent with a biological mechanism of increased lead absorption among iron deficient children.

Anemia, Iron-Deficiency↗
PubMed2003

Tobacco smoke exposure and decreased serum and red blood cell folate levels: data from the Third National Health and Nutrition Examination Survey.

The aim of this cross-sectional study was to determine the effects of smoke exposure on serum and red blood cell folate levels. Data collected as part of the Third National Health and Nutrition Examination Survey were analyzed. Serum and red blood cell folate levels were measured in active smokers and nonsmokers with high, moderate, and low exposure to environmental tobacco smoke. After adjusting for dietary intake of folate and other covariates, we found that both smokers and nonsmokers with high smoke exposure had lower red blood cell folate levels than did nonsmokers with low smoke exposure (-86 nmol/l [95% confidence interval, CI, -101 to -71 nmol/l] for smokers; -50 nmol/l [95% CI -69 to -31 nmol/l] for nonsmokers with high smoke exposure, compared with nonsmokers with low smoke exposure). Similarly, after adjustment of dietary intake of folate and other covariates, the log serum folate level also was decreased (-0.29 log nmol/l [95% CI -0.33 to -0.25 log nmol/l] for smokers; -0.16 log nmol/l [95% CI -0.20 to -0.12 log nmol/l] for nonsmokers with high smoke exposure, compared with nonsmokers with low smoke exposure). Tobacco smoke exposure is associated with decreased folate levels, which may be a mechanism for some of the health effects of active and passive smoking.

Adolescent↗
PubMed2003

A delta-aminolevulinic acid dehydratase (ALAD) polymorphism may modify the relationship of low-level lead exposure to uricemia and renal function: the normative aging study.

In this study we investigated whether a known delta-aminolevulinic acid dehydratase (ALAD) exon 4 polymorphism has a modifying effect on the association of blood or bone lead level with uricemia and indices of renal function among middle-aged and elderly men. We performed a cross-sectional study of subjects who participated between 1991 and 1995 in the Department of Veterans Affairs Normative Aging Study. Information on blood lead levels, bone lead levels (measured by K-shell X-ray fluorescence), serum uric acid, serum creatinine, estimated creatinine clearance, and ALAD polymorphism status was available in 709 subjects. Regression models were constructed to examine the relationships of serum uric acid, serum creatinine, and estimated creatinine clearance to blood or bone lead level, stratified by genotype. We also adjusted for age, body mass index, blood pressure, smoking, alcohol consumption, and ingestion of analgesic medications (n = 638). Of the 709 subjects, 7 (1%) and 107 (15%) were homozygous and heterozygous for the variant (ALAD-2) allele, respectively. The mean (range) serum uric acid and creatinine levels were 6.5 (2.9-10.6) and 1.2 (0.6-2.5) mg/dL. No significant differences were found in serum uric acid, serum creatinine, or estimated creatinine clearance by ALAD genotype. However, after adjusting for other potential confounders, we found a significant linear relationship between serum uric acid and patella bone lead (p = 0.040) among the ALAD 1-2/2-2 genotype individuals above a threshold patellar lead level of 15 micro g/g. In contrast, among the wild-type (ALAD 1-1) individuals, there was a suggestion of a significant linear relationship of serum uric acid with patella bone lead (p = 0.141), but only after a threshold of 101 micro g/g. There was evidence of a significant (p = 0.025) interaction of tibia lead with genotype (ALAD 1-1 vs. ALAD 1-2/2-2) regarding serum creatinine as an outcome, but in the same linear regression model tibia lead alone was not a significant predictor of serum creatinine. Conversely, for estimated creatinine clearance, patella lead, but not the interaction of patella lead with genotype, was a significantly independent predictor (p = 0.026). Our findings suggest that ALAD genotype may modify the effect of lead on the renal excretion of uric acid as well as overall renal function among middle-aged and elderly men who had community (nonoccupational) exposures to lead. Additional research is needed to ascertain whether this constitutes a true gene-environment interaction and, if so, its clinical impact.

Adult↗
PubMed2003

The work environment and workers' health in four large office buildings.

We conducted a 1-year epidemiologic study in Boston, Massachusetts, beginning May 1997, to examine the associations between environmental factors and office workers' health. We recruited 98 subjects (81 females and 17 males) in 21 offices in four office buildings. We conducted environmental sampling every 6 weeks and concurrently administered detailed questionnaires to collect information on work-related symptoms, psychosocial factors, and perceptions of the office environments. In multivariate analyses, eye irritation was positively correlated with floor dust [odds ratio (OR) = 1.46; 95% confidence intervals (CI), 1.14-1.86] and reported lack of office cleanliness (OR = 1.52; 95% CI, 1.11-2.08). Nonspecific symptoms were positively associated with unidentified chair fungi (OR = 1.87; 95% CI, 1.11-3.15) and several self-reported conditions, including a history of asthma (OR = 3.15; 95% CI, 1.26-7.87), more people in offices (OR = 1.71; 95% CI, 1.16-2.51), lack of office cleanliness (OR = 2.85; 95% CI, 1.72-4.73), and low job satisfaction (OR = 1.72; 95% CI, 1.06-2.81). Upper respiratory symptoms were positively associated with total fungal concentrations recovered from chair dust (OR = 1.35; 95% CI, 1.07-1.70) and the following self-reported conditions: more people in offices (OR = 1.45; 95% CI, 1.01-2.08), lack of office cleanliness (OR = 1.62; 95% CI, 1.15-2.30), and jobs frequently requiring hard work (OR = 1.43; 95% CI, 1.05-1.95). This study emphasizes the importance of maintaining a clean, uncrowded workspace and the importance of chair fungi as a correlate for health effects.

Adult↗
PubMed2003

The temporal pattern of respiratory and heart disease mortality in response to air pollution.

Short-term changes in ambient particulate matter with aerodynamic diameters < 10 micro m (PM10) have been associated with short-term fluctuations in mortality or morbidity in many studies. In this study, we tested whether those deaths are just advanced by a few days or weeks using a multicity hierarchical modeling approach for all-cause, respiratory, and cardiovascular deaths, for all ages and stratifying by age groups, within the APHEA-2 (Air Pollution and Health: A European Approach) project. We fit a Poisson regression and used an unconstrained distributed lag to model the effect of PM10 exposure on deaths up to 40 days after the exposure. In baseline models using PM10 the day of and day before the death, we found that the overall PM10 effect (per 10 micro g/m3) was 0.74% [95% confidence interval (95% CI), -0.17 to 1.66] for respiratory deaths and 0.69% (95% CI, 0.31-1.08) for cardiovascular deaths. In unrestricted distributed lag models, the effect estimates increased to 4.2% (95% CI, 1.08-7.42) for respiratory deaths and to 1.97% (95% CI, 1.38-2.55) for cardiovascular deaths. Our study confirms that most of the effect of air pollution is not simply advanced by a few weeks and that effects persist for more than a month after exposure. The effect size estimate for PM10 doubles when we considered longer-term effects for all deaths and for cardiovascular deaths and becomes five times higher for respiratory deaths. We found similar effects when stratifying by age groups. These larger effects are important for risk assessment.

Adolescent↗
PubMed2003

The U.S. Environmental Protection Agency Particulate Matter Health Effects Research Centers Program: a midcourse report of status, progress, and plans.

In 1998 Congress mandated expanded U.S. Environmental Protection Agency (U.S. EPA) health effects research on ambient air particulate matter (PM) and a National Research Council (NRC) committee to provide research oversight. The U.S. EPA currently supports intramural and extramural PM research, including five academically based PM centers. The PM centers in their first 2.5 years have initiated research directed at critical issues identified by the NRC committee, including collaborative activities, and sponsored scientific workshops in key research areas. Through these activities, there is a better understanding of PM health effects and scientific uncertainties. Future PM centers research will focus on long-term effects associated with chronic PM exposures. This report provides a synopsis of accomplishments to date, short-term goals (during the next 2.5 years) and longer-term goals. It consists of six sections: biological mechanisms, acute effects, chronic effects, dosimetry, exposure assessment, and the specific attributes of a coordinated PM centers program.

Air Pollutants↗
PubMed2002

Using sulfur as a tracer of outdoor fine particulate matter.

Six homes in the metropolitan Boston area were sampled between 6 and 12 consecutive days for indoor and outdoor particle volume and mass concentrations, particle elemental concentrations, and air exchange rates (AERs). Indoor/outdoor (I/O) ratios of nighttime (i.e., particle nonindoor source periods) sulfur, PM2.5 and the specific particle size intervals were used to provide estimates of the effective penetration efficiency. Mixed models and graphical displays were used to assess the ability of the I/O ratios for sulfur to estimate corresponding I/O ratios for PM2.5 and the various particle sizes. Results from this analysis showed that particulate sulfur compounds were primarily of outdoor origin and behaved in a manner that was representative of total PM2.5 in Boston, MA. These findings support the conclusion that sulfur can be used as a suitable tracer of outdoor PM2.5 for the homes sampled in this study. Sulfur was more representative of particles of similar size (0.06-0.5 microm), providing evidence that the size composition of total PM2.5 is an important characteristic affecting the robustness of sulfur-based estimation methods.

Air Pollution↗
PubMed2002

Correlates of bone and blood lead levels among middle-aged and elderly women.

In 1993-1995, the authors evaluated risk factors for elevated blood and bone lead levels in 264 Boston, Massachusetts, area women previously selected for a case-control study of lead and hypertension. Bone lead was measured at the tibia and patella with K x-ray fluorescence. Blood lead was analyzed by graphite furnace atomic absorption. Participants were aged 46-74 years and had mean lead levels of 3 (standard deviation, 2) micro g/dl (blood), 13 (standard deviation, 9) micro g/g (tibia), and 17 (standard deviation, 11) micro g/g (patella). In multivariate linear regression models, use of postmenopausal estrogen (inverse) and alcohol intake (positive) were significantly associated with blood lead levels. Both bone lead measures were significantly and positively associated with blood lead but only among postmenopausal women not using estrogen; for example, an increase from the first to the fifth quintile of tibia lead level (19 micro g/g) was associated with a 1.7- micro g/dl increase in blood lead (p = 0.0001) in this group. Older age and lower parity were associated with higher tibia lead; only age was associated with patella lead. The observed interaction of bone lead with estrogen status in determining blood lead supports the hypothesis that increased bone resorption, as occurs postmenopausally because of decreased estrogen production, results in heightened release of bone lead stores into blood.

Aged↗
PubMed2002

Impact of breastfeeding on the mobilization of lead from bone.

To evaluate the hypothesis that lactation stimulates lead release from bone to blood, the authors analyzed breastfeeding patterns and bone lead concentrations as determinants of blood lead levels among 425 lactating women in Mexico City for 7 months after delivery (1994-1995). The authors measured in vivo patella and tibia lead concentrations at 1 month postpartum using K x-ray fluorescence. Maternal blood samples and questionnaire information were collected at delivery and at 1, 4, and 7 months postpartum. Blood lead was analyzed using graphite furnace atomic absorption spectroscopy. Mean blood lead level at delivery was 8.4 microg/dl (range: 1.8--23.4). Mean cortical and trabecular lead levels were 10.6 microg/g (range: nondetectable to 76.5) and 15.3 microg/g (range: nondetectable to 85.9), respectively, reflecting a population with elevated and diverse past and current lead exposure. The association of bone lead and breastfeeding with blood lead was estimated using generalized estimating equations. Breastfeeding practices and maternal bone lead were important predictors of blood lead level. After adjustment for bone lead and environmental exposure, women who exclusively breastfed their infants had blood lead levels that were increased by 1.4 microg/dl and women who practiced mixed feeding had levels increased by 1.0 microg/dl, in relation to those who had stopped lactation. These results support the hypothesis that lactation is directly related to the amount of lead released from bone.

Adolescent↗
PubMed2002

Dustborne fungi in large office buildings.

Fungi are ubiquitous in our daily environments. However, their effects on office workers' health are of great interest to many environmental health researchers. Dust has been considered an important reservoir of indoor fungi from which aerosolization and exposure could occur. We have examined the characteristics of dustborne fungal populations recovered from floors and chairs in office buildings. We investigated twenty-one offices in four office buildings in Boston, MA over a year beginning May 1997. We conducted intensive environmental sampling every six weeks to measure culturable dustborne fungi from floors and chairs, surface dust levels and water activity in carpeting. Carbon dioxide, temperature, and relative humidity were monitored continuously. Concentrations of total dustborne fungi recovered from floors were positively related to carbon dioxide (beta = 0.00064; p-value = 0.0002) and temperatures between 20 and 22.5 degrees C (p-value = 0.0026). Also, total fungal concentrations in floors gradually increased over the year (p-value = 0.0028). Total fungi recovered from chairs varied significantly by season (p-value < 0.0001), highest in September and lowest in March, and were positively correlated with dust loads in floors (beta = 0.25; p-value < 0.0001). We used principal component analysis (PCA) to reduce various observed fungal species to fewer factors. Six groups (PCA factors) were obtained for dustborne fungi recovered from both floors and chairs. The models of the first PCA factors for both floors and chairs were similar to those for total fungal concentrations. The results of this study provide essential information to further evaluate the effects of dustborne fungi on office workers' health.

Air Microbiology↗
PubMed2002

The temporal pattern of mortality responses to air pollution: a multicity assessment of mortality displacement.

Although the association between particulate matter and mortality or morbidity is generally accepted, controversy remains about the importance of the association. If it is due solely to the deaths of frail individuals, which are brought forward by only a brief period of time, the public health implications of the association are fewer than if there is an increase in the number of deaths. Recently, other research has addressed the mortality displacement issue in single-city analysis. We analyzed this issue with a distributed lag model in a multicity hierarchic modeling approach, within the Air Pollution and Health: A European Approach (APHEA-2) study. We fit a Poisson regression model and a polynomial distributed lag model with up to 40 days of delay in each city. In the second stage we combined the city-specific results. We found that the overall effect of particulate matter less than 10 microM in aerodynamic diameter (PM10) per 10 microg/m3 for the fourth-degree distributed lag model is a 1.61% increase in daily deaths (95% CI = 1.02-2.20), whereas the mean of PM10 on the same day and the previous day is associated with only a 0.70% increase in deaths (95% CI = 0.43-0.97). This result is unchanged using an unconstrained distributed lag model. Our study confirms that the effects observed in daily time-series studies are not due primarily to short-term mortality displacement. The effect size estimate for airborne particles more than doubles when we consider longer-term effects, which has important implications for risk assessment.

Air Pollutants↗
PubMed2002

The association between personal measurements of environmental exposure to particulates and heart rate variability.

BACKGROUND: Epidemiologic evidence indicates that airborne particulates are associated with mortality risk, predominately from heart disease. This may occur through changes in the cardiac autonomic nervous system, witnessed by changes in heart rate variability. METHODS: This short-term longitudinal study used continuous personal particulate matter measurements to examine the effects of exposure to particulate matter less than 2.5 microm in diameter (PM2.5) on heart rate and rate variability in 20 relatively young, healthy male workers. Continuous exposure and cardiac monitoring were performed on each subject on a nonwork day. The 5-minute standard deviation of the normal-to-normal interval was used as the main measure of heart rate variability. RESULTS: Mixed-effects regression models estimate an average 1.4% (95% confidence limits = -2.1, -0.6) decrease in the 5-minute standard deviation of the normal-to-normal interval for each 100 microg/m3 increase in the 3-hour PM2.5 moving average, and small increases in heart rate, after adjustment for potential confounding factors. Predicted effects of exposure were greatest using the 3-hour averaging interval for PM2.5 and decreased in magnitude using shorter and longer intervals. CONCLUSIONS: These results reveal an association between cardiac autonomic function and environmental PM2.5 exposure. These observed associations may result from decreased vagal or increased sympathetic tone.

Adult↗