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Growing evidence suggests exposure to chemicals and industrial pollutants may increase risk of systemic lupus erythematosus (SLE). Here we review research on SLE associations with occupational and industrial exposures, primarily drawing on studies in human populations and summarizing epidemiologic research published in the past decade. The association of occupational silica exposure with SLE is well established, but key questions remain, including the required dose and susceptibility factors, and SLE risk due to other silicate exposures. Research on SLE and other exposures is less well developed, though several potential associations merit further consideration because of the consistency of preliminary human findings, experimental animal research, and biologic plausibility. These include pesticides and solvents, for which experimental findings also support investigation of specific agents, including organochlorines and trichloroethylene. Experimental findings and biologic plausibility suggest research on SLE and occupational exposure to hydrocarbons (i.e. mineral oils) is warranted, especially given the widespread exposures in the population. Experimental and limited human findings support further investigation of SLE related to mercury exposure, especially in dental occupations. Research on environmental risk factors in risk-enriched cohorts (family-based) is recommended, as is further investigation of exposures in relation to intermediate markers of effect (e.g. antinuclear antibodies), clinical features (e.g. nephritis), and outcomes. [ABSTRACT FROM PUBLISHER]

In an International Lymphoma Epidemiology Consortium pooled analysis, polymorphisms in 2 immune-system-related genes, tumor necrosis factor (TNF) and interleukin-10 (IL10), were associated with non-Hodgkin lymphoma (NHL) risk. Here, 8,847 participants were added to previous data (patients diagnosed from 1989 to 2005 in 14 case-control studies; 7,999 cases, 8,452 controls) for testing of polymorphisms in the TNF -308G>A (rs1800629), lymphotoxin-alpha (LTA) 252A>G (rs909253), IL10 -3575T>A (rs1800890, rs1800896), and nucleotide-binding oligomerization domain containing 2 (NOD2) 3020insC (rs2066847) genes. Odds ratios were estimated for non-Hispanic whites and several ethnic subgroups using 2-sided tests. Consistent with previous findings, odds ratios were increased for 'new' participant TNF -308A carriers (NHL: per-allele odds ratio (OR(allelic)) = 1.10, P(trend) = 0.001; diffuse large B-cell lymphoma (DLBCL): OR(allelic) = 1.23, P(trend) = 0.004). In the combined population, odds ratios were increased for TNF -308A carriers (NHL: OR(allelic) = 1.13, P(trend) = 0.0001; DLBCL: OR(allelic) = 1.25, P(trend) = 3.7 x 10(-6); marginal zone lymphoma: OR(allelic) = 1.35, P(trend) = 0.004) and LTA 252G carriers (DLBCL: OR(allelic) = 1.12, P(trend) = 0.006; mycosis fungoides: OR(allelic) = 1.44, P(trend) = 0.015). The LTA 252A>G/TNF -308G>A haplotype containing the LTA/TNF variant alleles was strongly associated with DLBCL (P = 2.9 x 10(-8)). Results suggested associations between IL10 -3575T>A and DLBCL (P(trend) = 0.02) and IL10 -1082A>G and mantle cell lymphoma (P(trend) = 0.04). These findings strengthen previous results for DLBCL and the LTA 252A>G/TNF -308A locus and provide robust evidence that these TNF/LTA gene variants, or others in linkage disequilibrium, are involved in NHL etiology. [ABSTRACT FROM AUTHOR]

Background: Traffic-related air pollution has been associated with adverse health outcomes, and the immune system may be a biologic mediator of health effects. Objectives: We analyzed associations between living near major roads and immune status as measured by five immune assays. We hypothesized that living near a freeway, arterial, or truck route would be associated with increased inflammation and decreased immune function. Methods: We used a geographic information system (GIS) to determine residential proximity to major roads among 115 postmenopausal, overweight women in the greater Seattle, Washington (USA) , area whose immunity was assessed at the baseline visit of an exercise intervention trial. We evaluated three inflammatory markers (C-reactive protein, serum amyloid A, and interleukin-6) and two functional assays of cellular immunity [natural killer (NK) cell cytotoxicity and T-lymphocyte proliferation]. Results: Women living within 150 m of arterial roads had 21% lower NK cytotoxicity compared with women who lived farther from an arterial [mean cytotoxicity, 19.5% ; 95% confidence interval (CI) , 15.6-23.5% ; vs. mean cytotoxicity, 24.8% ; 95% CI, 22.0-27.5%], after adjustment for both individual-level and census tract-level demographic characteristics. This association was limited to women who reported exercising near traffic. Fewer women lived near freeways and truck routes. Markers of inflammation and lymphocyte proliferation did not consistently differ according to proximity to major roads. Conclusions: If the observed association between residential proximity to traffic and decreased NK cytotoxicity is confirmed in other populations, our results may have implications for local land use policy. [ABSTRACT FROM AUTHOR]

To quantify nonresponse bias and estimate its potential impact, the authors compared census-based socioeconomic and demographic factors and geographic locations among respondents and nonrespondents in a multicenter case-control study of non-Hodgkin lymphoma (1998-2000). Using a geographic information system, the authors mapped current addresses and linked them to the 2000 US Census database to determine group-level demographic and socioeconomic information. They used logistic regression analysis to compute the risk of being a nonrespondent, separately for cases and controls. They used spatial scan methods to evaluate spatial clustering at each study center. Among cases at one or more centers, nonresponse was significantly associated with non-White race, lower household income, a greater proportion of multiple-unit housing, fewer years of education, and living in a more urbanized area. For most factors, the authors observed similar patterns among controls, although findings were mostly nonsignificant. They found two nonrandom elliptical clusters in Los Angeles, California, and Detroit, Michigan, that disappeared after adjustment for the demographic factors. The authors determined the bias in non-Hodgkin lymphoma risk associated with census-tract educational level by comparing risks among respondents and all subjects. The bias was 8%, indicating that the socioeconomic and demographic differences between respondents and nonrespondents did not result in a large bias in the risk estimate for education. [ABSTRACT FROM AUTHOR]

Prior research suggests that childhood brain tumors (CBTs) may be associated with exposure to pesticides. Organophosphorus insecticides (OPs) target the developing nervous system, and until recently, the most common residential insecticides were chlorpyrifos and diazinon, two OPs metabolized in the body through the cytochrome P450/paraoxonase 1 (PON1) pathway. To investigate whether two common PON1 polymorphisms, C-108T and Q192R, are associated with CBT occurrence, we conducted a population-based study of 66 cases and 236 controls using DNA from neonatal screening archive specimens in Washington State, linked to interview data. The risk of CBT was nonsignificantly increased in relation to the inefficient PON1 promoter allele [per PON1(-108T) allele, relative to PON1(-108CC): odds ratio (OR) = 1.4; 95% confidence interval (CI), 1.0-2.2; p-value for trend = 0.07]. Notably, this association was strongest and statistically significant among children whose mothers reported chemical treatment of the home for pests during pregnancy or childhood (per PON1(-108T) allele: among exposed, OR = 2.6; 95% CI, 1.2-5.5; among unexposed, OR = 0.9; 95% CI, 0.5-1.6) and for primitive neuroectodermal tumors (per PON1(-108T) allele: OR = 2.4; 95% CI, 1.1-5.4). The Q192R polymorphism, which alters the structure of PON1 and influences enzyme activity in a substrate-dependent manner, was not associated with CBT risk, nor was the PON1(C-108T/Q192R) haplotype. These results are consistent with an inverse association between PON1 levels and CBT occurrence, perhaps because of PON1's ability to detoxify OPs common in children's environments. Larger studies that measure plasma PON1 levels and incorporate more accurate estimates of pesticide exposure will be required to confirm these observations. [ABSTRACT FROM AUTHOR]

Glyphosate is a broad-spectrum herbicide that is one of the most frequently applied pesticides in the world. Although there has been little consistent evidence of genotoxicity or carcinogenicity from in vitro and animal studies, a few epidemiologic reports have indicated potential health effects of glyphosate. We evaluated associations between glyphosate exposure and cancer incidence in the Agricultural Health Study (AHS), a prospective cohort study of 57,311 licensed pesticide applicators in Iowa and North Carolina. Detailed information on pesticide use and other factors was obtained from a self-administered questionnaire completed at time of enrollment (1993-1997). Among private and commercial applicators, 75.5% reported having ever used glyphosate, of which > 97% were men. In this analysis, glyphosate exposure was defined as a) ever personally mixed or applied products containing glyphosate; b) cumulative lifetime days of use, or 'cumulative exposure days' (years of use x days/year); and c) intensity-weighted cumulative exposure days (years of use x days/year times symbol estimated intensity level). Poisson regression was used to estimate exposure-response relations between glyphosate and incidence of all cancers combined and 12 relatively common cancer subtypes. Glyphosate exposure was not associated with cancer incidence overall or with most of the cancer subtypes we studied. There was a suggested association with multiple myeloma incidence that should be followed up as more cases occur in the AHS. Given the widespread use of glyphosate, future analyses of the AHS will allow further examination of long-term health effects, including less common cancers. [ABSTRACT FROM AUTHOR]

Tocopherols are lipid-soluble antioxidants that may protect against some conditions of aging. The authors examined associations between radiographic knee osteoarthritis and serum levels of alpha-, delta-, and gamma-tocopherol and the alpha:gamma-tocopherol ratio in African-American and White adults from the Johnston County Osteoarthritis Project (North Carolina, 1991-1997). Two hundred cases with radiographic knee osteoarthritis (Kellgren-Lawrence grades > or = 2) and 200 controls (Kellgren-Lawrence grade 0) were randomly selected and matched by age, ethnicity, and sex. Serum tocopherol levels were measured by high performance liquid chromatography. Conditional logistic regression was used to estimate associations between radiographic knee osteoarthritis and tertiles of each tocopherol measure, independent of confounders. Persons in the highest tertile of the alpha:gamma-tocopherol ratio had half the odds of radiographic knee osteoarthritis as those in the lowest tertile (adjusted odds ratio = 0.5, 95% confidence interval: 0.2, 1.2). This inverse association occurred in all ethnic and sex subgroups, significantly in African Americans and men. Radiographic knee osteoarthritis was inversely associated with serum alpha-tocopherol in African Americans and men, positively associated with serum gamma-tocopherol in men, and unassociated with serum delta-tocopherol. Associations between radiographic knee osteoarthritis and tocopherol isoforms are complex and may vary by ethnicity and sex. [ABSTRACT FROM AUTHOR]

Background: An increased rate of non-Hodgkin's lymphoma (NHL) has been repeatedly observed among farmers, but identification of specific exposures that explain this observation has proven difficult.Methods: During the 1980s, the National Cancer Institute conducted three case-control studies of NHL in the midwestern United States. These pooled data were used to examine pesticide exposures in farming as risk factors for NHL in men. The large sample size (n = 3417) allowed analysis of 47 pesticides simultaneously, controlling for potential confounding by other pesticides in the model, and adjusting the estimates based on a prespecified variance to make them more stable.Results: Reported use of several individual pesticides was associated with increased NHL incidence, including organophosphate insecticides coumaphos, diazinon, and fonofos, insecticides chlordane, dieldrin, and copper acetoarsenite, and herbicides atrazine, glyphosate, and sodium chlorate. A subanalysis of these "potentially carcinogenic" pesticides suggested a positive trend of risk with exposure to increasing numbers.Conclusion: Consideration of multiple exposures is important in accurately estimating specific effects and in evaluating realistic exposure scenarios. [ABSTRACT FROM AUTHOR]

Few studies have explored variability of associations between greenspace and cardiovascular (CVD) mortality according to demographic or neighborhood contextual factors. We estimated overall and sex-stratified associations between greenspace and CVD mortality rates in Philadelphia, PA, and quantified effect modification of the sex-stratified associations by neighborhood violent crime rates. Sex- and age-stratified census tract CVD mortality rates (years 2008-2015) were linked with proportion tree canopy cover, grass/shrub cover, and total vegetation cover, and proportion of adult residents reporting access to a park. We used multivariable negative binomial models to estimate overall and sex-stratified associations between neighborhood greenspace and CVD mortality rates, and quantified effect modification by tract-level rates of violent crime. Higher proportion tree canopy cover and higher proportion adults reporting access to parks were associated with modestly lower rates of CVD mortality, with more pronounced estimates in males than females. In tracts with higher rates of crime, higher tree canopy coverage and perceived park access were associated with lower CVD mortality rates. We did not observe strong evidence of sex-based differences in interaction between neighborhood crime rates and greenspace. Results from this study reveal variability of associations between greenspace and CVD mortality rates according to sex categories, and according to neighborhood social environments. There is a need for further research exploring the extent to which differences in perceived safety explain gender-based differences in associations between greenspace and cardiovascular outcomes., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Mortgage discrimination refers to the systematic withholding of home mortgages from minoritized groups. In recent years, there has been an increase in empirical research investigating associations of historical and contemporary mortgage discrimination on contemporary  outcomes. Investigators have used a variety of measurement methods and approaches, which may have implications for results and interpretation., Purpose: We conducted a systematic review of peer-reviewed literature that has quantified links between both historical and current mortgage discrimination with contemporary adverse environmental, social, and health outcomes. Our goals were to document the methodology used to measure and assign mortgage discrimination, to assess implications for results and interpretation, and to make recommendations for future work., Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, literature searches were conducted in September 2022 using terms that combined concepts of mortgage discrimination, health, and neighborhood environment., Results: In total, 45 papers fit the eligibility criteria. In these, researchers investigated associations between mortgage discrimination and: (1) health outcomes (N = 28); (2) environmental and social exposures including heat, air pollution, greenspace, soil lead levels, and crime (N = 12); and (3) built environment features, including presence of retail alcohol, fast food, and tobacco stores (N = 5). Eleven included studies used Home Mortgage Discrimination Act (HMDA) data to identify racialized bias in mortgage discrimination or redlining, and 34 used Homeowner Loan Corporation (HOLC) maps. The construction and parametrization of mortgage discrimination or redlining and the spatial assignment of HOLC grades to contemporary addresses or neighborhoods varied substantially across studies., Conclusions: Results from our review suggest the need for careful consideration of optimal methods to analyze mortgage discrimination such as HOLC spatial assignment or HMDA index parametrization, contemplation of covariates, and place-based knowledge of the study location., (© 2024. The Author(s).)

Respiratory virus infections are related to over 80% of childhood asthma exacerbations. They enhance pro-inflammatory mediator release, especially for sensitized individuals exposed to pollens/molds. Using a time-series study design, we investigated possible effect modification by respiratory virus infections of the associations between aeroallergens/PM 2.5 and asthma exacerbation rates. Outpatient, emergency department (ED), and inpatient visits for asthma exacerbation among children with asthma (28,540/24,444 [warm/cold season]), as well as viral infection counts were obtained from electronic health records of the Children's Hospital of Philadelphia from 2011 to 2016. Rate ratios (RRs, 90th percentile vs. 0) for late-season grass pollen were 1.00 (0.85-1.17), 1.04 (0.95-1.15), and 1.12 (0.96-1.32), respectively, for respiratory syncytial virus (RSV) counts within each tertile. However, similar trends were not observed for weed pollens/molds or PM 2.5 . Overall, our study provides little evidence supporting effect modification by respiratory viral infections.

Background: Outdoor aeroallergens, such as pollens and molds, are known triggers of asthma exacerbation; however, few studies have examined children's aeroallergen response based on sensitization., Objective: Our aim was to compare the relative impact of aeroallergen levels on asthma exacerbation between pediatric patients with asthma who tested positive or negative for sensitization to particular allergens., Methods: A case-crossover design study was conducted to examine associations between outdoor aeroallergen levels and asthma exacerbation events among children living in Philadelphia, Pennsylvania, who were treated within a large pediatric care network. Sensitization to common allergens was characterized in a subset of patients with asthma exacerbation who had undergone skin prick testing (5.5%). Odds ratios (ORs) and 95% CIs were estimated in all patients with asthma exacerbation and in those sensitized or not sensitized to aeroallergens., Results: Children who were sensitized to a particular allergen had higher odds of asthma exacerbation with exposure to the allergen (ie, early-season tree pollen, oak tree pollen, early-season weed pollen, and late-season molds) than did all patients with asthma or nonsensitized patients. For example, the association between early-season tree pollen and asthma exacerbation among sensitized children (>90th percentile vs ≤25th, OR = 2.28 [95% CI = 1.23-4.22]) was considerably stronger than that estimated among all patients (OR = 1.34 [95% CI = 1.19-1.50]), and it was also substantially different from the lack of association seen among nonsensitized children (OR = 0.89 [95% CI = 0.51-1.55] [ P value for heterogeneity = .03])., Conclusion: More prevalent allergy testing may be useful for prevention of asthma exacerbation by informing interventions targeted to sensitized children and tailored for particular aeroallergens., Competing Interests: Supported by a grant from the Commonwealth Universal Research Enhancement (C.U.R.E) program, funded by the 10.13039/100004897Pennsylvania Department of Health 2015 Formula Award (no. SAP 4100072543), the 10.13039/100000002National Institutes of Health (grants K23HL136842, U01HL138687, R01MD015723, and R21ES032963 [to C.C.K.], the 10.13039/100000060National Institute of Allergy and Infectious Diseases (grant K08AI135091 [to S.E.H.], the 10.13039/100000066National Institute of Environmental Health Sciences (grant P30 ES013508 [to S.E.H.]), the 10.13039/100006792Hartwell Foundation, and the Chan Zuckerberg Foundation. Disclosure of potential conflict of interest: S.E. Henrickson is a member of an ad hoc Advisory Board for Horizon Therapeutics. The rest of the authors declare that they have no relevant conflicts of interest., (© 2024 The Authors.)

Valley Fever is a respiratory disease caused by inhalation of arthroconidia, a type of spore produced by fungi within the genus Coccidioides spp. which are found in dry, hot ecosystems of the Western Hemisphere. A quantitative microbial risk assessment (QMRA) for the disease has not yet been performed due to a lack of dose-response models and a scarcity of quantitative occurrence data from environmental samples. A literature review was performed to gather data on experimental animal dosing studies, environmental occurrence, human disease outbreaks, and meteorological associations. As a result, a risk framework is presented with information for parameterizing QMRA models for Coccidioides spp., with eight new dose-response models proposed. A probabilistic QMRA was conducted for a Southwestern US agricultural case study, evaluating eight scenarios related to farming occupational exposures. Median daily workday risks for developing severe Valley Fever ranged from 2.53 × 10 -7 (planting by hand while wearing an N95 facemask) to 1.33 × 10 -3 (machine harvesting while not wearing a facemask). The literature review and QMRA synthesis confirmed that exposure to aerosolized arthroconidia has the potential to result in high attack rates but highlighted that the mechanistic relationships between environmental conditions and disease remain poorly understood. Recommendations for Valley Fever risk assessment research needs in order to reduce disease risks are discussed, including interventions for farmers., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kerry Hamilton and other faculty at QMRA workshop (Charles Haas) reports financial support and travel were provided by NIH., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Growing evidence suggests psychosocial stressors may increase risk of developing autoimmune disease. We examined stressful life events and caregiving in relation to incident rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in the Women's Health Initiative Observational Study cohort., Methods: The sample of postmenopausal women included 211 incident RA or SLE cases reported within 3 years after enrollment, confirmed by use of disease-modifying antirheumatic drugs (i.e., probable RA/SLE), and 76,648 noncases. Baseline questionnaires asked about life events in the past year, caregiving, and social support. We used Cox regression models to calculate hazard ratios (HR) and 95% confidence intervals (95% CIs), adjusting for age, race/ethnicity, occupational class, education, pack-years of smoking and BMI., Results: Incident RA/SLE was associated with reporting 3 or more life events (e.g., age-adjusted HR 1.70 [95% CI 1.14, 2.53]; P for trend = 0.0026). Elevated HRs were noted for physical (HR 2.48 [95% CI 1.02, 6.04]) and verbal (HR 1.34 [0.89, 2.02]) abuse (P for trend = 0.0614), 2 or more interpersonal events (HR 1.23 [95% CI 0.87, 1.73]; P for trend = 0.2403), financial stress (HR 1.22 [95% CI 0.90, 1.64]), and caregiving 3 or more days per week (HR 1.25 [95% CI 0.87, 1.81]; P for trend = 0.2571). Results were similar, excluding women with baseline symptoms of depression or moderate-to-severe joint pain in the absence of diagnosed arthritis., Conclusion: Our findings support the idea that diverse stressors may increase risk of developing probable RA or SLE in postmenopausal women, supporting the need for further studies in autoimmune rheumatic diseases, including childhood adverse events, life event trajectories, and modifying psychosocial and socioeconomic factors., (© 2023 American College of Rheumatology. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Fine particulate matter (PM 2.5 ) and aeroallergens (i.e., pollen, molds) are known triggers of asthma exacerbation. Despite mechanistic evidence suggesting synergistic effects between PM 2.5 and asthma exacerbation, little epidemiologic work has been performed in children, which has exhibited inconsistency. We conducted a time-series study to explore their interactions using electronic health records (EHR) data in Philadelphia, PA, for asthma diagnoses in outpatient, emergency department [ED], and inpatient settings. Daily asthma exacerbation cases (28,540 asthma exacerbation case encounters) were linked to daily ambient PM 2.5 and daily aeroallergen levels during the aeroallergen season of a six-year period (mid-March to October 2011-2016). Asthma exacerbation counts were modeled using quasi-Poisson regression, where PM 2.5 and aeroallergens were fitted with distributed lag non-linear functions (lagged from 0 to 14-days), respectively, when modeled as the primary exposure variables. Regression models were adjusted for mean daily temperature/relative humidity, long-term and seasonal trends, day-of-week, and major U.S. holidays. Increasing gradient of RR estimates were observed for only a few primary exposure risk factors [PM 2.5 (90th vs. 5th percentile)/aeroallergens (90th percentile vs. 0)], across different levels of effect modifiers. For example, RRs for the association between late-season grass pollen (lag1) and asthma exacerbation were higher at higher levels of PM 2.5 , 5-days preceding the exacerbation event (low PM 2.5 : RR = 1.01, 95% CI: 0.93-1.09; medium PM 2.5 : 1.04, 95% CI: 0.96-1.12; high PM 2.5 : 1.09, 95% CI: 1.01-1.19). However, most of the highest RRs for aeroallergens were instead observed for days with low- or medium- PM 2.5 levels; likewise, when PM 2.5 was modeled as the primary exposure with aeroallergens as the effect modifier. Most of the RR estimates did not exhibit gradients that suggested synergism, and were of relatively high imprecision. Overall, our study suggested no evidence for interactions between PM 2.5 and aeroallergens in their relationships with childhood asthma exacerbation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

While past research suggests that urban greenspace is associated with weaker income-based mortality inequities, little is known about associations with racial inequities, which may be distinct owing to historical and contemporary forms of racism. We quantified the extent to which different measures of greenspace modified socioeconomic and racial/ethnic inequities in all-cause and cardiovascular disease mortality. For every residential census tract in Philadelphia, PA (N = 376), we linked counts of all-cause and cardiovascular mortality (years 2008-2015) with measures of greenspace (proportion tree canopy or grass/shrub cover, proportion residents reporting park access, and the normalized difference vegetation index measure of overall greenness) and American Community Survey-based measures of sociodemographic composition (proportion of residents living in poverty, proportion identifying as non-Hispanic Black, and the index of concentration at the extremes (ICE) representing racialized economic deprivation). We used age- and sex-adjusted negative binomial models, with the natural logarithm of age-specific population counts as an offset, to quantify the magnitude of inequities by each composition variable, overall and stratified by categories of each greenspace measure. Inequities in mortality were weaker among neighborhoods with higher proportion grass/shrub cover or overall greenness. The most substantially narrowed inequities were those by the ICE. Mortality inequities did not differ substantially by perceived park access, and tree canopy was associated with weaker ICE-based inequities only. In this ecologic analysis, neighborhood greenspace was associated with weaker mortality inequities. However, associations varied across greenspace type and sociodemographic composition metrics, with generally stronger associations with overall greenness and grass/shrub coverage, and for ICE-basedinequities., (© 2023. The New York Academy of Medicine.)

Although prediagnostic circulating concentrations of the immune activation markers soluble CD27 (sCD27), sCD30 and chemokine ligand-13 (CXCL13) have been associated with non-Hodgkin lymphoma (NHL) risk, studies have been limited by sample size in associations with NHL subtypes. We pooled data from eight nested case-control studies to investigate subtype-specific relationships for these analytes. Using polytomous regression, we calculated odds ratios (ORs) with 95% confidence intervals (CIs) relating study-specific analyte tertiles to selected subtypes vs controls (n = 3310): chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; n = 623), diffuse large B cell lymphoma (DLBCL; n = 621), follicular lymphoma (FL; n = 398), marginal zone lymphoma (MZL; n = 138), mantle cell lymphoma (MCL; n = 82) and T cell lymphoma (TCL; n = 92). We observed associations with DLBCL for elevated sCD27 [OR for third vs first tertile (OR T3 ) = 2.2, 95% CI = 1.6-3.1], sCD30 (OR T3  = 2.0, 95% CI = 1.6-2.5) and CXCL13 (OR T3  = 2.3, 95% CI = 1.8-3.0). We also observed associations with sCD27 for CLL/SLL (OR T3  = 3.3, 95% CI = 2.4-4.6), MZL (OR T3  = 7.7, 95% CI = 3.0-20.1) and TCL (OR T3  = 3.4, 95% CI = 1.5-7.7), and between sCD30 and FL (OR T3  = 2.7, 95% CI = 2.0-3.5). In analyses stratified by time from phlebotomy to case diagnosis, the sCD27-TCL and all three DLBCL associations were equivalent across both follow-up periods (<7.5, ≥7.5 years). For other analyte-subtype comparisons, associations were stronger for the follow-up period closer to phlebotomy, particularly for indolent subtypes. In conclusion, we found robust evidence of an association between these immune markers and DLBCL, consistent with hypotheses that mechanisms related to immune activation are important in its pathogenesis. Our other findings, particularly for the rarer subtypes MZL and TCL, require further investigation., (© 2022 UICC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Objectives: Given mixed evidence for carcinogenicity of current-use herbicides, we studied the relationship between occupational herbicide use and risk of non-Hodgkin's lymphoma (NHL) in a large, pooled study., Methods: We pooled data from 10 case-control studies participating in the International Lymphoma Epidemiology Consortium, including 9229 cases and 9626 controls from North America, the European Union and Australia. Herbicide use was coded from self-report or by expert assessment in the individual studies, for herbicide groups (eg, phenoxy herbicides) and active ingredients (eg, 2,4-dichlorophenoxyacetic acid (2,4-D), glyphosate). The association between each herbicide and NHL risk was estimated using logistic regression to produce ORs and 95% CIs, with adjustment for sociodemographic factors, farming and other pesticides., Results: We found no substantial association of all NHL risk with ever-use of any herbicide (OR=1.10, 95% CI: 0.94 to 1.29), nor with herbicide groups or active ingredients. Elevations in risk were observed for NHL subtypes with longer duration of phenoxy herbicide use, such as for any phenoxy herbicide with multiple myeloma (>25.5 years, OR=1.78, 95% CI: 0.74 to 4.27), 2,4-D with diffuse large B-cell lymphoma (>25.5 years, OR=1.47, 95% CI: 0.67 to 3.21) and other (non-2,4-D) phenoxy herbicides with T-cell lymphoma (>6 years, lagged 10 years, OR=3.24, 95% CI: 1.03 to 10.2). An association between glyphosate and follicular lymphoma (lagged 10 years: OR=1.48, 95% CI: 0.98 to 2.25) was fairly consistent across analyses., Conclusions: Most of the herbicides examined were not associated with NHL risk. However, associations of phenoxy herbicides and glyphosate with particular NHL subtypes underscore the importance of estimating subtype-specific risks., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The use of bio-indicators is an emerging, cost-effective alternative approach to identifying air pollution and assessing the need for additional air monitoring. This community science project explores the use of moss samples as bio-indicators of the distribution of metal air particulates in two residential neighborhoods of the industrial Duwamish Valley located in Seattle, WA (USA). We applied geographically weighted regression to data from 61 youth-collected samples to assess the location-specific area-level spatial predictors of the concentrations of 25 elements with focus on five heavy metals of concern due to health and environmental considerations. Spatial predictors included traffic volume, industrial land uses, major roadways, the airport, dirt roads, the Duwamish River, impervious surfaces, tree canopy cover, and sociodemographics. Traffic volume surrounding sample locations was the most consistent positive predictor of increasing heavy metal concentration. Greater distance from the heavy-industry corridor surrounding the Duwamish River predicted lower concentrations of all metals, with statistically significant associations for chromium and lead in some areas. As the distance from dirt roads increased, the concentration of arsenic and chromium decreased significantly. Percent tree canopy within 200 m of sample locations was a significant protective factor for cadmium concentrations. In addition, percent people of color was significantly positively associated with increasing lead, chromium and nickel concentrations. Our findings underscore the potential influence of heavy industry and mobile sources on heavy metal concentrations, the buffering potential of trees in local environments, and persistent opportunity to improve environmental justice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Vegetation may influence asthma exacerbation through effects on aeroallergens, localized climates, air pollution, or children's behaviors and stress levels. We investigated the association between residential vegetation and asthma exacerbation by conducting a matched case-control study based on electronic health records of asthma patients, from the Children's Hospital of Philadelphia (CHOP). Our study included 17,639 exacerbation case events and 34,681 controls selected from non-exacerbation clinical visits for asthma, matched to cases by age, sex, race/ethnicity, public payment source, and residential proximity to the CHOP main campus ED and hospital. Overall greenness, tree canopy, grass/shrub cover, and impervious surface were assessed near children's homes (250 m) using satellite imagery and high-resolution landcover data. We used generalized estimating equations to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between each vegetation/landcover measure and asthma exacerbation, with adjustment for seasonal and sociodemographic factors-for all cases, and for cases defined by diagnosis setting and exacerbation frequency. Lower odds of asthma exacerbation were observed in association with greater levels of tree canopy near the home, but only for children who experienced multiple exacerbations in a year (OR = 0.94 per 10.2% greater tree canopy coverage, 95% CI = 0.90-0.99). Our findings suggest possible protection for asthma patients from tree canopy, but differing results by case frequency suggest that potential benefits may be specific to certain subpopulations of asthmatic children., (© 2022. The New York Academy of Medicine.)

Background: A previous International Lymphoma Epidemiology (InterLymph) Consortium evaluation of joint associations between five immune gene variants and autoimmune conditions reported interactions between B-cell response-mediated autoimmune conditions and the rs1800629 genotype on risk of B-cell non-Hodgkin lymphoma (NHL) subtypes. Here, we extend that evaluation using NHL subtype-specific polygenic risk scores (PRS) constructed from loci identified in genome-wide association studies of three common B-cell NHL subtypes., Methods: In a pooled analysis of NHL cases and controls of Caucasian descent from 14 participating InterLymph studies, we evaluated joint associations between B-cell-mediated autoimmune conditions and tertile (T) of PRS for risk of diffuse large B-cell lymphoma (DLBCL; n = 1,914), follicular lymphoma (n = 1,733), and marginal zone lymphoma (MZL; n = 407), using unconditional logistic regression., Results: We demonstrated a positive association of DLBCL PRS with DLBCL risk [T2 vs. T1: OR = 1.24; 95% confidence interval (CI), 1.08-1.43; T3 vs. T1: OR = 1.81; 95% CI, 1.59-2.07; P-trend (Ptrend) < 0.0001]. DLBCL risk also increased with increasing PRS tertile among those with an autoimmune condition, being highest for those with a B-cell-mediated autoimmune condition and a T3 PRS [OR = 6.46 vs. no autoimmune condition and a T1 PRS, Ptrend < 0.0001, P-interaction (Pinteraction) = 0.49]. Follicular lymphoma and MZL risk demonstrated no evidence of joint associations or significant Pinteraction., Conclusions: Our results suggest that PRS constructed from currently known subtype-specific loci may not necessarily capture biological pathways shared with autoimmune conditions., Impact: Targeted genetic (PRS) screening among population subsets with autoimmune conditions may offer opportunities for identifying those at highest risk for (and early detection from) DLBCL., (©2022 The Authors; Published by the American Association for Cancer Research.)

Objectives: High ambient temperatures may contribute to acute asthma exacerbation, a leading cause of morbidity in children. We quantified associations between hot-season ambient temperatures and asthma exacerbation in children ages 0-18 years in Philadelphia, PA., Methods: We created a time series of daily counts of clinical encounters for asthma exacerbation at the Children's Hospital of Philadelphia linked with daily meteorological data, June-August of 2011-2016. We estimated associations between mean daily temperature (up to a 5-day lag) and asthma exacerbation using generalised quasi-Poisson distributed models, adjusted for seasonal and long-term trends, day of the week, mean relative humidity,and US holiday. In secondary analyses, we ran models with adjustment for aeroallergens, air pollutants and respiratory virus counts. We quantified overall associations, and estimates stratified by encounter location (outpatient, emergency department, inpatient), sociodemographics and comorbidities., Results: The analysis included 7637 asthma exacerbation events. High mean daily temperatures that occurred 5 days before the index date were associated with higher rates of exacerbation (rate ratio (RR) comparing 33°C-13.1°C days: 1.37, 95% CI 1.04 to 1.82). Associations were most substantial for children ages 2 to <5 years and for Hispanic and non-Hispanic black children. Adjustment for air pollutants, aeroallergens and respiratory virus counts did not substantially change RR estimates., Conclusions: This research contributes to evidence that ambient heat is associated with higher rates of asthma exacerbation in children. Further work is needed to explore the mechanisms underlying these associations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Evidence for the human health effects of pesticides is needed to inform risk assessment. We studied the relationship between occupational insecticide use and risk of non-Hodgkin lymphoma (NHL) by pooling data from nine case-control studies participating in the InterLymph Consortium, including 7909 cases and 8644 controls from North America, the European Union and Australia. Insecticide use was coded using self-report or expert assessment, for insecticide groups (eg, organophosphates, pyrethroids) and active ingredients (eg, malathion, permethrin). Associations with insecticides were estimated using logistic regression to produce odds ratios (ORs) and 95% confidence intervals (CI) for all NHL and NHL subtypes, with adjustment for study site, demographic factors and use of other pesticides. Occupational insecticide use, overall, was not associated with risk of NHL. Use of organophosphate insecticides was associated with increased risk of all NHL and the subtype follicular lymphoma, and an association was found with diazinon, in particular (ever use: OR = 2.05, 95%CI: 1.24-3.37). The carbamate insecticide, carbaryl, was associated with risk of all NHL, and the strongest associations were found with T-cell NHL for ever-use (OR = 2.44, 95%CI: 1.13-5.28) and longer duration (>8 years vs never: OR = 2.90, 95%CI: 1.02-8.25). There was no association of NHL with other broad groups of insecticides, including organochlorines and pyrethroids, and some inverse associations were estimated in relation to historical DDT use. Our findings contribute to the totality of evidence available to help inform risk decisions by public health and regulatory agencies of importance given continued, widespread use of organophosphate and carbamate insecticides., (© 2021 UICC.)

Background: Water total trihalomethanes (TTHMs) are disinfectant byproducts found in municipal water supplies. TTHM exposure has been linked to cancer and may be associated with adverse reproductive outcomes. A non-optimal cervicovaginal microbiota and low cervicovaginal beta-defensin-2 levels are associated with increased risk of spontaneous preterm birth. Whether TTHM exposure increases the risk of spontaneous preterm birth or alters the cervicovaginal microbial or immune state is unknown., Objective: Investigate associations of water TTHM levels with spontaneous preterm birth, a non-optimal cervicovaginal microbiota, and beta-defensin-2 levels in a completed, diverse, urban pregnancy cohort. We hypothesized that higher TTHM levels would be associated with spontaneous preterm birth, a non-optimal cervicovaginal microbiota, and lower beta-defensin-2 levels., Design: Methods: This was a secondary analysis of participants (n = 474) in the Motherhood & Microbiome (M&M) study (n = 2000), who lived in Philadelphia and had cervicovaginal samples analyzed for cervicovaginal microbiota composition and beta-defensin-2 levels. The microbiota was classified into community state types (CSTs). CST IV (non-optimal microbiota) is characterized by a paucity of Lactobacillus species and wide array of anaerobes. Municipal water TTHM levels were obtained from 16 sites monthly across the city of Philadelphia to establish mean residential water supply levels for each participant for the first four months of pregnancy (prior to vaginal swab collection at 16-20 weeks' gestation). Associations of water TTHM levels with spontaneous preterm birth and a non-optimal cervicovaginal microbiota birth were analyzed using multivariable logistic regression. Multivariable linear regression was used to model associations of water TTHM levels with log-transformed cervicovaginal beta-defensin-2 levels. Since water TTHM levels vary by season and beta-defensin-2 levels have been shown to differ by race, stratified models by warm (April-September) and cold (October-March) seasons as well as by self-identified race were utilized., Results: Participants' water supply TTHM levels (mean μg/L [SD]) were higher in the warm (53.5 [9.4]) than cold (33.4 [7.5]) season (p < 0.0001). TTHM levels were non-significantly higher among Black participants than non-Black participants (44.8 [13.5] vs. 41.8 [11.8], p = 0.07). No associations were detected between TTHM with spontaneous preterm birth (per SD increment of TTHM, aOR 0.94, 95%CI: 0.66, 1.34) or with CST IV (aOR 0.94, 95%CI: 0.86, 1.16). Counter to our hypothesis, we observed positive associations of water TTHM with log-transformed cervicovaginal beta-defensin-2 levels in unadjusted models (β 0.20 [95%CI: 0.02, 0.39]) per SD increment of TTHM), but the association was null after adjustment for season. However, in models adjusted for covariates including season and stratified by race, TTHM was significantly associated with lower beta-defensin-2 levels among non-Black participants (β -0.75 [95%CI: -1.43, -0.08]) but not among Black participants (β 0.17 [95%CI: -0.15, 0.49]), interaction p = 0.013)., Conclusion: We did not detect associations of water TTHM levels with spontaneous preterm birth or the structure of the cervicovaginal microbiota. However, the finding of a significant interaction between TTHM and race on beta-defensin-2 levels suggest that environmental exposures may contribute to differences in reproductive tract innate immune function by race. Future studies to delineate environmental contributions to the cervicovaginal microbial-immune state, a potentially important biologic underpinning for preterm birth, are warranted., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Fine particulate matter (PM 2.5 ) and ozone (O 3 ) air pollutants are known risk factors for asthma exacerbation. We studied the association of these air pollutants with pediatric asthma exacerbation in the Philadelphia metropolitan region, and evaluated potential effect modification by children's characteristics (e.g., race/ethnicity, atopic conditions) and environmental factors (e.g., neighborhood tree canopy, meteorological factors, aeroallergens). We conducted a time-stratified case-crossover study of 54,632 pediatric (age ≤18 years) asthma exacerbation cases occurring from 2011 to 2014, identified through electronic health records (EHR) of the Children's Hospital of Philadelphia (CHOP) health system. We applied conditional logistic regression to estimate associations between air pollution and asthma exacerbation, using daily census-tract level pollutant concentrations estimated from the EPA Fused Air Quality Surface Using Downscaling (FAQSD) files. The associations were estimated within warm (Apr-Sep) and cold (Oct-Mar) months for unlagged exposure and for cumulative effects up to 5 days after exposure, with adjustment for temperature, relative humidity, and holidays. We found small increases in odds of asthma exacerbation with higher pollutant concentrations, with positive associations (OR, comparing concentrations of 75th to 25th percentile) observed for PM 2.5 during both warm (1.03, 95% CI: 0.98-1.08) and cold months (1.05, 95% CI: 1.02-1.07), and for O 3 during cold months (1.08, 95% CI: 1.02-1.14). The exposure-response relationship with PM 2.5 during the cold months was essentially linear, whereas thresholds of effect were observed for the other associations at low-medium pollutant concentrations. Results were robust to multi-pollutant modeling and adjustment for additional covariates. We found no effect modification by most children's characteristics, while effect sizes were higher on days with detected tree and grass pollens during warm months. Our results suggest that even small decreases in pollutant concentrations could potentially reduce risk of childhood asthma exacerbation - an important finding, given the high burden of childhood asthma and known disparities in asthma control., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Research on the effect of occupation on cardiovascular health (CVH) among older women is limited., Methods: Each of the seven American Heart Association's CVH metrics was scored as ideal (1) or non-ideal (0) and summed. Multivariable logistic regression was used to estimate the odds of poor overall CVH (CVH score of 0 to 2) comparing women employed in each of the top 20 occupational categories to those not employed in that category, adjusting for age, marital status, and race/ethnicity., Results: (1) Bookkeeping, accounting, and auditing clerks; (2) first-line supervisors of sales workers; (3) first-line supervisors of office and administrative support workers; and (4) nursing, psychiatric, and home health aides were more likely to have poor overall CVH compared to women who did not work in these occupations., Conclusions: Several commonly held occupations among women were associated with poor CVH., Competing Interests: Michael, Nriagu, Ako, Wang, De Roos, Wallace, Allison, and Seguin have no relationships/conditions/circumstances that present potential conflict of interest., (Copyright © 2021 American College of Occupational and Environmental Medicine.)

Pollen from trees, grasses, and weeds can trigger asthma exacerbation in sensitized individuals. However, there are gaps in knowledge about the effects, such as the relative risks from different plant taxa and threshold levels of effect. We aimed to describe the local association between pollen and asthma exacerbation among children in the City of Philadelphia, and to evaluate whether effects are modified by children's characteristics and clinical factors (e.g., child's age, race/ethnicity, comorbidities). We conducted a time-stratified case-crossover study of pediatric (age <18 years) asthma exacerbation, with cases identified through electronic health records (EHR) of the Children's Hospital of Philadelphia (CHOP) health system from March through October in the years 2011-2016. Daily pollen counts were obtained from the local National Allergy Bureau certified pollen counter. We applied conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between the pollen level (vs. none detected) and odds of asthma exacerbation, adjusting for temperature, relative humidity, and holidays. We estimated same-day exposure effects, as well as effects from exposure lagged by up to 5 days. There were 35,040 asthma exacerbation events during the study period, with the majority occurring among black, non-Hispanic children (81.8%) and boys (60.4%). We found increased odds of asthma exacerbation among Philadelphia children in association with tree pollen, both for total tree pollen and most individual tree types. Increased odds from total tree pollen were observed at the lowest levels studied (≤5 grains/m 3 , unlagged, OR = 1.06, 95% CI: 1.02, 1.10), and exhibited a positive exposure-response pattern of effect; tree pollen levels above 1000 grains/m 3 (unlagged) were associated with 64% increased odds of asthma exacerbation (95% CI: 1.45, 1.84). Grass pollen was associated with asthma exacerbation only at levels above the 99 th percentile (52 grains/m 3 ), which occurred, on average, two days per year during the study period (with 2-day lag, OR = 1.38, 95% CI: 1.19, 1.60). There was an inverse association (reduced asthma exacerbation) with ragweed pollen that was consistent across analyses. Pollen from other weeds was associated with increased odds of asthma exacerbation, without a clear exposure-response pattern (2-day lag, significant increases ranging from 8% to 19%). Increased odds from tree pollen and weeds (other than ragweed) were higher among children with allergic rhinitis. While there are known benefits from urban vegetation for human health, there are risks as well. It is important to note, however, that pollen is released during a limited time frame each year, and advisories informed by local data can enable susceptible individuals to avoid outdoor exposure on high-risk days., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Our objectives were to 1) quantify the frequency of wheezing episodes and asthma diagnosis in young children in a large pediatric primary care network and 2) assess the variability in practice-level asthma diagnosis, accounting for common asthma risk factors and comorbidities. We hypothesized that significant variability in practice-level asthma diagnosis rates would remain after adjusting for associated predictors., Methods: We generated a retrospective longitudinal birth cohort of children who visited 1 of 31 pediatric primary care practices within the first 6 months of life from 1/2005 to 12/2016. Children were observed for up to 8 years or until the end of the observation window. We used multivariable discrete time survival models to evaluate predictors of asthma diagnosis by 3-month age intervals. We compared unadjusted and adjusted proportions of children diagnosed with asthma by practice., Results: Of the 161,502 children in the cohort, 34,578 children (21%) received at least 1 asthma diagnosis. In multivariable modeling, male gender, minority race/ethnicity, gestational age <34 weeks, allergic rhinitis, food allergy, and prior wheezing episodes were associated with asthma diagnosis. After adjusting for variation in these predictors across practices, the cumulative incidence of asthma diagnosis by practice by age 6 years ranged from 11% to 47% (interquartile range: 24%-29%)., Conclusions: Across pediatric primary care practices, adjusted incidence of asthma diagnosis by age 6 years ranged widely, though variation gauged by the interquartile range was more modest. Potential sources of practice-level variation, such as differing diagnosis thresholds and labeling of different wheezing phenotypes as "asthma," should be further investigated., (Copyright © 2020 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Extreme precipitation events may be an important environmental trigger for asthma exacerbations in children. We used a time stratified case-crossover design and data from a large electronic health record database at the Children's Hospital of Philadelphia (CHOP) to estimate associations of daily heavy precipitation (defined as > 95th percentile of the summertime distribution) with asthma exacerbation among children. We defined control days as those falling on the same day of the week within the same month and year as the case. We restricted our primary analyses to the summer months in years 2011-2016 and used conditional logistic regression models to estimate associations between heavy precipitation and acute asthma exacerbations in both outpatient (primary care, specialty care, and emergency department) and inpatient settings. We investigated numerous individual-level (e.g., age, sex, eczema diagnosis) and environmental measures (e.g., greenspace, particulate matter) as potential effect modifiers. The analysis include 13,483 asthma exacerbations in 10,434 children. Odds of asthma exacerbation were 11% higher on heavy precipitation vs. no precipitation days (95% CI: 1.02-1.21). There was little evidence of effect modification by most measures. These results suggest that heavy summertime precipitation events may contribute to asthma exacerbations. Further research using larger datasets from other health systems is needed to confirm these results, and to explore underlying mechanisms., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Timing and accumulation of work-related exposures may influence later life health. This study evaluates the association between women's work patterns and physical functioning. Method: Work history and physical functioning information was collected at baseline for U.S. women ages 50 to 79 years in the Women's Health Initiative Observational Study ( N = 75,507). We estimated life course workforce participation patterns using latent class analysis. Associations between work patterns and physical limitations were explored using modified Poisson regression. Results: Compared with working continuously, women who left the workforce early had 8% increased risk and women who worked intermittently had 5% reduced risk of physical limitations later in life. The negative association with intermittent workforce participation was stronger for women with substantively complex work (9% reduced risk) than for women with nonsubstantively complex work (2% reduced risk). Discussion : Life course work patterns and characteristics may contribute to physical functioning later in life among women.

Runoff from heavy precipitation events can lead to microbiological contamination of source waters for public drinking water supplies. Philadelphia is a city of interest for a study of waterborne acute gastrointestinal illness (AGI) because of frequent heavy precipitation, extensive impervious landcover, and combined sewer systems that lead to overflows. We conducted a time-series analysis of the association between heavy precipitation and AGI incidence in Philadelphia, served by drinking water from Delaware River and Schuylkill River source waters. AGI cases on each day during the study period (2015-2017) were captured through syndromic surveillance of patients' chief complaint upon presentation at local emergency departments. Daily precipitation was represented by measurements at the Philadelphia International Airport and by modeled precipitation within the watershed boundaries, and we also evaluated stream flowrate as a proxy of precipitation. We estimated the association using distributed lag nonlinear models, assuming a quasi-Poisson distribution of the outcome variable and with adjustment for potential confounding by seasonal and long-term time trends, ambient temperature, day-of-week, and major holidays. We observed an association between heavy precipitation and AGI incidence in Philadelphia that was primarily limited to the spring season, with significant increases in AGI that peaked from 8 to 16 days following a heavy precipitation event. For example, the increase in AGI incidence related to airport precipitation above the 95th percentile (vs no precipitation) during spring reached statistical significance on lag day 7, peaked on day 16 (102% increase, 95% confidence interval: 16%, 252%), and declined while remaining significantly elevated through day 28. Similar associations were observed in analyses of watershed-specific precipitation in relation to AGI cases within the populations served by drinking water from each river. Our results suggest that heavy precipitation events in Philadelphia result in detectable local increases in waterborne AGI., Competing Interests: The authors have declared that they have no competing interests.

Objective: To quantify the association between heat and infant mortality and identify factors that influence infant vulnerability to heat., Methods: We conducted a time-stratified case-crossover analysis of associations between ambient temperature and infant mortality in Philadelphia, Pennsylvania, during the warm months of 2000 through 2015. We used conditional logistic regression models to estimate associations of infant mortality with daily temperatures on the day of death (lag 0) and for averaging periods of 0 to 1 to 0 to 3 days before the day of death. We explored modification of associations by individual and census tract-level characteristics and by amounts of green space., Results: Risk of infant mortality increased by 22.4% (95% confidence interval [CI] = 5.0%, 42.6%) for every 1°C increase in minimum daily temperature over 23.9°C on the day of death. We observed limited evidence of effect modification across strata of the covariates., Conclusions: Our results contribute to a growing body of evidence that infants are a subpopulation that is particularly vulnerable to climate change effects. Further research using large data sets is critically needed to elucidate modifiable factors that may protect infants against heat vulnerability.

Background: Women comprise nearly half of the labor force in our society, but the impact of the occupational psychical activity on women's heart health in later life was unclear. We conducted a case-cohort study to assess the association of occupational physical activity (OPA), alone and jointly with leisure-time physical activity (LTPA) and risk of coronary heart disease (CHD)., Methods: We included women enrolled in Women's Health Initiative Observational Study who provided an occupational history at baseline and were followed until 2013 for the first occurrence of myocardial infarction or death from CHD (mean age ± SD = 63.4 ± 7.2). A total of 5,243 women free of CHD at baseline were randomly selected into a subcohort and 3,421 CHD events were adjudicated during follow-up. Through linkage of Standard Occupational Classification codes to the Occupational Information Network, we assessed cumulative and most recent exposure of OPA. LTPA was assessed through Women's Health Initiative's physical activity questionnaire. Weighted Cox proportional hazard models were used to evaluate CHD risk., Results: After adjustment for demographic and socioeconomic factors, levels of OPA were not associated with CHD risk. Compared with women with low OPA and high LTPA, women with moderate to high cumulative OPA and low LTPA had relative high CHD risk (hazard ratio [HR]: 1.54, 95% confidence interval [CI]: 1.26, 1.88 for moderate OPA and HR: 1.46. 95% CI: 1.20, 1.78 for high OPA)., Discussion: Results from this study suggest no overall association between lifetime OPA and CHD risk in women, but the impact of OPA varies by LTPA levels., (© The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Despite mounting evidence that urban greenspace protects against mortality in adults, few studies have explored the relationship between greenspace and death among infants. Here, we describe results from an analysis of associations between greenness and infant mortality in Philadelphia, PA. We used images of the normalized difference vegetation index (NDVI), derived from processed satellite data, to estimate greenness density in each census tract. We linked these data with census tract level counts of total infant mortality cases (n = 963) and births (n = 113,610) in years 2010-2014, and used Bayesian spatial areal unit, conditional autoregressive models to estimate associations between greenness and infant mortality. The models included a set of random effects to account for spatial autocorrelation between neighboring census tracts. Infant mortality counts were modeled using a Poisson distribution, and the logarithm of total births in each census tract was specified as the offset term. The following variables were included as potential confounders and effect modifiers: percentage non-Hispanic black, percentage living below the poverty line, an indicator of housing quality, and population density. In adjusted models, the rate of infant mortality was 27% higher in less green compared to more green tracts (95% CI 1.02-1.59). These results contribute further evidence that greenspace may be a health promoting environmental asset.

Epidemiological studies consistently show an association between wildfire-related smoke exposure and adverse respiratory health. We conducted a systematic review of evidence in published literature pertaining to heterogeneity of respiratory effects from this exposure in North America. We calculated the within-study ratio of relative risks (RRR) and 95% confidence intervals (CI) to examine heterogeneity of effect by population subgroup, and then summarized the RRRs using meta-analysis. We found evidence of a greater effect of wildfire smoke on respiratory health among females relative to males for asthma (RRR: 1.035, 95% CI: 1.013, 1.057) and chronic obstructive pulmonary disease (RRR: 1.018, 95% CI: 1.003, 1.032). There was evidence of a lower relative risk for all respiratory outcomes among youth compared to adults (RRR: 0.976, 95% CI: 0.963, 0.989). We also found wildfire smoke effects stratified by income, race, education, health behaviors, access to care, housing occupancy, geographic region, and urban/rural status. However, data were insufficient to quantitatively evaluate effect modification by these characteristics. While we found evidence that certain demographic subgroups of the population are more susceptible to respiratory health outcomes from wildfire smoke, it is unclear whether this information can be used to inform policy aimed to reduce health impact of wildfires.

Objectives: To investigate the association between occupational exposure to aromatic hydrocarbon solvents and risk of multiple myeloma (MM) in a large, consortium-based study., Methods: We pooled data on 2854 cases and 10 743 controls from nine studies participating in the InterLymph consortium. Occupational exposures to benzene, toluene and xylene were assigned by a job-exposure matrix, coupled with 'correction' of exposure probability by self-reported or expert-assessed exposure from the individual studies. Cumulative intensity was calculated as the job-specific exposure intensity multiplied by job duration, summed across jobs. Associations were estimated using logistic regression, with inclusion of covariates for study matching factors and other potential confounders. We repeated our main analysis using random-effects meta-analysis to evaluate heterogeneity of effect., Results: Benzene, toluene and xylene were each associated with MM. For the three solvents, the highest quartile of high-probability cumulative intensity exposure (vs unexposed) was associated with 42% to 63% increased risks of MM. Associations with toluene and xylene exposures were fairly consistent and robust to sensitivity analyses. The estimated effect for benzene was moderately heterogeneous between the studies. Each solvent's association with MM was stronger for exposure occurring within 20 years of diagnosis than with exposure lagged by more than 20 years., Conclusions: Our study adds important evidence for a role of aromatic hydrocarbon solvents in causation of MM. The difficulty in disentangling individual compounds in this group and a lack of data on potential carcinogenicity of toluene and xylene, in widespread current use, underscore a need for further epidemiological evaluation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Although many studies have investigated the association between trichloroethylene (TCE) exposure and non-Hodgkin's lymphoma (NHL), less is known about other chlorinated solvents. We extended our previous analysis of occupational TCE exposure in a multicentre population-based case-control study of NHL to investigate associations with five additional chlorinated solvents: 1,1,1,-trichloroethane, carbon tetrachloride, chloroform, methylene chloride and perchloroethylene., Methods: Cases (n=1189) and controls (n=982) provided detailed information on their occupational histories and workplace exposure to chlorinated solvents for selected occupations using job-specific interview modules. An industrial hygienist used this information and a review of the literature to assess occupational exposure to chlorinated solvents. We computed ORs and 95% CIs for different exposure metrics, with the unexposed group as the referent. We also computed ORs by NHL subtype., Results: High cumulative hours exposed to carbon tetrachloride was associated with NHL (>520 hours: OR 1.9; 95% CI 1.0 to 3.6; P trend =0.04). This association remained after restricting to jobs with high-intensity exposure (OR 2.0; 95% CI 1.1 to 3.8; P=0.03) and ≥90% exposure probability (OR 2.1; 95% CI 1.0 to 4.3; P=0.03), adjusting for TCE (OR 2.1; 95% CI 1.0- to 4.1; P=0.04) and incorporating a 15-year lag (OR 1.9; 95% CI 1.0 to 3.6; P=0.06). The other evaluated chlorinated solvents were not associated with NHL., Conclusions: This is the first study using high-quality quantitative exposure assessment methods to identify a statistically significant elevated association between occupational exposure to carbon tetrachloride and NHL. Our findings, although limited by a small number of exposed cases, offer evidence that carbon tetrachloride may be a lymphomagen., Competing Interests: Competing interests: PAS is employed by Stewart Exposure Assessments, LLC (Arlington, Virginia, USA)., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Glyphosate is the most commonly used herbicide worldwide, with both residential and agricultural uses. In 2015, the International Agency for Research on Cancer classified glyphosate as "probably carcinogenic to humans," noting strong mechanistic evidence and positive associations for non-Hodgkin lymphoma (NHL) in some epidemiologic studies. A previous evaluation in the Agricultural Health Study (AHS) with follow-up through 2001 found no statistically significant associations with glyphosate use and cancer at any site., Methods: The AHS is a prospective cohort of licensed pesticide applicators from North Carolina and Iowa. Here, we updated the previous evaluation of glyphosate with cancer incidence from registry linkages through 2012 (North Carolina)/2013 (Iowa). Lifetime days and intensity-weighted lifetime days of glyphosate use were based on self-reported information from enrollment (1993-1997) and follow-up questionnaires (1999-2005). We estimated incidence rate ratios (RRs) and 95% confidence intervals (CIs) using Poisson regression, controlling for potential confounders, including use of other pesticides. All statistical tests were two-sided., Results: Among 54 251 applicators, 44 932 (82.8%) used glyphosate, including 5779 incident cancer cases (79.3% of all cases). In unlagged analyses, glyphosate was not statistically significantly associated with cancer at any site. However, among applicators in the highest exposure quartile, there was an increased risk of acute myeloid leukemia (AML) compared with never users (RR = 2.44, 95% CI = 0.94 to 6.32, Ptrend = .11), though this association was not statistically significant. Results for AML were similar with a five-year (RRQuartile 4 = 2.32, 95% CI = 0.98 to 5.51, Ptrend = .07) and 20-year exposure lag (RRTertile 3 = 2.04, 95% CI = 1.05 to 3.97, Ptrend = .04)., Conclusions: In this large, prospective cohort study, no association was apparent between glyphosate and any solid tumors or lymphoid malignancies overall, including NHL and its subtypes. There was some evidence of increased risk of AML among the highest exposed group that requires confirmation.

Background: Landscape characteristics, including vegetation and impervious surfaces, influence urban microclimates and may lead to within-city differences in the adverse health effects of high ambient temperatures., Objective: Our objective was to quantitatively summarize the epidemiologic literature that assessed microclimate indicators as effect measure modifiers (EMM) of the association between ambient temperature and mortality or morbidity., Methods: We systematically identified papers and abstracted relative risk estimates for hot and cool microclimate indicator strata. We calculated the ratio of the relative risks (RRR) and 95% confidence intervals (95% CI) to assess differences in health effects across strata, and pooled the RRR estimates using random effects meta-analyses., Results: Eleven papers were retained. In the pooled analyses, people living in hotter areas within cities (based on land surface temperature or modeled estimates of air temperature) had 6% higher risk of mortality/morbidity compared to those in cooler areas (95% CI: 1.03-1.09). Those living in less vegetated areas had 5% higher risk compared to those living in more vegetated areas (95% CI: 1.00-1.11)., Discussion: There is epidemiologic evidence that those living in hotter, and less vegetated areas of cities have higher risk of morbidity or mortality from higher ambient temperature. Further research with improved assessment of landscape characteristics and investigation of the joint effects of physiologic adaptation and landscape will advance the current understanding., Conclusion: This review provides quantitative evidence that intra-urban differences in landscape characteristics and micro-urban heat islands contribute to within-city variability in the health effects of high ambient temperatures., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL., Methods: GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls. Data were pooled in a random-effects meta-analysis., Results: Among the 28 SLE-related SNPs investigated, the two most convincingly associated with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome 20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01 to 1.36, p=0.0362). Of additional possible interest were rs2205960 and rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95% CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene) risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765., Conclusions: These data suggest several plausible genetic links between DLBCL and SLE., Competing Interests: Competing interests: None declared.

Background: Turbidity has been used as an indicator of microbiological contamination of drinking water in time-series studies attempting to discern the presence of waterborne gastrointestinal illness; however, the utility of turbidity as a proxy exposure measure has been questioned., Objectives: We conducted a review of epidemiological studies of the association between turbidity of drinking-water supplies and incidence of acute gastrointestinal illness (AGI), including a synthesis of the overall weight of evidence. Our goal was to evaluate the potential for causal inference from the studies., Methods: We identified 14 studies on the topic (distinct by region, time period and/or population). We evaluated each study with regard to modeling approaches, potential biases, and the strength of evidence. We also considered consistencies and differences in the collective results., Discussion: Positive associations between drinking-water turbidity and AGI incidence were found in different cities and time periods, and with both unfiltered and filtered supplies. There was some evidence for a stronger association at higher turbidity levels. The studies appeared to adequately adjust for confounding. There was fair consistency in the notable lags between turbidity measurement and AGI identification, which fell between 6 and 10 d in many studies., Conclusions: The observed associations suggest a detectable incidence of waterborne AGI from drinking water in the systems and time periods studied. However, some discrepant results indicate that the association may be context specific. Combining turbidity with seasonal and climatic factors, additional water quality measures, and treatment data may enhance predictive modeling in future studies. https://doi.org/10.1289/EHP1090.

Background: The role of air pollution in increasing susceptibility to respiratory tract infections in the cystic fibrosis (CF) population has not been well described. We recently demonstrated that chronic PM 2.5 exposure is associated with an increased risk of initial Pseudomonas aeruginosa acquisition in young children with CF. The purpose of this study was to determine whether PM 2.5 exposure is a risk factor for acquisition of other respiratory pathogens in young children with CF., Methods: We conducted a retrospective study of initial acquisition of methicillin susceptible and methicillin resistant Staphylococcus aureus (MSSA and MRSA), Stenotrophomonas maltophilia and Achromobacter xylosoxidans in U.S. children <6 years of age with CF using the CF Foundation Patient Registry, 2003-2009. Multivariable Weibull regression with interval-censored outcomes was used to evaluate the association of PM 2.5 concentration in the year prior to birth and risk of acquisition of each organism., Results: During follow-up 63%, 17%, 24%, and 5% of children acquired MSSA, MRSA, S. maltophilia, and A. xylosoxidans, respectively. A 10 μg/m 3 increase in PM 2.5 exposure was associated with a 68% increased risk of MRSA acquisition (Hazard Ratio: 1.68; 95% Confidence Interval: 1.24, 2.27). PM 2.5 was not associated with acquisition of other respiratory pathogens., Conclusions: Fine particulate matter is an independent risk factor for initial MRSA acquisition in young children with CF. These results support the increasing evidence that air pollution contributes to pulmonary morbidities in the CF community.

Background: Seasonal variations are often observed for respiratory tract infections; however, limited information is available regarding seasonal patterns of acquisition of common cystic fibrosis (CF)-related respiratory pathogens. We previously reported differential seasonal acquisition of Pseudomonas aeruginosa in young children with CF and no such variation for methicillin-susceptible Staphylococcus aureus acquisition. The purpose of this study was to describe and compare the seasonal incidence of acquisition of other respiratory bacterial pathogens in young children with CF., Methods: We conducted a retrospective study to describe and compare the seasonal incidence of methicillin-resistant Staphylococcus aureus (MRSA), Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and Haemophilus influenzae acquisition in young CF patients residing in the U.S. using the Cystic Fibrosis Foundation National Patient Registry, 2003-2009. Log-linear overdispersed Poisson regression was used to evaluate seasonal acquisition of each of these pathogens., Results: A total of 4552 children met inclusion criteria. During follow-up 910 (20%), 1161 (26%), 228 (5%), and 2148 (47%) children acquired MRSA, S. maltophilia, A. xylosoxidans and H. influenzae, respectively. Compared to winter season, MRSA was less frequently acquired in spring (Incidence Rate Ratio [IRR]: 0.79; 95% Confidence Interval [CI]: 0.65, 0.96) and summer (IRR: 0.69; 95% CI: 0.57, 0.84) seasons. Similarly, a lower rate of A. xylosoxidans acquisition was observed in spring (IRR: 0.59; 95% CI: 0.39, 0.89). For H. influenzae, summer (IRR: 0.88; 95% CI: 0.78, 0.99) and autumn (IRR: 0.78; 95% CI: 0.69, 0.88) seasons were associated with lower acquisition rates compared to winter. No seasonal variation was observed for S. maltophilia acquisition., Conclusion: Acquisition of CF-related respiratory pathogens displays seasonal variation in young children with CF, with the highest rate of acquisition for most pathogens occurring in the winter. Investigation of factors underlying these observed associations may contribute to our understanding of the aetiology of these infections and guide future infection control strategies.

Background: Multiple myeloma risk increases with higher adult body mass index (BMI). Emerging evidence also supports an association of young adult BMI with multiple myeloma. We undertook a pooled analysis of eight case-control studies to further evaluate anthropometric multiple myeloma risk factors, including young adult BMI. Methods: We conducted multivariable logistic regression analysis of usual adult anthropometric measures of 2,318 multiple myeloma cases and 9,609 controls, and of young adult BMI (age 25 or 30 years) for 1,164 cases and 3,629 controls. Results: In the pooled sample, multiple myeloma risk was positively associated with usual adult BMI; risk increased 9% per 5-kg/m 2 increase in BMI [OR, 1.09; 95% confidence interval (CI), 1.04-1.14; P = 0.007]. We observed significant heterogeneity by study design ( P = 0.04), noting the BMI-multiple myeloma association only for population-based studies ( P trend = 0.0003). Young adult BMI was also positively associated with multiple myeloma (per 5-kg/m 2 ; OR, 1.2; 95% CI, 1.1-1.3; P = 0.0002). Furthermore, we observed strong evidence of interaction between younger and usual adult BMI ( P interaction <0.0001); we noted statistically significant associations with multiple myeloma for persons overweight (25-<30 kg/m 2 ) or obese (30+ kg/m 2 ) in both younger and usual adulthood (vs. individuals consistently <25 kg/m 2 ), but not for those overweight or obese at only one time period. Conclusions: BMI-associated increases in multiple myeloma risk were highest for individuals who were overweight or obese throughout adulthood. Impact: These findings provide the strongest evidence to date that earlier and later adult BMI may increase multiple myeloma risk and suggest that healthy BMI maintenance throughout life may confer an added benefit of multiple myeloma prevention. Cancer Epidemiol Biomarkers Prev; 26(6); 876-85. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Women make up almost half of the labor force with older women becoming a growing segment of the population. Work characteristics influence physical functioning and women are at particular risk for physical limitations. However, little research has explored the effects of work characteristics on women's physical functioning. U.S. women between the ages of 50 and 79 were enrolled in the Women's Health Initiative Observational Study between 1993 and 1998. Women provided job titles and years worked at their three longest-held jobs ( n = 79,147). Jobs were linked to characteristics in the Occupational Information Network. Three categories of job characteristics related to substantive complexity, physical demand, and social collaboration emerged. The association between job characteristics and physical limitations in later life, measured using a SF-36 Physical Functioning score <25th percentile, was examined using modified Poisson regression. After controlling for confounding variables, high physical demand was positively associated with physical limitations (RR = 1.09 CI: 1.06-1.12) and substantively complex work was negatively associated (RR = 0.94, CI: 0.91-0.96). Jobs requiring complex problem solving, active learning, and critical thinking were associated with better physical functioning. Employers should explore opportunities to reduce strain from physically demanding jobs and incorporate substantively complex tasks into women's work to improve long-term health.