A Comparison of Measured Airborne and Self-Reported Secondhand Smoke Exposure in the MADRES Pregnancy Cohort Study.

INTRODUCTION: Secondhand smoke (SHS) exposure during pregnancy is linked to adverse birth outcomes, such as low birth weight and preterm birth. While questionnaires are commonly used to assess SHS exposure, their ability to capture true exposure can vary, making it difficult for researchers to harmonize SHS measures. This study aimed to compare self-reported SHS exposure with measurements of airborne SHS in personal samples of pregnant women. METHODS: SHS was measured on 48-hour integrated personal PM2.5 Teflon filters collected from 204 pregnant women, and self-reported SHS exposure measures were obtained via questionnaires. Descriptive statistics were calculated for airborne SHS measures, and analysis of variance tests assessed group differences in airborne SHS concentrations by self-reported SHS exposure. RESULTS: Participants were 81% Hispanic, with a mean (SD) age of 28.2 (6.0) years. Geometric mean (SD) personal airborne SHS concentrations were 0.14 (9.41) µg/m3. Participants reporting lower education have significantly higher airborne SHS exposure (p=0.015). Mean airborne SHS concentrations were greater in those reporting longer duration with windows open in the home. There was no association between airborne SHS and self-reported SHS exposure; however, asking about the number of smokers nearby in the 48-hour monitoring period was most correlated with measured airborne SHS (Two+ smokers: 0.30µg/m3 vs. One: 0.12µg/m3 and Zero: 0.15µg/m3; p=0.230). CONCLUSIONS: Self-reported SHS exposure was not associated with measured airborne SHS in personal PM2.5 samples. This suggests exposure misclassification using SHS questionnaires and the need for harmonized and validated questions to characterize this exposure in health studies. IMPLICATIONS: This study adds to the growing body of evidence that measurement error is a major concern in pregnancy research, particularly in studies that rely on self-report questionnaires to measure secondhand smoke (SHS) exposure. The study introduces an alternative method of SHS exposure assessment using objective optical measurements, which can help improve the accuracy of exposure assessment. The findings emphasize the importance of using harmonized and validated SHS questionnaires in pregnancy health research to avoid biased effect estimates. This study can inform future research, practice, and policy development to reduce SHS exposure and its adverse health effects.

Outdoor artificial light at night, air pollution, and risk of childhood acute lymphoblastic leukemia in the California Linkage Study of Early-Onset Cancers.

Acute lymphoblastic leukemia (ALL) is the most common type of cancer in children (age 0-14 years); however, the etiology remains incompletely understood. Several environmental exposures have been linked to risk of childhood ALL, including air pollution. Closely related to air pollution and human development is artificial light at night (ALAN), which is believed to disrupt circadian rhythm and impact health. We sought to evaluate outdoor ALAN and air pollution on risk of childhood ALL. The California Linkage Study of Early-Onset Cancers is a large population-based case-control in California that identifies and links cancer diagnoses from the California Cancer Registry to birth records. For each case, 50 controls with the same year of birth were obtained from birth records. A total of 2,782 ALL cases and 139,100 controls were identified during 2000-2015. ALAN was assessed with the New World Atlas of Artificial Night Sky Brightness and air pollution with an ensemble-based air pollution model of particulate matter smaller than 2.5 microns (PM2.5). After adjusting for known and suspected risk factors, the highest tertile of ALAN was associated with an increased risk of ALL in Hispanic children (odds ratio [OR] = 1.15, 95% confidence interval [CI] 1.01-1.32). There also appeared to be a borderline association between PM2.5 level and risk of ALL among non-Hispanic White children (OR per 10 µg/m3 = 1.24, 95% CI 0.98-1.56). We observed elevated risk of ALL in Hispanic children residing in areas of greater ALAN. Further work is needed to understand the role of ALAN and air pollution in the etiology of childhood ALL in different racial/ethnic groups.

A geospatial assessment of industrial releases and pediatric neuroblastic tumours at diagnosis: A retrospective case series.

Environmental risk factors associated with malignancy of pediatric neuroblastic tumours are not well-known and few studies have examined the relationship between industrial emissions and neuroblastic tumour diagnosis. A retrospective case series of 310 patients was evaluated at a tertiary hospital in Toronto, Canada between January 2008, and December 2018. Data from the National Pollutant Release Inventory (NPRI) were used to estimate exposure for a dozen chemicals with known or suspected carcinogenicity or embryotoxicity. Comparative analysis and predictive logistic regression models for malignant versus benign neuroblastic tumours included variables for residential proximity, number, and type of industries, mean total emissions within 2 km, and inverse distance weighted (IDW) quantity of chemical-specific industrial emissions estimated within 10 and 50 km of cases. No significant difference was seen between malignant and benign cases with respect to the mean nearest residential distance to industry, the number or type of industry, or the mean total quantity of industrial emissions within a 2 km radius of residential location of cases. However, there were statistically significant differences in the interpolated IDW emissions of dioxins and furans released between 1993 and 2019 within 10 km. Concentrations were significantly higher in malignant neuroblastic tumours at 1.65 grams (g) toxic equivalent (TEQ) (SD 2.01 g TEQ) compared to benign neuroblastic tumours at 1.13 g TEQ (SD 0.84 g TEQ) (p = 0.05). Within 50 km 3 years prior to diagnosis, malignant cases were exposed to higher levels of aluminum, benzene, and nitrogen dioxide (p = 0.02, p = 0.04, and p = 0.02 respectively). Regression analysis of the IDW emissions within a 50 km radius revealed higher odds of exposure to benzene for malignant neuroblastic tumours (OR = 1.03, CI: 1.01-1.05, p = 0.01). These preliminary findings suggest a potential role of industrial emissions in the development of malignant pediatric neuroblastic tumours and underscore the need for further research to investigate these associations.

Use of predictive spatial modeling to reveal that primary cancers have distinct central nervous system topography patterns of brain metastasis.

OBJECTIVE: Brain metastasis is the most common intracranial neoplasm. Although anatomical spatial distributions of brain metastasis may vary according to primary cancer subtype, these patterns are not understood and may have major implications for treatment. METHODS: To test the hypothesis that the spatial distribution of brain metastasis varies according to cancer origin in nonrandom patterns, the authors leveraged spatial 3D coordinate data derived from stereotactic Gamma Knife radiosurgery procedures performed to treat 2106 brain metastases arising from 5 common cancer types (melanoma, lung, breast, renal, and colorectal). Two predictive topographic models (regional brain metastasis echelon model [RBMEM] and brain region susceptibility model [BRSM]) were developed and independently validated. RESULTS: RBMEM assessed the hierarchical distribution of brain metastasis to specific brain regions relative to other primary cancers and showed that distinct regions were relatively susceptible to metastasis, as follows: bilateral temporal/parietal and left frontal lobes were susceptible to lung cancer; right frontal and occipital lobes to melanoma; cerebellum to breast cancer; and brainstem to renal cell carcinoma. BRSM provided probability estimates for each cancer subtype, independent of other subtypes, to metastasize to brain regions, as follows: lung cancer had a propensity to metastasize to bilateral temporal lobes; breast cancer to right cerebellar hemisphere; melanoma to left temporal lobe; renal cell carcinoma to brainstem; and colon cancer to right cerebellar hemisphere. Patient topographic data further revealed that brain metastasis demonstrated distinct spatial patterns when stratified by patient age and tumor volume. CONCLUSIONS: These data support the hypothesis that there is a nonuniform spatial distribution of brain metastasis to preferential brain regions that varies according to cancer subtype in patients treated with Gamma Knife radiosurgery. These topographic patterns may be indicative of the abilities of various cancers to adapt to regional neural microenvironments, facilitate colonization, and establish metastasis. Although the brain microenvironment likely modulates selective seeding of metastasis, it remains unknown how the anatomical spatial distribution of brain metastasis varies according to primary cancer subtype and contributes to diagnosis. For the first time, the authors have presented two predictive models to show that brain metastasis, depending on its origin, in fact demonstrates distinct geographic spread within the central nervous system. These findings could be used as a predictive diagnostic tool and could also potentially result in future translational and therapeutic work to disrupt growth of brain metastasis on the basis of anatomical region.

Outdoor artificial light at night and risk of non-Hodgkin lymphoma among women in the California Teachers Study cohort.

BACKGROUND: Outdoor artificial light at night (ALAN) has been implicated in a growing number of adverse health outcomes. ALAN is believed to disrupt circadian rhythms and has been associated with increased inflammation, one of the hallmarks of cancer. We examined the association between outdoor ALAN and a cancer strongly associated with autoimmune and inflammatory conditions, non-Hodgkin lymphoma (NHL), in the prospective California Teachers Study cohort. METHODS: Outdoor ALAN was assigned to participant addresses at study baseline (1995-96) through use of the New World Atlas of Artificial Night Sky Brightness. Among 105,937 women followed from 1995 to 2015, linkage to the California Cancer Registry identified 873 incident cases of NHL. Age-stratified Cox proportional hazards models were used to calculate hazard ratios (HR) and 95 % confidence intervals (95 %CI) for overall NHL and the most common NHL subtypes; diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Multivariate analyses adjusted for previously reported subtype specific covariates (e.g. body mass index (BMI) for DLBCL). RESULTS: Compared to the lowest quintile, participants residing in the highest quintile of outdoor ALAN at baseline were more likely to develop NHL (HR = 1.32, 95 %CI = 1.07-1.63), and, in particular, DLBCL (HR = 1.87, 95 %CI = 1.16-3.02). The elevated risk for DLBCL remained statistically significant after adjusting for age, race/ethnicity, BMI, and socioeconomic status (DLBCL:HR = 1.87, 95 %CI = 1.16-3.02, NHL:HR = 1.32, 95 %CI = 1.07-1.63). There was no association between ALAN and FL or CLL/SLL. CONCLUSION: DLBCL risk was elevated among women residing in neighborhoods with greater outdoor ALAN. Future research in circadian disruption and DLBCL may clarify potential biological processes implicated in this association.

Flaring from Unconventional Oil and Gas Development and Birth Outcomes in the Eagle Ford Shale in South Texas.

BACKGROUND: Prior studies suggest exposure to oil and gas development (OGD) adversely affects birth outcomes, but no studies have examined flaring-the open combustion of natural gas-from OGD. OBJECTIVES: We investigated whether residential proximity to flaring from OGD was associated with shorter gestation and reduced fetal growth in the Eagle Ford Shale of south Texas. METHODS: We conducted a retrospective cohort study using administrative birth records from 2012 to 2015 (N=23,487) and satellite observations of flaring activity during pregnancy within 5km of maternal residence. Multivariate logistic and linear regression models were used to estimate associations between four outcomes (preterm birth, small-for-gestational age, continuous gestational age, and term birthweight) and exposure to a low (1-9) or high (≥10) number of nightly flare events, as compared with no exposure, while controlling for known maternal risk factors. We also examined associations with the number of oil and gas wells within 5km using data from DrillingInfo (now Enverus). RESULTS: Exposure to a high number of nightly flare events was associated with a 50% higher odds of preterm birth [odds ratio (OR)=1.50 (95% CI: 1.23, 1.83)] and shorter gestation [mean difference=-1.9 (95% CI: -2.8, -0.9) d] compared with no exposure. Effect estimates were slightly reduced after adjustment for the number of wells within 5km. In stratified models these associations were present only among Hispanic women. Flaring and fetal growth outcomes were not significantly associated. Women exposed to a high number of wells (fourth quartile, ≥27) vs. no wells within 5km had a higher odds of preterm birth [OR=1.31 (95% CI: 1.14, 1.49)], shorter gestation [-1.3 (95% CI: -1.9, -0.8) d], and lower average birthweight [-19.4 (95% CI: -36.7, -2.0) g]. DISCUSSION: Our study suggests exposure to flaring from OGD is associated with an increased risk of preterm birth. Our findings need to be confirmed in other populations. https://doi.org/10.1289/EHP6394.

Information fraction estimation based on the number of events within the standard treatment regimen.

For a Phase III randomized trial that compares survival outcomes between an experimental treatment versus a standard therapy, interim monitoring analysis is used to potentially terminate the study early based on efficacy. To preserve the nominal Type I error rate, alpha spending methods and information fractions are used to compute appropriate rejection boundaries in studies with planned interim analyses. For a one-sided trial design applied to a scenario in which the experimental therapy is superior to the standard therapy, interim monitoring should provide the opportunity to stop the trial prior to full follow-up and conclude that the experimental therapy is superior. This paper proposes a method called total control only (TCO) for estimating the information fraction based on the number of events within the standard treatment regimen. Based on theoretical derivations and simulation studies, for a maximum duration superiority design, the TCO method is not influenced by departure from the designed hazard ratio, is sensitive to detecting treatment differences, and preserves the Type I error rate compared to information fraction estimation methods that are based on total observed events. The TCO method is simple to apply, provides unbiased estimates of the information fraction, and does not rely on statistical assumptions that are impossible to verify at the design stage. For these reasons, the TCO method is a good approach when designing a maximum duration superiority trial with planned interim monitoring analyses.

Environmental Justice Dimensions of Oil and Gas Flaring in South Texas: Disproportionate Exposure among Hispanic communities.

Unconventional extraction techniques including hydraulic fracturing or "fracking" have led to a boom in oil and gas production in the Eagle Ford shale play, Texas, one of the most productive regions in the United States. Nearly 400000 people live within 5 km of an unconventional oil or gas well in this largely rural area. Flaring is associated primarily with unconventional oil wells and is an increasingly common practice in the Eagle Ford to dispose of excess gas through combustion. Flares can operate continuously for months and release hazardous air pollutants such as particulate matter and volatile organic compounds in addition to causing light and noise pollution and noxious odors. We estimated ethnic disparities in exposure to flaring using satellite observations from the Visible Infrared Imaging Spectroradiometer between March 2012-December 2016. Census blocks with majority Hispanic (>60%) populations were exposed to twice as many nightly flare events within 5 km as those with <20% Hispanics. We found that Hispanics were exposed to more flares despite being less likely than non-Hispanic White residents to live near unconventional oil and gas wells. Our findings suggest Hispanics are disproportionately exposed to flares in the Eagle Ford shale, a pattern known as environmental injustice, which could contribute to disparities in air pollution and other nuisance exposures.

Characterizing Flaring from Unconventional Oil and Gas Operations in South Texas Using Satellite Observations.

Over the past decade, increases in high-volume hydraulic fracturing for oil and gas extraction in the United States have raised concerns with residents living near wells. Flaring, or the combustion of petroleum products into the open atmosphere, is a common practice associated with oil and gas exploration and production, and has been under-examined as a potential source of exposure. We leveraged data from the Visible Infrared Imaging Spectroradiometer (VIIRS) Nightfire satellite product to characterize the extent of flaring in the Eagle Ford Shale region of south Texas, one of the most productive in the nation. Spatiotemporal hierarchical clustering identified flaring sources, and a regression-based approach combining VIIRS information with reported estimates of vented and flared gas from the Railroad Commission of Texas enabled estimation of flared gas volume at each flare. We identified 43887 distinct oil and gas flares in the study region from 2012 to 2016, with a peak in activity in 2014 and an estimated 4.5 billion cubic meters of total gas volume flared over the study period. A comparison with well permit data indicated the majority of flares were associated with oil-producing (82%) and horizontally drilled (92%) wells. Of the 49 counties in the region, 5 accounted for 71% of the total flaring. Our results suggest flaring may be a significant environmental exposure in parts of this region.