Patients With Spina Bifida Have Longer Length of Hospital Stay: Statewide Health Care Utilization in California From 1995 to 2017.

INTRODUCTION: Our goal was to better understand the health care utilization of patients with spina bifida (SB) by evaluating length of hospital stay (LOS) as well as identifying what characteristics within the SB population are contributing to shorter or longer LOS. METHODS: By querying the Department of Health Care Access and Information database of all encounters at California-licensed hospitals from January 1995 through December 2017, this study analyzed LOS as a measure of health care utilization. Patients with SB were identified using the International Classification of Diseases-9 and -10 coding system, and the data collected for both SB and control cohorts were compared using linear and logistic regression models. RESULTS: Patients with SB spent a mean LOS of 7.3 days compared to 4.7 days among the control cohort (P < .001). In multivariable analysis, SB was found to be an independent predictor of longer LOS. Within the SB encounters, increasing comorbidities and nonprivate insurance were associated with longer LOS, while being female and Hispanic were associated with a shorter LOS. CONCLUSIONS: SB is an independent predictor of longer LOS when compared to the control cohort. These findings highlight the importance of understanding the preventive health care access and needs of the vulnerable SB population to decrease hospital utilization rates.

Prospective analysis of sleep characteristics, chronotype, and risk of breast cancer in the california teachers study.

PURPOSE: Poor sleep quality and evening chronotype were associated with increased risk of breast cancer in a previous retrospective study in the California Teachers Study (CTS). The present analysis examines these sleep factors prospectively in the same cohort of women. METHODS: From the CTS, we included 1,085 incident breast cancer cases and 38,470 cancer-free participants from 2012 through 2019. We calculated time at risk and used Cox proportional hazards regression models to estimate the hazard ratios (HRs) and control for risk factors such as age, race, body mass index, family history of breast cancer, and reproductive history. The sleep factors examined were quality, latency, duration, disturbance, and sleep medication use, based on a shortened version of the Pittsburgh Sleep Quality Index, as well as chronotype (preference for morning or evening activity). This analysis was limited to women who were post-menopausal at the time they answered these sleep-related questions. RESULTS: Measures of sleep quality did not appear to be associated with subsequent breast cancer risk. The HR for evening chronotypes compared to morning chronotypes was somewhat elevated (HR 1.19, 95% CI 1.04, 1.36). CONCLUSION: While the measures of sleep quality and duration were not associated with post-menopausal breast cancer risk in this prospective analysis, the modestly elevated risk observed for evening chronotypes was consistent with the prior retrospective analysis.

Association between long-term exposure to particulate air pollution with SARS-CoV-2 infections and COVID-19 deaths in California, U.S.A.

Previous studies have reported associations between air pollution and COVID-19 morbidity and mortality, but most have limited their exposure assessment to a large area, have not used individual-level variables, nor studied infections. We examined 3.1 million SARS-CoV-2 infections and 49,691 COVID-19 deaths that occurred in California from February 2020 to February 2021 to evaluate risks associated with long-term neighborhood concentrations of particulate matter less than 2.5 µm in diameter (PM2.5). We obtained individual address data on SARS-CoV-2 infections and COVID-19 deaths and assigned 2000-2018 1km-1km gridded PM2.5 surfaces to census block groups. We included individual covariate data on age and sex, and census block data on race/ethnicity, air basin, Area Deprivation Index, and relevant comorbidities. Our analyses were based on generalized linear mixed models utilizing a Poisson distribution. Those living in the highest quintile of long-term PM2.5 exposure had risks of SARS-CoV-2 infections 20% higher and risks of COVID-19 mortality 51% higher, compared to those living in the lowest quintile of long-term PM2.5 exposure. Those living in the areas of highest long-term PM2.5 exposure were more likely to be Hispanic and more vulnerable, based on the Area Deprivation Index. The increased risks for SARS-CoV-2 Infections and COVID-19 mortality associated with highest long-term PM2.5 concentrations at the neighborhood-level in California were consistent with a growing body of literature from studies worldwide, and further highlight the importance of reducing levels of air pollution to protect public health.

Host characteristics associated with serologic inflammatory biomarkers in women.

BACKGROUND: There is growing evidence that exposure to low-grade inflammation may be associated with adverse health outcomes. METHODS: We conducted a cross-sectional study within the California Teachers Study prospective cohort, among female participants who had completed a questionnaire that asked about their health behaviors (e.g., diabetes, physical activity, body mass index, medication use) and who had donated blood within a year of their questionnaire. 822 women with stored serum were evaluated for 16 immune biomarkers. In addition, four immune pathways were constructed: Th1, pro-inflammatory/macrophage activation, B-cell activation, and T-cell activation. Odds ratios (ORs) and 95% confidence intervals (CI) for the association between host characteristics and immune biomarkers were assessed using logistic regression models. RESULT: Compared to women of a normal BMI, obese women (>30 kg/m2) were positively associated with sTNFR2, CD27, IL6, CXCL13, sIL-2Rα, and IL6Ra levels above the median, with odds ratios ranging from 1.5 to 6.0. The pro-inflammatory/macrophage activation pathway was positively associated with diabetes (OR = 2.12, 95% CI = 1.14-3.95), fueled by individual associations between diabetes and sTNF-R2, TNFα and sCD27. Physical activity was inversely associated with sTNF-R2, TNFα, CXCL13, IL6, IL10, and IFN-γ levels, particularly for the highest category of activity (5.88+ hours/week) (ORs = 0.32-0.69). In pathway-based analyses, the Th1 pathway which includes decreased levels of IL4 and IL10 was positively associated with elevated physical activity (OR = 1.5). In contrast, the pro-inflammatory, B- and T-cell activation pathways were positively associated with higher BMI (OR ranging from 1.6 to 3) and inversely associated with increasing levels of physical activity. CONCLUSIONS: Several host characteristics were associated with circulating levels of immune biomarkers, including markers of inflammation. Further understanding of associations between immune marker profiles with human disease are warranted.

Chronotype and risk of post-menopausal endometrial cancer in the California Teachers Study.

Working at night causes circadian disruption and it has been classified as a probable carcinogen. An evening chronotype, or preference for late day activity, has been shown to increase risk for several adverse health effects, such as metabolic disorders and recently, breast cancer. To further explore this emerging area of interest, we examined the association between endometrial cancer (EC) risk, another common cancer in women, and chronotype. The women in this study were members of the California Teachers Study cohort, which was established in 1995. Chronotype was reported on a subsequent questionnaire (Q5), administered in 2012-2013. The women included in this analysis were under age 90 years, were post-menopausal at Q5, and had no hysterectomy. The cancer cases, identified through linkages to the California Cancer Registry, were diagnosed between 1996 and 2014. We used unconditional logistic regression models to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of the associations between chronotype and EC diagnosis. There were 437 EC cases and 26,753 cancer-free controls included in this analysis. Controls were more likely to classify themselves as current morning chronotypes than were cases (39% and 34%, respectively). Compared to morning types, women who were definite evening types had a statistically significantly elevated OR of 1.44 (95% CI 1.09-1.91). This association was more pronounced among obese women as compared to non-obese women. For evening type compared to morning type, the OR among obese women was 2.01 (95% CI 1.23, 3.29) while the OR for non-obese women was 1.12 (95% CI 0.77, 1.63). To our knowledge, the association between EC risk and evening chronotype has not been previously reported, but is consistent with the small body of literature which suggests increased breast cancer risks among evening chronotypes. Because this study was based on a retrospective analysis in a cohort of mostly white female teachers in California, further analysis of chronotype as a potential EC risk factor should be considered in other cohorts and in prospective analyses in order to further explore this relationship.

Chronotype and postmenopausal breast cancer risk among women in the California Teachers Study.

Chronotype is the behavioral manifestation of an individual's underlying circadian rhythm, generally characterized by one's propensity to sleep at a particular time during the 24 hour cycle. Evening chronotypes ("night owls") generally suffer from worse physical and mental health compared to morning chronotypes ("morning larks") - for reasons that have yet to be explained. One hypothesis is that evening chronotypes may be more susceptible to circadian disruption, a condition where the coordinated timing of biologic processes breaks down. The role of chronotype as an independent or modifying risk factor for cancer has not been widely explored. The objective of the current study was to evaluate the risk of breast cancer associated with chronotype in a case-control study nested within the California Teachers Study (CTS) cohort. The study population consisted of 39686 post-menopausal CTS participants who provided information on chronotype by completing a questionnaire in 2012-2013. 2719 cases of primary invasive breast cancer diagnosed from 1995/1996 through completion of the chronotype questionnaire were identified by linkage of the CTS to the California Cancer Registry. 36967 CTS participants who had remained cancer-free during this same time period served as controls. Chronotype was ascertained by responses to an abbreviated version of the Horne-Ostberg Morningness-Eveningness Questionnaire (MEQ) and was characterized into five categories: definite morning, more morning than evening, neither morning or evening, more evening than morning, definite evening. Multivariable unconditional logistic regression analyses were performed to estimate the odds ratios (ORs) and 95% confidence intervals (95% CIs) for each of the chronotypes, adjusted for established breast cancer risk factors. Compared to definite morning types, definite evening types had an increased risk of breast cancer with elevated ORs that were statistically significant in both the crude (OR = 1.24, 95% CI: 1.10-1.40) and fully-adjusted models (OR = 1.20, 95% CI: 1.06-1.35). The risk estimates in the fully-adjusted model for all other chronotypes did not significantly differ from one. These results suggest that evening chronotype may be an independent risk factor for breast cancer among a population of women who are not known to have engaged in any substantial night shift work. Further research in other populations of non-shift workers is warranted.

A breast cancer case-control study of polybrominated diphenyl ether (PBDE) serum levels among California women.

PURPOSE: Polybrominated diphenyl ethers (PBDEs) are among the most persistent and pervasive global environmental contaminants. Their toxic and endocrine-disrupting properties have made them a focus of concern for breast cancer. Our objective was to evaluate the risk of breast cancer associated with serum PBDE levels in a case-control study nested within the California Teachers Study. METHODS: Participants were 902 women with invasive breast cancer (cases) and 936 with no such diagnosis (controls) who provided 10 mL of blood and were interviewed between 2011 and 2015. Blood samples were collected from cases an average of 35 months after diagnosis. PBDEs were measured in serum using automated solid phase extraction and gas chromatography/high resolution mass spectrometry. Statistical analyses were restricted to the three congeners with detection frequencies ≥75%: 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), 2,2',4,4',6-pentabromodiphenyl ether (BDE-100), and 2,2',4,4',5,5'-hexabromodiphenyl ether (BDE-153). Unconditional logistic regression was used to estimate multivariable-adjusted odds ratios (ORs) and their 95% confidence intervals (CI) for each BDE congener, adjusting for serum lipids and other potential confounders. RESULTS: The OR for each of the three BDE congeners was close to unity with a CI that included one. Analyses stratified by menopausal status, tumor hormone responsiveness, BMI, and changes in body weight yielded similarly null results. CONCLUSIONS: Our findings provide no evidence that serum levels of BDE-47, BDE-100 or BDE-153 are associated with breast cancer risk. These results should be interpreted in the context of study limitations which include the reliance on PBDE measurements that may not represent pre-diagnostic, early-life or chronic exposures and a lack of information on genetic polymorphisms and other factors which may affect endogenous estrogen levels.

Breast cancer risk and serum levels of per- and poly-fluoroalkyl substances: a case-control study nested in the California Teachers Study.

BACKGROUND: Per- and poly- fluoroalkyl substances (PFASs) are a large family of synthetic chemicals, some of which are mammary toxicants and endocrine disruptors. Their potential as breast carcinogens is unclear. Our objective was to evaluate the risk of breast cancer associated with serum PFAS concentrations in a nested case-control study within the California Teachers Study. METHODS: Participants were 902 women with invasive breast cancer (cases) and 858 with no such diagnosis (controls) who provided 10 mL of blood and were interviewed during 2011-2015, an average of 35 months after case diagnosis. PFASs were measured using automated online SPE-HPLC-MS/MS methods. Statistical analyses were restricted to six PFASs with detection frequencies ≥ 95%: PFOA (Perfluorooctanoic acid), PFNA (Perfluorononanoic acid), PFUnDA (Perfluoroundecanoic acid), PFHxS (Perfluorohexane sulfonic acid), PFOS (Perfluorooctane sulfonic acid), and MeFOSAA (2-(N-Methyl-perfluorooctane sulfonamido) acetic acid. Unconditional logistic regression was used to calculate adjusted odds ratios (ORs), estimating the breast cancer risk associated with each PFAS. RESULTS: For all cases of invasive breast cancer, none of the adjusted ORs were statistically significant but marginally significant ORs < 1.0 were observed for PFUnDA and PFHxS (p-trend = 0.08). Adjusted ORs < 1.0 for PFUnDA and PFHxS were statistically significant (p ≤ 0.05) among the 107 cases with hormone-negative tumors but not the 743 with hormone-positive tumors. CONCLUSION: Overall, these findings do not provide evidence that serum PFAS levels measured after diagnosis are related to breast cancer risk. The few inverse associations found may be due to chance or may be artifacts of study design. Future studies should incorporate information about genetic susceptibility, endogenous estrogen levels, and measurements of PFASs prior to diagnosis and treatment.

Global estimates of mortality associated with long-term exposure to outdoor fine particulate matter.

Exposure to ambient fine particulate matter (PM2.5) is a major global health concern. Quantitative estimates of attributable mortality are based on disease-specific hazard ratio models that incorporate risk information from multiple PM2.5 sources (outdoor and indoor air pollution from use of solid fuels and secondhand and active smoking), requiring assumptions about equivalent exposure and toxicity. We relax these contentious assumptions by constructing a PM2.5-mortality hazard ratio function based only on cohort studies of outdoor air pollution that covers the global exposure range. We modeled the shape of the association between PM2.5 and nonaccidental mortality using data from 41 cohorts from 16 countries-the Global Exposure Mortality Model (GEMM). We then constructed GEMMs for five specific causes of death examined by the global burden of disease (GBD). The GEMM predicts 8.9 million [95% confidence interval (CI): 7.5-10.3] deaths in 2015, a figure 30% larger than that predicted by the sum of deaths among the five specific causes (6.9; 95% CI: 4.9-8.5) and 120% larger than the risk function used in the GBD (4.0; 95% CI: 3.3-4.8). Differences between the GEMM and GBD risk functions are larger for a 20% reduction in concentrations, with the GEMM predicting 220% higher excess deaths. These results suggest that PM2.5 exposure may be related to additional causes of death than the five considered by the GBD and that incorporation of risk information from other, nonoutdoor, particle sources leads to underestimation of disease burden, especially at higher concentrations.

The influence of neighborhood socioeconomic status and ethnic enclave on endometrial cancer mortality among Hispanics and Asian Americans/Pacific Islanders in California.

PURPOSE: We investigated the role of neighborhood socioeconomic status (nSES) and residence in ethnic enclaves on mortality following endometrial cancer (EC) diagnosis among Hispanics and Asian Americans/Pacific Islanders (AAPI). METHODS: Using California Cancer Registry data, enhanced with census block group information on ethnic enclave and nSES, we examined 9,367 Hispanics and 5,878 AAPIs diagnosed with EC from 1988 to 2011. Cox proportional hazard models were used to estimate associations between all-cause and EC-specific mortality with nSES and ethnic enclaves, adjusting for subject sociodemographic and tumor characteristics. RESULTS: Hispanics in the lowest SES neighborhoods had a 39% and 36% increased risk of all-cause and EC-specific mortality, respectively, compared to Hispanics in the highest SES neighborhoods. AAPIs in the lowest SES neighborhoods had a 37% increased risk of all-cause mortality compared to AAPIs in the highest SES neighborhoods. Living in an ethnic enclave was associated with lower all-cause mortality risk for AAPIs. CONCLUSIONS: Mortality risk varied by nSES and ethnic enclave among Hispanics and AAPIs. Women living in lower SES communities experienced significantly higher risk, highlighting the need to identify the specific neighborhood factors underlying these associations so that community-based interventions may be properly targeted.

Time Trends in Per- and Polyfluoroalkyl Substances (PFASs) in California Women: Declining Serum Levels, 2011-2015.

After several decades of widespread use, some per- and polyfluoroalkyl substances (PFASs) were phased-out of use due to concerns raised by their persistent, bioaccumulative, and toxic properties. Our objective was to evaluate temporal trends in serum PFAS levels among 1257 middle-aged and older California women (ages 40-94) during a four year period, beginning approximately 5-10 years after these phase-outs began. An online SPE-HPLC-MS/MS was used to measure 10 long-chain PFASs in serum from blood collected cross-sectionally during 2011-2015 from a subset of participants in the California Teachers Study. Results from multivariable linear regression analyses indicated that serum concentrations of nearly all PFASs declined on average 10% to 20% per year. Serum levels of perfluorohexanesulfonic acid (PFHxS) did not significantly decline. With the exception of PFHxS, the downward trend in serum concentrations was evident for all PFASs across all ages, although declines were comparatively steeper among the oldest women. These findings suggest that the phase-out of some common PFASs has resulted in reduced human exposures to them. The lack of a decline for PFHxS suggests that these exposures may be ongoing and underscores the importance of continued biomonitoring and research efforts to elucidate current pathways of exposure.

Temporal Evaluation of Polybrominated Diphenyl Ether (PBDE) Serum Levels in Middle-Aged and Older California Women, 2011-2015.

In response to health concerns and widespread human exposures, two widely used commercial formulations of polybrominated diphenyl ethers (PBDEs) were banned in the United States in 2005. Initial biomonitoring data have provided early indications of reduced human exposures since these bans took effect. Our objective was to evaluate temporal trends in PBDE serum levels among a population of older California women during a four-year period, beginning approximately five years after these formulations were banned. Automated solid phase extraction and gas chromatography/high resolution mass spectrometry were used to measure PBDE levels in blood collected during 2011-2015 among 1253 women (ages 40-94) participating in the California Teachers Study. Only congeners with detection frequencies (DF) ≥ 75% were included in the present analysis: BDE-47 (DF = 88%); BDE-100 (DF = 78%); and BDE-153 (DF = 80%). Results from age- and race/ethnicity-adjusted linear regression analyses indicated modest, but statistically significant, average annual percent increases in the serum concentrations of all three PBDEs over the four-year study period. While not without limitations, these results, in the context of other biomonitoring data, suggest that earlier reported declines in PBDE levels may have plateaued and may now be starting to increase. Further biomonitoring to ascertain current trends and determinants of population exposures is warranted.

A CD80-Biased CTLA4-Ig Fusion Protein with Superior In Vivo Efficacy by Simultaneous Engineering of Affinity, Selectivity, Stability, and FcRn Binding.

Affinity- and stability-engineered variants of CTLA4-Ig fusion molecules with enhanced pharmacokinetic profiles could yield improved therapies with the potential of higher efficacy and greater convenience to patients. In this study, to our knowledge, we have, for the first time, used in vitro evolution to simultaneously optimize CTLA4 affinity and stability. We selected for improved binding to both ligands, CD80 and CD86, and screened as dimeric Fc fusions directly in functional assays to identify variants with stronger suppression of in vitro T cell activation. The majority of CTLA4 molecules showing the largest potency gains in primary in vitro and ex vivo human cell assays, using PBMCs from type 1 diabetes patients, had significant improvements in CD80, but only modest gains in CD86 binding. We furthermore observed different potency rankings between our lead molecule MEDI5265, abatacept, and belatacept, depending on which type of APC was used, with MEDI5265 consistently being the most potent. We then created fusions of both stability- and potency-optimized CTLA4 moieties with human Fc variants conferring extended plasma t1/2 In a cynomolgus model of T cell-dependent Ab response, the CTLA4-Ig variant MEDI5265 could be formulated at >100 mg/ml for s.c. administration and showed superior efficacy and significantly prolonged serum t1/2 The combination of higher stability and potency with prolonged pharmacokinetics could be compatible with very infrequent, s.c. dosing while maintaining a similar level of immune suppression to more frequently and i.v. administered licensed therapies.

Impact of Treatment and Insurance on Socioeconomic Disparities in Survival after Adolescent and Young Adult Hodgkin Lymphoma: A Population-Based Study.

BACKGROUND: Previous studies documented racial/ethnic and socioeconomic disparities in survival after Hodgkin lymphoma among adolescents and young adults (AYA), but did not consider the influence of combined-modality treatment and health insurance. METHODS: Data for 9,353 AYA patients ages 15 to 39 years when diagnosed with Hodgkin lymphoma during 1988 to 2011 were obtained from the California Cancer Registry. Using multivariate Cox proportional hazards regression, we examined the impact of sociodemographic characteristics [race/ethnicity, neighborhood socioeconomic status (SES), and health insurance], initial combined-modality treatment, and subsequent cancers on survival. RESULTS: Over the 24-year study period, we observed improvements in Hodgkin lymphoma-specific survival by diagnostic period and differences in survival by race/ethnicity, neighborhood SES, and health insurance for a subset of more recently diagnosed patients (2001-2011). In multivariable analyses, Hodgkin lymphoma-specific survival was worse for Blacks than Whites with early-stage [HR: 1.68; 95% confidence interval (CI): 1.14-2.49] and late-stage disease (HR: 1.68; 95% CI, 1.17-2.41) and for Hispanics than Whites with late-stage disease (HR: 1.58; 95% CI, 1.22-2.04). AYAs diagnosed with early-stage disease experienced worse survival if they also resided in lower SES neighborhoods (HR: 2.06; 95% CI, 1.59-2.68). Furthermore, more recently diagnosed AYAs with public health insurance or who were uninsured experienced worse Hodgkin lymphoma-specific survival (HR: 2.08; 95% CI, 1.52-2.84). CONCLUSION: Our findings identify several subgroups of Hodgkin lymphoma patients at higher risk for Hodgkin lymphoma mortality. IMPACT: Identifying and reducing barriers to recommended treatment and surveillance in these AYAs at much higher risk of mortality is essential to ameliorating these survival disparities.

Sleep duration and cancer risk in women.

PURPOSE: The objective was to conduct an analysis of sleep duration and risk of selected site-specific and groups of cancer among a large prospective cohort of California women. METHODS: The study population was comprised of 101,609 adult females participating in the California Teachers Study. All sites of invasive cancer prospectively diagnosed from baseline (1995-1996) through 2011 were identified through linkage to the California Cancer Registry (n = 12,322). Site-specific analyses focused on the following cancers: breast (n = 5,053), colorectal (n = 983), lung (n = 820), melanoma (n = 749), and endometrial (n = 957). Additionally, we evaluated a group of estrogen-mediated cancers consisting of breast, endometrial, and ovarian cancer (n = 6,458). Sleep duration was based on self-report of average time sleeping in the year prior to baseline. Cox proportional hazard models were used to calculate adjusted hazard ratios and 95 % confidence intervals (HRs, 95 % CI). RESULTS: Point estimates for all sites and site-specific cancers generally were near or below one for short sleepers (<6 h/night) and above one for long sleepers (10+ h/night); confidence intervals, however, were wide and included unity. Compared to average sleepers (7-9 h/night), long sleepers had an increased risk of the group of estrogen-mediated cancers (HR 1.22, 95 % CI 0.97-1.54, p (trend) = 0.04). CONCLUSIONS: These analyses suggest that longer sleep may be associated with increased risks of estrogen-mediated cancers. Further studies with more refined measures of sleep duration and quality are warranted.

Associations of mortality with long-term exposures to fine and ultrafine particles, species and sources: results from the California Teachers Study Cohort.

BACKGROUND: Although several cohort studies report associations between chronic exposure to fine particles (PM2.5) and mortality, few have studied the effects of chronic exposure to ultrafine (UF) particles. In addition, few studies have estimated the effects of the constituents of either PM2.5 or UF particles. METHODS: We used a statewide cohort of > 100,000 women from the California Teachers Study who were followed from 2001 through 2007. Exposure data at the residential level were provided by a chemical transport model that computed pollutant concentrations from > 900 sources in California. Besides particle mass, monthly concentrations of 11 species and 8 sources or primary particles were generated at 4-km grids. We used a Cox proportional hazards model to estimate the association between the pollutants and all-cause, cardiovascular, ischemic heart disease (IHD), and respiratory mortality. RESULTS: We observed statistically significant (p < 0.05) associations of IHD with PM2.5 mass, nitrate, elemental carbon (EC), copper (Cu), and secondary organics and the sources gas- and diesel-fueled vehicles, meat cooking, and high-sulfur fuel combustion. The hazard ratio estimate of 1.19 (95% CI: 1.08, 1.31) for IHD in association with a 10-µg/m3 increase in PM2.5 is consistent with findings from the American Cancer Society cohort. We also observed significant positive associations between IHD and several UF components including EC, Cu, metals, and mobile sources. CONCLUSIONS: Using an emissions-based model with a 4-km spatial scale, we observed significant positive associations between IHD mortality and both fine and ultrafine particle species and sources. Our results suggest that the exposure model effectively measured local exposures and facilitated the examination of the relative toxicity of particle species.

Adverse birth outcomes and maternal complications in licensed cosmetologists and manicurists in California.

PURPOSE: Due to concerns around occupational chemical exposures, this study sought to examine whether women working as cosmetologists (providing hair and nail care services) and manicurists (providing only nail care services) have an elevated risk for adverse pregnancy outcomes. METHODS: In this population-based retrospective study of cosmetologists and manicurists in California, we linked cosmetology licensee and birth registry files to identify births during 1996-2009. We compared outcomes among cosmetologists and manicurists to those of the general female population and to women from other industries. We also conducted restricted analyses for Vietnamese women, who comprise a significant proportion of the workforce. RESULTS: There was little evidence of increased risk for adverse birth outcomes, but we observed an association for small for gestational age (SGA) among Vietnamese manicurists (OR 1.39; 95 % CI 1.08-1.78) and cosmetologists (OR 1.40; 95 % CI 1.08-1.83) when compared to other working women. Some maternal complications were observed, notably an increased risk for gestational diabetes (OR 1.28; 95 % CI 1.10-1.50 for manicurists; OR 1.19; 95 % CI 1.07-1.33 for cosmetologists) compared with the general population, which further elevated when restricted to Vietnamese workers (OR 1.59; 95 % CI 1.20-2.11 for manicurists; OR 1.49; 95 % CI 1.04-2.11 for cosmetologists). Additionally, we observed an association for placentia previa among manicurists (OR 1.46; 95 % CI 1.08-1.97) and cosmetologists (OR 1.22; 95 % CI 1.02-1.46) compared with the general population. CONCLUSIONS: Women in the nail and hair care industry may be potentially at increased risk for some maternal complications, although further research is warranted. Vietnamese workers may also have increased risk for SGA.

Light at night and breast cancer risk among California teachers.

BACKGROUND: There is convincing evidence that circadian disruption mediated by exposure to light at night promotes mammary carcinogenesis in rodents. The role that light at night plays in human breast cancer etiology remains unknown. We evaluated the relationship between estimates of indoor and outdoor light at night and the risk of breast cancer among members of the California Teachers Study. METHODS: Indoor light-at-night estimates were based on questionnaire data regarding sleep habits and use of nighttime lighting while sleeping. Estimates of outdoor light at night were derived from imagery data obtained from the US Defense Meteorological Satellite Program assigned to geocoded addresses of study participants. Analyses were conducted among 106,731 California Teachers Study members who lived in California, had no prior history of breast cancer, and provided information on lighting while sleeping. Five thousand ninety-five cases of invasive breast cancer diagnosed 1995-2010 were identified via linkage to the California Cancer Registry. We used age-stratified Cox proportional hazard models to calculate hazard ratios (HRs) with 95% confidence intervals (CIs), adjusting for breast cancer risk factors and neighborhood urbanization and socioeconomic class. RESULTS: An increased risk was found for women living in areas with the highest quintile of outdoor light-at-night exposure estimates (HR = 1.12 [95% CI = 1.00-1.26]; test for trend, P = 0.06). Although more pronounced among premenopausal women (HR = 1.34 [95% CI = 1.07-1.69]; test for trend, P = 0.04), the associations did not differ statistically by menopausal status (test for interaction, P = 0.34). CONCLUSIONS: Women living in areas with high levels of ambient light at night may be at an increased risk of breast cancer. Future studies that integrate quantitative measurements of indoor and outdoor light at night are warranted.

Risk of colorectal cancer associated with active smoking among female teachers.

PURPOSE: The objective of this study was to examine the risk of colorectal cancer associated with active smoking among members of the California Teachers Study (CTS), a large cohort of female public school employees for whom highly detailed smoking information is available. METHODS: The analysis was conducted among the 122,264 CTS participants who lived in California at cohort entry in 1995/1996, had no prior history of colorectal cancer, and provided detailed smoking information. 1,205 cases of invasive colorectal cancer prospectively diagnosed in 1995-2009 were identified from the California Cancer Registry, including 650 in the proximal colon, 267 in the distal colon, and 288 in the rectum. Hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards models, stratified by age at cohort entry, and adjusted for race/ethnicity. RESULTS: Compared to never smokers, current smokers had an approximately 30% increased risk of colorectal cancer. Overall, a slightly elevated risk was also noted for former smokers. Among former smokers, risks appeared to remain elevated for up to 20 years following cessation. Risks among former and current smokers increased with greater intensity and duration of smoking. Little evidence for heterogeneity in risk was noted for colon versus rectal cancer or for different subsites within the colon. CONCLUSIONS: These results provide convincing evidence that heavy and/or long-term smoking is a risk factor for cancers of the colon and rectum. Such evidence should be considered when updating screening guidelines to include targeting people with long active smoking histories.