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This paper focuses on the understanding of the Random Telegraph Signal (RTS) in Single-Photon Avalanche Diodes (SPAD). We studied the RTS of two different SPAD layouts, designed and implemented in a 150-nm CMOS process, after proton irradiation. The two structures are characterized by different junction types: the first structure is constituted by a P+/Nwell junction, while the second is formed by a Pwell/Niso junction. RTS occurrence has been measured in about one thousand SPAD pixels and the differences addressed in two layouts are motivated and discussed. Hypotheses on the RTS origin are drawn by analyzing the RTS time constants and the RTS occurrence evolution as a function of the annealing temperature.

The Sister Study was designed to address gaps in the study of environment and breast cancer by taking advantage of more frequent breast cancer diagnoses among women with a sister history of breast cancer and the presumed enrichment of shared environmental and genetic exposures. The Sister Study sought a large cohort of women never diagnosed with breast cancer but who had a sister (full or half) diagnosed with breast cancer. A multifaceted national effort employed novel strategies to recruit a diverse cohort, and collected biological and environmental samples and extensive data on potential breast cancer risk factors. The Sister Study enrolled 50,884 U.S. and Puerto Rican women 35-74y of age (median 56 y). Although the majority were non-Hispanic white, well educated, and economically well off, substantial numbers of harder-to-recruit women also enrolled (race/ethnicity other than non-Hispanic white: 16%; no college degree: 35%; household income <$50,000: 26%). Although all had a biologic sister with breast cancer, 16.5% had average or lower risk of breast cancer according to the Breast Cancer Risk Assessment Tool (Gail score). Most were postmenopausal (66%), parous with a first full-term pregnancy <30y of age (79%), never-smokers (56%) with body mass indexes (BMIs) of <29.9 kg/m (70%). Few (5%) reported any cancer prior to enrollment. The Sister Study is a unique cohort designed to efficiently study environmental and genetic risk factors for breast cancer. Extensive exposure data over the life-course and baseline specimens provide important opportunities for studying breast cancer and other health outcomes in women. Collaborations are welcome. https://doi.org/10.1289/EHP1923.

Background Earlier age at menarche is an established risk factor for breast cancer. While age at menarche has been fairly stable over the past half-century, age at breast development (thelarche) has continued to decrease. Recently, earlier age at thelarche and a longer time between thelarche and menarche (pubertal tempo) were shown to be associated with increased breast cancer risk. Our objective was to examine how breast cancer risk was associated with pubertal timing and tempo in a prospective US cohort. Methods Women ages 35–74 years without a history of breast cancer, but who had a sister previously diagnosed with breast cancer, were enrolled in the Sister Study from 2003 to 2009 ( N  = 50,884). At enrollment, participants reported their ages at thelarche and menarche. Pubertal tempo was age at menarche minus age at thelarche. We estimated adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for each pubertal milestone and risk of breast cancer (invasive or ductal carcinoma in situ) using Cox proportional hazards regression. We examined whether associations between age at thelarche and breast cancer risk were modified by birth cohort, race/ethnicity, weight at age 10, and extent of breast cancer family history, as characterized by a Bayesian score based on first-degree family structure. Results During follow-up (mean = 9.3 years), 3295 eligible women were diagnosed with breast cancer. Early ages at thelarche (HR = 1.23, 95% CI 1.03–1.46 for < 10 vs. 12–13 years) and menarche (HR = 1.10, 95% CI 1.01–1.20 for < 12 vs. 12–13 years) were positively associated with breast cancer risk. Pubertal tempo was not associated with breast cancer risk (HR = 0.99, 95% CI 0.97–1.02 per 1-year longer tempo). When considering early thelarche (< 10 years) and early menarche (< 12 years) jointly, women with both had a 30% greater risk of breast cancer compared with women with neither risk factor (95% CI 1.07–1.57). The association between age at thelarche and breast cancer risk did not significantly vary by birth cohort, race/ethnicity, childhood weight, or Bayesian family history score. Conclusions Earlier ages at thelarche and menarche may enhance susceptibility to breast carcinogenesis. Age at thelarche is an important risk factor to consider given secular trends towards earlier development.

Exposure to traumatic childhood experiences (TCEs) may contribute to poor sleep in adulthood. Previous studies have been limited to mainly investigating physical and sexual abuse and did not consider betrayal trauma, or whether the victim regarded the perpetrator as someone socially close to them, the age group at occurrence, and trauma-related distress/anxiety. We used a large cohort of US women, 35-74 years old, enrolled in the Sister Study from 2003 to 2009. Self-reports of specific TCEs occurring before the age of 18 years included sexual, physical, and psychological/emotional trauma; natural disasters; major accidents; and household dysfunction. Participants self-reported average sleep duration (short: <7 hours vs recommended: 7-9 hours), sleep onset latency (SOL) at least 30 vs less than 30 minutes, at least 3 night awakenings once asleep at least 3 times/week (Night awakenings [NA], yes vs no), and napping at least 3 vs less than 3 times/week. Among 40 082 women, 55% reported a TCE, with 82% reporting betrayal trauma. Compared to women reporting no TCE, women with any TCE were more likely to report short sleep (prevalence ratio [PR] = 1.08, [95% confidence interval (CI) = 1.04 to 1.11]), longer SOL (1.11, [1.06 to 1.16]), frequent NAs (1.06, [1.00 to 1.11]), and frequent napping (1.05, [0.99 to 1.12]). The relationship between experiencing any TCE and short sleep was stronger for TCEs by a perpetrator considered socially close vs not close (1.12, [1.09 to 1.16]), SOL (1.27, [1.22 to 1.33]), NA (1.20, [1.14 to 1.27]), and napping (1.24, [1.17 to 1.32]). TCEs were associated with poor sleep in women with greater impact when the perpetrator was regarded as close. More research is warranted to better understand pathways between childhood trauma and sleep health in adulthood to develop effective interventions.

While human papillomavirus is the primary cause of cervical cancer, other factors may influence susceptibility and response to the virus. Candidates include douching and talcum powder applied in the genital area. We used Cox proportional hazards models to estimate confounder-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) in the Sister Study (2003–2009), a US cohort of women aged 35–74. We considered pre-baseline (n = 523) and incident (n = 31) cervical cancers. Douching at ages 10–13 was positively associated with pre-baseline cervical cancer (HR 1.32, 95% CI 0.86–2.03), though the association was not statistically significant. We did not observe an association between adolescent talc use and pre-baseline cervical cancer (HR 0.95, 95% CI 0.76–1.19). Douching in the year before enrollment was positively associated with incident cervical cancer (HR 2.56, 95% CI 1.10–5.99). The association between recent genital talc use and incident cervical cancer was positive, but not statistically significant (HR 1.79, 95% CI 0.78–4.11). The observed positive association between douching and incident cervical cancer is consistent with previous retrospective case–control studies. In the first study to examine genital talc use and cervical cancer, we did not see evidence of an association.

Air pollutants may contribute to the development of Parkinson's disease (PD), but empirical evidence is limited and inconsistent. This study aimed to prospectively investigate the associations of PD with ambient exposures to fine particulate matter with aerodynamic diameter ( ) and nitrogen dioxide ( ). We analyzed data from 47,108 US women from the Sister Study, enrolled from 2003-2009 (35-80 years of age) and followed through 2018. Exposures of interest included address-level ambient and in 2009 and their cumulative averages from 2009 to PD diagnosis with varying lag-years. The primary outcome was PD diagnosis between 2009 and 2018 ( ). We used multivariable Cox proportional hazards and time-varying Cox models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). exposure in 2009 was associated with PD risk in a dose-response manner. The HR and 95% CI were 1.22 (95% CI: 1.03, 1.46) for one interquartile [4.8 parts per billion (ppb)] increment in , adjusting for age, race and ethnicity, education, smoking status, alcohol drinking, caffeine intake, body mass index, physical activity, census region, residential area type, area deprivation index (ADI), and self-reported health status. The association was confirmed in secondary analyses with time-varying averaged cumulative exposures. For example, the multivariable adjusted HR for PD per increment in was 1.25 (95% CI: 1.05, 1.50) in the 2-year lag analysis using cumulative average exposure. Post hoc subgroup analyses overall confirmed the association. However, statistical interaction analyses found that the positive association of with PD risk was limited to women in urban, rural, and small town areas and women with percentile ADI but not among women from suburban areas or areas with percentile ADI. In contrast, exposure was not associated with PD risk with the possible exception for women from the Midwest region of the US ( , 95% CI: 1.20, 5.14) but not in other census regions. In this nationwide cohort of US women, higher level exposure to ambient is associated with a greater risk of PD. This finding needs to be independently confirmed and the underlying mechanisms warrant further investigation. https://doi.org/10.1289/EHP13009.

Background Early age at breast development (thelarche) has been associated with increased breast cancer risk. Average age at thelarche has declined over time, but there are few established risk factors for early thelarche. We examined associations between pre- and postnatal exposures and age at thelarche in a US cohort of women born between 1928 and 1974. Methods Breast cancer-free women ages 35–74 years who had a sister diagnosed with breast cancer were enrolled in the Sister Study from 2003 to 2009 (N = 50,884). At enrollment, participants reported information on early-life exposures and age at thelarche, which we categorized as early (≤ 10 years), average (11–13 years), and late (≥ 14 years). For each exposure, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) for early and late thelarche using polytomous logistic regression, adjusted for birth cohort, race/ethnicity and family income level in childhood. Results Early thelarche was associated with multiple prenatal exposures: gestational hypertensive disorder (OR = 1.25, 95% CI 1.09–1.43), diethylstilbestrol use (OR = 1.23, 95% CI 1.04–1.45), smoking during pregnancy (OR = 1.20, 95% CI 1.13–1.27), young maternal age (OR 1.30, 95% CI 1.16–1.47 for < 20 vs. 25–29 years), and being firstborn (OR = 1.25, 95% CI 1.17–1.33). Birthweight < 2500 g and soy formula use in infancy were positively associated with both early and late thelarche. Conclusions Associations between pre- and postnatal exposures and age at thelarche suggest that the early-life environment influences breast development and therefore may also affect breast cancer risk by altering the timing of pubertal breast development.

Poor olfaction is common in older adults and may have profound adverse implications on their health. However, little is known about the potential environmental contributors to poor olfaction. We investigated ambient fine particulate matter [PM in aerodynamic diameter ( )] and nitrogen dioxide ( ) in relation to poor olfaction in middle-aged to older women. The Sister Study is a nationwide cohort of 50,884 women in the United States with annual average air pollutant exposures estimated based on participants' residences from enrollment (2003-2009) through 2017. This analysis was limited to 3,345 women, 50-79 years of age as of January 2018, who completed the Brief Smell Identification Test (B-SIT) in 2018-2019. Poor olfaction was defined as a B-SIT score of in the primary analysis. We conducted multivariable logistic regressions, accounting for covariates and study sampling design. Overall, we found little evidence for associations of air pollutants with poor olfaction. The odds ratio (OR) and 95% confidence interval (CI) of poor olfaction for each interquartile range (IQR) increment of air pollutants in 2006 were 1.03 (95% CI: 0.91, 1.17) for (per ) and 1.08 (95% CI: 0.96, 1.22) for (per ). Results were similar in the analyses using the most recent (2017) or the cumulative average (2006-2017) air pollutant exposure data. Secondary analyses suggested potential association in certain subgroups. The OR per IQR was 1.35 (95% CI: 1.11, 1.65) for among younger participants ( years of age) and 1.87 (95% CI: 1.29, 2.71) for among current smokers. This study did not find convincing evidence that air pollutants have lasting detrimental effects on the sense of smell of women 50-79 years of age. The subgroup analyses are exploratory, and the findings need independent confirmation. https://doi.org/10.1289/EHP12066.

Background Women may have incomplete understanding of a breast cancer diagnosis, leading to inaccurate reporting in epidemiological studies. However, it is not feasible to obtain consent for medical records from all women participating in a study. Therefore, it is important to determine how well self-reported breast cancer characteristics correspond with what is found in medical records, but few studies have evaluated agreement of self-reported breast cancer characteristics with abstracted medical records. Methods We calculated the positive predictive value (PPV) of self-reports compared to medical records and explored whether participant characteristics may have influenced reporting accuracy. We analyzed data from 2518 reported breast cancer cases from the Sister Study, a large nationwide cohort of women with a family history of breast cancer. Results Medical records or pathology reports were obtained for 2066 of 2518 (82%) women who reported incident breast cancer. Breast cancer was confirmed for over 99% ( n  = 2054) of women with medical records. Confirmation rates were high for invasive, ductal, hormone receptor positive, and HER2 negative breast cancers, with little variation by race/ethnicity or age. Self-reported in situ breast cancer had a lower PPV (64.2%), with medical records showing invasive breast cancer instead, especially for older and Hispanic women. Hormone receptor (ER and PR) negative and HER2 positive self-reports had lower PPVs (83.0%, 71.6%, and 66.1% respectively). Hispanic women and women ages 65 or older at diagnosis were less able to accurately report breast cancer stage, excluding stage I. Conclusions Accuracy of reporting overall breast cancer and common subtypes is high. Despite having a family history of breast cancer and voluntarily enrolling in a study evaluating breast cancer risk factors, participants may have greater difficulty distinguishing between in situ and invasive breast cancer and may less accurately report other less common subtypes. Discrepancies may reflect women’s poor understanding of information conveyed by health care providers or lack of consistent terminology used to describe subtypes.

Background Depression could affect breast cancer risk; however, epidemiologic findings are mixed. We assessed the association of breast cancer risk with self-reported history of diagnosed depression and time-dependent antidepressant use. Methods We analyzed data from 45,746 women in the Sister Study cohort (2003–2009). Cox proportional hazard regression was used to estimate hazard ratios (HR) for breast cancer. Results During follow-up (mean = 11.7 years), 3,899 breast cancers were diagnosed. There was no association between history of diagnosed depression and risk of breast cancer (HR = 0.98, 95%CI = 0.91–1.06). However, antidepressant use was associated with reduced risk of breast cancer (HR = 0.92, 95%CI = 0.85–1.00). Comparison of antidepressant drug classes revealed a suggestion of an inverse association with selective serotonin reuptake inhibitors (SSRIs, HR = 0.90, 95%CI = 0.81–1.00). Reduction was stronger in those with BMI < 25 (HR = 0.72, 95%CI = 0.59–0.89). Conclusions Depression was not associated with breast cancer risk. We observed a suggestion of a reduction in risk associated with antidepressant use. The analysis evaluating the association by specific drug types, showed a suggestion of a reduction in breast cancer risk associated with use of SSRIs. The negative association with overall antidepressant use and SSRIs, was stronger in those with BMI < 25, which could reflect a dose effect. This was the first study to examine the association between depression, antidepressant use, and breast cancer risk in a large genetic-risk-enriched cohort.