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In this paper we introduce the concept of purely infinite rings, which in the simple case agrees with the already existing notion of pure infiniteness. We establish various permanence properties of this notion, with respect to passage to matrix rings, corners, and behaviour under extensions, so being purely infinite is preserved under Morita equivalence. We show that a wealth of examples falls into this class, including important analogues of constructions commonly found in operator algebras. In particular, for any (s-) unital K-algebra having enough nonzero idempotents (for example, for a von Neumann regular algebra) its tensor product over K with many non-simple Leavitt path algebras is purely infinite. [ABSTRACT FROM AUTHOR]

Background: Previous epidemiologic studies have considered the effects of individual air pollutants on birth outcomes, whereas a multiple-pollutant approach is more relevant to public health policy. Objectives: The present study compared the observed effect sizes of prenatal fine particulate matter (PM) and polycyclic aromatic hydrocarbons (PAH) (a component of PM) exposures on birth outcome deficits, assessed by the single vs. two-pollutant approaches. Methods: The study sample included 455 term infants born in Krakow to non-smoking mothers, among whom personal exposures to PM and PAH were monitored in the second trimester of pregnancy. The exposure effect estimates (unstandardized and standardized regression coefficients) on birth outcomes were determined using multivariable linear regression models, accounting for relevant covariates. Results: In the single-pollutant approach, each pollutant was inversely associated with all birth outcomes. The effect size of prenatal PAH exposure on birth weight and length was twice that of PM in terms of standardized coefficients. In the two-pollutant approach, the negative effect of PM on birth weight and length, adjusted for PAH exposure, lost its significance. The standardized effect of PAH on birth weight was 10-fold stronger ( β = −0.20, p = 0.004) than that estimated for PM ( β = −0.02, p = 0.757). Conclusion: The results provide evidence that PAH had a greater impact on several measures of fetal development, especially birth weight, than PM. Though in the single-pollutant models PM had a significant impact on birth outcomes, this effect appears to be mediated by PAH. [ABSTRACT FROM AUTHOR]

Background/Objectives:Cesarean section (CS) and antibiotic use during pregnancy may alter normal maternal-offspring microbiota exchange, thereby contributing to aberrant microbial colonization of the infant gut and increased susceptibility to obesity later in life. We hypothesized that (i) maternal use of antibiotics in the second or third trimester of pregnancy and (ii) CS are independently associated with higher risk of childhood obesity in the offspring.Subjects/Methods:Of the 727 mothers enrolled in the Northern Manhattan Mothers and Children Study, we analyzed the 436 mother-child dyads followed until 7 years of age with complete data. We ascertained prenatal antibiotic use by a questionnaire administered late in the third trimester, and delivery mode by medical record. We derived age- and sex-specific body mass index (BMI) z-scores using the CDC SAS Macro, and defined obesity as BMI z⩾95th percentile. We used binary regression with robust variance and linear regression models adjusted for maternal age, ethnicity, pre-gravid BMI, maternal receipt of public assistance, birth weight, sex, breastfeeding in the first year and gestational antibiotics or delivery mode.Results:Compared with children not exposed to antibiotics during the second or third trimester, those exposed had 84% (33-154%) higher risk of obesity, after multivariable adjustment. Second or third trimester antibiotic exposure was also positively associated with BMI z-scores, waist circumference and % body fat (all P<0.05). Independent of prenatal antibiotic usage, CS was associated with 46% (8-98%) higher offspring risk of childhood obesity. Associations were similar for elective and non-elective CS.Conclusions:In our cohort, CS and exposure to antibiotics in the second or third trimester were associated with higher offspring risk of childhood obesity. Future studies that address the limitations of our study are warranted to determine if prenatal antibiotic use is associated with offspring obesity. Research is also needed to determine if alterations in neonatal gut microbiota underlie the observed associations. [ABSTRACT FROM AUTHOR]

Prior work suggests that body size and fat content may influence carcinogen-DNA adduct levels measured in white blood cells. Here we consider energy balance more broadly by assessing the impact of body mass index (BMI), physical activity and calorie intake on the presence of benzo[a]pyrene-DNA (BP-DNA) adducts in white blood cell DNA. Our cross-sectional study employed subjects from a separately conducted intervention trial. Physical activity and food intake data were collected at 12 and 15 months of follow-up, respectively. BP-DNA adducts were measured by high-performance liquid chromatography (HPLC) in white blood cell samples collected at 12 months of follow-up. Complete data on all variables were available from 143 subjects. Logistic regression showed that BMI was inversely associated with the presence of detectable adducts (OR = 0.90, p=0.02), and that hours of moderate-intensity physical activity were positively associated with the presence of detectable adducts (OR = 1.04, p=0.04). These results provide further evidence that body fat content influences carcinogen-DNA adduct levels, probably by altering the distribution of the lipophilic parent compound. [ABSTRACT FROM AUTHOR]

Background: A large body of data shows that fetal brain development is vulnerable to disruption by air pollution experienced by the mother during pregnancy, adversely affecting cognitive and psychomotor capabilities during childhood (De Asis-Cruz et al., Biol Psychiatry 7:480-90, 2022; Morgan ZEM et al., Environ Health 22:11, 2023). This study has sought to identify gestational windows of susceptibility to prenatal exposure to air pollution., Methods: 470 African American and Latina mother/child pairs participated in a prospective cohort study based in the low-income communities of Northern Manhattan and the South Bronx, New York City. Gestational exposure to respirable particulate matter (PM 2.5 ) and nitrogen dioxide (NO 2 ) was assessed through validated models in relation to cognitive and motor development assessed at ages 1, 2, and 3 years using the Bayley-II Scales. Multiple linear regression models and distributed lag models (DLM) were used to identify critical windows of exposure by trimester and week of pregnancy., Results: By linear regression, average exposures to NO 2 during the first and second trimesters and the entire pregnancy were significantly and negatively associated with the mental developmental index (MDI) at age 1. Average exposures to PM 2.5 during the second trimester and the entire pregnancy were also significantly, inversely associated with age 1 MDI. No significant associations were found between these exposures and MDI at age 2. NO 2 exposure during the first trimester was significantly negatively associated with MDI at age 3. Using DLM, exposures to NO 2 at lags 29-30 weeks (within the first trimester) and PM 2.5 at lags 17-18 weeks (second trimester) were significantly and inversely associated with MDI at age 1. Significant, inverse associations were found between exposures to NO 2 at lag 29 weeks and PM 2.5 at lags 27-29 weeks and children's MDI at age 3. No significant associations were found between psychomotor index (PDI) and prenatal exposures to NO 2 or PM 2.5 at ages 1, 2 or 3., Conclusions: Our finding that prenatal exposure to air pollution in the first and second trimesters was associated with lower scores for cognitive development at ages 1 and 3 is of concern because of the potential consequences of these outcomes for long-term functioning. They underscore the need for stronger policies to protect pregnant individuals and offspring, particularly during vulnerable, early life-stage of development., (© 2024. The Author(s).)

Introduction: Air pollution poses serious health risks to humans, with particular harm to children., Objectives: To address the gap in understanding the efficacy of policies to reduce exposure to air pollution, we sought to assess the temporal relationship between the enactment of major air pollution and climate policies in NYC and trends in air quality during the period 1998-2021. We used previously available data from citywide monitoring and new data from the Columbia Center for Children's Environmental Health (CCCEH) longitudinal cohort studies of mothers and children living in communities in Northern Manhattan and the South Bronx., Methods: We utilized publicly available citywide air monitoring data for particulate matter (PM 2.5 ) and nitrogen dioxide (NO 2 ) from 2009 to 2021 from the New York City Community Air Survey (NYCCAS) database and CCCEH cohort data on residential exposure to PM 2.5 and NO 2 and personal exposure to polycyclic aromatic hydrocarbons (PAH) during pregnancies occurring from 1998-2016 and 1998-2021, respectively. We compared annual and overall reductions in PM 2.5 and NO 2 citywide and reductions in PAH concentrations in the cohort studies., Results: As previously reported, annual average concentrations of pollutants in NYC dropped significantly over time. Between 1998 and 2021, PM 2.5 and NO 2 concentrations were reduced citywide by 37 and 31%, respectively. In our CCCEH cohorts, between 1998 and 2016, the annual average PM 2.5 and NO 2 concentrations also decreased significantly by 51 and 48%, respectively. Between 1998 and 2020, PAH concentrations decreased significantly by 66%., Discussion/conclusion: While it is not possible to link improved air quality to a single policy, our analysis provides evidence of a cumulative beneficial effect of clean air and climate policies enacted between 1998 and 2021 both city-wide and in our cohorts residing in communities that have been disproportionately affected by air pollution. There are important implications for health benefits, particularly for children, who are known to be especially vulnerable to these exposures. The results support further environmental and social policy changes to prevent the serious health impacts of air pollution from fossil fuel emissions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lau, Guo, Miao, Ross, Riley, Wang, Herbstman and Perera.)

Background: Low mitochondria DNA copy number (mtDNAcn) has been linked to cognitive decline. However, the role of mtDNAcn in healthy cognitive development is unclear. We hypothesized early-life mtDNAcn would be associated with children's learning and memory., Methods: We quantified mtDNAcn in umbilical cord blood and child blood at ages 5-7 from participants in a prospective birth cohort. We administered the Children's Memory Scale (CMS) at ages 9-14 (N = 342) and the Wechsler Intelligence Scale for Children (WISC-IV) at ages 7 and 9 (N = 457). Associations between mtDNAcn tertiles and CMS and WISC were evaluated with linear regression and linear mixed-effects models, respectively. We examined non-linear associations using generalized additive mixed models., Results: Relative to the middle tertile of mtDNAcn, lower childhood mtDNAcn was associated with lower WISC Working Memory (β = -2.65, 95% CI [-5.24, -0.06]) and Full-Scale IQ (β = -3.71 [-6.42, -1.00]), and higher CMS Visual Memory (β = 4.70 [0.47, 8.93]). Higher childhood mtDNAcn was linked to higher CMS Verbal Memory (β = 7.75 [2.50, 13.01]). In non-linear models, higher childhood mtDNAcn was associated with lower WISC Verbal Comprehension., Conclusions: Our study provides novel evidence that mtDNAcn measured in childhood is associated with children's neurocognitive performance. mtDNAcn may be a marker of healthy child development., Impact: Mitochondrial DNA copy number (mtDNAcn) may serve as a biomarker for early-life neurocognitive performances in the children's population. Both low and high mtDNAcn may contribute to poorer neurocognition, reflected through learning and memory abilities. This research elucidated the importance of investigating mitochondrial biomarkers in healthy populations and facilitated advancements of future studies to better understand the associations between mitochondrial markers and adverse children's health outcomes., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Purpose: Previous studies suggest that external-beam partial breast irradiation (PBI) delivered twice a day can lead to increased adverse cosmesis (AC). The objective of our trial was to determine whether two regimens for PBI given once daily over 1 week resulted in acceptable AC to inform a phase III trial., Methods: Patients age ≥50 years with invasive breast cancer or ductal carcinoma in situ, ≤3 cm in size treated by lumpectomy with negative axillary nodes were randomly assigned to external-beam PBI of 30 Gy or 27.5 Gy, each given in five fractions once daily. The primary outcome was AC (fair or poor) by photographic assessment at 2 years. Secondary outcomes included AC assessed by nurse at 2 years, by patient self-assessment at 3 years, and late toxicity. On the basis of a 17% risk of AC with whole-breast irradiation, the upper bound of a two-sided 90% CI, 23% was set as the tolerance margin (OPAR, ClinicalTrials.gov identifier: NCT02637024)., Results: In total, 142 patients were randomly assigned to 30 Gy and 139 to 27.5 Gy. The median follow-up was 5 years. The mean age was 65 years, and the mean tumor size was 1.2 cm. Both schedules met acceptability criteria by photographic assessment (AC, 12.1% [90% CI, 8.2 to 17.6] for 30 Gy and 15.2% [90% CI, 10.8 to 21.1] for 27.5 Gy) and by nurse assessment. AC by patient self-assessment exceeded the 90% CI for the 30 Gy regimen. At 5 years, 16 (11.3%, 90% CI, 7.6 to 16.4) patients treated with 30 Gy and eight (5.8%, 90% CI, 3.3 to 9.9) patients treated with 27.5 Gy were observed to have grade 2 or more late toxicity., Conclusion: According to the study design, 30 Gy and 27.5 Gy resulted in acceptable cosmetic outcomes. In light of recent studies, a lower dose was chosen for the phase III trial.

Photodynamic therapy (PDT) has been used to treat cancers. It has also been used to treat infectious diseases and inflammatory conditions. PDT promotes wound healing, while clinical use of PDT for wound healing is uncommon and not thoroughly investigated. We report a 75-year-old female with a radiation-induced non-healing ulcer for five years on the chest wall postmastectomy radiotherapy. Biopsy showed epidermal erosion with dermal inflammation but no recurrent cancer. She was referred from the wound care clinic after multiple unsuccessful attempts to manage wound healing for two years involving daily home nursing visits. PDT was discussed with the patient who consented to PDT instead of hyperbaric oxygen therapy (HBOT) for fear of its side effects. Her wound improved after a total of three treatments and the process of wound healing continued for 14 months since her first treatment session. The presented case supports the beneficial effects of PDT on chronic ulceration impeding healing of a postmastectomy radiotherapy wound. To our knowledge, this report is unique in documenting details of PDT healing a chronic refractory ulcer of five years, which developed after cancer therapy (mastectomy and radiotherapy). Further clinical study of PDT is needed on wound healing post-surgery and radiation in cancer patients. An overview of HBOT in comparison with PDT for wound healing is presented., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Yu et al.)

This study aimed to assess a four-marker protein panel (4MP)'s performance, including the precursor form of surfactant protein B, cancer antigen 125, carcinoembryonic antigen, and cytokeratin-19, for predicting lung cancer in a cohort enriched with never- and ever-smokers. Blinded pre-diagnostic plasma samples collected within 2 years prior to a lung cancer diagnosis from 25 cases and 100 sex-, age-, and smoking-matched controls were obtained from the Physicians' Health Study (PHS). The 4MP yielded AUC performance estimates of 0.76 (95% CI: 0.61-0.92) and 0.69 (95% CI: 0.56-0.82) for predicting lung cancer within one year and within two years of diagnosis, respectively. When stratifying into ever-smokers and never-smokers, the 4MP had respective AUCs of 0.77 (95% CI: 0.63-0.92) and 0.72 (95% CI: 0.17-1.00) for a 1-year risk of lung cancer. The AUCs of the 4MP for predicting metastatic lung cancer within one year and two years of the blood draw were 0.95 (95% CI: 0.87-1.00) and 0.78 (95% CI: 0.62-0.94), respectively. Our findings indicate that a blood-based biomarker panel may be useful in identifying ever- and never-smokers at high risk of a diagnosis of lung cancer within one-to-two years.

Background: Obesity disproportionately affects marginalized and low-income populations. Birth parent obesity from the prenatal period and childhood has been associated with child obesity. It is unknown whether prenatal or postnatal birth parent obesity has differential effects on subsequent changes in adiposity and metabolic health in children., Objectives: We evaluated how birth parent obesity 7 y after delivery was associated with child body composition changes and cardiometabolic health in midchildhood and further assessed the influence of the perinatal and postpartum period on associations., Methods: Black and Dominican pregnant individuals were enrolled, and dyads ( n = 319) were followed up at child age 7 and 9 y. Measures included, height, weight, waist circumference (WC), and percent body fat (BF%). Multiple linear regression was used to relate postpartum weight status with child outcomes accounting for attrition, and a series of secondary analyses were conducted with additional adjustment for perinatal weight status, gestational weight gain (GWG), and/or long-term weight retention to evaluate how these factors influenced associations., Results: Almost one-quarter (23%) of birth parents and 24.1% children were classified with obesity at child age 7 y, while at 9 y, 30% of children had obesity. Birth parent obesity at child age 7 y was associated with greater changes, from ages 7 to 9 y, in child BMI z -score (β: 0.13; 95% CI: 0.02, 0.24) and BF% (β: 1.15; 95% CI: 0.22, 2.09) but not obesity at age 9 y. All observed associations crossed the null after additional adjustment for prenatal factors., Conclusions: Birth parent obesity at 7-y postpartum is associated with greater gains in child BMI z -score and BF% in midchildhood. These associations diminish after accounting for prenatal size, suggesting a lasting impact of the perinatal environment and that interventions supporting families from the prenatal period through childhood are needed., (© 2024 The Author(s).)

Determining biomarkers of responses to environmental exposures and evaluating whether they predict respiratory outcomes may help optimize environmental and medical approaches to childhood asthma. Relative mitochondrial (mt) DNA abundance and other potential mitochondrial indicators of oxidative stress may provide a sensitive metric of the child's shifting molecular responses to its changing environment. We leveraged two urban childhood cohorts (Environmental Control as Add-on Therapy in Childhood Asthma (ECATCh); Columbia Center for Children's Environmental Health (CCCEH)) to ascertain whether biomarkers in buccal mtDNA associate with airway inflammation and altered lung function over 6 months of time and capture biologic responses to multiple external stressors such as indoor allergens and fine particulate matter (PM 2.5 ). Relative mtDNA content was amplified by qPCR and methylation of transfer RNA phenylalanine/rRNA 12S (TF/RNR1), cytochrome c oxidase (CO1), and carboxypeptidase O (CPO) was measured by pyrosequencing. Data on residential exposures and respiratory outcomes were harmonized between the two cohorts. Repeated measures and multiple regression models were utilized to assess relationships between mitochondrial biomarkers, respiratory outcomes, and residential exposures (PM 2.5 , allergens), adjusted for potential confounders and time-varying asthma. We found across the 6 month visits, a 0.64 fold higher level of TF/RNR1 methylation was detected among those with asthma in comparison to those without asthma ((parameter estimate (PE) 0.64, standard error 0.28, p = 0.03). In prospective analyses, CPO methylation was associated with subsequent reduced forced vital capacity (FVC; PE -0.03, standard error 0.01, p = 0.02). Bedroom dust mouse allergen, but not indoor PM 2.5 , was associated with higher methylation of TF/RNR1 (PE 0.015, standard error 0.006, p = 0.01). Select mtDNA measures in buccal cells may indicate children's responses to toxic environmental exposures and associate selectively with asthma and lung function., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Rachel Miller reports financial support was provided by National Institutes of Health. Elizabeth Matsui reports financial support was provided by National Institutes of Health. Janelle RIvera reports financial support was provided by National Institutes of Health. Usha Govindarajulu reports financial support was provided by National Institutes of Health. Kyung Hwa Jung reports financial support was provided by National Institutes of Health. Stephanie Lovinsky-Desir reports financial support was provided by National Institutes of Health. Matthew Perzanowski reports financial support was provided by National Institutes of Health., (Copyright © 2023 Elsevier Inc. All rights reserved.)

High-quality evidence from prospective longitudinal studies in humans is essential to testing hypotheses related to the developmental origins of health and disease. In this paper, the authors draw upon their own experiences leading birth cohorts with longitudinal follow-up into adulthood to describe specific challenges and lessons learned. Challenges are substantial and grow over time. Long-term funding is essential for study operations and critical to retaining study staff, who develop relationships with participants and hold important institutional knowledge and technical skill sets. To maintain contact, we recommend that cohorts apply multiple strategies for tracking and obtain as much high-quality contact information as possible before the child's 18 th birthday. To maximize engagement, we suggest that cohorts offer flexibility in visit timing, length, location, frequency, and type. Data collection may entail multiple modalities, even at a single collection timepoint, including measures that are self-reported, research-measured, and administrative with a mix of remote and in-person collection. Many topics highly relevant for adolescent and young adult health and well-being are considered to be private in nature, and their assessment requires sensitivity. To motivate ongoing participation, cohorts must work to understand participant barriers and motivators, share scientific findings, and provide appropriate compensation for participation. It is essential for cohorts to strive for broad representation including individuals from higher risk populations, not only among the participants but also the staff. Successful longitudinal follow-up of a study population ultimately requires flexibility, adaptability, appropriate incentives, and opportunities for feedback from participants.

Purpose: The natural history of microinvasive (T1mi) breast cancer is uncertain. The objective was to evaluate long-term local and distant recurrence rates following breast conserving surgery (BCS) in a prospective cohort of patients with T1mi compared to T1a-2 disease who received whole breast irradiation (WBI) in the context of a randomized trial of hypofractionation., Methods: 1234 patients with T1-2 N0 breast cancer were randomized to receive adjuvant WBI of 42.5Gy in 16 daily fractions, or 50Gy in 25 daily fractions after BCS. An analysis of patients with T1mi tumors compared with T1a-2 disease was performed. Kaplan-Meier estimates of local recurrence (LR), distant recurrence, and overall survival (OS) were compared using the log-rank test., Results: Median follow-up was 12 years. T1mi was found in 3% (n = 38) of patients. The 10-year LR rate was 22.6% in T1mi vs. 6.9% in T1a-2 breast cancer [hazard ratio (HR) = 3.73; 95% confidence interval (CI): 1.93, 7.19; p < 0.001]. The 10-year risk of distant recurrence was 5.1% for T1mi, and 12.1% for T1a-2 disease (HR = 0.56; 95% CI: 0.19, 1.84; p = 0.36). Ten-year OS was 91.5% in T1mi and 84.4% in T1a-2 disease, (HR = 0.48; 95% CI: 0.18, 1.30; p = 0.14). Rates of LR did not differ whether treated by hypofractionation or conventional fractionation (HR = 1.21; 95% CI: 0.35, 4.18; p = 0.77)., Conclusions: The risk of LR was considerably higher in patients with T1mi compared to T1a-2 tumors, but OS remained very good. Future research should evaluate the utility of wider local excision and boost radiation to optimize local control for microinvasive breast cancer., Competing Interests: Declaration of competing interest Dr. Whelan has received in-kind funding from Exact Sciences for work not related to this study., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Polybrominated diphenyl ethers (PBDEs) were used as flame retardants and from their end-use products they can be released to accumulate within indoor environments. This may result in exposures to pregnant women with potential adverse effects on the developing fetus. While studies have shown associations between prenatal PBDE exposure and poor birth outcomes, research has mainly focused on birth weight and gestational age and may miss important indicators of newborn size., Methods: The sample included a cohort of Dominican and African American mother-child pairs from New York City recruited from 1998 to 2006. PBDE congeners (BDE-47, BDE-99, BDE-100, and BDE-153) were measured in cord serum at birth and dichotomized into low (<80th percentile) and high (>80th percentile) categories. Weight, length, head circumference, and gestational age were measured at birth and the ponderal index (birth weight/length x 100), size for gestational age, and population-based z-scores were calculated (n = 305). Separate regression analyses were conducted to estimate associations between PBDEs or PBDE sum (ng/g lipid) and birth outcomes. Quantile g-computation was performed to estimate the effect of total PBDE mixture. We also assessed effect modification by sex and ethnicity., Results: Adjusting for relevant covariates, the high exposure category of BDE-153 was associated with lower birth weight z-score (-0.25, 95% CI: -0.5, 0.0) and longer gestation (0.43 weeks, 95% CI: 0.07, 0.79). The high exposure category of BDE-99 was associated with lower birth length z-score (-0.55, 95% CI: -0.98, -0.12). There was a negative association between the overall PBDE mixture and birth length z-score (-0.10, 95% CI: -0.21, 0.00) per 1 quintile increase in PBDEs. There was no effect modification by sex or ethnicity., Conclusions: These results suggest that prenatal exposures to BDE-153, BDE-99, and total PBDE mixture are associated with birth outcomes in a cohort of Dominican and African American newborns., 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 © 2022 Elsevier Inc. All rights reserved.)

Background: Assessments of health and environmental effects of clean air and climate policies have revealed substantial health benefits due to reductions in air pollution, but have included few pediatric outcomes or assessed benefits at the neighborhood level., Objectives: We estimated benefits across a suite of child health outcomes in 42 New York City (NYC) neighborhoods under the proposed regional Transportation and Climate Initiative. We also estimated their distribution across racial/ethnic and socioeconomic groups., Methods: We estimated changes in ambient fine particulate matter (PM 2.5 ) and nitrogen dioxide (NO 2 ) concentrations associated with on-road emissions under nine different predefined cap-and-invest scenarios. Health outcomes, including selected adverse birth, respiratory, and neurodevelopmental outcomes, were estimated using a program similar to the U.S. EPA BenMAP program. We stratified the associated monetized benefits across racial/ethnic and socioeconomic groups., Results: The benefits varied widely over the different cap-and-investment scenarios. For a 25% reduction in carbon emissions from 2022 to 2032 and a strategy prioritizing public transit investments, NYC would have an estimated 48 fewer medical visits for childhood asthma, 13,000 avoided asthma exacerbations not requiring medical visits, 640 fewer respiratory illnesses unrelated to asthma, and 9 avoided adverse birth outcomes (infant mortality, preterm birth, and term low birth weight) annually, starting in 2032. The total estimated annual avoided costs are $22 million. City-wide, Black and Hispanic children would experience 1.7 times the health benefits per capita than White and Non-Hispanic White children, respectively. Under the same scenario, neighborhoods experiencing the highest poverty rates in NYC would experience about 2.5 times the health benefits per capita than the lowest poverty neighborhoods., Conclusion: A cap-and-invest strategy to reduce carbon emissions from the transportation sector could provide substantial health and monetized benefits to children in NYC through reductions in criteria pollutant concentrations, with greater benefits among Black and Hispanic children., 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 © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Prenatal exposure to air pollution disrupts cognitive, emotional, and behavioral development. The brain disturbances associated with prenatal air pollution are largely unknown., Methods: In this prospective cohort study, we estimated prenatal exposures to fine particulate matter (PM 2.5 ) and polycyclic aromatic hydrocarbons (PAH), and then assessed their associations with measures of brain anatomy, tissue microstructure, neurometabolites, and blood flow in 332 youth, 6-14 years old. We then assessed how those brain disturbances were associated with measures of intelligence, ADHD and anxiety symptoms, and socialization., Results: Both exposures were associated with thinning of dorsal parietal cortices and thickening of postero-inferior and mesial wall cortices. They were associated with smaller white matter volumes, reduced organization in white matter of the internal capsule and frontal lobe, higher metabolite concentrations in frontal cortex, reduced cortical blood flow, and greater microstructural organization in subcortical gray matter nuclei. Associations were stronger for PM 2.5 in boys and PAH in girls. Youth with low exposure accounted for most significant associations of ADHD, anxiety, socialization, and intelligence measures with cortical thickness and white matter volumes, whereas it appears that high exposures generally disrupted these neurotypical brain-behavior associations, likely because strong exposure-related effects increased the variances of these brain measures., Conclusions: The commonality of effects across exposures suggests PM 2.5 and PAH disrupt brain development through one or more common molecular pathways, such as inflammation or oxidative stress. Progressively higher exposures were associated with greater disruptions in local volumes, tissue organization, metabolite concentrations, and blood flow throughout cortical and subcortical brain regions and the white matter pathways interconnecting them. Together these affected regions comprise cortico-striato-thalamo-cortical circuits, which support the regulation of thought, emotion, and behavior., (© 2022 Association for Child and Adolescent Mental Health.)

Growing evidence links adolescent exposures to cancer risk later in life, particularly for common cancers like breast. The adolescent time period is also important for cancer risk reduction as many individual lifestyle behaviors are initiated including smoking and alcohol use. We developed a cancer risk-reduction educational tool tailored for adolescents that focused on five modifiable cancer risk factors. To contextualize risk factors in adolescents' social and physical environments, the intervention also focused on structural barriers to individual- and community-level change, with an emphasis on environmental justice or the fair treatment and meaningful involvement of all people regardless of race, color, national origin, or income with respect to the development, implementation, and enforcement of environmental laws, regulations, and policies. The educational tool consisted of a 50-min module that included an introduction to cancer biology including genetic susceptibility and environmental interactions, cancer burden in the local community, and risk reduction strategies. The module also included an interactive activity in which adolescent students identify cancer risk factors and brainstorm strategies for risk reduction at both the individual and community level. We administered the module to 12 classes of over 280 high school and college students in New York City. Cancer risk reduction strategies identified by the students included family- or peer-level strategies such as team physical activity and community-level action including improving parks and taxing sugary foods. We developed a novel and interactive cancer risk-reduction education tool focused on multiple cancers that can be adopted by other communities and educational institutions., (© 2021. American Association for Cancer Education.)

Background: Polycyclic aromatic hydrocarbons (PAH), which are found in air pollution, have carcinogenic and endocrine disrupting properties that might increase breast cancer risk. PAH exposure might be particularly detrimental during pregnancy, as this is a time when the breast tissue of both the mother and daughter is undergoing structural and functional changes. In this study, we tested the hypothesis that ambient PAH exposure during pregnancy is associated with breast tissue composition, measured one to two decades later, in adolescent daughters and their mothers., Methods: We conducted a prospective analysis using data from a New York City cohort of non-Hispanic Black and Hispanic mother-daughter dyads (recruited 1998-2006). During the third trimester of pregnancy, women wore backpacks containing a continuously operating air sampling pump for two consecutive days that measured ambient exposure to eight carcinogenic higher molecular weight nonvolatile PAH compounds (Σ8 PAH) and pyrene. When daughters (n = 186) and mothers (n = 175) reached ages 11-20 and 29-55 years, respectively, optical spectroscopy (OS) was used to evaluate measures of breast tissue composition (BTC) that positively (water content, collagen content, optical index) and negatively (lipid content) correlate with mammographic breast density, a recognized risk factor for breast cancer. Multivariable linear regression was used to evaluate associations between ambient PAH exposure and BTC, overall and by exposure to household tobacco smoke during pregnancy (yes/no). Models were adjusted for race/ethnicity, age, and percent body fat at OS., Results: No overall associations were found between ambient PAH exposure (Σ8 PAH or pyrene) and BTC, but statistically significant additive interactions between Σ8 PAH and household tobacco smoke exposure were identified for water content and optical index in both daughters and mothers (interaction p values < 0.05). Σ8 PAH exposure was associated with higher water content (β daughters  = 0.42, 95% CI = 0.15-0.68; β mothers  = 0.32, 95% CI = 0.05-0.61) and higher optical index (β daughters  = 0.38, 95% CI = 0.12-0.64; β mothers  = 0.38, 95% CI = 0.12-0.65) in those exposed to household tobacco smoke during pregnancy; no associations were found in non-smoking households (interaction p values < 0.05)., Conclusions: Exposure to ambient Σ8 PAH and tobacco smoke during pregnancy might interact synergistically to impact BTC in mothers and daughters. If replicated in other cohorts, these findings might have important implications for breast cancer risk across generations., (© 2022. The Author(s).)

Background: Given numerous publications and clinical trials regarding axillary management in breast cancer, we sought to summarize this complex literature to help clarify this field for clinicians. This systematic review focuses on the role of irradiation of the axillary nodes (locoregional nodal irradiation [LRNI]) in the management of the axilla in patients with early-stage breast cancer in various clinical settings., Methods: We searched MEDLINE and EMBASE databases, the Cochrane library, the proceedings of the ASCO, the ASTRO, the ESMO, the ESTRO, and the San Antonio Breast Cancer Symposium (2016-2019) meetings. The quality of the studies was assessed with design-specific tools. The study was registered in PROSPERO., Results: We included one systematic review, one individual patient data (IPD) meta-analysis, and five randomized controlled trials (RCTs). After axillary lymph node dissection (ALND), LRNI resulted in small benefits in breast cancer specific mortality, locoregional recurrence, and distant metastases-free survival but not overall survival. After a positive sentinel node biopsy (SLNB), LRNI may provide equivalent locoregional control and disease-free survival (DFS) compared to ALND with a lower risk of lymphedema. No randomized data is available for the neoadjuvant setting., Conclusions: The summary of the role of radiation, is relevant to radiation oncologists for choosing the correct cohort of patient requiring LRNI and to surgeons making clinical decisions regarding the timing and type of breast reconstruction offered to patients., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Adjuvant whole-breast radiotherapy (RT) is a significant part of the standard of care treatment after breast cancer (BC) conserving surgery. Modern techniques including intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) have constituted to better target coverage and critical organs sparing. However, BC survivors are at risk of developing radiation-induced cardiac toxicity. Hence, deep-inspiration breath-hold (DIBH) techniques have been implemented at many centers to further reduce cardiac exposure but require compliance. 4D-CT robust optimization can account for heart intrafractional motion per breathing phase. The optimization has been explored in cardiac sparing of breast IMRT compared to DIBH in a small sample size but has not been evaluated in substructures sparing, nor in VMAT. To provide patients who are not compliant to breath-hold with an optimal treatment approach, various heart sparing techniques need to be evaluated for statistical significance and clinical feasibility., Aim: This retrospective study aimed to provide an extensive dosimetric heart sparing comparison of free-breathing, 4D-CT-based treatment planning, including robust optimization with DIBH-based treatment planning. Combinations of forward and inverse IMRT and VMAT are also considered., Methods: Fifteen early stage left-sided BC standard treatment plans were selected. Breast, lung, left anterior descending artery (LAD), left ventricle (LV), and the whole heart were contoured on each 4D-CT phase and DIBH CT dataset. Each treatment plan was optimized using forward/inverse IMRT and VMAT on the following CT datasets: DIBH, average 4D-CT, and the complete 4D-CT dataset needed for robust optimization. Dose-volume histograms were used to compare V 5Gy Heart, mean heart dose, mean and max LAD dose, mean LV dose, and V 50% Lung., Results: All RT techniques assessed including 4D robust optimization were clinically feasible. Statistically significant differences in mean heart, LAD and LV dose, max LAD dose, and V 5Gy Heart (p < 0.01) but no difference in V 50% Lung (p = 0.29) were found between different techniques. IMRT DIBH achieved the optimal cardiac and substructure sparing among treatment plans. 4D robust IMRT had significantly greater mean heart and LV dose than DIBH IMRT (p ≤ 0.01), except LAD dose. Among free-breathing methods, no difference in all cardiac and substructure dose parameters was observed (p > 0.2) in comparing forward and inverse IMRT with average 4D-CT, inverse average 4D-CT, and 4D robust with IMRT, and between average 4D-CT VMAT and 4D robust VMAT. Only V 5Gy Heart and mean LV dose were significantly greater in 4D robust VMAT (p < 0.01) compared to DIBH VMAT. Mean heart and LV doses were significantly reduced (p < 0.01) in DIBH IMRT compared to DIBH VMAT. Moreover, mean heart and LV dose, V 5Gy Heart were significantly reduced in inverse IMRT average 4D-CT compared to average 4D-CT VMAT (p < 0.02) and in 4D robust IMRT compared to 4D robust VMAT (p < 0.04)., Conclusion: This study demonstrated the clinical feasibility of 4D robust optimization in limiting the cardiac and substructures dose during free-breathing RT with both IMRT/VMAT for patients who are not compliant with breath-hold RT. However, this study also presents that 4D robust optimization can reduce LAD dose but not fully outperform DIBH or conventional 4D-CT-based planning with IMRT/VMAT in heart sparing in treating early staged left-sided BC patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Chau et al.)

Purpose: The neoadjuvant treatment of breast cancer (NABC) is a rapidly changing area that benefits from guidelines integrating evidence with expert consensus to help direct practice. This can optimize patient outcomes by ensuring the appropriate use of evolving neoadjuvant principles., Methods: An expert panel formulated evidence-based practice recommendations spanning the entire neoadjuvant breast cancer treatment journey. These were sent for practice-based consensus across Canada using the modified Delphi methodology, through a secure online survey. Final recommendations were graded using the GRADE criteria for guidelines. The evidence was reviewed over the course of guideline development to ensure recommendations remained aligned with current relevant data., Results: Response rate to the online survey was almost 30%; representation was achieved from various medical specialties from both community and academic centres in various Canadian provinces. Two rounds of consensus were required to achieve 80% or higher consensus on 59 final statements. Five additional statements were added to reflect updated evidence but not sent for consensus., Conclusions: Key highlights of this comprehensive Canadian guideline on NABC include the use of neoadjuvant therapy for early stage triple negative and HER2 positive breast cancer, with subsequent adjuvant treatments for patients with residual disease. The use of molecular signatures, other targeted adjuvant therapies, and optimal response-based local regional management remain actively evolving areas. Many statements had evolving or limited data but still achieved high consensus, demonstrating the utility of such a guideline in helping to unify practice while further evidence evolves in this important area of breast cancer management., (© 2022. The Author(s).)

Introduction: Prenatal environmental exposures have been associated with children's cognitive, behavioral, and mental health problems, and alterations in DNA methylation have been hypothesized as an underlying biological mechanism. However, when testing this hypothesis, it is often difficult to overcome the problem of multiple comparisons in statistical testing when evaluating a large number of developmental outcomes and DNA methylation sites as potential mediators. The objective of this study is to implement a 'meet-in-the-middle' approach with a sequential roadmap to address this concern. Methods: In the Columbia Center for Children's Environmental Health birth cohort study, we implemented a 5-step sequential process for identifying CpG sites that mediate associations between prenatal environmental exposures and cognitive, behavioral, and mental health problems as measured by the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) and the Child Behavior Checklist (CBCL). These steps include 1) the identification of biological pathways that are relevant to each outcome of interest; 2) selection of a set of genes and CpGs on genes that are significantly associated with the outcomes; 3) identification of exposures that are significantly associated with selected CpGs; 4) examination of exposure-outcome relationships among those where significant CpGs were identified; and 5) mediation analysis of the selected exposures and corresponding outcomes. In this study, we considered a spectrum of environmental exposure classes including environmental phenols, pesticides, phthalates, flame retardants and air pollutants. Results: Among all considered exposures and outcomes, we found one CpG site (cg27510182) on gene (DAB1) that potentially mediates the effect of exposure to PAH on CBCL social problems at children aged 7. Conclusion: This 'meet-in-the-middle' approach attenuates concerns regarding multiple comparisons by focusing on genes and pathways that are biologically relevant for the hypothesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Guo, Riley, Durham, Margolis, Wang, Perera and Herbstman.)