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Abstract Background Evidence suggests that exposure to particulate matter with aerodynamic diameter less than 10 μm (PM10) is associated with reduced birth weight, but information is limited on the sources of PM10 and exposure misclassification from assigning exposures to place of residence at birth. Methods Trimester and source-specific PM10 exposures (PM10 from road source, local non-road source, and total source) in pregnancy were estimated using dispersion models and a full maternal residential history for 12,020 births from the Avon longitudinal study of parents and children (ALSPAC) cohort in 1990–1992 in the Bristol area. Information on birth outcomes were obtained from birth records. Maternal sociodemographic and lifestyle factors were obtained from questionnaires. We used linear regression models for continuous outcomes (birth weight, head circumference (HC), and birth length (BL) and logistic regression models for binary outcomes (preterm birth (PTB), term low birth weight (TLBW) and small for gestational age (SGA)). Sensitivity analysis was performed using multiple imputation for missing covariate data. Results After adjustment, interquartile range increases in source specific PM10 from traffic were associated with 17 to 18% increased odds of TLBW in all pregnancy periods. We also found odds of TLBW increased by 40% (OR: 1.40, 95%CI: 1.12, 1.75) and odds of SGA increased by 18% (OR: 1.18, 95%CI: 1.05, 1.32) per IQR (6.54 μg/m3) increase of total PM10 exposure in the third trimester. Conclusion This study adds to evidence that maternal PM10 exposures affect birth weight, with particular concern in relation to exposures to PM10 from road transport sources; results for total PM10 suggest greatest effect in the third trimester. Effect size estimates relate to exposures in the 1990s and are higher than those for recent studies – this may relate to reduced exposure misclassification through use of full residential history information, changes in air pollution toxicity over time and/or residual confounding.

Abstract Background Adolescence is a significant period for the gender-dependent development of lung function. Prior studies have shown that DNA methylation (DNA-M) is associated with lung function and DNA-M at some cytosine-phosphate-guanine dinucleotide sites (CpGs) changes over time. This study examined whether changes of DNA-M at lung-function-related CpGs are associated with changes in lung function during adolescence for each gender, and if so, the biological significance of the detected CpGs. Methods Genome-scale DNA-M was measured in peripheral blood samples at ages 10 (n = 330) and 18 years (n = 476) from the Isle of Wight (IOW) birth cohort in United Kingdom, using Illumina Infinium arrays (450 K and EPIC). Spirometry was conducted at both ages. A training and testing method was used to screen 402,714 CpGs for their potential associations with lung function. Linear regressions were applied to assess the association of changes in lung function with changes of DNA-M at those CpGs potentially related to lung function. Adolescence-related and personal and family-related confounders were included in the model. The analyses were stratified by gender. Multiple testing was adjusted by controlling false discovery rate of 0.05. Findings were further examined in two independent birth cohorts, the Avon Longitudinal Study of Children and Parents (ALSPAC) and the Children, Allergy, Milieu, Stockholm, Epidemiology (BAMSE) cohort. Pathway analyses were performed on genes to which the identified CpGs were mapped. Results For females, 42 CpGs showed statistically significant associations with change in FEV1/FVC, but none for change in FEV1 or FVC. No CpGs were identified for males. In replication analyses, 16 and 21 of the 42 CpGs showed the same direction of associations among the females in the ALSPAC and BAMSE cohorts, respectively, with 11 CpGs overlapping across all the three cohorts. Through pathway analyses, significant biological processes were identified that have previously been related to lung function development. Conclusions The detected 11 CpGs in all three cohorts have the potential to serve as the candidate epigenetic markers for changes in lung function during adolescence in females.

Abstract Background To identify novel epigenetic markers of adolescent asthma and replicate findings in an independent cohort, then explore whether such markers are detectable at birth, predictive of early-life wheeze, and associated with gene expression in cord blood. Methods We performed epigenome-wide screening with recursive random forest feature selection and internal validation in the IOW birth cohort. We then tested whether we could replicate these findings in the independent cohort ALSPAC and followed-up our top finding with children of the IOW cohort. Results We identified 10 CpG sites associated with adolescent asthma at a 5% false discovery rate (IOW, n = 370), five of which exhibited evidence of associations in the replication study (ALSPAC, n = 720). One site, cg16658191, within HK1 displayed particularly strong associations after cellular heterogeneity adjustments in both cohorts (ORIOW = 0.17, 95% CI 0.04–0.57) (ORALSPAC = 0.57, 95% CI 0.38–0.87). Additionally, higher expression of HK1 (OR = 3.81, 95% CI 1.41–11.77) in cord blood was predictive of wheezing in infancy (n = 82). Conclusion We identified novel associations between asthma and wheeze with methylation at cg16658191 and the expression of HK1, which may serve as markers of, predictors of, and potentially etiologic factors involved in asthma and early life wheeze.

Background Age of pubertal onset is associated with height and lung function in adulthood. It is unknown whether height growth in adolescence mediates the association of age at puberty with early adult lung function. Methods Data from the Isle of Wight (IOW) birth cohort (n=1261) were examined in the study. Ages of pubertal events, height at ages 10 and 18 years and lung function parameters (forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)) at 26 years were included in a path analysis to assess the mediation effects of height growth. Findings were tested in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Results In females in the IOW cohort, age at menarche and body hair growth showed a positive indirect association with FVC (menarche: indirect effect coefficient (IEC)=0.13, 95% CI 0.05–0.20, p=1.28×10−3; body hair growth: IEC=0.08, 95% CI 0.01–0.15, p=0.017) and FEV1 (menarche: IEC=0.09, 95% CI 0.01–0.17, p=0.028; body hair growth: IEC=0.07, 95% CI 0.01–0.14, p=0.043) at 26 years through height growth and lung function at 18 years. In males, age at body hair growth (IEC=0.08; 95% CI 0.01–0.15, p=0.047), growth spurt (IEC=0.09; 95% CI 0.01–0.17, p=0.034) and facial hair growth (IEC=0.09; 95% CI 0.02–0.16, p=0.014) had positive indirect effects on FVC at 26 years, but voice deepening did not show statistically significant indirect effects (p>0.05). For pubertal events available in the ALSPAC cohort, results consistent with the IOW cohort were found for both females and males. Conclusion Effects of age of puberty on FVC in early adulthood are likely mediated by height growth during adolescence.

The experience of childhood trauma is known to predict health-relevant outcomes across the lifespan. Previous reviews summarize existing knowledge of the implications of childhood trauma for health in young adults and adults more generally. The current theoretical review aims to integrate the existing literature on the relationship between childhood trauma and health-relevant outcomes specifically in college students, consolidating findings across specific health domains. Further, the following theoretical review highlights the need for more research in this area and discusses how college campuses may use the knowledge in this area of work to develop targeted interventions aimed at improving the health of college students who experienced trauma in childhood.

Large language models (LLMs) continue to exhibit noteworthy capabilities across a spectrum of areas, including emerging proficiencies across the health care continuum. Successful LLM implementation and adoption depend on digital readiness, modern infrastructure, a trained workforce, privacy, and an ethical regulatory landscape. These factors can vary significantly across health care ecosystems, dictating the choice of a particular LLM implementation pathway. This perspective discusses 3 LLM implementation pathways—training from scratch pathway (TSP), fine-tuned pathway (FTP), and out-of-the-box pathway (OBP)—as potential onboarding points for health systems while facilitating equitable adoption. The choice of a particular pathway is governed by needs as well as affordability. Therefore, the risks, benefits, and economics of these pathways across 4 major cloud service providers (Amazon, Microsoft, Google, and Oracle) are presented. While cost comparisons, such as on-demand and spot pricing across the cloud service providers for the 3 pathways, are presented for completeness, the usefulness of managed services and cloud enterprise tools is elucidated. Managed services can complement the traditional workforce and expertise, while enterprise tools, such as federated learning, can overcome sample size challenges when implementing LLMs using health care data. Of the 3 pathways, TSP is expected to be the most resource-intensive regarding infrastructure and workforce while providing maximum customization, enhanced transparency, and performance. Because TSP trains the LLM using enterprise health care data, it is expected to harness the digital signatures of the population served by the health care system with the potential to impact outcomes. The use of pretrained models in FTP is a limitation. It may impact its performance because the training data used in the pretrained model may have hidden bias and may not necessarily be health care–related. However, FTP provides a balance between customization, cost, and performance. While OBP can be rapidly deployed, it provides minimal customization and transparency without guaranteeing long-term availability. OBP may also present challenges in interfacing seamlessly with downstream applications in health care settings with variations in pricing and use over time. Lack of customization in OBP can significantly limit its ability to impact outcomes. Finally, potential applications of LLMs in health care, including conversational artificial intelligence, chatbots, summarization, and machine translation, are highlighted. While the 3 implementation pathways discussed in this perspective have the potential to facilitate equitable adoption and democratization of LLMs, transitions between them may be necessary as the needs of health systems evolve. Understanding the economics and trade-offs of these onboarding pathways can guide their strategic adoption and demonstrate value while impacting health care outcomes favorably.

A two-level hierarchical framework for early-stage sustainability assessment (FESSA) amongst a set of alternatives applicable from the earliest stages of process or product development is introduced, and its use in combination with an improved method weighted-sum method multi-criteria decision analysis (WSM-MCDA) in the presence of uncertainty is presented through application to a case study based upon a real-world decision scenario from speciality polymer manufacture. The approach taken addresses the challenge faced by those responsible for innovation management in the manufacturing process industries to make simultaneously timely and rational decisions early in the innovation cycle when knowledge gaps and uncertainty about the options tend to be at their highest. The Computed Uncertainty Range Evaluations (CURE) WSM-MCDA method provides better discrimination than the existing Multiple Attribute Range Evaluations (MARE) method without the computational burden of generating heuristic outcome distributions via Monte-Carlo simulation.

Objective: Investigate whether psychosocial risk in the childhood family environment moderates the relationship between childhood socioeconomic status (SES) and sleep, and the relationship between childhood SES and ambulatory blood pressure (ABP) in college students, two factors that are linked to future risk for cardiovascular disease. Participants: 124 American college students. Methods: Childhood SES and psychosocial risk in childhood family environments were measured by self-report instruments. Sleep was measured with self-report and actigraphy (over 5 days) and ABP over a 2-day period. Results: Linear regressions adjusting for age, sex, current SES, and current depressive symptoms indicated that SES and psychosocial risk in family environments during childhood interact to inform sleep quality, actigraphy derived wake after sleep onset (WASO), actigraphy derived Sleep Efficiency (SE) and ABP. Conclusions: Psychosocial risk in the childhood family environment may offset previously documented relationships between childhood SES and health-relevant outcomes in college students.

IntroductionPsychological factors linked to political participation are largely understudied in American Indians. Prior work notes relatively low levels of participation compared to other racial and ethnic groups and suggests that identification with being American Indian is linked to overall levels of civic engagement in part through perceptions of group discrimination.MethodsIn the current work, in a sample of 727 American Indian adults, we created two groups: Group 1 (N = 398) reported perceived discrimination related to race, and Group 2 (N = 329) reported perceived discrimination not related to race or ethnicity. We investigated the relationships between individual experiences of everyday discrimination related to race, levels of political efficacy, and political participation (Group 1), and individual experiences of everyday discrimination not related to race or ethnicity, political efficacy, and political participation (Group 2).ResultsWe found that greater experiences of everyday discrimination related to race was associated with higher levels of political participation through increased levels of internal and collective efficacy. In contrast, greater experiences of everyday discrimination related to race was associated with higher levels of political participation through lower external political efficacy. For Group 2, we found that greater experiences of everyday discrimination not related to race or ethnicity was not directly associated with political participation, but mediation analyses revealed a relationship with lower levels of political participation through decreased internal and collective efficacy. The indirect effect through external political efficacy was not significant.DiscussionGiven low levels of American Indian political participation, political efficacy could be a target for interventions aiming to increase participation in the political system.

Muscle sympathetic nerve activity (MSNA) responsiveness to mental stress is highly variable between individuals. Although stress perception has been posited as a contributor to the MSNA variability during mental stress, prior studies have been inconclusive. Furthermore, the importance of stress appraisal and coping on MSNA reactivity to mental stress has not been investigated. We hypothesize that appraisal of mental stress as a threat (i.e., perceived demands of stress exceed coping resources) versus a challenge (i.e., perceived coping resources sufficient for demands of stress) would be associated with greater MSNA reactivity. Twenty healthy adults (11 males, 9 females, 21 ± 3 yr, 23 ± 3 kg/m2) participated. Beat-by-beat blood pressure (finger plethysmography), heart rate (electrocardiography), and MSNA (microneurography) were recorded during a 10-min quiet rest followed by the Trier Social Stress Test (TSST). After each phase of the TSST (i.e., speech prep, speech, and mental arithmetic), participants reported threat versus challenge appraisal. Endorsement of a threat appraisal was positively associated with changes in MSNA burst frequency (r = 0.548, P = 0.018), burst incidence (r = 0.599, P = 0.009), and total MSNA (r = 0.697, P = 0.037) during the speech stress period. Moreover, increases in threat appraisal across tasks was associated with elevated MSNA burst frequency (r = 0.531, P = 0.023), incidence (r = 0.512, P = 0.030), and total MSNA (r = 0.727, P = 0.027) responsiveness. These findings support an association between stress appraisal processes and postganglionic sympathetic neural reactivity to psychosocial stress and may partially explain interindividual variability in MSNA responses to mental stress. NEW & NOTEWORTHY: The present study investigated the association between stress appraisal and muscle sympathetic nerve activity (MSNA) reactivity to the Trier Social Stress Test. Appraisal of the stress task as a threat (i.e., perceived inability to cope with the demands of the task) was associated with exaggerated MSNA reactivity to mental stress in humans. Threat appraisal is associated with exaggerated sympathetic reactivity to stress, potentially underlying the commonly observed interindividual variability in MSNA responsiveness to mental stress. [ABSTRACT FROM AUTHOR]

The experience of childhood trauma is known to predict health-relevant outcomes across the lifespan. Previous reviews summarize existing knowledge of the implications of childhood trauma for health in young adults and adults more generally. The current theoretical review aims to integrate the existing literature on the relationship between childhood trauma and health-relevant outcomes specifically in college students, consolidating findings across specific health domains. Further, the following theoretical review highlights the need for more research in this area and discusses how college campuses may use the knowledge in this area of work to develop targeted interventions aimed at improving the health of college students who experienced trauma in childhood. [ABSTRACT FROM AUTHOR]

Objective: To investigate associations between risk in family environments and health-relevant outcomes in college and the role of loneliness. Participants: College students at a state university (N = 360). Methods: We utilized linear regression to examine relationships between risk in family environments and loneliness, perceived stress, affect, and self-rated health. We tested for indirect effects of risk in family environments on outcomes through loneliness Results: Analyses showed that risk in family environments associated with loneliness ([beta] = 0.12 t[358] = 2.22, p = 0.03, R[superscript 2] change = 0.02), perceived social stress ([beta] = 0.20, t[357] = 3.88, p < 0.001, R[superscript 2] change = 0.04), negative and positive affect ([beta] = 2.44, t[357] = 3.95, p < 0.001, R[superscript 2] change = 0.04), and ([beta] = -0.18 t[357]= -3.44, p = 0.001, R[superscript 2] change = 0.03 respectively), and self-rated health ([beta] = 0.19, t[359] = 4.57, p < 0.001, R[superscript 2] change = 0.10). Significant indirect effects were observed for risk in early family on all outcomes through loneliness. Conclusion: These findings provide initial evidence that risk in childhood family environments may negatively affect health by increasing loneliness in college students.

We examined participation in an ethnically based residential program or “theme house” during the first year of college as a predictor of downstream immune system inflammation among undergraduates. Using a 4-year prospective design, we compared markers of inflammation among Latino/Latina students in a residential theme program with a matched sample of nonresidents. Students provided oral mucosal transudate samples for the assessment of circulating Interleukin 6 (IL-6), an inflammatory cytokine linked to health vulnerabilities. Findings suggest a protective benefit of theme house residency especially among students with anxious expectations of discrimination. Such expectations predicted higher levels of IL-6 after the first year of college among nonresidents only. In years 2–3, following exit from the theme house, the relationship between expected discrimination and IL-6 levels remained positive among nonresidents and was attenuated among residents, controlling for past IL-6 levels. Culturally based spaces may therefore offset the physiological burden of expected discrimination among undergraduates.

Low socioeconomic status (SES) during childhood confers risk for adverse health in adulthood. Accumulating evidence suggests that this may be due, in part, to the association between lower childhood SES and higher levels of pro-inflammatory cytokines. Drawing from literature showing that low childhood SES predicts exaggerated physiological reactivity to stressors and that lower SES is associated with a more communal, socially attuned orientation, we hypothesized that inflammatory reactivity would be more greatly affected by cues of social support among individuals whose childhood SES was low than among those whose childhood SES was high. In two studies, we found that individuals with lower subjective childhood SES exhibited greater reductions in pro-inflammatory cytokine reactivity to a stressor in the presence of a supportive figure (relative to conditions with an unsupportive or neutral figure). These effects were independent of current SES. This work helps illuminate SES-based differences in inflammatory reactivity to stressors, particularly among individuals whose childhood SES was low.

In response to social-evaluative threat induced in the laboratory, lower (compared to higher) subjective social class of a participant predicts greater increases in the inflammatory cytokine interleukin-6 (IL-6). In spite of the interpersonal nature of social-evaluation, little work has explored whether characteristics of the evaluator shape physiological responses in this context. In the current study, in a sample of 190 college students (male=66), we explored whether one's subjective social class interacts with the perceived social class of an evaluator to predict changes in Oral Mucosal Transudate (OMT) IL-6 in response to the Trier Social Stress Test (TSST). Participants were randomly assigned to be the speaker or the evaluator. Extending past work, we found that while speakers low in subjective social class consistently respond with strong increases in IL-6 regardless of their perception of their evaluator's social class, speakers high in subjective social class responded with greater increases in IL-6 when their evaluator was perceived as high social class compared to when they were perceived as low social class. This finding highlights the importance of perceptions of the evaluator in informing inflammatory responses to a social-evaluative task.

This research independently manipulated two potential attenuators of stereotype threat - reappraisal of anxiety and test framing - to explore their independent and combined effects. Female participants took a difficult math exam that was described as gender-biased or gender-fair and were told that anxious arousal could positively impact performance or were given no information regarding arousal. Levels of the cytokine Interleukin-6 (IL-6), an immune marker of inflammation, were measured in oral mucosal transudate (OMT) both before and after the exam. Our findings indicate that directing reappraisal of physiological arousal attenuated increases in IL-6 across test framing conditions, and was especially effective under stereotype threat (i.e., gender-biased test condition). Reappraisal also mapped onto better test performance in the threat condition. Together, these findings provide insight into the unique and interactive effects of two situational interventions meant to reduce stereotype threat, indexed here by both physiological and performance-based correlates of threat.

This research independently manipulated two potential attenuators of stereotype threat - reappraisal of anxiety and test framing - to explore their independent and combined effects. Female participants took a difficult math exam that was described as gender-biased or gender-fair and were told that anxious arousal could positively impact performance or were given no information regarding arousal. Levels of the cytokine Interleukin-6 (IL-6), an immune marker of inflammation, were measured in oral mucosal transudate (OMT) both before and after the exam. Our findings indicate that directing reappraisal of physiological arousal attenuated increases in IL-6 across test framing conditions, and was especially effective under stereotype threat (i.e., gender-biased test condition). Reappraisal also mapped onto better test performance in the threat condition. Together, these findings provide insight into the unique and interactive effects of two situational interventions meant to reduce stereotype threat, indexed here by both physiological and performance-based correlates of threat.

We experimentally tested whether negative stereotypes linked to lower socioeconomic status (SES), in addition to impairing academic performance (Croizet & Claire, 1998), instigate inflammation processes that are implicated in numerous disease processes. In Study 1, verbal test performance and activation of inflammation processes (measured by levels of an inflammatory protein, Interleukin-6 [IL-6]) varied as a function of SES and test framing (i.e., diagnostic vs. nondiagnostic of intellectual ability), with low SES students underperforming and exhibiting greater IL-6 production in the "diagnostic" condition. In Study 2, students expected their verbal exam performance to be compared to peers of higher or lower SES. Low SES students in the upward comparison condition displayed the greatest inflammatory response and worst test performance. Across both studies, different facets of SES predicted vulnerability to negative outcomes, such that low early life SES predicted heightened inflammation responses, while low current SES predicted impaired academic performance. © The Author(s) 2013.

BackgroundSubjective social status (captured by the MacArthur Scale of Subjective Social Status) is in many cases a stronger predictor of health outcomes than objective socioeconomic status (SES).PurposeThe study aims to test whether implicit beliefs about social class moderate the relationship between subjective social status and inflammation.MethodsWe measured implicit social class bias, subjective social status, SES, and baseline levels of interleukin-6 (IL-6), a marker of inflammation, in 209 healthy adults.ResultsImplicit social class bias significantly moderated the relationship between subjective social status and levels of IL-6, with a stronger implicit association between the concepts "lower class" and "bad" predicting greater levels of IL-6.ConclusionsImplicit social class bias moderates the relationship between subjective social status and health outcomes via regulation of levels of the inflammatory cytokine IL-6. High implicit social class bias, particularly when one perceives oneself as having low social standing, may increase vulnerability to inflammatory processes.