College of Science (COS)
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Browsing College of Science (COS) by Department "Center for Biostatistics and Health Data Science"
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- Altered toxicological endpoints in humans from common quaternary ammonium compound disinfectant exposureHrubec, Terry C.; Seguin, Ryan P.; Xu, L.; Cortopassi, G. A.; Datta, S.; Hanlon, Alexandra L.; Lozano, A. J.; McDonald, V. A.; Healy, C. A.; Anderson, T. C.; Musse, N. A.; Williams, R. T. (Elsevier, 2021-01-01)Humans are frequently exposed to Quaternary Ammonium Compounds (QACs). QACs are ubiquitously used in medical settings, restaurants, and homes as cleaners and disinfectants. Despite their prevalence, nothing is known about the health effects associated with chronic low-level exposure. Chronic QAC toxicity, only recently identified in mice, resulted in developmental, reproductive, and immune dysfunction. Cell based studies indicate increased inflammation, decreased mitochondrial function, and disruption of cholesterol synthesis. If these findings translate to human toxicity, multiple physiological processes could be affected. This study tested whether QAC concentrations could be detected in the blood of 43 human volunteers, and whether QAC concentrations influenced markers of inflammation, mitochondrial function, and cholesterol synthesis. QAC concentrations were detected in 80 % of study participants. Blood QACs were associated with increase in inflammatory cytokines, decreased mitochondrial function, and disruption of cholesterol homeostasis in a dose dependent manner. This is the first study to measure QACs in human blood, and also the first to demonstrate statistically significant relationships between blood QAC and meaningful health related biomarkers. Additionally, the results are timely in light of the increased QAC disinfectant exposure occurring due to the SARS-CoV-2 pandemic. Main Findings: This study found that 80 % of study participants contained QACs in their blood; and that markers of inflammation, mitochondrial function, and sterol homeostasis varied with blood QAC concentration.
- Breakfast Consumption Habits at Age 6 and Cognitive Ability at Age 12: A Longitudinal Cohort StudyLiu, Jianghong; Wu, Lezhou; Um, Phoebe; Wang, Jessica S.; Kral, Tanja V. E.; Hanlon, Alexandra L.; Shi, Zumin (MDPI, 2021-06-17)This study aimed to assess the relationship between breakfast composition and long-term regular breakfast consumption and cognitive function. Participants included 835 children from the China Jintan Cohort Study for the cross-sectional study and 511 children for the longitudinal study. Breakfast consumption was assessed at ages 6 and 12 through parental and self-administered questionnaires. Cognitive ability was measured as a composition of IQ at age 6 and 12 and academic achievement at age 12, which were assessed by the Chinese versions of the Wechsler Intelligence Scales and standardized school reports, respectively. Multivariable general linear and mixed models were used to evaluate the relationships between breakfast consumption, breakfast composition and cognitive performance. In the longitudinal analyses, 94.7% of participants consumed breakfast ≥ 4 days per week. Controlling for nine covariates, multivariate mixed models reported that compared to infrequent breakfast consumption, regular breakfast intake was associated with an increase of 5.54 points for verbal and 4.35 points for full IQ scores (p < 0.05). In our cross-sectional analyses at age 12, consuming grain/rice or meat/egg 6–7 days per week was significantly associated with higher verbal, performance, and full-scale IQs, by 3.56, 3.69, and 4.56 points, respectively (p < 0.05), compared with consuming grain/rice 0–2 days per week. Regular meat/egg consumption appeared to facilitate academic achievement (mean difference = 0.232, p = 0.043). No association was found between fruit/vegetable and dairy consumption and cognitive ability. In this 6-year longitudinal study, regular breakfast habits are associated with higher IQ. Frequent grain/rice and meat/egg consumption during breakfast may be linked with improved cognitive function in youth.
- The conduction velocity-potassium relationship in the heart is modulated by sodium and calciumKing, D. Ryan; Entz, Michael, II; Blair, Grace A.; Crandell, Ian; Hanlon, Alexandra L.; Lin, Joyce; Hoeker, Gregory S.; Poelzing, Steven (2021-03)The relationship between cardiac conduction velocity (CV) and extracellular potassium (K+) is biphasic, with modest hyperkalemia increasing CV and severe hyperkalemia slowing CV. Recent studies from our group suggest that elevating extracellular sodium (Na+) and calcium (Ca2+) can enhance CV by an extracellular pathway parallel to gap junctional coupling (GJC) called ephaptic coupling that can occur in the gap junction adjacent perinexus. However, it remains unknown whether these same interventions modulate CV as a function of K+. We hypothesize that Na+, Ca2+, and GJC can attenuate conduction slowing consequent to severe hyperkalemia. Elevating Ca2+ from 1.25 to 2.00 mM significantly narrowed perinexal width measured by transmission electron microscopy. Optically mapped, Langendorff-perfused guinea pig hearts perfused with increasing K+ revealed the expected biphasic CV-K+ relationship during perfusion with different Na+ and Ca2+ concentrations. Neither elevating Na+ nor Ca2+ alone consistently modulated the positive slope of CV-K+ or conduction slowing at 10-mM K+; however, combined Na+ and Ca2+ elevation significantly mitigated conduction slowing at 10-mM K+. Pharmacologic GJC inhibition with 30-mu M carbenoxolone slowed CV without changing the shape of CV-K+ curves. A computational model of CV predicted that elevating Na+ and narrowing clefts between myocytes, as occur with perinexal narrowing, reduces the positive and negative slopes of the CV-K+ relationship but do not support a primary role of GJC or sodium channel conductance. These data demonstrate that combinatorial effects of Na+ and Ca2+ differentially modulate conduction during hyperkalemia, and enhancing determinants of ephaptic coupling may attenuate conduction changes in a variety of physiologic conditions.
- County-level social distancing and policy impact in the United States: A dynamical systems modelMcKee, Kevin L.; Crandell, Ian C.; Hanlon, Alexandra L. (JMIR Publications, 2020-10-01)Background: Social distancing and public policy have been crucial for minimizing the spread of SARS-CoV-2 in the United States. Publicly available, county-level time series data on mobility are derived from individual devices with global positioning systems, providing a variety of indices of social distancing behavior per day. Such indices allow a fine-grained approach to modeling public behavior during the pandemic. Previous studies of social distancing and policy have not accounted for the occurrence of pre-policy social distancing and other dynamics reflected in the long-term trajectories of public mobility data. Objective: We propose a differential equation state-space model of county-level social distancing that accounts for distancing behavior leading up to the first official policies, equilibrium dynamics reflected in the long-term trajectories of mobility, and the specific impacts of four kinds of policy. The model is fit to each US county individually, producing a nationwide data set of novel estimated mobility indices. Methods: A differential equation model was fit to three indicators of mobility for each of 3054 counties, with T=100 occasions per county of the following: distance traveled, visitations to key sites, and the log number of interpersonal encounters. The indicators were highly correlated and assumed to share common underlying latent trajectory, dynamics, and responses to policy. Maximum likelihood estimation with the Kalman-Bucy filter was used to estimate the model parameters. Bivariate distributional plots and descriptive statistics were used to examine the resulting county-level parameter estimates. The association of chronology with policy impact was also considered. Results: Mobility dynamics show moderate correlations with two census covariates: population density (Spearman r ranging from 0.11 to 0.31) and median household income (Spearman r ranging from -0.03 to 0.39). Stay-at-home order effects were negatively correlated with both (r=-0.37 and r=-0.38, respectively), while the effects of the ban on all gatherings were positively correlated with both (r=0.51, r=0.39). Chronological ordering of policies was a moderate to strong determinant of their effect per county (Spearman r ranging from -0.12 to -0.56), with earlier policies accounting for most of the change in mobility, and later policies having little or no additional effect. Conclusions: Chronological ordering, population density, and median household income were all associated with policy impact. The stay-at-home order and the ban on gatherings had the largest impacts on mobility on average. The model is implemented in a graphical online app for exploring county-level statistics and running counterfactual simulations. Future studies can incorporate the model-derived indices of social distancing and policy impacts as important social determinants of COVID-19 health outcomes.
- Does meeting physical activity recommendations ameliorate association between television viewing with cardiovascular disease risk? A cross-sectional, population-based analysisPatterson, Freda; Mitchell, Jonathan A.; Dominick, Gregory; Lozano, Alicia J.; Huang, Liming; Hanlon, Alexandra L. (BMJ, 2020-01-01)Objectives: As a common form of sedentary behaviour, television viewing is associated with an increase in body mass index (BMI) as well as overall cardiovascular disease (CVD) risk. This study examined the extent to which meeting the recommended volume of weekly physical activity (PA) reduced the association between television viewing with the outcomes of BMI and CVD risk. A second aim was to determine the number of hours (ie, cut-point) of daily television viewing that conferred a higher BMI and CVD risk for a large population-based sample of adults. Design: Population-based, cross-sectional study. Setting UK Biobank recruited across 35 centres in the UK between 2006 and 2010. Primary outcome CVD risk, as measured by the 30-year Framingham risk score. Results Linear regression models indicated that every additional hour of television viewing per day was associated with a 3% increase in CVD risk (aCoeff=0.03, d=0.16, p<0.0001); the interaction between television viewing with meeting PA guidelines was marginally associated with CVD risk (aCoeff=0.0010, d=0.01, p=0.014). Each additional hour of television viewing per day was associated with a 0.54 increase in BMI (aCoeff=0.54, d=0.13, p<0.0001); the interaction between television viewing with meeting PA guidelines was not significantly associated with BMI. Regression tree models of the study outcomes revealed that 2.5 hours of television viewing was associated with pronounced increases in BMI and CVD risk. Conclusions: These data underscore the independent association between television viewing with cardiovascular risk and suggest that reducing television viewing to less than 2.5 hours per day, even in physically active adults, is a clinical and public health priority.