Browsing by Author "Hanlon, Alexandra L."

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    Altered toxicological endpoints in humans from common quaternary ammonium compound disinfectant exposure
    Hrubec, 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.
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    Antibiotic exposure is associated with decreased risk of psychiatric disorders
    Kerman, Ilan A.; Glover, Matthew E.; Lin, Yezhe; West, Jennifer L.; Hanlon, Alexandra L.; Kablinger, Anita S.; Clinton, Sarah M. (Frontiers, 2024-01-08)
    Objective: This study sought to investigate the relationship between antibiotic exposure and subsequent risk of psychiatric disorders. Methods: This retrospective cohort study used a national database of 69 million patients from 54 large healthcare organizations. We identified a cohort of 20,214 (42.5% male; 57.9 ± 15.1 years old [mean ± SD]) adults without prior neuropsychiatric diagnoses who received antibiotics during hospitalization. Matched controls included 41,555 (39.6% male; 57.3 ± 15.5 years old) hospitalized adults without antibiotic exposure. The two cohorts were balanced for potential confounders, including demographics and variables with potential to affect: the microbiome, mental health, medical comorbidity, and overall health status. Data were stratified by age and by sex, and outcome measures were assessed starting 6 months after hospital discharge. Results: Antibiotic exposure was consistently associated with a significant decrease in the risk of novel mood disorders and anxiety and stressor-related disorders in: men (mood (OR 0.84, 95% CI 0.77, 0.91), anxiety (OR 0.88, 95% CI 0.82, 0.95), women (mood (OR 0.94, 95% CI 0.89,1.00), anxiety (OR 0.93, 95% CI 0.88, 0.98), those who are 26–49 years old (mood (OR 0.87, 95% CI 0.80, 0.94), anxiety (OR 0.90, 95% CI 0.84, 0.97)), and in those ≥50 years old (mood (OR 0.91, 95% CI 0.86, 0.97), anxiety (OR 0.92, 95% CI 0.87, 0.97). Risk of intentional harm and suicidality was decreased in men (OR 0.73, 95% CI 0.55, 0.98) and in those ≥50 years old (OR 0.67, 95% CI 0.49, 0.92). Risk of psychotic disorders was also decreased in subjects ≥50 years old (OR 0.83, 95 CI: 0.69, 0.99). Conclusion: Use of antibiotics in the inpatient setting is associated with protective effects against multiple psychiatric outcomes in an age- and sex-dependent manner.
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    Breakfast Consumption Habits at Age 6 and Cognitive Ability at Age 12: A Longitudinal Cohort Study
    Liu, 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.
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    The conduction velocity-potassium relationship in the heart is modulated by sodium and calcium
    King, 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.
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    County-level social distancing and policy impact in the United States: A dynamical systems model
    McKee, 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.
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    Deepening Our Understanding of COVID-19 Vaccine Decision-Making amongst Healthcare Workers in Southwest Virginia, USA Using Exploratory and Confirmatory Factor Analysis
    Bendetson, Jesse; Swann, Mandy C.; Lozano, Alicia; West, Jennifer; Hanlon, Alexandra L.; Crandell, Ian; Jatta, Maimuna; Schleupner, Charles J.; Baffoe-Bonnie, Anthony W. (MDPI, 2023-02-27)
    Vaccine hesitancy amongst healthcare workers (HCWs) has been a major challenge throughout the COVID-19 pandemic. While many studies have identified HCW characteristics and specific attitudes associated with COVID-19 vaccine hesitancy, researchers are still working towards developing a holistic understanding of the psychological constructs that influence COVID-19 vaccine decision-making in this population. Between 15 March and 29 March 2021, we distributed an online survey assessing individual characteristics and vaccine-related perceptions to employees of a not-for-profit healthcare system in Southwest Virginia (N = 2459). We then performed exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) to describe patterns of vaccine-related thought amongst HCWs and identify latent psychometric constructs involved in vaccine decision-making. The goodness of model fit was assessed using the Tucker–Lewis Index (TLI), the Comparative Fit Index (CFI), and the Root Mean Square Error of Approximation (RMSEA). Internal consistency and reliability of each factor were assessed using Cronbach’s alpha. EFA identified four latent psychometric constructs: Lack of trust in the COVID-19 vaccine; Anti-science sentiment; Adverse side-effects; and Situational risk assessment. The goodness of EFA model fit was adequate (TLI > 0.90, RMSEA ≤ 0.08) with acceptable internal consistency and reliability for three of four factors (Cronbach’s alpha > 0.70). The CFA model also had adequate goodness of fit (CFI > 0.90, RMSEA ≤ 0.08). We believe the psychometric constructs identified in this study can provide a useful framework for interventions to improve vaccine uptake amongst this critical population.
  • Differences in Sleep Quality and Sleepiness among Veterinary Medical Students at Multiple Institutions before and after the Pandemic Induced Transition to Online Learning
    Nappier, Michael T.; Alvarez, Elizabeth E.; Bartl-Wilson, Lara; Boynton, Elizabeth P.; Hanlon, Alexandra L.; Lozano, Alicia J.; Ng, Zenithson; Ogunmayowa, Oluwatosin; Shoop, Tiffany; Welborn, Nancy D.; Wuerz, Julia (University of Toronto Press)
    Poor sleep health has been previously documented in veterinary medical students. However, it is not known how universal or widespread this problem is. This study evaluated Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) scores to measure sleep health among students at seven colleges of veterinary medicine in the United States (US). Inadvertently, the transition to online only learning due to the global COVID-19 pandemic was also captured. Veterinary students were found to have universally poor sleep quality and high daytime sleepiness. The transition to online only learning appeared to have little impact on sleep quality, but improved daytime sleepiness scores were observed. The findings suggest poor sleep health is common among veterinary medical students at multiple institutions in the US and that further investigation is necessary.
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    Does meeting physical activity recommendations ameliorate association between television viewing with cardiovascular disease risk? A cross-sectional, population-based analysis
    Patterson, 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.
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    Factors Related to Diabetes Mellitus among Asian-American Adults in the United States Using the 2011 to 2020 National Health and Nutrition Examination Survey
    Nichols, Quentin Zacharias (Virginia Tech, 2023-09-01)
    Type 2 diabetes mellitus (T2DM) disproportionality affects under-represented groups, specifically Asian Americans. Asian Americans are less likely to receive proper diabetes mellitus screening compared to other racial and ethnic groups, potentially due to improper screening guidelines by clinicians, and Asian Americans being unaware of their increased risk for diabetes mellitus. There are differences in the etiology of T2DM in Asian Americans compared to White Americans. Due to the increasing rates of T2DM among Asian Americans, new approaches in the screening of T2DM should be tailored based on race and ethnicity. The aging process is frequently associated with decreased muscle mass and increased adipose tissue, which can contribute to insulin resistance and lead to elevated hemoglobin A1c (HbA1c) percentages. Although sex has not been classified as an independent risk factor for T2DM, it is important to consider sex-specific conditions in the context of the disease. Body mass index (BMI) alone is insufficient to properly evaluate adiposity in Asian-American adults due to Asian Americans having a lower BMI with a higher body fat percentage. Waist circumference, waist-to-height ratio (WHtR), and visceral adiposity index (VAI) may be better for screening Asian Americans for T2DM. Multiple modifiable risk factors, such as sedentary behavior, and dietary intake (specifically dietary magnesium intake) can increase the risk for T2DM. Lack of physical activity can result in insulin resistance and impaired glucose metabolism as a result of muscle disuse and decreased lean body mass. Half of the Asian-American population is not consuming the recommended amounts of magnesium from foods, drinks, and dietary supplements. There is an inverse relationship between increased dietary magnesium intake and the risk of T2DM. In addition, the main language spoken in the household may influence lifestyle and risk of T2DM. The overarching goal of the present study was to establish which independent variables (age, sex, BMI, waist circumference, WHtR, VAI, sedentary behavior time, dietary magnesium intake, self-reported healthy diet status, and language) were the strongest predictors of HbA1c percentage (a measure of blood glucose control) in Asian-American adults using the National Health and Nutrition Examination Survey (NHANES) data from 2011 to 2020. The present study also evaluated the relationship among multiple predictors of HbA1c percentage, including age, sex, body composition, sedentary behavior time, dietary magnesium intake, self-reported healthy diet status, and language among Asian-American adults, 18 years of age and older, using the NHANES data from 2011 to 2020.
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    Favorable Biochemical Freedom From Recurrence With Stereotactic Body Radiation Therapy for Intermediate and High-Risk Prostate Cancer: A Single Institutional Experience With Long-Term Follow-Up
    Ricco, Anthony; Barbera, Gabrielle; Lanciano, Rachelle; Feng, Jing; Hanlon, Alexandra L.; Lozano, Alicia J.; Good, Michael; Arrigo, Stephen; Lamond, John; Yang, Jun (Frontiers, 2020-09-25)
    Purpose/Objective(s): The current study reports long-term overall survival (OS) and biochemical freedom from recurrence (BFFR) after stereotactic body radiation therapy (SBRT) for men with intermediate and high-risk prostate cancer in a single community hospital setting with early adoption. Materials/Methods: Ninety-seven consecutive men with intermediate and high-risk prostate cancer treated with SBRT between 2007 and 2015 were retrospectively studied. Categorical variables for analysis included National Comprehensive Cancer Network risk group, race, Gleason grade group, T stage, use of androgen deprivation therapy, and planning target volume dose. Continuous variables for analysis included pretreatment prostate-specific antigen (PSA), percent cores positive, age at diagnosis, PSA nadir, prostate volume, percent prostate that received 40 Gy, and minimum dose to 0.03 cc of prostate (Dmin). BFFR was assessed using the Phoenix nadir +2 definition. OS and BFFR were estimated using Kaplan–Meier (KM) methodology with comparisons accomplished using log-rank statistics. Multivariable analysis (MVA) was accomplished with a backwards selection Cox proportional-hazards model with statistical significance taken at the p < 0.05 level. Results: Median FU is 78.4 months. Five- and ten-year OS KM estimates are 90.9 and 73.2%, respectively, with 19 deaths recorded. MVA reveals pretreatment PSA (p = 0.032), percent prostate 40 Gy (p = 0.003), and race (p = 0.031) were predictive of OS. Five- and nine-year BFFR KM estimates are 92.1 and 87.5%, respectively, with 10 biochemical failures recorded. MVA revealed PSA nadir (p < 0.001) was the only factor predictive of BFFR. Specifically, for every one-unit increase in PSA nadir, there was a 4.2-fold increased odds of biochemical failure (HR = 4.248). No significant differences in BFFR were found between favorable intermediate, unfavorable intermediate, and high-risk prostate cancer (p = 0.054) with 7-year KM estimates of 96.6, 81.0, and 85.7%, respectively. Conclusions: Favorable OS and BFFR can be expected after SBRT for intermediate and high-risk prostate cancer with non-significant differences seen for BFFR between favorable intermediate, unfavorable intermediate, and high-risk groups. Our 5-year BFFR compares favorably with the HYPO-RT-PC trial of 84%. PSA nadir was predictive of biochemical failure. This study is ultimately limited by the small absolute number of high-risk patients included.
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    Gut-brain interactions in food reward
    Burns, Amber Lynn (Virginia Tech, 2024-01-11)
    Food choice and preference have been linked to post-ingestive consequences of food consumption. Many ultra-processed foods deliver calories rapidly and are highly rewarding. In literature surrounding substances of abuse, the speed at which a drug reaches the brain affects its abuse potential; this is known as the "rate hypothesis." Here, we test whether the rate hypothesis of addiction may apply to food, specifically whether caloric availability, or the speed at which carbohydrate becomes available for use, contributes to food reward and preference. To do this, we use beverages with novel flavors (conditioned stimulus (CS)) mixed with either a slow metabolizing carbohydrate (maltodextrin and inulin; CS+Slow), a fast-metabolizing carbohydrate (sucrose; CS+Fast), or no carbohydrate (sucralose; CS-). Participants are given each of these drinks 6 times to consume (conditioning period). 2 of these consumption periods occur during in-lab sessions. In one session, blood glucose is measured over one hour post-consumption. In another, we perform indirect calorimetry to assess post-consumption changes in substrate oxidation rates. At the post-testing session, changes in self-reported liking, wanting, and ad libitum intake of each beverage are recorded. Brain response to each flavor cue (without calories) is measured using fMRI at the post-test. We hypothesize the flavor paired with the CS+Fast will be the most liked, wanted, and consumed. We expect greater BOLD (blood oxygenated level dependent) activation to the CS+Fast relative to the CS+Slow and CS- in the nucleus accumbens and hypothalamus. This is an ongoing study and, here, we present our preliminary analysis of the data.
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    National assessment of obstetrics and gynecology and family medicine residents' experiences with CenteringPregnancy group prenatal care
    Place, Jean Marie; Van De Griend, Kristin; Zhang, Mengxi; Schreiner, Melanie; Munroe, Tanya; Crockett, Amy; Ji, Wenyan; Hanlon, Alexandra L. (2023-11-21)
    Objective To examine family medicine (FM) and obstetrician-gynecologist (OB/GYN) residents’ experiences with CenteringPregnancy (CP) group prenatal care (GPNC) as a correlate to perceived likelihood of implementing CP in future practice, as well as knowledge, level of support, and perceived barriers to implementation. Methods We conducted a repeated cross-sectional study annually from 2017 to 2019 with FM and OB/GYN residents from residency programs in the United States licensed to operate CP. We applied adjusted logistic regression models to identify predictors of intentions to engage with CP in future practice. Results Of 212 FM and 176 OB/GYN residents included in analysis, 67.01% of respondents intended to participate as a facilitator in CP in future practice and 51.80% of respondents were willing to talk to decision makers about establishing CP. Both FM and OB/GYN residents who spent more than 15 h engaged with CP and who expressed support towards CP were more likely to participate as a facilitator. FM residents who received residency-based training on CP and who were more familiar with CP reported higher intention to participate as a facilitator, while OB/GYN residents who had higher levels of engagement with CP were more likely to report an intention to participate as a facilitator. Conclusion Engagement with and support towards CP during residency are key factors in residents’ intention to practice CP in the future. To encourage future adoption of CP among residents, consider maximizing resident engagement with the model in hours of exposure and level of engagement, including hosting residency-based trainings on CP for FM residents.
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    Neighborhood historical redlining, present-day social vulnerability and sports and recreational injury hospitalizations in the United States
    Ogunmayowa, Oluwatosin Thompson (Virginia Tech, 2023-07-14)
    Historical redlining, a discriminatory practice of the 1930s, present-day social vulnerability (SVI), and sports and recreational injury (SRI) hospitalizations are interconnected topics that highlight the intersection of race, class, and health in the United States but the relationships have not been studied to date. Thus, the overall aim of this dissertation is to examine the effects of historical redlining and present-day social vulnerability on SRI hospitalizations in the United States. The first study systematically reviewed studies that examined the relationships between neighborhood characteristics and SRI using multilevel modeling approach. Studies reviewed show that certain neighborhood factors, such as living in urban communities, were associated with increased risk of SRI. The second study examined the association between historical redlining and present-day neighborhood SVI in the United States. Results show that formerly redlined areas have higher SVI presently. The third study examined the association between historical redlining and present-day SRI hospitalization in the United States. Results show that redlining was not associated with increased odds of SRI hospitalizations, but was associated with longer length of hospital stay (LOS) among Black and Hispanic patients, and higher total hospital charges among Hispanic patients. The fourth study examined the association between individual and neighborhood social vulnerability and sports and recreation-related traumatic brain injury (SR-TBI) hospitalizations among pediatric patients in the United States. Results show that Native American children had higher odds of hospitalization for SR-TBI, longer LOS, but lower odds of discharge to post-acute care compared to White children. Older age was associated with higher odds of hospitalization and longer LOS while male sex was associated with shorter LOS for SR-TBI in children. Compared to children with private insurance, children with public insurance had longer LOS while uninsured children had shorter LOS. Also, hospitalization in neighborhood with higher overall SVI was associated with longer LOS. This study advances our knowledge on the impact of structural racism on present-day SRI outcomes and will inform policy makers to prioritize health equity by addressing the underlying social determinants of health and the root causes of disparities in SRI outcomes.
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    P300 Event-Related Potentials Mediate the Relationship Between Child Physical Abuse and Externalizing Behavior
    Cui, Naixue; Raine, Adrian; Connolly, Cynthia A.; Richmond, Therese S.; Hanlon, Alexandra L.; McDonald, Catherine C.; Liu, Jianghong (2021-11-01)
    The psychophysiological mechanism linking early childhood experiences to behavior problems remains unclear. This study aimed to examine the association of child physical abuse with P300 event-related potentials (ERP), and to test the mediating effect of P300 amplitude and latency in the relationship between child physical abuse and externalizing behaviors. Cross-sectional secondary data were obtained from 155 children (55.5% boys, mean age: 11.28 +/- 0.57 years) who participated in the China Jintan Child Cohort Study. Children self-reported maternal and paternal physical abuse and externalizing behaviors, as well as P300 were obtained in 2013. Additionally, parents and teachers reported child externalizing behaviors in preschool in 2007. P300 were recorded during a standard novel auditory oddball task. Path analysis shows that after controlling for child sex, socioeconomic status, area of residence, IQ, and child externalizing behavior in preschool, children exposed to maternal physical abuse exhibited increased novelty P300 amplitude, which links to more externalizing behavior. Novelty P300 amplitude partially mediated the relationship between maternal physical abuse and externalizing behavior. These findings are the first to document the partial mediating effect of P300 amplitude on the abuse-externalizing relationship and are consistent with the view that physical abuse affects the attention bias to novel cues that likely places them at increased risk for the development and maintenance of externalizing behavior.
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    A Pedagogical Approach to Create and Assess Domain-Specific Data Science Learning Materials in the Biomedical Sciences
    Chen, Daniel (Virginia Tech, 2022-02-01)
    This dissertation explores creating a set of domain-specific learning materials for the biomedical sciences to meet the educational gap in biomedical informatics, while also meeting the call for statisticians advocating for process improvements in other disciplines. Data science educational materials are plenty enough to become a commodity. This provides the opportunity to create domain-specific learning materials to better motivate learning using real-world examples while also capturing intricacies of working with data in a specific domain. This dissertation shows how the use of persona methodologies can be combined with a backwards design approach of creating domain-specific learning materials. The work is divided into three (3) major steps: (1) create and validate a learner self-assessment survey that can identify learner personas by clustering. (2) combine the information from persona methodology with a backwards design approach using formative and summative assessments to curate, plan, and assess domain-specific data science workshop materials for short term and long term efficacy. (3) pilot and identify at how to manage real-time feedback within a data coding teaching session to drive better learner motivation and engagement. The key findings from this dissertation suggests using a structured framework to plan and curate learning materials is an effective way to identify key concepts in data science. However, just creating and teaching learning materials is not enough for long-term retention of knowledge. More effort for long-term lesson maintenance and long-term strategies for practice will help retain the concepts learned from live instruction. Finally, it is essential that we are careful and purposeful in our content creation as to not overwhelm learners and to integrate their needs into the materials as a primary focus. Overall, this contributes to the growing need for data science education in the biomedical sciences to train future clinicians use and work with data and improve patient outcomes.
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    Repeat Thoracic Stereotactic Body Radiation Therapy (SBRT) for Nonsmall Cell Lung Cancer: Long-Term Outcomes, Toxicity, and Dosimetric Considerations
    Ricco, Anthony; Barlow, Sara; Feng, Jing; Jacob, Janson; Lozano, Alicia J.; Hanlon, Alexandra L.; Arrigo, Stephen; Obayomi-Davies, Olusola; Lamond, John; Yang, Jun; Lanciano, Rachelle (2020-10)
    Purpose: Lung reirradiation for nonsmall cell lung cancer (NSCLC) is common for either recurrent disease or new primary cancer. Dose volume tolerance of the lung after multiple courses of radiation therapy (RT) is unknown. We review our experience with lung reirradiation for patients with NSCLC in a single community setting using stereotactic body radiation therapy (SBRT) to report lung cumulative doses, survival, and toxicity. Methods and Materials: Forty-four patients who received at least 2 curative courses of lung RT with the second course delivered between January 2012 and December 2017 were eligible. All patients had NSCLC and were treated with SBRT for reirradiation. Cumulative lung dose volume histograms for all courses were generated, summated, and converted into cumulative equivalent dose in 2 Gy fractions (EQD2). Actuarial overall survival (OS), local control, and toxicity is reported, including a subset of patients who received more than 2 courses of SBRT. Results: Median age of the group was 71 years (range, 51-87). Median survival of the entire group from diagnosis, first, and second courses of RT was 3.94, 3.03, and 2.03 years. Three-year actuarial OS for the entire group was 34.1% from second course of RT. The mean EQD2 Gy3 mean lung dose for all courses was 12.35 Gy (range, 2.7-26.52). The mean EQD2 Gy(3) V5Gy, V10Gy, V20Gy, V30Gy, and V40Gy were 40.9%, 25.5%, 14.7%, 10.2%, and 7.7%. Six-year actuarial freedom from grade >= 3 complications was 86.3%. The rate of grade >= 3 lung toxicity was 4.5% (2 of 44). Other late toxicities included grade 3 recurrent laryngeal nerve damage (n=1) and grade 3 chest wall pain/rib fracture (n = 1). Overall, 32% of patients had more than 2 courses of RT to the lung (range, 3-7). Conclusions: Long-term OS is possible with multiple RT courses to the lung for NSCLC with low toxicity. (C) 2020 The Author(s). Published by Elsevier Inc. on behalf of American Society for Radiation Oncology.
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    Shift Workers Have Higher Blood Pressure Medicine Use, But Only When They Are Short Sleepers: A Longitudinal UK Biobank Study
    Riegel, Barbara; Daus, Marguerite; Lozano, Alicia J.; Malone, Susan K.; Patterson, Freda; Hanlon, Alexandra L. (2019-10-15)
    Background-Some, but not all, studies report associations between shift work and hypertension, suggesting that particular subgroups may be at risk. We examined moderating effects of sleep duration and circadian preference on the relationship between shift work and new blood pressure (BP) medicine use at follow-up. Methods and Results-Baseline and 5-year follow-up data from the UK Biobank cohort (N=9200) were used to generate logistic regression models for shift workers and nonshift workers. The moderating effects of sleep duration (short <= 6 hours; adequate 7-8 hours; long >= 9 hours) and circadian preference (morning "larks;" intermediate; evening "owls") at baseline were examined with new BP medicine use at follow-up, adjusting for age, sex, race, education, employment, urban/rural, cardiovascular disease family history, depression, alcohol intake, physical activity, diet, smoking, and body mass index. The sample was predominately middle aged (55.3 +/- 7.4), female (57.3%), and white (97.9%). Most reported adequate sleep duration (7-8 hours, 73.7%) and were intermediate type (65.3%); 8.0% were shift workers at baseline. Only 6.5% reported new BP medicine use at follow-up. Short sleep duration was a significant moderator of new BP medicine use in shift workers. Among short sleepers, shift workers had a 2.1-fold increased odds of new BP medicine use compared with nonshift workers (odds ratio=2.08, 95% CI=1.21-3.58, P=0.008). In those reporting adequate (odds ratio=0.82, 95% CI=0.54-1.25, P=0.35) and long sleep (odds ratio=0.64, 95% CI=0.11-3.54, P=0.60), this relationship was protective but nonsignificant. Interaction between circadian preference and shift work on BP medicine use was nonsignificant. Conclusions-Shift workers with short sleep duration may be at risk for hypertension.
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    Sitting, Standing and Starting: Detailing Postural Control and Gait Anticipation for Children with Hemiplegic Cerebral Palsy
    Farah, Hassan-Galaydh Mohamud (Virginia Tech, 2023-10-05)
    Of all children in the US born with Cerebral Palsy (CP), 30-40% of them will be diagnosed with Hemiplegic CP (HCP), presenting with one side of the body weaker than the other. The resulting asymmetries impede the ability of children with HCP to distribute weight evenly between their lower limbs. This often contributes to poor postural control and 'favoring' of their uninvolved side for stability during balance and gait. Much is still unknown about the biomechanical characteristics of asymmetry in the lower limbs. There are a few previous research studies completed in biomechanics labs that highlight some gaps in knowledge regarding our understanding of posture and balance in this population of children, but the availability of clinical assessments that help inform the implementation and impact of treatment targets for posture and balance are sparse. This dissertation showcases two independent studies aimed at some of the gaps in knowledge for posture and balance in children with HCP. The first study in this dissertation presents and tests the reliability when a clinical measure, the Posture and Postural Ability Scale (PPAS) was modified for use in children with HCP going through a therapeutic process. The PPAS was originally developed and tested with adults in controlled settings, often with individuals being placed in postures for examination. For the study presented here, modifications focused on scoring postures when children with HCP naturally assumed various sitting and standing postures during treatment. Researchers and an experienced therapist video-coded the modified PPAS. Intrarater and interrater reliability was calculated via Cohen's kappa, percent agreement and Intraclass Correlation Coefficients. Although reliability amongst and between researchers were weak (kappas < 0.7), videos were successfully scored, demonstrating the tool is feasible. In addition, some high levels of intrarater reliability was obtained by a more experienced clinician. Suggestive that this modified PPAS could serve as a potential tool for qualified clinicians to collect meaningful posture and postural control data. The second study addressed a specific gap in knowledge about the characteristics of gait anticipation (GA, i.e., expectation of initiating a step) in children with HCP on balance. Balance and limb symmetry metrics were compared during standing in three children with HCP and typically developing (TD) peers that were matched by age and sex, alongside a third (independent) sample of 12 unmatched TD children. Motion capture analysis and force plate technology were utilized to record and follow how center of pressure (COP) and center of mass (COM) move during quiet standing (without anticipating gait) and standing with GA. This study applied a Symmetry Index (SI) to COP displacement and COP velocity allowing for quantification of asymmetries between the lower limbs during standing with and without the anticipation of gait. Children completed multiple standing trials where they were ask to stand for 35 seconds (5 seconds to obtain balance and 30 seconds of data collection). Standing trials, involved sets where children were instructed that they would not walk forward and GA trials where they were asked to stand knowing that a light would indicate they should walk forward. The light also indicated which limb (i.e. right or left) the child should step forward with first. Limb designation for stepping forward was randomly generated. Data was examined across and within (15 second blocks) 30 seconds of standing. We had the following hypotheses: 1) GA would increase COP displacement and COP velocity for children with HCP greater than TD peers who would have no change; 2) children with HCP would have different levels of symmetry between the lower limbs when expecting to walk than TD peers; and 3) children with HCP would have different reaction times based on the limb (i.e., involved versus uninvolved) they were asked to start walking with. The HCP group showed the largest increase in COP displacement when comparing standing with no expectation of walking where they had an average of 22.0 ± 10.0 mm over 30 seconds of standing to an average of 24.5 ±9.90mm during GA. The matched group average was 11.3 ±8.87mm with no expectation of walking and 4.6 ±12.6mm with GA. The TD group's COP displacement remained relatively similar with an average of 8.04 ±6.40mm during when not expecting to walk and an average of 8.29 ±6.70mm with GA. Similar increases were seen for COP velocity. Comparisons for symmetry between limbs showed that COP was displaced more underneath the uninvolved side (first 15s was 79.52%) for children with HCP, and that COP displacement asymmetry switched to become larger underneath the involved side over time (the latter 15s was -82.81%) when there was no expectation for walking. This was inverted during GA, where children with HCP initially had more COP displacement on the involved side (-72.68%) and transitioned to higher levels on the uninvolved side (99.66%) as they prepared for gait initiation. Children with HCP took 0.2 seconds longer to initiate gait with their uninvolved (not preferred) side and also took twice as long to initiate gait overall in comparison to TD peers. Our data suggests that our listed hypotheses may be correct. However, this study has limitations to sample size, demographics and biomechanical metrics. Future studies should replicate these findings and include larger, more diverse samples with further metrics such as load. If findings are confirmed, this data suggests that therapies should consider that children with HCP might change postural strategies during standing when they are anticipating walking forward in comparison to simply standing in place. This dissertation seeks to set a foundation for collaborations between biomechanists and therapists alike, potentially highlighting novel opportunities to develop more innovative treatment options for children with HCP.
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    Venous thromboembolism after penetrating femoral and popliteal artery injuries: an opportunity for increased prevention
    Ratnasekera, Asanthi; Pulido, Odessa; Durgin, Sandra; Nichols, Sharon; Lozano, Alicia J.; Sienko, Danielle; Hanlon, Alexandra L.; Martin, Niels D. (BMJ, 2020-01)
    Background Trauma patients with penetrating vascular injuries have a higher rate of venous thromboembolism (VTE). The objective of this study was to determine the risk of VTE formation in penetrating femoral and popliteal vascular injuries and the effects of endovascular management of these injuries. Methods A retrospective study of Pennsylvania Trauma Outcome Study registry was conducted during a 5-year period (2013-2017). All adult patients with a penetrating mechanism with femoral/popliteal vascular injuries were studied. Primary outcome was incidence of VTE in patients with isolated arterial injuries versus combined arterial/venous injuries. Secondary endpoints were intensive care unit (ICU) length of stay (LOS), hospital LOS and mortality. Statistical comparisons were accomplished using Fisher's exact tests, and parametric two-sample t-tests or non-parametric Wilcoxon rank-sum tests for categorical and continuous variables, respectively. Results: Of the 865 patients with penetrating extremity vascular injuries, 207 had femoral or popliteal artery injuries. Patients with isolated arterial injuries (n=131) had a significantly lower deep venous thrombosis (DVT) rate compared with those with concurrent venous injuries (n=76) (3.1% vs. 13.2%, p=0.008). There were 14 patients in the study who developed DVTs. Among the four patients with isolated femoral or popliteal arterial injuries who had developed DVTs, three had an open repair. Among patients with isolated arterial injuries, those with DVT spend significantly more time on the ventilator (median=2 vs. 0, p=0.0020) compared with patients without DVT. Patients with DVT also had longer stay in the hospital (median=17.5 vs. 8, p=0.0664) and in the ICU (median=3 vs. 1, p=0.0585). Conclusions: Risk of DVT exists in patients with penetrating isolated femoral and popliteal artery trauma. Open repair was associated with significantly higher DVT rates in isolated arterial injuries. Level of evidence: Level IV therapeutic care/management.