Assessment of finite element human body and ATD models in estimating injury risk in far-side impacts using field-based injury risk.

The objective of this study was to assess the ability of finite element human body models (FEHBMs) and Anthropometric Test Device (ATD) models to estimate occupant injury risk by comparing it with field-based injury risk in far-side impacts. The study used the Global Human Body Models Consortium midsize male (M50-OS+B) and small female (F05-OS+B) simplified occupant models with a modular detailed brain, and the ES-2Re and SID-IIs ATD models in the simulated far-side crashes. A design of experiments (DOE) with a total of 252 simulations was conducted by varying lateral ΔV (10-50kph; 5kph increments), the principal direction of force (PDOF 50°, 60°, 65°, 70°, 75°, 80°, 90°), and occupant models. Models were gravity-settled and belted into a simplified vehicle model (SVM) modified for far-side impact simulations. Acceleration pulses and vehicle intrusion profiles used for the DOE were generated by impacting a 2012 Camry vehicle model with a mobile deformable barrier model across the 7 PDOFs and 9 lateral ΔV's in the DOE for a total of 63 additional simulations. Injury risks were estimated for the head, chest, lower extremity, pelvis (AIS 2+; AIS 3+), and abdomen (AIS 3+) using logistic regression models. Combined AIS 3+ injury risk for each occupant was calculated using AIS 3+ injury risk estimations for the head, chest, abdomen, and lower extremities. The injury risk calculated using computational models was compared with field-based injury risk derived from NASS-CDS by calculating their correlation coefficient. The field-based injury risk was calculated using risk curves that were created based on real-world crash data in a previous study (Hostetler et al., 2020). Occupant age (40 years), seatbelt use (belted occupant), collision deformation classification, lateral ΔV, and PDOF of the crash event were used in these curves to estimate field injury risk. Large differences in the kinematics were observed between HBM and ATD models. ATD models tended to overestimate risk in almost every case whereas HBMs yielded better risk estimates overall. Chest and lower extremity risks were the least correlated with field injury risk estimates. The overall risk of AIS 3+ injury risk was the strongest comparison to the field data-based risk curves. The HBMs were still not able to capture all the variance but future studies can be carried out that are focused on investigating their shortfalls and improving them to estimate injury risk closer to field injury risk in far-side crashes.

Depressive Symptoms and Associated Health-Related Variables in Older Adult Breast Cancer Survivors and Non-Cancer Controls.

OBJECTIVES: To examine the prevalence of depressive symptoms and associated risk factors in older adult breast cancer survivors (BCS) and age-matched non-cancer controls. SAMPLE & SETTING: Using the Surveillance, Epidemiology, and End Results-Medicare Health Outcome Survey linked dataset from 1998 to 2012, BCS and non-cancer controls aged 65 years or older were identified. METHODS & VARIABLES: Depressive symptoms, comorbidities, functional limitations, socio-demographics, and health-related information were examined. Univariate and multivariable logistic regression and marginal models were performed. RESULTS: 5,421 BCS and 21,684 controls were identified. BCS and non-cancer controls had similar prevalence of depressive symptoms. Having two or more comorbidities and functional limitations were strongly associated with elevated risk of depressive symptoms in BCS and non-cancer controls. IMPLICATIONS FOR NURSING: Having multiple comorbidities and multiple functional status are key factors associated with depressive symptoms in older adult BCS and non-cancer controls. Nurses are in an ideal position to screen older adult BCS and non-cancer controls at risk for depressive symptoms.

Community economic factors influence outcomes for patients with primary malignant glioma.

BACKGROUND: Community economics and other social health determinants influence outcomes in oncologic patient populations. We sought to explore their impact on presentation, treatment, and survival in glioma patients. METHODS: A retrospective cohort of patients with glioma (World Health Organization grades III-IV) diagnosed between 1999 and 2017 was assembled with data abstracted from medical record review. Patient factors included race, primary care provider (PCP) identified, marital status, insurance status, and employment status. Median household income based on zip code was used to classify patients as residing in high-income communities (HICs; ie, above the median state income) or low-income communities (LICs; ie, below the median state income). The Kaplan-Meier method was used to assess overall survival (OS); Cox proportional hazards regression was used to explore associations with OS. RESULTS: Included were 312 patients, 73% from LICs. Survivors residing in LICs and HICs did not differ by age, sex, race, tumor grade, having a PCP, employment status, insurance, time to presentation, or baseline performance status. Median OS was 4.1 months shorter for LIC patients (19.7 vs 15.6 mo; hazard ratio [HR], 0.75; 95% CI: 0.56-0.98, P = 0.04); this difference persisted with 1-year survival of 66% for HICs versus 61% for LICs at 1 year, 34% versus 24% at 3 years, and 29% versus 17% at 5 years. Multivariable analysis controlling for age, grade, and chemotherapy treatment showed a 25% lower risk of death for HIC patients (HR, 0.75; 95% CI: 0.57-0.99, P < 0.05). CONCLUSIONS: The economic status of a glioma patient's community may influence survival. Future efforts should investigate potential mechanisms such as health care access, stress, treatment adherence, and social support.

Health-related quality of life and medical comorbidities in older patients with pancreatic adenocarcinoma: An analysis using the 1998-2011 surveillance, epidemiology, and end results-medicare health outcomes survey data.

OBJECTIVES: This study compares health-related quality of life (HRQoL) of older patients with pancreatic ductal adenocarcinoma (PDAC) to controls without cancer, and examines the impact of medical comorbidities on HRQoL. MATERIALS AND METHODS: We conducted a case-control study using the 1998-2011 Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey (SEER-MHOS) linked dataset. Cases were Medicare beneficiaries aged 65 and older diagnosed with PDAC (N = 128) and matched controls were without a history of cancer (N = 512). We used the Short Form 36 (SF-36) and Veterans-RAND-12 (VR-12) to examine HRQoL and calculated mental (MCS) and physical (PCS) component scores. Linear regression and mixed effects models were used to examine the impact of medical comorbidities on MCS and PCS for cases and controls, respectively. RESULTS: Cases reported significantly poorer PCS (29.3 vs. 36.3) and MCS (44.8 vs. 49.9) compared to controls. Comorbidities were significantly associated with lower PCS and MCS in controls. However, neither total number of comorbidities or comorbidities grouped by organ systems (cardiopulmonary disease, musculoskeletal disease, diabetes) were significantly related to PCS or MCS for cases. Comparison of regression coefficients estimates did not indicate that lack of significance was due to differences in sample size. CONCLUSIONS: The results of this study highlight the poor HRQoL reported by older patients with PDAC. HRQoL scores were very low in this population, particularly in physical health status, which were not explained by comorbidities.

Assessment of fenofibrate-methylation interactions on triglycerides using longitudinal family data.

BACKGROUND: Triglyceride (TG) concentrations decrease in response to fenofibrate treatment, and also are associated with DNA methylation. But how interactions between fenofibrate response and DNA methylation affect TGs remains unclear. METHODS: In the present study, we identified and compared differential methylation sites associated with TG concentrations in individuals before and after fenofibrate treatment. We then estimated interactions between fenofibrate treatment and methylation to identify differential methylation effects associated with fenofibrate treatment on TG concentrations using the entire longitudinal family sample. To account for within-family and within-individual corrections, the generalized estimating equations approach was used to estimate main and interaction effects between methylation sites and fenofibrate treatment, adjusting for potential confounders. Analyses were also performed with and without adjusting for high-density lipoprotein (HDL) concentrations. RESULTS: Prior to fenofibrate treatment, 23 cytosine-phosphate-guanine (CpG) sites were significantly associated with TG concentrations, while only 13 CpG sites were identified posttreatment, adjusting for HDL. Without adjusting for HDL, pretreatment, 20 CpG sites were significantly associated with TG concentrations, while only 12 CpG sites were identified posttreatment. Among these sites, only one differential site (cg19003390 in the CPT1A gene) overlapped from pre- and posttreatment measurements regardless of HDL adjustment. Furthermore, 11 methylation sites showed substantial interaction effects (p < 1.43 × 10-7with Bonferroni correction) with or without HDL adjustment when using the whole longitudinal data. CONCLUSIONS: Our analyses suggest that DNA methylation likely modified the effect of fenofibrate on TG concentrations. Differential fenofibrate-associated methylation sites on TGs differed with and without adjusting for HDL concentrations, suggesting that these HDLs and TGs might share some common epigenetic processes.

Structural and functional assessment of the brain in European Americans with mild-to-moderate kidney disease: Diabetes Heart Study-MIND.

BACKGROUND: Advanced chronic kidney disease (CKD) is associated with altered cerebral structure and function. Relationships between mild-to-moderate CKD and brain morphology and cognitive performance were evaluated in European Americans (EAs). METHODS: A total of 478 EAs with estimated glomerular filtration rate (eGFR) >45 mL/min/1.73 m(2) and urine albumin:creatinine ratio (UACR) < 300 mg/g, most with type 2 diabetes (T2D), were included. Measures of total intracranial volume (TICV), cerebrospinal fluid volume, total white matter volume (TWMV), total gray matter volume (TGMV), total white matter lesion volume (TWMLV), hippocampal white matter volume (HWMV) and hippocampal gray matter volume (HGMV) were obtained with magnetic resonance imaging. Cognitive testing included memory (Rey Auditory Visual Learning Test), global cognition (Modified Mini-Mental State Examination) and executive function (Stroop Task, Semantic Fluency, Digit Symbol Substitution Test). Associations with CKD were assessed using log-transformed eGFR and UACR, adjusted for age, sex, body mass index, smoking, hemoglobin A1c, blood pressure, diabetes duration, cardiovascular disease and education. RESULTS: Participants were 55.2% female, 78.2% had T2D; mean ± SD age 67.6 ± 9.0 years, T2D duration 16.4 ± 6.5 years, eGFR 92.0 ± 22.3 mL/min/1.73 m(2) and UACR 23.8 ± 39.6 mg/g. In adjusted models, eGFR was negatively associated with TICV only in participants with T2D [parameter estimate (ß): -72.2, P = 0.002]. In non-diabetic participants, inverse relationships were observed between eGFR and HGMV (ß: -1.0, P = 0.03) and UACR and normalized TWMLV (ß: -0.2, P = 0.03). Kidney function and albuminuria did not correlate with cognitive testing. CONCLUSIONS: In EAs with mild CKD enriched for T2D, brain structure and cognitive performance were generally not impacted. Longitudinal studies are necessary to determine when cerebral structural changes and cognitive dysfunction develop with progressive CKD in EAs.

A physical activity intervention to treat the frailty syndrome in older persons-results from the LIFE-P study.

BACKGROUND: The frailty syndrome is as a well-established condition of risk for disability. Aim of the study is to explore whether a physical activity (PA) intervention can reduce prevalence and severity of frailty in a community-dwelling elders at risk of disability. METHODS: Exploratory analyses from the Lifestyle Interventions and Independence for Elders pilot, a randomized controlled trial enrolling 424 community-dwelling persons (mean age=76.8 years) with sedentary lifestyle and at risk of mobility disability. Participants were randomized to a 12-month PA intervention versus a successful aging education group. The frailty phenotype (ie, ≥3 of the following defining criteria: involuntary weight loss, exhaustion, sedentary behavior, slow gait speed, poor handgrip strength) was measured at baseline, 6 months, and 12 months. Repeated measures generalized linear models were conducted. RESULTS: A significant (p = .01) difference in frailty prevalence was observed at 12 months in the PA intervention group (10.0%; 95% confidence interval = 6.5%, 15.1%), relative to the successful aging group (19.1%; 95% confidence interval = 13.9%,15.6%). Over follow-up, in comparison to successful aging participants, the mean number of frailty criteria in the PA group was notably reduced for younger subjects, blacks, participants with frailty, and those with multimorbidity. Among the frailty criteria, the sedentary behavior was the one most affected by the intervention. CONCLUSIONS: Regular PA may reduce frailty, especially in individuals at higher risk of disability. Future studies should be aimed at testing the possible benefits produced by multidomain interventions on frailty.

Alzheimer's disease risk assessment using large-scale machine learning methods.

The goal of this work is to introduce new metrics to assess risk of Alzheimer's disease (AD) which we call AD Pattern Similarity (AD-PS) scores. These metrics are the conditional probabilities modeled by large-scale regularized logistic regression. The AD-PS scores derived from structural MRI and cognitive test data were tested across different situations using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. The scores were computed across groups of participants stratified by cognitive status, age and functional status. Cox proportional hazards regression was used to evaluate associations with the distribution of conversion times from mild cognitive impairment to AD. The performances of classifiers developed using data from different types of brain tissue were systematically characterized across cognitive status groups. We also explored the performance of anatomical and cognitive-anatomical composite scores generated by combining the outputs of classifiers developed using different types of data. In addition, we provide the AD-PS scores performance relative to other metrics used in the field including the Spatial Pattern of Abnormalities for Recognition of Early AD (SPARE-AD) index and total hippocampal volume for the variables examined.

Assessment of gene-covariate interactions by incorporating covariates into association mapping.

The HLA region is considered to be the main genetic risk factor for rheumatoid arthritis. Previous research demonstrated that HLA-DRB1 alleles encoding the shared epitope are specific for disease that is characterized by antibodies to cyclic citrullinated peptides (anti-CCP). In the present study, we incorporated the shared epitope and either anti-CCP antibodies or rheumatoid factor into linkage disequilibrium mapping, to assess the association between the shared epitope or antibodies with the disease gene identified. Incorporating the covariates into the association mapping provides a mechanism 1) to evaluate gene-gene and gene-environment interactions and 2) to dissect the pathways underlying disease induction/progress in quantitative antibodies.