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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Signatures of cysteine oxidation on muscle structural and contractile proteins are associated with physical performance and muscle function in older adults: Study of Muscle, Mobility and Aging (SOMMA)

Oxidative stress is considered a contributor to declining muscle function and mobility during aging; however, the underlying molecular mechanisms remain poorly described. We hypothesized that greater levels of cysteine (Cys) oxidation on muscle proteins are associated with decreased measures of mobility. Herein, we applied a novel redox proteomics approach to measure reversible protein Cys oxidation in vastus lateralis muscle biopsies collected from 56 subjects in the Study of Muscle, Mobility and Aging (SOMMA), a community-based cohort study of individuals aged 70 years and older. We tested whether levels of Cys oxidation on key muscle proteins involved in muscle structure and contraction were associated with muscle function (leg power and strength), walking speed, and fitness (VO 2 peak on cardiopulmonary exercise testing) using linear regression models adjusted for age, sex, and body weight. Higher oxidation levels of select nebulin Cys sites were associated with lower VO 2 peak, while greater oxidation of myomesin-1, myomesin-2, and nebulin Cys sites was associated with slower walking speed. Higher oxidation of Cys sites in key proteins such as myomesin-2, alpha-actinin-2, and skeletal muscle alpha-actin were associated with lower leg power and strength. We also observed an unexpected correlation (R = 0.48) between a higher oxidation level of eight Cys sites in alpha-actinin-3 and stronger leg power. Despite this observation, the results generally support the hypothesis that Cys oxidation of muscle proteins impairs muscle power and strength, walking speed, and cardiopulmonary fitness with aging.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Associations between regional blood-brain barrier permeability, aging, and Alzheimer’s disease biomarkers in cognitively normal older adults

Background Increased blood-brain barrier permeability (BBBp) has been hypothesized as a feature of aging that may lead to the development of Alzheimer’s disease (AD). We sought to identify the brain regions most vulnerable to greater BBBp during aging and examine their regional relationship with neuroimaging biomarkers of AD. Methods We studied 31 cognitively normal older adults (OA) and 10 young adults (YA) from the Berkeley Aging Cohort Study (BACS). Both OA and YA received dynamic contrast-enhanced MRI (DCE-MRI) to quantify K trans values, as a measure of BBBp, in 37 brain regions across the cortex. The OA also received Pittsburgh compound B (PiB)-PET to create distribution volume ratios (DVR) images and flortaucipir (FTP)- PET to create partial volume corrected standardized uptake volume ratios (SUVR) images. Repeated measures ANOVA assessed the brain regions where OA showed greater BBBp than YA. In OA, K trans values were compared based on sex, Aβ positivity status, and APOE4carrier status within a composite region across the areas susceptible to aging. We used linear models and sparse canonical correlation analysis (SCCA) to examine the relationship between K trans and AD biomarkers. Results OA showed greater BBBp than YA predominately in the temporal lobe, with some involvement of parietal, occipital and frontal lobes. Within an averaged ROI of affected regions, there was no difference in K trans values based on sex or Aβ positivity, but OA who were APOE4carriers had significantly higher K trans values. There was no direct relationship between averaged K trans and global Aβ pathology, but there was a trend for an Ab status by tau interaction on K trans in this region. SCCA showed increased K trans was associated with increased PiB DVR, mainly in temporal and parietal brain regions. There was not a significant relationship between K trans and FTP SUVR. Discussion Our findings indicate that the BBB shows regional vulnerability during normal aging that overlaps considerably with the pattern of AD pathology. Greater BBBp in brain regions affected in aging is related to APOE genotype and may also be related to the pathological accumulation of Aβ.

Science & Technology - Other Topics↗
NASA NTRS2011

Integration of Evidence Base into a Probabilistic Risk Assessment

INTRODUCTION: A probabilistic decision support model such as the Integrated Medical Model (IMM) utilizes an immense amount of input data that necessitates a systematic, integrated approach for data collection, and management. As a result of this approach, IMM is able to forecasts medical events, resource utilization and crew health during space flight. METHODS: Inflight data is the most desirable input for the Integrated Medical Model. Non-attributable inflight data is collected from the Lifetime Surveillance for Astronaut Health study as well as the engineers, flight surgeons, and astronauts themselves. When inflight data is unavailable cohort studies, other models and Bayesian analyses are used, in addition to subject matters experts input on occasion. To determine the quality of evidence of a medical condition, the data source is categorized and assigned a level of evidence from 1-5; the highest level is one. The collected data reside and are managed in a relational SQL database with a web-based interface for data entry and review. The database is also capable of interfacing with outside applications which expands capabilities within the database itself. Via the public interface, customers can access a formatted Clinical Findings Form (CLiFF) that outlines the model input and evidence base for each medical condition. Changes to the database are tracked using a documented Configuration Management process. DISSCUSSION: This strategic approach provides a comprehensive data management plan for IMM. The IMM Database s structure and architecture has proven to support additional usages. As seen by the resources utilization across medical conditions analysis. In addition, the IMM Database s web-based interface provides a user-friendly format for customers to browse and download the clinical information for medical conditions. It is this type of functionality that will provide Exploratory Medicine Capabilities the evidence base for their medical condition list. CONCLUSION: The IMM Database in junction with the IMM is helping NASA aerospace program improve the health care and reduce risk for the astronauts crew. Both the database and model will continue to expand to meet customer needs through its multi-disciplinary evidence based approach to managing data. Future expansion could serve as a platform for a Space Medicine Wiki of medical conditions.

Saile, Lyn↗
DOE OSTI2022

Efficacy and safety of warfarin in patients with non-valvular atrial fibrillation and CKD G3–G5D

ABSTRACT Background Observational data comparing warfarin with no treatment for patients with non-valvular atrial fibrillation (NVAF) and severely reduced glomerular filtration rate (GFR) are conflicting and randomized controlled trials (RCTs) are lacking. Most studies do not provide information on warfarin treatment quality, making them difficult to compare. Methods This national cohort study investigates the risk of ischaemic stroke and major bleeding during warfarin treatment compared with no oral anticoagulants in patients with NVAF, GFR category 3–5 (G3–G5) or on dialysis (G5D), with kidney transplant recipients excluded, between 2009 and 2018. Data extracted from high-quality Swedish national healthcare registries, including the Swedish Renal Registry, AuriculA—the Swedish national quality registry for atrial fibrillation and anticoagulation—and the Stroke Registry. Results At enrolment of 12 106 patients, 21.4% were G3, 43.5% were G4, 11.6% were G5 and 23.6% were G5D. The mean time in the therapeutic range was 70%. Warfarin compared with no treatment showed a lower risk for ischaemic stroke for G3 {hazard ratio [HR] 0.37 [95% confidence interval (CI) 0.18–0.76]}, G4 [0.53 (0.38–0.74)] and G5D [0.49 (0.30–0.79)] and an increased risk of major bleeding in G4 [HR 1.22 (1.02–1.46)], G5 [1.52 (1.15–2.01)] and G5D [1.23 (1.00–1.51)]. All-cause mortality was more than halved on warfarin compared with no treatment in all GFR categories. Conclusions Warfarin treatment is associated with a lower risk of ischaemic stroke for patients with NVAF and G3, G4 and G5D at the cost of a higher risk of major bleeding for G4–G5D. Existing observational data are conflicting, stressing the need for RCTs on warfarin compared with no treatment in G4–G5D. Awaiting RCTs, it seems reasonable to treat selected patients on dialysis and NVAF with warfarin.

Welander, Frida (ORCID:0000000311117215)↗
DOE OSTI2023

Neurobehavioral symptoms in children born extremely preterm: A Swedish National Study

Abstract Aim To determine the prevalence of neurobehavioral symptoms at 6.5 years in children born extremely preterm (EPT, <27 weeks' gestation). Methods Population‐based cohort study of infants born EPT in Sweden from 2004 to 2007. Of 486 survivors 375 were assessed and compared with 369 matched term‐born controls. EPT children free from neurosensory and intellectual disabilities (neurodevelopmental disabilities [NDD]‐free, n = 236) were compared separately. Standardised questionnaires were used to assess parental ratings of hyperactivity and attention, emotional, peer‐relation, conduct and social problems; and deficits in perception, language and memory. Results EPT children had more reported problems in all assessed neurobehavioral domains than controls, with more than three times greater odds for most outcomes. Except for conduct problems, increased problems were identified also in NDD–free children. The odds of having neurobehavioral problems in ≥3 co‐occurring domains were five (whole EPT group) and three (NDD‐free group) times higher than in controls. Conclusion EPT children with or without NDD have more neurobehavioral problems in multiple domains than term peers. Ongoing assessments of behaviour until school age or beyond should recognise early symptoms of attention, everyday social problems, perceptual, emotional or language difficulties.

Serenius, Fredrik↗
DOE OSTI2024

Intra- and inter-subtype HIV diversity between 1994 and 2018 in southern Uganda: a longitudinal population-based study

There is limited data on human immunodeficiency virus (HIV) evolutionary trends in African populations. We evaluated changes in HIV viral diversity and genetic divergence in southern Uganda over a 24-year period spanning the introduction and scale-up of HIV prevention and treatment programs using HIV sequence and survey data from the Rakai Community Cohort Study, an open longitudinal population-based HIV surveillance cohort. Gag (p24) and env (gp41) HIV data were generated from people living with HIV (PLHIV) in 31 inland semi-urban trading and agrarian communities (1994–2018) and four hyperendemic Lake Victoria fishing communities (2011–2018) under continuous surveillance. HIV subtype was assigned using the Recombination Identification Program with phylogenetic confirmation. Inter-subtype diversity was evaluated using the Shannon diversity index, and intra-subtype diversity with the nucleotide diversity and pairwise TN93 genetic distance. Genetic divergence was measured using root-to-tip distance and pairwise TN93 genetic distance analyses. Demographic history of HIV was inferred using a coalescent-based Bayesian Skygrid model. Evolutionary dynamics were assessed among demographic and behavioral population subgroups, including by migration status. 9931 HIV sequences were available from 4999 PLHIV, including 3060 and 1939 persons residing in inland and fishing communities, respectively. In inland communities, subtype A1 viruses proportionately increased from 14.3% in 1995 to 25.9% in 2017 (P < .001), while those of subtype D declined from 73.2% in 1995 to 28.2% in 2017 (P < .001). The proportion of viruses classified as recombinants significantly increased by nearly four-fold from 12.2% in 1995 to 44.8% in 2017. Inter-subtype HIV diversity has generally increased. While intra-subtype p24 genetic diversity and divergence leveled off after 2014, intra-subtype gp41 diversity, effective population size, and divergence increased through 2017. Intra- and inter-subtype viral diversity increased across all demographic and behavioral population subgroups, including among individuals with no recent migration history or extra-community sexual partners. This study provides insights into population-level HIV evolutionary dynamics following the scale-up of HIV prevention and treatment programs. Continued molecular surveillance may provide a better understanding of the dynamics driving population HIV evolution and yield important insights for epidemic control and vaccine development.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Association between the findings of metachronous secondary primary malignancies and the number of Lugol-voiding lesions

Summary This study was designed to evaluate the relation between dysplastic squamous epithelium in the esophageal mucosa and the development of metachronous secondary primary malignancies (mSPM) other than esophagus after endoscopic resection (ER) in patients with early esophageal squamous cell carcinoma (SCC). We studied 330 patients with early esophageal SCC who underwent ER as a post hoc analysis of a prospective multicenter cohort study (UMIN Clinical Trials Registry ID UMIN000001676). Lugol-voiding lesions (LVL) were graded into 3 categories (A = no lesion; B = 1 to 9 lesions; C ≥ 10 lesions). The following variables were studied: (i) the incidences of mSPM other than esophagus; (ii) the standardized incidence ratios (SIRs) of mSPM; (iii) the cumulative incidence and total number of mSPM other than esophagus; and (iv) predictors of mSPM other than esophagus on analysis with a multivariate Cox proportional-hazards model. After a median follow-up of 46.6 months, mSPM other than esophagus was diagnosed in a total of 73 patients (90 lesions). Among the 106 patients in group C, 37 patients had mSPM (51 lesions), including head and neck cancer in 14 patients (24 lesions) and gastric cancer in 12 patients (16 lesions). The SIR of mSPM was 3.61 in this study subjects. An increase in the LVL grade (A to B to C) was associated with a progressive increase in the cumulative incidence rate of mSPM other than esophagus (P = 0.017 for A vs. C, P = 0.023 for B vs. C). An increase in the LVL grade (A to B to C) was also associated with a progressive increase in the total number of mSPM other than esophagus per 100 person-years (primary events, relative risk [RR] = 1.66 and 3.24 for grades B and C, respectively, vs. A, P = 0.002 for trend; all events, RR = 1.81 and 4.66 for grades B and C, respectively, vs. A, P < 0.0001 for trend). LVL grade C was a strong predictor of mSPM other than esophagus (RR = 3.41 for A vs. C). LVL grade may be a useful predictor of the risk of mSPM other than esophagus after ER in patients with early esophageal SCC.

Katada, Chikatoshi↗
DOE OSTI2025

Risk of Mortality in Family Members of Men Seeking Fertility Assessment

Objective: To assess mortality in family members of men seeking fertility assessment. Subfertility serves as a biomarker for overall somatic health, and poor semen quality is associated with increased risk of hospitalization and mortality from chronic conditions. However, it is unclear if these risks extend to family members of men with low sperm count. Design: Retrospective cohort study. Subjects: Family members, up to third-degree relatives, of men in the Subfertility, Health and Assisted Reproduction and the Environment cohort who underwent a semen analysis as part of a fertility assessment 1996–2017. Relatives of men with a recorded total sperm count who lived in Utah for ≥1 year 1904–2017 were included in the analysis (N = 22,280 families). Exposure: Individuals were classified by family membership. Families were classified as relatives of azoospermic (0M), oligozoospermic (<39M), or normozoospermic (≥39M) men. The average total sperm count of the proband (male relative) with fertility assessment was also included as a continuous exposure measure. Main Outcome Measures: The main outcomes were all-cause and cause-specific mortality risk by sex, age, and degree of relation: first-, second-, and third-degree. Cox proportional hazard models were used to test the association between fertility classification and mortality, controlling for sex, race/ethnicity, and birth year. Results: A total of 666,437 relatives of men with fertility assessment (N deaths = 183,974) were included in the analysis. Relative to normozoospermia families, all-cause mortality risk increased in oligozoospermia families (hazard ratio [HR] oligozoospermia , 1.03; 95% confidence interval [CI], 1.01–1.05). Close relatives, first- (HR oligozoospermia , 1.17; 95% CI, 1.07–1.28) and second-degree relatives (HR azoospermia , 1.11; 95% CI, 1.04–1.20; HR oligozoospermia , 1.05; 95% CI,1.01–1.09), of azoospermic and oligozoospermic men had the highest all-cause and cause-specific mortality risk, including death attributed to cardiovascular disease or congenital birth conditions. Conclusion: Our results suggest that familial all-cause and cause-specific mortality risk differ by fertility phenotype. Families of azoospermic and oligozoospermic men showed significantly increased risk, particularly for close relatives. This study provides further evidence that shared genetic and/or environmental factors could influence both fertility and somatic health.

Male fertility↗
DOE OSTI2022

Hearing impairment and tinnitus among older construction workers employed at DOE facilities

Few studies have defined the risk of hearing impairment and tinnitus after retirement. This report measures hearing impairment and tinnitus prevalence among older construction trades workers. The study cohort included 21,340 participants in a national medical screening program. Audiometric hearing impairment was classified according to the Global Burden of Disease Study. Tinnitus was determined by self-report. An internal subcohort of nonconstruction trades workers served as a reference group. Stratified analyses and multivariate analyses were used to measure the prevalence of hearing impairment and tinnitus by age, sex, and job category. Prevalence of any hearing impairment was 55.2% (males, 57.7%; females, 26.8%) and increased rapidly with age. Construction trades workers were 40% more likely to have hearing impairment than the reference group. The overall prevalence of tinnitus was 46.52% and followed patterns similar to hearing impairment. Workers with hearing impairment were more likely to also have tinnitus, but tinnitus was frequently reported in the absence of measured hearing impairment. Hearing impairment and tinnitus prevalence were much higher in this study than in previous research. A significant reason for the difference is that BTMed follows participants after they have retired. To draw conclusions about the risk for work-related chronic diseases and disorders it is important to monitor workers through their lifetimes. Also, tinnitus by itself should be given greater significance. We report the findings reinforce the need to promote noise reduction and hearing conservation in construction.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

The relationship between below average cognitive ability at age 5 years and the child’s experience of school at age 9

Background At age 5, while only embarking on their educational journey, substantial differences in children’s cognitive ability will already exist. The aim of this study was to examine the causal association between below average cognitive ability at age 5 years and child-reported experience of school and self-concept, and teacher-reported class engagement and emotional-behavioural function at age 9 years. Methods This longitudinal cohort study used data from 7,392 children in the Growing Up in Ireland Infant Cohort, who had completed the Picture Similarities and Naming Vocabulary subtests of the British Abilities Scales at age 5. Principal components analysis was used to produce a composite general cognitive ability score for each child. Children with a general cognitive ability score more than 1 standard deviation (SD) below the mean at age 5 were categorised as ‘Below Average Cognitive Ability’ (BACA), and those scoring above this as ‘Typical Cognitive Development’ (TCD). The outcomes of interest, measured at age 9, were child-reported experience of school, child’s self-concept, teacher-reported class engagement, and teacher-reported emotional behavioural function. Binary and multinomial logistic regression models were used to examine the association between BACA and these outcomes. Results Compared to those with TCD, those with BACA had significantly higher odds of never liking school [Adjusted odds ratio (AOR) 1.82, 95% CI 1.37–2.43, p < 0.001], of being picked on (AOR 1.27, 95% CI 1.09–1.48) and of picking on others (AOR 1.53, 95% CI 1.27–1.84). They had significantly higher odds of experiencing low self-concept (AOR 1.20, 95% CI 1.02–1.42) and emotional-behavioural difficulties (AOR 1.34, 95% CI 1.10–1.63, p = 0.003). Compared to those with TCD, children with BACA had significantly higher odds of hardly ever or never being interested, motivated and excited to learn (AOR 2.29, 95% CI 1.70–3.10). Conclusion Children with BACA at school-entry had significantly higher odds of reporting a negative school experience and low self-concept at age 9. They had significantly higher odds of having teacher-reported poor class engagement and problematic emotional-behavioural function at age 9. The findings of this study suggest BACA has a causal role in these adverse outcomes. Early childhood policy and intervention design should be cognisant of the important role of cognitive ability in school and childhood outcomes.

Bowe, Andrea K.↗
DOE OSTI2024

Tau Positron Emission Tomography for Predicting Dementia in Individuals With Mild Cognitive Impairment

An accurate prognosis is especially pertinent in mild cognitive impairment (MCI), when individuals experience considerable uncertainty about future progression. To evaluate the prognostic value of tau positron emission tomography (PET) to predict clinical progression from MCI to dementia. This was a multicenter cohort study with external validation and a mean (SD) follow-up of 2.0 (1.1) years. Data were collected from centers in South Korea, Sweden, the US, and Switzerland from June 2014 to January 2024. Participant data were retrospectively collected and inclusion criteria were a baseline clinical diagnosis of MCI; longitudinal clinical follow-up; a Mini-Mental State Examination (MMSE) score greater than 22; and available tau PET, amyloid-β (Aβ) PET, and magnetic resonance imaging (MRI) scan less than 1 year from diagnosis. A total of 448 eligible individuals with MCI were included (331 in the discovery cohort and 117 in the validation cohort). None of these participants were excluded over the course of the study. Exposures included Tau PET, Aβ PET, and MRI. Positive results on tau PET (temporal meta–region of interest), Aβ PET (global; expressed in the standardized metric Centiloids), and MRI (Alzheimer disease [AD] signature region) was assessed using quantitative thresholds and visual reads. Clinical progression from MCI to all-cause dementia (regardless of suspected etiology) or to AD dementia (AD as suspected etiology) served as the primary outcomes. The primary analyses were receiver operating characteristics. In the discovery cohort, the mean (SD) age was 70.9 (8.5) years, 191 (58%) were male, the mean (SD) MMSE score was 27.1 (1.9), and 110 individuals with MCI (33%) converted to dementia (71 to AD dementia). Only the model with tau PET predicted all-cause dementia (area under the receiver operating characteristic curve [AUC], 0.75; 95% CI, 0.70-0.80) better than a base model including age, sex, education, and MMSE score (AUC, 0.71; 95% CI, 0.65-0.77; P = .02), while the models assessing the other neuroimaging markers did not improve prediction. In the validation cohort, tau PET replicated in predicting all-cause dementia. Compared to the base model (AUC, 0.75; 95% CI, 0.69-0.82), prediction of AD dementia in the discovery cohort was significantly improved by including tau PET (AUC, 0.84; 95% CI, 0.79-0.89; P < .001), tau PET visual read (AUC, 0.83; 95% CI, 0.78-0.88; P = .001), and Aβ PET Centiloids (AUC, 0.83; 95% CI, 0.78-0.88; P = .03). In the validation cohort, only the tau PET and the tau PET visual reads replicated in predicting AD dementia. In this study, tau-PET showed the best performance as a stand-alone marker to predict progression to dementia among individuals with MCI. This suggests that, for prognostic purposes in MCI, a tau PET scan may be the best currently available neuroimaging marker.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

COVID ‐19 outcomes in patients with cancer: Findings from the University of California health system database

Abstract Background The interaction between cancer diagnoses and COVID‐19 infection and outcomes is unclear. We leveraged a state‐wide, multi‐institutional database to assess cancer‐related risk factors for poor COVID‐19 outcomes. Methods We conducted a retrospective cohort study using the University of California Health COVID Research Dataset, which includes electronic health data of patients tested for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) at 17 California medical centers. We identified adults tested for SARS‐CoV‐2 from 2/1/2020–12/31/2020 and selected a cohort of patients with cancer. We obtained demographic, clinical, cancer type, and antineoplastic therapy data. The primary outcome was hospitalization within 30d after the first positive SARS‐CoV‐2 test. Secondary outcomes were SARS‐CoV‐2 positivity and severe COVID‐19 (intensive care, mechanical ventilation, or death within 30d after the first positive test). We used multivariable logistic regression to identify cancer‐related factors associated with outcomes. Results We identified 409,462 patients undergoing SARS‐CoV‐2 testing. Of 49,918 patients with cancer, 1781 (3.6%) tested positive. Patients with cancer were less likely to test positive (RR 0.70, 95% CI: 0.67–0.74, p < 0.001). Among the 1781 SARS‐CoV‐2‐positive patients with cancer, BCR/ABL‐negative myeloproliferative neoplasms (RR 2.15, 95% CI: 1.25–3.41, p = 0.007), venetoclax (RR 2.96, 95% CI: 1.14–5.66, p = 0.028), and methotrexate (RR 2.72, 95% CI: 1.10–5.19, p = 0.032) were associated with greater hospitalization risk. Cancer and therapy types were not associated with severe COVID‐19. Conclusions In this large, diverse cohort, cancer was associated with a decreased risk of SARS‐CoV‐2 positivity. Patients with BCR/ABL‐negative myeloproliferative neoplasm or receiving methotrexate or venetoclax may be at increased risk of hospitalization following SARS‐CoV‐2 infection. Mechanistic and comparative studies are needed to validate findings.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Post-Combat-Injury Opioid Prescription and Alcohol Use Disorder in the Military

Previous studies have identified combat exposure and combat traumatic experience as problematic drinking risk factors. Increasing evidence suggests that opioid use increases the risk of alcohol use disorder. This study investigated the association between opioid prescription use after injury and (1) alcohol use disorder and (2) severity of alcohol use disorder among deployed military servicemembers. Deidentified health records data of 9,029 deployed servicemembers from a retrospective cohort study were analyzed. Data were randomly selected from the Department of Defense Trauma Registry and included servicemembers with combat injuries during deployment in Iraq or Afghanistan (2002–2016). Pharmacy records and International Classification of Diseases, Ninth and Tenth Revision diagnosis codes were used. Three groups were identified (no opioid prescription use, nonpersistent opioid prescription use, and persistent opioid prescription use) and were compared on the basis of alcohol use disorder risk using Cox proportional hazard models. Data analyses were performed in 2021. Of the 9,029 servicemembers with combat injury, 2,262 developed alcohol use disorder (1,322 developed severe alcohol use disorder). Compared with no opioid prescription use, increased alcohol use disorder risk was associated with persistent opioid prescription use, with a hazard ratio of 1.13 (95% CI=1.02, 1.26). After covariate adjustment, increased risk remained statistically significant (hazards ratio=1.24; 95% CI=1.10, 1.39). There was no significant difference in alcohol use disorder risk between no opioid prescription use and nonpersistent opioid prescription use. The risk of severe alcohol use disorder did not vary by opioid use among servicemembers with alcohol use disorder diagnosis. Furthermore, the findings of the study suggest that the incidence of alcohol use disorder was higher among injured servicemembers with persistent opioid prescription use than among those without opioid use. If replicated in prospective studies, the findings highlight the need for clinicians to consider the current and history of alcohol use of patients in initiating treatment involving opioids.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Association of post-COVID phenotypic manifestations with new-onset psychiatric disease

Acute COVID-19 infection can be followed by diverse clinical manifestations referred to as Post Acute Sequelae of SARS-CoV2 Infection (PASC). Studies have shown an increased risk of being diagnosed with new-onset psychiatric disease following a diagnosis of acute COVID-19. However, it was unclear whether non-psychiatric PASC-associated manifestations (PASC-AMs) are associated with an increased risk of new-onset psychiatric disease following COVID-19. A retrospective electronic health record (EHR) cohort study of 2,391,006 individuals with acute COVID-19 was performed to evaluate whether non-psychiatric PASC-AMs are associated with new-onset psychiatric disease. Data were obtained from the National COVID Cohort Collaborative (N3C), which has EHR data from 76 clinical organizations. EHR codes were mapped to 151 non-psychiatric PASC-AMs recorded 28–120 days following SARS-CoV-2 diagnosis and before diagnosis of new-onset psychiatric disease. Association of newly diagnosed psychiatric disease with age, sex, race, pre-existing comorbidities, and PASC-AMs in seven categories was assessed by logistic regression. There were significant associations between a diagnosis of any psychiatric disease and five categories of PASC-AMs with odds ratios highest for neurological, cardiovascular, and constitutional PASC-AMs with odds ratios of 1.31, 1.29, and 1.23 respectively. Secondary analysis revealed that the proportions of 50 individual clinical features significantly differed between patients diagnosed with different psychiatric diseases. Our study provides evidence for association between non-psychiatric PASC-AMs and the incidence of newly diagnosed psychiatric disease. Significant associations were found for features related to multiple organ systems. This information could prove useful in understanding risk stratification for new-onset psychiatric disease following COVID-19. Prospective studies are needed to corroborate these findings.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Machine learning approaches to predict gestational age in normal and complicated pregnancies via urinary metabolomics analysis

The elucidation of dynamic metabolomic changes during gestation is particularly important for the development of methods to evaluate pregnancy status or achieve earlier detection of pregnancy-related complications. Some studies have constructed models to evaluate pregnancy status and predict gestational age using omics data from blood biospecimens; however, less invasive methods are desired. Here we propose a model to predict gestational age, using urinary metabolite information. In our prospective cohort study, we collected 2741 urine samples from 187 healthy pregnant women, 23 patients with hypertensive disorders of pregnancy, and 14 patients with spontaneous preterm birth. Using gas chromatography-tandem mass spectrometry, we identified 184 urinary metabolites that showed dynamic systematic changes in healthy pregnant women according to gestational age. A model to predict gestational age during normal pregnancy progression was constructed; the correlation coefficient between actual and predicted weeks of gestation was 0.86. The predicted gestational ages of cases with hypertensive disorders of pregnancy exhibited significant progression, compared with actual gestational ages. This is the first study to predict gestational age in normal and complicated pregnancies by using urinary metabolite information. Minimally invasive urinary metabolomics might facilitate changes in the prediction of gestational age in various clinical settings.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2009

Parathyroid Hormone Levels and Cognition

Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, p<.01). There was no significant group difference in ionized calcium levels. Overall, PTH was correlated with the MMSE (r=-.323, p=.001). Individual regression analyses revealed a statistically significant correlation between PTH and MMSE in the self-neglect group (r=-.298, p=.024) and this remained significant after controlling for ionized calcium levels in the regression. No significant associations were revealed in the control group or among any of the other cognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.

Burnett, J.↗
DOE OSTI2024

Cancer Incidence Trends in Successive Social Generations in the US

Importance: The incidence of some cancers in the US is increasing in younger age groups, but underlying trends in cancer patterns by birth year remain unclear. Objective: To estimate cancer incidence trends in successive social generations. Design, Setting, and Participants: In this cohort study, incident invasive cancers were ascertained from the Surveillance, Epidemiology, and End Results (SEER) program’s 13-registry database (November 2020 submission, accessed August 14, 2023). Invasive cancers diagnosed at ages 35 to 84 years during 1992 to 2018 within 152 strata were defined by cancer site, sex, and race and ethnicity. Exposure: Invasive cancer. Main Outcome and Measures: Stratum-specific semiparametric age-period-cohort (SAGE) models were fitted and incidence per 100 000 person-years at the reference age of 60 years was calculated for single-year birth cohorts from 1908 through 1983 (fitted cohort patterns [FCPs]). The FCPs and FCP incidence rate ratios (IRRs) were compared by site for Generation X (born between 1965 and 1980) and Baby Boomers (born between 1946 and 1964). Results: A total of 3.8 million individuals with invasive cancer (51.0% male; 8.6% Asian or Pacific Islander, 9.5% Hispanic, 10.4% non-Hispanic Black, and 71.5% non-Hispanic White) were included in the analysis. In Generation X vs Baby Boomers, FCP IRRs among women increased significantly for thyroid (2.76; 95% CI, 2.41-3.15), kidney (1.99; 95% CI, 1.70-2.32), rectal (1.84; 95% CI, 1.52-2.22), corpus uterine (1.75; 95% CI, 1.40-2.18), colon (1.56; 95% CI, 1.27-1.92), and pancreatic (1.39; 95% CI, 1.07-1.80) cancers; non-Hodgkins lymphoma (1.40; 95% CI, 1.08-1.82); and leukemia (1.27; 95% CI, 1.03-1.58). Among men, IRRs increased for thyroid (2.16; 95% CI, 1.87-2.50), kidney (2.14; 95% CI, 1.86-2.46), rectal (1.80; 95% CI, 1.52-2.12), colon (1.60; 95% CI, 1.32-1.94), and prostate (1.25; 95% CI, 1.03-1.52) cancers and leukemia (1.34; 95% CI, 1.08-1.66). Lung (IRR, 0.60; 95% CI, 0.50-0.72) and cervical (IRR, 0.71; 95% CI, 0.57-0.89) cancer incidence decreased among women, and lung (IRR, 0.51; 95% CI, 0.43-0.60), liver (IRR, 0.76; 95% CI, 0.63-0.91), and gallbladder (IRR, 0.85; 95% CI, 0.72-1.00) cancer and non-Hodgkins lymphoma (IRR, 0.75; 95% CI, 0.61-0.93) incidence decreased among men. For all cancers combined, FCPs were higher in Generation X than for Baby Boomers because gaining cancers numerically overtook falling cancers in all groups except Asian or Pacific Islander men. Conclusions and Relevance: In this model-based cohort analysis of incident invasive cancer in the general population, decreases in lung and cervical cancers in Generation X may be offset by gains at other sites. Generation X may be experiencing larger per-capita increases in the incidence of leading cancers than any prior generation born in 1908 through 1964. On current trajectories, cancer incidence could remain high for decades.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Evaluation of Plasma Phosphorylated Tau217 for Differentiation Between Alzheimer Disease and Frontotemporal Lobar Degeneration Subtypes Among Patients With Corticobasal Syndrome

Plasma phosphorylated tau217 (p-tau217), a biomarker of Alzheimer disease (AD), is of special interest in corticobasal syndrome (CBS) because autopsy studies have revealed AD is the driving neuropathology in up to 40% of cases. This differentiates CBS from other 4-repeat tauopathy (4RT)–associated syndromes, such as progressive supranuclear palsy Richardson syndrome (PSP-RS) and nonfluent primary progressive aphasia (nfvPPA), where underlying frontotemporal lobar degeneration (FTLD) is typically the primary neuropathology. To validate plasma p-tau217 against positron emission tomography (PET) in 4RT-associated syndromes, especially CBS. This multicohort study with 6, 12, and 24-month follow-up recruited adult participants between January 2011 and September 2020 from 8 tertiary care centers in the 4RT Neuroimaging Initiative (4RTNI). All participants with CBS (n = 113), PSP-RS (n = 121), and nfvPPA (n = 39) were included; other diagnoses were excluded due to rarity (n = 29). Individuals with PET-confirmed AD (n = 54) and PET-negative cognitively normal control individuals (n = 59) were evaluated at University of California San Francisco. Operators were blinded to the cohort. Plasma p-tau217, measured by Meso Scale Discovery electrochemiluminescence, was validated against amyloid-β (Aβ) and flortaucipir (FTP) PET. Imaging analyses used voxel-based morphometry and bayesian linear mixed-effects modeling. Clinical biomarker associations were evaluated using longitudinal mixed-effect modeling. Of 386 participants, 199 (52%) were female, and the mean (SD) age was 68 (8) years. Plasma p-tau217 was elevated in patients with CBS with positive Aβ PET results (mean [SD], 0.57 [0.43] pg/mL) or FTP PET (mean [SD], 0.75 [0.30] pg/mL) to concentrations comparable to control individuals with AD (mean [SD], 0.72 [0.37]), whereas PSP-RS and nfvPPA showed no increase relative to control. Within CBS, p-tau217 had excellent diagnostic performance with area under the receiver operating characteristic curve (AUC) for Aβ PET of 0.87 (95% CI, 0.76-0.98; P < .001) and FTP PET of 0.93 (95% CI, 0.83-1.00; P < .001). At baseline, individuals with CBS-AD (n = 12), defined by a PET-validated plasma p-tau217 cutoff 0.25 pg/mL or greater, had increased temporoparietal atrophy at baseline compared to individuals with CBS-FTLD (n = 39), whereas longitudinally, individuals with CBS-FTLD had faster brainstem atrophy rates. Individuals with CBS-FTLD also progressed more rapidly on a modified version of the PSP Rating Scale than those with CBS-AD (mean [SD], 3.5 [0.5] vs 0.8 [0.8] points/year; P = .005). In this cohort study, plasma p-tau217 had excellent diagnostic performance for identifying Aβ or FTP PET positivity within CBS with likely underlying AD pathology. Plasma P-tau217 may be a useful and inexpensive biomarker to select patients for CBS clinical trials.

59 BASIC BIOLOGICAL SCIENCES↗