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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 OSTI2025

HighDimMixedModels.jl: Robust high-dimensional mixed-effects models across omics data

High-dimensional mixed-effects models are an increasingly important form of regression in which the number of covariates rivals or exceeds the number of samples, which are collected in groups or clusters. The penalized likelihood approach to fitting these models relies on a coordinate descent algorithm that lacks guarantees of convergence to a global optimum. Here, we empirically study the behavior of this algorithm on simulated and real examples of three types of data that are common in modern biology: transcriptome, genome-wide association, and microbiome data. Our simulations provide new insights into the algorithm’s behavior in these settings, and, comparing the performance of two popular penalties, we demonstrate that the smoothly clipped absolute deviation (SCAD) penalty consistently outperforms the least absolute shrinkage and selection operator (LASSO) penalty in terms of both variable selection and estimation accuracy across omics data. To empower researchers in biology and other fields to fit models with the SCAD penalty, we implement the algorithm in a Julia package, HighDimMixedModels.jl .

Gorstein, Evan↗
DOE OSTI2024

Evaluation of partial volume correction and analysis of longitudinal [ 18 F]GTP1 tau PET imaging in Alzheimer's disease using linear mixed-effects models

Purpose: We evaluated the impact of partial volume correction (PVC) methods on the quantification of longitudinal [ 18 F]GTP1 tau positron-emission tomography (PET) in Alzheimer's disease and the suitability of describing the tau pathology burden temporal trajectories using linear mixed-effects models (LMEM). Methods: We applied van Cittert iterative deconvolution (VC), 2-compartment, and 3-compartment, and the geometric transfer matrix plus region-based voxelwise methods to data acquired in an Alzheimer's disease natural history study over 18 months at a single imaging site. We determined the optimal PVC method by comparing the standardized uptake value ratio change (%ΔSUVR) between diagnostic and tau burden–level groups and the longitudinal repeatability derived from the LMEM. The performance of LMEM analysis for calculating %ΔSUVR was evaluated in a natural history study and in a multisite clinical trial of semorinemab in prodromal to mild Alzheimer's disease by comparing results to traditional per-visit estimates. Results: The VC, 2-compartment, and 3-compartment PVC methods had similar performance, whereas region-based voxelwise overcorrected regions with a higher tau burden. The lowest within-subject variability and acceptable group separation scores were observed without PVC. The LMEM-derived %ΔSUVR values were similar to the per-visit estimates with lower variability. Conclusion: The results indicate that the tested PVC methods do not offer a clear advantage or improvement over non-PVC images for the quantification of longitudinal [ 18 F]GTP1 PET data. LMEM offers a robust framework for the longitudinal tau PET quantification with low longitudinal test–retest variability. Clinical trial registration: NCT02640092 and NCT03289143.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Single reader between-cases AUC estimator with nested data

The area under the receiver operating characteristic curve (AUC) is widely used in evaluating diagnostic performance for many clinical tasks. It is still challenging to evaluate the reading performance of distinguishing between positive and negative regions of interest (ROIs) in the nested-data problem, where multiple ROIs are nested within the cases. To address this issue, we identify two kinds of AUC estimators, within-cases AUC and between-cases AUC. We focus on the between-cases AUC estimator, since our main research interest is in patient-level diagnostic performance rather than location-level performance (the ability to separate ROIs with and without disease within each patient). Another reason is that as the case number increases, the number of between-cases paired ROIs is much larger than the number of within-cases ROIs. We provide estimators for the variance of the between-cases AUC and for the covariance when there are two readers. We derive and prove the above estimators’ theoretical values based on a simulation model and characterize their behavior using Monte Carlo simulation results. We also provide a real-data example. Moreover, we connect the distribution-based simulation model with the simulation model based on the linear mixed-effect model, which helps better understand the sources of variation in the simulated dataset.

Health Care Sciences & Services↗
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↗
DOE OSTI2025

The temporal onset of associations of cortical proteins with cognitive resilience vary during late life

Background: Cortical proteins associated with cognitive resilience have been identified but their temporal onset in older adults is unknown. We present a multistage approach to first identify cortical proteins associated with cognitive resilience and then examine their associated temporal onset. Methods: We used data from a subset of 1088 decedents from two cohort-studies who had selected reaction monitoring proteomics from the dorsolateral prefrontal cortex, and at least 3 cognitive assessments. Cognition was assessed using a composite derived from 19 tests. We first used linear mixed-effects models to identify cortical proteins associated with cognitive resilience. We then used functional mixed-effects models to examine non-linear associations between proteins and cognitive resilience to identify their temporal onset. Results: Mean age at death was 90 years (SD = 6.4); 69 % were female. On average, cognition started to decline at around 15 years before death, with accelerated decline in the last 7 years. We identified 40 proteins associated with cognitive resilience, of which 17 proteins also showed non-linear associations. Non-linear associations indicated that higher levels of 10 proteins were associated with slower cognitive decline between 23 and 4 years before death. In contrast, higher levels of 7 proteins were associated with faster decline only within the last 7 years before death. Conclusions: Cognitive resilience proteins are differentially related to late-life cognitive aging; the onset of proteins that maintain cognition may begin many years before the onset of proteins that hasten cognitive decline. The temporal onset of cognitive resilience proteins may be crucial for timing efficacious interventions.

Zammit, Andrea↗
DOE OSTI2021

Do Remote Camera Arrangements and Image Capture Settings Improve Individual Identification of Golden Eagles?

Individual identification of animals from camera traps has become an important task in wildlife research, but camera deployment methods often do not facilitate this important undertaking. Identification of individual golden eagles (Aquila chrysaetos) is possible using uniquely marked rectrices, but no studies have explored methods to maximize the rate of individual identification from camera images. Furthermore, our objectives were to assess whether different camera heights (1 m vs. 3 m), image capture settings (one image after a 1-min delay vs. burst of 5 images after a 30 sec delay), and arrangements relative to bait (dorsally vs. ventrally aimed) affected views of rectrices on golden eagles and our ability to identify individuals. We conducted our study from 15 December 2016 to 3 March 2017 on the Savannah River Site, South Carolina. First, we developed a scoring system based on views of rectrices and used a linear mixed-effects model to compare image scores among different camera arrangements and image settings. Next, after identifying individual eagles, we used generalized linear mixed-effects models to compare total individual eagle detections, total days an individual was detected, and probability of obtaining an unknown individual identification among camera arrangements and settings. Overall, we scored a total of 27,499 images, with 8,083 providing views of marked rectrices that allowed identification of 18 individual eagles. Average image scores and proportion of images suitable for individual identification were higher from elevated (3 m) camera arrangements than standard arrangements (1 m) across sites. Regardless of camera height, faster frequency of image capture provided more images that could be used to identify individuals and the most trap days per individual. Researchers and managers should consider deploying elevated cameras traps with faster frequency of image capture to improve data quality and potential for analysis of golden eagle populations and trends across the species’ range.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Accuracy of Tau Positron Emission Tomography as a Prognostic Marker in Preclinical and Prodromal Alzheimer Disease: A Head-to-Head Comparison Against Amyloid Positron Emission Tomography and Magnetic Resonance Imaging

Importance: Tau positron emission tomography (PET) tracers have proven useful for the differential diagnosis of dementia, but their utility for predicting cognitive change is unclear. Objective: To examine the prognostic accuracy of baseline fluorine 18 ( 18 F)-flortaucipir and [18F]RO948 (tau) PET in individuals across the Alzheimer disease (AD) clinical spectrum and to perform a head-to-head comparison against established magnetic resonance imaging (MRI) and amyloid PET markers. Design, setting, and participants: This prognostic study collected data from 8 cohorts in South Korea, Sweden, and the US from June 1, 2014, to February 28, 2021, with a mean (SD) follow-up of 1.9 (0.8) years. A total of 1431 participants were recruited from memory clinics, clinical trials, or cohort studies; 673 were cognitively unimpaired (CU group; 253 [37.6%] positive for amyloid-β [Aβ]), 443 had mild cognitive impairment (MCI group; 271 [61.2%] positive for Aβ), and 315 had a clinical diagnosis of AD dementia (315 [100%] positive for Aβ). Exposures: [ 18 F]Flortaucipir PET in the discovery cohort (n = 1135) or [ 18 F]RO948 PET in the replication cohort (n = 296), T1-weighted MRI (n = 1431), and amyloid PET (n = 1329) at baseline and repeated Mini-Mental State Examination (MMSE) evaluation. Main outcomes and measures: Baseline [ 18 F]flortaucipir/[ 18 F]RO948 PET retention within a temporal region of interest, MRI-based AD-signature cortical thickness, and amyloid PET Centiloids were used to predict changes in MMSE using linear mixed-effects models adjusted for age, sex, education, and cohort. Mediation/interaction analyses tested whether associations between baseline tau PET and cognitive change were mediated by baseline MRI measures and whether age, sex, and APOE genotype modified these associations. Results: Among 1431 participants, the mean (SD) age was 71.2 (8.8) years; 751 (52.5%) were male. Findings for [ 18 F]flortaucipir PET predicted longitudinal changes in MMSE, and effect sizes were stronger than for AD-signature cortical thickness and amyloid PET across all participants (R 2 , 0.35 [tau PET] vs 0.24 [MRI] vs 0.17 [amyloid PET]; P < .001, bootstrapped for difference) in the Aβ-positive MCI group (R2, 0.25 [tau PET] vs 0.15 [MRI] vs 0.07 [amyloid PET]; P < .001, bootstrapped for difference) and in the Aβ-positive CU group (R 2 , 0.16 [tau PET] vs 0.08 [MRI] vs 0.08 [amyloid PET]; P < .001, bootstrapped for difference). These findings were replicated in the [ 18 F]RO948 PET cohort. MRI mediated the association between [ 18 F]flortaucipir PET and MMSE in the groups with AD dementia (33.4% [95% CI, 15.5%-60.0%] of the total effect) and Aβ-positive MCI (13.6% [95% CI, 0.0%-28.0%] of the total effect), but not the Aβ-positive CU group (3.7% [95% CI, -17.5% to 39.0%]; P = .71). Age (t = -2.28; P = .02), but not sex (t = 0.92; P = .36) or APOE genotype (t = 1.06; P = .29) modified the association between baseline [ 18 F]flortaucipir PET and cognitive change, such that older individuals showed faster cognitive decline at similar tau PET levels. Conclusions and relevance: The findings of this prognostic study suggest that tau PET is a promising tool for predicting cognitive change that is superior to amyloid PET and MRI and may support the prognostic process in preclinical and prodromal stages of AD.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Determinants of cognitive and brain resilience to tau pathology: a longitudinal analysis

Mechanisms of resilience against tau pathology in individuals across the Alzheimer’s disease spectrum are insufficiently understood. Longitudinal data are necessary to reveal which factors relate to preserved cognition (i.e. cognitive resilience) and brain structure (i.e. brain resilience) despite abundant tau pathology, and to clarify whether these associations are cross-sectional or longitudinal. We used a longitudinal study design to investigate the role of several demographic, biological and brain structural factors in yielding cognitive and brain resilience to tau pathology as measured with PET. In this multicentre study, we included 366 amyloid-β-positive individuals with mild cognitive impairment or Alzheimer’s disease dementia with baseline 18 F-flortaucipir-PET and longitudinal cognitive assessments. A subset (n = 200) additionally underwent longitudinal structural MRI. We used linear mixed-effects models with global cognition and cortical thickness as dependent variables to investigate determinants of cognitive resilience and brain resilience, respectively. Models assessed whether age, sex, years of education, APOE-ε4 status, intracranial volume (and cortical thickness for cognitive resilience models) modified the association of tau pathology with cognitive decline or cortical thinning. We found that the association between higher baseline tau-PET levels (quantified in a temporal meta-region of interest) and rate of cognitive decline (measured with repeated Mini-Mental State Examination) was adversely modified by older age (Stβ interaction = -0.062, P = 0.032), higher education level (Stβ interaction = -0.072, P = 0.011) and higher intracranial volume (Stβ interaction = -0.07, P = 0.016). Younger age, higher education and greater cortical thickness were associated with better cognitive performance at baseline. Greater cortical thickness was furthermore associated with slower cognitive decline independent of tau burden. Higher education also modified the negative impact of tau-PET on cortical thinning, while older age was associated with higher baseline cortical thickness and slower rate of cortical thinning independent of tau. Our analyses revealed no (cross-sectional or longitudinal) associations for sex and APOE-ε4 status on cognition and cortical thickness. In this longitudinal study of clinically impaired individuals with underlying Alzheimer’s disease neuropathological changes, we identified education as the most robust determinant of both cognitive and brain resilience against tau pathology. The observed interaction with tau burden on cognitive decline suggests that education may be protective against cognitive decline and brain atrophy at lower levels of tau pathology, with a potential depletion of resilience resources with advancing pathology. Finally, we did not find major contributions of sex to brain nor cognitive resilience, suggesting that previous links between sex and resilience might be mainly driven by cross-sectional differences.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Linking soil phosphorus with forest litterfall resistance and resilience to cyclone disturbance: A pantropical meta-analysis

While tropical cyclone regimes are shifting with climate change, the mechanisms underpinning the resistance (ability to withstand disturbance-induced change) and resilience (capacity to return to pre-disturbance reference) of tropical forest litterfall to cyclones remain largely unexplored pantropically. Single-site studies in Australia and Hawaii suggest that litterfall on low-phosphorus (P) soils is more resistant and less resilient to cyclones. Here, we conducted a meta-analysis to investigate the pantropical importance of total soil P in mediating forest litterfall resistance and resilience to 22 tropical cyclones. We evaluated cyclone-induced and post-cyclone litterfall mass (g/m 2 /day), and P and nitrogen (N) fluxes (mg/m 2 /day) and concentrations (mg/g), all indicators of ecosystem function and essential for nutrient cycling. Across 73 case studies in Australia, Guadeloupe, Hawaii, Mexico, Puerto Rico, and Taiwan, total litterfall mass flux increased from ~2.5 ± 0.3 to 22.5 ± 3 g/m 2 /day due to cyclones, with large variation among studies. Litterfall P and N fluxes post-cyclone represented ~5% and 10% of the average annual fluxes, respectively. Post-cyclone leaf litterfall N and P concentrations were 21.6 ± 1.2% and 58.6 ± 2.3% higher than pre-cyclone means. Mixed-effects models determined that soil P negatively moderated the pantropical litterfall resistance to cyclones, with a 100 mg P/kg increase in soil P corresponding to a 32% to 38% decrease in resistance. Based on 33% of the resistance case studies, total litterfall mass flux reached pre-disturbance levels within one-year post-disturbance. A GAMM indicated that soil P, gale wind duration and time post-cyclone jointly moderate the short-term resilience of total litterfall, with the nature of the relationship between resilience and soil P contingent on time and wind duration. Across pantropical forests observed to date, our results indicate that litterfall resistance and resilience in the face of intensifying cyclones will be partially determined by total soil P.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

The influence of dietary intake of omega-3 polyunsaturated fatty acids on the association between short-term exposure to ambient nitrogen dioxide and respiratory and cardiovascular outcomes among healthy adults

Background: Short-term exposure to ambient nitrogen dioxide (NO 2 ) is associated with adverse respiratory and cardiovascular outcomes. Supplementation of omega-3 polyunsaturated fatty acids (PUFA) has shown protection against exposure to fine particulate matter. This study aims to investigate whether habitual omega-3 PUFA intake differentially modify the associations between respiratory and cardiovascular responses and short-term exposure to ambient NO 2 . Methods: Sixty-two healthy participants were enrolled into low or high omega-3 groups based on their habitual omega-3 PUFA intake. Each participant was repeatedly assessed for lung function, blood lipids, markers of coagulation and fibrinolysis, vascular function, and heart rate variability (HRV) in up to five sessions, each separated by at least 7 days. This study was carried out in the Research Triangle area of North Carolina, USA between October 2016 and September 2019. Daily ambient NO 2 concentrations were obtained from an area air quality monitoring station on the day of outcome assessment (Lag0), 4 days prior (Lag1-4), as well as 5-day moving average (5dMA). The associations between short-term exposure to NO 2 and the measured indices were evaluated using linear mixed-effects models stratified by omega-3 levels and adjusted by covariates including relative humidity and temperature. Results: The average concentration of ambient NO 2 during the study periods was 5.3±3.8 ppb which was below the National Ambient Air Quality Standards (NAAQS). In the high omega-3 group, an interquartile range (IQR) increase in short-term NO 2 concentrations was significantly associated with increased lung function [e.g. 1.2% (95%CI: 0.2%, 2.2%) in FVC at lag1, 2.6% (95%CI: 0.4%, 4.8%) in FEV1 at 5dMA], decreased blood lipids [e.g. -2.6% (95%CI: -4.4%, -0.9%) in total cholesterol at lag2, -3.1% (95%CI: -6.1%, 0.0%) in HDL at 5dMA, and -3.1% (95%CI: -5.5%, -0.7%) in LDL at lag2], improved vascular function [e.g. 8.9% (95%CI: 0.6%, 17.2%) increase in FMD and 43.1% (95%CI: -79.8%, -6.3%) decrease in endothelin-1 at 5dMA], and changed HRV parameters [e.g. -7.2% (95%CI: -13.6%, -0.8%) in HFn and 13.4% (95%CI: 0.2%, 28.3%) in LF/HF ratio at lag3]. In the low omega-3 group, an IQR increase in ambient NO 2 was associated with elevations in coagulation markers (von Willebrand Factor, D-dimer) and a decrease in HRV (very-low frequency); however, null associations were observed between short-term NO 2 exposure and changes in lung function, blood lipids, and vascular function. Conclusions: The results in this study imply that dietary omega-3 PUFA consumption may offer respiratory and vascular benefits in response to short-term exposure of healthy adults to NO 2 levels below the NAAQS.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2022

Omega-3 fatty acids attenuate cardiovascular effects of short-term exposure to ambient air pollution

Background: Exposure to air pollution is associated with elevated cardiovascular risk. Evidence shows that omega-3 polyunsaturated fatty acids (omega-3 PUFA) may attenuate the adverse cardiovascular effects of exposure to fine particulate matter (PM 2.5 ). However, it is unclear whether habitual dietary intake of omega-3 PUFA protects against the cardiovascular effects of short-term exposure to low-level ambient air pollution in healthy participants. In the present study, sixty-two adults with low or high dietary omega-3 PUFA intake were enrolled. Blood lipids, markers of vascular inflammation, coagulation and fibrinolysis, and heart rate variability (HRV) and repolarization were repeatedly assessed in 5 sessions separated by at least 7 days. This study was carried out in the Research Triangle area of North Carolina, USA between October 2016 and September 2019. Daily PM 2.5 and maximum 8-h ozone (O 3 ) concentrations were obtained from nearby air quality monitoring stations. Linear mixed-effects models were used to assess the associations between air pollutant concentrations and cardiovascular responses stratified by the omega-3 intake levels. Results: The average concentrations of ambient PM 2.5 and O 3 were well below the U.S. National Ambient Air Quality Standards during the study period. Significant associations between exposure to PM 2.5 and changes in total cholesterol, von Willebrand factor (vWF), tissue plasminogen activator, D-dimer, and very-low frequency HRV were observed in the low omega-3 group, but not in the high group. Similarly, O 3 -associated adverse changes in cardiovascular biomarkers (total cholesterol, high-density lipoprotein, serum amyloid A, soluable intracellular adhesion molecule 1, and vWF) were mainly observed in the low omega-3 group. Lag-time-dependent biphasic changes were observed for some biomarkers. Conclusions: This study demonstrates associations between short-term exposure to PM 2.5 and O 3 , at concentrations below regulatory standard, and subclinical cardiovascular responses, and that dietary omega-3 PUFA consumption may provide protection against such cardiovascular effects in healthy adults.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Cortical Proteins and Individual Differences in Cognitive Resilience in Older Adults

Background and objectives: Cognitive resilience is a well-recognized concept, but knowledge gaps about its underlying mechanisms have made it difficult to develop instruments that identify older adults with high or low resilience. We tested whether aggregating cortical peptides associated with cognitive resilience into an index can identify adults with higher or lower cognitive resilience. Methods: We used data from 1,192 older decedents, including annual clinical testing, indices of 10 Alzheimer disease (AD) and related dementia (ADRD) pathologies, and 226 proteotypic peptides measured in the dorsal lateral prefrontal cortex. We used linear mixed-effects models to identify peptides that were related to cognitive resilience (i.e., cognitive decline not explained by ADRD pathologies [false discovery rate <0.05]). We aggregated the expression levels of these resilience peptides into a person-specific cognitive resilience index and examined its association with AD clinical and pathologic phenotypes. Results: We constructed a resilience index from 52 of 226 peptides related to cognitive resilience. A higher index was associated with slower cognitive decline (estimate 0.05, SE 0.003, p < 0.001) and slower motor decline (estimate 0.005, SE 0.001, p < 0.001). Most resilience peptides (70%) were specific to cognitive decline, but 30% also provided resilience for motor decline. A higher index was also related to a lower burden of AD pathologies (odds ratio [OR] 0.41, SE 0.01, p < 0.001) and modified the association of AD pathology with cognition in that a higher index modified the negative effects of AD pathology on AD dementia proximate to death (OR 0.70, SE 0.14, p = 0.010). Up to 90% of cognitive resilience peptides were related to AD pathologic phenotypes. Discussion: Cortical proteins may provide some degree of cognitive resilience. These multifunctional proteins also seem to provide resilience to other AD clinical phenotypes and have independent associations with ADRD pathologies. Resilience proteins may be high-value therapeutic targets for drug discovery of interventions that maintain brain health in aging adults via multiple pathways.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Trust in News as Moderated by Known Truth Assessments and Source

Disinformation has become a problem in various spaces, from social media to organizations. Given the lack of evidence and transparency surrounding organizational disinformation, we aim to understand issue of information exposure effect and source trust from the lens of traditional information consumption online. Using an online experiment and multi-level mixed-effects modeling, we find that the exposure effect exists even over only two exposures to a headline, as long as participants are not shown fact-checking. Fact-checking can be effective in reducing the impact of the exposure effect. Additionally, we find that participants trusted sources significantly more before seeing the headlines. The possible presence of disinformation reduces trust in sources, even when considered highly neutral and reputable. These findings can inform simulations of agent interactions with misinformation as well as future experimental designs focused on evaluations of belief and trust based on recognizability of a source.

99 GENERAL AND MISCELLANEOUS↗
DOE OSTI2023

Soil fertility and drought interact to determine large variations in wood production for a hyperdominant Amazonian tree species

The productivity of the Amazon Rainforest is related to climate and soil fertility. However, the degrees to which these interactions influence multiannual to decadal variations in tree diameter growth are still poorly explored. To fill this gap, we used radiocarbon measurements to evaluate the variation in tree growth rates over the past decades in an important hyperdominant species, Eschweilera coriacea (Lecythidaceae), from six sites in the Brazilian Amazon that span a range of soil properties and climate. Using linear mixed-effects models, we show that temporal variations in mean annual diameter increment evaluated over a specific time period reflect interactions between soil fertility and the drought index (SPEI-Standardized Precipitation and Evapotranspiration Index). Our results indicate that the growth response of trees to drought is strongly dependent on soil conditions, a facet of forest productivity that is still underexplored, and which has great potential for improving predictions of future tropical tree growth in the face of projected climate change.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2022

Annual Herbaceous Plants Exhibit Altered Morphological Traits in Response to Altered Precipitation and Drought Patterns in Semiarid Sandy Grassland, Northern China

The frequency and intensity of extreme precipitation events and severe drought are predicted to increase in semiarid areas due to global climate change. Plant morphological traits can reflect plant responses to a changing environment, such as altered precipitation or drought patterns. In this study, we examined the response of morphological traits of root, stem, leaf and reproduction meristems of annual herbaceous species to altered precipitation and drought patterns in a semiarid sandy grassland. The study involved a control treatment (100% of background precipitation) and the following six altered precipitation treatments: (1) P(+): precipitation increased by 30%, (2) P(++): precipitation increased by 60%, (3) P(-): precipitation decreased by 30%, (4) P(--): precipitation decreased by 60%, (5) drought 1 (D1): 46-day drought from May 1st to June 15th, and (6) drought 2 (D2): 46-day drought from July 1st to August 15th. P(++) significantly increased root length, flower length-to-width ratio, both P(+) and P(++) significantly increased stem length and flower number in the plant growing seasons, while all of them decreased under P(-) and P(--). The annual herbaceous plants marginally increased the number of second-level stem branches and stem diameter in order to better resist the severe drought stress under P(--). P(+) and P(++) increased the root, stem, leaf, and flower dry weight, with the flower dry weight accounting for a larger proportion than the other aboveground parts. Under D2, the plants used the limited water resources more efficiently by increasing the root-to-shoot ratio compared with P(-), P(--) and D1, which reflects biomass allocation to belowground increased. The linear mixed-effects models and redundancy analysis showed that the root-to-shoot ratio and the dry weight of various plant components were significantly affected by morphological traits and altered precipitation magnitude. Our results showed that the herbaceous species have evolved morphological trait responses that allow them to adapt to climate change. Such differences in morphological traits may ultimately affect the growing patterns of annual herbaceous species, enhancing their drought-tolerant capacity in semiarid sandy grassland during the ongoing climate change.

Sun, Shan-Shan↗
DOE OSTI2022

Global estimates of the fitness advantage of SARS-CoV-2 variant Omicron

Abstract New variants of SARS-CoV-2 show remarkable heterogeneity in their relative fitness over both time and space. In this paper we extend the tools available for estimating the selection strength for new SARS-CoV-2 variants to a hierarchical, mixed-effects, renewal equation model. This formulation allows us to estimate selection effects at the global level while incorporating both measured and unmeasured heterogeneity among countries. Applying this model to the spread of Omicron in forty countries, we find evidence for very strong but very heterogeneous selection effects. To test whether this heterogeneity is explained by differences in the immune landscape, we considered several measures of vaccination rates and recent population-level infection as covariates, finding moderately strong, statistically significant effects. We also found a significant positive correlation between the selection advantage of Delta and Omicron at the country level, suggesting that other region-specific explanatory variables of fitness differences do exist. Our method is implemented in the Stan programming language, can be run on standard consumer-grade computing resources, and will be straightforward to apply to future variants.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Validation Metrics for Fixed Effects and Mixed-Effects Calibration

The modern scientific process often involves the development of a predictive computational model. To improve its accuracy, a computational model can be calibrated to a set of experimental data. A variety of validation metrics can be used to quantify this process. Some of these metrics have direct physical interpretations and a history of use, while others, especially those for probabilistic data, are more difficult to interpret. In this work, a variety of validation metrics are used to quantify the accuracy of different calibration methods. Frequentist and Bayesian perspectives are used with both fixed effects and mixed-effects statistical models. Through a quantitative comparison of the resulting distributions, the most accurate calibration method can be selected. Two examples are included which compare the results of various validation metrics for different calibration methods. It is quantitatively shown that, in the presence of significant laboratory biases, a fixed effects calibration is significantly less accurate than a mixed-effects calibration. This is because the mixed-effects statistical model better characterizes the underlying parameter distributions than the fixed effects model. The results suggest that validation metrics can be used to select the most accurate calibration model for a particular empirical model with corresponding experimental data.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2021

A hierarchical Bayesian model for background variation in radiation source localization

In this paper, we apply a new model to account for varying background radiation in radiological source localization. We present a hierarchical Bayesian model that simultaneously infers background and source location parameters without requiring separate estimation of the background radiation at each detector location. We employ a simplified photon transport model to reduce the computational expense of Bayesian model calibration. Furthermore, we demonstrate the model accuracy by localizing a cesium-137 source in a simulated city block, and we analyze experimental field measurements with varying background. In both cases, the model provides sufficient fidelity that we can locate the source while simultaneously estimating background radiation.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗