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DOE OSTI2022

Longitudinal Trajectories of Memory Performance in Patients with Early-Stage Breast Cancer

Background. While breast cancer and its treatments may affect cognition, the longitudinal trajectories of cognition among those receiving differing cancer treatment types remain poorly understood. Prior research suggests hippocampal-prefrontal cortex network integrity may influence cognition, although how this network predicts performance over time remains unclear. Methods. We conducted a prospective trial including 69 patients with early-stage breast cancer receiving adjuvant therapy and 12 controls. Longitudinal cognitive testing was conducted at four visits: pretreatment-baseline, 6-7 months, 14-15 months, and 23-24 months. Cognitive composite scores of episodic memory, executive functioning, and processing speed were assessed at each timepoint. Baseline structural MRI was obtained in a subset of these participants, and hippocampal and prefrontal cortex regional volumes were extracted. Results. Longitudinal linear mixed modeling revealed significant group by time interactions on memory performance, controlling for age and education. Post hoc analyses revealed this effect was driven by patients treated with chemotherapy or chemotherapy plus hormone therapy, who demonstrated the least improvement in memory scores over time. Treatment group did not significantly influence the relationship between time and processing speed or executive functioning. Neither pretreatment hippocampal nor prefrontal volume differed between groups, and there were no significant group by time by baseline regional volume effects on cognition. Conclusion. Patients with early-stage breast cancer treated with chemotherapy or chemotherapy plus hormone therapy benefit less from practice effects seen in healthy controls on memory tests. Loss of longitudinal practice effect may be a new and clinically relevant measure for capturing patients’ experience of cognitive difficulties after treatment.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2023

Longitudinal Changes in Immune Activation Serum Biomarkers Prior to Diagnosis and Risk of B-cell NHL Subtypes

To examine the contribution of B-cell activation molecules to B-cell follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL), a prospective study was conducted using pre-diagnosis serial serum samples from the US Department of Defense Serum Repository. Each case (n = 142 FL, n = 211 DLBCL) was matched to two controls on age, gender, race, military branch, and blood collection dates. Immune activation molecules (IL1β, IL2, IL4, IL5, IL6, IL10, IL12, CXCL13, IL8, TNFα, IFNγ, GM-CSF, VEGF, sCD30, IgE) were quantified using ELISA or multiplex immunometric (Luminex) assay. Longitudinal data were analyzed using linear mixed modeling. As serial specimens were collected over several years before diagnosis, we evaluated the temporal dynamics of these markers. Increased serum levels of sCD30, CXCL13, and to a lesser extent IL10, were associated with both FL and DLBCL in cases compared with controls, with a median follow-up of 5.5 years from the earliest specimen collection to diagnosis date. Significant increasing sCD30 and CXCL13 trajectories for FL and DLBCL subtypes were noted starting at the earliest time points and with IL10 levels increasing significantly at time points closer to diagnosis. In conclusion, these results suggest that sCD30, CXCL13, and IL10 may contribute to the etiology of FL and DLBCL and are potential biomarkers for these non–Hodgkin lymphoma subtypes. The increasing trajectories of the B-cell activation molecules, sCD30, CXCL13, and to a lesser extent IL10, may indicate early disease-induced effects or reflect the chronic stimulation of B-cells that promotes the development of FL and DLBCL subtypes.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2018

An Evaluation of Army Wellness Center Clients’ Health-Related Outcomes

Purpose: To examine whether Army community members participating in a best-practice based workplace health promotion program (WHPP) experience goal-moderated improvements in health-related outcomes. Design: Pretest/posttest outcome evaluation examining an autonomously participating client cohort over 1 year. Setting: Army Wellness Center facilities on 19 Army installations. Participants: Army community members sample (N = 5703), mostly Active Duty Soldiers (64%). Intervention: Assessment of health risks with feedback, health assessments, health education classes, and health coaching sessions conducted by health educators at a recommended frequency of once a month for 3 to 12 months. Measures: Initial and follow-up outcome assessments of body mass index (BMI), body fat, cardiorespiratory fitness, blood pressure, and perceived stress. Analysis: Mixed model linear regression testing for goal-moderated improvements in outcomes. Results: Clients experienced significant improvements in body fat (−2% change), perceived stress (−6% to −12% change), cardiorespiratory fitness (+6% change), and blood pressure (−1% change) regardless of health-related goal. Only clients with a weight loss goal experienced BMI improvement (−1% change). Follow-up outcome assessment rates ranged from 44% (N = 2509) for BMI to 6% (N = 342) for perceived stress. Conclusion: Army Wellness Center clients with at least 1 follow-up outcome assessment experienced improvements in military readiness correlates and chronic disease risk factors. Evaluation design and follow-up-related limitations notwithstanding results suggest that best practices in WHPPs can effectively serve a globally distributed military force.

Rivera, L. Omar↗

DOE OSTI2014

Circumstances and outcomes of falls among high risk community-dwelling older adults

For older adults, falls threaten their health, independence, and quality of life. Knowing the circumstances surrounding falls is essential for understanding how behavioral and environmental factors interact in fall events. It is also important for developing and implementing interventions that are effective and acceptable to older adults. This study investigated the circumstances and injury outcomes of falls among community-dwelling older adults at high risk for falls. In this secondary analysis, we examined the circumstances and outcomes of falls experienced by 328 participants in the Dane County (Wisconsin) Safety Assessment for Elders (SAFE) Research Study. SAFE was a randomized controlled trial of a community-based multifactorial falls intervention for older adults at high risk for falls, conducted from October 2002 to December 2007. Participants were community-dwelling adults aged ≥65 years who reported at least one fall during the year after study enrollment. Falls were collected prospectively using monthly calendars. Everyone who reported a fall was contacted by telephone to determine the circumstances surrounding the event. Injury outcomes were defined as none, mild (injury reported but no treatment sought), moderate (treatment for any injury except head injury or fracture), and severe (treatment for head injury or fracture). Data were available for 1,172 falls. A generalized linear mixed model analysis showed that being aged ≥85 (OR = 2.1, 95% confidence interval [CI] = 1.2–3.9), female (OR = 2.1, 95% CI = 1.3–3.4), falling backward and landing flat (OR = 5.6, 95% CI = 2.9–10.5), sideways (OR = 4.6, 95% CI = 2.6–8.0) and forward (OR = 3.3, 95% CI = 2.0–5.7) were significantly associated with the likelihood of injury. Of 783 falls inside the home, falls in the bathroom were more than twice as likely to result in an injury compared to falls in the living room (OR = 2.4, 95% CI = 1.2–4.9). Most falls among these high risk older adults occurred inside the home. The likelihood of injury in the bathroom supports the need for safety modifications such as grab bars, and may indicate a need for assistance with bathing. These findings will help clinicians tailor fall prevention for their patients and have practical implications for retirement and assisted living communities and community-based fall prevention programs.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2023

Structure-informed clustering for population stratification in association studies

Background: Identifying variants associated with complex traits is a challenging task in genetic association studies due to linkage disequilibrium (LD) between genetic variants and population stratification, unrelated to the disease risk. Existing methods of population structure correction use principal component analysis or linear mixed models with a random effect when modeling associations between a trait of interest and genetic markers. However, due to stringent significance thresholds and latent interactions between the markers, these methods often fail to detect genuinely associated variants. Results: To overcome this, we propose CluStrat, which corrects for complex arbitrarily structured populations while leveraging the linkage disequilibrium induced distances between genetic markers. It performs an agglomerative hierarchical clustering using the Mahalanobis distance covariance matrix of the markers. In simulation studies, we show that our method outperforms existing methods in detecting true causal variants. Applying CluStrat on WTCCC2 and UK Biobank cohorts, we found biologically relevant associations in Schizophrenia and Myocardial Infarction. CluStrat was also able to correct for population structure in polygenic adaptation of height in Europeans. Conclusions: CluStrat highlights the advantages of biologically relevant distance metrics, such as the Mahalanobis distance, which captures the cryptic interactions within populations in the presence of LD better than the Euclidean distance.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2022

COMPILE: a GWAS computational pipeline for gene discovery in complex genomes

Abstract Background Genome-Wide Association Studies (GWAS) are used to identify genes and alleles that contribute to quantitative traits in large and genetically diverse populations. However, traits with complex genetic architectures create an enormous computational load for discovery of candidate genes with acceptable statistical certainty. We developed a streamlined computational pipeline for GWAS (COMPILE) to accelerate identification and annotation of candidate maize genes associated with a quantitative trait, and then matches maize genes to their closest rice and Arabidopsis homologs by sequence similarity. Results COMPILE executed GWAS using a Mixed Linear Model that incorporated, without compression, recent advancements in population structure control, then linked significant Quantitative Trait Loci (QTL) to candidate genes and RNA regulatory elements contained in any genome. COMPILE was validated using published data to identify QTL associated with the traits of α-tocopherol biosynthesis and flowering time, and identified published candidate genes as well as additional genes and non-coding RNAs. We then applied COMPILE to 274 genotypes of the maize Goodman Association Panel to identify candidate loci contributing to resistance of maize stems to penetration by larvae of the European Corn Borer ( Ostrinia nubilalis ). Candidate genes included those that encode a gene of unknown function, WRKY and MYB-like transcriptional factors, receptor-kinase signaling, riboflavin synthesis, nucleotide-sugar interconversion, and prolyl hydroxylation. Expression of the gene of unknown function has been associated with pathogen stress in maize and in rice homologs closest in sequence identity. Conclusions The relative speed of data analysis using COMPILE allowed comparison of population size and compression. Limitations in population size and diversity are major constraints for a trait and are not overcome by increasing marker density. COMPILE is customizable and is readily adaptable for application to species with robust genomic and proteome databases.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2019

A Comparison of Patient-Reported Outcomes After Breast-Conserving Surgery and Mastectomy with Implant Breast Reconstruction

Background: Many factors influence decisions regarding choice of breast-conserving surgery (BCS) versus mastectomy with reconstruction for early invasive breast cancer. The purpose of this study was to compare patient satisfaction following BCS and mastectomy with implant reconstruction (M-iR) utilizing the BREAST-Q patient-reported outcome measure. Methods: Women with stage I or II breast cancer undergoing BCS or M-iR who completed a BREAST-Q from 2010 to 2016 were identified by retrospective review of a prospective database. Baseline characteristics were compared, and linear mixed models were used to analyze associations with BREAST-Q scores over time. Results: Our study group was composed of 3233 women; 2026 (63%) had BCS, 123 (3.8%) had nipple-sparing mastectomy, and 1084 (34%) had skin-sparing or total mastectomy. Median time from surgery to BREAST-Q was 205 days for BCS and 639 days for M-iR (p < 0.001). Regardless of type of surgery, breast satisfaction scores decreased significantly over time (p < 0.001), whereas psychosocial (p = 0.001) and sexual (p = 0.004) well-being scores increased significantly over time. BCS was associated with significantly higher scores over time compared with M-iR across all subscales (all p < 0.001). Radiation was significantly associated with decreased scores over time across all subscales (all p < 0.05). Conclusions: Breast satisfaction and quality-of-life scores were higher for BCS compared with M-iR in early-stage invasive breast cancer. These findings may help in counseling women who have a choice for surgical treatment. Breast satisfaction scores decreased over time in all women, highlighting the need for further evaluation with longer follow-up.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2021

Comprehensive Physical Activity Assessment During U.S. Army Basic Combat Training

Abstract Alemany, JA, Pierce, JR, Bornstein, DB, Grier, TL, Jones, BH, and Glover, SH. Comprehensive physical activity assessment during U.S. Army Basic Combat Training. J Strength Cond Res 36(12): 3505–3512, 2022—Physical activity (PA) volume, intensity, and qualitative contextual information regarding activity type and loads carried are limited during U.S. Army Basic Combat Training (BCT). The purpose of this study was to characterize daily (05:00–20:00 hours) PA during BCT using a comprehensive approach. During 2 10-week BCT cycles ( n = 40 trainees per cycle), pedometers, accelerometers, and direct observation were used to estimate daily step count, PA volume, and intensity. Physical activity intensity was categorized by metabolic equivalents (METs) such as “sedentary” (1–2 METs), “light” (2–3 METs), “moderate” (3–6 METs), or “vigorous” (≥6 METs). Daily PA data were analyzed longitudinally using linear mixed models, with significance set at p ≤ 0.05. The mean daily step count was 13,459 ± 4,376 steps, and the mean daily accelerometer-assessed PA volume and intensity were as follows: sedentary: 505 ± 98 minutes, light: 190 ± 78 minutes, moderate: 168 ± 51 minutes, and vigorous: 14 ± 14 minutes, with no differences between cycles for all measures ( p > 0.50). Cumulative time on feet (∼50%) and sitting (20–25%) accounted for most daily activity types during both cycles. Trainees, on average, carried between 3 and 9 kg, and ≥9 kg, for 60% and 10% of the monitored day, respectively. Basic Combat Training's physical demands are high, where trainees achieved 1.7 to 2.7 times greater daily ambulation and 6 times the recommended weekly moderate-to-vigorous PA compared with civilian counterparts and performed weight-bearing load carriage for nearly half of the day. Basic Combat Training-associated PA may increase injury risk among trainees unaccustomed to arduous PA and exercise. Implementing national PA policies to improve physical fitness and facilitate acclimatization to BCT's high physical demands could reduce public health burdens and military nonreadiness.

Sport Sciences↗

DOE OSTI2019

Reported light in the sleep environment: enhancement of the sleep diary

Light is the primary synchronizing cue for the circadian timing system, capable of exerting robust physiological effects, even with very dim and/or brief photic exposure. Mammals, including humans, are particularly susceptible to light at night. As such, measures of light in the sleeping environment are critical for evaluating sleep health. Sleep diaries provide inexpensive measures of sleep, but do not typically include light information. Four questions probing visual perception of light in the bedtime and waking environments were added to the Consensus Sleep Diary for Morning administration. As part of a lighting intervention study, 18 hospital Labor and Delivery Department personnel completed the sleep diary for 1 week in each of two experimental conditions while wearing Actiwatch devices equipped with photosensors. Diary responses were evaluated against photosensor values from the beginning and end of each rest interval (n=194 rest intervals), as well as against sleep measures, utilizing linear mixed models. Responses to light questions were related to actual light measures at bedtime, controlling for shift type and experimental condition. In addition, subjective light information at bedtime and waking was related to both objective and subjective sleep parameters, with data generally indicating poorer sleep with light in the sleeping environment. Questions addressing perception of light in the sleeping environment may provide a crude yet affordable metric of relative photic intensity. Further, as responses relate to sleep outcomes, subjective light information may yield valuable insights regarding mechanisms and outcomes of clinical significance in sleep and circadian research.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2024

Enhanced Resistance Pines for Improved Renewable Biofuel and Chemical Production (Technical Report)

We completed phenotyping constitutive and inducible oleoresin flow across two seasons, constitutive resin canal number and density and wood terpene content in our ADEPT2 and CCLONES populations. We completed genetic association between 19 oleoresin phenotypes and a total of 523,192 SNP markers from ADEPT2 and 13,883 SNP markers in CCLONES using four mixed linear models. A total of 293 significant SNPs (FDR = 0.20) were identified. We used the MENTOR tool to mine mechanistic connections from a multiplex network constructed from poplar multi-omic data to construct a conceptual model for a subset of these significant SNPs. Our model contains 6 transcriptional regulators in addition to 3 monoterpene synthases. To generate more lines of evidence for these significant SNPs, we completed a time course RNAseq experiment after inducing vascular zone cells to differentiate into new resin canals with a methyl jasmonate treatment, a single nuclei RNAseq that identified differentiating resin canal epithelial cells and are completing analysis for a QTL study in a hybrid pine population. The time course identified 4634 significantly down and 1890 significantly up regulated transcripts after treatment with methyl jasmonate, an inducer of new resin canal formation in the vascular cambial meristem. To analyze this large set of differentially regulated genes, we created a predictive expression network and analyzed it with random walk restart using 6 seed genes coding for transcription factors regulating xylem differentiation in poplar. Of the top ranked 200 transcripts, 119 transcripts were significant differentially expressed supporting these transcripts as potential candidates regulating resin canal formation. Analysis of single nuclei sequencing of shoot tips that contain differentiating resin canals, identified 10 clusters. One cluster was highly enriched in transcripts coding for 9 of the enzymes in the MEP pathway 3 prenyl synthetases, and 3 monoterpene synthases strongly suggesting that this cluster represents resin canal epithelial cells. We are mining the additional transcripts to create a trajectory analysis. In summary, we have identified > 10 novel genes that are strongly supported candidates for further analysis in breeding lines and for genetic engineering over- and under- expressing lines to increase wood terpene content to improve resistance to insect and fungal pathogens while simultaneously increasing terpene supplies for renewable chemicals and biofuels.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2024

Phase and Morphology of Water-ice Grains Formed in a Cryogenic Laboratory Plasma

Abstract Grains of ice are formed spontaneously when water vapor is injected into a weakly ionized laboratory plasma in which the background gas has been cooled to cryogenic temperatures comparable to those of deep space. These ice grains are levitated indefinitely within the plasma so that their time evolution can be observed under free-floating conditions. Using microscope imaging, ice grains are shown to have a spindle-like fractal structure and grow over time. Both crystalline and amorphous phases of ice are observed using Fourier transform infrared spectroscopy. A mix of crystalline and amorphous grains coexists under certain thermal conditions, and a linear mixing model is used on the ice absorption band surrounding 3.2 μ m to examine the ice phase composition and its temporal stability. The extinction spectrum is also affected by inelastic scattering as grains grow, and characteristic grain radii are obtained from Mie scattering theory and compared to size measurements from direct imaging. Observations are used to compare possible ice nucleation mechanisms, and it is concluded that nucleation is likely catalyzed by ions, as ice does not nucleate in the absence of plasma and impurities are not detected. Ice grain properties and infrared extinction spectra show similarity to observations of some astrophysical ices observed in protoplanetary disks, implying that the fractal morphology of the ice and observed processes of homogeneous ice nucleation could occur as well in such astrophysical environments with weakly ionized conditions.

Astronomy & Astrophysics↗

NASA NTRS1972

Compositional characteristics of some Apollo 14 clastic materials.

Eighty-two subsamples of Apollo 14 materials have been analyzed by instrumental neutron activation analysis techniques for as many as 25 elements. In many cases, it was necessary to develop new procedures to allow analyses of small specimens. Compositional relationships among Apollo 14 materials indicate that there are small but systematic differences between regolith from the valley terrain and that from Cone Crater ejecta. Fragments from 1-2 mm size fractions of regolith samples may be divided into compositional classes, and the 'soil breccias' among them are very similar to valley soils. Multicomponent linear mixing models have been used as interpretive tools in dealing with data on regolith fractions and subsamples from breccia 14321. These mixing models show systematic compositional variations with inferred age for Apollo 14 clastic materials.

Lindstrom, M. M.↗

NASA NTRS1982

Detection and evaluation of mixed pixels in Landsat agricultural scenes

A major problem area encountered in the identification and estimation of agricultural crop proportions in Landsat imagery involves the large proportion of the pixels which are mixed pixels, whose spectral response is influenced by more than one ground cover type. The development of methods for the detection and estimation of crop proportions in mixed pixels is presently reported. The procedure designated CASCADE, based on the estimation of the gradient image for the detection of mixed pixels, considers the consequences of a linear mixing model and is found to provide a method for the allocation of mixed pixels to the surrounding homogeneous region.

Merickel, M. B.↗

NASA NTRS1989

Shade images of forested areas obtained from LANDSAT MSS data

The pixel size in the present day Remote Sensing systems is large enough to include different types of land cover. Depending upon the target area, several components may be present within the pixel. In forested areas, generally, three main components are present: tree canopy, soil (understory), and shadow. The objective is to generate a shade (shadow) image of forested areas from multispectral measurements of LANDSAT MSS (Multispectral Scanner) data by implementing a linear mixing model, where shadow is considered as one of the primary components in a pixel. The shade images are related to the observed variation in forest structure, i.e., the proportion of inferred shadow in a pixel is related to different forest ages, forest types, and tree crown cover. The Constrained Least Squares (CLS) method is used to generate shade images for forest of eucalyptus and vegetation of cerrado using LANDSAT MSS imagery over Itapeva study area in Brazil. The resulted shade images may explain the difference on ages for forest of eucalyptus and the difference on three crown cover for vegetation of cerrado.

Shimabukuro, Yosio Edemir↗

NASA NTRS1989

Shade images of forested areas obtained from Landsat MSS data

The objective of this report is to generate a shade (shadow) image of forested areas from Landsat MSS data by implementing a linear mixing model, where shadow is considered as one of the primary components in a pixel. The shade images are related to the observed variation in forest structure; i.e., the proportion of inferred shadow in a pixel is related to different forest ages, forest types, and tree crown cover. The constrained least-squares method is used to generate shade images for forest of eucalyptus and vegetation of 'cerrado' over the Itapeva study area in Brazil. The resulted shade images may explain the difference on ages for forest of eucalyptus and the difference on tree crown cover for vegetation of cerrado.

Shimabukuro, Yosio Edemir↗

NASA NTRS1991

Relationships of soil, grass, and bedrock over the Kaweah serpentine melange through spectral mixture analysis of AVIRIS data

A linear mixing model is used to model the spectral variability of an AVIRIS scene from the western foothills of the Sierra Nevada and calibrate these radiance data to reflectance. Five spectral endmembers from the AVIRIS data, plus an ideal 'shade' endmember were required to model the continuum reflectance of each pixel in the image. Three of the endmembers were interpreted to model the surface constituents green vegetation, dry grass, and illumination. These are the main transient surface constituents that are expected to change with shifts in land use or climatic influences and viewing conditions ('shade' only). The spectral distinction between the other three endmembers is very small, yet the spatial distributions are coherent and interpretable. These distributions cross anthropogenic and vegetation boundaries and are best interpreted as different soil types. Comparison of the fraction images to the bedrock geology maps indicates that substrate composition must be a factor contributing to the spectral properties of these endmembers. Detailed examination of the reflectance spectra of the three soil endmembers reveals that differences in the amount of ferric and ferrous iron and/or organic constituents in the soils is largely responsible for the differences in spectral properties of these endmembers.

Mustard, John F.↗

NASA NTRS1993

Relationships of soil, grass, and bedrock over the Kaweah Serpentinite Melange through spectral mixture analysis of AVIRIS data

Mustard, John F.↗

NASA NTRS1993

The history of mare volcanism in the Orientale Basin: Mare deposit ages, compositions and morphologies

The eruptive history of mare basalts in the Orientale Basin has been studied, using Lunar Orbiter 4 high-resolution photographs, Zond 8 photographs, and recently acquired Galileo EM-1 multispectral images. This work represents a refined set of compositional data incorporating the use of a linear mixing model for mare compositions, crater count data, and a comprehensive morphologic analysis of Orientale Basin mare deposits. Evidence for multiple eruptive episodes has been found, with compositions ranging from medium- to high-Ti basalt (less than 4 to greater than 6 wt. percent TiO2). Eruptive styles included flood, rille-forming, and shield-forming eruptions. Impact crater densities of mare units in the Orientale Basin enable determination of the ages of these deposits, using the method of Neukum et al. Earliest eruptions of mare basalt in the basin occurred at greater than or equal to 3.80 Ga and the latest eruptions occurred at about 2.3-2.5 Ga. Hence, mare volcanism occurred over a period of nearly 1.5 Ga.

Kadel, S. D.↗