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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 OSTI2022

Evaluation of Long-Term Outcomes and Toxicity After Stereotactic Phosphorus-32–Based Intracavitary Brachytherapy in Patients With Cystic Craniopharyngioma

Interstitial brachytherapy based on phosphorus-32 (P-32) has an established role as a minimally invasive treatment modality for patients with cystic craniopharyngioma. However, reporting on long-term outcomes with toxicity profiles for large cohorts is lacking in the literature. The purpose of this study is therefore to evaluate the long-term visual, endocrinal, and neurocognitive functions in what is the largest patient series having received this treatment to date.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2026

A Critical Review of Heliostat Design for Concentrating Solar Thermal Technologies

Heliostat designs have undergone a widespread and eclectic development process, with many unique designs demonstrated. However, recent developments do not show the overall cohort converging toward a globally accepted universal design. Here, this study characterizes heliostats by breaking down and evaluating design traits based on emergent patterns from a comprehensive compilation of known heliostat designs spanning several decades. Four main categories for evaluation emerged: heliostat base, heliostat primary axis, heliostat drive, and facet support. Each of these four categories is further defined by four subtypes so that all heliostats fall into a single subtype within each category. The classified heliostats are ranked, yielding several view slices into the heliostat compilation or a breakdown of heliostats by type. An analysis of the breakdown shows several trends: a scale-up of established designs, new approaches at small to medium scales, and a movement toward greater adoption of linear drives. These trends reflect the most meaningful contributing factors to a proposed trajectory for a new era of heliostat designs striving to meet widely considered cost targets of $\$$50/m 2 or $\$$75/m 2 .

14 SOLAR ENERGY↗
DOE OSTI2024

Salinity Stress and the Holobiont: Investigating Algal-Bacterial Interactions in Chrysochromulina tobinii

Algae and bacteria form a symbiotic partnership, known as a ”holobiont”, in which both partners provide critical nutrients to each other. Previous research indicates that the composition and structure of the holobiont plays a crucial role in the algal response to environmental stressors, with expression trends varying under stress conditions. Given the increasing prevalence of salinity shifts due to climate change, investigating the responses of these aquatic organisms to salt stress is essential. This is especially true because algae are ecologically and economically important, serving as a nutritive food source for a large range of eco-cohorts and holding potential for biofuel and nutraceutical applications. This study aimed to examine how holobiont community structure is altered in response to salinity shifts and to assess the corresponding changes in gene expression. Metagenomic and metatranscriptomic approaches were utilized to analyze the interactions between the algae, Chrysochromulina tobinii, and its associated bacterial community under varying salinity conditions. Our findings provide insight into the metabolic adaptations of the holobiont and enhance understanding of the survival mechanisms employed in response to osmotic stress.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Spatial Microsimulation and Activity Allocation in Python: An Update on the Likeness Toolkit

Understanding human security and social equity issues within human systems requires large-scale models of population dynamics that simulate high-fidelity representations of individuals and access to essential activities (work/school, social, errands, health). Likeness is a Python toolkit that provides these capabilities for Oak Ridge National Laboratory's (ORNL) UrbanPop spatial microsimulation project. In step with the initial development phase for Likeness (2021 - 2022), we built out several foundational examples of work/school and health service access. In this paper, we describe expansion and scaling of Likeness capabilities to metropolitan areas in the United States. We then provide an integrated demonstration of our methods based on a case study of Leon County, FL and perform validation exercises on 1) neighborhood demographic composition and 2) visits by demographic cohorts (gender/age) obtained from point of interest (POI) footfall data for essential services (grocery stores). Taking into account lessons learned from our case study, we scope improvements to our model as well as provide a roadmap of the anticipated Likeness development cycle into 2023 - 2024.

Tuccillo, Joe↗
DOE OSTI2023

Prescribed fires, smoke exposure, and hospital utilization among heart failure patients

Abstract Background Prescribed fires often have ecological benefits, but their environmental health risks have been infrequently studied. We investigated associations between residing near a prescribed fire, wildfire smoke exposure, and heart failure (HF) patients’ hospital utilization. Methods We used electronic health records from January 2014 to December 2016 in a North Carolina hospital-based cohort to determine HF diagnoses, primary residence, and hospital utilization. Using a cross-sectional study design, we associated the prescribed fire occurrences within 1, 2, and 5 km of the patients’ primary residence with the number of hospital visits and 7- and 30-day readmissions. To compare prescribed fire associations with those observed for wildfire smoke, we also associated zip code-level smoke density data designed to capture wildfire smoke emissions with hospital utilization amongst HF patients. Quasi-Poisson regression models were used for the number of hospital visits, while zero-inflated Poisson regression models were used for readmissions. All models were adjusted for age, sex, race, and neighborhood socioeconomic status and included an offset for follow-up time. The results are the percent change and the 95% confidence interval (CI). Results Associations between prescribed fire occurrences and hospital visits were generally null, with the few associations observed being with prescribed fires within 5 and 2 km of the primary residence in the negative direction but not the more restrictive 1 km radius. However, exposure to medium or heavy smoke (primarily from wildfires) at the zip code level was associated with both 7-day (8.5% increase; 95% CI = 1.5%, 16.0%) and 30-day readmissions (5.4%; 95% CI = 2.3%, 8.5%), and to a lesser degree, hospital visits (1.5%; 95% CI: 0.0%, 3.0%) matching previous studies. Conclusions Area-level smoke exposure driven by wildfires is positively associated with hospital utilization but not proximity to prescribed fires.

Raab, Henry↗
DOE OSTI2021

Conditional Point Sampling: A Monte Carlo Method for Radiation Transport in Stochastic Media.

Current methods for stochastic media transport are either computationally expensive or, by nature, approximate. Moreover, none of the well-developed, benchmarked approximate methods can compute the variance caused by the stochastic mixing, a quantity especially important to safety calculations. Therefore, we derive and apply a new conditional probability function (CPF) for use in the recently developed stochastic media transport algorithm Conditional Point Sampling (CoPS), which 1) leverages the full intra-particle memory of CoPS to yield errorless computation of stochastic media outputs in 1D, binary, Markovian-mixed media, and 2) leverages the full inter-particle memory of CoPS and the recently developed Embedded Variance Deconvolution method to yield computation of the variance in transport outputs caused by stochastic material mixing. Numerical results demonstrate errorless stochastic media transport as compared to reference benchmark solutions with the new CPF for this class of stochastic mixing as well as the ability to compute the variance caused by the stochastic mixing via CoPS. Using previously derived, non-errorless CPFs, CoPS is further found to be more accurate than the atomic mix approximation, Chord Length Sampling (CLS), and most of memory-enhanced versions of CLS surveyed. In addition, we study the compounding behavior of CPF error as a function of cohort size (where a cohort is a group of histories that share intra-particle memory) and recommend that small cohorts be used when computing the variance in transport outputs caused by stochastic mixing.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2023

Finding middle ground: Flow regimes designed for salmon and energy value

In regulated rivers, shaping seasonal flows to recover species at risk depends on understanding when to expect conflicts with competing water users and when their interests are aligned. Multi-objective optimization can be used to reveal such conflicts and commonalities. When species are involved, multi-objective optimization is challenged by the need to simulate complex species responses to flow regimes. Previously, we addressed that challenge by developing a simplified salmon model (Quantus) that defines cohorts of salmon by the river section and time in which they were spawned. Salmon in these space-time cohorts are tracked from the time redds (nests) are constructed until the cohort exits the tributary en route to the ocean. In this study, we modeled seasonal patterns in energy value and developed a Pareto-optimal frontier of seasonal flow patterns to maximize in-river salmon survival and hydropower value. Candidate flow regimes were characterized by two pulse flows varying in magnitude, timing, and duration and constrained by a total annual flow near the historical median. Our analysis revealed times when economic and salmon objectives were aligned and times when they differed. Pulse flows that favored higher energy value were timed to meet demand during extreme temperatures. Both salmon and hydropower objectives produced optimal flow regimes with pulse flows in early summer, but only solutions favoring hydropower value included high flows in mid-winter. Solutions favoring higher age-0 salmon survival provided an extended pulse flow in late winter/early spring, which suggests that access to productive floodplain habitat allowed faster growth and earlier out-migration and reduced the need for higher temperature-moderating flows later in spring. Minimum flows were also higher among solutions favoring salmon over energy. The tools used to produce these results can help to design simplified seasonal flow regimes by revealing compromise solutions that satisfy both fish and energy producers and highlighting when potential conflicts are likely.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2022

A genome-wide association study of suicide attempts in the million veterans program identifies evidence of pan-ancestry and ancestry-specific risk loci

In this study, to identify pan-ancestry and ancestry-specific loci associated with attempting suicide among veterans, we conducted a genome-wide association study (GWAS) of suicide attempts within a large, multi-ancestry cohort of U.S. veterans enrolled in the Million Veterans Program (MVP). Cases were defined as veterans with a documented history of suicide attempts in the electronic health record (EHR; N = 14,089) and controls were defined as veterans with no documented history of suicidal thoughts or behaviors in the EHR ( N = 395,064). GWAS was performed separately in each ancestry group, controlling for sex, age and genetic substructure. Pan-ancestry risk loci were identified through meta-analysis and included two genome-wide significant loci on chromosomes 20 ( p = 3.64 × 10 -9 ) and 1 ( p = 3.69 × 10 -8 ). A strong pan-ancestry signal at the Dopamine Receptor D2 locus ( p = 1.77 × 10 -7 ) was also identified and subsequently replicated in a large, independent international civilian cohort ( p = 7.97 × 10 -4 ). Additionally, ancestry-specific genome-wide significant loci were also detected in African-Americans, European-Americans, Asian-Americans, and Hispanic-Americans. Pathway analyses suggested over-representation of many biological pathways with high clinical significance, including oxytocin signaling, glutamatergic synapse, cortisol synthesis and secretion, dopaminergic synapse, and circadian rhythm. These findings confirm that the genetic architecture underlying suicide attempt risk is complex and includes both pan-ancestry and ancestry-specific risk loci. Moreover, pathway analyses suggested many commonly impacted biological pathways that could inform development of improved therapeutics for suicide prevention.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2019

Exploring Beyond Earth's Atmosphere with Human-Machine Teams

NASA's highly successful Kepler Mission has revolutionized our understanding of the Galaxy. We now know that planets, even Earth-size planets in the habitable zone, are common. With the end of the Kepler Mission we now look to the future with the Transiting Exoplanet Survey Satellite (TESS) which will discover thousands of exoplanets in orbit around the brightest stars in the sky. In a two-year survey, TESS will perform an all-sky search of more than 200,000 stars for temporary drops in brightness caused by planetary transits. With Kepler and TESS, humanity is finally at the verge of studying the masses, sizes, densities, orbits, and atmospheres of a large cohort of small planets, including a sample of rocky worlds in the habitable zones of their host stars which may prove to host life. The massive data sets generated by Kepler and TESS must be meticulously combed for the weakest planetary signals every month. While a daunting and error-prone task for humans, this is an exciting opportunity for the breakthroughs recently seen in machine learning. Specifically, traditional methods for identifying planet transits require extensive data processing pipelines followed by extensive human vetting. This manual process risks loss of information due to the data processing and to inconsistency and biases due to individual human vetters. The latest advancements in machine learning will allow an objective classifier to minimize the losses of information and greatly lessen the burden on the human vetters, in addition to providing assessment of quality and score to each planet candidate, freeing the humans to concentrate on border cases and other more interesting investigations.

Smith, Jeffrey C.↗
NASA NTRS2016

Bone Turnover Does Not Reflect Skeletal Aging in Older Hispanic Men with Type 2 Diabetes

The paradox of fragility fracture in the presence of non-osteoporotic bone mineral density in older patients with type 2 diabetes mellitus (DM2) makes it difficult to clinically predict fracture in this vulnerable group. Serum osteocalcin (OC), a marker of bone turnover, increases with normal skeletal aging indicating risk of fracture. However, OC has been reported to be lower in patients with DM2. An inverse association between higher glycated hemoglobin levels (HbA1c) and lower serum OC in older DM2 patients triggered discussions encouraging further investigation. A key question to be answered is whether changes in glucose metabolism is responsible for bone metabolic changes, ultimately leading to increased risk of fragility fractures in DM2 patients. While these studies were conducted among Caucasian and Asian populations, this has not been studied in Hispanic populations who suffer from a higher prevalence of DM2. The Cameron County Hispanic Cohort (CCHC) in Texas is a homogeneous Hispanic cohort known to have high prevalence of DM2 (30%). Our preliminary data from this cohort reported OC levels lower than the suggested threshold for fragility fracture in post-menopausal women. We further investigated whether bone turnover in older CCHC adults with DM2 show a normal pattern of skeletal aging. Samples and data were obtained from a nested cohort of 68 (21 men and 47 women) Hispanic older adults (≥50 years) who had a diagnosis of DM2. Given high prevalence of uncontrolled DM2 in this cohort, we divided population into two groups: i) poor DM2 control with HbA1c level ≥8 (48% men and 38% women) and ii) good DM2 control with HbA1c level <8). A crosssectional analysis documented associations between serum OC and age adjusted HbA1c levels. There was no direct association between age and OC concentrations in our study. Higher HbA1c was associated with lower serum OC in men (odds ratio -6.5, 95% confidence interval -12.7 to - 0.3, p < 0.04). No significant associations were identified in women. Bone turnover in older Hispanic men with DM2 in our study does not reflect normal pattern of skeletal aging. It is unclear why similar results were not identified in women. We will continue to follow this cohort to investigate longitudinal trend of changes of bone turnover and its relationship with HbA1c in both men and women of this cohort.

Rianon, N.↗
DOE OSTI2020

Accuracy of self‐reported weight, height and body mass index among older people in Japan

Aim Weight and height are usually self‐reported in population‐based epidemiological surveys. While the accuracy of self‐reports has been extensively studied in younger populations, less is known in older populations. We investigated the accuracy of self‐reported weight, height and body mass (BMI) in an older cohort in Japan, where overweight/obesity and underweight coexist. Methods We used data from older Japanese adults (≥65 years) participating in the Japan Gerontological Evaluation Study in 2016 to 2017 (7357 men and 9271 women). Self‐report data were linked to objective data obtained from clinical examinations. Results The mean ± standard deviation (SD) age was 74.5 ± 5.8 years, mean ± SD weight, height and BMI were 55.7 ± 10.1 kg, 156.0 ± 8.9 cm and 22.8 ± 3.1, respectively. Results showed high intraclass correlation coefficients for self‐reported and measured values (0.97 for weight; 0.96 for height). While weight/height were overestimated among men (weight by 0.096 kg; height by 0.27 cm) and women (weight by 0.18 kg; height by 0.27 cm), BMI tended to be slightly underestimated (−0.034 kg/m 2 for men; −0.037 kg/m 2 for women). However, the absolute differences between self‐reported and measured values were not negligible; people had a higher risk for both under‐ and overestimation of their BMI category with increasing age. Lower education predicted BMI overestimation, whereas lower income predicted BMI underestimation. Conclusions Overall accuracy of self‐reported body habitus was higher in this cohort of older Japanese compared with previous reports. Nevertheless, misclassification of BMI due to the misreporting of their weight/height was more common among the oldest‐old, as well as those with lower education and income. Geriatr Gerontol Int 2020; 20: 803–810 .

Yazawa, Aki↗
DOE OSTI2026

Myriad World Baseline: Global Geodemographic Estimates

The LandScan Myriad World Baseline (MWB) method produces global, residential (nighttime/home-location) gridded geodemographic estimates based on 5-year age/gender cohorts—at 30-arcsecond (≈1 km) resolution. MWB is designed to fill gaps where detailed, georeferenced survey data (e.g., Demographic and Health Surveys (DHS)) are missing or outdated, and to provide a baseline that can support human security analysis, including consequence assessment, “patterns of life” modeling, and scenario-based population futures. MWB’s workflow spatializes household-level age/gender characteristics from the GLOPOP-S dataset by conflating household and gridded expected relative wealth adapted from Global Gridded Relative Deprivation Index (GRDI), then adjusts them to a target year of interest. Age/gender estimates are then applied to harmonize lowest-administrative-level statistics with LandScan residential counts, yielding final geodemographic estimates. Two validation case studies are presented: Ghana (2021) and Tokyo/Kanagawa, Japan (2020), illustrating spatial variability in demographic cohorts and comparing MWB outputs to official gridded statistics. Results show close overall alignment relative to validation criteria including population pyramids and age-dependency ratios.

Tuccillo, Joe [ORNL] (ORCID:0000000259300943)↗
DOE OSTI2024

Comparative Uptake Patterns of Radioactive Iodine and [18F]-Fluorodeoxyglucose (FDG) in Metastatic Differentiated Thyroid Cancers

Background: Metastatic differentiated thyroid cancer (DTC) represents a molecularly heterogeneous group of cancers with varying radioactive iodine (RAI) and [ 18 F]-fluorodeoxyglucose (FDG) uptake patterns potentially correlated with the degree of de-differentiation through the so-called “flip-flop” phenomenon. However, it is unknown if RAI and FDG uptake patterns correlate with molecular status or metastatic site. Materials and Methods: A retrospective analysis of metastatic DTC patients (n = 46) with radioactive 131-iodine whole body scan (WBS) and FDG-PET imaging between 2008 and 2022 was performed. The inclusion criteria included accessible FDG-PET and WBS studies within 1 year of each other. Studies were interpreted by two blinded radiologists for iodine or FDG uptake in extrathyroidal sites including lungs, lymph nodes, and bone. Cases were stratified by BRAF V600E mutation status, histology, and a combination of tumor genotype and histology. The data were analyzed by McNemar’s Chi-square test. Results: Lung metastasis FDG uptake was significantly more common than iodine uptake (WBS: 52%, FDG: 84%, p = 0.04), but no significant differences were found for lymph or bone metastases. Lung metastasis FDG uptake was significantly more prevalent in the papillary pattern sub-cohort (WBS: 37%, FDG: 89%, p = 0.02) than the follicular pattern sub-cohort (WBS: 75%, FDG: 75%, p = 1.00). Similarly, BRAF V600E+ tumors with lung metastases also demonstrated a preponderance of FDG uptake (WBS: 29%, FDG: 93%, p = 0.02) than BRAF V600E- tumors (WBS: 83%, FDG: 83%, p = 1.00) with lung metastases. Papillary histology featured higher FDG uptake in lung metastasis (WBS: 39%, FDG: 89%, p = 0.03) compared with follicular histology (WBS: 69%, FDG: 77%, p = 1.00). Patients with papillary pattern disease, BRAF V600E+ mutation, or papillary histology had reduced agreement between both modalities in uptake at all metastatic sites compared with those with follicular pattern disease, BRAF V600E- mutation, or follicular histology. Low agreement in lymph node uptake was observed in all patients irrespective of molecular status or histology. Conclusions: The pattern of FDG-PET and radioiodine uptake is dependent on molecular status and metastatic site, with those with papillary histology or BRAF V600E+ mutation featuring increased FDG uptake in distant metastasis. Further study with an expanded cohort may identify which patients may benefit from specific imaging modalities to recognize and surveil metastases.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2026

Multi-Semester Mentoring and GPA Trajectories in SPINS: A Longitudinal Program Evaluation of STEM Scholars

This exploratory longitudinal program evaluation examined GPA trajectories among 14 STEM scholars participating in the Scholarly Partnership in Nuclear Security (SPINS) mentoring program at an HBCU. Using de-identified administrative data (37 scholar-semester observations), the study compared baseline and latest term GPAs anchored to each scholar’s first funded semester. A Wilcoxon signed-rank test was used to assess within-student change. Mean GPA increased modestly from 3.46 (SD = 0.30) at baseline to 3.61 (SD = 0.33) at the latest observed semester, with 12 of 14 scholars (85.7%) showing net improvement (median change = +0.12). The Wilcoxon signed-rank test indicated a statistically significant positive shift (W = 18, p = 0.030). However, scholars entered the program with a high baseline GPA, and ceiling effects were evident for several participants. Grounded in Social Cognitive Career Theory, findings suggest that multi-semester participation in SPINS is associated with GPA stability and modest improvement in an already high-performing cohort. Results should be interpreted cautiously given the small sample size and single-group design. The study highlights the value of sustained, culturally responsive mentoring at an HBCU while underscoring the need for larger evaluations with comparison cohorts and broader psychosocial outcomes. An evidence-informed mentoring framework is proposed to strengthen multi-semester support.

42 ENGINEERING↗
DOE OSTI2023

Human NCR3 gene variants rs2736191 and rs11575837 alter longitudinal risk for development of pediatric malaria episodes and severe malarial anemia

Background: Plasmodium falciparum malaria is a leading cause of pediatric morbidity and mortality in holoendemic transmission areas. Severe malarial anemia [SMA, hemoglobin (Hb) < 5.0 g/dL in children] is the most common clinical manifestation of severe malaria in such regions. Although innate immune response genes are known to influence the development of SMA, the role of natural killer (NK) cells in malaria pathogenesis remains largely undefined. As such, we examined the impact of genetic variation in the gene encoding a primary NK cell receptor, natural cytotoxicity-triggering receptor 3 (NCR3), on the occurrence of malaria and SMA episodes over time. Methods: Susceptibility to malaria, SMA, and all-cause mortality was determined in carriers of NCR3 genetic variants (i.e., rs2736191:C > G and rs11575837:C > T) and their haplotypes. The prospective observational study was conducted over a 36 mos. follow-up period in a cohort of children (n = 1,515, aged 1.9–40 mos.) residing in a holoendemic P. falciparum transmission region, Siaya, Kenya. Results: Poisson regression modeling, controlling for anemia-promoting covariates, revealed a significantly increased risk of malaria in carriers of the homozygous mutant allele genotype (TT) for rs11575837 after multiple test correction [Incidence rate ratio (IRR) = 1.540, 95% CI = 1.114–2.129, P = 0.009]. Increased risk of SMA was observed for rs2736191 in children who inherited the CG genotype (IRR = 1.269, 95% CI = 1.009–1.597, P = 0.041) and in the additive model (presence of 1 or 2 copies) (IRR = 1.198, 95% CI = 1.030–1.393, P = 0.019), but was not significant after multiple test correction. Modeling of the haplotypes revealed that the CC haplotype had a significant additive effect for protection against SMA (i.e., reduced risk for development of SMA) after multiple test correction (IRR = 0.823, 95% CI = 0.711–0.952, P = 0.009). Although increased susceptibility to SMA was present in carriers of the GC haplotype (IRR = 1.276, 95% CI = 1.030–1.581, P = 0.026) with an additive effect (IRR = 1.182, 95% CI = 1.018–1.372, P = 0.029), the results did not remain significant after multiple test correction. None of the NCR3 genotypes or haplotypes were associated with all-cause mortality. Conclusions: Variation in NCR3 alters susceptibility to malaria and SMA during the acquisition of naturally-acquired malarial immunity. These results highlight the importance of NK cells in the innate immune response to malaria.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Archival records housed at USTUR support radium dial worker dosimetry

The American radium dial worker (RDW) cohort of over 3200 persons is being revisited as part of the Million Person Study (MPS) to include a modern approach to RDW dosimetry. An exceptional source of data and contextualization in this project is an extensive collection of electronic records (digitized from existing microfilm and microfiche) housed at the United States Transuranium and Uranium Registries (USTUR). Although the type, extent, and quality (e.g. legibility) of record(s) varies between individuals, the remarkable occupational, medical and demographic data include in vivo radiation measurements (e.g. radon breath, whole body counts), autopsy results, medical records (including copies of radiographs), interviews over the years, and correspondence. Of particular dosimetric interest are the details of radiation measurements. For example, there are some instances where hand-written and transcribed values are both available, along with notes providing context for why a particular measurement in a series of measurements was chosen to assign an intake, or if there were concerns about a particular measurement. Born prior to 1935, RDW have nearly all passed away. Thus, the updated dosimetry, especially for the skeletal tissues, will allow the correlation of lifetime cumulative dose with radiation risk. Here we review typical information available in this collection of historical records and highlight some interesting finds. Additionally, we discuss the relevance to current and ongoing work related to updating the dosimetry of the RDW in the MPS, including providing an example of the usefulness of information contained in these records. The RDW cohort provides a unique historical perspective on occupational exposure to radium, making it a valuable dataset for understanding long-term health effects and improving current radiation protection standards.

Million Person Study↗
DOE OSTI2021

Coding and noncoding variants in EBF3 are involved in HADDS and simplex autism

Abstract Background Previous research in autism and other neurodevelopmental disorders (NDDs) has indicated an important contribution of protein-coding (coding) de novo variants (DNVs) within specific genes. The role of de novo noncoding variation has been observable as a general increase in genetic burden but has yet to be resolved to individual functional elements. In this study, we assessed whole-genome sequencing data in 2671 families with autism (discovery cohort of 516 families, replication cohort of 2155 families). We focused on DNVs in enhancers with characterized in vivo activity in the brain and identified an excess of DNVs in an enhancer named hs737. Results We adapted the fitDNM statistical model to work in noncoding regions and tested enhancers for excess of DNVs in families with autism. We found only one enhancer (hs737) with nominal significance in the discovery (p = 0.0172), replication (p = 2.5 × 10 −3 ), and combined dataset (p = 1.1 × 10 −4 ). Each individual with a DNV in hs737 had shared phenotypes including being male, intact cognitive function, and hypotonia or motor delay. Our in vitro assessment of the DNVs showed they all reduce enhancer activity in a neuronal cell line. By epigenomic analyses, we found that hs737 is brain-specific and targets the transcription factor gene EBF3 in human fetal brain. EBF3 is genome-wide significant for coding DNVs in NDDs (missense p = 8.12 × 10 −35 , loss-of-function p = 2.26 × 10 −13 ) and is widely expressed in the body. Through characterization of promoters bound by EBF3 in neuronal cells, we saw enrichment for binding to NDD genes (p = 7.43 × 10 −6 , OR = 1.87) involved in gene regulation. Individuals with coding DNVs have greater phenotypic severity (hypotonia, ataxia, and delayed development syndrome [HADDS]) in comparison to individuals with noncoding DNVs that have autism and hypotonia. Conclusions In this study, we identify DNVs in the hs737 enhancer in individuals with autism. Through multiple approaches, we find hs737 targets the gene EBF3 that is genome-wide significant in NDDs. By assessment of noncoding variation and the genes they affect, we are beginning to understand their impact on gene regulatory networks in NDDs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Normative Ranges for, and Interrater Reliability of, Rotational Vestibular and Balance Tests in U.S. Military Service Members and Veterans

Purpose: The objectives of this study were to (a) describe normative ranges—expressed as reference intervals (RIs)—for vestibular and balance function tests in a cohort of Service Members and Veterans (SMVs) and (b) to describe the interrater reliability of these tests. Method: As part of the Defense and Veterans Brain Injury Center (DVBIC)/Traumatic Brain Injury Center of Excellence 15-year Longitudinal Traumatic Brain Injury (TBI) Study, participants completed the following: vestibulo-ocular reflex suppression, visual-vestibular enhancement, subjective visual vertical, subjective visual horizontal, sinusoidal harmonic acceleration, the computerized rotational head impulse test (crHIT), and the sensory organization test. RIs were calculated using nonparametric methods and interrater reliability was assessed using intraclass correlation coefficients between three audiologists who independently reviewed and cleaned the data. Results: Reference populations for each outcome measure comprised 40 to 72 individuals, 19 to 61 years of age, who served either as noninjured controls (NIC) or injured controls (IC) in the 15-year study; none had a history of TBI or blast exposure. A subset of 15 SMVs from the NIC, IC, and TBI groups were included in the interrater reliability calculations. RIs are reported for 27 outcome measures from the seven rotational vestibular and balance tests. Interrater reliability was considered excellent for all tests except the crHIT, which was found to have good interrater reliability. Conclusion: This study provides clinicians and scientists with important information regarding normative ranges and interrater reliability for rotational vestibular and balance tests in SMVs.

Audiology & Speech-Language Pathology↗