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NASA NTRS2010

Correlate Life Predictions and Condition Indicators in Helicopter Tail Gearbox Bearings

Research to correlate bearing remaining useful life (RUL) predictions with Helicopter Health Usage Monitoring Systems (HUMS) condition indicators (CI) to indicate the damage state of a transmission component has been developed. Condition indicators were monitored and recorded on UH-60M (Black Hawk) tail gearbox output shaft thrust bearings, which had been removed from helicopters and installed in a bearing spall propagation test rig. Condition indicators monitoring the tail gearbox output shaft thrust bearings in UH-60M helicopters were also recorded from an on-board HUMS. The spal-lpropagation data collected in the test rig was used to generate condition indicators for bearing fault detection. A damage progression model was also developed from this data. Determining the RUL of this component in a helicopter requires the CI response to be mapped to the damage state. The data from helicopters and a test rig were analyzed to determine if bearing remaining useful life predictions could be correlated with HUMS condition indicators (CI). Results indicate data fusion analysis techniques can be used to map the CI response to the damage levels.

Dempsey, Paula J.↗

NASA NTRS2014

Stardust Interstellar Preliminary Examination VII: Synchrotron X-Ray Fluorescence Analysis of Six Stardust Interstellar Candidates Measured with the Advanced Photon Source 2-ID-D Microprobe

The NASA Stardust spacecraft exposed an aerogel collector to the interstellar dust passing through the solar system. We performed X-ray fluorescence element mapping and abundance measurements, for elements 19 < or = Z < or = 30, on six "interstellar candidates," potential interstellar impacts identified by Stardust@Home and extracted for analyses in picokeystones. One, I1044,3,33, showed no element hot-spots within the designated search area. However, we identified a nearby surface feature, consistent with the impact of a weak, high-speed particle having an approximately chondritic (CI) element abundance pattern, except for factor-of-ten enrichments in K and Zn and an S depletion. This hot-spot, containing approximately 10 fg of Fe, corresponds to an approximately 350 nm chondritic particle, small enough to be missed by Stardust@Home, indicating that other techniques may be necessary to identify all interstellar candidates. Only one interstellar candidate, I1004,1,2, showed a track. The terminal particle has large enrichments in S, Ti, Cr, Mn, Ni, Cu, and Zn relative to Fe-normalized CI values. It has high Al/Fe, but does not match the Ni/Fe range measured for samples of Al-deck material from the Stardust sample return capsule, which was within the field-of-view of the interstellar collector. A third interstellar candidate, I1075,1,25, showed an Al-rich surface feature that has a composition generally consistent with the Al-deck material, suggesting that it is a secondary particle. The other three interstellar candidates, I1001,1,16, I1001,2,17, and I1044,2,32, showed no impact features or tracks, but allowed assessment of submicron contamination in this aerogel, including Fe hot-spots having CI-like Ni/Fe ratios, complicating the search for CI-like interstellar/interplanetary dust.

Stardust↗

NASA NTRS2017

Determination of the Risk of Radiation-Associated Circulatory and Cancer Disease Mortality in a NASA Early Astronaut Cohort

Of the many possible health challenges posed during extended exploratory missions to space, the effects of space radiation on cardiovascular disease and cancer are of particular concern. There are unique challenges to estimating those radiation risks; care and appropriate and rigorous methodology should be applied when considering small cohorts such as the NASA astronaut population. The objective of this work was to determine if there was sufficient evidence for excess risk of cardiovascular disease and cancer in early NASA astronaut cohorts. NASA astronauts in selection groups 1-7 were chosen; this relatively homogeneous cohort consists of 73 white males, who unlike today's astronauts, maintained similar smoking and drinking habits to the general US population, and have published radiation doses. The participants flew in space on missions Mercury through Shuttle and received space radiation doses between 0-74.1 milligrays. Cause of death information was obtained from the Lifetime Surveillance of Astronaut Health (LSAH) program at NASA Johnson Space Center. Mortality was compared with the US male population. Trends of mortality with dose were assessed using a logistic model, fitted by maximum likelihood. Only 32 (43.84 percent) of the 73 early astronauts have died. Standard mortality ratios (SMRs) for cancer (n=7, SMR=43.4, 95 percent CI 17.8, 84.9), all circulatory disease (n=7, SMR=33.2, 95 percent CI 13.7, 65.0), and ischemic heart disease (IHD) (n=5, SMR=40.1, 95 percent CI 13.2, 89.4) were significantly lower than for the US white male population. For cerebrovascular disease, the upper confidence interval for SMR included 100, indicating it was not significantly different from the US population (n=2, SMR = 77.0, 95 percent CI 9.4, 268.2). The power of the study is low and remains below 10 percent even when risks 10 times those reported in the literature are assumed. Due to small sample size, there is currently insufficient statistical power to evaluate space radiation exposure effects on mortality in NASA astronauts. In addition to a comprehensive longitudinal study of NASA astronauts, a research strategy of low dose epidemiology data integration with cell and animal studies should be utilized for space radiation risk assessment in the astronauts.

Elgart, S. R.↗

NASA NTRS2017

BrO and Inferred Bry Profiles over the Western Pacific: Relevance of Inorganic Bromine Sources and a Bry Minimum in the Aged Tropical Tropopause Layer

We report measurements of bromine monoxide (BrO) and use an observationally constrained chemical box model to infer total gas-phase inorganic bromine (Br(sub y)) over the tropical western Pacific Ocean (tWPO) during the CONTRAST field campaign (January-February 2014). The observed BrO and inferred Bry profiles peak in the marine boundary layer (MBL), suggesting the need for a bromine source from sea-salt aerosol (SSA), in addition to organic bromine (CBry ). Both profiles are found to be C-shaped with local maxima in the upper free troposphere (FT). The median tropospheric BrO vertical column density (VCD) was measured as 1.6 x 10(exp 13) molec cm(exp -2), compared to model predictions of 0.9 x 10(exp 13) molec cm(exp -2) in GEOS-Chem (CBr(sub y) but no SSA source), 0.4 x 10(exp 13) molec cm(exp -2) in CAM-Chem (CBr(sub y) and SSA), and 2.1 x 10(exp 13) molec cm(exp -2) in GEOS-Chem (CBry and SSA). Neither global model fully captures the Cshape of the Br(sun y) profile. A local Br(sub y) maximum of 3.6 ppt (2.9-4.4 ppt; 95% confidence interval, CI) is inferred between 9.5 and 13.5 km in air masses influenced by recent convective outflow. Unlike BrO, which increases from the convective tropical tropopause layer (TTL) to the aged TTL, gas-phase Br(sub y) decreases from the convective TTL to the aged TTL. Analysis of gas-phase Br(sub y) against multiple tracers (CFC-11, H2O/O3 ratio, and potential temperature) reveals a Br(sub y) minimum of 2.7 ppt (2.3-3.1 ppt; 95% CI) in the aged TTL, which agrees closely with a stratospheric injection of 2.6 +/- 0.6 ppt of inorganic Br(sub y) (estimated from CFC-11 correlations), and is remarkably insensitive to assumptions about heterogeneous chemistry. Bry increases to 6.3 ppt (5.6-7.0 ppt; 95% CI) in the stratospheric "middleworld" and 6.9 ppt (6.5-7.3 ppt; 95% CI) in the stratospheric "overworld". The local Br(sub y) minimum in the aged TTL is qualitatively (but not quantitatively) captured by CAM-Chem, and suggests a more complex partitioning of gas-phase and aerosol Br(sub y) species than previously recognized. Our data provide corroborating evidence that inorganic bromine sources (e.g., SSA-derived gas-phase Br(sub y) ) are needed to explain the gas-phase Br(sub y) budget in the upper free troposphere and TTL. They are also consistent with observations of significant bromide in Upper Troposphere-Lower Stratosphere aerosols. The total Br(sub y) budget in the TTL is currently not closed, because of the lack of concurrent quantitative measurements of gas-phase Br(sub y) species (i.e., BrO, HOBr, HBr, etc.) and aerosol bromide. Such simultaneous measurements are needed to (1) quantify SSA-derived Br(sub y) in the upper FT, (2) test Br(sub y) partitioning, and possibly explain the gas-phase Br(sub y) minimum in the aged TTL, (3) constrain heterogeneous reaction rates of bromine, and (4) account for all of the sources of Br(sub y) to the lower stratosphere.

Atmospheric Chemistry; bromine; troposphere; CONTR↗

NASA NTRS2018

A Comprehensive Model of Earth's Magnetic Field Determined from 4 Years of Swarm Satellite Observations

The European Space Agency's three-satellite constellation Swarm, launched in November 2013, has provided unprecedented monitoring of Earth's magnetic field via a unique set of gradiometric and multi-satellite measurements from low Earth orbit. In order to exploit these measurements, an advanced "Comprehensive Inversion" (CI) algorithm has been developed to optimally separate the various major magnetic field sources in the near-Earth regime. The CI algorithm is used to determine Swarm Level-2 (L2) magnetic field data products that include the core, lithospheric, ionospheric, magnetospheric, and associated induced sources. In addition, it has become apparent that the CI is capable of extracting the magnetic signal associated with the oceanic principal lunar semi-diurnal tidal constituent M(sub 2) to such an extent that it has been added to the L2 data product line. This paper presents the parent model of the Swarm L2 CI products derived with measurements from the first four years of the Swarm mission and from ground observatories, denoted as "CIY4", including the new product describing the magnetic signal of the M(sub 2) oceanic tide.

Swarm Satellites↗

NASA NTRS2019

Completeness Index for Earthquake-Induced Landslide Inventories

Understanding the global relation between Earthquake-Induced Landslides (EQILs) and the factors contributing to their initiation is still an open topic within the geomorphological community. Accessing EQIL inventories and analyzing them concerning their potential causes is the key to explore such relation. However, each of the existing EQIL inventories has its level of completeness and associated uncertainty which makes any unified relationship which is challenging to obtain. So far, the completeness of EQIL inventories has never been clearly defined. As a result, it has never been accounted for in global EQIL predictive models. In this technical note, we propose a simple definition for the completeness of EQIL inventories. We analyze 30 digital EQIL for 21 earthquakes and develop a semi-quantitative method to estimate the completeness level, which we refer to as Completeness Index (CI). The CI results from a combination of topographic factors, ground shaking parameters, and a measure derived from landslide size statistics. The proposed CI consists of Low, Moderate, and High completeness classes which can be used to evaluate any landslide inventory. We made the whole procedure to compute the CI accessible in an ArcGIS toolbox together with a test dataset.

Hakan Tanyas↗

NASA NTRSDate not supplied

Reflectance spectra measurement plan of captured samples from Ryugu: current status

Hayabusa2 spacecraft is equipped with Optical Navigation Camera (ONC) andNear-infrared Spectrometer (NIRS3), and has obtained reflectance spectra of the C-type near-Earth asteroid Ryugu over a wavelength range of 0.40–0.95 μm and 1.8–3.2 μm, respectively. It was revealed that Ryugu exhibits globally very low albedo (less than 0.02 at 0.55 and 2.0 μm), a slightly positive spectral slope, and an ubiquitous weak but sharp OH absorption band centered at 2.72 μm,showing a little regional heterogeneities. Thus, the surface material of Ryugu can be estimated as relatively similar to moderately heated carbonaceous chondrites, e.g., moderately dehydrated CI and CM, and enriched in carbon (Kitazato et al., 2019; Sugita et al., 2019; Tatsumi et al., 2020).Hayabusa2 successfully has performed twice touch down operations, and the captured sample will be brought back to the Earth in late 2020 (Morota et al., 2020; Tachibana et al., in preparation). To clarify Ryugu’s mineralogical and physicochemical properties and their varieties, effective for spectral characteristics obtained by ONC and NIRS3, several grains are planned to be distributed to several primary analysis groups. In this study, we report the current status of our spectral analysis plan in Hayabusa2 MINeralogy and PETrology of coarse grains (MIN-PET CG) team led by T. Nakamura, and the latest rehearsal analysis result using carbonaceous chondrite samples. MIN-PET CG rehearsal measurements have been performed to obtain detailed spectral properties of Ryugu grains with diverse spatial resolutions ranging from μm to mm scale or larger; using a few mm size polished CM sample with several microscopic imaging spectrometers covering various spatial range; with 200 μmor finer spatial resolution at Institut d’Astrophysique Spatiale, ~50 and 150 μm spatial resolution invisible and IR ranges at Brown University, and with 40 μm or larger spatial resolution at Tohoku University, and using mm-size CM and CI grains with a diffuse reflectance spectrometer with a few mm resolution at Tohoku University. Diffuse reflectance spectroscopy measurements undergo to use several mm-size CM or CI chondrite grains with Bruker VERTEX 70v, which covers ~0.38–15 μm in wavelength. To keep returned samples out of atmosphere avoiding any terrestrial contamination, wehave prepared an air shutoff cell to put samples and standard materials together kept in a N2 purged condition (Amano et al., 2020). Samples are Murchison CM chondrite showing typically ~5%reflectance with a strong OH absorption band at ~2.8 μm, and laboratory heated CI chondrite showing~3% reflectance, and a weak OH absorption band at ~2.7 μm. We will perform (1) fixed angle condition as laboratory standard setting at incident, emission, and phase angles of 30°, 0°, 30°, or 0°,30°, 30°, and (2) various angle conditions for photometric corrections. Future lab analyses of samples returned from Ryugu will provide direct and detailed information on the mineralogical and physicochemical properties of Ryugu, and relationship of spectral characteristics obtained by remote sensing and laboratory instruments.

M. Matsuoka↗

NASA NTRS2022

Changes in Optic Nerve Head and Retinal Morphology During Spaceflight and Acute Fluid Shift Reversal

Importance: Countermeasures that reverse the headward fluid shift experienced in weightlessness have the potential to mitigate spaceflight-associated neuro-ocular syndrome. This study investigated whether use of the countermeasure lower-body negative pressure during spaceflight was associated with changes in ocular structure. Objective: To determine whether changes to the optic nerve head and retina during spaceflight can be mitigated by brief in-flight application of 25-mm Hg lower-body negative pressure. Design, Setting, and Participants: In the National Aeronautics and Space Administration’s “Fluid Shifts Study,” a prospective cohort study, optical coherence tomography scans of the optic nerve head and macula were obtained from US and international crew members before flight, in-flight, and up to 180 days after return to Earth. In-flight scans were obtained both under normal weightless conditions and 10 to 20 minutes into lower-body negative pressure exposure. Preflight and postflight data were collected in the seated, supine, and head-down tilt postures. Crew members completed 6- to 12-month missions that took place on the International Space Station. Data were analyzed from 2016 to 2021. Interventions or Exposures: Spaceflight and lower-body negative pressure. Main Outcomes and Measures: Changes in minimum rim width, optic cup volume, Bruch membrane opening height, peripapillary total retinal thickness, and macular thickness. Results: Mean (SD) flight duration for the 14 crew members (mean [SD] age, 45 [6] years; 11 male crew members [79%]) was 214 (72) days. Ocular changes on flight day 150, as compared with preflight seated, included an increase in minimum rim width (33.8 μm; 95% CI, 27.9-39.7 μm; P < .001), decrease in cup volume (0.038 mm^3; 95% CI, 0.030-0.046 mm^3; P < .001), posterior displacement of Bruch membrane opening (−9.0 μm; 95% CI, −15.7 to −2.2 μm; P = .009), and decrease in macular thickness (fovea to 500 μm, 5.1 μm; 95% CI, 3.5-6.8 μm; P < .001). Brief exposure to lower-body negative pressure did not affect these parameters. Conclusions and Relevance: Results of this cohort study suggest that peripapillary tissue thickening, decreased cup volume, and mild central macular thinning were associated with long-duration spaceflight. Acute exposure to 25-mm Hg lower-body negative pressure did not alter optic nerve head or retinal morphology, suggesting that longer durations of a fluid shift reversal may be needed to mitigate spaceflight-induced changes and/or other factors are involved.

Laura P. Pardon↗

NASA NTRS2022

Oxygen Isotopes of Anhydrous Primary Minerals Show Kinship Between Asteroid Ryugu and Comet 81P/Wild2

The extraterrestrial materials returned from asteroid (162173) Ryugu consist predominantly of low-temperature aqueously formed secondary minerals and are chemically and mineralogically similar to CI (Ivuna-type) carbonaceous chondrites. Here we show that high-temperature anhydrous primary minerals in Ryugu and CI chondrites exhibit a bimodal distribution of oxygen isotopic compositions: 16 O-rich (associated with refractory inclusions) and 16 O-poor (associated with chondrules). Both the 16 O-rich and 16 O-poor minerals probably formed in the inner solar protoplanetary disk and were subsequently transported outwards. The abundance ratios of the 16 O-rich to 16 O-poor minerals in Ryugu and CI chondrites are higher than in other carbonaceous chondrite groups, but are similar to that of comet 81P/Wild2, suggesting that Ryugu and CI chondrites accreted in the outer Solar System closer to the accretion region of comets.

Noriyuki Kawasaki↗

NASA NTRSDate not supplied

Preservation of Previously Unsampled Primordial Isotopic Components in Ryugu and Bennu Samples

Ivuna-type (CI) carbonaceous chondrites are primitive meteorites whose relative elemental abundances closely match the solar photosphere 1 , making them critical benchmarks for the bulk chemical and isotopic composition of the planet-forming disk. Recent sample-return missions to Ryugu 2 and Bennu 3 have enabled direct laboratory analysis of these rubble-pile CI-like asteroids 4 , formed from the reaccumulated fragments of once-larger parent bodies. As such, they may retain a broader spectrum of primordial nucleosynthetic components than is preserved in known meteorites. Here, we report the nucleosynthetic compositions of silicon (μ 30 Si), magnesium (μ 26 Mg*), and iron (μ 54 Fe), three of the four most abundant planet-building elements, in samples from Ryugu and Bennu, along with the newly discovered Oued Chebeika 002 CI chondrite 5 . In contrast to the isotopic homogeneity of CI chondrites, Ryugu and Bennu preserve resolvable μ 26 Mg* and μ 30 Si heterogeneity, revealing μ 26 Mg*- and μ 30 Si-rich nucleosynthetic components not sampled in meteorites. These components may reflect the preservation of previously unsampled primordial isotopic signals, prior to thermal processing 6,7 and late infall of primordial molecular cloud material to the outer disk 8,9 . Additionally, Ryugu particle C0002 exhibits a μ 26 Mg*-poor and μ 54 Cr-rich signature, consistent with incorporation of presolar material from massive supernovae 10,11 . Ryugu and Bennu samples define one end of a μ 54 Fe–μ 30 Si array among carbonaceous asteroid materials 9 , suggesting that the isotopic compositions of these asteroidal materials reflect mixing between early disk isotopic components identified in this study and material derived from the outermost disk 9 . This observation demonstrates that materials with solar chemical abundances can nonetheless exhibit markedly distinct nucleosynthetic signatures. Thus, Ryugu and Bennu samples are critical records of nucleosynthetic diversity among carbonaceous asteroids and underscore the value of sample-return missions in accessing primitive isotopic signatures absent from meteorite collections.

Martin Bizzarro↗

DOE OSTI2022

INVESTIGATION OF TURBULENT JETS, SPRAYS, AND SUPERCRITICAL MIXING BY TIME RESOLVED RAINBOW SCHLIEREN DEFLECTOMETRY

As technological advancements have enabled higher efficiency compression ignition (CI) engines (diesel engines) by operating at higher pressures and temperatures, the mechanisms of fuel-air mixing are postulated to change. Thus, there is a greater need for experimental data to develop and verify new phenomena. However, the fast time scales and harsh environments associated with CI engines present many experimental difficulties and requires high quality non-intrusive diagnostics to obtain useful data. The diagnostics itself must be validated prior to its implementation in an engine environment. The purpose of this research is to advance rainbow schlieren deflectometry (RSD) to study turbulent fuel sprays including the effects of supercritical mixing in CI engine environments. This objective is met by developing and applying quantitative RSD, for the first time, to three separate aspects of fuel sprays: 1) turbulent mixing, 2) phase boundaries, and 3) non-ideal gas mixing. First, quantitative RSD is demonstrated for turbulent mixing in a canonical helium jet. Rayleigh scattering data in the literature is used to validate the concentration measurements obtained by RSD. The results also provide explanations for phenomena occurring in the helium jet and provide data not yet present in the literature. Second, RSD is applied to high pressure multi-phase fuel sprays and new methodologies are developed to distinguish the liquid region from the vapor region and to quantify the in-between region on a probabilistic basis. Isolating liquid and vapor regions generally requires two separate diagnostics, e.g., Mie scattering (liquid region) and Rayleigh scattering (vapor region). However, the results of this study demonstrate that RSD can be used as a single diagnostic to measure both liquid and vapor boundaries. Third, the optical-to-thermodynamic relations associated with refrac-tometry are investigated under non-ideal gas mixing conditions to develop a generalized relationship valid for both ideal or non-ideal gas mixing. The last part of this research develops the theoretical tools to understand and experimentally realize supercritical mixing at diesel conditions. Guided by the theoretical analysis, RSD is applied to compare supercritical versus transcritical mixing at CI conditions using a constant pressure test rig. It is found that while fully supercritical mixing ers benefits in diesel engines, i.e, faster mixing times (50% higher velocities), the absence of droplets which cause high levels of particulate emissions, etc., it would be difficult to achieve in practice because of the requirements of fuels with low critical temperature and/or substantial fuel preheating.

02 PETROLEUM↗

DOE OSTI2023

Operational Intelligence in the ATLAS Continuous Integration System

Describes the role of the ATLAS Continuous Integration (CI) System in the ATLAS offline software development infrastructure • Outlines the CI system components and processes • Details Operational Intelligence techniques to accelerate CI jobs and lower operating costs • Explains the Directed Acyclic Graph (DAG) approach in CI pipelines • Reports achieved improvements

97 MATHEMATICS AND COMPUTING↗

DOE OSTI2024

Historical Savannah River Site Tritium Releases, Pathways, and Transport

† Releases of tritium from the production reactors were due almost entirely to releases of moderator, either as liquid or vapor from the reactor systems and from the heavy water rework facility. Small amounts could have been released from the reactor blanket gas system and from irradiated lithium-bearing control rods and targets stored underwater in the disassembly basins (Longtin et al. 1973; Jacober et al. 1973). ‡Only a part of the tritium released to the seepage and retention basins leave the site. Of the 3,015,000 Ci of tritium released to the basins, 27% (0.81M Ci) evaporated from the basin surfaces, 40% (1.2M Ci) migrated to outcrops and entered surface streams, and 33% (0.99M Ci) remains under the basins.

Chiswell, Steven R.↗

DOE OSTI2020

Configuration–Interaction Perturbation Theory Calculations of Pu II

Configuration–interaction perturbation theory (CI–PT) is applied to calculations of low-energy states of Pu II. This ion is quite challenging due to a large number of possible determinants arising from seven valence electrons and strong relativistic effects. The CI–PT calculations agree with experiments for the energies and g-factors for many low-energy states that allowed positive identification of the theoretical levels. Isotope shifts were also used to aid in identification, and, in case of the odd states, fitting with three independent parameters was used to match theoretical isotope shifts to the experimental values with good accuracy. The CI–PT approach tested here on the Pu II ion can be generally used to calculate properties of many complex atoms, including U I that can find application in fundamental and applied science.

74 ATOMIC AND MOLECULAR PHYSICS↗

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 OSTI2020

Iron Heterogeneity in Early Active Multiple Sclerosis Lesions

Objective: Multiple sclerosis (MS) is a heterogeneous inflammatory demyelinating disease. Iron distribution is altered in MS patients' brains, suggesting iron liberation within active lesions amplifies demyelination and neurodegeneration. Whether the amount and distribution of iron are similar or different among different MS immunopatterns is currently unknown. Methods: We used synchrotron X-ray fluorescence imaging, histology, and immunohistochemistry to compare the iron quantity and distribution between immunopattern II and III early active MS lesions. We analyzed archival autopsy and biopsy tissue from 21 MS patients. Results: Immunopattern II early active lesions contain 64% more iron (95% confidence interval [CI] = 17-127, p = 0.004) than immunopattern III lesions, and 30% more iron than the surrounding periplaque white matter (95% CI = 3–64%, p = 0.03). Iron in immunopattern III lesions is 28% lower than in the periplaque white matter (95% CI = -40 to -14%, p < 0.001). When normalizing the iron content of early active lesions to that of surrounding periplaque white matter, the ratio is significantly higher in immunopattern II (p < 0.001). Microfocused X-ray fluorescence imaging shows that iron in immunopattern II lesions localizes to macrophages, whereas macrophages in immunopattern III lesions contain little iron. Interpretation: Iron distribution and content are heterogeneous in early active MS lesions. Iron accumulates in macrophages in immunopattern II, but not immunopattern III lesions. This heterogeneity in the two most common MS immunopatterns may be explained by different macrophage polarization, origin, or different demyelination mechanisms, and paves the way for developing new or using existing iron-sensitive magnetic resonance imaging techniques to differentiate among immunopatterns in the general nonbiopsied MS patient population.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2020

Adult weight change and premenopausal breast cancer risk: A prospective pooled analysis of data from 628,463 women

Early-adulthood body size is strongly inversely associated with risk of premenopausal breast cancer. It is unclear whether subsequent changes in weight affect risk. We pooled individual-level data from 17 prospective studies to investigate the association of weight change with premenopausal breast cancer risk, considering strata of initial weight, timing of weight change, other breast cancer risk factors and breast cancer subtype. Hazard ratios (HR) and 95% confidence intervals (CI) were obtained using Cox regression. Among 628,463 women, 10,886 were diagnosed with breast cancer before menopause. Models adjusted for initial weight at ages 18–24 years and other breast cancer risk factors showed that weight gain from ages 18–24 to 35–44 or to 45–54 years was inversely associated with breast cancer overall (e.g., HR per 5 kg to ages 45–54: 0.96, 95% CI: 0.95–0.98) and with oestrogen-receptor(ER)-positive breast cancer (HR per 5 kg to ages 45–54: 0.96, 95% CI: 0.94–0.98). Weight gain from ages 25–34 was inversely associated with ER-positive breast cancer only and weight gain from ages 35–44 was not associated with risk. None of these weight gains were associated with ER-negative breast cancer. Weight loss was not consistently associated with overall or ER-specific risk after adjusting for initial weight. Weight increase from early-adulthood to ages 45–54 years is associated with a reduced premenopausal breast cancer risk independently of early-adulthood weight. Biological explanations are needed to account for these two separate factors.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2024

Association of female reproductive and hormonal factors with gallbladder cancer risk in Asia: A pooled analysis of the Asia Cohort Consortium

Abstract The female predominance of gallbladder cancer (GBC) has led to a hypothesis regarding the hormone‐related aetiology of GBC. We aimed to investigate the association between female reproductive factors and GBC risk, considering birth cohorts of Asian women. We conducted a pooled analysis of 331,323 women from 12 cohorts across 4 countries (China, Japan, Korea, and Singapore) in the Asia Cohort Consortium. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) to assess the association between reproductive factors (age at menarche, parity, age at first delivery, breastfeeding, and age at menopause) and GBC risk. We observed that a later age at menarche was associated with an increased risk of GBC (HR 1.4, 95% CI 1.16–1.70 for 17 years and older vs. 13–14 years), especially among the cohort born in 1940 and later (HR 2.5, 95% CI 1.50–4.35). Among the cohort born before 1940, women with a later age at first delivery showed an increased risk of GBC (HR 1.56, 95% CI 1.08–2.24 for 31 years of age and older vs. 20 years of age and younger). Other reproductive factors did not show a clear association with GBC risk. Later ages at menarche and at first delivery were associated with a higher risk of GBC, and these associations varied by birth cohort.

Shin, Aesun↗