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NASA NTRS2014

Comparing and Reconciling Traditional Field and Photogeologic Mapping Techniques: Lessons from the San Francisco Volcanic Field, Arizona

Cartographic products and - specifically - geologic maps provide critical assistance for establishing physical and temporal frameworks of planetary surfaces. The technical methods that result in the creation of geologic maps vary depending on how observations are made as well as the overall intent of the final products [1-3]. These methods tend to follow a common linear work flow, including the identification and delineation of spatially and temporally discrete materials (units), the documentation of their primary (emplacement) and secondary (erosional) characteristics, analysis of the relative and absolute age relationships between these materials, and the collation of observations and interpretations into an objective map product. The "objectivity" of a map is critical cross comparison with overlapping maps and topical studies as well as its relevance to scientific posterity. However, the "accuracy" and "correctness" of a geologic map is very subject to debate. This can be evidenced by comparison of existing geologic maps at various scales, particularly those compiled through field- and remote-based mapped efforts. Our study focuses on comparing the fidelity of (1) "Apollo-style" geologic investigations, where typically non-geologist crew members follow static traverse routes established through pre-mission planning, and (2) "traditional" field-based investigations, where geologists are given free rein to observe without preplanned routes. This abstract summarizes the regional geology wherein our study was conducted, presents the geologic map created from traditional field mapping techniques, and offers basic insights into how geologic maps created from different tactics can be reconciled in support of exploratory missions. Additional abstracts [4-6] from this study discuss various exploration and science results of these efforts.

Skinner, J. A., Jr.↗

NASA NTRS2014

Erasing the Variable: Empirical Foreground Discovery for Global 21 cm Spectrum Experiments

Spectral measurements of the 21 cm monopole background have the promise of revealing the bulk energetic properties and ionization state of our universe from z approx. 6 − 30. Synchrotron foregrounds are orders of magnitude larger than the cosmological signal, and are the principal challenge faced by these experiments. While synchrotron radiation is thought to be spectrally smooth and described by relatively few degrees of freedom, the instrumental response to bright foregrounds may be much more complex. To deal with such complexities, we develop an approach that discovers contaminated spectral modes using spatial fluctuations of the measured data. This approach exploits the fact that foregrounds vary across the sky while the signal does not. The discovered modes are projected out of each line-of-sight of a data cube. An angular weighting then optimizes the cosmological signal amplitude estimate by giving preference to lower-noise regions. Using this method, we show that it is essential for the passband to be stable to at least approx. 10(exp −4). In contrast, the constraints on the spectral smoothness of the absolute calibration are mainly aesthetic if one is able to take advantage of spatial information. To the extent it is understood, controlling polarization to intensity leakage at the approx. 10(exp −2) level will also be essential to rejecting Faraday rotation of the polarized synchrotron emission. Subject headings: dark ages, reionization, first stars - methods: data analysis - methods: statistical

Variable↗

NASA NTRS2017

The Fundamental Stellar Parameters of FGK Stars in the SEEDS Survey Norman, OK 73071, USA

Large exoplanet surveys have successfully detected thousands of exoplanets to-date. Utilizing these detections and non-detections to constrain our understanding of the formation and evolution of planetary systems also requires a detailed understanding of the basic properties of their host stars. We have determined the basic stellar properties of F, K and G stars in the Strategic Exploration of Exoplanets and Disks with Subaru (SEEDS) survey from Echelle spectra taken at the Apache Point Observatory's 3.5m telescope. Using ROBOSPECT to extract line equivalent widths and Temperature Gravity microtrubulent Velocity ITerations to calculate the fundamental parameters, we have computed T(sub eff), log(g), v(sub t), [Fe/H], chromospheric activity and the age for our sample. Our methodology was calibrated against previously published results for a portion of our sample. The distribution of [Fe/H] in our sample is consistent with that typical of the Solar neighbourhood. Additionally, we find the ages of most of our sample are less than 500 Myr, but note that we cannot determine robust ages from significantly older stars via chromospheric activity age indicators. The future meta-analysis of the frequency of wide stellar and sub-stellar companions imaged via the SEEDS survey will utilize our results to constrain the occurrence of detected comoving companions with the properties of their host stars.

Strategic Exploration of Exoplanets and Disks with↗

NASA NTRS2020

Spatial U-Pb Age Distribution in Shock-Recrystallized Zircon – A Case Study from the Rochechouart Impact Structure, France

Age determination of impact structures via the zircon U–Pb system remains challenging and often ambiguous due to highly variable effects of shock metamorphism on U-Pb geochronology. It is, therefore, crucial to link the observed zircon microtextures, including their temperature and pressure conditions associated with their formation, directly to the U–Pb ages preserved. Here, we analyzed three recrystallized zircon grains and one plastically deformed zircon crystal from the medium-sized Rochechouart impact structure in the northwestern Massif Central of France. For the Rochechouart impact structure the impact age (206.92 ± 0.32 Ma [40Ar/39Ar]) as well as the 2 tectono-themal history is well established making this study site ideal to test concepts about U-Pb systematics in shocked zircon and to differentiate between shock-driven age resetting and preimpact crystallization and metamorphic overprinting. Zircon microstructures were studied using scanning electron imaging, cathodoluminescence imaging, and electron backscatter diffraction (EBSD) mapping. Further, we conducted U–Pb Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) depth-profiling analysis, allowing us to interpret the resultant age data in discrete steps with increasing ablation time/depth. The U–Pb depth profiling data demonstrate that plastically strained grains are incompletely reset and preserve rim and interior age domains reflecting typical pre-impact (pre-Variscan and Variscan) regional tectonic ages. Our results also reveal that the granular crystals encountered contain microstructural evidence for “former reidite in granular neoblastic” (FRIGN) zircon, reflecting both high-pressure (⩾30GPa) and high temperature (⩾1200℃) conditions. This signifies that FRIGN zircon is now known from an additional, medium sized, impact structure further supporting the hypothesis that this impact induced microstructure is commonly preserved. In addition, FRIGN zircon has a high potential to preserve completely impact-reset crystal domains (~204 to 207 Ma) that can be identified by our combined analytical approach of U–Pb depth profiling and EBSD mapping, and thus are suitable for determining reliable impact ages

U-Pb depth profiling↗

NASA NTRS1980

Mitochondrial role in cell aging

The experimental studies on the mitochondria of insect and mammalian cells are examined with a view to an analysis of intrinsic mitochondrial senescence, and its relation to the age-related changes in other cell organelles. The fine structural and biochemical data support the concept that the mitochondria of fixed postmitotic cells may be the site of intrinsic aging because of the attack by free radicals and lipid peroxides originating in the organelles as a by-product of oxygen reduction during respiration. Although the cells have numerous mechanisms for counteracting lipid peroxidation injury, there is a slippage in the antioxidant protection. Intrinsic mitochondrial aging could thus be considered as a specific manifestation of oxygen toxicity. It is proposed that free radical injury renders an increasing number of the mitochondria unable to divide, probably because of damage to the lipids of the inner membrane and to mitochondrial DNA.

Miquel, J.↗

NASA NTRS1995

Global stratigraphy of Venus: Analysis of a random sample of thirty-six test areas

Basilevsky, Alexander T.↗

NASA NTRS1995

Global Stratigraphy of Venus: Analysis of a Random Sample of Thirty-Six Test Areas

The age relations between 36 impact craters with dark paraboloids and other geologic units and structures at these localities have been studied through photogeologic analysis of Magellan SAR images of the surface of Venus. Geologic settings in all 36 sites, about 1000 x 1000 km each, could be characterized using only 10 different terrain units and six types of structures. These units and structures form a major stratigraphic and geologic sequence (from oldest to youngest): (1) tessera terrain; (2) densely fractured terrains associated with coronae and in the form of remnants among plains; (3) fractured and ridged plains and ridge belts; (4) plains with wrinkle ridges; (5) ridges associated with coronae annulae and ridges of arachnoid annulae which are contemporary with wrinkle ridges of the ridged plains; (6) smooth and lobate plains; (7) fractures of coronae annulae, and fractures not related to coronae annulae, which disrupt ridged and smooth plains; (8) rift-associated fractures; and (9) craters with associated dark paraboloids, which represent the youngest 1O% of the Venus impact crater population (Campbell et al.), and are on top of all volcanic and tectonic units except the youngest episodes of rift-associated fracturing and volcanism; surficial streaks and patches are approximately contemporary with dark-paraboloid craters. Mapping of such units and structures in 36 randomly distributed large regions (each approximately 10(exp 6) sq km) shows evidence for a distinctive regional and global stratigraphic and geologic sequence. On the basis of this sequence we have developed a model that illustrates several major themes in the history of Venus. Most of the history of Venus (that of its first 80% or so) is not preserved in the surface geomorphological record. The major deformation associated with tessera formation in the period sometime between 0.5-1.0 b.y. ago (Ivanov and Basilevsky) is the earliest event detected. In the terminal stages of tessera fon-nation, extensive parallel linear graben swarms representing a change in the style of deformation from shortening to extension were formed on the tessera and on some volcanic plains that were emplaced just after, and perhaps also during the latter stages of the major compressional phase of tessera emplacement. Our stratigraphic analyses suggest that following tessera formation, extensive volcanic flooding resurfaced at least 85% of the planet in the form of the presently-ridged and fractured plains. Several lines of evidence favor a high flux in the post-tessera period but we have no independent evidence for the absolute duration of ridged plains emplacement. During this time, the net state of stress in the lithosphere apparently changed from extensional to compressional, first in the form of extensive ridge belt development, followed by the formation of extensive wrinkle ridges on the flow units. Subsequently, there occurred local emplacement of smooth and lobate plains units which are presently essentially undefortned. The major events in the latest 10% of the presently preserved history of Venus (less than 50 m.y. ago) are continued rifting and some associated volcanism, and the redistribution of eolian material largely derived from impact crater deposits.

Basilevsky, Alexander T.↗

NASA NTRS1990

Prediction of functional aerobic capacity without exercise testing

The purpose of this study was to develop functional aerobic capacity prediction models without using exercise tests (N-Ex) and to compare the accuracy with Astrand single-stage submaximal prediction methods. The data of 2,009 subjects (9.7% female) were randomly divided into validation (N = 1,543) and cross-validation (N = 466) samples. The validation sample was used to develop two N-Ex models to estimate VO2peak. Gender, age, body composition, and self-report activity were used to develop two N-Ex prediction models. One model estimated percent fat from skinfolds (N-Ex %fat) and the other used body mass index (N-Ex BMI) to represent body composition. The multiple correlations for the developed models were R = 0.81 (SE = 5.3 ml.kg-1.min-1) and R = 0.78 (SE = 5.6 ml.kg-1.min-1). This accuracy was confirmed when applied to the cross-validation sample. The N-Ex models were more accurate than what was obtained from VO2peak estimated from the Astrand prediction models. The SEs of the Astrand models ranged from 5.5-9.7 ml.kg-1.min-1. The N-Ex models were cross-validated on 59 men on hypertensive medication and 71 men who were found to have a positive exercise ECG. The SEs of the N-Ex models ranged from 4.6-5.4 ml.kg-1.min-1 with these subjects.(ABSTRACT TRUNCATED AT 250 WORDS).

Oxygen Consumption↗

NASA NTRS1996

Relating the Hadamard Variance to MCS Kalman Filter Clock Estimation

The Global Positioning System (GPS) Master Control Station (MCS) currently makes significant use of the Allan Variance. This two-sample variance equation has proven excellent as a handy, understandable tool, both for time domain analysis of GPS cesium frequency standards, and for fine tuning the MCS's state estimation of these atomic clocks. The Allan Variance does not explicitly converge for the nose types of alpha less than or equal to minus 3 and can be greatly affected by frequency drift. Because GPS rubidium frequency standards exhibit non-trivial aging and aging noise characteristics, the basic Allan Variance analysis must be augmented in order to (a) compensate for a dynamic frequency drift, and (b) characterize two additional noise types, specifically alpha = minus 3, and alpha = minus 4. As the GPS program progresses, we will utilize a larger percentage of rubidium frequency standards than ever before. Hence, GPS rubidium clock characterization will require more attention than ever before. The three sample variance, commonly referred to as a renormalized Hadamard Variance, is unaffected by linear frequency drift, converges for alpha is greater than minus 5, and thus has utility for modeling noise in GPS rubidium frequency standards. This paper demonstrates the potential of Hadamard Variance analysis in GPS operations, and presents an equation that relates the Hadamard Variance to the MCS's Kalman filter process noises.

Hutsell, Steven T.↗

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.↗

NASA NTRS2016

Discordant K-Ar and Young Exposure Dates for the Windjana Sandstone, Kimberley, Gale Crater, Mars

K-Ar and noble gas surface exposure age measurements were carried out on the Windjana sandstone, Kimberley region, Gale Crater, Mars, by using the Sample Analysis at Mars instrument on the Curiosity rover. The sandstone is unusually rich in sanidine, as determined by CheMin X-ray diffraction, contributing to the high K2O concentration of 3.09 +/- 0.20 wt % measured by Alpha-Particle X-ray Spectrometer analysis. A sandstone aliquot heated to approximately 915 C yielded a K-Ar age of 627 +/- 50 Ma. Reheating this aliquot yielded no additional Ar. A second aliquot heated in the same way yielded a much higher K-Ar age of 1710 +/- 110 Ma. These data suggest incomplete Ar extraction from a rock with a K-Ar age older than 1710 Ma. Incomplete extraction at approximately 900 C is not surprising for a rock with a large fraction of K carried by Ar-retentive K-feldspar. Likely, variability in the exact temperature achieved by the sample from run to run, uncertainties in sample mass estimation, and possible mineral fractionation during transport and storage prior to analysis may contribute to these discrepant data. Cosmic ray exposure ages from He-3 and Ne-21 in the two aliquots are minimum values given the possibility of incomplete extraction. However, the general similarity between the He-3 (57 +/- 49 and 18 +/- 32 Ma, mean 30 Ma) and Ne-21 (2 +/- 32 and 83 +/- 24 Ma, mean 54 Ma) exposure ages provides no evidence for underextraction. The implied erosion rate at the Kimberley location is similar to that reported at the nearby Yellowknife Bay outcrop.

K-Ar↗

NASA NTRS2019

FIGS: spectral fitting constraints on the star formation history of massive galaxies since the cosmic noon

We constrain the stellar population properties of a sample of 52 massive galaxies – with stellar mass log (M(s)/M(⊙)) ≳ 10.5 – over the redshift range 0.5 < z < 2 by use of observer-frame optical and near-infrared slitless spectra from Hubble Space Telescope’s ACS and WFC3 grisms. The deep exposures (∼100 ks) allow us to target individual spectra of massive galaxies to F160W = 22.5 AB. Our spectral fitting approach uses a set of six base models adapted to the redshift and spectral resolution of each observation, and fits the weights of the base models, including potential dust attenuation, via a Markov Chain Monte Carlo method. Our sample comprises a mixed distribution of quiescent (19) and star-forming galaxies (33). We quantify the width of the age distribution (Δt) that is found to dominate the variance of the retrieved parameters according to principal component analysis. The population parameters follow the expected trend towards older ages with increasing mass, and Δt appears to weakly anticorrelate with stellar mass, suggesting a more efficient star formation at the massive end. As expected, the redshift dependence of the relative stellar age (measured in units of the age of the Universe at the source) in the quiescent sample rejects the hypothesis of a single burst (aka monolithic collapse). Radial colour gradients within each galaxy are also explored, finding a wider scatter in the star-forming subsample, but no conclusive trend with respect to the population parameters.

Ignacio Ferreras↗

NASA NTRS2010

Failure Analysis at the Kennedy Space Center

History has shown that failures occur in every engineering endeavor, and what we learn from those failures contributes to the knowledge base to safely complete future missions. The necessity of failure analysis is at its apex at the end of one aged program and at the beginning of a new and untested program. The information that we gain through failure analysis corrects the deficiencies in the current vehicle to make the next generation of vehicles more efficient and safe. The Failure Analysis and Materials Evaluation Branch in the Materials Science Division at the Kennedy Space Center performs metallurgical, mechanical, electrical, and non-metallic materials failure analyses and accident investigations on both flight hardware and ground support equipment for the Space Shuttle, International Space Station, Constellation, and Launch Services Programs. This paper will explore a variety of failure case studies at the Kennedy Space Center and the lessons learned that can be applied in future programs.

Salazar, Victoria L.↗

NASA NTRS2021

The Far Ultraviolet M-dwarf Evolution Survey. I. The Rotational Evolution of High-energy Emissions

M-dwarf stars are prime targets for exoplanet searches because of their close proximity and favorable properties for both planet detection and characterization. However, the potential habitability and atmospheric characterization of these exoplanetary systems depends critically on the history of high-energy stellar radiation from X-rays to NUV, which drive atmospheric mass loss and photochemistry in the planetary atmospheres. With the Far Ultraviolet M-dwarf Evolution Survey, we have assessed the evolution of the FUV radiation, specifically eight prominent emission lines, including Lyα, of M-dwarf stars with stellar rotation period and age. We demonstrate tight power-law correlations between the spectroscopic FUV features, and measure the intrinsic scatter of the quiescent FUV emissions. The luminosity evolution with rotation of these spectroscopic features is well-described by a broken power law, saturated for fast rotators, and decays with increasing Rossby number, with a typical power-law slope of −2, although likely shallower for Lyα. Our regression fits enable FUV emission-line luminosity estimates relative to bolometric from known rotation periods to within ∼0.3 dex, across eight distinct UV emission lines, with possible trends in the fit parameters as a function of source layer in the stellar atmosphere. Our detailed analysis of the UV luminosity evolution with age further shows that habitable-zone planets orbiting lower-mass stars experience much greater high-energy radiative exposure relative the same planets orbiting more massive hosts. Around early- to mid-M dwarfs, these exoplanets, at field ages, accumulate up to 10–20× more EUV energy, relative to modern Earth. Moreover, the bulk of this UV exposure likely takes place within the first Gyr of the stellar lifetime.

J Sebastian Pineda↗

NASA NTRS1996

Relation of systemic and local muscle exercise capacity to skeletal muscle characteristics in men with congestive heart failure

OBJECTIVES. The present study was undertaken to further characterize changes in skeletal muscle morphology and histochemistry in congestive heart failure and to determine the relation of these changes to abnormalities of systemic and local muscle exercise capacity. BACKGROUND. Abnormalities of skeletal muscle appear to play a role in the limitation of exercise capacity in congestive heart failure, but information on the changes in muscle morphology and biochemistry and their relation to alterations in muscle function is limited. METHODS. Eighteen men with predominantly mild to moderate congestive heart failure (mean +/- SEM New York Heart Association functional class 2.6 +/- 0.2, ejection fraction 24 +/- 2%) and eight age- and gender-matched sedentary control subjects underwent measurements of peak systemic oxygen consumption (VO2) during cycle ergometry, resistance to fatigue of the quadriceps femoris muscle group and biopsy of the vastus lateralis muscle. RESULTS. Peak VO2 and resistance to fatigue were lower in the patients with heart failure than in control subjects (15.7 +/- 1.2 vs. 25.1 +/- 1.5 ml/min-kg and 63 +/- 2% vs. 85 +/- 3%, respectively, both p < 0.001). Patients had a lower proportion of slow twitch, type I fibers than did control subjects (36 +/- 3% vs. 46 +/- 5%, p = 0.048) and a higher proportion of fast twitch, type IIab fibers (18 +/- 3% vs. 7 +/- 2%, p = 0.004). Fiber cross-sectional area was smaller, and single-fiber succinate dehydrogenase activity, a mitochondrial oxidative marker, was lower in patients (both p < or = 0.034). Likewise, the ratio of average fast twitch to slow twitch fiber cross-sectional area was lower in patients (0.780 +/- 0.06 vs. 1.05 +/- 0.08, p = 0.019). Peak VO2 was strongly related to integrated succinate dehydrogenase activity in patients (r = 0.896, p = 0.001). Peak VO2, resistance to fatigue and strength also correlated significantly with several measures of fiber size, especially of fast twitch fibers, in patients. None of the skeletal muscle characteristics examined correlated with exercise capacity in control subjects. CONCLUSIONS. These results indicate that congestive heart failure is associated with changes in the characteristics of skeletal muscle and local as well as systemic exercise performance. There are fewer slow twitch fibers, smaller fast twitch fibers and lower succinate dehydrogenase activity. The latter finding suggests that mitochondrial content of muscle is reduced in heart failure and that impaired aerobic-oxidative capacity may play a role in the limitation of systemic exercise capacity.

Non-NASA Center↗

NASA NTRS2003

Aging of microstructural compartments in human compact bone

Composition of microstructural compartments in compact bone of aging male subjects was assessed using Raman microscopy. Secondary mineralization of unremodeled fragments persisted for two decades. Replacement of these tissue fragments with secondary osteons kept mean composition constant over age, but at a fully mineralized limit. Slowing of remodeling may increase fracture susceptibility through an increase in proportion of highly mineralized tissue. In this study, the aging process in the microstructural compartments of human femoral cortical bone was investigated and related to changes in the overall tissue composition within the age range of 17-73 years. Raman microprobe analysis was used to assess the mineral content, mineral crystallinity, and carbonate substitution in fragments of primary lamellar bone that survived remodeling for decades. Tissue composition of the secondary osteonal population was investigated to determine the composition of turned over tissue volume. Finally, Raman spectral analysis of homogenized tissue was performed to evaluate the effects of unremodeled and newly formed tissue on the overall tissue composition. The chemical composition of the primary lamellar bone exhibited two chronological stages. Organic matrix became more mineralized and the crystallinity of the mineral improved during the first stage, which lasted for two decades. The mineral content and the mineral crystallinity did not vary during the second stage. The results for the primary lamellar bone demonstrated that physiological mineralization, as evidenced by crystal growth and maturation, is a continuous process that may persist as long as two decades, and the growth and maturation process stops after the organic matrix becomes "fully mineralized." The average mineral content and the average mineral crystallinity of the homogenized tissue did not change with age. It was also observed that the mineral content of the homogenized tissue was consistently greater than the osteons and similar to the "fully mineralized" stage of primary bone. The results of this study demonstrated that unremodeled compartments of bone grow older through maturation and growth of mineral crystals in a protracted fashion. However, the secondary osteonal remodeling impedes this aging process and maintains the mean tissue age fairly constant over decades. Therefore, slowing of remodeling may lead to brittle bone tissue through accumulation of fully mineralized tissue fragments.

Non-NASA Center↗

NASA NTRS2013

Population Pharmacokinetics of Intranasal Scopolamine

Introduction: An intranasal gel dosage formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness (SMS).The bioavailability and pharmacokinetics (PK) was evaluated using data collected in Phase II IND protocols. We reported earlier statistically significant gender differences in PK parameters of INSCOP at a dose level of 0.4 mg. To identify covariates that influence PK parameters of INSCOP, we examined population covariates of INSCOP PK model for 0.4 mg dose. Methods: Plasma scopolamine concentrations versus time data were collected from 20 normal healthy human subjects (11 male/9 female) after a 0.4 mg dose. Phoenix NLME was employed for PK analysis of these data using gender, body weight and age as covariates for model selection. Model selection was based on a likelihood ratio test on the difference of criteria (-2LL). Statistical significance for base model building and individual covariate analysis was set at P less than 0.05{delta(-2LL)=3.84}. Results: A one-compartment pharmacokinetic model with first-order elimination best described INSCOP concentration ]time profiles. Inclusion of gender, body weight and age as covariates individually significantly reduced -2LL by the cut-off value of 3.84(P less than 0.05) when tested against the base model. After the forward stepwise selection and backward elimination steps, gender was selected to add to the final model which had significant influence on absorption rate constant (ka) and the volume of distribution (V) of INSCOP. Conclusion: A population pharmacokinetic model for INSCOP has been identified and gender was a significant contributing covariate for the final model. The volume of distribution and Ka were significantly higher in males than in females which confirm gender-dependent pharmacokinetics of scopolamine after administration of a 0.4 mg dose.

Wu, L.↗

NASA NTRSDate not supplied

Changes in Oculomotor Behavior and PVT Reaction Time During One Night of Sleep Deprivation

INTRODUCTION: The Psychomotor Vigilance Test (PVT) is a widely used objective measure of sustained attention, alertness, and fatigue. Previous studies consistently show that prolonged wakefulness and disrupted sleep patterns lead to increased lapses of attention and slower reaction times. These findings have critical implications for various professions, including healthcare, aviation, transportation safety, and spaceflight. In this study, we employed linear mixed models (LMM) to investigate hourly-measured 5-minute PVT reaction times during one night of total sleep deprivation. Our goal was to characterize the contribution of homeostatic sleep pressure (time awake) and circadian phase (salivary melatonin levels) on the dynamics of PVT reaction time. MATERIALS & METHODS: Data from twelve human participants were used in the analysis. Participants were healthy non-smokers, aged 18 and 40, with normal sleep habits defined as Pittsburg Sleep Quality Index scores < 5, and Morningness – Eveningness Questionnaire scores > 42 and < 58, respectively. Participants followed a constant-routine protocol and arrived at the NASA sleep laboratory approximately 1 to 2 hours after their habitual waking time. Tympanic temperature was measured every 30 min to provide a real-time estimate of circadian phase. Participants were required to stay awake throughout the laboratory experiment, which continued until their tympanic temperature had returned to baseline levels. This approach ensured that we could capture each participant's circadian trough and recovery, typically occurring between 24 and 26 hours after waking. The PVT and saliva melatonin were measured every hour, starting approximately from 3 hours after awakening. More information about the measurement protocol can be found in the publication by Stone et al. We used PVT reaction times between 100 and 10000 ms to calculate Reciprocal Reaction Times (RRTs). LMM models were employed to assess the contribution of time awake and saliva melatonin levels on changes in RRTs. Two models were created: the first model treated time awake as a fixed effect and the second model considered both the salivary melatonin level and time awake as fixed effects. Participants were included as a random effect in both models. We compared the models using an Analysis of Variance (ANOVA). The models were computed using the 'lmer' function from the 'lme4' package in R, and LMM p-values were determined using Satterthwaite's method. RESULTS: We found that time awake had a statistically significant effect on PVT RRTs during one night of sleep deprivation [χ2 = 2132.4, df = 1, p < 0.001]. In addition, the model including both saliva melatonin levels and time awake was statistically significantly better than one that uses just time awake [χ2 = 17.4, df = 1, p < 0.001]. DISCUSSION & CONCLUSION: As expected, these preliminary results suggest that the time awake and circadian phase each contribute to performance reductions as measured by the PVT. Future analyses will explore the contributions of other factors to the model.

sleep deprivation↗